`
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`Page 1
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` HEI-MUN CHRISTINA FAN and STEPHEN QUAKE }
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` Junior Party, }
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` vs. }
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` }
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` YUK-MING DENNIS LO, ROSSA WAI KWUN CHIU,
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` and KWAN CHEE CHAN, }
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` Senior Party. }
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` PATENT 8,195,415
`
` CASE IPR2013-00390
`
` - and -
`
` PATENT 8,195,415
`
` APPLICATION 13/070,266
`
` PATENT INTERFERENCE NO. 105,922 (DK)
`
` Deposition of JOHN C. DETTER, Ph.D.
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` Washington, D.C.
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` July 1, 2014
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` 9:13 a.m.
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` Veritext Legal Solutions
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` Mid-Atlantic Region
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` Washington, D.C. 20005
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`SEQUENOM EXHIBIT 1090
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`
`
`Page 2
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` Deposition of JOHN C. DETTER, Ph.D.,
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` held at the offices of:
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` ROTHWELL, FIGG, ERNST & MANBECK, PC
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` 607 14th Street, Northwest, Suite 800
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` Washington, D.C. 20005
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` (202) 783-6040
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` Pursuant to Notice, before Michele E.
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` Eddy, Registered Professional Reporter, Certified
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` Realtime Reporter, and Notary public in and for the
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` District of Columbia.
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` A P P E A R A N C E S
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`Page 3
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` ON BEHALF OF THE JUNIOR PARTY:
`
` R. DANNY HUNTINGTON, ESQUIRE
`
` SETH E. COCKRUM, ESQUIRE
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` Rothwell, Figg, Ernst & Manbeck, P.C.
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` 607 14th Street, Northwest, Suite 800
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` Washington, D.C. 20005
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` (202) 783-6040
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` dhuntington@rfem.com
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` scockrum@rfem.com
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` A T T E N D A N C E , C o n t i n u e d
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`Page 4
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` O N B E H A L F O F T H E S E N I O R P A R T Y :
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` M I C H A E L J . W I S E , E S Q U I R E
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` P e r k i n s C o i e , L L P
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` 1 8 8 8 C e n t u r y P a r k E a s t , S u i t e 1 7 0 0
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` L o s A n g e l e s , C a l i f o r n i a 9 0 0 6 7
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` ( 3 1 0 ) 7 8 8 - 3 2 1 0
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` M W i s e @ p e r k i n s c o i e . c o m
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` - A N D -
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` P A T R I C K M O R R I S , P h . D . , E S Q U I R E
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` P e r k i n s C o i e , L L P
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` F o u r E m b a r c a d e r o C e n t e r , S u i t e 2 4 0 0
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` S a n F r a n c i s c o , C a l i f o r n i a 9 4 1 1 1
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` ( 4 1 5 ) 3 4 4 - 7 1 0 5
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` EXAMINATION INDEX
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` PAGE
`
` EXAMINATION BY MR. WISE 7
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`Page 5
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` E X H I B I T S
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` (Attached to the Transcript)
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` DEPOSITION EXHIBIT PAGE
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` Exhibit 1101 Article titled "Initial 64
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` Sequencing and Analysis of
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` the Human Genome"
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` Exhibit 1105 Article titled "Supplementary 64
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` Information for Initial
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` Sequencing and Analysis of the
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` Human Genome, Methods and
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` Additional Notes"
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` EXHIBIT INDEX CONTINUED
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`Page 6
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` EXHIBITS PREVIOUSLY MARKED AND REFERRED TO
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` (Retained by Counsel)
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` DEPOSITION EXHIBIT PAGE
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` Exhibit 1001 50
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` Exhibit 1002 110
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` Exhibit 1005 85
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` Exhibit 1036 32
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` Exhibit 2049 157
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` Exhibit 2110 24
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` Exhibit 2112 23
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` Exhibit 2113 23
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` Exhibit 2117 56
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` Exhibit 2132 19
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` Exhibit 2138 10
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`Page 7
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` P R O C E E D I N G S
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` Washington, D.C.
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` July 1, 2014, 9:13 A.M.
`
` - - -
`
` JOHN C. DETTER, PH.D.,
`
` having been duly sworn, testified as follows:
`
` EXAMINATION BY COUNSEL FOR SENIOR PARTY
`
` BY MR. WISE:
`
` Q Good morning.
`
` A Good morning.
`
` Q At the beginning of cross-examination,
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` since this involves an interference, I'm required to
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` tell you the following. The party conducting the
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` cross-examination must instruct the witness on the
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` record as to opposing counsel, that's me, rather
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` than the witness' own counsel, that's
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` Mr. Huntington, for clarifications, definitions, or
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` explanations of any words, questions, or documents
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` presented during the cross-examination. The witness
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` must follow these instructions.
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` Will you do that?
`
` A Yes.
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` Q Just to refresh, we've been here a couple
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` of times already. You remember?
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` A I do, unfortunately.
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` Q We want verbal responses so please avoid
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` nonverbal responses like shaking or nodding of the
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` head. Would you do that for me today, please?
`
` A Yes.
`
` Q Again, you and I tend to talk over each
`
` other a bit. So would you please wait for me to
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` finish the question and I will try to wait for you
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` to finish your answer.
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` A I will certainly try.
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` Q Any reason, drugs, medication, something
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` of that nature, that prevent you from giving
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` truthful testimony today?
`
` A No.
`
` Q Okay. How many times have you been
`
` deposed now in proceedings other than the one that
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` I've taken?
`
` A They all kind of run together, I think
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` twice.
`
` Q Let me ask you it a different way.
`
` Have all of the -- I've taken your
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` deposition twice.
`
` A Correct.
`
` Q Okay. Other than me, has anybody else
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` taken your deposition?
`
` A Yes.
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` Q Okay. Other than Michele Bosch, the woman
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` that was with me, has anybody else taken your
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`Page 9
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` deposition?
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` A Yes.
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` Q What was that deposition?
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` A I do not recall everything. It was -- I
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` don't recall the name -- the number of the
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` deposition or what it was.
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` Q Do you remember the name of the parties?
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` A Not without guessing.
`
` Q So other than the depositions that have
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` occurred that I've been present at and this other
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` one that you don't recall --
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` A Yes.
`
` Q -- any other depositions?
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` A Not that I recall.
`
` Q Any live testimony in front of a judge or
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` a jury?
`
` A No.
`
` Q How much time did you prepare for today?
`
` A I would say approximately two days' worth,
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` not full 24-hour days, so maybe, I would say,
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` approximately 16 hours.
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` Q And when? When did you do that
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` preparation?
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` A Last night --
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` Q Yes.
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` A -- over the weekend a few hours, and then
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` a little bit last Friday.
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` (Exhibit 2138 was previously marked and
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` referred to.)
`
` Q All right.
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` Now, there are some -- we're going to talk
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` about Exhibit 2138, and I believe there were some
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` edits that you made to that; is that correct?
`
` A Yes.
`
` Q When did you make those?
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` A On Friday of last week.
`
` Q Okay.
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` A On -- as a written process. Verbally,
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` there were discussions. I don't remember all the
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` discussions, but written process was on Friday.
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` Q Why did you make the edits?
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` A As we were reviewing those, we saw that
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` the pages had a few pages that were off by a page or
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` two and then saw that there were some misquoted
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` comments and words left out from when the quotes
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` were done from one document to the other.
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` Q Now, if you turn to Exhibit 2138, and if
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` you look at paragraph 7, it sets forth claim 1 of
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`Page 11
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` the '415 patent?
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` A Yes.
`
` Q Have you ever practiced that claim?
`
` A As a scientist?
`
` Q Yes.
`
` A No, I have not.
`
` Q Have you ever detected fetal aneuploidy
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` with massively parallel sequencing?
`
` A As a scientist, I have not, no.
`
` Q Ever used windows to normalize data as a
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` scientist?
`
` A I have had staff that have done that, yes.
`
` Q Personally know the people that work for
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` you did it for you; is that correct?
`
` A Correct.
`
` Q In what context did you do that, or did
`
` they do that for you?
`
` A Mostly comparative genomic type of
`
` activities. When you're comparing one genome to
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` another genome, that's -- usually you have a
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` control, some sort of -- you have some sort of
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` control genome that you're comparing a recently
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` sequenced genome to or a region to, and you're doing
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` that. So you're comparing different regions.
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` Q When?
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`Page 12
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` A I would say numerous times between the
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` years of 2005 and 2012. I do not remember all the
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` occasions.
`
` Q Is that a standard statistical or
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` conventional statistical tool for normalizing data?
`
` A Yes, it is.
`
` Q How about sliding windows?
`
` A Yes. That's a standard tool as well.
`
` Going back, yes, as long as I've been in the field,
`
` at least since 1999.
`
` Q Right. So either sliding windows or
`
` dividing a genome or a chromosome into numerous
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` windows of defined length?
`
` A Using windows for comparative genomics has
`
` been in the field for a long time, I don't remember
`
` the exact date but at least since 2005, if not
`
` earlier, using the windows for comparative analyses.
`
` Q Okay. Any of your windows -- any of the
`
` windows work that you worked on for normalizing
`
` data, was that ever published?
`
` A I don't recall the context in which it was
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` published. The work that I had done as a result of
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` a number of publications, for me directly, I don't
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` remember the exact context of the sliding windows or
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` the data analysis, what components have been in
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`Page 13
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` there. I do know data analysis has been in there.
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` Q I guess let me put it a different way.
`
` If I were looking for a particular paper
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` of yours from your CV that would identify windows
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` analysis, is there any one that you can think of
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` that I could look to to see that?
`
` A Not that I recall.
`
` Q Have you ever used windows to measure GC
`
` content?
`
` A That is part of the analyses one would do,
`
` yes. Me personally? No. When we do comparative
`
` genomics and we look at biases, we look at mixed
`
` genomes, genomes -- when you sequence one genome and
`
` you look at the biases within that genome, you do
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` analyses like that.
`
` Q Same time frame, from 2000 to 2005?
`
` A From 2005 to 2012 is what I mentioned.
`
` Q You did, I apologize.
`
` Same question for windows to measure GC
`
` content. Can you recall a publication of yours that
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` would contain that information?
`
` A Not without reviewing all of my
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` publications, going through it, no.
`
` Q By "reviewing your publications," you
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` don't mean looking in your CV, do you?
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` A No, I don't.
`
` Q You mean physically reading through the
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` publications?
`
` A I would have to go through and actually
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` flip through them, yes, correct.
`
` Q Okay.
`
` A Most of the genomes I did, you know, I
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` said from 2005 to 2012, lots of details, lots of
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` information of context like that, but I would have
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` to look through them.
`
` Q Okay. And GC bias, is that a function of
`
` the -- a functioning of the sequencing process?
`
` A Can you, I guess, narrow your question
`
` down a little bit.
`
` Q Let me ask it a different way.
`
` A Okay.
`
` Q What is GC bias?
`
` A In one sense, GC bias is when you
`
` sequence -- a genome has various contents of As, Ts,
`
` Gs, and Cs. A 50/50 ratio is not what -- some
`
` genomes has a 50/50 ratio. Genome sequencers seem
`
` to have an easier time with the 50/50 ratio.
`
` Unfortunately, most genomes are not 50/50, and if
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` they are, they're not 50/50 within all regions.
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` Certain regions of a genome have higher GCs or ATs,
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`Page 15
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` depending on what you want to call it, AT bias or GC
`
` bias, depending on what you want to call it.
`
` Sequencers have issues in certain regions
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` of high AT or certain regions of high GC for
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` different reasons, that the sequencing process has a
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` hard time either getting through that region, kills
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` the sequencing reaction, causes data issues.
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` Different sequencers have different problems
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` associated with GC, depending on the type of
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` chemistry it uses.
`
` Q Is your answer complete?
`
` A I think so.
`
` Q Just a note. You and I talk quickly. We
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` need to slow it down a little bit for her.
`
` A I'll try. A lot of people have tried.
`
` I'm sorry, I apologize.
`
` Q Have you ever met Christina Fan?
`
` A No, I have not.
`
` Q Now, if you look at paragraph 3, you
`
` indicate that you read her declaration. I guess it
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` says "reviewed." Is there a difference between
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` reviewed and read?
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` A Depends on the context. I've reviewed her
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` declaration.
`
` Q What do you mean by "reviewed"?
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` A I have looked through her declaration. I
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` have done a quick read of some sections and a
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` detailed read of other sections.
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` Q Okay. Read every page, word for word?
`
` A I've reviewed every page.
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` Q Did you read every page word for word?
`
` A I do not recall.
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` Q Did you read any other declarations that
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` were submitted by party Quake besides the Christina
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` Fan declaration?
`
` A For this case here specifically? Or my --
`
` Q Well, we're here on -- yes, for this case
`
` specifically. And what I mean by "this case
`
` specifically" is the 922 interference of the
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` priority contest and then the IPR for, essentially,
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` the swear behind, I think is what you have on the
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` note on the document.
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` A I don't recall all the documents I've read
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` without having them in front of me. I would have
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` to ...
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` Q Did you read Dr. Quake's declaration, for
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` example?
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` A Not that I recall.
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` Q And then if you look in here, there's
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` other references to some of the documents. For
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` example, if you look at paragraph 6, there's a
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` person by the name of Yair Blumenfeld. Did you read
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` a declaration from Yair Blumenfeld?
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` A Not that I recall.
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` Q Paragraph 8, did you read a declaration
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` from a guy by -- a person by the name of Dr. Leonard
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` Herzenberg?
`
` A Not that I recall.
`
` Q Okay. So as we sit here today, to the
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` best of your recollection, in this proceeding,
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` you've only read the Fan declaration; is that
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` correct?
`
` A I've only read the Fan declaration to my
`
` best recollection in this specific instance, yes.
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` Q Did you ask if there were additional
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` declarations when you were reviewing the Fan
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` declaration?
`
` A Not that I recall.
`
` Q Did you notice that Dr. Fan made similar
`
` errors in her declaration as to yours with respect
`
` to documents that -- let me rephrase.
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` Did you notice that Dr. Fan made similar
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` errors in her declaration as the corrections you
`
` made in yours, Exhibit 2138?
`
` A Yes, I did.
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` Q Did you double-check your changes this
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` time? In other words, did you double-check the
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` paragraphs and the line numbers and all of these
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` changes that you made in Exhibit 2138 to the
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` originals, or did you just compare them to Dr. Fan's
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` changes?
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` A To the originals. Then that's when I made
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` the changes.
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` Q What's an actual reduction to practice?
`
` It's in paragraph 5.
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` A Thank you.
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` Q At least that's where you --
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` A That's where I refer to reduction in
`
` practice.
`
` Q Correct.
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` You can take your time looking at the
`
` whole thing if you would like.
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` A Okay, thank you.
`
` (Pause in proceedings.)
`
` Q You also refer to it in paragraph 7.
`
` A Thank you.
`
` So as far as a legal definition, I won't
`
` probably give you that, but my nonlegal definition,
`
` a reduction to practice is when a previous set of
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` work actually generates the experiments, data
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` necessary to carry out a set of experiments that
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` have -- that are also done in the future, so to
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` speak, for a set of claims or something like that.
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` The legal definition here is, it's essentially
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` stating that a previous set of documents and work
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` and protocols and processes actually are -- generate
`
` the data necessary to develop the claims of, like,
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` for this instance, the '415 patent.
`
` Q What do you mean by "generate the data
`
` necessary to develop the claims in the '415 patent"?
`
` (Exhibit 2132 was previously marked and
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` referred to.)
`
` A The actual experiments that were done
`
` previously. For example, the work in 21 -- let me
`
` see here, experiments that were outlined in 2132.
`
` Without referring back to the actual documents,
`
` those experiments actually -- the protocols and
`
` processes of carrying out those experiments actually
`
` resulted in each and every claim of the '415 patent.
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` Without doing those experiments, the '415 patent
`
` claims would not have been possible. So by doing
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` the experiments previously, you were able to
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` generate the claims in the '415 patent.
`
` Q Do you know if there's any other
`
` requirements for a reduction -- actual reduction to
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` practice other than doing experiments that generate
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` the claims?
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` A Not that I recall without looking at the
`
` legal definitions.
`
` Q Did you ever have the legal definitions?
`
` A I can't say for sure if I've looked at the
`
` actual law definitions, web.
`
` Q Now, all of this work that you're talking
`
` about in Exhibit 2138 that Dr. Fan did and the
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` publications and whatnot --
`
` A Yes.
`
` Q -- when did you first learn of that
`
` information? And just give me a year. I don't need
`
` a specific date.
`
` A The work that was done, all of the work
`
` that was done to generate the 2138 document or the
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` protocols and processes that I'm referring to?
`
` Q Well, if I look through paragraph 21 --
`
` here's my question.
`
` A Okay.
`
` Q You weren't around at the time that's
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` referenced here in these documents, like, for
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` example, the experiments she performed in 2132
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` referenced in paragraph 4. You weren't
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` contemporaneously around at that time working with
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` Dr. Fan and seeing this documentation, correct?
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` A That is correct. I was not working with
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` Dr. Fan during these experiments.
`
` Q Right. So, for example, a lot of this
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` declaration refers to occurrences in 2008, and in
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` 2008, were you involved with the legal -- with Quake
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` and Fan at all?
`
` MR. HUNTINGTON: Objection, irrelevant.
`
` A I have -- to my knowledge, I have not been
`
` involved with Dr. Quake, Dr. Fan in any way other
`
` than the proceedings that we're talking about here.
`
` Q Right. So when you talk about, you know,
`
` what's in the documents and, you know, what's in the
`
` Fan declaration, what's in the Fan notebook, what's
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` in the Fan draft manuscript, those things in this
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` declaration, you're using hindsight as opposed to
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` testifying as to occurrences that occurred at that
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` particular moment in time, correct?
`
` A I'm not sure how to exactly answer that.
`
` I'm using -- I've been given a list of documents to
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` use and provide my subject matter expertise on that,
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` my opinion on that. I was not involved in these
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` experiments.
`
` Q Right. So you're looking back at the
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` experiments that occurred in 2008 and testifying
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` today about what you think of them, right?
`
` A That sounds -- I'm looking at the
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` documents that were generated from the data that was
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` generated in 2008.
`
` Q Right. And testifying today about what
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` they mean to you as opposed to confirming what
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` happened in 2008 because you weren't there.
`
` MR. HUNTINGTON: Objection.
`
` A I was not there in 2008, nor have I tried
`
` to replicate in the wet lab these experiments.
`
` Q Fair enough.
`
` When does an actual reduction to practice
`
` occur?
`
` A I don't -- I don't understand exactly your
`
` question.
`
` Q Well, referring back to your answer, let
`
` me read it to you? "So as far as a legal
`
` definition, I won't probably give you that, but my
`
` nonlegal definition, reduction to practice is when a
`
` previous set of work actually generates the
`
` experiments, data necessary to carry out a set of
`
` experiments that have -- are also done in the
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` future, so to speak, for a set of claims or
`
` something like that. The legal definition here is,
`
` it's essentially stating that a previous set of
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` documents, work and protocols and processes actually
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` are -- generate the data necessary to develop the
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` claims of, for instance, the '415 patent."
`
` So my question is really kind of directed
`
` to some of this discussion you have about the future
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` work. So when does it occur?
`
` MR. HUNTINGTON: Objection.
`
` Q When do we have an actual reduction to
`
` practice?
`
` MR. HUNTINGTON: Objection, irrelevant.
`
` (Exhibit 2112 and Exhibit 2113 were previously
`
` marked and referred to.)
`
` A So, yes, once again, without understanding
`
` all the legal definitions, my understanding is, and
`
` common sense, the work was done initially in the
`
` documents that we discussed and the draft 2113 and
`
` 2112, that's when the work was actually done.
`
` That's when the experiments were done. That's when
`
` the protocols and processes were done. So that
`
` would be -- that would be the date set for the type
`
` of work that was done.
`
` Q Is there -- is there -- so if we look at
`
` claim 1, for example, and you say here in paragraph
`
` 5 that the series of experiments described by Fan is
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` an actual reduction to practice of each and every
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` claim of the '415 patent, is there a particular date
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` when that occurred?
`
` A The date the experiments occurred are the
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` dates that that was set, and that was -- that was
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` the date for me, is the date that it was set. That
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` was the date that reduction to practice --
`
` Q When the experiments begin or when the
`
` experiments are completed?
`
` A That's probably a nuance that I can't
`
` answer.
`
` I don't --
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` (Exhibit 2110 was previously marked and
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` referred to.)
`
` Q Now, can you turn to your copy of Exhibit
`
` 2110. And my question for you is, what page of the
`
` notebook of 2110 does Dr. Fan record her actual
`
` reduction to practice?
`
` MR. HUNTINGTON: Objection, outside the
`
` scope of direct testimony.
`
` A The experiments that I was asked to review
`
` and that set the date for me is -- starts on page
`
` 18. So at least as early as April 21st, 2008. I
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` have not been asked to review any documents any
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` earlier than that date in her experiment book. So
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` those are the first set of experiments that I was
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` asked to review that do result in a reduction to
`
` practice for the claims of '415.
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` Q Let me get with you. What page is that?
`
` A 18. They're kind of hard to see. They're
`
` on the top left.
`
` Q There we go.
`
` What is Dr. Fan doing here?
`
` A She's extracting DNA from plasma patients
`
` that are normal male fetuses.
`
` Q Okay. And how does extracting DNA from
`
` normal male fetuses constitute an actual reduction
`
` to practice of a claim that's testing or looking for
`
` an aneuploidy?
`
` A It's setting off a set of experiments, and
`
` those would be the controls since they're normal
`
` male fetuses.
`
` Q So in your definition of actual reduction
`
` to practice, the establishment of a control for the
`
` experiment is an actual reduction to practice?
`
` MR. HUNTINGTON: Objection.
`
` A You would have to put a lot of context
`
` behind -- with it. This is a beginning of a set of
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` experiments that result in reduction to practice.
`
` Q When did that reduction to practice occur?
`
` A I don't know all the legal nuances and
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` definitions. All I know is the experiments began
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` April 21st, 2008, that I was made aware of, to
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` review to see if they began the process of the
`
` reduction to practice for every claim of '415.
`
` Q Well, if there's a beginning to a
`
` reduction to practice, there must be an end. So
`
` when would the end be for a reduction to practice?
`
` A Without guessing, I couldn't tell you.
`
` Q I'm not asking the specific end for the
`
` particular Fan reduction to practice, but in your
`
` definition of a reduction to practice, you have a
`
` beginning and an end, and we note that the beginning
`
` is at least the establishment of a control. When's
`
` the end, under your definition, of a reduction to
`
` practice?
`
` A In my definition, the experiments that
`
` result in data generated to show that the process
`
` works would be the time period that one would use to
`
` confirm that the process actually reduces -- is a
`
` reduction to practice.
`
` Q So that be would the end, when the data
`
` confirms the claims?
`
` A I can't say that for sure. It would have
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` to be in context. You would have to take that
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` experiment into play with process.
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` Q Is it fair to say you don't know?
`
` A You asked me my opinion, and that's my
`
` opinion of when I would say -- you would start the
`
` experiments, and when the experiments result in data
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` that reduces the claims, that's the time period that
`
` we would be looking at. To my knowledge, the
`
` date -- let me see. Let's see here.
`
` So the draft -- the draft publication,
`
` which is generally the dates that people say that
`
` they completed the experiments and everything checks
`
` off, was June 19th, 2008, was the first draft
`
` publication.
`
` Q Okay.
`
` A And so that, for me, would set the date of
`
` the reduction to practice.
`
` Q Okay. Now, do you keep a lab notebook?
`
` A When I was working in a laboratory, I did
`
` keep a lab notebook, yes.
`
` Q Do the people who work for you keep a lab
`
` notebook?
`
` A Yes, they keep a lab notebook.
`
` Q Are there any requirements for keeping a
`
` lab notebook?
`
` A There are a lot of requirements for
`
` keeping a lab notebook.
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` Q Fair enough.
`
` Is it required that you sign them?
`
` A At my institution it's not a requirement.
`
` Q What if it's something really important
`
` like you think you've really discovered something?
`
` A You asked me if there was a requirement.
`
` At my institution there's not a requirement to sign
`
` the lab notebook. You're dating the lab notebook,
`
` and you keep a chronological date from begi