1
`
`
`CIVIL ACTION NUMBER:
` 11-3962
`
` TRIAL
`WITH SEALED PORTIONS
`
` 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 15, 2015
`B E F O R E: 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
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`United States District Court
`Trenton, New Jersey
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`Helsinn Healthcare Exhibit 2011
`Dr. Reddy's Laboratories, Ltd., et al. v. Helsinn Healthcare S.A.
`Trial PGR2016-00008
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`Page 1 of 7
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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
` HUA 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
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`WITNESS VOIR DIRECT CROSSREDIRECT RECROSS
` DIRE
`(Video deposition of Maurie Markman), 7
`(Video deposition of Valentino Stella), 28
`(Video deposition of Navin Vaya), 81
`(Video deposition of Limor Zahavi), 96
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`GORDON AMIDON
`By Mr. Dittmann 126 143
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`Colloquy
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`(In open court. June 15, 2015, 9:30 a.m.)
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`THE COURT: Good morning, everyone.
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`ALL: Good morning, your Honor.
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`THE COURT: How is everybody today?
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`ALL: Good.
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`THE COURT: Okay. What would you like to start with
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`this morning?
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`MR. ASHKENAZI: Your Honor, we're planning on playing
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`some deposition designations this morning.
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`THE COURT: All right. Is there any dispute about
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`them, these?
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`MR. ASHKENAZI: Not that I'm aware of.
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`MR. SENDER: Other than the sort of the standing 403
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`objection to our experts who did not appear, you know, we've
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`designated what we could out of it to try to provide some
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`context.
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`THE COURT: All right. Well, I'll see them, and I'll
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`rule at some point. But we'll definitely know what we're
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`delineating as your objection.
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`MR. SENDER: Thank you, your Honor.
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`MR. LIZZA: Your Honor, in that regard as requested
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`by your Honor for the line-by-line analysis, we've prepared a
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`chart with the designations and with our basis for relevance
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`and probative value. So if I may approach, I can hand that
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`chart up.
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`Colloquy
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`5
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`THE COURT: Sure. Have you served it?
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`MR. SENDER: No, they have not, your Honor.
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`MR. LIZZA: We're serving it now.
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`THE COURT: Okay. And, again, you don't need to
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`respond until you've had a chance to digest it and me, too.
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`Okay? Fine.
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`MR. ASHKENAZI: Your Honor, at this time, we'd like
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`to play the deposition designation of Dr. Maurie Markman who
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`is DRL's expert clinical oncologist. According to DRL, Dr.
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`Markman is the president of medicine and science at Cancer
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`Treatment Centers of America. Dr. Markman has more than 20
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`years of experience in cancer treatment. He has held
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`clinical, research, teaching and management positions in
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`several highly regarded medical institutions in the U.S.
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`Dr. Markman has extensive experience with all the 5-HT
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`3
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`receptor antagonist drugs approved in the U.S. Dr. Markman
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`was deposed regarding his expert opinions in this case.
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`And for the record, your Honor, we have a binder with
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`the corresponding deposition exhibits. Markman Deposition
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`Exhibit 1 corresponds to DTX-1206.
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`THE COURT: I'm sorry. Just a second, please. I'll
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`tell you when I'm ready.
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`MR. ASHKENAZI: Okay.
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`THE COURT: Was he deposed once or twice?
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`MR. ASHKENAZI: Once, your Honor.
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`Colloquy
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`Markman - Deposition
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`THE COURT: Okay. I'm just reviewing what you've
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`already told me.
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`What is this institution where he practices? President
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`of medicine and science at the organization called Cancer
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`Treatment Centers of America. This is a whole consortium of
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`hospitals? Where does he practice?
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`MR. ASHKENAZI: Your Honor, that was the description
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`provided to us about Dr. Markman. He's DRL's expert. I guess
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`I would defer to them on what that institution is.
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`THE COURT: All right. Never mind.
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`Thank you. So, what were you saying?
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`MR. ASHKENAZI: Just providing for the record which
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`DTXs correspond to the deposition exhibits identified during
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`the video.
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`So, Markman Deposition Exhibit 1 corresponds to
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`DTX-1206. And, your Honor, this is in the binder under tabs.
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`Markman Deposition Exhibit 1, Exhibit I is DTX-283. Markman
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`Deposition Exhibit 4 is PTX-398, and Markman Deposition
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`Exhibit 11 is PTX-297.
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`THE COURT: Okay. Will you be showing on the screen
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`these exhibits, or is that going to be too cumbersome?
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`MR. ASHKENAZI: I believe we will be showing them on
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`the screen, your Honor.
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`THE COURT: Okay.
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`MR. ASHKENAZI: Thank you.
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`So, I've used all of the serotonin antagonists, and
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`this is -- obviously a wonderful product and used it -- I've
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`used it extensively.
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`Q.
`
`Can you elaborate on what it is about Aloxi® that you
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`think makes it a wonderful product?
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`A.
`
`Well, I -- you know, I think it's a -- you know,
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`serotonin antagonists have been around for a long time. And
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`they were -- when they first came into existence now many,
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`many years ago, they changed the way we thought about the
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`management of chemotherapy-induced emesis.
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`What Aloxi® -- I'll say Aloxi®, it's easier, shorter,
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`the benefit of that drug was that it had a very important
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`effect on -- we divide nausea and vomiting in chemotherapy at
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`least with a highly emetogenic chemotherapy, like platinum,
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`into what we call acute, and then we call it delayed emesis.
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`And -- and what had been very well recognized is that the
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`serotonin antagonists were quite effective and the -- that is,
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`the first generation, again, I -- when I use the term "first
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`generation," to be.
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`THE COURT: Just a second, I'm sorry. There's a
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`transcription error back there, and I wouldn't want the court
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`reporter here to not be informed about that transcription
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`error in the dep.
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`If you'll just scroll back a moment. And I'm not going
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`to pick up every one, but if I think that it's worth noting, I
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`Markman - Deposition
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`Markman - Deposition
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`THE COURT: Fine. And about how long is this video?
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`MR. ASHKENAZI: This one is 23 minutes, your Honor.
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`THE COURT: Okay. Fine.
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` (The video deposition of Maurie Markman was played as
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` follows:)
`
`Q.
`
`A.
`
`Q.
`
`Dr. Markman, good morning.
`
`Good morning.
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`Let's take a look at your opening report, Exhibit 1,
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`specifically Paragraph 4. It states here that you were asked
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`by counsel for DRL to provide expert opinions on certain
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`issues related to the clinical aspects of the asserted claims
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`of the '219 patent, correct?
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`A.
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`Q.
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`That's correct.
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`Can you tell me generally what your experience is with
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`respect to palonosetron, perhaps starting with any use of
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`palonosetron you have in your clinics?
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`A.
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`Well, it's a drug that I've used, you know, extensively
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`since the day it was -- came on the market. I can't tell you,
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`you know, the number of times. I treat patients with
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`gynecological malignancies, that's my clinical expertise, and
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`we use a lot of platinum, which is not only the drug that gave
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`chemotherapy its bad name 20, 30 years ago, but it's also the
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`drug that is the one -- from the point of view of nausea and
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`vomiting, but it's also the drug that -- where -- the class of
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`drugs where we have most use for serotonin antagonists.
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`will.
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`A.
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`That drug was that it had a very important effect on --
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`we divide nausea and vomiting in chemotherapy at least with a
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`highly emetogenic chemotherapy, like platinum, into what we
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`call acute and we call delayed emesis.
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`THE COURT: Okay. Stop it. You see that word, "but"
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`that he's about to reach? What he actually says is "what had
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`been." "What had been very well recognized." I think you'll
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`agree with me when you hear it.
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`THE WITNESS: Very well recognized --
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`THE COURT: Back it up. We missed it.
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`THE WITNESS: -- shorter, the benefit of that drug
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`was that it had a very important effect on -- we divide nausea
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`and vomiting in chemotherapy at least with a highly emetogenic
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`chemotherapy, like platinum, into what we call acute and we
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`call delayed emesis. And what had been very well recognized
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`is that the serotonin antagonists were quite effective in
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`the -- that is, the first --
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`THE COURT: "In the." "In the" not "and the."
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`THE WITNESS: But I'll use the term "first
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`generation" to be ondansetron, granisetron were very effective
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`in the acute nausea and prevention of acute nausea and
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`vomiting, not perfect, but certainly a lot better than the
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`existing standards at that time when they came on existence.
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`But they were not very effective in delayed nausea and
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`Markman - Deposition
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`vomiting, and Aloxi® was the first drug of that category or
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`actually any category that was effective both for acute and
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`delayed. And, so, nausea and vomiting induced by highly
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`emetogenic chemotherapy. So, with the introduction of this
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`drug, it became, you know, widely utilized by oncologists,
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`including me.
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`Q.
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`So, just to make sure I have that, you mentioned that the
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`Aloxi® was the first drug approved for delayed emesis in
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`connection with highly emetogenic chemotherapy?
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`A.
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`Well, the one thing I want to -- I mean, you know, I'm
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`not 100 percent sure about who approved what, when or things
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`like that, I'll tell you. From my perspective at a clinical
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`level, their registration strategies and things get approved,
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`but at a clinical level I think what I said is certainly
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`correct, and it may actually registration true, too, I'm not
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`-- I'm speaking at the clinical level.
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`Q.
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`Would you agree that one of the benefits of Aloxi® versus
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`the first generation of 5-HT
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`s was its ability to treat
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`3
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`delayed emesis associated with CINV generally?
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`A.
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`Q.
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`Yes.
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`So, you mentioned that you continue today to prescribe
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`Aloxi®; is that correct?
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`A.
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`Q.
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`Absolutely.
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`And you started prescribing Aloxi® when it was first
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`approved back in 2003?
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`Markman - Deposition
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`NK-1 receptor antagonists?
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`Right.
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`So, I'm asking about that POSA standard you've applied,
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`Q.
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`A.
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`Q.
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`this hypothetical person, would that hypothetical POSA, in
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`deciding what drug molecule to pursue for development, take
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`into account the sort of market considerations we have been
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`discussing?
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`A.
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`Q.
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`I believe so.
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`Do you have an opinion as yes or no what standards you
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`applied in this case whether a POSA would take those generic
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`competition and number of competitor products into account in
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`deciding whether to pursue a drug product or not?
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`A.
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`Q.
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`I believe they probably would, yes.
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`So, we've done a little bit of this already, so I'll try
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`not to be duplicative, but I want to talk about the state of
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`the art in antiemetics in 2002.
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`So, that's the time period that's relevant to your
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`opinions in this case. Roughly 2002, 2003, correct?
`
`A.
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`Q.
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`Correct.
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`So, is it correct that in this time period you were
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`obviously a practicing clinician, correct?
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`A.
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`Q.
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`Correct.
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`And I assume that you studied the literature and remained
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`up to date on developments in the field at that time?
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`A.
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`That's correct.
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`Markman - Deposition
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`A.
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`Q.
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`If that was the date, yes.
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`Not to be a memory test.
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`Have -- over the course of the last roughly, say,
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`decade that you've been prescribing Aloxi®, have your -- the
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`frequency of your prescriptions with respect to Aloxi® changed
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`at all during that time period?
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`A.
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`Q.
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`I would say I don't -- I don't think so.
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`Do you prescribe other antiemetics in connection with
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`your practice?
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`A.
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`I do. And I would certainly -- I think it's appropriate
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`to add when you go back to your previous question and, I'm
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`sorry, I should have answered you know some of the
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`determinations are made today by a contracting issues and, you
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`know, this is a market, there are other opportunities and
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`there are other approaches towards management of acute and
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`delayed emesis. And, so, some of those decisions are actually
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`made, I don't want to say at a higher level than me, but a
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`different level than me.
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`Q.
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`For example, I would imagine that given the presence
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`of -- or the availability of generic 5-HT
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`s that at times I
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`would assume you prescribed generic?
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`A.
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`Well, I would say that's certainly one approach. And the
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`other approach is, of course, there are the use of generics
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`and the other categories of drugs that could prevent delayed
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`emesis, specifically Emend, for example.
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`Q.
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`You were comfortable providing opinions about what the
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`state of the art at that time was, correct?
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`A.
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`Q.
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`That's correct.
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`And did you stay up to date on potential new therapies
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`under development in the antiemetic field?
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`A.
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`Q.
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`Um, yes.
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`And did that include potential new therapies that would
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`treat CINV, for example?
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`A.
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`Q.
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`That's correct.
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`And I think you said this before, but, please, I don't
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`want to put words in your mouth, so correct me if I'm wrong,
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`but I think you essentially said that the 5-HT
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` antagonists
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`that were available in 2002 weren't -- weren't -- weren't
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`satisfactory in terms of treating delayed CINV; is that
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`correct?
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`A.
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`I believe that was the -- it would be a fair statement of
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`my opinion, as well as that of what the clinical community
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`would -- would say, as well.
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`Q.
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`Was it also true in 2002 that the available setrons were
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`comparable in effectiveness and toxicity?
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`A.
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`Q.
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`A.
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`Q.
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`The serotonin antagonist inhibitors, yes.
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`Then available?
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`Yes.
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`Would you also agree that in the 2002 time period,
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`chemotherapy-induced emesis was extremely difficult to
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`Markman - Deposition
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`Markman - Deposition
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`control?
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`A.
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`Well, you know, again, it's a -- it -- your -- it's a
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`little hard to answer that question. I mean, you could say
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`today we're not perfect either. I think we -- what -- what
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`happened with the availability of the serotonin antagonists,
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`there was a tremendous improvement, and certainly with the
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`acute nausea and vomiting, and it became the delayed that was
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`a greater concern, but even then we still had a, as we do now,
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`still a percentage of patients where at least they would say
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`the therapies are not as good as we'd like them to do.
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`So, it's a -- I think it's a relative answer. I would
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`certainly have said then, and I'll say now, we're not perfect.
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`We have gotten better, but, you know, if you look at 2002,
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`2003 compared to ten years earlier before the availability of
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`the serotonin antagonists, we were much better. It's you
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`know, again, it is all relative.
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`Q.
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`It would be helpful if you could get Tab 7. It's very
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`convenient in fact that you wrote a paper in 2002 that I think
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`touches upon a lot of this, so it is very convenient.
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`A.
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`Q.
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`A.
`
`Q.
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`A.
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`Thank you.
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`Do you recognize this document, Exhibit 4?
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`Well, yes.
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`Can you tell me what it is?
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`It's a review article I wrote for the Cleveland Clinic
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`Journal of Medicine when I was at that institution in 2002.
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`Q.
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`Do you agree with that statement, as well, in terms of
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`the state of the art in antiemetics in 2002?
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`A.
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`Q.
`
`Yes.
`
`And the paragraph continues, "Furthermore, although the
`
`neurophysiology of acute emesis is fairly well characterized,
`
`our understanding is extremely limited of the pathways
`
`involved with either delayed or anticipatory nausea and
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`vomiting."
`
`Do you see that?
`
`Yes.
`
`Is that also in your opinion an accurate view of the
`
`A.
`
`Q.
`
`state of the art of antiemetics in 2002?
`
`A.
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`Q.
`
`Yes.
`
`If you can turn next to Page 612. And I'm interested in
`
`the text that is underneath the heading delayed emesis. Do
`
`you see that, the left side?
`
`A.
`
`Q.
`
`Yes.
`
`It states, "Unfortunately, the pathophysiology and
`
`neuropharmacology of delayed emesis are poorly understood."
`
`Do you see that?
`
`Yes.
`
`And do you agree that also accurately reflects the state
`
`A.
`
`Q.
`
`of the art of antiemetics in 2002?
`
`A.
`
`Q.
`
`Yes.
`
`Is it correct that it was known in 2002 that the
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`Markman - Deposition
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`Q.
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`And does it sort of generally summarize the paper is
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`discussing essentially the state of the art in the treatment
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`of CINV in the 2002 time period?
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`A.
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`I haven't looked at this for a long time, but I -- I
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`certainly would have every reason to believe that that is
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`exactly what this paper does.
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`Q.
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`Okay. So, for example, on the first page, we were just
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`talking about on the right side column, it's about midway down
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`the page you see there's a sentence that starts, "Given the
`
`complexity of"...
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`A.
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`Q.
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`Yes.
`
`All right. If you could just -- well, I'll read it into
`
`is the record. "Given the complexity of the emetic process
`
`and the multiple neuroreceptors involved, chemotherapy-induced
`
`emesis has been extremely difficult to control completely."
`
`Do you see that?
`
`Yes.
`
`And do you agree that that was consistent with the state
`
`A.
`
`Q.
`
`of the art in 2002 concerning antiemetics?
`
`A.
`
`Q.
`
`Yes.
`
`All right. You state here, "For example, an antiemetic
`
`agent that completely inhibits a specific neuroreceptor
`
`involved in emesis may activate another receptor that leads to
`
`nausea and vomiting by an alternative pathway," correct?
`
`A.
`
`Yes.
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`Markman - Deposition
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`pathophysiologic processes of delayed and acute emesis
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`differed?
`
`A.
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`Well, what we knew is that if a patient had, you know,
`
`very good control or fairly good control, it didn't --
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`THE COURT: All right. Let's back it up to where he
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`begins his answer. This word "pathophysiology" is kind of a
`
`new one.
`
`Q.
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`Is it correct it was known in 2002 that the
`
`pathophysiologic processes of delayed and acute emesis
`
`differed?
`
`A.
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`Well, what we knew is that if a patient had, you know,
`
`very good control or fairly good control, it didn't -- of
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`acute, it didn't -- it didn't necessarily translate into a
`
`control of delayed. That's what we knew.
`
`Q.
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`So, you knew the mechanisms between acute and delayed
`
`were different?
`
`A.
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`Well, again, we -- what we knew is was the clinical
`
`outcome was different, and --
`
`Q.
`
`A.
`
`Okay.
`
`And whether, you know, this was the entirely different
`
`process or somehow we weren't adequately controlling the acute
`
`process, again, we -- we didn't know the mechanism, still
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`don't know the mechanism. We have hypotheses of the
`
`mechanisms and we have much better therapies, but, certainly,
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`at a clinical level, control of the acute does not translate
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`Page 5 of 7
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`

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`Markman - Deposition
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`into the -- necessarily into the control of the chronic -- or
`
`the delayed, not the chronic, the delayed. Delayed.
`
`Q.
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`What I'm trying to drill down on is that in this time
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`period, the mechanism for what caused delayed emesis was
`
`unknown, although there were hypotheses, correct?
`
`A.
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`Q.
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`That is correct.
`
`And at the time, it was difficult to control delayed
`
`CINV, correct, with the available medications?
`
`A.
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`Q.
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`That is correct.
`
`So, if a company approached you with a new 5-HT
`
` molecule
`
`3
`
`and said we believe this will work to reduce the likelihood of
`
`delayed CINV, without seeing any efficacy data, would you have
`
`any reasonable expectation that it would, in fact, work for
`
`that purpose?
`
`A.
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`I think it would be fair to say the answer to that would
`
`be no.
`
`Q.
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`Dr. Markman, if you could turn to Page 616 of Exhibit 4
`
`in your 2002 paper.
`
`Is it correct in Table 4 you set forth here the best
`
`options at the time to try to treat delayed CINV?
`
`A.
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`I believe those are -- I list two regimens. Those are
`
`perfectly reasonable regimens at that time, yes.
`
`Q.
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`One of them was ondansetron plus dexamethasone,
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`8 milligrams orally each twice a day?
`
`A.
`
`Yes.
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`Markman - Deposition
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`ondansetron had differences --
`
`THE COURT: Right. In the dep transcript the word
`
`"palonosetron" is incorrect, and it should be replaced with
`
`"dolasetron," right? Dolasetron.
`
`MR. ASHKENAZI: Yes, your Honor.
`
`THE COURT: Okay. We can go on.
`
`Q.
`
`This is in pharmacokinetic and pharmacodynamic processes,
`
`correct?
`
`A.
`
`Again, that's not my area of expertise, but I certainly
`
`would accept the argument they were not the same drugs.
`
`Q.
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`And despite the differences they had with respect to
`
`those properties, clinically they were considered equivalent
`
`in terms of efficacy and toxicity in 2002, correct?
`
`A.
`
`Yes. I believe they were essentially equivalent in terms
`
`of efficacy, and I -- I believe pretty much in terms of
`
`toxicity.
`
`Q.
`
`Can you turn to Page 616. I want to focus you on the
`
`bottom right paragraph on that page, starting "Recent data
`
`suggest." Do you see that?
`
`A.
`
`Q.
`
`Yes.
`
`I'll read it for the record. It states, "Recent data
`
`suggests that a new class of agents, neurokinin-1 receptor
`
`antagonists, may be particularly effective in preventing
`
`delayed emesis due to highly emetogenic chemotherapy such as
`
`high-dose cisplatin."
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`Markman - Deposition
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`Q.
`
`Maybe if we can take a look at Page 615 of your article.
`
`And you see here listed as serotonin receptor antagonists
`
`dolasetron, granisetron, and ondansetron?
`
`A.
`
`Q.
`
`That's correct.
`
`Does that refresh your memory that those three setron
`
`molecules that are listed in Table 2 were available for
`
`treatment of CINV in 2002?
`
`A.
`
`Q.
`
`I think that's probably what I mean there.
`
`Right. And, so, what -- what I'm getting at is these
`
`three molecules, for example, dolasetron, granisetron and
`
`ondansetron, had significances in pharmacokinetic and
`
`pharmacodynamic process, correct?
`
`A.
`
`Again, that's not my area of expertise.
`
`MR. O'MALLEY: Maybe it's me, but I think there was a
`
`key mistake there. He didn't say "palonosetron," but --
`
`THE COURT: Let's back it up.
`
`THE WITNESS: Again, that's not my area of expertise,
`
`but I certainly would accept the argument they were not the
`
`same drugs.
`
`Q.
`
`And despite the -- does that refresh your memory that
`
`those three setron molecules that are listed in Table 2 were
`
`available for treatment of CINV in 2002?
`
`A.
`
`Q.
`
`I think that's probably what I mean there.
`
`Right. And, so, what I -- what I'm getting at is these
`
`three molecules, for example, dolasetron, granisetron, and
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`Do you see that?
`
`Yes.
`
`And do you agree that that sentence reflected the state
`
`A.
`
`Q.
`
`of the art in antiemetics in 2002?
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`Well, I think the statement is correct.
`
`It was correct in 2002 was, I guess, my question?
`
`Yes. Yes.
`
`As the paragraph continues, is it correct that these NK-1
`
`receptor antagonists were also believed in 2002 to potentially
`
`be able to increase the effects of 5-HT
`
`s preventing acute
`
`3
`
`CINV?
`
`A.
`
`Q.
`
`There was certainly data to support that, yes.
`
`Do you recall that Dr. Amidon talked about certain 5-HT
`
`3
`
`compounds that were touted as promising in the 1990s, but had
`
`been abandoned by 2002?
`
`A.
`
`I do not remember the specific statement, but I certainly
`
`would accept that statement as being correct.
`
`Q.
`
`But to go back to the original question, do you agree
`
`that it was known in 2002 that there were at least certain
`
`setrons that were touted as promising only to have been
`
`abandoned in advance of the January 2002 date?
`
`A.
`
`Q.
`
`Yes.
`
`Can we please turn to your opening report, Exhibit 33.
`
`I'm sorry, Paragraph 33.
`
`A.
`
`Okay.
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`Page 6 of 7
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`Markman - Deposition
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`Q.
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`In this paragraph you discuss the Eglen 1995 article; is
`
`that correct?
`
`A.
`
`Q.
`
`That's correct.
`
`And as a preliminary matter, I just want to confirm that
`
`you rely on Eglen 1995 only as support for your opinion that
`
`palonosetron would have been a molecule that a POSA would have
`
`been motivated to pursue, correct?
`
`A.
`
`Q.
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`That's correct.
`
`You're not using any preclinical data in Eglen to try and
`
`compute what human dosage might be --
`
`A.
`
`Q.
`
`A.
`
`Q.
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`No.
`
`-- that would be efficacious?
`
`No.
`
`In your experience, have you ever heard of scientists
`
`relying on animal data to estimate a human dose when there was
`
`human clinical data available with respect to that molecule?
`
`A.
`
`Well, I guess all I would say is it usually goes the
`
`other way around.
`
`Q.
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`Right. So in your opinion, you would not look to
`
`preclinical data to attempt to extrapolate a human dose?
`
`A.
`
`Q.
`
`That's correct.
`
`If you turn back to the right side of 865, the
`
`second-to-last sentence of Eglen states, "As the present study
`
`lacks extensive antiemetic efficacy data with granisetron, it
`
`is unclear as to how palonosetron would compare with
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`to a POSA as of January 30th, 2003, correct?
`
`A.
`
`Q.
`
`You mean six months later after this, yes.
`
`I'd like to turn next to your opinions on secondary
`
`considerations, and maybe we can take a look at your reply
`
`report to get the context.
`
`Well, first let me ask you a general question: For a
`
`given pharmaceutical drug product if that product is not
`
`sufficiently stable to be shipped and stored, is it correct
`
`that that formulation could not be used to treat patients?
`
`A.
`
`Well, obviously you're -- you're talking to a clinician
`
`about pharmaceutical product issues at a basic level, so, you
`
`know, I could be wrong on this, but it certainly would seem to
`
`me that you would need to have it stable to be shipped and
`
`stored.
`
`Now, that being said, there are -- obviously things get
`
`shipped in certain ways and then they get, you know, combined
`
`and -- at the time of administration. So, the way you ship it
`
`is not necessarily the way you give it, but whatever you ship
`
`and in some way it's got to be stable to allow you to do
`
`whatever you need to do later.
`
`Q.
`
`So, do you agree that unless a pharmaceutical product has
`
`sufficient stability, that it would not be efficacious enough
`
`to treat patients?
`
`A.
`
`I mean as a general statement, sure, that's absolutely
`
`true.
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`Markman - Deposition
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`23
`
`granisetron."
`
`Do you see that?
`
`Yes.
`
`The Eglen 1995 authors are stating here that potency
`
`A.
`
`Q.
`
`comparisons between palonosetron and granisetron cannot be
`
`made based on the preclinical data they present, correct?
`
`A.
`
`Well, that's true because they studied ondansetron and --
`
`well, they did. Hum.
`
`Well, in this particular animal model, they did have
`
`granisetron in it at Table 1, so I'm not exactly sure why they
`
`made that statement, but they did make the statement.
`
`Q.
`
`Would you agree that a POSA reading Eglen 1995 wouldn't
`
`draw any conclusions about the relative potencies of
`
`palonosetron and granisetron based on the data in Eglen 1995?
`
`A.
`
`Q.
`
`I would certainly think that's a reasonable conclusion.
`
`I'm now showing you what's been marked for identification
`
`as Exhibit 11. This is an abstract from an MACC meeting from
`
`June 23rd to 26th 2002 in Boston, correct?
`
`A.
`
`Q.
`
`Yes.
`
`If you can take a look at the abstract, can you confirm,
`
`and please take the time to read the abstract, for me that
`
`what's being reported here is that a 0.25-milligram dose of
`
`palonosetron was found to be effective in treating CINV?
`
`A.
`
`Q.
`
`Yes. The answer is yes.
`
`The information in Exhibit 11 would have been well known
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`Markman - Deposition
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`25
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`Q.
`
`Dr. Markman, could you please look at Footnote 17 on Page
`
`17 of your rebuttal report. And can you please read that
`
`paragraph to yourself and let me know when you've done that.
`
`A.
`
`Q.
`
`Yes, I have.
`
`What did you do to formulate the opinion in this footnote
`
`that Aloxi®'s antiemetic activity is due solely to
`
`palonosetron, not the formulations claimed in the '219 patent?
`
`A.
`
`I don't remember specifically what I looked at, but
`
`there's obviously information that it has -- it's been given
`
`in other ways and shown to be effective.
`
`MR. ASHKENAZI: Your Honor, that's the end of this
`
`video deposition.
`
`THE COURT: Okay. Fine. Thank you.
`
`MR. ASHKENAZI: Would you like to move on to the next
`
`one?
`
`Honor.
`
`THE COURT: How long is the next one?
`
`MR. ASHKENAZI: About an hour and 17 minutes, your
`
`THE COURT: Okay. Sure. Well, let's get started.
`
`MR. ASHKENAZI: So your Honor we'll be playing now
`
`the deposition testimony of Dr. Valentino Stella. We
`
`submitted a declaration which corresponds to DTX-1037 in
`
`connection with the prosecution history of the '725 patent.
`
`Dr. Stella was deposed by defendants in this case. Dr.
`
`Stella is a distinguished professor in pharmaceutical
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`United States District Court
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`United States District Court
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