`
`Transcript of Ian A. Wilson, D.Phil.
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`Date: April 21, 2018
`Case: Pfizer, Inc. -v- Genentech, Inc. (PTAB)
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`Planet Depos
`Phone: 888.433.3767
`Email:: transcripts@planetdepos.com
`www.planetdepos.com
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`WORLDWIDE COURT REPORTING | INTERPRETATION | TRIAL SERVICES
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`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01488
`PFIZER EX. 1197, Page 1
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`Transcript of Ian A. Wilson, D.Phil.
`Conducted on April 21, 2018
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`1 (1 to 4)
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` A P P E A R A N C E S
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`ON BEHALF OF THE PETITIONER PFIZER, INC.:
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` BENJAMIN LASKY, ESQ.
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` KIRKLAND & ELLIS, LLP
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` 601 Lexington Avenue
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` New York, New York 10022
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` (212) 446-6415
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` blasky@kirkland.com
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` -and-
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` SHARICK NAQI, ESQ.
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` KIRKLAND & ELLIS, LLP
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` 300 North LaSalle
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` Chicago, Illinois 60654
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` (312) 862-3235
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` sharick.naqi@kirkland.com
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`ON BEHALF OF THE PETITIONER CELLTRION INC.:
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` ROBERT V. CERWINSKI, ESQ.
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` GOODWIN PROCTER, LLP
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` 620 Eighth Avenue
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` New York, New York 10018
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` (212) 459-7240
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` rcerwinski@goodwinlaw.com
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` UNITED STATES PATENT AND TRADEMARK OFFICE
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` BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`PFIZER, INC. and SAMSUNG BIOEPIS
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`CO., LTD.,
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` Petitioners, Case No.:
` IPR2017-01488
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` IPR2017-01489
` Patent 6,407,213
`-vs.-
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`GENENTECH, INC.,
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` Patent Owner.
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` Case IPR2017-02139 has been joined with this
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`proceeding.
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` Case IPR2017-02140 has been joined with this
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`proceeding.
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` Deposition of IAN A. WILSON, D.Phil.
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` La Jolla, California
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` Saturday, April 21, 2018
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` 9:07 a.m.
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`Job No.: 185272
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`Pages: 1 - 299
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`Reported by: Tricia Rosate, RDR, RMR, CRR, CCRR
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`CSR No. 10891
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` A P P E A R A N C E S (Continued)
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`ON BEHALF OF THE PETITIONER SAMSUNG BIOEPIS:
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` AMIT THAKORE, ESQ.
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` WHITE & CASE, LLP
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` 1221 Avenue of the Americas
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` New York, New York 10020-1095
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` (212) 819-2692
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` athakore@whitecase.com
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` ANDREW J. DANFORD, ESQ.
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` WILMER CUTLER PICKERING HALE and DORR, LLP
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` 60 State Street
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` Boston, Massachusetts 02109
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` (617) 526-6806
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` andrew.danford@wilmerhale.com
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` -and-
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` NORA Q.E. PASSAMANECK, ESQ.
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` WILMER CUTLER PICKERING HALE and DORR, LLP
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` 1225 17th Street
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` Suite 2600
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` Denver, Colorado 80202
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` (720) 274-3152
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` nora.passamaneck@wilmerhale.com
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`2
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`Deposition OF IAN A. WILSON, D.Phil, held at:
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` Residence Inn by Marriott
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` 8901 Gilman Drive
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` La Jolla, California 92037
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` (858) 587-1770
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` Pursuant to Notice, before Tricia Rosate, RDR,
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`RMR, CRR, CCRR, Certified Shorthand Reporter No.
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`10891 in and for the State of California.
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`PLANET DEPOS
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`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01488
`PFIZER EX. 1197, Page 2
`
`

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`Transcript of Ian A. Wilson, D.Phil.
`Conducted on April 21, 2018
`
`2 (5 to 8)
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` A P P E A R A N C E S (Continued)
`
`ALSO PRESENT:
`
` SARAH MILLER, The Videographer
`
` TRACI ROPP, Genentech
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`5
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`7
` LA JOLLA, CALIFORNIA; SATURDAY, APRIL 21, 2018
` 9:07 A.M. - 6:15 P.M.
` - - - -
` THE VIDEOGRAPHER: Here begins Tape No. 1 in
`the videotaped deposition of Dr. Ian Wilson in the
`matter of Pfizer vs. Genentech and Celltrion vs.
`Genentech, Case No. IPR2017-01486-01489 [sic] and
`Case No. IPR2017-01373-01374.
` Today's date is April 21, 2018. The time on
`the video monitor is 9:07 a.m.
` The videographer today is Sarah Miller,
`representing Planet Depo.
` This video deposition is taking place at
`8901 Gilman Drive, La Jolla, California.
` Will counsel please voice identify
`themselves and state whom they represent.
` MR. LASKY: My name's Ben Lasky from
`Kirkland & Ellis. I represent Pfizer.
` With me today from Kirkland & Ellis is
`Sharick Naqi.
` MR. CERWINSKI: I'm Robert Cerwinski. I'm
`with Goodwin Procter, LLP, and I represent Celltrion,
`petitioner.
` MR. THAKORE: Amit Thakore from White & Case
`representing petitioner Samsung Bioepis.
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` MR. DANFORD: Andrew Danford from WilmerHale
`representing patent owner, Genentech and the witness,
`and I'm joined today by Nora Passamaneck of
`WilmerHale and Traci Ropp of Genentech.
` THE VIDEOGRAPHER: Okay. The court reporter
`today is Tricia Rosate representing Planet Depo.
` Will the reporter please swear in the
`witness.
` IAN A. WILSON, D.Phil.,
` having been first duly sworn, testified as follows:
`0
` EXAMINATION
`11
`BY MR. LASKY:
`12
` Q Good morning, Dr. Wilson.
`13
` I just need to say something for the record.
`14
`The first case number, 2017-01488, and that's my
`15
`fault, my handwriting. So --
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` Good morning.
`17
` A Good morning.
`18
` Q Could you please state your full name for
`19
`the record.
`20
` A Ian Andrew Wilson.
`21
` Q And have you had your deposition taken
`22
`before?
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` A Yes.
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` Q How many times?
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` C O N T E N T S
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`EXAMINATION OF IAN A. WILSON, D.Phil. PAGE
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`By Mr. Lasky ....................... 8, 146, 280
`
`By Mr. Cerwinski ....................... 268
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`By Mr. Danford ....................... 270
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` E X H I B I T S
`
` (Attached to transcript)
`
`WILSON DEPOSITION EXHIBIT PAGE
`
`Exhibit 1194 "Humanization of a mouse 187
`
` anti-human IgE antibody: a
`
` potential therapeutic for
`
` IgE-mediated allergies"
`
`
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`Exhibit 1195 "Applications and Engineering 217
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` of Monoclonal Antibodies"
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` P R E V I O U S L Y M A R K E D E X H I B I T S
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` Exhibit 1001 Exhibit 1055
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` Exhibit 1002 Exhibit 1071
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` Exhibit 1003 Exhibit 1125
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` Exhibit 1021 Exhibit 1193
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` Exhibit 1034 Exhibit 2041
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` Exhibit 1052
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`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01488
`PFIZER EX. 1197, Page 3
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`

`

`Transcript of Ian A. Wilson, D.Phil.
`Conducted on April 21, 2018
`9
`
` A I can't remember how many. About three or
`four.
` Q Okay. And were they all in connection with
`expert witness work?
` A Yes.
` Q Okay. How many times have you previously
`served as an expert witness in a litigation or
`patent office proceeding?
` A Could you explain?
` Q Sure. Well, let's start with a
`district court action.
` Have you ever served as an expert in a court
`action?
` A One. One time.
` Q Okay. And who were you retained by in that
`case?
` A WilmerHale.
` Q Okay. And who was the --
` Well, first of all, was Genentech the party
`that you were representing there?
` A I don't think so.
` Q Okay. Do you know who the party was?
` A I can't remember.
` Q Okay. Was the party the patent owner?
` Well, strike that.
`
`3 (9 to 12)
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` You -- I'm not understanding some of the
`questions.
` Q Okay. Sure. So you understand that the
`proceeding that you're here for today is an
`inter partes review in the U.S. Patent and Trademark
`Office?
` Do you understand that?
` A I understand it now.
` Q Oh, okay. Okay. Well, why don't you tell
`me. What other cases have you been involved in as an
`expert witness?
` A They've -- they'e largely been to do -- to
`do with -- cases to do with -- with patents. By and
`large, I think it's been patents.
` I had one other case that had noth- -- that
`was -- that was a separate issue that was just a
`dispute between parties on some scientific grounds.
` Q Okay. Have you ever previously been
`retained by Genentech in a legal matter?
` A Yes.
` Q And -- and what -- what did that involve?
` A That involved -- similar to dealing with
`patents.
` Q And was it relating to the product
`Herceptin?
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` Was this a patent case?
` A It's such a long time ago, I can't -- I
`don't actually remember the details of the case. I
`actually destroy the documents, and I destroy it from
`my memory, too. So --
` Q Fair enough.
` Do you know what the issues were that you
`were giving an opinion on in that case?
` A It had to do with epitopes on -- on a
`receptor.
` Q And was it relating to a therapeutic
`product?
` A As far as I -- I recall, yes.
` Q Do you recall what the product was?
` A No.
` Q Okay. And you were deposed in that case?
` A Yes.
` Q Okay. Other than that case, have you ever
`been involved in a case in the district court or in
`any court?
` A No.
` Q All right. Have you ever served as an
`expert witness previously in an action before the
`U.S. Patent and Trademark Office?
` A In what sense? I don't really --
`
` A Other than this case?
` Q Yes.
` A No.
` Q Okay.
` A Not -- not that I remember.
` Q Okay. So the other case that you worked
`with -- worked on with Genentech, what product was
`involved in that case?
` A I can't remember what -- what those were.
` Q Okay. Was -- was that in the U.S. or
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`somewhere else?
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` A U.S. Or those -- those are Brazilian
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`proceedings as well.
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` Q Okay. And when was this?
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` A That's been ongoing for the last year or so.
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` Q Okay. And were you -- have you had a
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`deposition taken in that case?
`17
` A No.
`18
` Q Okay. Other than in litigation or in the
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`patent office, have you ever been retained by
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`Genentech as a consultant?
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` A Not to the -- not to my knowledge.
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` Q Have you ever received funding from
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`Genentech?
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` A Funding from -- personally or for my lab?
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`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01488
`PFIZER EX. 1197, Page 4
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`

`

`Transcript of Ian A. Wilson, D.Phil.
`Conducted on April 21, 2018
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` Q For your lab.
` A No.
` Q Okay. And personally?
` A No.
` Q Okay. The declarations --
` I've handed you two documents, Dr. Wilson.
`One is marked Exhibit 2041 in IPR2017-01488, and one
`is marked Exhibit 2041 in IPR2017-01489.
` These are the two declarations that you've
`submitted in these proceedings?
` A I just wanted to make sure my signature is
`on there.
` Yes, they are.
` Q Okay. Is it fair to say that the two
`declarations are substantively identical in terms of
`their content?
` A As far as I remember, yes.
` Q Okay. At the time you signed them, you
`believed them to be true and accurate to the best of
`your knowledge; is that right?
` A Yes, I did.
` Q Okay. Is there anything that you now
`realize is -- was in error or that you want to
`change?
` A No. I -- I -- there's one or two typos,
`
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` A I -- to the extent that I was required to --
`that I was required to for my deposition, yes -- for
`my declaration.
` Q Okay. Do you know if there's any documents
`here that you didn't review completely?
` A "Completely" meaning --
` Q Like, read it from start to finish.
` A I think I've -- I've opened most of the
`documents, whether -- and -- and skimmed through
`them. I -- I can't -- there's so many documents
`here, I can't -- I can't recall every single document
`that's in this particular list as to when I reviewed
`it.
` Q Okay. Is it fair to say, though, if it's
`listed here, it's something that you opened,
`considered relevant enough to consider it, and place
`it on your "Materials Considered" list?
` MR. DANFORD: Objection to form.
` THE WITNESS: Most of the -- the things I --
`I recognize, yes.
`BY MR. LASKY:
` Q Is there anything you're aware of that you
`considered that's missing from this list?
` A Whoa.
` Q And I guess I'm asking if you're aware of
`
`15
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`very minor things, a missing word, a missing comma, a
`missing exponent on the 9. But as far as substance
`are concerned, no.
` Q Okay. Well, as we go through, if there's
`anything you see that you --
` A Sure.
` Q -- need to change in terms of typos --
` A Sure.
` Q -- please let me know.
` Now, at the back of each of your
`declarations, you will see that there is a list of
`the materials that -- well, it's a "Materials
`Considered" list.
` Do you see that?
` A Exhibit B?
` Q Exhibit B. Yes.
` A I see that.
` Q Okay. And did you review and consider each
`of the documents in that "Materials Considered" list
`in each of your declarations?
` A I don't -- I don't remember every single one
`of them, but I recognize most of these, yes.
` Q Okay. And you read and understood all of
`these references before providing your declaration;
`is that right?
`
`it.
` A I'm not aware of any. I'd have to go
`through and -- and check, but I'm not aware of -- of
`any. Most of the papers, of course, I recognize
`right away, and --
` Yes.
` Q Okay. Before -- I want to focus on the time
`before you submitted your declarations up to when you
`submitted them.
` How much time did you spend on the case?
`0
` A Before I submitted the declaration?
`11
` Q Right. Up to the date that you submitted
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`the declaration. How much time would you have
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`submitted on --
`14
` A Many, many hours.
`15
` Q How many -- how many would you --
`16
` A I haven't added them up yet, but it would be
`17
`tens of hours.
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` Q Tens of hours?
`19
` A Yeah. Uh-huh.
`20
` Q Less than 100?
`21
` A I couldn't say if it was less than 100 or
`22
`more than 100, but it was a -- a large number of
`23
`hours.
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` Q Okay. And did you read the '213 patent in
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`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01488
`PFIZER EX. 1197, Page 5
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`

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`Transcript of Ian A. Wilson, D.Phil.
`Conducted on April 21, 2018
`17
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`before the invention that's described in the '213
`patent. And I know there's some dispute about that
`date. So I just want to focus on the time before the
`invention was made. Is that okay? I'm going to ask
`you questions about that.
` A Yeah. Sure.
` Q Okay. Now, before that invention date of
`the '213 patent, you would agree that it was known
`that overexpression of the HER2 protein led to a poor
`prognosis in cancer, including breast cancer; right?
` MR. DANFORD: Objection. Outside the scope.
` THE WITNESS: If you're asking if there were
`papers on that protein, the answer would be yes.
`BY MR. LASKY:
` Q Right. You don't dispute, though, that it
`was known that overexpression of HER2 led to a
`particularly poor prognosis in breast cancer prior to
`the '213 patent invention; right?
` MR. DANFORD: Objection. Outside the scope.
` THE WITNESS: I believe that there was some
`correlation. Yes.
`BY MR. LASKY:
` Q And prior to the '213 patent invention, work
`had been done to identify murine antibodies that
`would target the HER2 receptor; is that right?
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`preparation of your declaration?
` A Yes.
` Q Okay. Do you know how much time you spent
`reviewing that patent?
` A Again, it -- it would -- it's hard to
`estimate because I've reviewed it multiple times. So
`I've read --
` It would be a number of hours.
` Q Okay. And have you read it again since
`you've provided your declaration?
` A I've looked through it. Yeah.
` Q And do you consider yourself to be familiar
`with its contents?
` MR. DANFORD: Objection to form.
` THE WITNESS: I'm generally familiar with
`it.
`BY MR. LASKY:
` Q Okay. And did -- did you review the claims
`that are at the end of the '213 patent?
` A Yes, I did.
` Q Okay. And do you consider yourself to
`understand what the claims mean in providing your
`opinions in this case?
` A As far --
` I believe I understand the claims, yes.
`
`18
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` A I believe that is the case. Yes.
` Q Okay. Other than counsel for Genentech,
` Q And so, for example, in the Hudziak,
`have you had any discussions with anyone in
`H-u-d-z-i-a-k, reference, the authors described the
`connection with this case?
` A No.
`generation of a number of antibodies, mouse
`antibodies, against the HER2 receptor; is that right?
` Q I've handed you a copy of what's been marked
` A That is correct.
`as Pfizer Exhibit 1001 in the 01488 IPR.
` Q And Hudziak and co-authors, prior to the
` Is this the '213 patent that's at issue in
`'213 patent invention, had tested those mouse
`this case?
` A Was that a question?
`antibodies for their ability to stem cell
`proliferation; right?
` Q Yeah. Is it -- yeah.
`0
` A Could you show me the patent to -- show me
` Just for the record, is this the '213 patent
`11
`the paper to refresh my memory.
`that you considered for this case?
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` A It says '213 at the top, so I'll take it as
` Q Okay. Sorry.
`13
`'213. Yes.
` Dr. Wilson, I've handed you a copy of what's
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`been marked as Pfizer Exhibit 1021 in the 01488 IPR,
` Q Okay. Do you recognize it, though, as
`15
`and this is the Hudziak reference I was referring to.
`the -- as the patent that you have provided opinions
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` Have you reviewed this for purposes of this
`on in this case?
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` A Yes.
`case?
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` A Yes, I have.
` Q Okay. I just want to -- you've -- you've
`19
` Q Okay. And it's published in March 1989; is
`provided some opinions that you disagree with
`20
`that right?
`Dr. Foote and Dr. Riechmann and their opinions
`21
` A That is correct.
`regarding the '213 patent; right?
`22
` A Correct.
` Q And that's before the '213 patent invention;
`23
`is that right?
` Q I just want to try to get some points of
`24
` A Yes.
`agreement, though. And I want to focus on the date
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`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01488
`PFIZER EX. 1197, Page 6
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`

`

`Transcript of Ian A. Wilson, D.Phil.
`Conducted on April 21, 2018
`21
`
` Q Okay. And -- and if you -- if you look at
`the introduction, Hudz- -- in the last paragraph of
`the introduction, the authors note that, to
`facilitate investigation of the normal role of the
`HER2 gene product --
` Oh, I'm sorry.
` A So where are we?
` Q In the introduction to the paper and the
`last paragraph.
` A Okay.
` Q They note that, to facilitate investigation
`of the normal biological role of the HER2 gene
`product, they prepared monoclonal antibodies against
`the extracellular domain of the p185 HER2 protein.
` Do you see that?
` A Yes, I see that.
` Q And then one of those monoclonal antibodies,
`the 4D5, was characterized in more detail and shown
`to inhibit in vitro proliferation of human
`breast canc- -- tumor cells overexpressing HER2 and
`furthermore to increase the sensitivity of these
`cells to the cytotoxic effects of TNF-alpha.
` Do you see that?
` A Yes, I see that.
` Q And then, if you look over to page 11 of the
`
`6 (21 to 24)
`
`23
`
` Q And prior to the '213 patent invention, it
`was known that mouse antibodies had limited value as
`human therapeutics due to the likelihood of
`immunogenicity; is that right?
` MR. DANFORD: Objection to form.
` THE WITNESS: There was a concern that you
`might get a reaction against a mouse antibody if you
`give it to a human. Yes.
`BY MR. LASKY:
` Q Okay. Prior to the '213 patent invention,
`scientists investigated ways to avoid or minimize the
`immunogenetic -- immugenic -- immunogenic potential
`of murine monoclonal antibodies; right?
` MR. DANFORD: Objection to form.
` THE WITNESS: Yes.
`BY MR. LASKY:
` Q And you don't dispute in your declaration
`that, prior to the '213 patent invention, there was a
`motivation to try to develop the 4D5 monoclonal
`antibody as a human therapeutic agent; right?
` MR. DANFORD: Objection to form.
` THE WITNESS: I don't really know if I quite
`understand the question.
`BY MR. LASKY:
` Q Okay.
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`exhibit and table 1 of the reference, you see there
`is a test of certain mono- -- the -- the ability of
`certain monoclonal antibodies to inhibit tumor
`cell -- tumor cell line proliferation by
`anti-HER2 [sic] monoclonal antibodies.
` Do you see that?
` A I do.
` Q And the 4D5 antibody was shown to have
`the -- the greatest effect of relative cell
`proliferation.
` Do you see that?
` A That is correct.
` Q Okay. And -- and so back to my original
`question. Before the '213 patent invention, Hudziak
`and colleagues had shown that the 4D5 antibody was
`able to inhibit cell proliferation through targeting
`the HER2 receptor; is that right?
` MR. DANFORD: Objection to form.
` THE WITNESS: It was shown to inhibit the
`proliferation of the SK-BR-3 breast tumor cells.
`Yes.
`BY MR. LASKY:
` Q And the 4D5 antibody that was being tested
`by Hudziak was a mouse antibody; is that right?
` A Yes.
`
` A I understand, but I don't understand the
`intent of the question is really --
` Q Oh, okay. I mean, there's no intent. I'm
`just trying to --
` A No. There's -- there's many -- there's
`many -- many antibodies you could actually have
`looked at. 4D4 -- 4D5 was an antibody that had been
`identified.
` Q Okay.
` A Yep.
`0
` Q And in -- and Hudziak, at least, had shown
`11
`4D5 to be the -- the most effective at
`12
`antiproliferative activity against HER2
`13
`overexpressing breast cancer cells; right?
`14
` MR. DANFORD: Objection to form.
`15
` THE WITNESS: In the study that they did.
`16
`BY MR. LASKY:
`17
` Q Uh-huh.
`18
` A I don't know if that -- if there could have
`19
`been a better antibody, but in the part they looked
`20
`at, yes.
`21
` Q Okay. So my question is: Prior to the '213
`22
`patent invention, you would agree that, based on
`23
`Hudziak's data, there was a motivation to investigate
`24
`the 4D5 antibody as a human therapeutic agent against
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`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01488
`PFIZER EX. 1197, Page 7
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`

`

`Transcript of Ian A. Wilson, D.Phil.
`Conducted on April 21, 2018
`25
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`HER2 overexpressing breast cancer; right?
` MR. DANFORD: Objection. Asked and
`answered.
` THE WITNESS: That antibody was one of many,
`but that is -- Hudziak identified that as a
`potential.
`BY MR. LASKY:
` Q And with respect to that 4D5 antibody,
`though, again, it was known that, as a murine
`antibody, it would be likely to be ineffective as a
`human therapeutic agent due to the immunogenic
`potential; right?
` MR. DANFORD: Objection to form.
` THE WITNESS: One can't tell until one did,
`actually, the experiment, but that would have been a
`concern from -- generally from mouse antibodies.
`BY MR. LASKY:
` Q Okay. Now, prior to the '213 patent
`invention, scientists had investigated ways to reduce
`the immunogenic potential of murine monoclonal
`antibodies, one way being to develop a chimeric
`antibody; right?
` A That is correct.
` Q And the chimeric antibody was made by
`placing the murine variable domain on a human
`
`26
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`constant domain; right?
` A That's my understanding.
` Q And prior to the '213 patent invention, it
`was known that, while the chimeric approach could
`reduce the immunogenic potential of a murine
`monoclonal antibody, in some instances, it was not
`effective to do that; right?
` MR. DANFORD: Objection to form.
` THE WITNESS: My understanding is that you
`still had a lot of mouse sequence there that could
`lead to the potential of immunogenicity.
`BY MR. LASKY:
` Q And so one further solution to the
`immunogenicity problem that was known before the '213
`patent invention was to "humanize the monoclonal
`antibody"; right?
` MR. DANFORD: Objection to form.
` THE WITNESS: Yes.
`BY MR. LASKY:
` Q And humanizing a mouse monoclonal antibody
`differed from chimer- -- a chimeric approach in that
`not all of the variable domain from the mouse
`antibody was transferred into the human antibody;
`right?
` MR. DANFORD: Objection to form.
`
` A Yes.
` Q And so, prior to the '213 patent invention,
`one approach to try to regain the binding affinity
`that was lost through moving the CDRs from the mouse
`to the human framework was to make additional
`substitutions back to mouse in the human framework
`region; right?
` A There were attempts to try to do that. Yes.
` Q Now, prior to the '213 patent invention,
`several humanization efforts had been attempted using
`0
`different approaches to choosing the acceptor
`11
`framework sequence; right?
`12
` MR. DANFORD: Objection to form.
`13
` THE WITNESS: Yes.
`14
`BY MR. LASKY:
`15
` Q And so one approach that was used to choose
`16
`the acceptor framework prior to the '213 patent
`17
`invention was to identify a -- a human acceptor for
`18
`which the 3-D crystal structure was known; right?
`19
` MR. DANFORD: Objection to form.
`20
` THE WITNESS: That was one -- one approach.
`21
`BY MR. LASKY:
`22
` Q Another approach to choosing the acceptor
`23
`framework for a humanization project prior to the
`24
`'213 patent invention was to identify a human
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` THE WITNESS: Yes.
`BY MR. LASKY:
` Q And so, prior to the '213 patent invention,
`for example, it was known to humanize an antibody by
`taking just the complementarity-determining regions,
`the CDRs, from the mouse monoclonal antibodies and
`placing them in the human antibody framework; right?
` A Placing the CDRs in the human framework,
`yes. Mouse CDRs in the human framework, yes.
` Q And prior to the '213 patent invention, it
`was known that, in some cases, humanizing an antibody
`by placing the CDRs from the mouse antibody into the
`human framework would give satisfactory binding
`affinity, but in some cases, the binding affinity
`would be greatly reduced; right?
` MR. DANFORD: Objection to form.
`Lacks foundation.
` THE WITNESS: If the answer is could you --
`could you retain some binding affinity towards the
`original antigen by doing this process, the answer
`was yes, but it was hard to regain, often, the
`original affinity.
`BY MR. LASKY:
` Q Right. And that was known prior to the
`invention of the '213 patent; right?
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`PFIZER and SAMSUNG v. GENENTECH
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`PFIZER EX. 1197, Page 8
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`

`

`8 (29 to 32)
`
`Transcript of Ian A. Wilson, D.Phil.
`Conducted on April 21, 2018
`29
`
`antibody that had the most homology to the donor
`mouse antibody; right?
` A As far as the sequence is concerned, yes.
` Q And a third approach to choosing the
`acceptor framework for a humanization project known
`prior to the '213 patent invention was to use -- a
`consensus sequence identified from the Kabat
`reference; right?
` MR. DANFORD: Objection. Lacks foundation.
` THE WITNESS: No.
`BY MR. LASKY:
` Q Why do you say "no"?
` A Because Kabat is not -- does not give a
`sequence of a -- a consensus sequence's understanding
`in the terms of the '213 patent.
` Q Why do you say that Kabat does not give you
`a sequence -- consensus sequence as used in the '213
`patent?
` A Because Kabat simply adds up the number of
`residues at each position for which there's a
`particular amino acid. It was not intended as a --
`as a linear sequence. It was intended as -- as, at
`that time, the prevalence of a particular amino acid
`at any particular position.
` Q Okay. If you took -- if you made a sequence
`
`because I don't -- I haven't compared Kabat with the
`sequence that's actually in the '213 patent to figure
`out how they made that choice when there were
`ambiguities, for instance.
`BY MR. LASKY:
` Q Okay. Now, Kabat -- well, strike that.
` There have been multiple editions of the
`Kabat reference; right?
` A Correct.
` Q And so, for example, one edition was Kabat
`1987. Are you familiar with that?
` A I'm very familiar with that.
` Q And prior to that, there was another
`edition, Kabat 1983; right?
` A Yes.
` Q And then, subsequent to that, there was
`Kabat 1991.
` A '91. Yes.
` Q Have there been additional editions after
`1991?
` A I'm not aware of any, and I certainly don't
`have it on my shelf.
` Q Okay. Now, the sequences -- well, strike
`that.
` Between the three Kabat editions, the
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`using the most prevalent amino acid at every
`particular position, would you consider that to be a
`consensus sequence within the meaning of the '213
`patent?
` MR. DANFORD: Objection. Calls for a legal
`conclusion. Calls for speculation.
` THE WITNESS: There's -- Kabat has
`ambiguities in it. There -- there -- there are
`always clear indications of what sequence you would
`take. There -- there are sometimes sequences where
`the residues at a particular position are almost
`equivalent. So it would be very hard to actually
`identify even what was the prevalent amino acid in
`that position, and you'd have to choose one.
`BY MR. LASKY:
` Q Okay. And so, if you used a sequence that
`included the most prevalent amino acids that were
`indicated in Kabat at each position and, where
`multiple amino acids were identified, you choose --
`chose one of them, would the result be a consensus
`sequence within the meaning of the '213 patent, in
`your opinion?
` MR. DANFORD: Objection. Calls for a legal
`conclusion. Calls for speculation.
` THE WITNESS: I can't -- I can't tell
`
`sequences listed for any given subgroup are not
`identical; right?
` MR. DANFORD: Objection.
` THE WITNESS: I -- I --
` Oh, sorry.
` MR. DANFORD: Go ahead.
` Objection. Lacks foundation.
` THE WITNESS: I haven't compared them all,
`so I can't tell. But the intent of publish- -- if
`you were going to publish another version would be
`0
`that you would have added some sequences in the book
`11
`and the book certainly got thicker. So --
`12
`BY MR. LASKY:
`13
` Q Okay. And as new sequences are added, the
`14
`most relevant amino acid in a given position could
`15
`change between the editions; right?
`16
` MR. DANFORD: Objection. Lacks foundation.
`17
`Calls for speculation.
`18
` THE WITNESS: It is -- that is potential,
`19
`because you would add up -- you'd take all the
`20
`sequences, and you'd add them up, and you'd come up
`21
`with some number. And that number, depending on the
`22
`sequences