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` UNITED STATES DISTRICT COURT
` FOR THE DISTRICT OF DELAWARE
` -----------------------------X
` NOVARTIS PHARMACEUTICALS
` C.A. No. 14-1196-RGA
` CORPORATION and NOVARTIS AG,
`
` Plaintiffs,
`
` v.
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` WEST-WARD PHARMACEUTICALS,
`
` Defendant.
` -----------------------------X
` NOVARTIS PHARMACEUTICALS
` C.A. No. 15-128-RGA
` CORPORATION and NOVARTIS AG,
`
` Plaintiffs,
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` v.
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` UNITED STATES DISTRICT COURT
` FOR THE DISTRICT OF DELAWARE
` -----------------------------X
` NOVARTIS PHARMACEUTICALS
` C.A. No. 14-1196-RGA
` CORPORATION and NOVARTIS AG,
`
` Plaintiffs,
`
` v.
`
` WEST-WARD PHARMACEUTICALS,
`
` Defendant.
` -----------------------------X
` NOVARTIS PHARMACEUTICALS
` C.A. No. 15-128-RGA
` CORPORATION and NOVARTIS AG,
`
` Plaintiffs,
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` v.
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`NOVARTIS PHARMACEUTICALS
` C.A. No. 14-1508-RGA
`CORPORATION and NOVARTIS AG,
`
` Plaintiffs,
`
` v.
`
`WEST-WARD PHARMACEUTICALS,
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` Defendant.
`-----------------------------X
`NOVARTIS PHARMACEUTICALS
` C.A. No. 15-474-RGA
`CORPORATION and NOVARTIS AG,
` Plaintiffs,
` v.
`WEST-WARD PHARMACEUTICALS,
` Defendant.
`-----------------------------X
` March 3, 2017
` 9:30 a.m.
` Videotaped deposition of DANIEL CHANG
` CHO, M.D., held at the offices of GOODWIN
` PROCTER LLP, 620 Eighth Avenue, New York,
` New York, pursuant to Notice, before
` Annette Arlequin, a Certified Court
` Reporter, a Registered Professional
` Reporter, a Certified Realtime Reporter,
` and a Notary Public of the State of New York.
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`A P P E A R A N C E S:
` FITZPATRICK, CELLA, HARPER & SCINTO
` Attorneys for Plaintiffs
` 1290 Avenue of the Americas
` New York, New York 10104
` BY: CHARLOTTE JACOBSEN, ESQ.
` SUSANNE FLANDERS, ESQ.
`
` GOODWIN PROCTER
` Attorneys for Defendant
` The New York Times Building
` 620 Eighth Avenue
` New York, New York 10018
` BY: MICHAEL COTTLER, ESQ.
`
`ALSO PRESENT:
`
` RODOLFO DURAN, Legal Video Specialist
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` IT IS HEREBY STIPULATED AND AGREED by
`and between the attorneys for the
`respective parties herein, that filing and
`sealing be and the same are hereby waived;
` IT IS FURTHER STIPULATED AND AGREED
`that all objections, except as to the form
`of the question, shall be reserved to the
`time of the trial;
` IT IS FURTHER STIPULATED AND AGREED
`that the within deposition may be sworn to
`and signed before any officer authorized to
`administer an oath, with the same force and
`effect as if signed and sworn to before the
`Court.
`
` - o0o -
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` D. Cho
` THE VIDEOGRAPHER: This is DVD No. 1
`of the video-recorded deposition of Daniel
`Chang Cho, M.D. in the matter Novartis
`Pharmaceuticals Corporation and Novartis AG
`versus Roxane Laboratories, Inc. in the
`United States District Court for the
`District of Delaware.
` This deposition is being held at the
`law offices of Goodwin Procter LLP located
`at 620 Eighth Avenue, New York, New York,
`on March 3rd, 2017, approximately 9:34 a.m.
` My name is Rodolfo Duran. I am the
`legal video specialist. The court reporter
`today is Annette Arlequin and we are both
`in association with TSG Reporting, Inc.
` Will counsel please introduce
`yourselves.
` MS. JACOBSEN: Charlotte Jacobsen
`from Fitzpatrick on behalf of the Novartis
`plaintiffs. And with me is Susanne
`Flanders, also from Fitzpatrick.
` MR. COTTLER: Michael Cottler from
`the law firm of Goodwin Procter on behalf
`of the defendant, which is now Westward,
`
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` D. Cho
` formerly Roxane.
` THE VIDEOGRAPHER: Will the court
` reporter please swear in the witness.
` * * *
`D A N I E L C H A N G C H O, M.D.,
` called as a witness, having been duly
` sworn by a Notary Public, was examined
` and testified as follows:
`EXAMINATION BY
`MS. JACOBSEN:
` Q. Good morning, Dr. Cho.
` A. Hello.
` Q. Have you been deposed before?
` A. Yes.
` Q. About how many times?
` A. Once.
` Q. And was that in connection with a
`patent matter?
` A. No.
` Q. Just before we get started, I just
`want to discuss a couple of sort of ground rules
`that will help today go more smoothly.
` The first, as you see, we have a
`stenographer taking down what is said today.
`
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` D. Cho
`means of 28 hours and 60 hours respectively."
` Do you see that?
` A. Yes.
` Q. And you have not disputed that as of
`February 2001, it had been reported that
`everolimus had an approximately twofold shorter
`half-life than rapamycin, correct?
` A. That is correct.
` Q. There's also a quote from Neumayer
`1999 that reads, "Under multiple dosing
`conditions, the accumulation potential of
`everolimus was expected to be smaller than that
`of rapamycin."
` Do you see that?
` A. I do.
` Q. And you do not dispute that that was
`a difference between everolimus and rapamycin
`that had been reported as of February of 2001?
` MR. COTTLER: Counsel, do you have
` the original document that the report is
` citing to?
` MS. JACOBSEN: We can --
`BY MS. JACOBSEN:
` Q. Dr. Cho, do you have any issue with
`
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`this quotation?
` A. I do not have any issue with that
`quotation.
` Q. Okay. And so you don't dispute that
`there was a difference between everolimus and
`rapamycin that had been reported as of February
`of 2001?
` MR. COTTLER: Objection to form.
` Vague. Mischaracterizes the document.
` A. I don't object that these two
`quotations were present in that reference.
` Q. Okay. And you don't dispute that
`there were known differences, for example, in
`the half-life between rapamycin and everolimus
`as of February of 2001?
` MR. COTTLER: Objection to form.
` A. I do not dispute that.
` Q. Okay. And if we can look at
`paragraph 244. This first sentence reads,
`"Hidalgo II 2000 also reported that the
`half-life of temsirolimus was 15.2 hours, which
`is different from both everolimus and
`rapamycin."
` Do you see that?
`
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` D. Cho
` A. Yes.
` Q. And you haven't disputed that as of
`February 2001, it had been reported that the
`half-life of temsirolimus was different from
`both everolimus and rapamycin, correct?
` MR. COTTLER: Objection to form. If
` you give him the document that's being
` cited, that would probably be more fair.
` A. Do you happen to have the document?
` Q. We can look at it. But, I mean, just
`to try to short-circuit this, I'm just trying to
`understand where we have disagreement and where
`we don't. And if you need to look at your reply
`report to see if this is an issue that you think
`you've disputed, then by all means go ahead.
`But, you know, we have a lot to get through
`today, and I'm trying to see what you disagree
`with and what you don't.
` MR. COTTLER: Objection.
`BY MS. JACOBSEN:
` Q. So with that understanding, Dr. Cho,
`let me reask my question.
` You haven't disputed that as of
`February of 2001, it had been reported that the
`
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`half-life of temsirolimus was different from
`both everolimus and rapamycin, correct?
` MR. COTTLER: Objection to form. He
` asked for the document, so you should give
` it to him. This is not a memory test or a
` race.
` A. No, I do not dispute that.
` Q. And then Dr. Burris also opines that
`a POSA would have understood that the
`elimination half-life of a drug is a complex
`function of drug distribution, biotransformation
`and elimination.
` Do you see that?
` A. I do.
` Q. And you have not disputed that
`opinion, have you?
` MR. COTTLER: Objection to form.
` A. No, I do not dispute that.
` Q. And you also don't dispute that
`everolimus's binding to FKBP12 had been reported
`to be about threefold weaker than that of
`rapamycin, correct?
` MR. COTTLER: Objection to form.
` Again, this is without the benefit of the
`
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` cited references.
` A. No, I don't dispute that either.
` Q. And by February of 2001 -- sorry,
`strike that.
` You don't dispute by February of
`2001, it had been reported that FKBP12 binding
`was necessary for mTOR inhibitor, correct?
` MR. COTTLER: Objection to form.
` A. I don't understand that question.
` When you say FKB12 was -- binding was
`necessary for mTOR inhibitor, I don't know what
`that means.
` Q. Sorry, I'll reask the question. If
`that's what I said, I misspoke. It appears from
`the record it is, so I did misspeak. Strike
`that.
` You don't dispute that by February of
`2001, it had been reported that FKBP12 binding
`was necessary for an mTOR inhibitor to inhibit
`mTOR, correct?
` MR. COTTLER: Objection to form.
` A. I dispute that.
` Q. Is that an opinion that you've
`offered in your reply report?
`
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` D. Cho
`their analogs is dependent upon mTOR inhibition
`would interpret that as actually -- that they
`actually are both mTOR inhibitors.
` Q. You said the similar biological
`activity in the statement as you understand a
`POSA would understand it refers to inhibition of
`mTOR activity?
` A. Yes.
` Q. And Hallensleben 2000 doesn't teach a
`POSA that everolimus and rapamycin have the same
`antitumor activity, correct?
` MR. COTTLER: Objection to form.
` A. No, it does not teach that they have
`the same antitumor activity.
` Q. Let's look at a different document.
` Actually, before we do that, you
`don't dispute Dr. Burris's opinion that no drug
`is effective for all types of cancer, correct?
` MR. COTTLER: Objection to form.
` A. I don't feel I can have an opinion on
`that one way or the other, but I don't dispute
`that.
` Q. And you don't dispute Dr. Burris's
`opinion that just because a compound showed
`
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` D. Cho
`be irrelevant in a tissue cancer model, a tissue
`culture model where there is no vasculature to
`be inhibited.
` Moreover, a POSA would have known,
`been aware clinical data, early Phase I clinical
`data showing responses in patients with renal
`cell carcinoma as a sign that that is a cancer
`that is likely to be sensitive to CCI-779.
` And, finally, a POSA would have
`interpreted this sentence not to refer to
`necessarily which tumors but also within certain
`cancers are there subsets of patients, either
`due to certain molecular features would be more
`sensitive.
` Q. Now one thing you said in connection
`with that answer was that a POSA would have been
`aware of the Phase I data showing responses in
`patients with renal cell carcinoma, correct?
` A. Yes.
` Q. Do you recall that?
` And you would agree with me that
`Hidalgo summarized that Phase I clinical trial
`data and -- including the responses that had
`been seen in renal cell carcinoma patients,
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`correct?
` A. Yes.
` Q. And notwithstanding that, the
`conclusion that this author -- the conclusion
`the authors of this paper was that it remained
`to be a developmental challenge predicting which
`tumors will be particularly sensitive to
`CCI-779, correct?
` MR. COTTLER: Objection.
` Mischaracterizes the document.
` A. I am -- I will concede that that
`sentence is there. I do not know what they mean
`by that sentence.
` A POSA would, I believe, still have
`been motivated to pursue CCI-779 based on the
`clinical activity seen in renal cell carcinoma.
` With respect to the developmental
`challenges, I believe they could be referring to
`other cancer types. And, furthermore, a POSA
`would have been aware that the drug company
`which -- was manufacturing CCI-779, which I
`believe was why at that time had already
`committed to doing a Phase II clinical trial in
`renal cell carcinoma. So they would have felt
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`that that was worth pursuing as well.
` Q. Okay. But they don't conclude that
`CCI-779 would be expected to be effective
`against RCC, correct?
` MR. COTTLER: Objection to form.
` A. That was not a specific conclusion of
`this paper.
` Q. And just reading from one of your
`previous answers, you say, "a POSA would
`understand" -- sorry. Strike that.
` You say, "These are all tissue
`cultures, so the very mechanism of action by
`which a POSA would understand this drug to have
`benefit would be irrelevant in a tissue culture
`model where there's no vascular to be
`inhibited," I think.
` A. Vasculature to be inhibited.
` Q. So is it your opinion that the in
`vitro data with respect to temsirolimus is not
`relevant to the POSA's expectations of
`temsirolimus's clinical use?
` MR. COTTLER: Objection to form.
` Mischaracterizes the testimony.
` A. No. You can use in vitro data to
`
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`show that the drug can function as an mTOR
`inhibitor.
` The more appropriate model would be
`an in vivo xenograft model in which a tumor has
`a vasculature, and that is what was provided in
`the '442 patent.
` Q. Why do you mean the tumor has a
`vasculature?
` A. In a cell culture, the tumors are
`basically lining the plastic. There is no blood
`vessels and they are bathed in nutrients. For a
`drug to function as a potentially, what we call,
`an antiangiogenic agent, those function by
`killing blood vessels. So you cannot test that
`principle in tissue culture. You would need a
`model and a xenograft with you implant a tumor
`in the flank of a mouse.
` Which I believe the tumor they used,
`that -- those tumors are three dimensional and
`have blood vessels. So that is a better test of
`the principle of an antiangiogenic agent.
` Q. Okay. Do all xenograft models have
`vasculature?
` A. Yes.
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` Do you see that?
` A. Yes.
` Q. And as I understand it, it's your
`opinion that Phase I studies are not powered to
`demonstrate efficacy like Phase II or III
`studies; is that right?
` A. Yes, I see that.
` Q. So what is the purpose of a Phase I
`study in your opinion?
` A. The primary objective of Phase I
`studies can vary, but most typically are to
`assess safety and determine dose of experimental
`therapies.
` Q. And the primary objective of Phase I
`study is not to assess the efficacy of an
`experimental therapy, correct?
` MR. COTTLER: Objection to form.
` Vague.
` A. I think it is correct to say that it
`is most typically not to assess efficacy.
` Q. And in this paragraph, you say that
`"Phase I studies can provide a signal as to
`whether a drug may be effective against a
`particular tumor type."
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` What I believe is necessary for a
`POSA to actually have also in addition to a
`reasonable expectation of success includes the
`scientific rationale.
` Q. But you're not suggesting that a POSA
`would understand from the mere fact that a
`compound entered Phase II trials that there was
`a reasonable expectation that the compound would
`be effective, are you?
` MR. COTTLER: Objection.
` Mischaracterizes the testimony.
` A. I would agree that a POSA would not
`assume that a drug will have -- just on the
`basis of a drug entering Phase II testing, a
`POSA would not necessarily assume that it would
`have a reasonable expectation of success.
` Q. And earlier you said that a Phase I
`trial can't provide certainty that a drug will
`be effective against a particular tumor type.
` Do you recall that testimony?
` A. Yes, I do.
` Q. And why is that?
` A. Well, I think that that really
`depends on how we define certainty. But
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` D. Cho
` A. Yes, I do.
` Q. And prior to providing that opinion,
`did you research what was known about the cell
`lines that were tested in the 446 patent?
` A. Prior to reading that, I was already
`aware of those cell lines, having worked with
`them.
` Q. You did not cite to any prior art
`that discusses the cell lines that were tested
`in the '446 patent, correct?
` A. I did not.
` Q. You didn't cite any prior art
`discussing whether these cell lines were good or
`poor models for RCC, correct?
` MR. COTTLER: Objection to form.
` A. I did not.
` Q. Would you agree there is some cancer
`models that don't predict efficacy in the
`clinic, correct?
` MR. COTTLER: Objection. Incomplete
` hypothetical. Vague.
` A. Yes, there are some models that don't
`predict efficacy.
` Q. You'd agree that just because a cell
`
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`line is derived from a RCC tumor doesn't mean
`it's a good model for RCC, correct?
` MR. COTTLER: Objection. Vague.
` Incomplete hypothetical.
` A. Again, I don't know how to
`characterize the word "good."
` RCC cell lines derived from RCC and
`the ones we were talking about actually are VHL
`null and mimic and actually reliably reproduce
`the consequences of VHL loss.
` So they are good models to test
`certain biologic principles. They are very
`imperfect at predicting the efficacy of drugs in
`humans.
` It does not necessarily mean they are
`bad models. I believe you can still learn quite
`a bit from them.
` Q. And you would agree, though, that
`cell lines can change in culture, correct?
` MR. COTTLER: Objection to form.
` Vague. Incomplete hypothetical.
` A. A cell line can change in culture.
` MS. JACOBSEN: Can we have a look at
` Dr. Burris's surreply report?
`
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` A F T E R N O O N S E S S I O N
` (Time noted: 1:32 p.m.)
` * * *
`D A N I E L C H A N G C H O, resumed
` and testified as follows:
` THE VIDEOGRAPHER: The time is
` 1:32 p.m., and we are back on the record. This
` also begins DVD No. 4.
`EXAMINATION BY (Cont'd)
`MS. JACOBSEN:
` Q. Dr. Cho, just before lunch we were
`discussing the '446 patent and the clinical
`trial results in that.
` A. Okay.
` Q. Do you have that still? Great.
` When we were discussing those
`results, we'll look back at the record, but I
`think you used the term "promising."
` Do you recall that?
` A. Yes.
` Q. Did you mean that to have the same
`meaning you gave me before with respect to
`promising results and that they are worthy of
`further investigation?
`
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` D. Cho
` A. Yes.
` Q. You agree that this patent, the '446
`patent, reports results of two Phase I clinical
`trials?
` A. Yes, I do.
` Q. The first study enrolled 63 patients;
`is that right?
` A. Yes.
` Q. And the second one enrolled 24
`patients?
` A. Yes.
` Q. Okay. And that is a total of 87
`patients; is that right?
` A. That is correct.
` Q. And then if we look at the results on
`the top of column 4, it gives the results for
`the weekly schedule first; is that right?
` A. That's correct.
` Q. And I think the weekly schedule is
`actually the second study?
` MR. COTTLER: Objection to form.
` A. In the second study referred to the
`first paragraph under the heading "Clinical
`Trial," then, yes, that is the weekly schedule.
`
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` A. Yes, I do not dispute it.
` Q. Okay. Thank you.
` And you don't dispute that PTLDs were
`known to be a life-threatening complication of
`immunosuppressive therapy necessary for
`prevention of graft rejection, correct?
` A. Yes.
` Q. And you don't dispute the Majewski
`2000 was not concerned with the potential use of
`everolimus in a non-immunosuppressed agent,
`correct?
` A. I'm sorry, can you repeat the
`question?
` Q. I read a lot of negatives. I'll
`rephrase. Strike that.
` Majewski 2000 did not concern the use
`of everolimus in a non-immunosuppressed setting,
`correct?
` MR. COTTLER: Objection to form.
` Vague.
` A. Yes, I would agree with that.
` Q. And you don't dispute that a POSA
`would not have reasonably expected in vitro or
`in vivo activity against an Epstein-Barr virus
`
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`transformed B cell lymphoma PTLD model to
`reasonably predict activity in RCC, correct?
` A. I do not.
` Q. And you don't dispute that as of
`February of 2001, chemotherapy drugs used to
`treat lymphoma, such as doxorubicin and
`cyclophosphamide had already failed in RCC?
` A. I don't dispute that at all.
` Q. Okay.
` MS. JACOBSEN: I think we've been
` going almost an hour and I'm about to move
` something else. I think it might be a
` great idea to take a break.
` MR. COTTLER: Sure.
` MS. JACOBSEN: Thanks.
` THE VIDEOGRAPHER: The time is
` 2:18 p.m. and we are going off the record.
` (Recess is taken.)
` THE VIDEOGRAPHER: The time is
` 2:32 p.m. We are back on the record. This
` also begins DVD No. 5.
`BY MS. JACOBSEN:
` Q. Dr. Cho, before the break we were
`talking about Majewski 2000. I believe you said
`
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` D. Cho
`greatly, greatly out of proportion in the
`general populous for sporadic renal cell
`carcinoma, would have seen this data and known
`that VHL loss or strongly suspected that VHL
`loss was central to the biology of the formation
`of renal cell carcinoma.
` Q. In VHL -- you are talking about in
`VHL-diseased patients?
` A. In VHL-diseased patients, but also
`abstracting that towards the sporadic population
`where a POSA would have also have been aware
`that 56 to 57 percent of sporadic RCCs possess
`VHL mutations.
` Q. But as of February 2001, VHL gene
`mutations were not the only type of genetic
`mutations that were hypothesized to be
`associated with RCC, correct?
` MR. COTTLER: Objection. Vague.
` A. It was by far the most common. There
`weren't even others even close.
` Q. But there were others, right?
` MR. COTTLER: Objection. Asked and
` answered. Vague.
` A. Yes.
`
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` D. Cho
` Q. And a POSA would not know without
`testing whether an RCC patient had a VHL gene,
`correct?
` MR. COTTLER: Objection.
`BY MS. JACOBSEN:
` Q. Gene mutation. Sorry.
` A. That is correct. But, again, a POSA
`would be aware that the majority of sporadic
`clear cell RCC would have been expected to have
`a VHL mutation.
` Q. And you said that the VHL gene
`mutation was the most common. There weren't --
`there weren't even others that were even close.
` And included in that is the PTEN
`mutations weren't even close to VHL; is that
`correct?
` A. That would be accurate, yes.
` Q. And at the time in February of 2001,
`it was not common to test an RCC patient to see
`whether or not they had the VHL gene mutation
`prior to treating them, correct?
` MR. COTTLER: Objection, vague.
` A. As of February 2001, that is correct.
` Q. Okay. We'll look at another paper.
`
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` D. Cho
`of the left-hand column.
` A. Yes.
` Q. That testing was done in vitro; is
`that right?
` A. Yes.
` Q. And Sekulic 2000 does not mention
`RCC, correct?
` A. This paper does not specifically
`mention RCC.
` Q. And if you can turn to page 3512, in
`the middle of the left-hand column, there is a
`paragraph that starts "Rapamycin..."
` Do you see that?
` A. Yes.
` Q. And the third sentence in that
`paragraph reads: "The phenotypic parameters
`that govern tumor cell sensitivity versus
`resistance to rapamycin are poorly understood."
` Do you see that?
` A. Yes.
` Q. A person of ordinary skill in the art
`as of February of 2001 would have understood
`that some cell lines are sensitive to rapamycin
`and other cell lines are resistant to rapamycin;
`
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` D. Cho
`is that fair?
` A. That is likely the case.
` Q. And sensitive to rapamycin refers to
`rapamycin inhibiting the tumor cell growth; is
`that correct?
` A. Sensitive with respect to an in vitro
`or in vivo assay likely reflects that, yes.
` Q. And what does resistance to rapamycin
`refer to?
` A. I can only speculate what the author
`is referring to. But in the context of in vitro
`and in vivo studies, it would be a continued
`growth despite treatment with rapamycin.
` Q. Okay. And is that how a POSA would
`understand the reference to resistance in the
`sentence we have just been discussing?
` A. Yes, I believe so.
` Q. And this sentence read that the
`phenotypic parameters that govern tumor cell
`sensitivity versus resistance to rapamycin were
`poorly understood.
` Would a POSA dispute that sentence?
` A. No.
` Q. So a POSA would have understood that
`
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`reference that you referred to?
` A. Yes, it is.
` Q. And that's entitled "PTEN/MMAC1/TEP1
`Mutations in Human Primary Renal Cell Carcinomas
`and Renal Carcinoma Cell Lines."
` Do you see that?
` A. That is correct.
` Q. I want to ask you a question about
`the bold text on the top left-hand corner of the
`left column, Kondo page 219.
` A. Page 209?
` Q. 219. The page that you're on.
` A. Okay.
` Q. The bold text, left-hand corner?
` A. Yes.
` Q. This indicates in the third sentence,
`do you see it says, "To investigate..."?
` A. Yes.
` Q. And this indicates, "The purpose of
`this study was to investigate the potential role
`of the PTEN gene in renal tumor genesis."
` Do you see that?
` A. Yes.
` Q. And you agree with me that the role
`
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`of the PTEN gene in renal tumor genesis was not
`understood in 2001?
` MR. COTTLER: Objection. Vague.
` A. Yes, I would agree with that.
` Q. And this paper found that out of 68
`RCC samples tested, only five had a somatic
`mutation at the PTEN gene?
` MR. COTTLER: Objection. Vague.
`BY MS. JACOBSEN:
` Q. Is that right?
` A. That is the results they reported.
` Q. And that equates to 7.5 of the
`prime -- 7.5 percent of the primary RCCs having
`somatic mutation in the PTEN gene, correct?
` A. That is correct.
` Q. And a POSA wouldn't have been able to
`determine in advance of testing whether a
`patient's RCC tumor had a PTEN mutation,
`correct?
` A. That is correct.
` Q. And you'd agree with me that even
`today, no biomarker or genetic mutation has been
`shown to predict efficacy of an mTOR inhibitor
`against RCC?
`
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` MR. COTTLER: Objection.
` A. Today?
` MR. COTTLER: Objection to form.
` A. As of today, no, there has been no
`biomarkers proven or validated.
` Q. And the same was true in 2001, that
`no genetic mutational biomarker, including PTEN
`or VHL gene status, has been shown to reasonably
`predict the efficacy of an mTOR inhibitor in the
`treatment of RCC?
` MR. COTTLER: Objection to form.
` A. Yes, that is true.
` Q. I'd like to look at another
`reference, this time the Raghavan Kozlowski
`reference. I'm not doing justice to that name.
` (Plaintiffs' Cho Exhibit 32, Chapter
` 78 of a textbook. The chapter is entitled,
` "Renal Cell Carcinoma Tumor Markers,"
` written by Kozlowski, Bates stamped
` ROX_EV_00149173 through 9182, marked for
` identification, as of this date.)
`BY MS. JACOBSEN:
` Q. I'm handing you a document marked
`Exhibit 32. It's chapter 78 of a
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