Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 1 of 24 PageID #: 2207
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`C.A. No. 20-cv-1580-LPS
`
`JURY TRIAL DEMANDED
`
`FILED UNDER SEAL
`
`)))))))))
`
`GUARDANT HEALTH, INC.,
`
`Plaintiff,
`
`v.
`
`FOUNDATION MEDICINE, INC.,
`
`Defendant.
`
`PLAINTIFF GUARDANT HEALTH INC.’S OPENING BRIEF IN SUPPORT OF ITS
`MOTION FOR PRELIMINARY INJUNCTION
`
`Brian E. Farnan (Bar No. 4089)
`Michael J. Farnan (Bar No. 5165)
`FARNAN LLP
`919 North Market Street, 12th Floor
`Wilmington, DE 19801
`Telephone: (302) 777-0300
`Facsimile: (302) 777-0301
`bfarnan@farnanlaw.com
`mfarnan@farnanlaw.com
`
`Attorneys for Plaintiff, Guardant Health, Inc.
`
`OF COUNSEL:
`Edward R. Reines (pro hac vice pending)
`edward.reines@weil.com
`Derek C. Walter (pro hac vice pending)
`derek.walter@weil.com
`WEIL, GOTSHAL & MANGES LLP
`201 Redwood Shores Parkway
`Redwood Shores, CA 94065
`Telephone: (650) 802-3000
`Facsimile: (650) 802-3100
`
`Garland T. Stephens (pro hac vice pending)
`Justin L. Constant (pro hac vice pending)
`WEIL, GOTSHAL & MANGES LLP
`700 Louisiana, Suite 1700
`Houston, TX 77002
`Telephone: (713) 546-5000
`Facsimile: (713) 224-9511
`
`Dated: December 10, 2020
`
`

`

`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 2 of 24 PageID #: 2208
`
`TABLE OF CONTENTS
`
`Page
`
`I.
`
`II.
`
`III.
`
`IV.
`
`NATURE AND STAGE OF THE PROCEEDING ............................................................ 1
`
`SUMMARY OF THE ARGUMENT ................................................................................. 1
`
`STATEMENT OF FACTS ................................................................................................. 2
`
`ARGUMENT .................................................................................................................... 14
`
`A.
`
`Guardant is likely to succeed on the merits. ......................................................... 14
`
`1.
`
`2.
`
`FoundationOne® Liquid CDx infringes the ’085 and ’086 Patents ......... 15
`
`FMI’s invalidity position is insubstantial. ................................................ 16
`
`FMI’s infringement is causing and threatening irreparable harm to
`Guardant. ............................................................................................................... 16
`
`The balance of harms favors a preliminary injunction. ........................................ 18
`
`The public interest is best served by an injunction. .............................................. 19
`
`B.
`
`C.
`
`D.
`
`V.
`
`CONCLUSION ................................................................................................................. 20
`
`
`
`
`
`
`
`
`
`i
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`

`

`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 3 of 24 PageID #: 2209
`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`Cases
`Abbott Labs. v. Sandoz, Inc.,
`544 F.3d 1341 (Fed. Cir. 2008) ................................................................................................ 18
`
`Apple, Inc. v. Samsung Elec. Co., Ltd.,
`678 F.3d 1314 (Fed. Cir. 2012) ................................................................................................ 17
`
`Celsis In Vitro, Inc. v. CellzDirect, Inc.,
`664 F.3d 922 (Fed. Cir. 2012) .................................................................................................. 17
`
`Douglas Dynamics, LLC v. Buyers Prods. Co.,
`717 F. 3d 1336 (Fed. Cir. 2013) ............................................................................................... 17
`
`Foundation Medicine, Inc. v. Guardant Health, Inc.,
`IPR2019-00636 ..................................................................................................................... 1, 16
`
`Foundation Medicine, Inc. v. Guardant Health, Inc.,
`IPR2019-00637 ..................................................................................................................... 1, 16
`
`Guardant Health, Inc. v. Foundation Medicine, Inc.,
`C.A. No. 17-cv-1616-LPS-CJB (D. Del.) (“the 1616 Action”) .......................... 1, 12, 13, 14, 15
`
`Hybritech Inc. v. Abbott Labs.,
`849 F.2d 1446 (Fed. Cir. 1988) .......................................................................................... 18, 19
`
`In re BRCA1- & BRCA2-Based Hereditary Cancer Test Patent Lit.,
`3 F.Supp.3d 1213 (D. Utah 2014) ............................................................................................. 19
`
`Pfaff v. Wells Elecs., Inc.,
`525 U.S. 55 (1998) .................................................................................................................... 19
`
`QBAS Co., Ltd. v. C Walters Intercoastal Corp.,
`No. 10-cv-406 AG (MLGx), 2010 WL 7785955 (C.D. Cal. Dec. 16, 2010) ........................... 17
`
`Reebok Int’l Ltd. v. J. Baker, Inc.,
`32 F.3d 1552 (Fed. Cir. 1994) .................................................................................................. 14
`
`Titan Tire Corp. v. Case New Holland, Inc.,
`566 F.3d 1372 (Fed. Cir. 2009) ................................................................................................ 14
`
`Statutes and Regulations
`35 U.S.C. § 314 ............................................................................................................................. 16
`
`
`
`ii
`
`

`

`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 4 of 24 PageID #: 2210
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`I.
`
`NATURE AND STAGE OF THE PROCEEDING
`
`Plaintiff Guardant Health, Inc. (“Guardant”) is a pioneer in the field of blood-based cancer
`
`diagnostics using comprehensive genomic profiling, and brings this suit for patent infringement
`
`against Guardant’s most significant direct competitor, Defendant Foundation Medicine, Inc.
`
`(“FMI”). This motion for preliminary injunction seeks to stop FMI from infringing Guardant’s
`
`U.S. Patent No. 10,704,085 (“the ’085 Patent”) and U.S. Patent No. 10,704,086 (“the ’086 Patent”)
`
`through FMI’s recently-introduced FoundationOne® Liquid CDx diagnostic test.
`
`II.
`
`SUMMARY OF THE ARGUMENT
`
`FoundationOne® Liquid CDx is the only FDA-approved liquid biopsy that competes
`
`directly with Guardant’s pioneering FDA-approved liquid biopsy, Guardant360® CDx. It is
`
`causing and threatening irreparable harm to Guardant as a result. Guardant is likely to succeed on
`
`the merits because FoundationOne® Liquid CDx infringes the ’085 and ’086 Patents, and the
`
`patents are not invalid. The claims resemble those of U.S. Patent No. 9,902,992 Patent (“the ’992
`
`Patent”) asserted in Guardant Health, Inc. v. Foundation Medicine, Inc., C.A. No. 17-cv-1616-
`
`LPS-CJB (D. Del.) (“the 1616 Action”)1 but are not subject to FMI’s only noninfringement defense
`
`for the ’992 Patent. The claims do, however, include a limitation that the Patent Trademark and
`
`Appeal Board found distinguishes the ’992 claims from the prior art in Foundation Medicine, Inc.
`
`v. Guardant Health, Inc., IPR2019-00636 and IPR2019-00637. The balance of hardships favors
`
`an injunction because liquid biopsies are the focus of Guardant’s business, but a sideline for FMI,
`
`and FMI is a part of a large multinational conglomerate that can readily withstand an injunction.
`
`
`1 In the 1616 Action, Guardant is seeking a permanent injunction against FMI from infringing
`four patents. See D.I. 149 in the 1616 Action [Guardant’s Third Amended Complaint]. The
`1616 Action was scheduled for trial starting November 20, 2020. That trial has now been
`postponed and no trial date has been set. See D.I. 513 in 1616 Action [Memorandum and Order
`postponing trial].
`
`1
`
`

`

`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 5 of 24 PageID #: 2211
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`The public interest also favors an injunction because Guardant’s test performs better than FMI’s
`
`test and Guardant can provide liquid biopsies meeting the standard of care for any cancer patients
`
`who would otherwise use FoundationOne® Liquid CDx.
`
`III.
`
`STATEMENT OF FACTS
`
`Guardant is a precision oncology company focused on helping conquer cancer through use
`
`of proprietary blood-based tests, large data sets and advanced analytics. Guardant360® CDx is the
`
`first FDA-approved liquid biopsy for comprehensive genomic profiling (CGP) for all solid
`
`cancers. Simon Decl. ¶ 4. Guardant360® CDx was granted FDA approval on August 7, 2020.
`
`Simon Decl. ¶ 26. The FDA’s press announcement said that the approval “marks a new era for
`
`mutation testing”:
`
` “Approval of a companion diagnostic that uses a liquid biopsy and leverages next-
`generation sequencing marks a new era for mutation testing,” said Tim Stenzel,
`M.D., Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health
`in the FDA’s Center for Devices and Radiological Health. “In addition to
`benefitting from less invasive testing, patients are provided with a simultaneous
`mapping of multiple biomarkers of genomic alterations, rather than one biomarker
`at a time, which can translate to decreased wait times for starting treatment and
`provide insight into possible resistance mechanisms.”
`
`Simon Decl. ¶ 38; Stephens Decl. Ex. 1 [FDA Announcement].
`
`
`
`
`
`
`FMI’s FoundationOne® Liquid CDx infringes at least claim 1 of the ’085 Patent and claim 1 of
`
`the ’086 Patent. Cooper Decl. ¶¶ 212-256. FoundationOne® Liquid CDx was approved by the
`
`FDA on August 26, 2020. It is the only FDA-approved liquid biopsy that competes directly with
`
`Guardant360® CDx. Simon Decl. ¶ 39.
`
`2
`
`

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`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 6 of 24 PageID #: 2212
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`A. FMI’s infringing FoundationOne® Liquid CDx is causing and threatening to cause
`irreparable harm to Guardant.
`
`The market for liquid CGP biopsies is at an early stage. But for FMI’s infringement,
`
`Guardant360® CDx would be the only FDA approved CGP liquid biopsy on the market. Simon
`
`Decl. ¶¶ 38, 42.
`
`The success of Guardant’s liquid biopsy products depends critically on a number of factors
`
`that are irreparably harmed or threatened by FoundationOne® Liquid CDx. Simon Decl. ¶41.
`
`Many of these effects are self-reinforcing. Simon Decl. ¶60. For example, as FMI has admitted
`
`in its own SEC filings, clinical trials, studies, publications and presentations at leading conferences
`
`are critical to broad adoption of cancer diagnostic services:
`
`We believe that the successful completion of clinical trials, publication of scientific
`and medical results in peer-reviewed journals, and presentations at leading
`conferences are critical to the broad adoption of our services. Publication in leading
`medical journals is subject to a peer-review process, and peer reviewers may not
`consider the results of studies involving our services sufficiently novel or worthy
`of publication.
`
`Simon Decl. ¶ 51; Stephens Decl. Ex. 2 [FMI 2017 Form 10-K] at 42. Importantly, successful
`
`trials, studies, publications and presentations concerning a test also increase the likelihood that
`
`others will use the same test in future clinical trials, studies, publications and presentations.
`
`Simon Decl. ¶ 52.
`
`The opposite is also true. Once the results of a clinical study using an FMI liquid biopsy
`
`are published, a second study establishing equivalent results with a Guardant biopsy is typically
`
`of less interest to researchers, journals and conferences. Further, clinical trials and studies
`
`generally standardize on one biopsy vendor and do not change once the trial or study starts.
`
`Therefore, each clinical trial or study that uses an FMI liquid biopsy generally does not use a
`
`Guardant liquid biopsy, depriving Guardant of important opportunities to gain market acceptance
`
`3
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`

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`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 7 of 24 PageID #: 2213
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`and valuable clinical data for its liquid biopsies, and adversely affecting the chances that
`
`Guardant’s tests will be used in similar trials and studies in the future. Simon Decl. ¶¶ 52-53.
`
`Guardant has lost numerous opportunities to FMI to provide liquid biopsies for clinical
`
`trials and studies, including TRITON3, a prostate cancer study published in the Journal of Clinical
`
`Oncology; a study of metastatic bladder cancer by Rainier Therapeutics; a study and trial
`
`concerning non-small cell lung cancer (NSCLC) by Genentech published in the Annals of
`
`Oncology; a joint study and trial by the University of California and Genentech concerning
`
`NSCLC published in Nature Medicine; a study by Aix Marseilles University of NSCLC published
`
`in Therapeutic Advances
`
`in Respiratory Disease; and a study of bile duct cancer
`
`(cholangiocarcinoma) by Incyte. These studies and trials have collectively involved thousands of
`
`test subjects. Simon Decl. ¶ 54.
`
`The success of Guardant’s CGP liquid biopsy products also depends critically on
`
`developing and maintaining relationships with biopharmaceutical companies. Simon Decl. ¶ 46.
`
`FMI has also acknowledged the importance of these relationships in its SEC filings:
`
`Our success in the future depends in part on our ability to maintain relationships
`and to enter into new relationships with biopharmaceutical partners. This can be
`difficult due to several factors, including internal and external constraints placed on
`these organizations that can limit the number and type of relationships with
`companies like us they can consider and consummate….If we fail to maintain these
`relationships, or enter into new ones, our business could suffer.
`
`Simon Decl. ¶ 47; Stephens Decl. Ex. 2 [FMI 2017 Form 10K] at 46.
`
`Guardant and FMI compete for relationships with biopharmaceutical partners for CGP
`
`liquid biopsies. FMI’s participation in such relationships restricts Guardant’s ability to cultivate
`
`and maintain such relationships. It also means that Guardant may be required to offer less
`
`favorable terms to its biopharmaceutical partners. Simon Decl. ¶ 48
`
`4
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`

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`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 8 of 24 PageID #: 2214
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`Despite its later entry into the field of liquid biopsies, FMI has used its position as a trusted
`
`tissue biopsy provider, and Guardant’s patented liquid biopsy technology, to develop
`
`collaborations with a number biopharmaceutical companies for use of FoundationOne® Liquid
`
`CDx as a companion diagnostic test. The FDA Label for FoundationOne® Liquid CDx includes
`
`companion diagnostic test indications for six different therapeutic drugs: gefitinib, osimertinib,
`
`erlotinib, alectinib, rucaparib and alpelisib. Simon Decl. ¶ 49; Cooper Decl. Ex. 7
`
`[FoundationOne® Liquid CDx FDA Label] at 1.
`
`Guardant and FMI also compete for the support of Key Opinion Leaders, such as
`
`prestigious cancer institutions and oncology networks, for its liquid biopsies. FMI has
`
`acknowledged that key opinion leaders are important in “validating [a company’s] testing
`
`platform, driving adoption, or establishing [a company’s] molecular information platform and tests
`
`as a standard of care….” Simon Decl. ¶ 55; Stephens Decl. Ex. 2 [FMI 2017 Form 10-K] at 46.
`
`FMI’s engagement with Key Opinion Leaders restricts Guardant’s opportunities to engage with
`
`the same Key Opinion Leaders to validate its CGP liquid biopsies, drive adoption of them, and
`
`establish them as a standard of care. Simon Decl. ¶ 57.
`
`FMI has claimed to have relationships with a number of Key Opinion Leaders, including
`
`the Children’s Hospital of Philadelphia Cancer Center, the Sylvester Comprehensive Cancer
`
`Center at the University of Miami, The Ohio State University Comprehensive Cancer Center -
`
`Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, and the Sidney Kimmel
`
`Comprehensive Cancer Center at Johns Hopkins University. Simon Decl. ¶ 56; Stephens Decl.
`
`Ex. 2 [FMI 2017 Form 10-K] at 46. Since FoundationOne® Liquid CDx received FDA approval,
`
`it has attracted attention from key opinion leaders that would otherwise have been focused on
`
`5
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`

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`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 9 of 24 PageID #: 2215
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`Guardant360® CDx. FMI’s sales and marketing team has also focused attention on Guardant’s
`
`leading customers, especially those in an academic setting. Simon Decl. ¶ 58.
`
`Guardant’s revenue depends significantly on third-party commercial payers such as
`
`insurance companies. FMI’s competition with Guardant for biopharmaceutical partners, Key
`
`Opinion Leaders, clinical trials and studies affects Guardant’s ability to persuade commercial
`
`payers to provide coverage for Guardant’s CGP liquid biopsies. By appropriating such
`
`opportunities with its infringing test, FMI reduces Guardant’s abilities to persuade commercial
`
`payers to cover Guardant’s CGP liquid biopsies. Coverage decisions have broad and lasting
`
`effects, as many patients and their oncologists are reluctant to order a Guardant CGP liquid biopsy
`
`if it is not covered by the patient’s insurance. Simon Decl. ¶ 59.
`
`These effects are self-reinforcing. Positive coverage decisions result in wider adoption,
`
`which makes it easier to recruit Key Opinion Leaders, biopharmaceutical partners, clinical trials,
`
`studies, peer-reviewed publications and presentations at prestigious conferences. All of these
`
`factors are important to the success of Guardant’s CGP liquid biopsies. Simon Decl. ¶ 60.
`
`FMI’s infringing liquid biopsy also deprives Guardant of access to data critical to
`
`Guardant’s success. CGP liquid biopsies generate large amounts of data concerning the genomic
`
`profiles of patients and their associated disease states. This information has great potential to
`
`enable progress in cancer diagnostics and to enhance the value of the CGP liquid biopsies to
`
`patients and doctors. Simon Decl. ¶ 61. As the Chief Medical Officer of Illumina, the leading
`
`maker of next generation DNA sequencers explained in August of 2019, “[t]hough we’re only
`
`beginning to understand how to use this information to optimize patient outcomes, blood samples
`
`are already outlining cancer aggressiveness, identifying treatment options, tracking efficacy, and
`
`6
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`

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`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 10 of 24 PageID #: 2216
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`precisely managing each patient’s unique disease….” Simon Decl. ¶61; Stephens Decl. Ex. 3
`
`[Febbo Liquid Biopsy].
`
`Guardant uses the data from its liquid biopsies in its machine learning facilities to enhance
`
`the performance and capabilities of subsequent tests and to develop new applications for
`
`Guardant’s liquid biopsy technology. As a result, the data from every Guardant CGP biopsy
`
`potentially enhances the value of subsequent biopsies. Every CGP liquid biopsy that is performed
`
`by FMI instead of Guardant deprives Guardant of the opportunity to utilize the data from that test
`
`to enhance future tests. Simon Decl. ¶ 62.
`
`B. Overview of Comprehensive Genetic Profiling For Oncology
`
`Traditional oncology categorizes cancer by the organ in which it is first located and treats
`
`it independently of its genomic profile. But an individual’s response to specific therapies often
`
`depends on the genomic profile of their tumor. The goal of precision oncology is to match cancer
`
`patients with personalized therapies based on the genomic profiles of their tumors. Such therapies
`
`can provide better outcomes, and fewer side effects, than broad-based chemotherapy. Simon Decl.
`
`¶¶ 12, 13. Precision oncology is an increasingly important approach to cancer treatment. Many
`
`important types of cancer, including lung, breast, colorectal and melanoma, for example, are often
`
`classified and treated on the basis of their genomic profile. Simon Decl. ¶ 14.
`
`Precision oncology is also an important focus for biopharmaceutical drug development.
`
`Many drug companies are working to develop therapies for patients with alterations in specific
`
`genes. This can significantly increase the likelihood that clinical trials will succeed, and do so with
`
`fewer patients, shortening time to market and accelerating patient access. Simon Decl. ¶ 15.
`
`As new genomic biomarkers are discovered, cancer populations may be further divided
`
`into sub-classifications for treatment. This may lead to yet more optimal treatments, and outcomes,
`
`for patients, but it can also make the oncologist’s job of matching patients with the right treatments
`7
`
`

`

`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 11 of 24 PageID #: 2217
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`even more complicated. Simon Decl. ¶ 16. Previously, most genomic liquid biopsies were for
`
`single mutations in a gene, or a short selection of nucleotides within a gene (called a “hotspot”).
`
`These biopsies were usually targeted for a single type of cancer. Matching a patient with a targeted
`
`therapy using these tests often requires repeated testing as multiple genes should be tested. As the
`
`number of available therapies has increased, it has become more difficult to select an appropriate
`
`therapy using single-gene tests. Simon Decl. ¶ 17.
`
`Traditionally, tissue biopsies were used to analyze tumors. Tissue biopsies are often
`
`expensive, time-consuming and invasive, requiring, for example, a needle to be inserted into a
`
`tumor to collect a sample. Medical imaging is typically required to locate a tumor for biopsy, a
`
`procedure is usually required to collect it, and a pathologist required to analyze it, which all
`
`requires complex coordination among multiple doctors. This can require additional time, which
`
`advanced-stage cancer patients cannot always afford. Invasive tissue biopsy procedures, such as
`
`surgery, are also often associated with increased morbidity and mortality. Simon Decl. ¶ 20.
`
`Tissue biopsies typically sample just a small portion of the patient’s tumor, which may not
`
`be representative of the rest of the tumor, or tumor metastases, which may have spread to other
`
`parts of the body, and may thus not include all relevant and actionable biomarkers. This can result
`
`in targetable mutations going undetected. Simon Decl. ¶ 21.
`
`C. Guardant’s CGP Liquid Biopsies
`
`Compared to tissue biopsies, Guardant’s liquid biopsies are minimally invasive, quick and
`
`easy to administer, cost effective and readily available. Guardant’s liquid biopsy requires only a
`
`routine blood draw and typically takes seven days or less to provide a comprehensive genotype,
`
`allowing the oncologist to select an effective treatment or potential clinical trial enrollment, if any
`
`appropriate alterations are found. The genotype can reflect the entire molecular profile of the
`
`8
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`

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`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 12 of 24 PageID #: 2218
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`patient’s tumor or tumors and not just a portion of a single tumor, potentially identifying more
`
`targetable mutations than a tissue biopsy. Simon Decl. ¶ 29.
`
`Guardant’s liquid biopsies use cell-free DNA (“cfDNA”) from a patient’s blood to develop
`
`the comprehensive genetic profile. cfDNA from tumors circulating in blood plasma is called
`
`circulating tumor DNA (“ctDNA”). Analyzing cfDNA poses challenges in part because it is found
`
`at very low concentrations. Although the sensitivity and specificity of next generation DNA
`
`sequencing platforms is sufficient for genomic profiling of tumors from tissue biopsies, it is
`
`inadequate, without the technology Guardant has developed, for liquid biopsies because of the low
`
`concentration of ctDNA found in blood. Simon Decl. ¶ 30.
`
`The figure below is from a Guardant publication describing its technology for detecting
`
`cancer-causing mutations in cfDNA. True mutations are highlighted in red, and deviations from
`
`the normal human sequence that are not real, but are nothing more than standard sequencing errors,
`
`are shown by black dots. Normal human genetic variation is present in much higher quantities,
`
`shown in green. As the figure shows, the prevalence of true mutations that cause cancer is so low
`
`that they are indistinguishable from noise. Cooper Decl. ¶¶ 43-44.
`
`
`
`9
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`

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`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 13 of 24 PageID #: 2219
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`Cooper Decl. ¶ 44; Cooper Decl. Ex. 5 [R.B. Lanman, et al., Analytical and clinical validation of
`
`a digital sequencing panel], Fig. 2A (annotation supplied).
`
`D. The Patented Technology
`
`The ’085 and ’086 Patents are continuations of a common parent and share a common
`
`specification. They describe and claim methods for detecting cancer-causing mutations using
`
`cfDNA extracted from an ordinary blood sample. Before Guardant’s patented innovations, the
`
`low concentration of cfDNA in blood meant that tumor mutations present in cfDNA were
`
`indistinguishable from errors, or noise, that result from the typical DNA preparation and
`
`sequencing process. Cooper Decl. ¶¶ 40-42.
`
`The common specification explains that the noise results primarily from the process of
`
`amplifying, or copying, DNA sequences to increase the amount of DNA for analysis, and from the
`
`sequencing process itself. Cooper Decl. ¶ 45. Guardant’s approach processes amplified copies of
`
`an original cfDNA molecule so as to be analyzed as a group, or family of related sequences. By
`
`analyzing families of sequences, a consensus sequence can be generated that substantially
`
`eliminates errors that may have arisen in any single sequence analysis. Cooper Decl. ¶ 46. This is
`
`shown in the figure below, again from Guardant’s publication.
`
`
`
`10
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`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 14 of 24 PageID #: 2220
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`Cooper Decl. ¶ 48; Cooper Decl. Ex. 5 [R.B. Lanman, et al., Analytical and clinical validation of
`
`a digital sequencing panel], Fig. 2B. With Guardant’s technology, the noise, which is shown as
`
`the black dots, largely vanishes. The true mutations, shown in red, are easily identified. Cooper
`
`Decl. ¶ 48.
`
`Guardant’s patented method tags cfDNA molecules prior to amplification with molecular
`
`identifiers called barcodes. The figure below is from another of Guardant’s publications. On the
`
`left, there is cell-free DNA. The red and green colored fragments are the tumor DNA. Barcodes
`
`are shown as colored segments at the ends of each piece of DNA. Later, the barcoded cfDNA
`
`fragments are copied, or amplified, to increase the overall signal. The molecular tags are copied
`
`along with them and then ultimately sequenced. Because each copy of a tagged molecule will have
`
`the same barcodes, the barcodes can be used to help identify the DNA sequence information that
`
`originated from a particular tagged cell-free DNA molecule. Cooper Decl. ¶¶ 47, 49, 50.
`
`
`
`Cooper Decl. ¶ 49; Cooper Decl. Ex. 6 [J.J. Odegaard, et al., Validation of a plasma-based
`
`comprehensive cancer genotyping assay utilizing orthogonal tissue-and plasma-based
`
`methodologies] at 3542.
`
`Tagging each fragment of cfDNA with a different barcode is challenging because there are
`
`often billions of fragments that must be identified. It is difficult to generate so many distinct bar
`
`11
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`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 15 of 24 PageID #: 2221
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`codes without generating sequences that reduce the consistency, efficiency or accuracy of the test.
`
`The inventors of the ’085 and ’086 Patents recognized that uniquely tagging each cfDNA fragment
`
`is not necessary. Rather, the number of tags need only meet a sufficient threshold, depending on
`
`the amount of DNA that is being analyzed. Cooper Decl. ¶¶ 51-52.
`
`Once cfDNA is tagged, it is amplified using known techniques. The amplified DNA is
`
`sequenced, generating sequence reads. Guardant’s patented algorithms compare each single
`
`sequence read to a previously determined sequence for a representative human genome. This
`
`process is commonly referred to as mapping or aligning. The mapping process provides additional
`
`context to determine whether sequence reads are copies of the same parent. This is especially
`
`important when not every cfDNA is uniquely tagged. Cooper Decl. ¶¶ 53-55.
`
`Errors during amplification and sequencing can result in false positives, shown as purple
`
`X’s, which may be indistinguishable from real mutations, shown with red X’s:
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`Cooper Decl. ¶ 552
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`
`
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`2 Guardant Health, Inc.’s Technology Tutorial from Case Nos. 1:17-cv-01616 (D.I. 52) and 1:17-
`cv-01623 (D.I. 58).
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`12
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`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 16 of 24 PageID #: 2222
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`Because Guardant’s tagging process tracks each sequence read back to their original parent,
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`Guardant can group sequence reads into families representing an original cfDNA molecule.
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`Families are sequence reads that have the same barcodes and map to the same position in the
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`genome. Mutations that only appear in a subset of sequence reads in a family, shown circled in
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`purple in the below figure, likely stem from amplification or sequencing errors. Mutations that
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`appear in all or a threshold number of sequence reads in a family are shown as red X’s and likely
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`correspond to true mutations in the original cfDNA fragment pool.
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`
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`Cooper Decl. ¶¶ 57-583
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`
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`As shown below, a consensus sequence can be generated using the information from the
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`sequence reads of each family. As noted, mutations that only appear in one or a few sequence reads
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`are eliminated from the consensus sequence. Mutations that appear in at least a certain threshold
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`number of sequence reads are likely true mutations and are preserved.
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`3 Guardant Health, Inc.’s Technology Tutorial from Case Nos. 1:17-cv-01616 (D.I. 52) and 1:17-
`cv-01623 (D.I. 58).
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`13
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`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 17 of 24 PageID #: 2223
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`
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`Cooper Decl. ¶ 584. Determinations of rare mutations associated with cancer can be then made
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`by comparing entire families of sequence reads. Cooper Decl. ¶ 59.
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`IV. ARGUMENT
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`“The factors the trial court considers when determining whether to grant a preliminary
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`injunction are of longstanding and universal applicability. As the Supreme Court recently
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`reiterated, there are four: ‘[a] plaintiff seeking a preliminary injunction must establish [1] that he
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`is likely to succeed on the merits, [2] that he is likely to suffer irreparable harm in the absence of
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`preliminary relief, [3] that the balance of equities tips in his favor, and [4] that an injunction is in
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`the public interest.’” Titan Tire Corp. v. Case New Holland, Inc., 566 F.3d 1372, 1375–76 (Fed.
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`Cir. 2009). All of these factors weigh strongly in favor of preliminarily enjoining FMI from
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`offering or performing its FoundationOne® Liquid CDx liquid biopsy.
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`A.
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`Guardant is likely to succeed on the merits.
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`A reasonable likelihood of success requires a showing of infringement and that the asserted
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`patent will withstand a validity challenge. See, e.g., Reebok Int’l Ltd. v. J. Baker, Inc., 32 F.3d
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`1552, 1555 (Fed. Cir. 1994).
`
`
`4 Guardant Health, Inc.’s Technology Tutorial from Case Nos. 1:17-cv-01616 (D.I. 52) and 1:17-
`cv-01623 (D.I. 58).
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`14
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`Case 1:20-cv-01580-LPS Document 13 Filed 12/18/20 Page 18 of 24 PageID #: 2224
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`1.
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`FoundationOne® Liquid CDx infringes the ’085 and ’086 Patents
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`In his declaration, Dr. Cooper establishes that FoundationOne® Liquid CDx uses the
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`methods disclosed and claimed in Guardant’s ’085 and ’086 Patents. Cooper Decl. ¶¶ 76-211.
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`The FDA Label states that FoundationOne® Liquid CDx is “performed at Foundation Medicine,
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`Inc. in Cambridge, MA.” Cooper Decl. Ex. 7 [FoundationOne® Liquid CDx FDA Label] at 2.
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`The ’085 and ’086 Patents are both continuations of U.S. Application No. 15/669,779,
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`which is in turn a continuation of U.S. Application No. 15/076,565, which issued as U.S. Patent
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`No. 9,902,992 (“the ’992 Patent). Stephens Decl. Exs. 4-6 [’085, ’086 and ’992 Patents] cover
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`pages, Cooper Decl. ¶ 67. Guardant has accused FMI’s liquid biopsies of infringing the ’992
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`Patent in the 1616 Action. The FoundationOne® Liquid CDx FDA Label states that it is based on
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`the same liquid biopsies Guardant accuses in the 1616 Action, and that the workflow is
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`substantially similar. Cooper Decl. Ex. 7 [FoundationOne® Liquid CDx FDA Label] at 31. The
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`chart at Cooper Decl. ¶ 136 shows that Claim 1 of the ’992 Patent includes similar limitations to
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`those of Claim 1 of the ’085 Patent and the chart at Cooper Decl. ¶ 77¶ 136 shows the same for
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`Claim 1 of the ’086 Patent.
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`In the 1616 case, the only non-infringement argument FMI offered for Claim 1 of the ‘’992
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`Patent was (e): “the accused products do not