`
`UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF NEW JERSEY
`__________________________________
`HELSINN HEALTHCARE, S.A. and
`ROCHE PALO ALTO, LLC,
`Plaintiffs,
`-vs-
`DR. REDDY'S LABORATORIES, LTD.,
`DR. REDDY'S LABORATORIES, INC.,
`TEVA PHARMACEUTICALS USA, INC.,
`and TEVA PHARMACEUTICAL
`INDUSTRIES, LTD.
`Defendants.
`__________________________________
`Clarkson S. Fisher United States Courthouse
`402 East State Street
`Trenton, New Jersey 08608
`June 2, 2015
`B E F O R E:
`
`CIVIL ACTION NUMBERS:
`11-3962
`
`TRIAL
`
`THE HONORABLE MARY L. COOPER
`UNITED STATES DISTRICT JUDGE
`
`Certified as True and Correct as required by Title 28, U.S.C.,
`Section 753
`/S/ Regina A. Berenato-Tell, CCR, CRR, RMR, RPR
`/S/ Carol Farrell, CCR, CRR, RMR, CCP, RPR, RSA
`
`Dr. Reddy’s Laboratories, Ltd., et al.
`v.
`United States District Court
`Helsinn Healthcare S.A., et al.
`U.S. Patent No. 9,(cid:20)(cid:26)(cid:22),(cid:28)(cid:23)(cid:21)
`Trenton, New Jersey
`Reddy Exhibit 1045
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`1
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`UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF NEW JERSEY
`__________________________________
`HELSINN HEALTHCARE, S.A. and
`ROCHE PALO ALTO, LLC,
`Plaintiffs,
`-vs-
`DR. REDDY'S LABORATORIES, LTD.,
`DR. REDDY'S LABORATORIES, INC.,
`TEVA PHARMACEUTICALS USA, INC.,
`and TEVA PHARMACEUTICAL
`INDUSTRIES, LTD.
`Defendants.
`__________________________________
`Clarkson S. Fisher United States Courthouse
`402 East State Street
`Trenton, New Jersey 08608
`June 2, 2015
`B E F O R E:
`
`CIVIL ACTION NUMBERS:
`11-3962
`
`TRIAL
`
`THE HONORABLE MARY L. COOPER
`UNITED STATES DISTRICT JUDGE
`
`Certified as True and Correct as required by Title 28, U.S.C.,
`Section 753
`/S/ Regina A. Berenato-Tell, CCR, CRR, RMR, RPR
`/S/ Carol Farrell, CCR, CRR, RMR, CCP, RPR, RSA
`
`United States District Court
`Trenton, New Jersey
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`2
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`A P P E A R A N C E S:
`PAUL HASTINGS
`BY:
`JOSEPH O'MALLEY, ESQUIRE
`ERIC W. DITTMANN, ESQUIRE
`ISAAC S. ASHKENAZI, ESQUIRE
`SAUL EWING
`CHARLES M. LIZZA, ESQUIRE
`BY:
`Attorneys for the Plaintiffs
`
`BUDD LARNER
`BY: STUART D. SENDER, ESQUIRE
`MICHAEL H. IMBACUAN, ESQUIRE
`H. HOWARD WANG, ESQUIRE
`CONSTANCE S. HUTTNER, ESQUIRE
`KENNETH E. CROWELL, ESQUIRE
`Attorneys for the Defendant, Dr. Reddy's Laboratories
`WINSTON & STRAWN
`BY: JOVIAL WONG, ESQUIRE
`GEORGE LOMBARDI, ESQUIRE
`JULIA MANO JOHNSON, ESQUIRE
`BRENDAN F. BARKER, ESQUIRE
`LITE DePALMA, GREENBERG, LLC
`BY: MAYRA V. TARANTINO, ESQUIRE
`Attorneys for the Defendant, Teva
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`Exh. 1045
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`3
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`I N D E X
`
`WITNESS
`
`DIRECT
`
`CROSSREDIRECT
`
`RECROSS
`
`OPENING ARGUMENTS:
`By Mr. Lombardi, 13
`By Ms. O'Malley 61
`GIORGIO CALDERARI
`By Mr. Lombardi 105
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`Exh. 1045
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`Calderari - Direct
`
`105
`
`THE COURT: Okay. Thank you. I should have been
`told this before now. This is not seemly for me to be
`unpacking boxes.
`MR. LOMBARDI: I apologize.
`THE COURT: So go right ahead, and we'll do that at a
`break. But I'll watch on the monitor.
`MR. LOMBARDI: And we will be showing everything on
`the monitor.
`THE COURT: Okay. Fine.
`GIORGIO CALDERARI, DEFENDANTS' WITNESS, SWORN.
`THE DEPUTY CLERK: Please state and spell your full
`name for the record.
`THE WITNESS: Dr. Calderari.
`THE DEPUTY CLERK: Can you spell your name, please.
`THE WITNESS: G-I-O-R-G-I-O, C-A-L-D-E-R-A-R-I.
`MR. LOMBARDI: Thank you, your Honor.
`(Direct Examination of Giorgio Calderari By Mr. Lombardi:)
`BY MR. LOMBARDI:
`Q. Dr. Calderari, I'm going to show you documents on the
`screen. I have the hard copies there in case you prefer to
`look at them, and if they're in your way, you can move them in
`whatever way makes you comfortable.
`All set?
`A. Yes.
`Q. Dr. Calderari, my name is George Lombardi. We haven't
`
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`Exh. 1045
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`Calderari - Direct
`
`106
`
`met; is that right?
`A. Yup.
`Q. And, Doctor, you are the Giorgio Calderari who was an
`inventor on the four patents that are at issue in this case;
`is that right?
`A. Right.
`Q. You're a scientist by training?
`A. Yes.
`Q. You graduated from university in Europe in 1982; is that
`right?
`A. Right.
`Q. And that was in Zurich?
`A. It was in Zurich.
`Q. You were studying chemistry?
`A. I studied chemistry in Zurich, and I finished with my
`degree in 1982.
`Sorry.
`MR. LOMBARDI: Your Honor, may I ask that the doctor
`pull the microphone a little bit closer?
`THE COURT: I'm not sure it is going to amplify. Oh,
`there. That's better.
`BY MR. LOMBARDI:
`Q. Okay. Thank you, Doctor.
`And you studied chemistry in university; is that right?
`A. Right.
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`Exh. 1045
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`107
`
`Calderari - Direct
`Q. And then you entered a Ph.D. program in organic
`chemistry, at least that was the general area; is that right?
`A. Right.
`Q. And you finished that up in 1985?
`A. Right.
`Q. Then you joined Helsinn?
`A. Yes.
`Q. As an employee?
`A. Right.
`Q. And you have been at Helsinn continuously since the mid
`1980s; is that right?
`A. That is right.
`Q. And you have held a variety of different roles at
`Helsinn; is that right?
`A. Right.
`Q. You started off as a scientist; is that right?
`A. Yes.
`Q. And today you're what in Helsinn's terminology is called
`a group general manager?
`A. Yes. I am the group general manager and chief operating
`officer.
`Q. Right. And that's what I -- and that has essentially the
`functions of what we would call a chief operating officer here
`in the United States; is that right?
`A. Right.
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`Exh. 1045
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`
`108
`
`Calderari - Direct
`Q. Okay. And you went from your role as a chemist to a role
`in quality assurance; is that right?
`THE COURT: Sir, where is your office?
`THE WITNESS: My office is in Lugano, southern part
`of Switzerland.
`THE COURT: Thank you.
`THE WITNESS: Lugano in Switzerland, L-U-G-A-N-O.
`BY MR. LOMBARDI:
`Q. And you had a quality assurance role; is that right?
`A. Also, yes.
`Q. And that was a role you had during the 1990s?
`A. That was a role that also I had during the 1990s, yes.
`Q. Okay. And you became head of technical affairs in 2000
`or thereabouts?
`A. Yeah, right.
`Q. And then chief manufacturing officer in 2002; is that
`right?
`A. Right. Yeah.
`Q. Now, you have no medical training?
`A. This is right, yes.
`Q. And you have no degrees in clinical study designs; is
`that right?
`A. This is right, yeah.
`Q. And your experience on conducting formulation
`optimization is limited to the drug palonosetron; is that
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`Exh. 1045
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`Calderari - Direct
`
`109
`
`right?
`A. This is right, yes.
`Q. And with respect to palonosetron, you weren't personally
`involved in determining the excipients; is that right?
`A. You were or you weren't?
`Q. You were not?
`A. I were not, no.
`Q. An excipient, by excipients we mean inactive ingredients;
`is that right?
`A. Right.
`Q. And you were not personally involved in stability testing
`that was done with palonosetron; is that right?
`A. Well, when I took over the role for the development of
`palonosetron, I had to read a variety of results from Syntex.
`And starting from them, then together with our team --
`THE COURT: Together with our team.
`THE WITNESS: Yes, then together with our team and
`the clinician, we had to decide about how to continue that,
`and then we run other experiment, including stability testing.
`BY MR. LOMBARDI:
`Q. Okay. And eventually you became what you referred to as
`the CMC leader for the palonosetron project.
`A. Oh, yes. This was in, back in 1998 when we acquired the
`license. We build a project team, and we collected the best
`people around the company, and I was in charge of the CMC
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`Exh. 1045
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`Calderari - Direct
`
`110
`
`part.
`Q. Okay. And so it's clear on the record, could you tell
`the Court what a CMC is?
`A. Yes. The CMC means chemistry manufacturing and control.
`It's all what about developing the API process and quality
`control, the drug product processes in quality control, up to
`having everything ready for the release and collecting all the
`necessary chemical stability data for filing a New Drug
`Application, and, yeah.
`Q. Okay. Now, Helsinn, as you have said, has headquarters
`in Switzerland; is that right?
`A. Is headquartered in Switzerland, yes.
`Q. Okay. And it has a business strategy of in-licensing new
`chemical entities at a certain stage of development; is that
`right?
`A. Yeah.
`Q. And by in-licensing, you mean taking licenses from others
`who have come up with the new chemical entities; is that
`right?
`A. This is right, yes.
`Q. And then Helsinn's strategy is to complete the
`development process and, ultimately, manufacture and sell the
`product; is that right?
`A. Well, not exactly, because during the phase that we are
`development, we seek partner for then that they can distribute
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`Calderari - Direct
`
`111
`
`the product around the world. We do not have sales force
`directly, so it's a so-called B-to-B, business-to-business way
`of doing business, so...
`Q. Okay. And Helsinn is not a drug discovery company; is
`that right?
`A. Was not. Now in the meantime, we have some -- some drug
`discovery capacity.
`Q. Fair enough. At the times that the work on palonosetron
`was going on, it was not a drug discovery company; is that
`right?
`A. Yup.
`Q. And Helsinn operated -- actually, the only patents you
`have in the United States are related to palonosetron; is that
`right?
`A. Oh, I -- I can't recall.
`Q. Okay. Helsinn operated, according to its business plan,
`this in-licensing plan, with respect to palonosetron; is that
`right?
`A. Right, yeah.
`Q. Didn't discover palonosetron?
`A. No.
`Q. Another company called Syntex discovered palonosetron; is
`that right?
`A. Right.
`Q. So, Doctor, before we get on, just to confirm for the
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`Exh. 1045
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`Calderari - Direct
`
`112
`
`record, I'm going to show you one of the patents just as an
`example just so that we can identify.
`I'm going to show you the '219 patent, and that is
`DTX-0268. It's in your binders if you want, but I'm going to
`put it on the screen, and if you can't see it well enough on
`the screen, let me know. This is just the first page, and I'm
`going to blow it up for you, Doctor, so you can see it better.
`MR. LOMBARDI: DJ, if we can just do the top half,
`
`say.
`BY MR. LOMBARDI:
`Q. Are you able to read that now, Doctor?
`A. Yes.
`Q. Okay. And So, you see this is the '219 patent on which
`you're listed as an inventor.
`A. Right.
`Q. And the other inventors are listed there where DJ has
`placed the cursor.
`Do you see that?
`A. I see that.
`Q. And the patent -- well, this is the '219. Let's just
`skip back and just look at a claim here just so that we see
`that. Let's go to Column 10, which is Page 11 of the patent.
`That's where the claims are, Doctor.
`Do you see that?
`A. Yes.
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`Exh. 1045
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`
`
`113
`
`Calderari - Direct
`Q. Okay. And let's just look at Claim 1. And you recognize
`that as one of the claims in the patent and one of the claims
`that's asserted here in this litigation; is that right?
`A. I recognize, yes.
`Q. Okay. And it's got the preamble language on reducing the
`likelihood of cancer chemotherapy, you see that?
`A. I see that.
`Q. And then it has the dosage of palonosetron. See that, at
`.25 milligrams?
`A. Yes.
`Q. And then it has a range for EDTA?
`A. Yes.
`Q. And it has a range for mannitol?
`A. Yes.
`Q. And it talks about being stable at 24 months; is that
`right?
`A. Right.
`Q. Okay. And you recognize, also, Example 4 in this patent,
`I'm going to move back a page, to Page 10. Example 4 has a
`particular formulation that fits within the ranges that we
`just talked about; is that right?
`A. Right.
`Q. And Example 4, the formulation that's there, is this the
`formulation for Aloxi®?
`A. It is.
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`114
`
`Calderari - Direct
`Q. Okay. And, so, this is a formulation that has the same,
`basically, the same plus a few of the ingredients we just
`looked at in the claim, Claim 1 of this patent; is that right?
`A. Right.
`Q. Now, it's true, isn't it, Doctor, that -- well, Syntex
`had been working on palonosetron for a period of time before
`Helsinn got involved; is that right?
`A. Right.
`Q. And Syntex got involved -- was working on it in the early
`'90s through roughly 1995; is that right?
`A. Right, yes.
`Q. And when did Helsinn first start considering a
`palonosetron product?
`A. It was in 1997.
`Q. Okay. And when Helsinn started considering a
`palonosetron product, they first looked to what Syntex had
`done; is that right?
`A. Right.
`Q. You obtained -- you were part of Helsinn's due diligence
`in considering entering into a transaction with Syntex; is
`that right?
`A. This is correct.
`Q. And being involved in that due diligence, you reviewed
`lots of documents, lots of scientific materials; is that
`right?
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`Calderari - Direct
`
`115
`
`A. Is right, yes.
`Q. And they were about palonosetron.
`A. Yes.
`Q. And one of the things that you discovered in your review
`of the scientific materials from Syntex when you first got
`involved is that the formulation of Example 4 had been arrived
`at by the folks at Syntex already; is that right?
`A. No, this is not the formulation that we are using now
`that were in the documentation of Syntex at that time.
`Q. Okay. Well, one of -- you got a few documents from
`Syntex, right? You got something called a preformulation
`book?
`A. Right, yeah.
`Q. And you got a document called the formulation book?
`A. Yes.
`Q. And that's where Syntex did work on coming up with a
`formula for a palonosetron I.V. administration product; is
`that right?
`A. Can you say again?
`Q. Yes. And any time you have trouble understanding, please
`tell me, and I'll try to reframe the question in a way that's
`understandable.
`A formulation book in the case of Syntex's formulation
`book was a book where the scientific materials and rationale
`for coming up with a formulation for a palonosetron I.V.
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`Calderari - Direct
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`116
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`product was kept; is that right?
`A. Yeah, this is where they describe the attempt, their
`experiment to arrive to a formulation that might be suitable
`for clinical trial and then after for commercialization.
`But to my surprise, when I made the first due
`diligence, they had never manufactured that formulation, that
`they had absolutely no any data about the stability of
`potential formulation to be used in a clinical trial.
`Q. Okay. So it is clear, Doctor, I'm not asking you whether
`they had actually manufactured a formulation. I'm asking you
`whether they came up with the formulation that's in Example 4?
`A. Not for the use in the CINV.
`Q. Well, that wasn't my question either. I asked you did
`they come up with that formulation that's --
`A. Can you show me the formulation book, please?
`Q. Absolutely. But I'm just asking do you remember, as you
`sit here today, whether they came up with that formulation?
`A. They came up? What do you mean, "came up"?
`Q. Did they create that formulation?
`A. They propose some formulations to be used in clinical
`trials for different indication.
`THE COURT: Some formulations plural?
`THE WITNESS: Some formulations, yes, plural.
`THE COURT: Formulations.
`THE WITNESS: Formulation, yeah. Remember, that
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`117
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`there are two indications in the emesis, one is the CINV in
`the morning, one is PONV and one is CINV. So they were
`proposing alternative formulation for use in clinical trials,
`depending on which indication you want to achieve.
`BY MR. LOMBARDI:
`Q. Okay. Is this one of the formulations that Syntex
`created?
`A. Again, if you maybe show me the formulation book, it's
`easier because there are so many data in this picture.
`Q. Okay.
`THE COURT: Counsel, your question is whether Example
`4 in the '219 patent spec is seen in the Syntex formulation
`book?
`
`MR. LOMBARDI: Correct, your Honor. Correct.
`BY MR. LOMBARDI:
`Q. Let's look at DTX-0219, Doctor. And, again, I'll put it
`up on the screen. I'm sorry I said that wrong. DTX-0254. My
`apologies.
`A. I wait anyway. Okay.
`Q. Okay. Now, is that the formulation book that Syntex
`created?
`A. Yes, it is.
`Q. And you saw that shortly after Helsinn got involved in
`doing due diligence -- excuse me -- due diligence concerning
`palonosetron?
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`118
`
`Calderari - Direct
`A. Well, shortly don't know, but for sure I had access to
`this document, yes.
`Q. And you read this document; is that right?
`A. Yeah, that's right, yes.
`Q. And, so, Doctor, if you look at Page DTX-0254-0010, are
`there some formulations listed on that page?
`A. Can you enlarge a bit?
`Q. Yes, absolutely. Do you see formulations listed there?
`A. Yes, I see that.
`Q. And for the record so it's clear, you recognize the
`reference to RS-25259-197 to be to palonosetron.
`A. Palonosetron hydrochloride, yes.
`Q. Okay. And do you see that the ingredients listed there
`are the same ones that were in Example 4?
`A. Yes.
`Q. And do you see that for Formulation 90, the number 90,
`those are the same as appear in Example 4; is that right?
`A. Yeah, but if I may qualify this, the Formulation 90
`probably if you go a bit over in the -- in the file, they were
`suggested by Syntex to be used in clinical trial for achieving
`treatment of emesis in PONV.
`Q. And I was going to get to that.
`A. Yeah.
`Q. But just bear with me for a minute. I promise you we'll
`talk about PONV --
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`119
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`A. Okay.
`Q. -- and CINV.
`A. Okay.
`Q. Just bear with me for a minute.
`If we compare that formulation, No. 90, to the
`formulation we just looked at in Example 4, they would be the
`same; is that right?
`A. They would be the same in term of concentration; but, for
`example, I mean, when you create a dose for a clinical trial,
`you also have to speak about the volume. At the end is the
`final dosage that you use.
`So the formulation in term of quality and quantity
`presence of excipient is the same, but they were meant to be
`used in another clinical trials than actually run, the CINV,
`and, also, the volume, the dose they would have proposed would
`be different because it was for a PONV indication.
`Q. Okay. And just so it's clear, I'll just make it clear on
`the record.
`A. Yeah.
`MR. LOMBARDI: If you expand the column going up just
`a little bit, up, DJ, up from "Formulation."
`BY MR. LOMBARDI:
`Q. Right here it says, it identifies what Formulations 89
`and 90 are.
`Do you see that?
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`Calderari - Direct
`A. I see that, yeah.
`Q. And it says, "Formulation 89 has been selected for Phase
`III and commercial formulation for CIN" it says "E." We've
`been calling it CINV in this case. Same thing to you?
`A. Yes, is the same things, yes.
`Q. And then it says, "Formulation ending in 90 has been
`selected for PONV"; is that right?
`A. This is right, yes.
`Q. And PONV is post-operative nausea and vomiting; is that
`right?
`A. Right, yes.
`Q. Okay. But my question to you is just very simple --
`A. Yeah.
`Q. -- the actual formulation, whatever it's going to be used
`for of palonosetron in an I.V. formulation is there in this
`Syntex formulation book; is that correct?
`A. Yes, it is correct.
`Q. Okay. And Syntex actually was proposing at this time in
`the formulation book that this formulation would be used in
`Phase III clinical trials; is that right?
`A. Yes, for PONV studies.
`Q. And it wasn't long after you got involved that CINV
`became the focus of use of that formulation; isn't that
`correct?
`A. Sorry, say again?
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`Q. It wasn't long after you and Helsinn became involved in
`the product -- in the project; I apologize. It wasn't long
`after you and Helsinn became involved in the project that that
`formulation that's in the Syntex formulation book, No. 90, was
`the focus of CINV studies; is that right?
`A. Yeah, but, again, the formulation, yes, but the dose are
`totally different. I mean, at the end of the study, you want
`to have a formulation, but you have to have a dose to
`experiment in human being. Okay.
`Q. Let me explain my question. I might not have made it
`clear.
`A. Okay.
`Q. That formulation for 90 --
`A. Okay.
`Q. -- that Formulation 90 --
`A. Right.
`Q. -- which right now is for use, selected for use in Phase
`III and commercial formulation for PONV, was switched to CINV;
`isn't that correct?
`A. I think -- switched? It's not exactly what we did, I
`mean.
`Q. Well, that formulation was used with CINV.
`A. Was? Well, the composition of this formulation has been
`used, yes, but, again, with different volume.
`Q. Okay. And, so, what happened was that Syntex developed
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`122
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`this formulation, these -- the formulation of palonosetron
`through Phase II studies; is that right?
`A. While this is not totally correct because for the Phase
`II study, they use different solution that we can't even not
`call a formulation. They were simple saline solution that
`they were using for running the Phase II because at that time,
`they could not get any formulation that could be stable enough
`to be shelf stable. So they were using a saline solution, and
`they was continuously supplying this to the investigation of
`Syntex. And then, by running several experiments in the lab
`and then computing this with the very complicated computer
`system, they came out with proposal of what could have been
`potential formulation to be created and developed for the
`clinical trial.
`But when we got to see all those data, there have been
`absolutely no experiment run to actually prepare those
`formulation and test for stability or for clinical efficacy.
`This was the status of the project when I first read all the
`document.
`Q. Have you finished what you wanted to say?
`A. Yes.
`Q. So, let me just try again because I'm asking, I think, a
`simple question. So, let me take a step back.
`The formulation that's right here from the formulation
`
`book --
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`123
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`A. Uh-huh.
`Q. -- ultimately gets used by Helsinn in CINV Phase III
`studies; is that right?
`A. The quality and quantity formulation is being used.
`Q. But --
`A. But you have asked if it was developed -- sorry, but you
`have asked if it was developed by just --
`Q. And then --
`THE COURT: Just a second, counsel. I'm not sure I'm
`following.
`The Formula 90 in the Syntex formulation book page that
`you have up on the screen shows palonosetron in a quantity of
`.0056. Is that a dose or a concentration?
`MR. LOMBARDI: That is -- well, go ahead, Doctor,
`what's the answer to that?
`THE WITNESS: Should I answer?
`BY MR. LOMBARDI:
`Q. Yes. I'm asking --
`A. It is a concentration. It is not a dose.
`Q. And that's the concentration that appears in the Example
`4 in the patent; is that right?
`A. Concentration, yes.
`Q. And, so, we know that this formulation goes into the
`Phase III -- is used in the Phase III studies with CINV.
`You've answered that yes, correct?
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`124
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`A. Uh-huh.
`Q. And then we know that it's used in the patent, that
`formulation is used, that same formulation is used in the
`patent; is that correct?
`A. The formulation in term of percentage, yes. The dose was
`totally different.
`Q. Okay. Well, let's -- let's look at some more documents
`about what Syntex did, because we know that Syntex did Phase
`II studies; is that right?
`A. This is correct, yes.
`Q. And Phase II clinical studies are to help determine the
`safety and efficacy of a compound; is that right?
`A. It's more about finding the right dose for then going to
`the Phase III.
`Q. Did you have an opportunity to look at -- well, part of
`finding the right dose is to determine the efficacy, isn't it?
`A. Right.
`Q. So, you had a chance to look at the Syntex Phase II
`studies at the time that you were doing your due diligence; is
`that right?
`A. Well, not me personally, but people on the team, yes.
`Q. Okay. And we have the Phase II clinical study, and I
`want to show it to you. It is DTX-0227. Again, I'm going to
`put it on the screen --
`A. Sure.
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`Calderari - Direct
`Q. -- and you tell me if you have trouble seeing it, Doctor.
`This is the first page, and, actually, to orient you to
`the document we have here, Doctor, I'm going to blow up the
`very top. And do you see in the upper left, it says,
`Helfinn -- excuse me -- "Helsinn Healthcare SA palonosetron
`NDA 21-372."
`Do you see that?
`A. I see that.
`Q. Do you recognize that as an indication that this is a
`portion of the NDA submitted by Helsinn on palonosetron?
`A. Yes. Right.
`MR. LOMBARDI: Okay. And, so, if we go a couple
`pages in to DTX-0227-0005, and let's if we can blow up kind of
`the text there, DJ, that would be great.
`Thank you.
`BY MR. LOMBARDI:
`Q. Is that big enough for you to read, Doctor?
`A. Yes, it is big enough, yes.
`Q. And, so, it says that this is a final report, and it
`gives a long title of that report, but do you recognize that
`as being the Phase II clinical studies that were done by
`Syntex?
`A. Yeah. Let me find -- it should be, but I think they
`had -- yes. 2330, it is the Phase II study, yes.
`Q. Okay. And the Phase II study --
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`126
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`THE COURT: How can you tell it's Phase II, sir?
`What on that page tells you it is Phase II?
`THE WITNESS: Well, I see on the top left it is
`259259 S 2330, and even if I'm not sure, but I recall the code
`of the Phase II study was 2330, so it must have been this one.
`BY MR. LOMBARDI:
`Q. Right. You're referring to that 2330 in the upper left;
`is that right?
`A. Yes. This is my best guess on that, yeah.
`Q. And if you look, you can see a date down at the bottom of
`what we have blown up there, which is the study was started in
`May of 1994 and the report came out in July of 1995.
`Do you see that?
`A. I see that.
`Q. And that's consistent with your general recollection of
`when this study was done; is that right?
`A. Well, yeah, I see now. I don't recall, but --
`Q. You saw this study. This study was part of what was
`given --
`A. Yes.
`Q. -- to you by Syntex, right?
`A. Yes, yes.
`THE COURT: You know, up there in the right hand top
`corner it says "Roche Palo Alto." Who's that in this scene?
`Ask him.
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`127
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`BY MR. LOMBARDI:
`Q. Who is Roche?
`A. Yeah, so -- it's a complicated story.
`THE COURT: The short version. You got rights from
`Syntex, right?
`THE WITNESS: Well, Syntex ran the studies, and then
`Syntex has been acquired by Roche.
`THE COURT: Okay. That's all I need.
`THE WITNESS: And then we got the rights from Roche
`Syntex, so I don't know if Syntex was still are existing, but
`anyway, yes, this is the story.
`BY MR. LOMBARDI:
`Q. Okay. Let's go to DTX-0227-0014 where there's a summary
`of the study, Doctor, so we'll skip forward to that.
`MR. LOMBARDI: And let's just start by blowing up the
`top half, please, DJ.
`BY MR. LOMBARDI:
`Q. So, there you see again there's the summary. Do you see
`that at the top?
`A. Yes. Yes, I see it. Let me read it a bit, because...
`Okay. Yes.
`Q. And then you see that the study, the number that you're
`referring to before with 2330 at the end is there under the
`study numbers; is that right?
`A. Yup.
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`Calderari - Direct
`Q. Okay. And then you see your Honor's question, what does
`it say after "clinical phase"?
`A. Two.
`Q. So, this is a Phase II study; is that right?
`A. Uh-huh, yeah. You got it.
`Q. And in this Phase II study, we're studying palonosetron
`itself and its effect in human beings; is that right?
`A. Right, yes.
`Q. So, you can see -- if we go down just a little bit on the
`page, DJ -- the objectives of this study were to -- and I'm
`going to read the first one, Doctor, or at least part of the
`first one: "Determine the dose-response relationship among
`single I.V. doses of RS-25259" -- again, that number is
`palonosetron?
`A. Is palonosetron.
`Q. "Over the dose range" and it gives a range "and the
`primary endpoint was the proportion of patients with a
`complete antiemetic response," meaning no vomiting or
`retching, "for 24 hours after highly emetogenic chemotherapy
`in chemotherapy-naive cancer patients."
`Do you see that?
`A. I see that.
`Q. Okay. So, I want to go through and translate some of the
`words there, if we can, Doctor.
`So when we talk about or when the study talks about an
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`129
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`antiemetic response, emesis refers to vomiting or nausea; is
`that right?
`A. This is right, yes.
`Q. So, an antiemetic response means no vomiting or nausea;
`is that right?
`A. Yes.
`Q. And it talks about emetogenic chemotherapy. What does
`that mean?
`A. It means that when you are subject to chemotherapy, there
`are some agents which are causing very high emetic episodes.
`This is called highly emetogenic chemotherapy.
`So, they cause very high frequency of nausea and
`vomiting. It's a classification that has been given. And
`others that cause moderately emetogenic episodes or they are
`called MEC, Moderate Emetogenic Chemotherapies. Chemical
`substances that you use during the chemotherapy for defeating
`the cancer.
`Q. Okay. And, so, what they're doing, one of the objectives
`that's being talked about in No. 1 is to determine a
`dose-response relationship between the administration of
`palonosetron and this antiemetogenic response, is that right?
`A. Is right, yes.
`Q. And they're doing that in people?
`A. Sure, in patient.
`Q. In patients. And so they determined -- and then the next
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`part of the objective of No. 1 is the efficacy of each of the
`doses that was described above was compared to the efficacy of
`the lowest dose.
`Do you see that?
`A. I see that.
`Q. Okay. So, No. 2 is they're assessing the safety, this
`Phase II study is -- one of the purposes is to assess the
`safety of palonosetron; is that right?
`A. Right, yes.
`Q. In people?
`A. In people, patients.
`Q. And in Phase III, they're assessing pharmacokinetics?
`A. Sorry, say again?
`Q. Pharmacokinetics.
`THE COURT: You said Phase III?
`THE WITNESS: Phase III.
`MR. LOMBARDI: I apologize. I meant Phase II, and I
`don't remember where I said it, so I'll restate the question.
`THE COURT: You just said -- what you mean is the
`third objective.
`THE WITNESS: Right.
`MR. LOMBARDI: I'm sorry. That's what I do mean.
`Sorry, Doctor. Thanks for pointing that out.
`BY MR. LOMBA