1
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`
`CIVIL ACTION NUMBER:
` 11-3962
`
` TRIAL
`
` 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 5, 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
`
`United States District Court
`Trenton, New Jersey
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`Helsinn Healthcare Exhibit 2004
`Dr. Reddy's Laboratories, Ltd., et al. v. Helsinn Healthcare S.A.
`Trial PGR2016-00007
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`Page 1 of 8
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`4
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`Colloquy
`
`(In open court. June 5, 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: Shall we continue?
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`MR. WONG: Yes.
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`THE COURT: Call your witness, Mr. Wong.
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`MR. WONG: Good morning, your Honor.
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`THE COURT: Call your witness, Mr. Wong.
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`MR. WONG: Sorry. I didn't hear you.
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`Just a bit of housekeeping. There were some exhibits
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`that we didn't move into evidence yesterday from Dr.
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`Fruehauf's testimony. If we can move them into evidence now.
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`Just a couple of Exhibits. They are DTX-0015, DTX-0289 and
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`DTX-0290.
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`MR. O'MALLEY: No objection.
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`THE COURT: Thank you. Those are admitted into
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`evidence.
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`Just so you know, I have conferred with the court
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`reporters and have told them not to put into the transcripts
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`the admission of individual exhibits. Instead, we will rely
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`upon the signed list that the parties give us at the end of
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`the trial.
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`MR. WONG: Understood. Thank you.
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`Your Honor, today we're going to shift gears a little
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`bit and talk about the obviousness of the claim formulations.
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`United States District Court
`
`Trenton, New Jersey
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`Kirsch - Voir Dire
`
`5
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`As our first witness, defendants call Dr. Lee Kirsch.
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`(Whereupon, LEE EDWIN KIRSCH, witness for the
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`Defendant Teva, sworn.)
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`THE DEPUTY CLERK: Please state and spell your full
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`name for the record. Have a seat.
`
`THE WITNESS: My name is Lee Edwin Kirsch,
`
`K-I-R-S-C-H.
`
`LEE EDWIN KIRSCH, DEFENDANT TEVA'S WITNESS, SWORN,
`
`VOIR DIRE EXAMINATION BY MR. WONG:
`
`Q.
`
`A.
`
`Q.
`
`Good morning, Dr. Kirsch.
`
`Good morning.
`
`Dr. Kirsch, have you been asked to provide expert
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`opinions in this case?
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`A.
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`Q.
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`A.
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`I have.
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`And, in general, what do your expert opinions relate to?
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`They relate to the formulation in question and the
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`invalidity of that formulation based on obviousness.
`
`Q.
`
`A.
`
`Thank you. Let's review some background.
`
`Dr. Kirsch, where are you currently employed?
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`I'm at the University of Iowa, faculty member at the
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`University of Iowa in the College of Pharmacy.
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`Q.
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`And what is your current position at the College of
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`Pharmacy?
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`A.
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`I'm a professor in the division of pharmaceutics and
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`translational therapeutics.
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`United States District Court
`
`Trenton, New Jersey
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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
`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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`2
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`3
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`WITNESS VOIR DIRECT CROSS REDIRECT RECROSS
`
` DIRE
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`Lee Edwin Kirsch
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`By Mr. Wong 5 18
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`By O'Malley 92
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`United States District Court
`Trenton, New Jersey
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`Page 2 of 8
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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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`Kirsch - Direct
`
`Yes, I have.
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`And in that -- was it a trial?
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`Yes, it was.
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`And in that trial, what expertise did you offer?
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`I offered expertise in the development of formulations.
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`MR. WONG: Defendants tender Dr. Kirsch as an expert
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`in the field of pharmaceutical formulation development with an
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`emphasis on drug stability.
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`MR. O'MALLEY: No objection.
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`THE COURT: Admitted as such. Thank you.
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`DIRECT EXAMINATION BY MR. WONG:
`
`Q.
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`A.
`
`Q.
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`A.
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`Q.
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`A.
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`Let's get to your opinions, Dr. Kirsch.
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`Have you reviewed the asserted patents in this case?
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`Yes, I have.
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`Are the asserted patents shown here on Kirsch 2?
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`Yes, there are four patents that I've considered.
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`And, in general, what are the four patents about?
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`Well, the four patents are directed to the development of
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`a stable formulation of the antiemetic drug palonosetron.
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`Q.
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`Have you also reviewed the asserted claims in this
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`litigation?
`
`A.
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`Q.
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`A.
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`Q.
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`I have.
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`And are the asserted claims up here on Kirsch 2 now?
`
`Yes, that's correct.
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`Have you identified a representative claim among the
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`United States District Court
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`Kirsch - Direct
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`their academic training and experience. They would draw on
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`the pharmaceutical science literature, general textbooks.
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`They would draw upon research articles and abstracts
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`and other sources of information that gave them some idea of
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`the current state of knowledge of palonosetron and related
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`compounds, compounds that had a chemical or therapeutic
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`similarity to palonosetron.
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`Q.
`
`Okay. And in the course of --
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`THE COURT: And patents, of course.
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`THE WITNESS: And patents, yes, they would certainly
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`look at patents.
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`MR. WONG: Thank you.
`
`BY MR. WONG:
`
`Q.
`
`In the course of a POSA's practice, would he or she
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`collaborate with others of ordinary skill in the art?
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`A.
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`Yes, certainly they would. I mean, one of the mechanisms
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`for that interaction, of course, is a project team; but even
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`in the absence of a project team, they would draw upon the
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`knowledge and expertise of clinicians and pharmacologists and
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`other scientists in the field.
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`Q.
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`So, that would be the same whether the POSA is working in
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`industry or is in academia?
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`A.
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`Q.
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`Yes, absolutely.
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`Now, in forming your opinions in this case, what is the
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`relevant date that you tied your opinions to?
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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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`Kirsch - Direct
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`eight asserted claims?
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`A.
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`Yes. Claim 7 in the '219 patent really contains the
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`elements that are relevant.
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`Q.
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`And we'll get to each of these elements in a bit, but
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`what is your general opinion regarding each of the components
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`listed here for Claim 7?
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`A.
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`Well, it's my opinion that these elements are a
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`description or involve the description of a common -- commonly
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`used conditions and components in I.V. formulations that are
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`used for their common uses. So, in my opinion, this patent is
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`invalid because of obviousness.
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`Q.
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`Now, have you considered who a person of ordinary skill
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`in the art would be with respect to the four patents?
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`A.
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`Q.
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`A.
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`Yes, I have.
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`And who would that person be?
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`The person of ordinary skill in the art, a POSA, would be
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`a formulation scientist typically with a Ph.D. in
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`pharmaceutics or a related field and would have a couple of
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`years of experience in developing I.V. formulations.
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`Q.
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`Okay. Now, in your opinion, would this POSA have actual
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`experience preparing formulations at the bench?
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`A.
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`Q.
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`Yes.
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`And what is the scope of resources that a POSA would draw
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`upon when developing a formulation?
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`A.
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`Well, a POSA would have their training and background,
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`Kirsch - Direct
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`A.
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`Q.
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`So, the relevant date is January 30th, 2003.
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`Okay. And as of January 30th, 2003, how would you
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`describe the field of pharmaceutical formulation development?
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`A.
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`Well, it was a well-established and well-trodden process
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`by 2000 -- by the beginning of the 21st century. It had been
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`practiced for some decades before, and successfully practiced.
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`Q.
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`Okay. Let's talk a little bit about how a POSA would
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`develop a pharmaceutical formulation.
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`Is there a standard formulation development process
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`that a POSA would typically follow in developing a
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`formulation?
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`A.
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`Q.
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`Yes, there is.
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`Have you prepared some slides to explain to the Court
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`this process?
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`A.
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`Q.
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`Yes, I have.
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`Okay. This is Kirsch Demonstrative 4.
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`Dr. Kirsch, please explain the product development
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`process that's up on this demonstrative from the standpoint of
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`a formulator.
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`A.
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`Right. So what I have tried to do in this picture is to
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`describe the formulation development process, which is shown
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`with these green boxes in the context of the overall
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`development process, the clinical trial phase timeline.
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`And, so, you know, this is a typical -- the typical
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`stages that the formulation scientists work through to develop
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`United States District Court
`
`Trenton, New Jersey
`
`United States District Court
`
`Trenton, New Jersey
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`Page 3 of 8
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`

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`Kirsch - Direct
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`Kirsch - Direct
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`LVPs, which are large volume parenterals, you know, which are
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`typically the, you know, the liter bag of D5W or some other,
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`you know, some other solvent that's slowly dripped into the
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`patient.
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`BY MR. WONG:
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`Q.
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`Okay. In addition to the routine formulation development
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`activities and textbooks we just reviewed, what else would a
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`POSA consider in developing an I.V. formulation?
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`A.
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`So, of course, as we mentioned before, their training and
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`their expertise, but they would also look to the available
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`literature, the public literature that dealt with palonosetron
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`and related compounds, therapeutically- and chemically­related
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`compounds. So they would look to whatever is published that
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`would inform them and would assist them in the design and
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`development of their desired injectable formulation.
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`Q.
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`Have you reviewed the relevant literature that a POSA
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`would have considered with regard to developing palonosetron
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`formulation?
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`A.
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`Yes. So this was the, you know, the first thing that I
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`did when I got involved in this -- in this situation, was to
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`attempt to put myself in the position of a POSA as of 2003 and
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`to do a search through the literature to see what -- what I
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`found that -- that I thought would be relevant to a POSA.
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`Q.
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`And for the record, did you only rely on publicly
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`available documents of prior art in forming your opinions on
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`Q.
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`You mentioned that the '333 patent was published in 1993.
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`Who was the assignee of the '333 patent?
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`A.
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`So, this was a patent that was generated by Syntex, the
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`Syntex Research Group.
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`Q.
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`And, in general, what does the '333 patent disclose to a
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`POSA?
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`A.
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`So the '333 patent is again a compound patent that
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`describes an entire class of compounds of related --
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`chemically­related compounds which also they discuss some of
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`their pharmacological properties as well, but, in particular,
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`they describe the chemical structure of the -- of palonosetron
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`in this -- in this patent.
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`Q.
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`Let's go to the next slide. This is pages from DTX-0343
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`at 2 and 4.
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`Dr. Kirsch, what is disclosed here?
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`A.
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`So, you know, this gives the general formula for the
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`compounds that they disclose in the patent and then goes on to
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`describe, you know, what chemical features at each of these
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`positions -- R3, R2, and R1, that make up the chemical
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`formulation of what later became known as palonosetron.
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`THE COURT: This chemical drawing that contains what
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`you just said, R1, R2, and R3, as well as some actual chemical
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`names, oxygen, right, nitrogen?
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`THE WITNESS: Right. So --
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`THE COURT: So R1, 2 and 3 are variables; is that
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`United States District Court
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`Trenton, New Jersey
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`United States District Court
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`Trenton, New Jersey
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`Kirsch - Direct
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`47
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`obviousness?
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`A.
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`Q.
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`Yes.
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`Have you prepared a slide that reviews the relevant prior
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`art that a POSA would have uncovered?
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`A.
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`Yeah, I put together a timeline that shows the
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`publication dates of various documents and information that a
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`POSA would likely use in helping them -- helping to inform
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`them about what they need to do in the formulation development
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`process.
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`Q.
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`Okay. And we'll cover these individually as we move
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`forward, but how would you characterize the prior art relevant
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`to palonosetron prior to the filing date?
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`A.
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`Well, there was quite a bit of information that was
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`available in various forms that described palonosetron.
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`Q.
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`Okay. And would these be -- would these references,
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`these prior art, be helpful to a POSA in developing a
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`palonosetron formulation?
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`A.
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`Q.
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`A.
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`Yes.
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`So what is the first piece of prior art we'll review?
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`So, the first piece of art is the -- the product patent,
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`the three -- what's called here the '333 patent published in
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`1993.
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`MR. WONG: Okay. And for the record, we're looking
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`here at an excerpt of DTX-0343 on Page 1.
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`BY MR. WONG:
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`United States District Court
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`Trenton, New Jersey
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`right?
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`THE WITNESS: That's correct.
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`THE COURT: Okay.
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`BY MR. WONG:
`
`Q.
`
`A.
`
`So what does this next slide show, on Kirsch 13?
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`So this is the chemical structure, the assembled chemical
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`structure of palonosetron, and also identifies that the -- the
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`number that they gave it as part of the series. So the
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`RS-26259 is the -- is the compound number for palonosetron
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`that they refer to in the patent.
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`Q.
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`Okay. And is the structure of palonosetron itself --
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`strike that.
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`The structure of palonosetron, would that be important
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`to a POSA?
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`A.
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`The formulator is definitely going to look at the
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`structure because it will inform him, as a starting point,
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`about potential issues with solubility. He can make some
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`predictions about solubility based on structure. And, also,
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`he will look at that structure to see whether or not there are
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`particular types of structures in it, what we call moieties in
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`it, which have the potential to undergo chemical instability.
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`THE COURT: What is the -- just out of curiosity,
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`there is a two­letter abbreviation that's just sitting in the
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`space there.
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`THE WITNESS: Right here?
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`United States District Court
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`Trenton, New Jersey
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`Page 4 of 8
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`

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`Kirsch - Cross
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`Kirsch - Cross
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`THE COURT: Deposition transcript maybe?
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`MR. O'MALLEY: Yes, that's what I intended.
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`BY MR. O'MALLEY:
`
`Q.
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`You haven't reviewed the deposition testimony of Dr.
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`DeLuca either, have you?
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`A.
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`Q.
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`I don't recall seeing it, no.
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`Okay. So, that's fair to say you haven't taken any
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`analysis of the extent to which, if any, Dr. DeLuca's opinions
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`conflict with your own?
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`A.
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`Q.
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`I have not conducted that analysis, no.
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`Okay. Now, at your most recent deposition in this case,
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`do you recall going through the various references that were
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`listed on the face of the '219 patent with my associate and
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`comparing them to the references you rely on for your
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`obviousness opinion?
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`A.
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`Q.
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`I do recollect having that discussion with him, yes.
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`And do you recall him pointing out to you that each of
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`the references you rely on are cited references on the face of
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`the '219 patent?
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`A.
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`Q.
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`I do recall that, yes.
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`Okay. Now, I would like to look at the '219 patent,
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`DTX-0248, Page 6.
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`MR. O'MALLEY: In the right-hand column, if you can
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`find that for me, Roy. There we go.
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`BY MR. O'MALLEY:
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`United States District Court
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`Trenton, New Jersey
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`you.
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`Do you see that?
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`Uh-huh.
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`And do you see that this is the report whereby you
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`A.
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`Q.
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`summarize your opinions as to obviousness at least as to the
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`first three patents-in-suit?
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`A.
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`Q.
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`Yes, that's correct.
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`Now, your opinions as to obviousness, do you have any
`
`difference in the structure of your opinions with respect to
`
`the '219 patent versus the first three patents-in-suit?
`
`A.
`
`Q.
`
`In general, I don't believe so.
`
`Okay. So, now going back to '219 references cited just
`
`to close the loop, Page 6, and there it is there.
`
`Do you see, again, this expert report containing your
`
`opinions of obviousness, at least with respect to the first
`
`three patents-in-suit, is one of the references cited on the
`
`face of the '219 patent.
`
`Do you see that?
`
`Yes, sir, I do.
`
`Okay. Now, you've testified that you were first retained
`
`A.
`
`Q.
`
`in connection with this action roughly towards the end of 2012
`
`or maybe early 2013.
`
`Do you recall that?
`
`A.
`
`Q.
`
`I believe that those dates are correct, yes.
`
`Okay. Now, let's look at Teva's invalidity contentions.
`
`United States District Court
`
`Trenton, New Jersey
`
`Kirsch - Cross
`
`Kirsch - Cross
`
`99
`
`101
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`Q.
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`Do you see that your own expert report in this litigation
`
`is among the references cited on the face of the '219 patent?
`
`A.
`
`Q.
`
`Yes, I do see that.
`
`And do you understand, from the date, that that was the
`
`first expert report that you submitted in this litigation?
`
`A.
`
`Q.
`
`I believe that's correct.
`
`Okay.
`
`THE COURT: There may have been a claim construction
`
`report separate from that expert report, but I'll allow you to
`
`question him.
`
`BY MR. O'MALLEY:
`
`Q.
`
`That report, if you need to verify my question, should be
`
`in your notebook.
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`Again, DTX-0268?
`
`Yes. So, if you'd turn to DTX-1175.
`
`Do you see that?
`
`Yes, I do see it.
`
`And let's turn to the back page for the date. There's an
`
`appendix, actually. There we go.
`
`Do you see that's dated September 9?
`
`Yes. I see it's dated that.
`
`Okay. And do you see that that's your first expert
`
`A.
`
`Q.
`
`report you submitted in this litigation?
`
`A.
`
`Q.
`
`That is my recollection, yes.
`
`Well, you can look at the table of contents if that helps
`
`United States District Court
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`Trenton, New Jersey
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`And I don't have a DTX number. They're in your notebook while
`
`we pull them up.
`
`Oh, okay. Have you located those, or do you want to
`
`look at them from the screen?
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`The screen, I think, will be okay.
`
`Have you seen these before?
`
`Yes, I believe I have.
`
`Okay. Now, let's look at Page 47.
`
`Do you see the date for these contentions, December 1,
`
`2011?
`
`A.
`
`Q.
`
`Yes.
`
`Yeah, and that's about a year before you were retained by
`
`Teva, correct? As best you recall?
`
`A.
`
`Q.
`
`As best as I recall, that's correct.
`
`Okay. Now, let's take a look at Page 4 of Teva's
`
`invalidity contentions.
`
`Do you see there's a heading on Page 4 with the title
`
`"Identification of Prior Art Under L.Pat.R.3.3(a)"?
`
`A.
`
`Q.
`
`Yes, I see that title.
`
`And if you turn to Page 5, you see a list of references,
`
`correct?
`
`Do you see that?
`
`Yes, I do.
`
`And do you see the first reference is what the parties
`
`A.
`
`Q.
`
`have been referred referring to, Eglen, 1995.
`
`United States District Court
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`Trenton, New Jersey
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`Page 5 of 8
`
`

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`102
`
`104
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`Kirsch - Cross
`
`Do you see that?
`
`Yes.
`
`And that's one of the references you relied on today as
`
`A.
`
`Q.
`
`part of your obviousness analysis?
`
`A.
`
`Q.
`
`It is.
`
`Now, you testified that you did a prior art search; is
`
`that correct?
`
`A.
`
`Q.
`
`That's correct.
`
`Well, let's continue. Now, the next reference is what
`
`the parties have been referring to as Tang, 1998.
`
`Do you see that?
`
`I do.
`
`And, again, that's one of the references you relied on
`
`A.
`
`Q.
`
`for your testimony today?
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`That's correct.
`
`Now, the next reference is the '333 patent.
`
`Do you see that?
`
`Yes, I do.
`
`And, again, that's one of the references you relied on
`
`today?
`
`It is.
`
`And the next reference after that is Wade.
`
`Do you see that?
`
`I do.
`
`A.
`
`Q.
`
`A.
`
`Q.
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`Kirsch - Cross
`
`Correct.
`
`And if you move down to reference 20, that's the
`
`A.
`
`Q.
`
`Swarbrick reference.
`
`Do you see that?
`
`A.
`
`Q.
`
`I do.
`
`And that's one of the references that you've relied on
`
`today?
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`That's correct.
`
`Now, I would like to turn to your definition of POSA.
`
`Okay.
`
`Now, your definition of POSA is, basically, a
`
`pharmaceutical formulator, correct?
`
`A.
`
`Q.
`
`That's correct.
`
`So, your POSA definition does not include clinicians,
`
`correct?
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`That's correct.
`
`Or pharmaceutically trained marketing people, right?
`
`That's correct.
`
`Or pharmacologists, correct?
`
`That's correct.
`
`The -- Well, do you recall testifying at trial in the
`
`AstraZenica v. Anchen, A-N-C-H-E-N, case in front of Judge
`
`Pisano?
`
`A.
`
`Q.
`
`Yes, I do.
`
`Let's look at Page 5 of Judge Pisano's AstraZenica
`
`And, again, that's one of the references you relied on
`
`United States District Court
`
`Trenton, New Jersey
`
`United States District Court
`
`Trenton, New Jersey
`
`Kirsch - Cross
`
`Kirsch - Cross
`
`103
`
`105
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`today, correct?
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`That's correct.
`
`And if you move down to No. 7, we see Won.
`
`Do you see that?
`
`I do.
`
`And that's one of the references you relied on today?
`
`That's correct.
`
`Now, if we turn to Page 6 of Teva's invalidity
`
`contentions and look at reference number 8, that's the Clark,
`
`1993 reference.
`
`Do you see that?
`
`It is.
`
`And that's one of the references you relied on today,
`
`A.
`
`Q.
`
`correct?
`
`A.
`
`Q.
`
`That's correct.
`
`And if you move down to reference 10, that's the
`
`Broadhead reference.
`
`Do you see that?
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`I do.
`
`And that's one of the references you relied on today?
`
`That's correct.
`
`If you move down to reference Number 19, that's the
`
`Wells, 1998 reference, correct?
`
`A.
`
`Q.
`
`That's correct.
`
`And that's one of the references you've relied on today?
`
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`opinion, and I just want to highlight Claim 1.
`
`And, basically, it was a formulation claim including a
`
`sustained-release formulation of a gelling agent, a certain
`
`active ingredient defined there, and a pharmaceutically
`
`acceptable salt together with one or more pharmaceutically
`
`acceptable excipients.
`
`Do you recall that?
`
`Yes, I recall it.
`
`And that's what you referred to as a formulation claim?
`
`Well, there was more specificity later on, but, yeah.
`
`Okay. And like in this case, you testified that with
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`respect to the identity of the POSA "that the '437 patent is
`
`all about formulation and that no clinician is necessary in
`
`the POSA definition," correct? Do you recall that generally?
`
`A.
`
`Q.
`
`I believe that's correct, yes.
`
`Okay. And are you aware that Judge Pisano rejected your
`
`definition of a POSA and specified that a clinician was
`
`included in the definition of a POSA?
`
`A.
`
`Q.
`
`Um, I think generally what you're saying is correct.
`
`Okay. And I don't want you to take my word for it. Why
`
`don't we pull up Page 21 of the decision. Starting with
`
`"Consequently". And this is, I'll represent to you, the
`
`district court decision: "Consequently, upon examination of
`
`all of the evidence presented at trial, the Court finds that
`
`the person of ordinary skill in the art pertinent to the '437
`
`United States District Court
`
`Trenton, New Jersey
`
`United States District Court
`
`Trenton, New Jersey
`
`Page 6 of 8
`
`

`
`Kirsch - Cross
`
`Kirsch - Cross
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`158
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`160
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`report, your first expert report, you testified that you rely
`
`on a reference by Dr. DeLuca for that teaching as to the range
`
`of typical volumes of SVPs. Do you remember that?
`
`A.
`
`You know, I don't remember what reference we used.
`
`Certainly, that's not an uncommon value.
`
`Q.
`
`Well, let's look at Paragraph 78 of your opening report,
`
`and the second-to-last sentence on Page 42. "For example,"
`
`I'm quoting, "intravenous formulations, e.g. small volume
`
`parenterals, can typically include volumes from 1 milliliter
`
`up to 100 milliliters." And there is a Footnote 104. Do you
`
`see that?
`
`A.
`
`Q.
`
`Yes, I do.
`
`Let's go to Footnote 104. And do you see that you are
`
`citing -- your first cite is to a DeLuca reference. Do you
`
`see that?
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`I see that, yes.
`
`And you know Dr. DeLuca, correct?
`
`I do know him, yes.
`
`He's had a distinguished career as a pharmaceutical
`
`scientist, correct?
`
`A.
`
`Q.
`
`Yes, he has.
`
`You consider Dr. DeLuca to be an expert in I.V.
`
`solutions, correct?
`
`A.
`
`Q.
`
`Yes, I do.
`
`And are you aware that Dr. DeLuca has been retained by
`
`United States District Court
`
`Trenton, New Jersey
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`directly into the blood vessel or it's going to go into the
`
`I.V. line that is already in the patient.
`
`MR. O'MALLEY: Right.
`
`THE COURT: I don't know.
`
`MR. O'MALLEY: This isn't me, but previewing, I
`
`believe we will present evidence to the fact that most -- most
`
`physicians want a so-called single bolus injection. It's not
`
`often right into the vein, but they want to be able to draw it
`
`out, plunger it in.
`
`THE COURT: Into what?
`
`MR. O'MALLEY: Into that I.V. thing.
`
`THE WITNESS: It's usually in a Y­site is usually --
`
`THE COURT: In a what?
`
`THE WITNESS: What's called a Y-site. They usually
`
`have a -- like a butter -- what's called a butterfly catheter
`
`that goes into a vein, and usually there's a Y-site there
`
`where there's two ports, one port that's open and the other
`
`port goes to a large volume parenteral to keep the vein open.
`
`And then what they would typically do is to inject the drug
`
`into the Y-site, which then goes directly into the vein, and
`
`that would be a typical way to administer these medicines.
`
`THE COURT: So they don't -- they're not inserting it
`
`into the I.V. line that comes from the bag that's hanging on
`
`the hook? They're inserting it into a separate prong --
`
`THE WITNESS: Right.
`
`United States District Court
`
`Trenton, New Jersey
`
`161
`
`159
`
`defendant Reddy's in this case?
`
`Kirsch - Cross
`
`A.
`
`Q.
`
`I am aware of that.
`
`And are you aware of Dr. DeLuca's opinion on volume in
`
`this case?
`
`A.
`
`Q.
`
`I don't recall seeing that.
`
`And are you aware that he testified that if you want just
`
`a single use, then you're going to try to keep the volume low,
`
`1 milliliter, 2 milliliters, up to 5. Are you familiar with
`
`the fact that he testified to that?
`
`A.
`
`Q.
`
`No.
`
`And are you aware that he also testified, "I wouldn't
`
`want to have somebody inject me intravenously directly with 5
`
`mLs"? Are you aware of that testimony?
`
`A.
`
`Q.
`
`No, I'm not aware of that testimony.
`
`Are you aware, though, that the majority of the 5-HT
`
`3
`
`products that were available on the market in the 2002 and
`
`2003 time period had volumes of roughly 1 to 2 milliliters?
`
`A.
`
`I recall looking at the volumes that were associated with
`
`the other setrons that were on the market.
`
`Q.
`
`A.
`
`Q.
`
`And they were 1 to 2 milliliters; do you recall that?
`
`Yeah, they were -- they were in that range, yes.
`
`Okay.
`
`THE COURT: This raises just a passing question that
`
`I have had which is whether the formulators anticipate that if
`
`they create a vial for I.V. administration, it's going to go
`
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`Kirsch - Cross
`
`THE COURT: -- that's in the shape of a Y?
`
`THE WITNESS: Well, that's correct. But the -- the
`
`I.V. line itself is also draining, so, you know, where they
`
`come together, so it --
`
`THE COURT: They come together just before it enters
`
`the patient?
`
`THE WITNESS: Yeah, a little ways, that's correct,
`
`Your Honor.
`
`THE COURT: Okay.
`
`BY MR. O'MALLEY:
`
`Q.
`
`Now, the Tang authors were testing the --
`
`THE COURT: But it was apropos of your comment that I
`
`wouldn't want 5 milliliters injected into me. If it's in an
`
`I.V. line, you don't know that it's flowing in, and it's
`
`diluted by the -- by the whatever --
`
`MR. O'MALLEY: Yeah, I don't want to misstate what
`
`the doctors are going to say, but you're going to hear a lot
`
`more about that, just by way of --
`
`THE COURT: But bolus does not refer just to putting
`
`a needle in somebody's arm. It refers to, that it is all
`
`being -- the vial is being emptied in one operation.
`
`THE WITNESS: The distinction is typically the time
`
`period that it takes to inject, you know, so an infusion would
`
`be something that would occur over a longer period of time.
`
`They have what are called short­term infusions which may occur
`
`United States District Court
`
`Trenton, New Jersey
`
`United States District Court
`
`Trenton, New Jersey
`
`Page 7 of 8
`
`

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`Kirsch - Cross
`
`Kirsch - Cross
`
`162
`
`164
`
`over 30 minutes or even a little bit more, and then the bolus
`
`which occurs in a matter of minutes or even seconds.
`
`THE COURT: Okay. That's good enough for now. Thank
`
`you.
`
`MR. O'MALLEY: All right. Thank you. This is way
`
`beyond my knowledge.
`
`THE COURT: And it may not come up, but you were
`
`talking about volumes.
`
`MR. O'MALLEY: Yeah.
`
`BY MR. O'MALLEY:
`
`Q.
`
`Getting back to Tang, the Tang authors are testing --
`
`were testing the efficacy of palonosetron to treat PONV,
`
`right?
`
`A.
`
`Q.
`
`That's correct.
`
`And you don't have any basis to dispute that the doses
`
`required for 5-HT
`
` antagonists to treat CINV were usually
`
`3
`
`greater than those required to fully treat PONV, correct?
`
`A.
`
`Q.
`
`I have no opinion.
`
`Because, again, you're not a pharmacologist or expert in
`
`clinical sciences, correct?
`
`A.
`
`Q.
`
`That's correct.
`
`Now, I want to talk to you about your opinions regarding
`
`chelating agents in the EDTA in particular. Now, nowhere in
`
`the publicly available prior art is there a disclosure of any
`
`instability problem specific to palonosetron, correct?
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`instances, but it's conceivable to me that that could happen.
`
`Q.
`
`Okay. Fair enough.
`
`Now, before I get into Won, I want to drop back and
`
`talk about a couple more of your concentration-related
`
`demonstratives.
`
`If we can go to Kirsch Demonstrative 23, please. Now,
`
`again, this slide is based on Eglen 1995, correct?
`
`A.
`
`Q.
`
`That is correct.
`
`And you're making a comparison based on predicted
`
`palonosetron to effective ondansetron dose, employing data
`
`from that article?
`
`A.
`
`Q.
`
`That is correct.
`
`And you recall by -- just to refresh our recollection,
`
`that the authors caution against using their data for
`
`comparisons of ondansetron and palonosetron. Do you recall
`
`that?
`
`A.
`
`Q.
`
`For the purposes of efficacy, yes.
`
`Okay. You're making a comparison for the purpose of what
`
`a POSA would predict as a concentration range for efficacy.
`
`A.
`
`No, I'm not. I'm making a determination of what
`
`concentration range the POSA would investigate in terms of
`
`stabilizing the compound in the formulation.
`
`Q.
`
`You believe that the dose of palonosetron is relevant
`
`only to stabilization?
`
`A.
`
`Absolutely not. But the purpose of the POSA's
`
`United States District Court
`
`United States District Court
`
`Trenton, New Jersey
`
`Kirsch - Cross
`
`That's correct.
`
`163
`
`And, likewise, the prior art does not disclose any
`
`A.
`
`Q.
`
`formulation of palonosetron to which EDTA has been added for
`
`any purpos