`
`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Paul J. Carter, Ph.D.
`
`Date: April 27, 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
`IPR2017-01489
`PFIZER EX. 1698, Page 1
`
`

`

`Page 3
`
`1 A P P E A R A N C E S
`2 ON BEHALF OF PETITIONER PFIZER, INC.:
`3 BENJAMIN LASKY, ESQUIRE
`4 SHARICK NAQI, ESQUIRE
`5 KIRKLAND & ELLIS, LLP
`6 601 Lexington Avenue,
`7 New York, New York 10022
`8 (212) 446-6415
`9 ON BEHALF OF PETITIONER CELLTRION:
`10 LINNEA P. CIPRIANO, ESQUIRE
`11 (Via videoconference)
`12 GOODWIN PROCTER LLP
`13 620 Eighth Avenue
`14 New York, New York 10019
`15 (212) 813-8800
`16 ON BEHALF OF PATENT OWNER GENENTECH, INC.:
`17 ANDREW J. DANFORD, ESQUIRE
`18 NORA Q.E. PASSAMANECK, ESQUIRE
`19 WILMER CUTLER PICKERING HALE AND DORR, LLP
`20 60 State Street,
`21 Boston, Massachusetts 02109
`22 (617) 526-6022
`23 ALSO PRESENT:
`24 Joseph A. Mourgos, Videographer
`25 Traci Ropp, Genentech
`
`1 I N D E X
`2 WITNESS
`3 PAUL J. CARTER, Ph.D.
`4 Examination by
`Mr. Lasky
`5 Examination by
`Mr. Danford
`6 Further Examination by Mr. Lasky
`
`Page 4
`
`PAGE
`
`7
`174
`175
`
`7 8 9
`
`I N D E X O F E X H I B I T S
`10 EXHIBITS DESCRIPTION
`11
`(None offered)
`12
`PREVIOUSLY MARKED EXHIBITS
`13
`PAGE
`14 EXHIBIT DESCRIPTION
`15 Exhibit 1001 U.S. Patent Number 6,407,213
`16 Exhibit 1193 Leopoldina-Symposium
`17
`Functional and Regulatory Aspects
`18
`of Enzyme Action article,
`19
`"Humanized Antibodies"
`20 Exhibit 2003 Copy of laboratory notebook
`21 number 11268
`22 Exhibit 2004 Copy of laboratory notebook
`23 number 11643
`24 Exhibit 2017 Declaration of Dr. Paul J. Carter 8
`25 in Case IPR2017-01488
`
`PAGE
`
`34
`19
`
`130
`
`130
`
`Pages 1 - 4
`
`Page 1
`1 UNITED STATES PATENT AND TRADEMARK OFFICE
`2 -----------------------------------
`3 BEFORE THE PATENT TRIAL AND APPEAL BOARD
`4 -----------------------------------
`5 PFIZER, INC. And SAMSUNG BIOEPIS CO., LTD.,
`6
`Petitioner,
`7
`v.
`8
`GENENTECH, INC.,
`9
`Patent Owner.
`10 -----------------------------------
`11 Case Nos. IPR2017-01488, IPR2017-01489
`12 -----------------------------------
`13
`CELLTRION, INC.,
`14
`Petitioner,
`15
`v.
`16
`GENENTECH, INC.,
`17
`Patent Owner.
`18 -----------------------------------
`19 Case Nos. IPR2017-01373, IPR2017-01374
`20
`21 ** CONFIDENTIAL - UNDER PROTECTIVE ORDER **
`22 VIDEOTAPED DEPOSITION OF PAUL J. CARTER, Ph.D.
`23 San Francisco, California
`24
`Friday, April 27, 2018
`25
`9:09 a.m.
`
`Page 2
`
`1 Job No.: 186256
`2 Pages: 1 - 177
`3 Reported By: Charlotte Lacey, RPR, CSR No. 14224
`
`4 5
`
` VIDEOTAPED DEPOSITION OF PAUL J. CARTER, Ph.D.,
`6 held at the offices of DURIE TANGRI, 217 Leidesdorff
`7 Street, San Francisco, California
`
`8 9
`
`10
`11
`12 Pursuant to notice, before Charlotte Lacey,
`13 Certified Shorthand Reporter, in and for the State of
`14 California.
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`[4/27/2018] Carter, Paul 2018-04-27 v01
`
`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Paul Carter, Ph.D.
`Conducted on April 27, 2018
`
`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01489
`PFIZER EX. 1698, Page 2
`
`

`

`Page 7
`
`1 THE VIDEOGRAPHER: Thank you.
`2 On the video conference we have:
`3 MS. CIPRIANO: Linnea Cipriano of Goodwin
`4 Procter representing Celltrion.
`5 THE VIDEOGRAPHER: The court reporter today is
`6 Charlotte Lacey representing Planet Depos.
`7 Would the reporter please administer the oath.
`8 PAUL J. CARTER, Ph.D.,
`9 the witness herein, having been first duly sworn, was
`10 examined and testified as follows:
`11 EXAMINATION
`12 BY MR. LASKY:
`13 Q Good morning, Dr. Carter.
`14 A Good morning.
`15 Q Do you understand today that you're being
`16 deposed in proceedings before the Patent Office
`17 challenging your patent, the '213 patent?
`18 A Yes, I do I understand that.
`19 Q Okay.
`20 And you've submitted several declarations in
`21 the proceedings relating to that patent, correct?
`22 A There's at least one declaration that I'm
`23 aware of.
`24 Q Right. Okay.
`25 And that same declaration, are you aware that
`
`Page 5
`1 Exhibit 2017 Declaration of Dr. Paul J. Carter 8
`2 in Case IPR2017-01489
`3 Exhibit 2020 Article, "Humanization of an 15
`4 anti-p185HER2 antibody for human
`5 cancer therapy"
`
`6 7 8 9
`
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`Page 6
`
`Page 8
`
`1 P R O C E E D I N G S
`2 THE VIDEOGRAPHER: Here begins video number 1
`3 in the videotaped deposition of Paul J. Carter, Ph.D.,
`4 in the matter of Pfizer Incorporated, et al. versus
`5 Genentech Incorporated in the United States Patent and
`6 Trademark Office before the Patent Trial and Appeal
`7 Board, IPR numbers 2017-01488 and 01489 regarding Pfizer
`8 versus Genentech and 01373 and 01374 regarding Celltrion
`9 versus Genentech.
`10 Today's date is April 27th, 2018. The time on
`11 the video monitor is 9:10 a.m. The videographer is
`12 Joseph Mourgos representing Planet Depos. This video
`13 deposition is taking place at 217 Leidesdorff Street,
`14 San Francisco, California.
`15 Would counsel please voice identify yourselves
`16 and state whom you represent, beginning with those in
`17 the room.
`18 MR. LASKY: My name is Benjamin Lasky. I'm
`19 from Kirkland & Ellis, and I represent Pfizer. And with
`20 me today is my colleague Sharick Naqi, also from
`21 Kirkland & Ellis.
`22 MR. DANFORD: And I'm Andrew Danford,
`23 WilmerHale. I represent Genentech. And I'm joined
`24 today by colleague, Nora Passamaneck of WilmerHale and
`25 Traci Ropp of Genentech.
`
`1 it has been submitted different times in different
`2 proceedings?
`3 A I am aware of that.
`4 Q Okay.
`5 Dr. Carter, I've handed you what has been
`6 marked as Exhibit 2017 in two different proceedings.
`7 And I'm just doing this for the record. The proceedings
`8 are IPR2017-01488 and 2017-01489.
`9 Are these the declarations that you submitted
`10 in these proceedings?
`11 A Let me look at them, and then I'll be able to
`12 answer your question.
`13 Q Sure.
`14 A This one looks good. So this is 01488.
`15 Let me look at 01489. Is this the same...
`16 Q Well, let me ask you this --
`17 A Well, let me look first.
`18 Q Sure. You can -- you can look. Take your
`19 time.
`20 A So this is declaration 01489. This also seems
`21 to be in order.
`22 Q Okay. Do you know of any differences between
`23 the two declarations or are they substantively
`24 identical?
`25 A To the best of my knowledge, they're the same.
`
`[4/27/2018] Carter, Paul 2018-04-27 v01
`
`Pages 5 - 8
`
`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Paul Carter, Ph.D.
`Conducted on April 27, 2018
`
`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01489
`PFIZER EX. 1698, Page 3
`
`

`

`Page 9
`
`Page 11
`
`1 Q Okay.
`2 And I guess for all of these proceedings
`3 regarding the '213 patent, do you remember preparing
`4 more than one declaration with the -- with differences?
`5 That's a bad question. Let me -- strike that.
`6 Are you aware of any differences between the
`7 declarations that I've put before you that were
`8 submitted in the Pfizer proceedings and the declarations
`9 that were submitted in other proceedings involving
`10 Celltrion?
`11 A To the best of my knowledge, there are no
`12 differences.
`13 Q Okay.
`14 Did you review your declarations in
`15 preparation for the deposition today?
`16 A Yes, I did review the declaration.
`17 Q Okay.
`18 In re-reviewing the declaration, have you
`19 found anything that was inaccurate?
`20 A To the best of my knowledge, there -- I'm
`21 unaware of anything that's inaccurate.
`22 Q Okay.
`23 And in reviewing -- re-reviewing your
`24 declarations, did you find anything that you would now
`25 change?
`
`1 Q Okay.
`2 And from the time you began in Sir Gregory
`3 Winter's lab, were you working on antibody chemistry at
`4 that time?
`5 A Most of the time, I was working on a -- my
`6 thesis project, which was, Site-directed mutagenesis of
`7 tyrosyl tRNA synthetase from -- from Bacillus --
`8 Bacillus stearothermophilus.
`9 Q Okay.
`10 That work did not involve work with
`11 antibodies; is that right?
`12 A This particular project did not.
`13 Q Okay.
`14 When -- strike that.
`15 Did you do any antibody-related work while you
`16 were in the Winter lab?
`17 A I did a very small amount of antibody work.
`18 Q Okay.
`19 And when would that have started?
`20 A To the best of my recollection, that was
`21 towards the end of my Ph.D., actually after I had
`22 submitted my thesis.
`23 Q Okay.
`24 And would that be, then, around about 1985
`25 onwards?
`
`Page 10
`
`Page 12
`
`1 A There's nothing that I would change after
`2 re-reviewing.
`3 Q Okay.
`4 I'd like to ask you some questions about the
`5 background section of your declaration. And we can
`6 focus on the 01488 declaration. You can put the other
`7 one aside. If there's any differences you work out, you
`8 can let me know.
`9 So you obtained your BA in Natural Sciences
`10 from Cambridge in 1982; is that correct?
`11 A Yes, that is correct.
`12 Q And the Ph.D. in Molecular Biology in 1986 was
`13 obtained at the Medical Research Counsel Laboratory; is
`14 that right?
`15 A Laboratory of Molecular Biology --
`16 Q Uh-huh.
`17 A -- correct.
`18 Q And is that -- was that Dr. Winter's lab at
`19 the time?
`20 A It is Dr. Gregory Winter. Actually now,
`21 Sir Gregory Winter.
`22 Q Okay. And when did you begin working in
`23 Dr. Winter's lab, either as a Ph.D., researcher,
`24 postdoctoral fellow, or otherwise?
`25 A So I began in Sir Gregory's lab in 1982.
`
`1 A That period would have been from late 1985
`2 through early 1986.
`3 Q Okay.
`4 And at that point, is that when you joined
`5 Genentech as a postdoctoral fellow?
`6 A That is correct.
`7 Q Okay.
`8 The work that you did in late 1985 through
`9 early 1986, what was the project?
`10 A It was a project that I initiated trying to
`11 explore a new technology that had just been published
`12 using polymerase chain reaction.
`13 Q And how was -- and polymerase chain reaction
`14 also referred to as PCR?
`15 A Correct. We can call it PCR.
`16 Q Okay.
`17 PCR, how was that being used in the project
`18 that you were doing at the Winter lab in late 1985
`19 through early 1986?
`20 A I was trying to get the PCR technology to --
`21 to work, and I chose a human -- humanized antibody gene
`22 to -- to do that.
`23 Q Which gene did you choose?
`24 A I believe it would have been one of the genes
`25 from the early humanization work from the -- from the
`
`[4/27/2018] Carter, Paul 2018-04-27 v01
`
`Pages 9 - 12
`
`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Paul Carter, Ph.D.
`Conducted on April 27, 2018
`
`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01489
`PFIZER EX. 1698, Page 4
`
`

`

`Page 13
`
`Page 15
`
`1 Winter laboratory.
`2 Q Okay.
`3 You don't recall which particular project?
`4 A I believe that it was the antibody genes in
`5 the -- in the Jones, et al., publication, to the best of
`6 my knowledge, something which is more than 30 years
`7 later.
`8 Q Yes. Understandable.
`9 The -- who at the Winter lab was working with
`10 you on this project at the time?
`11 A It was really nobody else. It was just
`12 myself.
`13 Q Okay.
`14 Were you seeking advice from anyone in the
`15 laboratory at that time on this project?
`16 MR. DANFORD: Objection to form.
`17 A I was -- I don't remember clearly this --
`18 this -- these number of years later. Sorry.
`19 Q Okay.
`20 Did you ever overlap in time at the Winter lab
`21 with Lutz Riechmann?
`22 A To the best of my recollection, Lutz Riechmann
`23 joined the -- Sir Gregory Winter's laboratory after I
`24 joined at Genentech.
`25 Q Okay.
`
`1 A I was aware of at least some of that work,
`2 including work that had begun prior to my joining
`3 Genentech.
`4 Q Okay. One of the projects that was undertaken
`5 in the Winter lab in the late 1980s was attempts to
`6 humanize an anti-lysozyme protein antibody. Is that --
`7 well, strike that.
`8 Are you aware of a project that was undertaken
`9 in the Winter labs in the 1980s to humanize an
`10 anti-lysozyme antibody?
`11 MR. DANFORD: Objection; outside the scope.
`12 A Yes. I am aware of that antibody humanization
`13 project.
`14 Q Were you aware of that project while you were
`15 at Genentech between 1986 and 1989?
`16 A I was aware of that work, in part because it
`17 was published.
`18 Q Okay. Do you happen do you recall where it
`19 was published?
`20 A If you can provide me with my PNAS paper, we
`21 can -- we can look at the exact reference.
`22 Q Okay. Dr. Carter, I've handed you a copy of
`23 what's been marked as Genentech Exhibit 2020 in both the
`24 1488 and 1499 -- 89 proceedings. And it's a copy of an
`25 article titled "Humanization of an anti-p185HER2
`
`Page 14
`
`1 And did you overlap in the Winter lab at any
`2 time with Jeffrey Foote?
`3 A To the best of my recollection, Jeff Foote
`4 joined Sir Gregory Winter's lab after I left --
`5 actually, my recollection is that Jeff inherited my
`6 bench.
`7 Q Okay.
`8 At the time that you joined Genentech in 1986
`9 through -- to the spring of 1989, when you started your
`10 own laboratory, did you have any contact with the Winter
`11 lab anymore?
`12 A I had intermittent contact.
`13 Q And did any of that contact involve Jeff
`14 Foote?
`15 MR. DANFORD: Objection to form.
`16 A I don't honestly remember this far -- it was a
`17 long time ago.
`18 Q Okay.
`19 And is the same true with respect to Lutz
`20 Riechmann?
`21 A I don't remember. It's a very long time ago.
`22 Q Okay. At the time that you were in -- at
`23 Genentech in the 1986 to 1989 time frame, were you aware
`24 of the work that was being done at Winter lab in
`25 humanization of antibodies?
`
`Page 16
`1 antibody for human cancer therapy," from the Proceedings
`2 of the National Academy of Sciences, U.S.A., in May 2 of
`3 1982. Is this the PNA reference that you were referring
`4 to?
`5 A It's May 1992.
`6 Q Sorry.
`7 A It is the right -- it is the right reference,
`8 yes.
`9 Q Apologize. I misspoke. Yes. May 1992.
`10 And you were referring to a paper that
`11 published the anti-lysozyme work. Is that one of the
`12 cited references?
`13 A Yes. It is one of cited references.
`14 Q And which one is this?
`15 A To the best -- best of my recollection, it's
`16 the reference on ATN, that's the Verhoeyen, et al.,
`17 Science, Volume 239, pages 1534 to 1536.
`18 Q And for the record, Verhoeyen,
`19 V-e-r-h-o-e-y-e-n?
`20 A Correct.
`21 Q Okay. Other than through the published
`22 literature or the Verhoeyen reference, were you aware of
`23 the work being done to humanize the anti-lysozyme
`24 antibody at the Winter lab?
`25 A I have no clear recollection beyond this
`
`[4/27/2018] Carter, Paul 2018-04-27 v01
`
`Pages 13 - 16
`
`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Paul Carter, Ph.D.
`Conducted on April 27, 2018
`
`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01489
`PFIZER EX. 1698, Page 5
`
`

`

`Page 17
`
`Page 19
`
`1 publication at this -- at this point, 30-plus years
`2 later.
`3 Q Were you aware, in the 1986 to 1989 time frame
`4 while you were at Genentech, of the work being done at
`5 the Winter lab to humanize the Campath antibody,
`6 C-a-m-p-a-t-h?
`7 A Yes. I was aware of that work.
`8 Q Okay. And how were you aware of that work?
`9 A Again, I was aware, at least in part, through
`10 publication.
`11 Q And is that the Riechmann 1988 publication
`12 that is reference 17 of your PNAS reference?
`13 A To the best of my knowledge, that is correct.
`14 Q Okay. Other than through that paper, were you
`15 aware of the work being done at the Winter lab to
`16 humanize the Campath antibody?
`17 A You know, now at this point 30 years later, I
`18 don't remember that aspect very clearly. I do remember
`19 there -- the publication.
`20 Q Okay. Is it possible that you were aware
`21 through communications you had with your former
`22 colleagues at the Winter lab?
`23 A That is possible, but I have no clear
`24 recollection of that now, you know, 30 years later.
`25 Q And is it possible that you were aware of how
`
`1 humanized based on a consensus sequence?
`2 MR. DANFORD: Objection; lacks foundation.
`3 A Again, I would have read their paper at about
`4 the time, but I don't remember, you know, clearly at
`5 this point, every --every detail of the -- of the
`6 humanization methodology for work which was done more
`7 than three decades ago.
`8 Q Dr. Carter, I've handed you a copy of what was
`9 previously marked as Exhibit 1193 during the deposition
`10 of Jeffrey Foote -- Jefferson Foote -- excuse me --
`11 Ph.D. It's an article published in Nova Acta
`12 Leopoldina, and it's titled Humanized Antibody.
`13 And the -- Humanized Antibodies. And the author is
`14 Jefferson Foote.
`15 Have you seen this publication before?
`16 MR. DANFORD: I object to this whole line as
`17 outside the scope.
`18 MR. LASKY: Just so I understand the
`19 objection, what's the scope that you believe is relevant
`20 to this testimony today?
`21 MR. DANFORD: He's here to talk about his
`22 declaration and the work that he did at Genentech. And
`23 I don't think that this exhibit has anything to do with
`24 that.
`25 MR. LASKY: Okay. Your objection is noted.
`
`Page 18
`
`Page 20
`
`1 the antibody was humanized -- strike that.
`2 Is it possible that at the time you were at
`3 Genentech between 1986 and 1989, you were aware of how
`4 the Campath antibody was humanized through
`5 communications you had with former colleagues at the
`6 Winter lab?
`7 MR. DANFORD: Objection; calls for
`8 speculation.
`9 A I -- I feel that I've already, sort of,
`10 answered that. I don't have a clear recollection of
`11 discussions. I do have a clear recollections of having,
`12 sort of, read the papers around the time that they were
`13 originally published.
`14 Q Now, were you aware, at the time you were at
`15 Genentech, in 1986 to 1989, that the anti-lysozyme
`16 antibody humanized at the Winter lab had a light chain
`17 that was humanized based on a consensus sequence?
`18 MR. DANFORD: Objection; lacks foundation.
`19 A My -- my recollection is just that the work
`20 was -- was, you know, published. At this point more
`21 than 30 years later, I do -- I don't remember every
`22 detail of how that humanization work was done.
`23 Q Okay. And were you aware at the time you were
`24 at Genentech in 1986 to 1989 that the Campath antibody
`25 humanized at the Winter lab had a light chain that was
`
`1 Q The question was we -- have you seen this
`2 paper before?
`3 A After looking over this paper, I don't have
`4 any recollection of having seen it before.
`5 Q Okay. Were you aware, in the 1980s time
`6 frame, of the Nova Acta Leopoldina publication?
`7 A This is not exactly a, sort of, a household
`8 name in scientific journals. To the best, I think, of
`9 my knowledge, I have never even heard of this journal
`10 before.
`11 Q Okay. My understanding is this is an East
`12 German publication. Were you aware of any East German
`13 publications at the time?
`14 MR. DANFORD: Objection to form.
`15 A To the best of my knowledge, I was not aware
`16 of their East German publications -- scientific
`17 publications of -- of -- that appeared in 19 -- I think,
`18 was it 1986 to 1989?
`19 Q Well, this particular publication is 1989.
`20 A Oh, this is -- sorry. I'm sorry. Please,
`21 could you repeat the question?
`22 Q I think you've answered it, but I can ask it
`23 again. The question was -- and it was a follow-up to
`24 your testimony that you had not heard of this
`25 publication before. And I was just asking if you were
`
`[4/27/2018] Carter, Paul 2018-04-27 v01
`
`Pages 17 - 20
`
`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Paul Carter, Ph.D.
`Conducted on April 27, 2018
`
`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01489
`PFIZER EX. 1698, Page 6
`
`

`

`Page 21
`1 aware of any East German publications relating to
`2 humanized antibodies in the 1986 to 1989 time frame.
`3 A To the best of my knowledge, no.
`4 Q Okay. You joined Genentech as a postdoctoral
`5 fellow in 1986, according to paragraph 3 of your
`6 declaration, correct?
`7 A That is correct.
`8 Q And so -- well, strike that.
`9 Going back to your work in the 1985 to 1986
`10 time frame at the Winter lab, was the work that you were
`11 doing with PCR on the antibody involved in humanizing
`12 that antibody?
`13 MR. DANFORD: Objection to form.
`14 A No. The antibody had already been humanized.
`15 Q Okay. So is it the first time that you worked
`16 on humanizing an antibody after you joined Genentech?
`17 A That is correct.
`18 Q Okay. When did you begin your first project
`19 humanizing an antibody?
`20 A So if we look to the acts of declaration, that
`21 really just describes the time. And I just need to find
`22 the relevant part.
`23 So an overview of the work is described in
`24 paragraph 10 which includes some aspects of the -- of
`25 timing.
`
`Page 23
`
`1 the murine monocolonal antibody muMAb4D5 -- that's
`2 m-u-M-A-b 4D5 -- directed against the extracellular
`3 domain ECD of p185HER2, specifically inhibits the growth
`4 of tumor cell lines overexpressing p185HER2 in monolayer
`5 culture or in soft agar. Do you see that?
`6 A I do see that, yes.
`7 Q And then citations are papers 7 and 8 of your
`8 paper. And if we -- if we see there, paper 7 is the
`9 Hudziak 1989 paper. Do you see that?
`10 A I actually have a correction here. If you
`11 read the entire sentence.
`12 Q Uh-huh.
`13 A It's not just 7 and 8 that's cited. It's also
`14 reference 6 and 9. So there are specific clauses within
`15 that sentence. And it's parsed so that the reference
`16 supports that clause.
`17 Q Understood. One of the references that's
`18 cited in that paragraph is the Hudziak 1989 paper which
`19 is reference 7.
`20 A Well, it's not a paragraph. It's a sentence.
`21 But, yes, the Hudziak is one of the reference cited.
`22 Q Okay. And are you familiar with the Hudziak
`23 reference today?
`24 A Frankly, at this point, it's many, many years
`25 since I've read the Hudziak paper.
`
`Page 22
`
`Page 24
`
`1 Q Was your work on humanization of the 4D5
`2 antibody the first humanization project you had worked
`3 on?
`4 A Yes, it was the first humanization project.
`5 Q Okay. Now, the -- who was it who decided that
`6 it was the 4D5 antibody that you would try to humanize
`7 in that project?
`8 MR. DANFORD: Objection to form.
`9 A I'm going to parse that question into two
`10 pieces. One is choice of 4D5, and the other part is
`11 sessions humanized. Are you interested in one or both
`12 parts?
`13 Q Well, before you began your work to humanize
`14 4D5, there had been work to generate the mouse antibody
`15 and test it for anti-HER2 activity; is that correct?
`16 A There was a project in the late 1980s to
`17 generate monocolonal antibodies to p185HER2.
`18 Q And is that the work that was being led by
`19 Dr. Hudziak, H-u-d-z-i-a-k?
`20 A Dr. Hudziak was one of the people who was
`21 involved in the project. I don't know if he led it or
`22 not.
`23 Q Okay. If we go back to your PNAS paper and
`24 if -- if we look at the first page, we see a statement
`25 in the left-hand column -- and this is Exhibit 2020 --
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`[4/27/2018] Carter, Paul 2018-04-27 v01
`
`Pages 21 - 24
`
`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Paul Carter, Ph.D.
`Conducted on April 27, 2018
`
`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01489
`PFIZER EX. 1698, Page 7
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Page 25
`
`Page 27
`
`6 Q Okay.
`7 Before you proposed to humanize 4D5, it was
`8 known in the field that mouse antibodies, if given to
`9 humans, could lead to generation of antibodies against
`10 the antibody, correct?
`11 A Yes. If you -- if you look at Exhibit 2020,
`12 at the left-hand column, there are -- the lowest
`13 paragraph, you can see a sentence there which begins, "A
`14 major limitation in the clinical use of rodents mAbs is
`15 an antiglobulin response during therapy." And the
`16 citations are to references 10 and 11, and -- so 10
`17 being Miller, et al., 1983; 11 being Schroff, et al.,
`18 1985.
`19 Q Prior to your proposing humanization of the
`20 4D5 antibody, scientists had proposed to address the
`21 problem of antiglobulin response by humanizing
`22 antibodies, correct?
`23 MR. DANFORD: Objection to form.
`24 A So in response to your question, again
`25 referring you to -- the -- the publication Exhibit 2020,
`
`Page 26
`
`Page 28
`
`1 and I'll direct your attention to the first page,
`2 right-hand column. And there's a paragraph there which
`3 speaks to humanization and using this technology as a --
`4 as a way to potentially overcome the antiglobulin
`5 response to -- and it refers to Campath, the antibody.
`6 Q Prior to your proposal of humanizing the 4D5
`7 antibody, scientists had proposed humanization through
`8 grafting the complementary determining regions of the
`9 mouse antibody into the human framework and then making
`10 framework region substitutions back to mouse at certain
`11 positions, correct?
`12 MR. DANFORD: Objection to form.
`13 A What you have just stated is, I believe,
`14 consistent with the early humanization -- antibody
`15 humanization examples from Sir Gregory Winter's
`16 laboratory, and there is more citations in the -- in
`17 Exhibit 2020. So specifically, references -- one or
`18 more of the references 16 to 18, that's the Jones,
`19 et al., 1986; Riechmann, et al., 1988; and Verhoeyen,
`20 et al., 1988.
`
`
`
`
`
`
`
`[4/27/2018] Carter, Paul 2018-04-27 v01
`
`Pages 25 - 28
`
`CONFIDENTIAL - UNDER PROTECTIVE ORDER
`Transcript of Paul Carter, Ph.D.
`Conducted on April 27, 2018
`
`PFIZER and SAMSUNG v. GENENTECH
`IPR2017-01489
`PFIZER EX. 1698, Page 8
`
`

`

`Page 29
`
`Page 31
`
`4 Q Okay. The -- at the time that you proposed
`5 humanizing 4D5
`, were you aware of
`6 the work that was also being done by Cary Queen and
`7 colleagues? That's C-a-r-y.
`8 A So I was aware of a publication for -- from
`9 Cary Queen and his colleagues. And I believe that is
`10 cited in the PNAS paper. Yes. It's reference 20,
`11 Queen, et al., Proceedings of the National Academy of
`12 Sciences USA, Volume 86, starting on page 10029.
`13 Q Okay.
`14 I'd like to ask some questions focusing on the
`15 declaration. If you need any other documents, let me
`16 know.
`17 When you proposed to create humanized versions
`18 of the 4D5 antibody, what was the purpose to which you
`19 considered those antibody -- humanized antibodies could
`20 be put?
`21 MR. DANFORD: Objection; form.
`22 A Our hope in humanizing the 4D5 antibody was
`23 that it would overcome at least some of the limitations
`24 of mouse antibodies that had previously been seen in the
`25 clinic. And I refer back to Exhibit 2020, the PNAS
`
`1 A I think there are a few aspects of that. One
`2 is to recapitulate as best we could the properties of
`3 the parent antibody, including binding affinity for
`4 p185HER2. Another aspect is recapitulating activity as
`5 far as possible in antiproliferative activity.
`6 Q And is another important aspect of the project
`7 to minimize the antiglobulin response in the human
`8 patient that was seen with the parent antibody?
`9 MR. DANFORD: Objection to form.
`10 A It would be fair to say that what I just
`11 described is only kind of a subset of their desired
`12 outcome. The chief and low immune response in patients
`13 was one other aspect.
`14 Q Are there any others that you can think of
`15 other than obtaining binding affinity for the HER2
`16 protein attaining antiproliferative activity and
`17 minimizing immune response in patients?
`18 MR. DANFORD: Objection to form.
`19 A Yes, I can.
`20 MR. DANFORD: Objection to form.
`21 Go ahead, if you can answer it.
`22 A Yes, I can think of other things.
`23 Q Okay. And what are they?
`24 A One other aspect is endowing the humanized
`25 antibody with the ability to kill tumor cells by an
`
`Page 30
`
`Page 32
`
`1 paper which we've discussed previously. So the
`2 left-hand column, last paragraph, "A major limitation of
`3 the clinical use of rodent maps as an antiglobulin
`4 response during therapy." And so I think that's 10 and
`5 11.
`6 Q And was the ultimate purpose of humanizing the
`7 4D5 antibody to generate a humanized antibody that could
`8 be used as a therapeutic agent in humans?
`9 MR. DANFORD: Objection to form.
`10 A I'm sorry. Could you repeat the question?
`11 Q Sure. Was the ultimate purpose of humanizing
`12 the 4D5 antibody that you were involved in to generate a
`13 humanized antibody that could be used as a therapeutic
`14 agent in humans?
`15 MR. DANFORD: Objection to form.
`16 A Certainly, our hope is -- is that this
`17 humanized antibody would be beneficial to patients.
`18 Q Okay.
`19 What are the characteristics of a humanized
`20 antibody -- well, strike that.
`21 In -- in your work to humanize the 4D5
`22 antibody, what were the characteristics of the humanized
`23 antibody that you considered important in generating a
`24 potential therapeutic agent for humans?
`25 MR. DANFORD: Objection to form.
`
`1 immune-effector mechanism called ADCC, or
`2 antibody-dependent cellular cytotoxicity.
`3 Q Any others?
`4 A Another aspect is that in the so-called
`5 pharmacokinetics of mouse antibodies in human, they tend
`6 to be cleared quickly from circulation. So we were
`7 hoping that the humanized antibody might be cleared more
`8 slowly.
`9 Q Any other factors you considered important for
`10 the humanization project of 4D5?
`11 MR. DANFORD: Objection to form.
`12 A So in trying to search my recollection from --
`13 from 30 years ago, and that's what I can recall from --
`14 from that period from '89, 1990 about the -- the major
`15 motivations to humanize this 4D5 antibody.
`16 Q At the time you were conducting your
`17 humanization project, was the mechanism by which 4D5 led
`18 to antiproliferation of tumor cells known?
`19 A I believe that there were aspects -- certain
`20 experiments characterizing the anti -- anti-HER2
`21 antibodies for growth inhibitory activity were described
`22 in -- prior to their humanization. I don't recall
`23 clearly exactly how much was known, exactly the
`24 molecular basis for that growth inhibitor activity.
`25 Q Now, in paragraph 4 of your declaration, you
`
`[4/27/2018] Carter, Paul 2018-04-27 v01
`
`Pages 29 - 32
`
`CONFIDENTIAL - UNDER PROTECTIVE