2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 1
`
` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`___________________
`Foresight Diagnostics Inc.,
`Petitioner,
`v.
`Personalis, Inc.,
`Patent Owner.
`____________________
`IPR2023-00224 U.S. Patent No. 11,384,394
`IPR2023-00317 U.S. Patent No. 11,408,033
`____________________
`
`DEPOSITION OF DR. JOHN QUACKENBUSH
`APPEARING REMOTELY
`February 1, 2024
`10:00 a.m.
`
`Reported by: Eileen Mulvenna, CSR/RMR/CRR
`______________________________________________________
`DIGITAL EVIDENCE GROUP
`1730 M Street, NW, Suite 812
`Washington, D.C. 20036
`(202) 232-0646
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 1
`
` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`___________________
`Foresight Diagnostics Inc.,
`Petitioner,
`v.
`Personalis, Inc.,
`Patent Owner.
`____________________
`IPR2023-00224 U.S. Patent No. 11,384,394
`IPR2023-00317 U.S. Patent No. 11,408,033
`____________________
`
`DEPOSITION OF DR. JOHN QUACKENBUSH
`APPEARING REMOTELY
`February 1, 2024
`10:00 a.m.
`
`Reported by: Eileen Mulvenna, CSR/RMR/CRR
`______________________________________________________
`DIGITAL EVIDENCE GROUP
`1730 M Street, NW, Suite 812
`Washington, D.C. 20036
`(202) 232-0646
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 2
`REMOTE DEPOSITION of DR. JOHN QUACKENBUSH,
`a witness on behalf of Foresight Diagnostics in the
`above-titled action, held on Thursday, February 1,
`2024, commencing at approximately 10:00 a.m., before
`Eileen Mulvenna, CSR/RMR/CRR/RDR, Certified
`Shorthand Reporter, Registered Merit Reporter,
`Certified Realtime Reporter, Registered Diplomate
`Reporter, and Notary Public of the State of New
`York.
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`A P P E A R A N C E S:
`
`Page 3
`
`ANDREW KRAUSE, ESQUIRE
`Attorneys for Petitioner and the Witness
`Irell & Manella LLP
`1800 Avenue of the Stars, Suite 900
`Los Angeles, California 90067
`310.277.1010
`akrause@irell.com
`
`NATHANAEL LUMAN, Ph.D., ESQUIRE
`Attorneys for Patent Owner
`KNOBBE MARTEN OLSON & BEAR LLP
`2040 Main Street, 14th Floor
`Irvine, California 92614
`949.760.0404
`nate.luman@knobbe.com
`
`ALSO PRESENT:
`Stephen Moore, Esquire (Personalis)
`Henry Marte, Exhibit Technician
`
`1
`
`2 3
`
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 4
`
` I N D E X
`WITNESS EXAMINATION BY PAGE
`DR. JOHN QUACKENBUSH
` MR. LUMAN 12
` MR. KRAUSE 292
`
` E X H I B I T S
` PAGE
`Exhibit 1002 No Bates Numbers, 149
` Development of Personalized
` Tumor Biomarkers Using
` Massively Parallel
` Sequencing, Cancer
` Genetics, 2010, Leary et
` al.
`Exhibit 1006 No Bates Numbers, Targeted 62
` enrichment of genomic DNA
` regions for next-generation
` sequencing, Briefings in
` Functional Genomics, Vol.
` 10, No. 6, 2011, Mertes et
` al.
`
`1
`2
`3
`4
`5
`
`6 7
`
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 5
`
`(Continued)
`
`PAGE
`E X H I B I T S
`Exhibit 1008 No Bates Numbers, Cancer 273
`Genome Scanning in Plasma:
`Detection of
`Tumor-Associated Copy
`Number Aberrations,
`Single-Nucleotide Variants,
`and Tumoral Heterogeneity
`by Massively Parallel
`Sequencing, Clinical
`Chemistry 59:1, 2013, Chan
`et al.
`Exhibit 1020 No Bates Numbers,
`Declaration of John
`Quackenbush, Ph.D. in
`Support of Petition for
`Inter Partes Review,
`IPR2023-00317
`
`82
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`(Continued)
`
`Page 6
`
`PAGE
`16
`
`E X H I B I T S
`Exhibit 1030 No Bates Numbers,
`Noninvasive Identification
`and Monitoring of Cancer
`Mutations by Targeted Deep
`Sequencing of Plasma DNA,
`Tim Forshew et al., Science
`Translational Medicine 4,
`2012, Tim Forshew et al.
`Exhibit 1033 No Bates Numbers,
`High-Throughput Detection
`of Actionable Genomic
`Alterations in Clinical
`Tumor Samples by Targeted,
`Massively Parallel
`Sequencing, Research
`Article, Wagle et al.
`Exhibit 1216 No Bates Numbers, Amplicon 22
`NGS battles begin in
`earnest - Enseqlopedia
`
`90
`
`1
`
`2 3
`
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 7
`
`1
`
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`(Continued)
` E X H I B I T S PAGE
`Exhibit 1223 No Bates Numbers, 180
` Deposition of Henry Morrice
` Furneaux, Ph.D.
`Exhibit 1225 No Bates Numbers, 15
` Declaration of John
` Quackenbush, Ph.D. in
` Support of Petitioner's
` Reply to Patent Owner
` Response, IPR2023-0024 and
` IPR2023-00317
`Exhibit 2031 No Bates Numbers, 145
` Declaration of Henry
` Morrice Furneaux, Ph.D.
`Exhibit 2157 No Bates Numbers, 113
` Gender-Specific Molecular
` and Clinical Features
` Underlie Malignant Pleural
` Mesothelioma, Molecular and
` Cellular Pathobiology,
` 2015, DeRienzo and
` Quackenbush et al.
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 8
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`(Continued)
`
`PAGE
`E X H I B I T S
`Exhibit 2158 No Bates Numbers, Exome 124
`sequencing-based
`copy-number variation and
`loss of heterozygosity
`detection: Exome CNV,
`Bioinformatics, Vol. 27,
`No. 19, 2011,
`Sathirapongsasuti and
`Quackenbush et al.
`Exhibit 2166 No Bates Numbers, Detection 141
`and Diagnostic Utilization
`of Cellular and Cell-Free
`Tumor DNA, Annual Review of
`Pathology: Mechanisms of
`Disease, 2021, Jonathan C.
`Dudley and Maximilian Diehn
`Exhibit 2178 No Bates Numbers, The 31
`Chicago Manual of Style,
`Sixteenth Edition, The
`University of Chicago Press
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 9
`
`PAGE
`38
`
`82
`
`170
`
`(Continued)
`
`E X H I B I T S
`Exhibit 2179 No Bates Numbers, The
`American Heritage
`Dictionary of the English
`Language Fourth Edition
`Exhibit 2180 No Bates Numbers,
`Declaration of John
`Quackenbush, Ph.D. in
`Support of Petition for
`Inter Partes Review,
`IPR2023-002247, U.S. Patent
`No. 11,408,033
`Exhibit 2182 No Exhibit Numbers,
`Declaration of John
`Quackenbush, Ph.D. in
`Support of Petition for
`Inter Partes Review,
`IPR2023-00546, U.S. Patent
`No. 10,450,611
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 10
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`(Continued)
`
`E X H I B I T S PAGE
`Exhibit 2183 No Bates Numbers, Detection 211
`of Chromosomal Alterations
`in the Circulation of
`Cancer Patients with
`Whole-Genome Sequencing,
`Diagnostics,
`www.ScienceTranslationalMed
`icine.org 28 November 2012
`Exhibit 2184 No Bates Numbers, Cancer 218
`detection using
`whole-genome sequencing of
`cell free DNA, Oncotarget,
`August, Vol. 4, No. 8, 2013
`Exhibit 2185 No Bates Numbers, 255
`Predicting Radiotherapy
`Responses and Treatment
`Outcomes Through Analysis
`of Circulating Tumor DNA,
`Seminars in Radiation
`Oncology, 2015
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 11
`
` (Continued)
`
`E X H I B I T S PAGE
` Exhibit 2186 No Bates Numbers, Potential 259
`clinical utility of
`ultrasensitive circulating
`tumor DNA detection withx
`CAPP-Seq, Expert Reviews
`Mol. Diagn., 2015
` Exhibit 2187 No Bates Numbers, Accurate 277
`whole human genome
`sequencing using reversible
`terminator chemistry,
`Nature, 2008, David Bentley
`et al.
`Exhibit 2022 No Bates Numbers, Sequencing 174
`depth and coverage: key
`considerations in genomic
`analyses, Nature Reviews |
`Genetics, 2014, Sims et al.
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 12
`
`(Witness sworn.)
`MR. LUMAN: The time is 7:01 Pacific.
`Good morning. My name is Nate Luman, and I'm
`going to be taking the deposition today.
` DR. JOHN QUACKENBUSH,
` having been duly sworn by Eileen Mulvenna,
` a Notary Public of the State of New York,
` was examined and testified as follows:
` EXAMINATION
` BY MR. LUMAN:
`Dr. Quackenbush, can you hear me okay?
`Q.
`Yes, I can. Can you hear me well?
`A.
`I can.
`Q.
`Thank you.
`A.
`Would you please state your full name
`Q.
` and home address for the record?
`A.
`Sure. My name is John, J-O-H-N,
` Quackenbush, Q-U-A-C-K-E-N-B-U-S-H. And I live at
` 86 Walpole, W-A-L-P-O-L-E, Street in Dover,
` Massachusetts. The ZIP is 02030.
`Q.
`Do you understand that you're under
` oath today?
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 13
`
` A. Yes, sir.
` Q. Is there any reason that you would be
` unable to give truthful and accurate testimony
` today?
` A. No, there is not.
` Q. So I'll just do the ground rules
` quickly. I'm going to be asking questions, and the
` court reporter is taking down my questions and your
` answers.
` Do you agree to give verbal responses
` today?
` A. Yes, I do. And if I fail to, please
` remind me.
` Q. Will do.
` And I'm going to try to refrain from
` speaking over you, and I would ask that you would
` try to refrain from speaking over me.
` Is that okay?
` A. I love those ground rules. So yes.
` Q. Thank you.
` And if you don't understand a
` question, please let me know. Otherwise, I'll
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 14
` assume that you've understood my question; is that
` fair?
` A. That's fair.
` Q. Your attorney may object to my
` questions from time to time, but you'll still need
` to answer the questions unless you're specifically
` instructed not to.
` Do you understand that?
` A. Yes, that's my understanding.
` Q. And I'll probably take a break every
` hour or so, but if you ever need to take a break,
` please let me know, but just first answer any
` pending question before we take a break.
` Is that okay?
` A. That will be fine with me, yes.
` MR. LUMAN: So what I'd like to do is
` make Exhibit 1225 available to
` Dr. Quackenbush.
` Henry, can you handle that for us?
` THE DOCUMENT TECH: No problem.
` MR. LUMAN: Thank you.
`
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 15
` (Exhibit 1225 , No Bates Numbers,
` Declaration of John Quackenbush, Ph.D. in
` Support of Petitioner's Reply to Patent Owner
` Response, IPR2023-0024 and IPR2023-00317,
` received and marked.)
` MR. LUMAN: So let's see. If I
` understand right, that will go in the Box?
` THE DOCUMENT TECH: And it is. All
` you need to do is just refresh, and you
` should see 1225 up.
` THE WITNESS: All right.
` BY MR. LUMAN:
` Q. Dr. Quackenbush, if you can give me a
` verbal queue once you've had a chance to download
` that document, I'd appreciate it.
` A. I have it downloaded, and it is open.
` Q. Okay. So, Dr. Quackenbush, is this a
` copy of the declaration that you submitted in
` IPR 2023-00224 and 00317?
` A. Yes, December 22, 2023, in response to
` Dr. Furneaux's declaration.
` Q. Thank you.
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 16
` Let's see, would you turn with me to
` paragraph 56? If you could let me know when you
` arrive there.
` A. All right, I'm there.
` Q. And there's a block quote from the
` Encyclopedia blog from James Hadfield.
` Do you see that?
` A. Yes, Enseqlopedia.
` Q. Thank you.
` Now, James Hadfield was one of the
` coauthors of the Forshew reference; is that right?
` A. I don't have the Forshew reference in
` front of me, but I will take your word for it.
` Q. We don't mind looking at the Forshew
` reference to verify that.
` MR. LUMAN: Would you mind making
` Exhibit 1030 available to Dr. Quackenbush,
` please.
` (Exhibit 1030, No Bates Numbers,
` Noninvasive Identification and Monitoring of
` Cancer Mutations by Targeted Deep Sequencing
` of Plasma DNA, Tim Forshew et al., Science
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 17
` Translational Medicine 4, 2012, Tim Forshew
` et al., marked for identification.)
` THE DOCUMENT TECH: It's coming up.
` THE WITNESS: All right. It hasn't
` appeared yet.
` THE DOCUMENT TECH: Try again.
` MR. LUMAN: There it is. If you could
` go to the next page, please.
` BY MR. LUMAN:
` Q. And, Dr. Quackenbush, is the James
` Hadfield who put the Enseqlopedia blog that you
` quoted in paragraph 56 one of the coauthors of
` Forshew, Exhibit 1030 in this case?
` A. Yes, he is.
` Q. If you could turn back to paragraph 56
` of your declaration, please.
` A. All right.
` Q. And I'm looking at the -- I mean, the
` block quote starts with the "Fluidigm Access Array,"
` and then there's the bold italicized sentences. I
` want to look at the second bolded italicized
` sentence that starts with "Microfluidics."
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 18
`
` Do you see that?
` A. Yes, I do.
` Q. So it says, "Microfluidics, emulsion
` PCR probes and oligo-probes are the different
` 'capture' mechanisms."
` Do you see that?
` A. Yes, I do.
` Q. I wanted to know what the
` microfluidics refers to. Is that something from the
` Fluidign Access Array, the RainDance? What is that
` microfluidics referring to?
` A. So I don't have the entire
` Enseqlopedia blog entry here in front of me. So the
` top of the block quote, he talks about "Fluidigm's
` Access Array, RainDance's new ThunderStorm, Halo
` Genomics, MIPs, traditional multiplex PCR are all
` competition from the in-house kits of Illumina and
` Life Technologies. The major differences with all
` the platforms are the way in which multiple loci are
` captured and amplified."
` And then I believe when he's talking
` about microfluidics, emulsion PCR -- so
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 19
`
` microfluidics, I believe he's referring to
` Fluidigm's Access Array, possibly RainDance's
` ThunderStorm. So I'm not sure about Halo Genomics.
` Emulsion PCR, he might be referring to
` RainDance. I don't know. I'd have to look more
` fully at the blog to fully answer that.
` But he's talking about different
` PCR-based assays. As he says in the next sentence,
` "All rely on PCR for amplification and to add to the
` sequencing platform adapters and bar codes [sic]."
` Q. And I'm interested in the next part
` where there's oligo-probes. Are those oligo-probes
` referring to solution-based hybridization capture
` probes, or is that referring to something else?
` A. So I'm not sure I understand your
` question. It says, "Microfluidics, emulsion PCR and
` oligo-probes are the different 'capture'
` mechanisms." So I would believe here that he's
` referring in general to all the nucleotidic probes
` like those in PCR, PCR primers, where those are
` capture probes. He's also referring back to MIPS,
` which are molecular inversion probes.
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 20
` I'm not sure what Halo Genomics does,
` but -- and then they're in-house kits from Illumina,
` Life Technologies. Life Technologies at the time
` was definitely doing emulsion PCR.
` So he's trying to distinguish between
` the three. But, you know, as he states in the next
` sentence, there is reliance to all of these on PCR.
` So my interpretation is that the oligo-probes are
` oligonucleotides that are used to capture the
` different individual molecules, and that would
` include PCR probes.
` Q. So in the context of this blog post
` and referring to PCR, the oligo-probes would refer
` to the PCR primers and not solution-based
` hybridization capture probes; is that fair?
` MR. KRAUSE: Objection,
` mischaracterizes testimony.
` THE WITNESS: So I don't think that's
` fair. I don't think that's what I would say.
` As we've discussed previously, capture
` probes, especially in the context of the '394
` and '033 patents, have pretty broad
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 21
` definitions, and those broad definitions are
` consistent with actually what appears in the
` contemporaneous literature and actually with
` Dr. West's testimony and Dr. Furneaux's
` testimony in deposition.
` So the oligonucleotide probes are
` simply the oligonucleotides that are used in
` different capture moieties, which would
` include, based on the PTAB's claim
` construction, techniques such as solution or
` solid phase hybridization, but also the use
` of PCR capture probes.
` BY MR. LUMAN:
` Q. I'm interested in what the
` oligo-probes in this blog refer to. And I was
` wondering if your interpretation is that the
` oligo-probes here include both PCR primers and
` solution-based hybridization capture probes?
` A. So would it be possible to provide me
` with the full blog so that I can review it?
` Q. Yes.
` MR. LUMAN: That's Exhibit 1216. Can
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 22
` we make that available to Dr. Quackenbush,
` please.
` (Exhibit 1216, No Bates Numbers,
` Amplicon NGS battles begin in earnest -
` Enseqlopedia, received and marked.)
` THE DOCUMENT TECH: It's up.
` MR. LUMAN: Thank you.
` THE WITNESS: All right. It's
` appeared.
` BY MR. LUMAN:
` Q. When you've had a chance to review it,
` can you give me a verbal cue?
` A. I just have it open now.
` (Document review.)
` BY MR. LUMAN:
` Q. Are you waiting for me, or are you
` still reviewing, Dr. Quackenbush?
` A. Oh, I'm still looking at it, just a
` second. I was just about to ask you to repeat the
` question, please. Okay.
` (Document review.)
` THE WITNESS: So please repeat the
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 23
`
` question.
` BY MR. LUMAN:
` Q. In this blog post, when the author
` refers to oligo-probes, is he referring to just PCR
` primers, or is he also referring to solution-based
` hybridization capture probes?
` A. So based on what's presented here,
` it's hard for me to fully conclude the breadth of
` what he's referring to. He talks about doing PCR
` and sequencing.
` I believe Fluidigms Access -- I'd have
` to -- I don't recall these technologies fully. I
` think Fluidigms Access Array was a solid state
` capture assay or maybe -- I don't recall. I don't
` recall exactly what it was. I did some work with
` that, but it was a long time ago.
` We did look at RainDance's technology,
` and that prepared basically emulsion PCR.
` Halo Genomics, I'm not familiar with,
` but I believe he was trying to be -- to the best of
` my knowledge to understand what he's presenting
` here, to be inclusive.
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 24
` And since he mentions microfluidics,
` emulsion PCR, and oligo-probes, I think he's talking
` about these oligo-probes generally. And that would
` include not only the solution phase capture that you
` were referring to, but also potentially solid-phase
` capture and then varieties or different variations
` on PCR.
` MR. LUMAN: If we could take down the
` exhibit and have paragraph 56 back on the
` screen, please.
` BY MR. LUMAN:
` Q. And so my question is -- well, I'm
` looking at the sentence that says they have
` different "capture" mechanisms. And my question
` would be, what is the different capture mechanism
` between microfluidics and oligo-probes?
` A. So saying that they're different
` doesn't necessarily mean that there aren't shared
` similarities too, right. So I'd have to look at the
` individual microfluidics. He may be -- so there are
` microfluidics techniques that are similar to digital
` droplet PCR in which you take nucleic acids and
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 25
` solution and then you take PCR-based reagents and
` you fuse them together in microfluidic channels
` through which an oil -- oil is flowing, and what you
` end up doing is creating little droplets that are
` individual reaction vessels.
` So it's a technique in which one could
` do PCR by flowing in PCR reagents. And so the
` difference is rather than doing it as a multiplex
` PCR in a single tube, what one is doing is creating
` little reaction vessels which are often then
` amplified together in emulsion PCR.
` Emulsion PCR, as implemented by Life
` Technologies, used a different approach to create
` emulsions. But, again, the goal was to try to get
` single DNA molecules with the appropriate PCR
` reagents to perform amplification. And I think he's
` talking about a variety of different oligo-probes.
` So every single mechanism he refers
` to, to the best of my understanding -- again, I'm
` really not familiar with Halo Genomics -- relies on
` the binding between complementary strands of DNA
` that could be hybridization capture probes that you
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 26
` were referring to earlier either in liquid -- I
` guess in this case it would all be liquid phase,
` unless Access Array had a solid phase component, or
` PCR capture probes where the PCR primers are serving
` to capture individual molecules as Dr. West
` testified they can be used for.
` Q. And so what are the different capture
` mechanisms between emulsion PCR and oligo-probes?
` A. So emulsion PCR is PCR that's
` performed typically in droplets. The droplets are
` often in a single tube, but the capture probes in
` that case would be the PCR primers that are used to
` amplify the individual molecules.
` So, you know, the difference might be
` a multiplex PCR versus an emulsion PCR. I would
` describe those as different mechanisms, but they're
` all based on the same underlying base-pair between
` one or more capture probes and the target molecule,
` where those capture probes can be hybridization
` capture probes or PCR capture probes; right?
` MIPS is a different technology in
` which essentially two PCR primers are linked
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 27
`
` together -- or the two PCR probes are linked
` together, and they bind around a target region.
` They're all based on complementary base-pairing.
` So, you know, I guess the differences
` here, again, are sort of in the details, but the
` underlying mechanism of all nucleic acid-based
` capture is this complementary base-pairing.
` Q. And I see that the word "capture" has
` quotes around it. What would a person of ordinary
` skill in the art understand about the meaning of the
` word "capture" being in quotes?
` A. So I can't speculate on what
` Dr. Hadfield was trying to present here, what he was
` trying to represent by putting quotes around
` "capture." I can tell you that a person of ordinary
` skill in the art reading this entire paragraph is
` that he's simply talking about the growing number of
` ways that were available to one skilled in the
` art -- available as commercial platforms to use
` complementary base-pairing. And, again, there are a
` variety of different techniques one can use, but to
` use this complementary base-pairing biological
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 28
` mechanism as a way of targeting specific regions of
` the genome.
` And, you know, as we've discussed
` previously, this is not limited. This could include
` hybridization-based capture either in liquid phase
` or solid phase, but could also include the use of
` PCR capture probes.
` So, yeah, I'm not sure what
` Dr. Hadfield was trying to imply here, but as a
` person of ordinary skill in the art, I see this as
` something that would be inclusive rather than
` exclusive.
` Q. Do you think that -- well, let me ask
` it this way: Do the quotes inform the reader that
` Dr. Hadfield is using the word "capture" in a way
` that's unusual or not usually complied?
` MR. KRAUSE: Objection, vague. Form,
` as well.
` THE WITNESS: I can't really speak to
` what Dr. Hadfield was -- what his intent was.
` In rereading this entire paragraph, my
` interpretation of this, at least as a person
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 29
` of ordinary skill in the art, is that what
` Dr. Hadfield is -- would most likely be
` trying to imply is that capture is pretty
` broad, right, that it's not something which
` is just narrowly defined; but, again, as
` we've discussed in the past, that capture
` could include a variety of different methods.
` And he lists a number of them here,
` and I think what he's trying to say is that
` despite what one might perceive as
` differences between these platforms, that
` ultimately each one of them is providing a
` capture mechanism that is based on
` complementary base-pairing, and that capture
` process would include PCR and other steps,
` right.
` So the very next sentence says all of
` the methods he discusses, rely on PCR for the
` amplification and to add sequencing platform
` adapters and bar codes. So I don't think
` he's trying to exclude things. I think he's
` trying to be more inclusive and really to
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 30
` reflect the state of the art, that "capture"
` was defined in a pretty broad manner.
` BY MR. LUMAN:
` Q. And during that answer, you made a
` gesture with your hands like a pair of quotes; is
` that correct?
` A. Yes, I was trying to say,
` quote-unquote, capture, since we referred to the
` quotation -- single quotation marks, since he's
` British, around the word "capture."
` Q. Did you consider any treatise on
` grammar regarding the use of quotation marks when
` you were considering how a person of ordinary skill
` in the art would interpret the word "capture" being
` in quotes here?
` A. I don't know what Dr. Hadfield would
` refer to. I can tell you that having written and
` edited many, many papers and published some in
` journals like Nature, which are published in the UK,
` that standard utility in the UK is for single
` quotes, where we would typically use double quotes.
` But, you know, you would have to ask Dr. Hadfield
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`
`www.DigitalEvidenceGroup.comDigital Evidence Group C'rt 2024
`
`202-232-0646
`
`Personalis EX2188
`
`
`
`2/1/2024
`
`Foresight Diagnostics Inc. v. Personalis, Inc.
`
`Dr. John Quackenbush
`
`Page 31
` what he was referring to here -- or what he was
` trying to -- what he was trying to encompass.
` I can tell you that as a person of
` ordinary skill in the art thinking about this and
` now really rereading this paragraph is that he was
` trying to talk about "capture" being sort of
` inclusive not trying to limit it to one form of
` "capture," right. Because he says "different
` 'capture' mechanisms." So he's really trying to
` talk about this in an inclusive way.
` MR. LUMAN: I'd like to mark an
` exhibit. This will be Exhibit 2178 and the
` exhibit I'd like marked is the one called The
` Chicago Manual of Style.
` (Exhibit 2178, No Bates Numbers, The
` Chicago Manual of Style
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
