Case 1:20-cv-01580-LPS Document 43 Filed 03/05/21 Page 1 of 194 PageID #: 9891
`
`
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`GUARDANT HEALTH, INC.,
`
`Plaintiff,
`
`v.
`
`FOUNDATION MEDICINE, INC.,
`
`Defendant.
`
`
`
`
`
`C. A. No. 20-cv-1580-LPS
`
`
`)
`)
`)
`)
`)
`)
`)
`)
`)
`
`
`
`DECLARATION OF STACEY GABRIEL, PH.D.
`
`
`
`
`
`ii
`
`Public Version Filed: March 5, 2021
`
`Confidential Version Filed: February 26, 2021
`
`PUBLIC VERSION
`
`

`

`Case 1:20-cv-01580-LPS Document 43 Filed 03/05/21 Page 2 of 194 PageID #: 9892
`
`TABLE OF CONTENTS
`
`
`
`I.
`
`II.
`
`INTRODUCTION AND SCOPE OF OPINIONS ..........................................................1
`
`MATERIALS CONSIDERED .......................................................................................3
`
`III.
`
`QUALIFICATIONS AND PROFESSIONAL EXPERIENCE .......................................3
`
`IV.
`
`A PERSON OF ORDINARY SKILL IN THE ART ......................................................5
`
`V.
`
`RELEVANT LEGAL STANDARD ..............................................................................6
`
`A.
`
`B.
`
`Obviousness .......................................................................................................6
`
`Indefiniteness .....................................................................................................9
`
`C. Written Description ............................................................................................9
`
`VI.
`
`CLAIM CONSTRUCTION ...........................................................................................9
`
`VII. TECHNOLOGY BACKGROUND AND STATE OF THE ART ................................ 12
`
`A.
`
`B.
`
`C.
`
`D.
`
`E.
`
`F.
`
`G.
`
`H.
`
`I.
`
`DNA ................................................................................................................ 12
`
`Genetic Mutations ............................................................................................ 13
`
`Discovery and Subsequent Analysis of Cell-Free DNA .................................... 15
`
`Sequencing ...................................................................................................... 18
`
`Alignment/Mapping ......................................................................................... 21
`
`Analysis of Sequence Reads ............................................................................. 22
`
`Molecular Barcodes ......................................................................................... 22
`
`Identifying Errors ............................................................................................. 26
`
`Known Error-Correction Methods for Cell Free DNA ...................................... 28
`
`VIII. SUMMARY OF THE '085 AND '086 PATENTS ........................................................ 30
`
`IX.
`
`THE ASSERTED CLAIMS ARE OBVIOUS .............................................................. 33
`
`A.
`
`Overview of Prior Art References .................................................................... 34
`
`1.
`
`2.
`
`Schmitt ................................................................................................. 34
`
`Hendricks ............................................................................................. 37
`
`
`
`i
`
`

`

`Case 1:20-cv-01580-LPS Document 43 Filed 03/05/21 Page 3 of 194 PageID #: 9893
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`
`
`3.
`
`4.
`
`5.
`
`Fan ....................................................................................................... 38
`
`Forshew ................................................................................................ 38
`
`Rava ..................................................................................................... 39
`
`B.
`
`Schmitt in view of Common Knowledge Renders the Asserted
`Claims Obvious ............................................................................................... 40
`
`1.
`
`Claim 1 of the '085 Patent Is Obvious over Schmitt in view of
`Common Knowledge ............................................................................ 40
`
`a.
`
`b.
`
`c.
`
`d.
`
`e.
`
`f.
`
`g.
`
`h.
`
`i.
`
`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.............. 41
`
`obtaining a population comprising the double-
`stranded cfDNA molecules from the blood sample
`from the subject......................................................................... 49
`
`ligating a set of molecular barcodes to both ends of a
`plurality of the double-stranded cfDNA molecules..................... 51
`
`using more than a 30× molar excess of molecular
`barcodes relative to the double-stranded cfDNA
`molecules to produce tagged parent polynucleotides ................. 53
`
`wherein a given molecular barcode is a member of a
`set of molecular barcodes comprising 2 to 1,000,000
`different molecular barcode sequences ...................................... 56
`
`wherein at least 20% of the double-stranded cfDNA
`molecules from the population of cfDNA molecules
`are attached to molecular barcodes .......................................... 58
`
`amplifying a plurality of the tagged parent
`polynucleotides to produce progeny polynucleotides
`with associated molecular barcodes .......................................... 75
`
`selectively enriching a subset of the progeny
`polynucleotides for target regions associated with
`cancer, whereby enriched progeny polynucleotides
`are generated ............................................................................ 76
`
`sequencing a portion of the enriched progeny
`polynucleotides to produce sequencing reads of the
`
`
`
`ii
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`

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`Case 1:20-cv-01580-LPS Document 43 Filed 03/05/21 Page 4 of 194 PageID #: 9894
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`
`
`progeny polynucleotides with associated molecular
`barcodes ................................................................................... 78
`
`aligning a plurality of the sequencing reads to a
`reference sequence .................................................................... 82
`
`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 ................................................................................. 83
`
`detecting, from among the families, the presence or
`absence of somatic genetic variants .......................................... 87
`
`quantifying a plurality of somatic genetic variants
`detected as present to generate the genetic profile of
`the tumor .................................................................................. 89
`
`j.
`
`k.
`
`l.
`
`m.
`
`1.
`
`Claim 1 of the '086 Patent Is Obvious over Schmitt in view of
`Common Knowledge ............................................................................ 91
`
`a.
`
`b.
`
`c.
`
`d.
`
`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, ................................................ 92
`
`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 ................................................... 92
`
`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 .................................................... 95
`
`using more than a 10× molar excess of molecular
`barcodes relative to the population of cfDNA
`molecules .................................................................................. 95
`
`
`
`iii
`
`

`

`Case 1:20-cv-01580-LPS Document 43 Filed 03/05/21 Page 5 of 194 PageID #: 9895
`
`e.
`
`f.
`
`g.
`
`h.
`
`i.
`
`j.
`
`
`
`wherein the 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 and fewer than a number of cfDNA
`molecules that map to the mappable base position .................... 96
`
`wherein at least 20% of the cfDNA molecules from the
`population of cfDNA molecules are attached to
`molecular barcodes ................................................................... 98
`
`amplifying a plurality of the non-uniquely tagged
`parent polynucleotides to produce progeny
`polynucleotides with associated molecular barcodes ................. 99
`
`sequencing a plurality of the progeny polynucleotides
`to produce sequencing reads of the progeny
`polynucleotides with associated molecular barcodes ................. 99
`
`mapping a plurality of the sequencing reads to the
`reference sequence to generate mapped sequencing
`reads ....................................................................................... 100
`
`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 .................................................................. 100
`
`k.
`
`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 ............................ 101
`
`C.
`
`Schmitt, Hendricks, and Common Knowledge Render the Asserted
`Claims Obvious ............................................................................................. 101
`
`1.
`
`Claim 1 of the '085 Patent Is Obvious over Schmitt and
`Hendricks in view of Common Knowledge......................................... 101
`
`a.
`
`Using more than a 30× molar excess of molecular
`barcodes relative to the double-stranded cfDNA
`molecules to produce tagged parent polynucleotides
`… wherein at least 20% of the double-stranded cfDNA
`
`
`
`iv
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`

`

`Case 1:20-cv-01580-LPS Document 43 Filed 03/05/21 Page 6 of 194 PageID #: 9896
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`
`
`
`
`molecules from the population of cfDNA molecules
`are attached to molecular barcodes ........................................ 102
`
`b.
`
`Motivation to Combine Schmitt and Common
`Knowledge with Hendricks ..................................................... 104
`
`c.
`
`Reasonable Expectation of Success ......................................... 105
`
`2.
`
`Claim 1 of the '086 Patent Is Obvious over Schmitt and
`Hendricks in view of Common Knowledge......................................... 106
`
`a.
`
`Using more than a 10× molar excess of molecular
`barcodes relative to the population of cfDNA
`molecules… wherein at least 20% of the cfDNA
`molecules from the population of cfDNA molecules
`are attached to molecular barcodes ........................................ 106
`
`b.
`
`Motivation to Combine Schmitt and Common
`Knowledge with Hendricks ..................................................... 107
`
`c.
`
`Reasonable Expectation of Success ......................................... 107
`
`D.
`
`Schmitt and Hendricks in view of Fan or Forshew Render the
`Asserted Claims Obvious ............................................................................... 107
`
`1.
`
`Claim 1 of the '085 Patent Is Obvious over Schmitt and
`Hendricks in view of Fan or Forshew ................................................. 107
`
`a.
`
`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
`… obtaining a population comprising the double-
`stranded cfDNA molecules from the blood sample
`from the subject … ligating a set of molecular
`barcodes to both ends of a plurality of the double-
`stranded cfDNA molecules ...................................................... 108
`
`b.
`
`Motivation to Combine Schmitt, Hendricks, Fan or
`Forshew .................................................................................. 109
`
`c.
`
`Reasonable Expectation of Success ......................................... 114
`
`2.
`
`Claim 1 of the '086 Patent Is Obvious over Schmitt and
`Hendricks in view of Fan or Forshew ................................................. 118
`
`a.
`
`A method for detecting a presence or absence of one
`or more somatic genetic variants in cell-free
`
`
`
`v
`
`

`

`Case 1:20-cv-01580-LPS Document 43 Filed 03/05/21 Page 7 of 194 PageID #: 9897
`
`
`
`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 different
`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 ........................ 118
`
`b.
`
`Motivation to Combine Schmitt and Hendricks with
`Fan or Forshew ....................................................................... 119
`
`c.
`
`Reasonable Expectation of Success ......................................... 119
`
`E.
`
`Rava, alone or as evidenced by the NEB manual, and Schmitt Render
`the Asserted Claims Obvious ......................................................................... 120
`
`1.
`
`Claim 1 of the '085 Patent Is Obvious over Rava, alone or as
`evidenced by the NEB manual, in view of Schmitt ............................. 120
`
`a.
`
`b.
`
`c.
`
`d.
`
`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 ................................................ 120
`
`obtaining a population comprising the double-
`stranded cfDNA molecules from the blood sample
`from the subject....................................................................... 122
`
`ligating a set of molecular barcodes to both ends of a
`plurality of the double-stranded cfDNA molecules................... 124
`
`using more than a 30× molar excess of molecular
`barcodes relative to the double-stranded cfDNA
`molecules to produce tagged parent polynucleotides ............... 125
`
`
`
`vi
`
`

`

`Case 1:20-cv-01580-LPS Document 43 Filed 03/05/21 Page 8 of 194 PageID #: 9898
`
`
`
`wherein a given molecular barcode is a member of a
`set of molecular barcodes comprising 2 to 1,000,000
`different molecular barcode sequences .................................... 129
`
`wherein at least 20% of the double-stranded cfDNA
`molecules from the population of cfDNA molecules
`are attached to molecular barcodes ........................................ 129
`
`amplifying a plurality of the tagged parent
`polynucleotides to produce progeny polynucleotides
`with associated molecular barcodes ........................................ 130
`
`selectively enriching a subset of the progeny
`polynucleotides for target regions associated with
`cancer, whereby enriched progeny polynucleotides
`are generated .......................................................................... 131
`
`sequencing a portion of the enriched progeny
`polynucleotides to produce sequencing reads of the
`progeny polynucleotides with associated molecular
`barcodes ................................................................................. 132
`
`aligning a plurality of the sequencing reads to a
`reference sequence .................................................................. 133
`
`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 ............................................................................... 134
`
`detecting, from among the families, the presence or
`absence of somatic genetic variants ........................................ 134
`
`quantifying a plurality of somatic genetic variants
`detected as present to generate the genetic profile of
`the tumor ................................................................................ 135
`
`Motivation to Combine Rava, alone or as evidenced
`by the NEB Manual, and Schmitt ............................................ 136
`
`e.
`
`f.
`
`g.
`
`h.
`
`i.
`
`j.
`
`k.
`
`l.
`
`m.
`
`n.
`
`
`
`vii
`
`

`

`Case 1:20-cv-01580-LPS Document 43 Filed 03/05/21 Page 9 of 194 PageID #: 9899
`
`
`
`o.
`
`Reasonable Expectation of Success ......................................... 137
`
`2.
`
`Claim 1 of the '086 Patent Is Obvious over Rava, alone or as
`evidenced by the NEB manual, in view of Schmitt ............................. 138
`
`a.
`
`b.
`
`c.
`
`d.
`
`e.
`
`f.
`
`g.
`
`h.
`
`i.
`
`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, .............................................. 138
`
`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 ................................................. 139
`
`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 .................................................. 140
`
`using more than a 10× molar excess of molecular
`barcodes relative to the population of cfDNA
`molecules ................................................................................ 140
`
`wherein the 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 and fewer than a number of cfDNA
`molecules that map to the mappable base position .................. 141
`
`wherein at least 20% of the cfDNA molecules from the
`population of cfDNA molecules are attached to
`molecular barcodes ................................................................. 141
`
`amplifying a plurality of the non-uniquely tagged
`parent polynucleotides to produce progeny
`polynucleotides with associated molecular barcodes ............... 142
`
`sequencing a plurality of the progeny polynucleotides
`to produce sequencing reads of the progeny
`polynucleotides with associated molecular barcodes ............... 142
`
`mapping a plurality of the sequencing reads to the
`reference sequence to generate mapped sequencing
`reads ....................................................................................... 143
`
`
`
`viii
`
`

`

`Case 1:20-cv-01580-LPS Document 43 Filed 03/05/21 Page 10 of 194 PageID #: 9900
`
`
`
`j.
`
`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 .................................................................. 143
`
`k.
`
`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 ............................ 144
`
`l.
`
`Motivation to Combine Rava and Schmitt................................ 144
`
`m.
`
`Reasonable Expectation of Success ......................................... 145
`
`X.
`
`THE ASSERTED CLAIMS ARE INDEFINITE ........................................................ 145
`
`A.
`
`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 …wherein a given molecular barcode is a member of a set
`of molecular barcodes comprising 2 to 1,000,000 different molecular
`barcode sequences .......................................................................................... 146
`
`wherein the 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 and fewer than a number
`of cfDNA molecules that map to the mappable base position ......................... 149
`
`XI.
`
`THE ASSERTED CLAIMS LACK SUFFICIENT WRITTEN
`DESCRIPTION ......................................................................................................... 152
`
`A.
`
`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 …wherein a given molecular barcode is a member of a set
`of molecular barcodes comprising 2 to 1,000,000 different molecular
`barcode sequences .......................................................................................... 153
`
`XII.
`
`SUPPLEMENTATION OF OPINIONS .................................................................... 154
`
`
`
`ix
`
`

`

`Case 1:20-cv-01580-LPS Document 43 Filed 03/05/21 Page 11 of 194 PageID #: 9901
`
`
`
`I.
`
`INTRODUCTION AND SCOPE OF OPINIONS
`
`1.
`
`I, Stacey Gabriel, have been retained as an expert in this case by counsel for
`
`Foundation Medicine, Inc. (“Foundation Medicine”). I have previously offered expert opinions in
`
`other proceedings involving Foundation Medicine and Guardant Health, Inc. (“Guardant”),
`
`including Guardant Health, Inc. v. Foundation Medicine, Inc., Case No. 1:17-cv-01616 (D. Del.
`
`Nov. 9, 2017) (the “1616 Action”) and related inter partes review (“IPR”) proceedings in front of
`
`the United States Patent Trial and Appeal Board.
`
`2.
`
`I understand that on December 10, 2020, Guardant filed a motion for a preliminary
`
`injunction to prohibit Foundation Medicine from performing or offering FoundationOne® Liquid
`
`CDx (the “Accused Product”) in the United States. I also understand that Guardant submitted a
`
`Declaration of Gregory Cooper, Ph.D. in support of its motion (the “Cooper Declaration”).
`
`3.
`
`I am informed that for purposes of the preliminary injunction Guardant asserts only
`
`independent Claim 1 of United States Patent Number 10,704,085 (the “'085 patent”) and
`
`independent Claim 1 of United States Patent Number 10,704,086 (the “'086 patent”) (collectively
`
`the “Asserted Claims”).1 I am also aware that Guardant has asserted five additional U.S. Patents
`
`that are not at issue in this preliminary injunction. These patents are U.S. Patent Nos. 10,501,810,
`
`10,793,916, 10,801,063, 9,840,743, and 9,834,822 (the “'822 patent”). My opinions in this
`
`declaration pertain solely to the Asserted Claims of the '085 and '086 patents.
`
`4.
`
`I have been asked by counsel for Foundation Medicine to provide opinions for
`
`purposes of this preliminary injunction proceeding only regarding (1) whether the Asserted Claims
`
`would have been obvious to a person of ordinary skill in the art (a “POSA”) as of the alleged
`
`
`1 I understand copies of the '085 and '086 patents were submitted previously by Guardant. See D.I. 9, Exs. 4, 5.
`
`
`
`1
`
`

`

`Case 1:20-cv-01580-LPS Document 43 Filed 03/05/21 Page 12 of 194 PageID #: 9902
`
`
`
`priority date of the '085 and '086 patents; (2) whether the Asserted Claims are indefinite; and (3)
`
`whether the Asserted Claims have adequate written description support.
`
`5.
`
`I understand that Foundation Medicine also asserts that it does not infringe the
`
`Asserted Claims. I have not provided an opinion herein as to infringement.
`
`6.
`
`As discussed in Sections IX, X, and XI, in my opinion, the Asserted Claims of the
`
`'085 and '086 patents are invalid for at least the following reasons:
`
`a. The Asserted Claims are invalid because they are obvious over Schmitt2 in
`
`view of common knowledge in the art as shown by certain other prior art
`
`references described below, and further specifically in view of Hendricks3;
`
`b. The Asserted Claims are invalid because they are obvious over Schmitt in
`
`view of Hendricks and either Fan4 or Forshew5;
`
`c. The Asserted Claims are invalid because they are obvious over Rava6 in view
`
`of Schmitt as evidenced by the New England Biolabs (NEB) Manual7 in view
`
`of Schmitt;
`
`d. Step (b) of Claim 1 of the '085 patent is invalid because it is indefinite;
`
`e. Step (a) of Claim 1 of the '086 patent is invalid because it is indefinite;
`
`f. Step (b) of Claim 1 of the '085 patent is invalid for lack of written description.
`
`7.
`
`I am being compensated for the time I spend on this matter at a rate of
`
`.
`
`My compensation is not contingent on reaching any particular finding or conclusion, or on any
`
`
`2 Ex. 93, U.S. Patent No. 9,752,188 (“Schmitt”).
`3 Ex. 72, International Publication Number WO 2012/099832 A2 (“Hendricks”).
`4 Ex. 39, Fan et al., “Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood,”
`Proc. Natl. Acad. Sci. USA 2008, 105(42), 16266-16271 (“Fan”).
`5 Ex. 59, Forshew et al., “Noninvasive Identification and Monitoring of Cancer Mutations by Targeted Deep
`Sequencing of Plasma DNA,” Sci. Transl. Med. 2012, 4(136), 1-12 (“Forshew”).
`6 Ex. 51, WO 2011/091046 (“Rava”).
`7 Ex. 61, NEBNext® DNA Library Prep Reagent Set for Illumina®: Instruction Manual, NEB (June 2012) (“NEB
`Manual”).
`
`
`
`2
`
`

`

`Case 1:20-cv-01580-LPS Document 43 Filed 03/05/21 Page 13 of 194 PageID #: 9903
`
`
`
`outcome in the case. The opinions contained in this declaration are mine and are based upon my
`
`knowledge, direct experience in the field, and study of the materials discussed below.
`
`II. MATERIALS CONSIDERED
`
`8.
`
`In forming the opinions herein expressed, I have considered and/or relied upon:
`
`a. The '085 and '086 patents, including their prosecution histories;
`
`b. The prior art references relied upon herein;
`
`c. The additional references, documents, deposition testimony, and publicly
`
`available information cited herein; and
`
`d. My expertise in the field.8
`
`9.
`
`I reserve the right to supplement, change, clarify, or modify my opinions should
`
`additional information and/or documentation become available to me. I also reserve the right to
`
`create graphics for use in connection with any hearing or trial testimony.
`
`III. QUALIFICATIONS AND PROFESSIONAL EXPERIENCE
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`10. My qualifications are described below and more fully in my curriculum vitae, a
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`copy of which is attached as Appendix A to this declaration.
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`11.
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`I am Senior Director of the Genomics Platform at the Broad Institute of MIT and
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`Harvard. I joined the Broad Institute, which was formerly known as the Whitehead Institute Center
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`for Genome Research, in 1998. I have a Bachelor of Science degree from Carnegie Mellon
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`University (1993), and a Ph.D. in Genetics from Case Western Reserve University (1998). I am a
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`co-author on more than 230 publications in the fields of cancer genomics and human genetics. My
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`publications authored in the previous 10 years are listed in my curriculum vitae.
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`8 All exhibits referred to herein are attached to the Appendix in Support of Foundation Medicine’s Brief in Opposition
`to Guardant’s Motion for Preliminary Injunction.
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`3
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`12. My research has been primarily directed to genome sequencing. As a result, most
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`of my publications involve the application of sequencing technology to the study of human disease.
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`My research often involves comparing the DNA of individuals with and without a specific disease
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`to determine whether there is association of genetic variation with that disease. My publications
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`describe the identification of genes and mutations that are associated with diseases including
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`cancer, diabetes, arthritis, multiple sclerosis, and cardiovascular diseases. Additionally, I have
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`published protocols for methods that I have helped develop to prepare DNA for use in massively
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`parallel or “next generation” sequencing.
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`13.
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`The unit of the Broad Institute, which I have directed for the past 12 years, has been
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`the major data producer for The Cancer Genome Atlas (“TCGA”) (funded by the National Cancer
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`Institute and the National Human Genome Research Institute). This has been one of the largest
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`and most comprehensive research programs in cancer genomics ever undertaken, involving the
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`characterization of more than 10,000 tumor samples across 20 tumor types. I have been involved
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`with this program since its initiation in 2005. I have served as a Principle Investigator for TCGA
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`grants and contracts, and I have served on the program’s Executive and Steering committee. I am
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`also an author on at least 15 TCGA manuscripts. Just last year, in 2019, I was part of a team that
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`received an award from the American Association for Cancer Research (“AACR”) for our work
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`on TCGA.
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`14.
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`I have served and continue to serve on various editorial and advisory boards related
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`to genomic research. For example, from February 2007 to December 2010, I served on the
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`External Advisory Committee for National Heart, Lung, and Blood Institute (“NHLBI”)
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`Resequencing and Genotyping Service. From July 2009 to June 2013, I was a standing member
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`of the NIH Study Section of Genomics, Computational Biology and Technology. I have also
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`served on numerous ad hoc review panels for the NIH. From May 2010 to the present, I have
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`served on the Scientific Advisory Board of Genome Canada. I also have served on the editorial
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`boards of the journals Human Genetics and Genome Research.
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`15.
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`I have presented lectures at a variety of academic and industry conferences. I
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`typically lecture about 6 to 8 times per year at conferences involving genomics. For example, I
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`have presented at conferences held by the International Congress of Human Genetics, the
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`American Society of Human Genetics, the American Association for Cancer Research, the
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`American Heart Association, the Multiple Myeloma Research Foundation, and the American
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`Association for Cancer Research. These presentations were primarily focused on using genomics
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`to understand the genetic basis of human disease. I was named to the list of the World’s Most
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`Influential Scientific Minds in 2014 and 2015 because I published the l