Page 3
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
`
` THE VIDEOGRAPHER: This is the
` video operator speaking, David Peloza
` for Merrill Legal Solutions.
` Today's date is December 23, 2014.
` The time is 9:29. We are at 1675
` Broadway, New York City for the
` deposition of Dr. Saul J. Silverstein in
` the matter of Bristol-Myers Squibb
` Company versus Genentech, Inc.
` I would like the attorneys to
` introduce themselves starting with Mr.
` Brausa.
` MR. BRAUSA: Sure. Adam Brausa
` here for Genentech.
` MR. McCORMICK: Richard
` McCormick, Mayer Brown for Brisol-Myers
` and Medarex.
` MR. DAHIYA: Neal Dahiya for
` Brisol-Myers and Medarex.
` MR. SCHWARTZ: Robert Schwartz
` from the Fitzpatrick firm for Lilly.
`
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`Page 4
`1
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
`2
` SAUL J. SILVERSTEIN, PH.D.,
`3
` having been first duly sworn by the
`4
` Notary Public (Tammey M. Pastor), was
`5
` examined and testified as follows:
`6
` EXAMINATION CONDUCTED BY
`7
` MR. BRAUSA:
`8
` Q. Good morning, Dr. Silverstein.
`9
` Can you state your full name for the record.
`10
` A. Saul J. Silverstein.
`11
` Q. And you have been deposed
`12
` before; correct?
`13
` A. I have.
`14
` Q. So you are familiar with the
`15
` rules, but if I ask questions and you don't
`16
` understand them, you can ask me to clarify,
`17
` I'll try and do that.
`18
` A. Very good.
`19
` Q. If you need to take a break at
`20
` any time we can do that. The only thing I
`21
` ask if there is a question pending we finish
`22
` the question on the record, okay.
`23
` You have submitted two Expert
`24
` Reports in this litigation; correct?
`25
` A. I have submitted an Expert
`1 (Pages 1 to 4)
`MERCK v. GENENTECH
`IPR2016-01373
`GENENTECH 2013
`
`Page 1
`
`UNITED STATES DISTRICT COURT
`CENTRAL DISTRICT OF CALIFORNIA
`-----------------------------------x
`BRISTOL-MYERS SQUIBB COMPANY
` Plaintiff and Counter-Defendant,
` -against- Case No.
` 2:13-cv-05400-MRP-JEM
`
`GENENTECH, INC., and CITY OF HOPE,
` Defendant and Counter-Plaintiffs.
`-----------------------------------x
`GENENTECH, INC., and CITY OF HOPE,
` Third-Party Plaintiffs,
` -against-
`MEDAREX, L.L.C.,
` Third-Party Defendant.
`-----------------------------------x
` CONFIDENTIAL
`
` December 23, 2014
` 9:30 a.m.
`
` Videotaped Deposition of
`SAUL J. SILVERSTEIN, PH.D., taken by Defendant,
`pursuant to Notice, at the offices of MAYER BROWN
`LLP, 1675 Broadway, New York, New York, before
`TAMMEY M. PASTOR, a Registered Professional
`Reporter, Certified LiveNote Reporter and Notary
`Public within and for the State of New York.
`
`Page 2
`
`A P P E A R A N C E S:
` MAYER BROWN LLP
` Attorneys for Bristol-Myers Squibb and
` Medarex, L.L.C
` 1675 Broadway
` New York, New York 10019
` BY: RICHARD J. McCORMICK, ESQ.
` (Mccormick@mayerbrown.com)
`
` DURIE TANGRI
` Attorneys for Genentech, Inc. And
` City of Hope
` 217 Leidesdorff Street
` San Francisco, California 94111
` BY: ADAM R. BRAUSA, ESQ.
` (Abrausa@durietangri,com)
`
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`ALSO PRESENT:
`21
`NEAL DAHIYA, Bristol-Myers Squibb
`22
`DAVID PELOZA, Videographer
`23 Merrill Legal Solutions
`24
`25
`
` FITZPATRICK CELLA HARPER & SCINTO
` Attorneys for Eli Lilly and
` ImClone Systems LLC
` 1290 Avenue of the Americas
` New York, New York 10104
`
` BY: ROBERT J. SCHWARTZ, Ph.D., ESQ.
` (Rschwartz@fchs.com)
`
`

`
`Page 5
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` Report and rebuttal.
` Q. And the rebuttal was in
` response to a report submitted by
` Dr. Matthew Scott?
` A. Yes. Yes.
` MR. BRAUSA: I am going to go
` ahead and mark Silverstein 1.
` (Silverstein Exhibit 1
` for identification, Expert Report of
` Saul J. Silverstein, no production
` numbers.)
`BY MR. BRAUSA:
` Q. After you have taken a look at
` that can you confirm for me that is the
` opening report you submitted in this
` litigation?
` A. Yes, this is the opening
` report.
` MR. BRAUSA: We will mark
` Silverstein 2 as well right now.
` (Silverstein Exhibit 2
` for identification, Silverstein Rebuttal
` Expert Report, no production numbers.)
`BY MR. BRAUSA:
`
`Page 6
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` Q. Can you confirm for me that is
` the rebuttal report you submitted in this
` litigation?
` A. Yes, this is the rebuttal.
` Q. Now I've read your opening
` report, Dr. Scott's response to your report
` and your Rebuttal Report and the impression
` I came away with was you and Dr. Scott
` disagree on several issues; is that fair?
` A. I would say that's fair, yes.
` Q. Before we get into some
` detailed questions about your opinions and
` disagreements you have with Dr. Scott, I'd
` like to make sure I understand all the
` disagreements that you have with Dr. Scott.
` Is that okay?
` A. Fair enough.
` Q. Okay. We are going to be
` referring to the Cabilly patents during this
` questioning. And as I think you know there
` is a Cabilly II and a Cabilly III patent;
` correct?
` A. Yes.
` Q. When I say Cabilly II patent I
`
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`Page 7
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` am referring to U.S. patent 6,331,415. Okay.
` A. Okay.
` Q. And when I say Cabilly III
` patent I'm going to be referring to
` 7,923,221. Okay?
` A. Very good.
` Q. I think those are the same
` terms you use in your Expert Reports to
` describe the Cabilly patents; correct?
` A. Yes.
` Q. Okay. If there is ever any
` question about which specific Cabilly patent
` I'm referring to, just let me know.
` Now, I think your report, my
` impression was you have some specific
` factual disagreements with Dr. Scott about
` whether certain sections of the Cabilly
` specification would provide guidance to one
` of skill in the art in April 1983 about in
` vivo assembly of heavy and light
` immunoglobulin chains in eukaryotic cells;
` right?
` A. That's correct.
` Q. There are several sections of
`
`Page 8
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` the Cabilly specifications that you disagree
` with Dr. Scott as to whether one of skill in
` the art would understand those two be
` referring to in vivo assembly of heavy and
` light chains in eukaryotic cells; correct?
` A. That's also true.
` Q. So first there is a section at
` column 12, actually we can just refer to the
` paragraph in your report, if you can turn to
` paragraph 35 of Silverstein 1.
` A. I'm just going to get another
` pair of glasses. Okay.
` Q. In paragraph 35 of Silverstein
` 1 you quote a section from the Cabilly II
` patent at column 12, lines 47 through 49. Do
` you see where I'm referring?
` A. Yes.
` Q. That is a statement that says,
` "Tissue culture cells as hosts also appear
` in general to permit reasonably facile
` recovery of heterologous protein." Correct?
` A. Yes.
` Q. And my understanding you and
` Dr. Scott disagree about whether that clause
`2 (Pages 5 to 8)
`
`

`
`Page 9
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` would tell one of skill in the art that the
` Cabilly inventors intended their invention
` to cover in vivo assembly of heavy and light
` chains in eukaryotes; correct?
` A. That's correct.
` Q. Dr. Scott is of the opinion
` you'd agree that section of the Cabilly
` patent does in fact refer to in vivo
` assembly of heavy and light chains in
` eukaryotic host cells; right?
` A. He believes that to be true.
` Q. And do you disagree with
` Dr. Scott on that point?
` A. I disagree with him.
` Q. You don't think that that is
` section of the Cabilly II patent refers to
` in vivo assembly of heavy and light chains
` in a eukaryotic host cell?
` A. I do not believe that it does.
` Q. That is not exactly what you
` say in paragraph 35; is it?
` A. I think that's open to
` interpretation.
` Q. That is sort of what you're
`
`Page 10
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` saying in paragraph 35 about the section of
` the Cabilly patents we've been discussing
` you say it is not an unambiguous disclosure
` that that includes recovery of in vivo
` assembled immunoglobulins?
` MR. McCORMICK: Objection.
` A. It is not directed to
` immunoglobulins.
` Q. What do you mean when you say
` it is not unambiguous in paragraph 35 of
` your report?
` A. Well, I think that it's
` difficult to interpret the meaning of that
` phrase in terms of reasonably facile
` recovery because nothing is -- there is no
` description for what that is.
` Q. Your opinion in paragraph 35
` doesn't say Dr. Scott is wrong, correct, it
` just says his interpretation of that section
` of the Cabilly II patent isn't clear?
` MR. McCORMICK: Objection to
` form.
` A. Well, actually, actually this
` paragraph relates to the patent per se and
`
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`Page 11
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` not so much to Dr. Scott's opinion at this
` point.
` Q. Okay. And your opinion about
` the patent is that that section of the
` patent referring to reasonably facile
` recovery is that's that is an unambiguous --
` that is an ambiguous statement rather?
` A. Absolutely.
` Q. It is just not clear whether
` that is referring to in vivo assembly in
` eukaryotic host cells or something else;
` right?
` A. It is not clear as to what it
` is that is being recovered or how it is
` being recovered or for that matter what it
` is that -- what it is they are trying to do.
` Q. Okay. When you say it is not
` clear from that clause what is being
` recovered, what else would that be referring
` to aside from heavy and light chains based
` on the rest of the specification of the
` Cabilly II patent?
` A. Well, regardless of the rest of
` the specifications what it is referring to
`
`Page 12
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` here is heterologous proteins, at that time
` there were just a few proteins that had been
` made. As I said, they don't describe
` immunoglobulins as one of the proteins at
` this point.
` Q. Is your opinion one of skill in
` the art would read this phrase, referring to
` treasonably facile recovery of heterologous
` proteins and conclude that the reference to
` heterologous proteins did not include
` immunoglobulins?
` A. I'm not sure what it includes.
` Q. In your opinion as the expert
` in this case do you think it includes
` immunoglobulins when they refer to facile
` recovery of heterologous proteins?
` A. I would assume that that is
` what they meant. But it is not what they
` said.
` Q. Why would you assume that's
` what they meant when they said, "reasonably
` facile recovery of heterologous proteins?"
` A. Well the subject matter is the
` production of immunoglobulins by recombinant
`3 (Pages 9 to 12)
`
`

`
`Page 13
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` technology.
` Q. So based on the fact?
` MR. McCORMICK: Let him finish.
` A. Continue.
` MR. McCORMICK: Did you want to
` finish your answer?
` A. No. I want to hear the next
` question.
` Q. Based on the fact the Cabilly
` II patent is about the recovery of
` heterologous immunoglobulins, it is fair to
` conclude that when they refer to
` heterologous proteins and recovering those,
` that includes immunoglobulins as well;
` right?
` MR. McCORMICK: Objection.
` A. I would say that you've got to
` say what it is that you're referring to to
` be specific.
` And, of course I think more to
` the point is that this entire patent is
` dedicated to its work in bacterial cells.
` There is no demonstration of using tissue
` culture cells for anything.
`
`Page 14
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` Q. I understand that's one of your
` opinions. We'll get to that point. But I
` guess I'm still focused on your opinion
` about whether the reference to reasonably
` facile recovery of heterologous proteins
` includes the recovery of immunoglobulins
` based on the specification of the Cabilly II
` and Cabilly III patents?
` A. I think we've actually answered
` that question and addressed it. I think that
` there is reasonable doubt about what this
` includes. I think they would like it to have
` been, but I don't think they state that's
` the case. I think that's a big difference.
` Q. When you refer to "they," and
` "we would like to be," who are you referring
` to?
` A. The authors of the patent.
` Q. So the PTO would like it to
` include immunoglobulins; is that your
` testimony?
` MR. McCORMICK: Objection,
` mischaracterizes his testimony. Go
` ahead.
`
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`Page 15
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` A. I'm saying that in the context
` of having written this patent, whoever wrote
` it would like to be all inclusive.
` Q. Okay. I guess my question for
` you as the technical expert in this case,
` looking at this sentence as one of ordinary
` skill in the art as of April 1983, do you
` think the reasonably facile recovery of
` heterologous proteins would refer to the
` recovery of immunoglobulins, given the
` specification of the Cabilly patents?
` MR. McCORMICK: Objection, asked
` and answered.
` A. I would say somebody of
` ordinary skill in the art would not be able
` to make that conclusion.
` Q. So they just wouldn't be able
` to make a conclusion at all about what
` heterologous proteins refers to or includes?
` A. Well, I think that specifically
` we are talking about immunoglobulins. At
` this point in time, to my knowledge the only
` proteins that had been made were single
` chain proteins.
`
`Page 16
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` Q. So the fact that the entirety
` of the Cabilly patent or large part of the
` Cabilly patent specification is about the
` recovery of heterologous heavy and light
` immunoglobulin chains, would not give one of
` skill in the art any guidance as to what
` they were referring to when they said the
` reasonably facile recovery of heterologous
` proteins in the patent?
` A. I think you can read into that,
` but I don't think the specifications say
` that. I'll leave it at that.
` Q. I understand the specification
` does not say the word immunoglobulin in this
` sentence. It says heterologous proteins. But
` throughout the specification the word
` immunoglobulin is used; correct?
` A. That's true.
` Q. That's what the specification
` is about; right? Recovery of heavy and
` light immunoglobulin chains?
` A. Yes.
` Q. So your opinion is that after
` reading that specification when one of skill
`4 (Pages 13 to 16)
`
`

`
`Page 17
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` in the art arrived at this sentence that
` states "Tissue culture cells as host cells
` also appear in general to permit reasonably
` facile recovery of heterologous proteins"
` they wouldn't be sure whether that was a
` reference to immunoglobulins?
` MR. McCORMICK: Objection, asked
` and answered.
` A. I would state that this is an
` extension of the ideas in the patent. But it
` not stated. And you can say it can be
` recovery of anything you like.
` Q. At a minimum, you'd agree with
` me, though, I think, and correct me if I'm
` wrong, but you'd agree with me that sentence
` is open to interpretation? That's your
` opinion; correct?
` A. I would think so, otherwise we
` wouldn't be having this discussion.
` Q. That is just a factual dispute
` between yourself and Scott; right? About how
` one of skill in the art would understand
` this sentence?
` A. Well, yes.
`
`Page 18
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` Q. Now, there is another section
` at, that is referred to actually in the next
` paragraph of your report, that refers to
` column 12, lines 36 through 49 of the
` Cabilly patents; right?
` A. Uh-huh. Yes.
` Q. And this is another section of
` the patent that Dr. Scott is of the opinion
` refers to in vivo assembly of heavy and
` light chains in eukaryotic host cell; right?
` A. Yes.
` Q. And you disagree with that
` opinion of Dr. Scott as well?
` A. I do.
` Q. Again, there is a sentence that
` starts "More over at the bottom of page 13
` in paragraph 36 of your report. Where you
` say, "Moreover, recovery of antibody would
` not necessarily be understood by a person of
` ordinary skill in the art to refer to only
` to recovery of already assembled antibody."
` Do you see that?
` A. Yes.
` Q. So I want to focus on when you
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`Page 19
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` say it would not necessarily be understood
` by a person of ordinary skill in the art.
` When you say that, the way I read that
` sentence, is that you're saying they could
` understand it, in the way that Dr. Scott
` interprets it; is that correct?
` A. I think you have to include the
` rest of this sentence before we can continue
` this discussion.
` Q. What portion of the sentence
` would you like to include?
` A. The part that refers to when
` Dr. Scott says that additional steps and
` processes must be undertaken before the
` thing that is recovered is actually
` recovered.
` Q. Why is that important to take
` into consideration?
` A. Because there is no evidence
` that complete assembled antibody is made in
` the bacteria. What we know is that they
` extracted material from bacteria and
` reconstituted antibody in the fashion of
` Adelman, et al.
`
`Page 20
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` Q. The description of recovery of
` antibody from spun bound whole cells or from
` cell culture containing both the medium and
` suspended cells that's referred to in
` paragraph 36 of your report, is a reference
` to bacterial host cells, in your mind?
` A. Yes. It's a reference to in the
` patent, I believe.
` Q. We were discussing earlier,
` with respect to paragraph 35, that's not
` what the patent says. I don't see the word
` bacterial or E. coli or anything synonymous
` with bacteria in this section of the Cabilly
` patent.
` A. May I have a copy of the
` patent, please?
` Q. Sure.
` MR. BRAUSA: I will mark as
` Silverstein Exhibit 3 the Cabilly II
` patent, U.S. patent --
` A. Give me II or III, the specs
` are the same.
` Q. -- 6,331,415.
` (Silverstein Exhibit 3
`5 (Pages 17 to 20)
`
`

`
`Page 21
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` for identification, U.S. Patent
` 6,331,415, production numbers
` GNE-LILLY-BMS 00072446 through
` GNE-LILLY-BMS 00072488.)
`BY MR. BRAUSA:
` Q. I can direct your attention to
` column 12 starting at line 36.
` A. Yes.
` Q. So can you find for me in
` column 12, starting at line 36 the sections
` that are referred to in paragraph 36 of your
` report?
` A. Well you have to go back a
` little further than that. You have to go to
` column 11, 57 when you talk about successful
` transformants, that of course is bacteria.
` Q. That is not referred to in
` paragraph 36 of your report; is it?
` A. I would say by inference it is.
` Q. What would allow me to make the
` inference that section of the patent is
` included in paragraph 36 of your report?
` A. Because it is a continuation
` and explanation of what preceded it.
`
`Page 22
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` Q. So you would agree portions of
` the patent are read in context with other
` portions of the patent; right?
` A. I would hope so, yes.
` Q. But you didn't feel it was
` appropriate to read the section of the
` patent that you referred to in paragraph 35
` of your report in context with the rest of
` the patent that talks about recovery of
` immunoglobulin heavy and light chain?
` A. I would say that misrepresents
` my opinion.
` Q. Okay. My understanding of your
` opinion with respect to paragraph 35 and our
` previous discussion was that because they
` use the word heterologous proteins, not
` immunoglobulin specifically, one of skill in
` the art as of April 1983 wouldn't be able to
` determine whether they meant to include
` immunoglobulins in that clause?
` A. So, I think you have to be
` careful here because there is, in the
` specifications there are no descriptions of
` using tissue culture cells, other than a
`
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`Page 23
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` laundry list of possibilities. Things that
` might happen as opposed to the in vitro
` reconstitution of antibody from proteins
` made in bacterial cells where there are step
` by steps elucidation of how.
` Q. So is a step by step
` experimental elucidation of how to recover
` immunoglobulin heavy and light chain
` necessary to comply with the written
` description requirement in your opinion?
` MR. McCORMICK: Objection.
` A. I would think that at this
` point, it being a very -- it is 1983, it is
` very early on in this game, if you will.
` Many things are not obvious. It is not a
` time where you can say you add this to that
` and one would immediately understand what
` that might mean.
` So, without a written
` description of how to do something, I think
` it is rather vague and difficult. Certainly
` there is no enablement of this as opposed to
` in vitro assembly of the chains into a what
` appears to be a functional antibody.
`
`Page 24
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` Q. You agree the in vitro assembly
` of heavy and light chain in the E. coli
` example is enabled by the specification of
` the patent?
` MR. McCORMICK: Objection to
` form.
` A. I would say to some minimal
` extent. The recovery is horrible.
` Q. That is a yield issue; right?
` That's what you mean?
` A. Well, I don't know what that
` is. I'm -- fair enough.
` Q. You mentioned that not many
` things were obvious or many things were not
` obvious, pardon me. Can you tell me about
` what things in your mind that relate to this
` patents weren't obvious as of April 1983?
` A. I think you'd have to be a
` little more specific so that I don't take up
` the rest of the day.
` Q. Sure?
` A. Was expression of a
` heterologous protein in a mammalian host
` cell obvious?
`
`6 (Pages 21 to 24)
`
`

`
`Page 25
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` MR. McCORMICK: Objection, vague
` and ambiguous.
` A. It depends on the protein.
` There were many proteins that were attempted
` to be produced that were not recovered, not
` made.
` Q. Expression of a light or heavy
` chain in a mammalian host cell as of April
` of 1983, was that enabled?
` A. There were instances of --
` MR. McCORMICK: Let me get an
` objection, vague and ambiguous in that.
` A. There were instances of light
` and heavy chains, light and heavy chains --
` certainly light chains being, DNA sequences
` in coding light chains being introduced into
` lymphocytes of some sort, myeloma cells or
` other permanent lymphocyte lines where
` proteins were made and demonstrated to
` interact with resident chains.
` Q. So, with respect to if we focus
` on immunoglobulin heavy or light chain as
` the heterologous protein, do you think one
` of ordinary skill in the art, as of April 8,
`
`Page 26
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` 1983 would have been able to express a light
` chain in a heterologous host cell?
` A. Depend on --
` MR. McCORMICK: Hold on, just let
` me read it.
` Objection, incomplete
` hypothetical. Vague and ambiguous.
` A. Depends on the cell type. There
` were too many instances of tried and failed
` at that point. Which are well documented and
` there were a number of instances of
` successful transcription with no real proof
` of translation of the protein. So --
` Q. Did you have any personal
` experience trying to express a protein in a
` recombinant host cell and not achieving
` translation, transcription or some failure
` along the way as of April 8, 1983?
` A. Yes.
` Q. Can you describe for me those?
` A. Beta globin in HeLa cells,
` whereas it was successfully done by Dean
` Hamer. I really can't remember what else. I
` can tell you that I was a colleague of
`
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`Page 27
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` Sherry Morrison's who was very involved with
` this and we spent a lot of time discussing
` successes and failures at that point.
` Q. Based on my review of your CV
` and publications you are also a colleague of
` Dr. Richard Axel.
` A. That's correct.
` Q. What is your opinion of
` Dr. Axel as a scientist?
` A. They don't come much brighter.
` Q. So if he has a technical
` opinion on something, you'd be inclined to
` think that was right; correct?
` MR. McCORMICK: Objection.
` A. I might be.
` Q. Have you ever found yourself in
` disagreement with Dr. Axel on a factual
` issue?
` A. Frequently.
` Q. Have any of those disagreements
` involved recombinant production of
` antibodies?
` A. Not openly.
` Q. Just so I'm clear, that is sort
`
`Page 28
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` of something that happens among scientists?
` A. Absolutely.
` Q. Factual disputes, one scientist
` thinks one thing, another scientist thinks
` another?
` A. That's fair.
` Q. Okay. In your work with
` Dr. Axel, Dr. Axel's group I believe in the
` 1980s, early 1980s along with Michael
` Wigler, did you ever have any problem
` expressing proteins in a heterologous host
` cell?
` A. We had a lot of trouble. We had
` a the lot of trouble getting things into
` cells. We had a lot of trouble with things
` being expressed. It was very much cell type
` dependent. Very much a function of what it
` is we were trying to introduce. So the
` answer is yes.
` Q. Okay. I want to go back to this
` paragraph 36 of your report. I'd suggest to
` you that I think there is a typographical
` error in your report because I don't see the
` quoted materials in the first sentence of
`7 (Pages 25 to 28)
`
`

`
`Page 29
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` recovery of antibody, spun bound whole
` cells, or from the cell culture containing
` both the medium and the suspended cells in
` column 12, 36 through 49.
` MR. McCORMICK: I was just going
` to note that.
` A. That's correct.
` Q. I think I can direct your
` attention to where that is referred to, if
` we can turn to that section of the patent,
` it is in column 8, found in the paragraph
` starting on line 33 of the Cabilly patent.
` A. Yes.
` Q. So that's the section that I
` asked you earlier about as to whether there
` is a reference to bacterial host cells;
` correct?
` A. No.
` Q. I will go ahead and ask you
` does this section refer specifically to
` bacterial host cells?
` MR. McCORMICK: Object, vague and
` ambiguous.
` A. Again, it is a little bit out
`
`Page 30
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` of context in that starting on line 3 where
` they describe expression vectors they're
` talking about plasmids that are used to, I
` guess for the cloning steps. And that they
` have tetracycline resistance which would be
` of value only in a prokaryotic cell for
` selection.
` Q. There were selectable markers
` that would work in eukaryotic cells as of
` April 8, 1983?
` A. Yes.
` Q. You are pretty familiar with
` those selectable markers?
` A. I think I am.
` Q. You reference the definition of
` expression vector, the section referring to
` spun bound whole cells or cell culture
` containing both medium and suspended cells
` that Dr. Scott is of the opinion refers to
` in vivo assembly, that is in the definition
` of recombinant host cells; correct? It is a
` completely separate definition?
` A. Well it is certainly included
` here, so I'd have to of go look again at
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`Page 31
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` Dr. Scott's.
` Q. Will you grant me in the
` definition of recombinant host cells, at
` column 8, line 26, that goes to line 39,
` that doesn't specify what type of host cell;
` does it?
` A. Oh, I see what you're saying.
` In general terms, no, it doesn't.
` Q. In specific terms it doesn't
` refer to a specific type of host cell
` either; does it?
` A. No, but if you go down a little
` bit further down they talk only about
` prokaryotes.
` Q. I understand the experimental
` data is prokaryotes, when they define
` recombinant host cells in the Cabilly patent
` it doesn't say whether it is prokaryotic or
` eukaryotic; does it?
` A. At this point, no, it does not.
` Q. There are sections in the
` patent you acknowledge in your report that
` do describe host cells that could be used
` that are eukaryotic and expression vectors
`
`Page 32
` SAUL J. SILVERSTEIN, PH.D.-CONFIDENTIAL
` that could be used in those eukaryotic host
` cells for