`
`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Leonard George
`Presta, Ph.D.
`
`Date: May 1, 2018
`Case: Pfizer, Inc. -v- Genentech, Inc. (PTAB)
`
`Planet Depos
`Phone: 888.433.3767
`Email:: transcripts@planetdepos.com
`www.planetdepos.com
`
`WORLDWIDE COURT REPORTING | INTERPRETATION | TRIAL SERVICES
`
`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01488
`PFIZER EX. 1199, Page 1
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`

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`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Leonard George Presta, Ph.D.
`Conducted on May 1, 2018
`
`1 (1 to 4)
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` A P P E A R A N C E S
`ON BEHALF OF PETITIONER PFIZER, INC.:
` BENJAMIN LASKY, ESQUIRE
` SHARICK NAQI, ESQUIRE
` KIRKLAND & ELLIS, LLP
` 601 Lexington Avenue
` New York, New York 10022
` (212) 446-6415
`ON BEHALF OF PETITIONER CELLTRION:
` LINNEA P. CIPRIANO, ESQUIRE (videoconference)
` ROBERT CERWINSKI, ESQUIRE (videoconference)
` GOODWIN PROCTER LLP
` 620 Eighth Avenue
` New York, New York 10019
` (212) 813-8800
`ON BEHALF OF PATENT OWNER GENENTECH, INC.:
` ANDREW J. DANFORD, ESQUIRE
` NORA Q.E. PASSAMANECK, ESQUIRE
` WILMER CUTLER PICKERING HALE AND DORR, LLP
` 60 State Street
` Boston, Massachusetts 02109
` (617) 526-6022
`ALSO PRESENT:
` Joseph A. Mourgos, Videographer
` Traci Ropp, Genentech
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` I N D E X
` WITNESS PAGE
` LEONARD GEORGE PRESTA, Ph.D.
` Examination by Mr. Lasky 7
` Examination by Mr. Danford 170
` Further Examination by Mr. Lasky 174
` Further Examination by Mr. Danford 178
` Further Examination by Mr. Lasky 179
` Further Examination by Mr. Danford 183
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` I N D E X O F E X H I B I T S
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` EXHIBITS DESCRIPTION PAGE
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`Exhibit 1196 Annual Reports in Medicinal 131
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` Chemistry, Volume 29, Chapter 32,
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` "Humanized Monoclonal Antibodies"
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` PREVIOUSLY MARKED EXHIBITS
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` EXHIBIT DESCRIPTION PAGE
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`Exhibit 1001 U.S. Patent Number 6,407,213 81
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`Exhibit 1193 Leopoldina-Symposium 53
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` Functional and Regulatory Aspects
`23
` of Enzyme Action article,
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` "Humanized Antibodies"
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`PLANET DEPOS
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` UNITED STATES PATENT AND TRADEMARK OFFICE
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` -----------------------------------
`
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
` -----------------------------------
`
` PFIZER, INC. and SAMSUNG BIOEPIS CO., LTD.,
`
` Petitioner,
`
` v.
`
` GENENTECH, INC.,
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` Patent Owner.
`
`0
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` -----------------------------------
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`1 2 3 4 5 6 7 8 9 1
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` Case Nos. IPR2017-01488, IPR2017-01489
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` -----------------------------------
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` CELLTRION, INC.,
`
` Petitioner,
`
` v.
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` GENENTECH, INC.,
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` Patent Owner.
`
` -----------------------------------
`
` Case Nos. IPR2017-01373, IPR2017-01374
`
`
`
` ** CONFIDENTIAL - UNDER PROTECTIVE ORDER **
`
`VIDEOTAPED DEPOSITION OF LEONARD GEORGE PRESTA, Ph.D.
`
` San Francisco, California
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` Tuesday, May 1, 2018
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` 8:58 a.m.
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`Job No.: 186258
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`Pages: 1 - 185
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`Reported By: Charlotte Lacey, RPR, CSR No. 14224
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` VIDEOTAPED DEPOSITION OF LEONARD GEORGE
`
`PRESTA, Ph.D., held at the offices of DURIE TANGRI,
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`217 Leidesdorff Street, San Francisco, California
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` Pursuant to notice, before Charlotte Lacey,
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`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01488
`PFIZER EX. 1199, Page 2
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`

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`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Leonard George Presta, Ph.D.
`Conducted on May 1, 2018
`5
`Exhibit 1194 Article, "Humanization of a mouse 138
` anti-human IgE antibody: A
` potential therapeutic for
` IgE-mediated allergies"
`Exhibit 2001 Copy of laboratory notebook 59
` number 10098
`Exhibit 2002 Copy of laboratory notebook 59
` number 10823
`Exhibit 2003 Copy of laboratory notebook 160
` number 11268
`Exhibit 2016 Declaration of Dr. Leonard G. 12
` Presta in Case IPR2017-01488
`Exhibit 2016 Declaration of Dr. Leonard G. 12
` Presta in Case IPR2017-01489
`Exhibit 2020 Article, "Humanization of an 21
` anti-p185HER2 antibody for human
` cancer therapy."
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` MS. CIPRIANO: Linnea Cipriano of Goodwin
`Procter representing Celltrion.
` THE VIDEOGRAPHER: Thank you. The court
`reporter is Charlotte Lacey representing Planet Depos.
` Would the reporter please administer the oath.
`
` LEONARD GEORGE PRESTA, Ph.D.,
`the witness herein, having been first duly sworn, was
`examined and testified as follows:
`
` EXAMINATION
`BY MR. LASKY:
` Q Good morning, Dr. Presta.
` A Good morning.
` Q Can you please state your name for the record.
` A Leonard George Presta.
` Q And have you had your deposition taken before?
` A Yes.
` Q How many times?
` A Three times.
` Q Okay.
` When was the first time you had your
`deposition taken?
` A That was in the mid-'90s.
` Q And what was the subject matter of that
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`2 (5 to 8)
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` P R O C E E D I N G S
` THE VIDEOGRAPHER: Here begins video number 1
`in the videotaped deposition of Dr. Leonard G. Presta in
`the matter of Pfizer Incorporated, et al., versus
`Genentech Incorporated, IPR number 2017-01488 and 01489,
`and Celltrion versus Genentech, IPR number 2017-01373
`and 01374. In the United States Patent and Trademark
`Office before the Patent Trial and Appeal Board.
` Today's date is May 1st, 2018, and the time on
`the video monitor is 8:59 a.m. The videographer today
`is Joseph Mourgos representing Planet Depos. This video
`deposition is taking place at 217 Leidesdorff Street,
`San Francisco, California.
` Would counsel please voice identify yourselves
`and state whom you represent.
` MR. LASKY: Good morning. My name is Ben
`Lasky. I'm from Kirkland & Ellis. I represent Pfizer.
`With me today is my colleague, Sharick Naqui, also from
`Kirkland & Ellis.
` MR. DANFORD: My name is Andrew Danford of
`WilmerHale. I'm here today representing Genentech and
`the witness. And I'm joined today by my colleague Nora
`Passamaneck and Traci Ropp of Genentech.
` THE VIDEOGRAPHER: And on the telephone, we
`have...
`
`deposition?
` A It was for a European Union Patent Office
`action, Genentech, et al. versus Protein Design Labs.
` Q And what was that patent dispute about, to the
`extent that you recall?
` A It was the -- the humanization patent of Cary
`Queen.
` Q And was Genentech challenging that
`humanization patent of Cary Queen to the best of your
`recollection?
`0
` A I think Genentech and I think the total there
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`were 18 companies at the...
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` Q And were you representing Genentech as an
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`expert witness in that case?
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` A No, I was an employee.
`15
` Q Okay.
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` And what was the subject matter of your
`17
`testimony in that case?
`18
` A I never actually gave testimony, just did the
`19
`declaration.
`20
` Q Okay.
`21
` The declaration -- sorry. Strike that.
`22
` So just to be clear, did you actually have a
`23
`deposition taken in that case?
`24
` A Yes.
`25
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`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01488
`PFIZER EX. 1199, Page 3
`
`

`

`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Leonard George Presta, Ph.D.
`Conducted on May 1, 2018
`9
`
` Q Okay.
` So what, in general, was the subject matter of
`the declaration you submitted in that case?
` A The -- it was so long ago. It was primarily
`just countering the -- the Cary Queen PDL humanization
`patent.
` Q Okay.
` The second deposition that you had taken, out
`of the three that you mentioned, what -- what case was
`that for?
` A These were not Genentech cases. These were
`for consulting clients.
` Q Okay.
` And you were representing them as a -- an
`expert witness in those cases?
` A Expert witness, yes.
` Q Okay.
` Which -- starting with the first deposition,
`which company were you retained consultant for in that
`case?
` A I don't think they want me divulging that.
` Q Is this -- well, let me -- let me start with
`when was this?
` A The first -- this was 2013 to 2014.
` Q Okay.
`
`3 (9 to 12)
`
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` Q Okay.
` A So it never went to court.
` Q Okay.
` Do you know if the dispute was filed in a
`court?
` A No, I do not.
` Q Okay. The third deposition you had taken,
`that was also as a retained expert?
` A Yes.
` Q Was any -- were any of your opinions in that
`case made publicly available through submission to a
`court or otherwise.
` A I do not know.
` Q Okay.
` When -- when was this?
` A This was soon after that same company.
` Q Okay.
` So it's also for Alder Pharmaceuticals?
` A Right.
` Q Okay.
` The only time you have had your deposition
`taken, when an employee of Genentech, related to that
`action challenging PDL's patent; is that right?
` A Correct.
` Q Okay.
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` And were any of your opinions made public at
`that time through -- through either, you know, being
`included in a submission to a court or otherwise?
` A Submission to the court.
` Q Okay.
` So just focusing on what was made public as a
`submission to the court, what was your -- what was the
`company that you were retained by?
` A Alder Pharmaceuticals.
` Q Okay.
` And what was the subject matter of your
`testimony that was made public?
` A They were challenge --
` Q Just -- I apologize -- that was made public
`through submission to the court.
` A They were challenging the patent of another
`company.
` Q Okay.
` And do you recall what company that was?
` A No, I don't. It was a very small company. I
`don't remember the name.
` Q Okay. Do you remember what jurisdiction it
`was in in the sense of was it in the patent office or in
`a court?
` A It -- it -- I think they settled.
`
` Have you submitted any declarations in any
`proceedings other -- for Genentech other than the inter
`partes review proceedings that we are here for today?
` A Other than the PDL case, I cannot remember
`any.
` Q Okay. What is your current position?
` A I'm retired. And I do -- but I do do
`consulting for various companies.
` Q Okay.
` When did you retire?
`0
` A December 2012.
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` Q Okay.
`12
` In December 2012 when you retired or before
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`you retired, what was your position at that point?
`14
` A I was a scientist at Merck & Company in Palo
`15
`Alto, California.
`16
` Q Okay.
`17
` Dr. Presta, I've handed you copies of two
`18
`documents. For the record, the first document I've
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`handed you has been marked as Genentech Exhibit 2016 in
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`IPR2017-01488, and the second document that I handed you
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`has been marked Genentech Exhibit 2016 in IPR2017-01489.
`22
` Do you recognize these documents?
`23
` A Yes.
`24
` Q Are these the declarations that you prepared
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`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01488
`PFIZER EX. 1199, Page 4
`
`

`

`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Leonard George Presta, Ph.D.
`Conducted on May 1, 2018
`13
`
`that have been submitted in the inter partes reviews
`brought by Pfizer relating to U.S. patent
`number 6,407,213?
` A Yes.
` Q And if I refer to that patent as the
`'213 patent in this deposition, will you understand what
`I'm saying?
` A Yes.
` Q Okay.
` There are also declarations -- well, strike
`that.
` Are you aware of any differences between the
`two declarations that I've handed you?
` A No.
` Q Okay.
` Are you aware that declarations in your name
`have also been submitted in proceedings brought by
`Celltrion relating to the '213 patent?
` A Yes.
` Q And are those declarations substantively
`identical to the declarations that you provided in the
`Pfizer case?
` A As far as I know, yes.
` Q Okay.
` And so if I focus on one of the declarations
`
`4 (13 to 16)
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` Now, prior to joining -- well, strike that.
` Your position at Genentech was your first
`position in industry; is that right?
` A Correct.
` Q And prior to that, had you had any experience
`working on antibody humanization projects?
` A No.
` Q Okay.
` As a postdoctoral -- well, strike that.
` In paragraph 3, you mention that after
`obtaining your Ph.D., you took a postdoctoral position
`in the group of Dr. George Rose at Hershey Medical
`Center, Penn State University.
` Do you see that?
` A Yes.
` Q And you worked on molecular modeling in that
`position, right?
` A Correct.
` Q What was the purpose of the molecular modeling
`you did while in postdoctoral position at the Hershey
`Medical Center?
` A I came up with a hypothesis governing how
`alpha helices, the protein sequence in a protein, starts
`and stops alpha helices.
` Q And did you consider at the time that that
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`today, will your testimony generally apply to all of the
`declarations in your name that have been submitted in
`this IPR proceeding?
` A Yes.
` Q Okay. So let's focus on the Exhibit 2016 in
`IPR2017-01488. Are you aware of any errors in that
`declaration?
` A No.
` Q Is there anything in the declaration you would
`change if you had the opportunity today?
` A No.
` Q Okay.
` If you can open up to the background section
`of your declaration, which starts in paragraph 1 and it
`goes through to paragraph 8, I want to focus on that
`section first.
` As you mention in paragraph 4, you joined
`Genentech as a molecular modeler in the protein
`engineering department in 1988.
` Do you see that?
` A Yes.
` Q Do you recall when in 1988 you joined
`Genentech?
` A September 1st.
` Q Okay.
`
`work might have any further applications beyond the
`study itself?
` MR. DANFORD: Objection to form.
` Q I'm -- I'm asking for you --
` A Yeah.
` Q -- what you were thinking at the time.
` A This was purely scientific.
` Q Okay.
` A Protein folding.
` Q Uh-huh. Okay.
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` And was any of that protein folding
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`investigation specific to antibodies?
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` A No.
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` Q Now, during your Ph.D. work at the Texas A&M
`14
`University, you also did work on molecular modeling and
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`X-ray crystallography, right?
`16
` A Correct.
`17
` Q And what was the focus of that research?
`18
` A A class of proteins called serine proteases.
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` Q And what was known about the function of
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`serine proteases at that time?
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` A They are enzymes that clip specific sequences
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`and other proteins.
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` Q And what were you modeling the serine
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`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01488
`PFIZER EX. 1199, Page 5
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`

`

`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Leonard George Presta, Ph.D.
`Conducted on May 1, 2018
`17
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`5 (17 to 20)
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` Now, in paragraph 5, you begin your discussion
`of the project that ultimately led to the humanization
`of the antibody now known as Herceptin, right?
` A Correct.
` Q And you said you "began to apply your modeling
`skills and knowledge to that project
` Do you see that?
` A Yes.
`
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` A That should be in the laboratory notebook.
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` Q Okay. Okay. We'll get there.
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` A I worked on a -- on an enzyme called elastase,
`which is potentially involved, for example, in COPD, and
`it was to design inhibitors for that enzyme.
` Q Okay.
` And for the record, what is COPD?
` A Chronic obstructive pulmonary disease.
` Q Okay.
` So in that sense -- in that sense, this work
`was -- had a potential therapeutic application down the
`road?
` A That was the hope, yes.
` Q Okay.
` Did any of the work that you did while doing
`your Ph.D. have any relation to antibodies specifically?
` A No.
` Q Okay.
` Did you also do any study of modeling during
`your Bachelor of Science degree at the University of
`Arizona?
` A No.
` Q Okay.
` Going back now to the time when you began at
`Genentech in September 1988, you note here in
`paragraph 4 that your initial role was "to create
`computer models representing proteins with actual or
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`hypothetical by using known information about the
`proteins' amino acid sequences and the crystal
`structures of related proteins."
` Do you see that?
` A Yes.
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`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01488
`PFIZER EX. 1199, Page 6
`
`

`

`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Leonard George Presta, Ph.D.
`Conducted on May 1, 2018
`21
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`6 (21 to 24)
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` MR. DANFORD: Objection to form.
` A I was provided -- once we started the project,
`I was provided with a sequence of the 4D5 from the
`hybridoma.
` Q Okay. And so at the time that you got
`involved in the project, it -- it had already been
`decided that the 4D5 is the antibody that should be
`humanized; is that right?
` A Correct.
` Q And you weren't involved in the decision as --
`to go forward with humanizing 4D5 rather than any other
`anti- -- HER2 antibody; is that right?
` A Correct.
` Q Do you -- did you have knowledge at that time
`of why the 4D5 antibody was chosen for humanization?
` A No, I did not.
` Q Okay. Do you now have such knowledge?
` A Yes.
` Q Okay. And -- and why was the 4D5 antibody
`chosen to be humanized?
` A In the -- in the set of antibodies that passed
`all of the assays, both binding and bio assay, this is
`the one -- the 4D5 had the particular attributes that
`they were looking for.
` Q Okay. Are you familiar with the reference in
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` Your understanding, though, is that the
`laboratory notebook that we've been supplied with would
`identify the first work that you did on this project?
` A Yes.
` Q Okay.
` Now, how is it that you've began to work on
`this project?
` A Genentech had an anti-HER2 antibody campaign.
`They had antibodies that they had screened, and Paul
`Carter came to me and having -- he was previously in
`Greg Winter's lab, so he was aware of the technique of
`humanization and wanted to know if I thought we could --
`could do this at Genentech.
` Q Okay.
` And at that time that you were first
`contacted, did you have any experience with
`humanization?
` A No.
` Q Did you have knowledge of the -- the work that
`had been ongoing in the field at that time in
`humanization?
` A No.
` Q Okay. Dr. Presta, I've handed you what was
`previously marked as Genentech Exhibit 2020 in these
`proceedings. It's a copy of an article from the
`
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`proceedings of the National Academy of Sciences, U.S.A.,
`May 1992, and it's titled "Humanization of an
`anti-p185HER2 antibody for human cancer therapy."
` Do you recognize this document?
` A Yes.
` Q And this is a document that you are a coauthor
`on; is that right?
` A Correct.
` Q And this is the article that was published in
`1992 describing the humanization project leading to
`humanized 4D5 antibody, right?
` A Correct.
` Q I'm going to ask you questions about this
`later, but I'm giving it to you now so that if you need
`to refresh your recollection about any of the
`background, you can take a look at it, okay?
` A Okay.
` Q Okay.
` So at the time that you were brought into the
`project to humanize 4D5, the -- the work to generate and
`screen anti-HER2 antibodies had already been done; is
`that correct?
` A Correct.
` Q And did -- were you provided the results at
`that time?
`
`which the results of that screening were published?
` A Don't understand that.
` Q Okay. Do you understand that the results of
`the initial screen that ultimately led to choosing the
`4D5 antibody were published?
` MR. DANFORD: Objection to form.
` A Prior to -- you mean prior to this paper?
` Q Yes.
` A Okay. No, I -- at the time, I was not aware
`of that.
`0
` Q Okay. And so if we take a look at -- at your
`11
`paper, if we look at the -- so this is Exhibit 2020. If
`12
`we look at the left-hand column in the introduction,
`13
`about halfway down the first paragraph, there's a
`14
`sentence beginning, "The murine monoclonal antibody."
`15
`Do you see that?
`16
` A The one with reference 6 in it?
`17
` Q That's right.
`18
` A Okay.
`19
` Q And -- and so there it states, "The murine
`20
`monoclonal antibody muMAb4D5," that's m-u-M-A-b 4D5,
`21
`"directed against the extracellular domain of p185HER2,
`22
`specifically inhibits the growth of tumor cell lines
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`overexpressing p185HER2 in monoclonal" -- sorry -- "in
`24
`monolayer culture or in soft agar," and then there's two
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`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Leonard George Presta, Ph.D.
`Conducted on May 1, 2018
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`every time for a different framework, you do it once,
`and then you can just make the changes in that piece of
`DNA.
` Q Okay. And did it come -- did there come a
`time when you shared your idea of a consensus sequence
`with Dr. Carter?
` A Yes.
` Q And when was that?
` A I don't recollect exactly, but it -- it must
`have been soon after we started the project.
` Q Okay. Do you recall what his reaction to that
`idea was?
` A No, I do not.
` Q Now, when you came up with the idea of a
`consensus sequence and you presented it to Dr. Carter,
`at that time, did you -- had you determined how a
`consensus sequence might be generated?
` MR. DANFORD: Objection to form.
` A I knew at that time, after familiarizing
`myself with some of the antibody literature, that
`earlier Elvin Kabat had taken all known
`human/mouse/rabbit antibody sequences, published them in
`a government publication, and that there were human
`subgroups of sequences within the heavy and the light
`chains.
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`more references, 7, 8. Do you see that?
` A Yes.
` Q And so if we look at the references, for
`example, reference 7 is a -- is a reference where
`Dr. Hudziak, H-u-d-z-i-a-k, is the first named author.
`And it's published in 1989. Do you see that?
` A Yes.
` Q Are you familiar with that reference?
` A I have read that, but that was decades ago.
` Q Sure. And -- and by the way, I'm trying to
`get your best recollection. If you don't remember
`anything, you -- you just let me know.
` Does this refresh your recollection that the
`results of the assays on the murine antibodies had been
`published before your paper, Exhibit 2020?
` A Could you state that again?
` Q Sure. Understand.
` Looking now at the reference in your -- in
`your paper, Exhibit 2020, to the Hudziak paper,
`reference 7, does that refresh your recollection that
`the results of the assays that were done on the 4D5
`murine antibodies and others had been published?
` A Yes.
` Q Okay. Now, in paragraph 5 of your
`declaration, you state that you began --
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` So the first thought was I want a consensus of
`, you began to apply your modeling skills and
`one of the human subgroups. I don't want a consensus of
`knowledge to create a human consensus sequence for an
`all human antibodies; that wouldn't be very useful.
`antibody with the idea that such a consensus sequence
` Q Okay. And as -- as you -- well, strike that.
`could be used as a broadly applicable framework to
` At that time, how was it that you knew about
`create humanized antibodies. Do you see that?
` A Yes.
`the Kabat work?
` A It was -- once you started getting into
` Q Now, whose idea was it to generate a human
`reading the papers, people quoted these -- these
`consensus sequence for the project?
`references.
` A That was mine.
` Q Okay. Now, so at -- at the time you came up
` Q Okay. And what was your thinking at the time?
`0
` A So I was aware of the PNAS Cary Queen
`with the idea of the consensus sequence, you were aware
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`publication, as well as the earlier publications of
`of the Kabat reference; is that right?
`12
` A As -- as I -- as one of many references, yes.
`Winter's group. The -- the reason for doing a human
`13
`consensus sequence was multifold. First, that I -- I
` Q Right. And you were aware of the Queen 1989
`14
`had hope that Genentech would do many antibodies. So
`reference describing their humanization of the anti-Tac
`15
`having the same framework in all of the therapeutic
`antibody; is that right?
`16
` A Yes.
`antibodies would hopefully make manufacturing easier.
`17
` A second reason was that if you used the best
` Q And you were also aware of the Riechmann
`18
`fit method in the -- in the Cary Queen publication, that
`publication describing the humanization of Campath at --
`19
` A Yes.
`there was potential because you are -- you are using
`20
`antibody sequences from individuals that there could be
` Q -- sorry -- at the Winter lab; is that right?
`21
` A Yes.
`some idiosyncratic sequences that might not be
`22
`acceptable as a therapeutic.
` Q And were you also aware of the Jones
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` And third was, back then, synthesizing DNA was
`publication describing the very first humanization at
`24
`a real effort, and instead of having to create the DNA
`the Winter lab?
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`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Leonard George Presta, Ph.D.
`Conducted on May 1, 2018
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` A Yes.
` Q Now, when did you look into that literature
`after Dr. Carter -- well, strike that.
` Who was it who first approached you to join
`the project of humanizing 4D5?
` A Paul Carter.
` Q Okay. Now, was it after Dr. Carter approached
`you that you looked into the existing literature about
`antibody humanization?
` A Yes.
` Q Okay. Now, did you -- strike that.
` For the antibodies that were generated at the
`Winter lab, did you go beyond the published literature
`to contact anyone at the Winter lab to understand how
`their humanization had taken place?
` A I did that.
` MR. DANFORD: Objection to form.
` Q And do you know if Dr. Carter did?
` A No, I do not know if he did.
` Q Okay. Now, focusing on your three reasons for
`humanizing with a consensus sequence that you mentioned,
`the first one you -- you gave was the hope that if
`Genentech was going to humanize multiple antibodies
`using -- well, strike that.
` Let me go back up -- back up a step. You
`
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`available.
` Q Okay. And then of course beyond what was
`published at the time, there were also sequences that
`existed within humans that had not been published,
`right?
` MR. DANFORD: Objection to form.
` A Correct.
` Q Okay. And so beyond what was -- well, strike
`that.
` And you understand that multiple editions of
`Kabat exist; is that right?
` MR. DANFORD: Objection to form.
` A As far as I am aware, there are only two
`editions.
` Q Which editions --
` THE REPORTER: I'm sorry?
` THE WITNESS: Pardon?
` THE REPORTER: Only two?
` THE WITNESS: As far as I know, there are only
`two editions.
` THE REPORTER: Thank you.
` Q And which editions are you aware of?
` A 1987 and 1991.
` Q Okay. Now, the 1991 Kabat would -- well,
`strike that.
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` Do you know if the 1991 edition of Kabat
`mentioned that in determining the way to generate a
`includes additional sequences beyond those that were
`consensus sequence, you were aware of the Kabat 1987
`published in Kabat 1987?
`reference, right?
` A I don't know for sure.
` A Correct.
` Q Okay. Do you have an expectation in that
` Q Now, at the time, were there other ways to
`regard?
`generate a consensus sequence other than by reference to
` MR. DANFORD: Objection to form.
`Kabat 1987?
` A I -- I would assume he did a second
` MR. DANFORD: Objection to form.
`publication because there were more sequences.
` A The only other way I could think of to do that
`would be to retrieve all of the antibody sequences that
` Q Okay. And the most common sequence at every
`0
`Kabat had already done and, in essence, repeat the --
`position in an antibody in a given subgroup may change
`11
`getting all of these -- these sequences from the
`depending on which sequences you are using to generate
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`independent publications.
`that, right?
`13
` MR. DANFORD: Objection to form, calls for
` Q Okay. So at the time, there were sequences of
`14
`speculation.
`antibodies within particular subgroups that were known
`15
` A I -- I'm still unclear of the question.
`based on published literature; is that right?
`16
` A Correct.
` Q Okay. The most common residue at any given
`17
`position identified in a Kabat edition is based on the
` Q And then at least some of those were
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`sequences that Kabat collected in that edition, right?
`identified by Kabat and listed in the Kabat 1987
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` A Correct.
`reference; is that right?
`20
` A Correct.
` Q And so if Kabat identified additional
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`sequences to include in a different edition than the
` Q Now, do you know if Kabat included all of the
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`most common residue at any given position might also be
`immunoglobulin sequences, that had been pu