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`CIVIL ACTION NUMBERS:
` 11-3962
`
`
`
` 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: THE HONORABLE MARY L. COOPER
`
`UNITED STATES DISTRICT JUDGE
`
`TRIAL
`
`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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`Helsinn Healthcare Exhibit 2001
`Dr. Reddy's Laboratories, Ltd., et al. v. Helsinn Healthcare S.A.
`Trial PGR2016-00007
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`Page 1 of 13
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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
`BY: CHARLES M. LIZZA, ESQUIRE
`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
`
`United States District Court
`Trenton, New Jersey
`
`I N D E X
`
`WITNESS DIRECT CROSSREDIRECT RECROSS
`
`OPENING ARGUMENTS:
`
`By Mr. Lombardi, 13
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`By Ms. O'Malley 61
`
`GIORGIO CALDERARI
`
`By Mr. Lombardi 105
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`2
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`3
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`4
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`Colloquy
`
`(In open court. June 2, 2015, 9:40 a.m.)
`
`THE COURT: Good morning, everyone.
`
`ALL: Good morning, your Honor.
`
`THE COURT: Welcome. Today we start the trial in
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`this consolidated action that's at docket number 11-3962.
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`We'll start with opening statements. We may have a few minor
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`matters to clear up before the opening statements are
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`delivered, so let's all be seated, except for counsel, who are
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`at counsel table who will state their appearances, starting
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`with plaintiff.
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`MR. LIZZA: Good morning, your Honor. Charles M.
`
`Lizza of the Saul Ewing firm for the plaintiffs.
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`MR. O'MALLEY: Good morning, your Honor. Joe
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`O'Malley, Paul Hastings, for plaintiff.
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`MR. DITTMANN: Good morning, your Honor. Eric
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`Dittmann, Paul Hastings, also for plaintiffs.
`
`MR. ASHKENAZI: Good morning, your Honor. Isaac
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`Ashkenazi, Paul Hastings, also for plaintiffs.
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`MR. LOMBARDI: Good morning, your Honor. George
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`Lombardi, Winston & Strawn, for Teva.
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`MR. WONG: Good morning, your Honor. Jovial Wong
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`from Winston & Strawn for Teva.
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`MR. SENDER: Good morning, your Honor. Stuart Sender
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`from Budd Larner for Dr. Reddy's Laboratories, defendants.
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` MR. WANG: Good morning, your Honor. Howard Wang
`
`United States District Court
`
`Trenton, New Jersey
`
`5
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`from Budd Larner for Dr. Reddy's.
`
`Colloquy
`
`MR. IMBACUAN: Good morning, your Honor. Michael
`
`Imbacuan from Budd Larner for Dr. Reddy's.
`
`MS. HUTTNER: Good morning, your Honor. Connie
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`Huttner from Budd Larner for Dr. Reddy's.
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`MS. TARANTINO: Good morning, your Honor. Mayra
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`Tarantino from Lite DePalma Greenberg for Teva.
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`MR. CROWELL: Good morning, your Honor. Ken Crowell
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`with Budd Larner for defendants Dr. Reddy's Labs.
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`THE COURT: I can't hear you, sir.
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`MR. CROWELL: Dr. Reddy's Labs.
`
`THE COURT: Yes.
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`MR. CROWELL: Thank you.
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`MS. JOHNSON: Good morning, your Honor. Julia
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`Johnson from Winston & Strawn for Teva.
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`MR. BARKER: Good morning, your Honor. Brendan
`
`Barker from Winston & Strawn for Teva.
`
`THE COURT: Thank you very much. Welcome, everyone.
`
`Now, what have we got? I got a letter from Mr. Lizza,
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`copy to everybody, about the other case, docket number
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`12-2867. I just wanted to acknowledge receipt of that. We
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`don't need to discuss it right now.
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`And we got a letter from a nonparty Cipla Limited, et
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`al., and they evidently are in litigation with Helsinn in the
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`federal district in Delaware, and they have requested daily
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`Page 2 of 13
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`

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`Calderari - Direct
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`Calderari - Direct
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`part.
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`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.
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`It's all what about developing the API process and quality
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`control, the drug product processes in quality control, up to
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`having everything ready for the release and collecting all the
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`necessary chemical stability data for filing a New Drug
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`Application, and, yeah.
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`Q.
`
`Okay. Now, Helsinn, as you have said, has headquarters
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`in Switzerland; is that right?
`
`A.
`
`Q.
`
`Is headquartered in Switzerland, yes.
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`Okay. And it has a business strategy of in-licensing new
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`chemical entities at a certain stage of development; is that
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`right?
`
`A.
`
`Q.
`
`Yeah.
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`And by in-licensing, you mean taking licenses from others
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`who have come up with the new chemical entities; is that
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`right?
`
`A.
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`Q.
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`This is right, yes.
`
`And then Helsinn's strategy is to complete the
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`development process and, ultimately, manufacture and sell the
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`product; is that right?
`
`A.
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`Well, not exactly, because during the phase that we are
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`development, we seek partner for then that they can distribute
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`United States District Court
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`Trenton, New Jersey
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`record, I'm going to show you one of the patents just as an
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`example just so that we can identify.
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`I'm going to show you the '219 patent, and that is
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`DTX-0268. It's in your binders if you want, but I'm going to
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`put it on the screen, and if you can't see it well enough on
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`the screen, let me know. This is just the first page, and I'm
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`going to blow it up for you, Doctor, so you can see it better.
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`MR. LOMBARDI: DJ, if we can just do the top half,
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`say.
`
`BY MR. LOMBARDI:
`
`Q.
`
`A.
`
`Q.
`
`Are you able to read that now, Doctor?
`
`Yes.
`
`Okay. And So, you see this is the '219 patent on which
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`you're listed as an inventor.
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`A.
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`Q.
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`Right.
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`And the other inventors are listed there where DJ has
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`placed the cursor.
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`Do you see that?
`
`I see that.
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`And the patent -- well, this is the '219. Let's just
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`A.
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`Q.
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`skip back and just look at a claim here just so that we see
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`that. Let's go to Column 10, which is Page 11 of the patent.
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`That's where the claims are, Doctor.
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`Do you see that?
`
`A.
`
`Yes.
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`United States District Court
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`Trenton, New Jersey
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`Calderari - Direct
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`Calderari - Direct
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`111
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`113
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`Q.
`
`Okay. And let's just look at Claim 1. And you recognize
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`the product around the world. We do not have sales force
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`directly, so it's a so-called B-to-B, business-to-business way
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`of doing business, so...
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`Q.
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`Okay. And Helsinn is not a drug discovery company; is
`
`that right?
`
`A.
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`Was not. Now in the meantime, we have some -- some drug
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`discovery capacity.
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`Q.
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`Fair enough. At the times that the work on palonosetron
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`was going on, it was not a drug discovery company; is that
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`right?
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`A.
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`Q.
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`Yup.
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`And Helsinn operated -- actually, the only patents you
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`have in the United States are related to palonosetron; is that
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`right?
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`A.
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`Q.
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`Oh, I -- I can't recall.
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`Okay. Helsinn operated, according to its business plan,
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`this in-licensing plan, with respect to palonosetron; is that
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`right?
`
`A.
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`Q.
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`A.
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`Q.
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`Right, yeah.
`
`Didn't discover palonosetron?
`
`No.
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`Another company called Syntex discovered palonosetron; is
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`that right?
`
`A.
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`Q.
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`Right.
`
`So, Doctor, before we get on, just to confirm for the
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`United States District Court
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`Trenton, New Jersey
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`that as one of the claims in the patent and one of the claims
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`that's asserted here in this litigation; is that right?
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`A.
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`Q.
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`I recognize, yes.
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`Okay. And it's got the preamble language on reducing the
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`likelihood of cancer chemotherapy, you see that?
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`A.
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`Q.
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`I see that.
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`And then it has the dosage of palonosetron. See that, at
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`.25 milligrams?
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`A.
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`Q.
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`A.
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`Q.
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`A.
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`Q.
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`Yes.
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`And then it has a range for EDTA?
`
`Yes.
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`And it has a range for mannitol?
`
`Yes.
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`And it talks about being stable at 24 months; is that
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`right?
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`A.
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`Q.
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`Right.
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`Okay. And you recognize, also, Example 4 in this patent,
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`I'm going to move back a page, to Page 10. Example 4 has a
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`particular formulation that fits within the ranges that we
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`just talked about; is that right?
`
`A.
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`Q.
`
`Right.
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`And Example 4, the formulation that's there, is this the
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`formulation for Aloxi®?
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`A.
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`It is.
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`United States District Court
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`Trenton, New Jersey
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`Page 3 of 13
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`

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`Calderari - Direct
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`Q.
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`Okay. And, so, this is a formulation that has the same,
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`basically, the same plus a few of the ingredients we just
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`looked at in the claim, Claim 1 of this patent; is that right?
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`A.
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`Q.
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`Right.
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`Now, it's true, isn't it, Doctor, that -- well, Syntex
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`had been working on palonosetron for a period of time before
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`Helsinn got involved; is that right?
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`A.
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`Q.
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`Right.
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`And Syntex got involved -- was working on it in the early
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`'90s through roughly 1995; is that right?
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`A.
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`Q.
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`Right, yes.
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`And when did Helsinn first start considering a
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`palonosetron product?
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`A.
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`Q.
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`It was in 1997.
`
`Okay. And when Helsinn started considering a
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`palonosetron product, they first looked to what Syntex had
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`done; is that right?
`
`A.
`
`Q.
`
`Right.
`
`You obtained -- you were part of Helsinn's due diligence
`
`in considering entering into a transaction with Syntex; is
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`that right?
`
`A.
`
`Q.
`
`This is correct.
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`And being involved in that due diligence, you reviewed
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`lots of documents, lots of scientific materials; is that
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`right?
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`United States District Court
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`Calderari - Direct
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`product was kept; is that right?
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`A.
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`Yeah, this is where they describe the attempt, their
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`experiment to arrive to a formulation that might be suitable
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`for clinical trial and then after for commercialization.
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`But to my surprise, when I made the first due
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`diligence, they had never manufactured that formulation, that
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`they had absolutely no any data about the stability of
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`potential formulation to be used in a clinical trial.
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`Q.
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`Okay. So it is clear, Doctor, I'm not asking you whether
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`they had actually manufactured a formulation. I'm asking you
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`whether they came up with the formulation that's in Example 4?
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`A.
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`Q.
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`Not for the use in the CINV.
`
`Well, that wasn't my question either. I asked you did
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`they come up with that formulation that's --
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`A.
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`Q.
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`Can you show me the formulation book, please?
`
`Absolutely. But I'm just asking do you remember, as you
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`sit here today, whether they came up with that formulation?
`
`A.
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`Q.
`
`A.
`
`They came up? What do you mean, "came up"?
`
`Did they create that formulation?
`
`They propose some formulations to be used in clinical
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`trials for different indication.
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`THE COURT: Some formulations plural?
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`THE WITNESS: Some formulations, yes, plural.
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`THE COURT: Formulations.
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`THE WITNESS: Formulation, yeah. Remember, that
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`United States District Court
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`Trenton, New Jersey
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`Trenton, New Jersey
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`Calderari - Direct
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`Is right, yes.
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`And they were about palonosetron.
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`Yes.
`
`A.
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`Q.
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`A.
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`Q.
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`And one of the things that you discovered in your review
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`of the scientific materials from Syntex when you first got
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`involved is that the formulation of Example 4 had been arrived
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`at by the folks at Syntex already; is that right?
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`A.
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`No, this is not the formulation that we are using now
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`that were in the documentation of Syntex at that time.
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`Q.
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`Okay. Well, one of -- you got a few documents from
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`Syntex, right? You got something called a preformulation
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`book?
`
`A.
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`Q.
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`A.
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`Q.
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`Right, yeah.
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`And you got a document called the formulation book?
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`Yes.
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`And that's where Syntex did work on coming up with a
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`formula for a palonosetron I.V. administration product; is
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`that right?
`
`A.
`
`Q.
`
`Can you say again?
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`Yes. And any time you have trouble understanding, please
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`tell me, and I'll try to reframe the question in a way that's
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`understandable.
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`A formulation book in the case of Syntex's formulation
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`book was a book where the scientific materials and rationale
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`for coming up with a formulation for a palonosetron I.V.
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`Calderari - Direct
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`there are two indications in the emesis, one is the CINV in
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`the morning, one is PONV and one is CINV. So they were
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`proposing alternative formulation for use in clinical trials,
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`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
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`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.
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`A.
`
`Q.
`
`I wait anyway. Okay.
`
`Okay. Now, is that the formulation book that Syntex
`
`created?
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`A.
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`Q.
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`Yes, it is.
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`And you saw that shortly after Helsinn got involved in
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`doing due diligence -- excuse me -- due diligence concerning
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`palonosetron?
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`United States District Court
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`Trenton, New Jersey
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`Page 4 of 13
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`118
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`120
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`A.
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`Well, shortly don't know, but for sure I had access to
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`Calderari - Direct
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`this document, yes.
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`Q.
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`A.
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`Q.
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`And you read this document; is that right?
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`Yeah, that's right, yes.
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`And, so, Doctor, if you look at Page DTX-0254-0010, are
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`there some formulations listed on that page?
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`A.
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`Q.
`
`A.
`
`Q.
`
`Can you enlarge a bit?
`
`Yes, absolutely. Do you see formulations listed there?
`
`Yes, I see that.
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`And for the record so it's clear, you recognize the
`
`reference to RS-25259-197 to be to palonosetron.
`
`A.
`
`Q.
`
`Palonosetron hydrochloride, yes.
`
`Okay. And do you see that the ingredients listed there
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`are the same ones that were in Example 4?
`
`A.
`
`Q.
`
`Yes.
`
`And do you see that for Formulation 90, the number 90,
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`those are the same as appear in Example 4; is that right?
`
`A.
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`Yeah, but if I may qualify this, the Formulation 90
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`probably if you go a bit over in the -- in the file, they were
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`suggested by Syntex to be used in clinical trial for achieving
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`treatment of emesis in PONV.
`
`Q.
`
`A.
`
`Q.
`
`And I was going to get to that.
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`Yeah.
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`But just bear with me for a minute. I promise you we'll
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`Calderari - Direct
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`I see that, yeah.
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`And it says, "Formulation 89 has been selected for Phase
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`A.
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`Q.
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`III and commercial formulation for CIN" it says "E." We've
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`been calling it CINV in this case. Same thing to you?
`
`A.
`
`Q.
`
`Yes, is the same things, yes.
`
`And then it says, "Formulation ending in 90 has been
`
`selected for PONV"; is that right?
`
`A.
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`Q.
`
`This is right, yes.
`
`And PONV is post-operative nausea and vomiting; is that
`
`right?
`
`A.
`
`Q.
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`A.
`
`Q.
`
`Right, yes.
`
`Okay. But my question to you is just very simple --
`
`Yeah.
`
`-- 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.
`
`Q.
`
`Yes, it is correct.
`
`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.
`
`Q.
`
`Yes, for PONV studies.
`
`And it wasn't long after you got involved that CINV
`
`became the focus of use of that formulation; isn't that
`
`correct?
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`A.
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`Sorry, say again?
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`A.
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`Q.
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`A.
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`Q.
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`Okay.
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`-- and CINV.
`
`Okay.
`
`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
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`same; is that right?
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`A.
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`They would be the same in term of concentration; but, for
`
`example, I mean, when you create a dose for a clinical trial,
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`you also have to speak about the volume. At the end is the
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`final dosage that you use.
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`So the formulation in term of quality and quantity
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`presence of excipient is the same, but they were meant to be
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`used in another clinical trials than actually run, the CINV,
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`and, also, the volume, the dose they would have proposed would
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`be different because it was for a PONV indication.
`
`Q.
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`Okay. And just so it's clear, I'll just make it clear on
`
`the record.
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`A.
`
`Yeah.
`
`MR. LOMBARDI: If you expand the column going up just
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`a little bit, up, DJ, up from "Formulation."
`
`BY MR. LOMBARDI:
`
`Q.
`
`Right here it says, it identifies what Formulations 89
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`and 90 are.
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`Do you see that?
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`Q.
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`It wasn't long after you and Helsinn became involved in
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`the product -- in the project; I apologize. It wasn't long
`
`after you and Helsinn became involved in the project that that
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`formulation that's in the Syntex formulation book, No. 90, was
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`the focus of CINV studies; is that right?
`
`A.
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`Yeah, but, again, the formulation, yes, but the dose are
`
`totally different. I mean, at the end of the study, you want
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`to have a formulation, but you have to have a dose to
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`experiment in human being. Okay.
`
`Q.
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`Let me explain my question. I might not have made it
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`clear.
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`A.
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`Q.
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`A.
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`Q.
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`A.
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`Q.
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`Okay.
`
`That formulation for 90 --
`
`Okay.
`
`-- that Formulation 90 --
`
`Right.
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`-- which right now is for use, selected for use in Phase
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`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.
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`Q.
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`A.
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`Well, that formulation was used with CINV.
`
`Was? Well, the composition of this formulation has been
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`used, yes, but, again, with different volume.
`
`Q.
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`Okay. And, so, what happened was that Syntex developed
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`this formulation, these -- the formulation of palonosetron
`
`through Phase II studies; is that right?
`
`A.
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`While this is not totally correct because for the Phase
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`II study, they use different solution that we can't even not
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`call a formulation. They were simple saline solution that
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`they were using for running the Phase II because at that time,
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`they could not get any formulation that could be stable enough
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`to be shelf stable. So they were using a saline solution, and
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`they was continuously supplying this to the investigation of
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`Syntex. And then, by running several experiments in the lab
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`and then computing this with the very complicated computer
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`system, they came out with proposal of what could have been
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`potential formulation to be created and developed for the
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`clinical trial.
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`But when we got to see all those data, there have been
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`absolutely no experiment run to actually prepare those
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`formulation and test for stability or for clinical efficacy.
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`This was the status of the project when I first read all the
`
`document.
`
`Q.
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`A.
`
`Q.
`
`Have you finished what you wanted to say?
`
`Yes.
`
`So, let me just try again because I'm asking, I think, a
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`simple question. So, let me take a step back.
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`The formulation that's right here from the formulation
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`book --
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`Uh-huh.
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`And then we know that it's used in the patent, that
`
`A.
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`Q.
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`formulation is used, that same formulation is used in the
`
`patent; is that correct?
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`A.
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`The formulation in term of percentage, yes. The dose was
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`totally different.
`
`Q.
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`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.
`
`Q.
`
`This is correct, yes.
`
`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.
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`Did you have an opportunity to look at -- well, part of
`
`finding the right dose is to determine the efficacy, isn't it?
`
`A.
`
`Q.
`
`Right.
`
`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.
`
`Q.
`
`Well, not me personally, but people on the team, yes.
`
`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
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`put it on the screen --
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`A.
`
`Sure.
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`Uh-huh.
`
`-- ultimately gets used by Helsinn in CINV Phase III
`
`A.
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`Q.
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`studies; is that right?
`
`A.
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`Q.
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`A.
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`The quality and quantity formulation is being used.
`
`But --
`
`But you have asked if it was developed -- sorry, but you
`
`have asked if it was developed by just --
`
`Q.
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`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.
`
`A.
`
`Q.
`
`Yes. I'm asking --
`
`It is a concentration. It is not a dose.
`
`And that's the concentration that appears in the Example
`
`4 in the patent; is that right?
`
`A.
`
`Q.
`
`Concentration, yes.
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`And, so, we know that this formulation goes into the
`
`Phase III -- is used in the Phase III studies with CINV.
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`You've answered that yes, correct?
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`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?
`
`I see that.
`
`Do you recognize that as an indication that this is a
`
`A.
`
`Q.
`
`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.
`
`A.
`
`Q.
`
`Is that big enough for you to read, Doctor?
`
`Yes, it is big enough, yes.
`
`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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`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.
`
`Q.
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`Yes. This is my best guess on that, yeah.
`
`And if you look, you can see a date down at the bottom of
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`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.
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`Do you see that?
`
`I see that.
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`And that's consistent with your general recollection of
`
`A.
`
`Q.
`
`when this study was done; is that right?
`
`A.
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`Q.
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`Well, yeah, I see now. I don't recall, but --
`
`You saw this study. This study was part of what was
`
`given --
`
`A.
`
`Q.
`
`A.
`
`Yes.
`
`-- to you by Syntex, right?
`
`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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`Okay. And then you see your Honor's question, what does
`
`it say after "clinical phase"?
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`Two.
`
`So, this is a Phase II study; is that right?
`
`Uh-huh, yeah. You got it.
`
`And in this Phase II study, we're studying palonosetron
`
`itself and its effect in human beings; is that right?
`
`A.
`
`Q.
`
`Right, yes.
`
`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.
`
`Q.
`
`Is palonosetron.
`
`"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?
`
`I see that.
`
`Okay. So, I want to go through and translate some of the
`
`A.
`
`Q.
`
`words there, if we can, Doctor.
`
`So when we talk about or when the study talks about an
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`BY MR. LOMBARDI:
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`Q.
`
`A.
`
`Who is Roche?
`
`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.
`
`Q.
`
`Yes. Yes, I see it. Let me read it a bit, because...
`
`Okay. Yes.
`
`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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`antiemetic response, emesis refers to vomiting or nausea; is
`
`that right?
`
`A.
`
`Q.
`
`This is right, yes.
`
`So, an antiemetic response means no vomiting or nausea;
`
`is that right?
`
`A.
`
`Q.
`
`Yes.
`
`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.
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`This is called highly emetogenic chemotherapy.
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`So, they cause very high frequency of nausea and
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`vomiting. It's a classification that has been given. And
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`others that cause moderately emetogenic episodes or they are
`
`called MEC, Moderate Emetogenic Chemotherapies. Chemical
`
`substances that you use during the chemotherapy for defeating
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`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.
`
`Q.
`
`A.
`
`Q.
`
`Is right, yes.
`
`And they're doing that in people?
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`Sure, in patient.
`
`In patients. And so they determined -- and then the next
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`and at DTX-0258-0006, there's a Paragraph 3. This is called
`
`scope of work. Do you remember that document?
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`Yes.
`
`Okay. And it talks about product manufacture.
`
`Um-hum. Yes.
`
`Okay. And this is -- this is just generally talking
`
`about the manufacture of the product which is going to be the
`
`formulation of palonosetron that is in the patent; is that
`
`right?
`
`A.
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`Q.
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`Right.
`
`Okay. And then let's continue back to the appendix at
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`DTX-0258-0021. And this is an appendix, and it's titled --
`
`it's Appendix A, and it's titled, "Pricing" and "Technology
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`Transfer;" is that right?
`
`A.
`
`Q.
`
`Right.
`
`And it's talking specifically about two products, a .25
`
`milligram per vial and a .75 milligram per vial of
`
`palonosetron I.V. injection; is that right?
`
`A.
`
`Q.
`
`Right.
`
`And it sets forth some batches that are going to be
`
`manufactured and the price associated with those batches; is
`
`that right?
`
`A.
`
`Q.
`
`Right.
`
`Okay.
`
`MR. LOMBARDI: So if we look at that first page down,
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`the manufacture of those vials, those 10,000 vials; is that
`
`right?
`
`A.
`
`Q.
`
`Right.
`
`Okay.
`
`THE COURT: Are you asking him whether this work
`
`actually got done?
`
`MR. LOMBARDI: Yes.
`
`THE COURT: Because we're looking at a letter of
`
`intent.
`
`BY MR. LOMBARDI:
`
`Q.
`
`This work -- SP actually did do the work of creating
`
`lots; is that right?
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`Yeah.
`
`Okay. Development lots and clinical lots; is that right?
`
`Right. Yes.
`
`Yes, thank you.
`
`All right. Let's look at -- to make sure the record is
`
`clear, let's look at DTX-0259. This is the development and
`
`manufacturing agreement between SP and Helsinn; is that right?
`
`MR. O'MALLEY: I'm sorry to interrupt. It seems we
`
`don't have this in our exhibit book.
`
`MR. LOMBARDI: Sorry. Can we get a copy, please?
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`THE COURT: Looks like this Helsinn is an Ira --
`
`Ireland company, but it's all in the Helsinn family; is that
`
`right, sir?
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`Calderari - Direct
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`I guess it's probably just above where you are, pre-stability
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`test batch. It's just above the middle, DJ, right in there.
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`BY MR. LOMBARDI:
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`Q.
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`Do you see the heading, "Pre-Stability Test Batch
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`(Non-GMP Conditions) includes: 500 - 5 milliliter vials;" do
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`you see that?
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`A.
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`Q.
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`A.
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`Right.
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`And it provides a price per batch; is that right?
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`Right. That's part of the overall services put in there,
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`yeah. Yes.
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`Q.
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`But this part of the agreement talks about the actual
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`manufacture of batches and the price for that manufacture; is
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`that right?
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`A.
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`Q.
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`Yes.
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`All right. And let's go to the next page, DTX-0258-0022.
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`At the top of the page, there are