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`CIVIL ACTION NUMBER:
` 12-2867(MLC)
`MARKMAN HEARING
`
`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.,
`et al.,
` Defendants.
`__________________________________
` Clarkson S. Fisher United States Courthouse
` 402 East State Street
` Trenton, New Jersey 08608
` October 21, 2014
`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, RMR, CRR, CCR
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`United States District Court
`Trenton, New Jersey
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`Helsinn Healthcare Exhibit 2022
`Dr. Reddy's Laboratories, Ltd., et al. v. Helsinn Healthcare S.A.
`Trial PGR2016-00007
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`Page 1 of 4
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`

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`A P P E A R A N C E S:
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`PAUL HASTINGS
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`BY: JOSEPH O'MALLEY, ESQUIRE
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` ERIC W. DITTMANN, ESQUIRE
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`SAUL EWING
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`BY: CHARLES M. LIZZA, ESQUIRE
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`Attorneys for the Plaintiffs
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`BUDD LARNER
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`BY: STUART D. SENDER, ESQUIRE
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` MICHAEL H. IMBACUAN, ESQUIRE
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` KENNETH E. CROWELL
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`Attorneys for the Defendant, Dr. Reddy's Laboratories
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`United States District Court
`Trenton, New Jersey
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`I N D E X
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`WITNESS DIRECT CROSS REDIRECT RECROSS
`
`CHRISTIAN SCHÖNEICH
`By Mr. Ditttmann 14
`By Mr. Sender 59
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`ROBERT HANCOCK
`By Mr. Imbacuan 93 171
`By Mr. O'Malley 146 173
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`United States District Court
`Trenton, New Jersey
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`Colloquy
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`4
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`TRENTON, NEW JERSEY, TUESDAY, OCTOBER 21, 2014, 9:30 A.M.
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`(In open court.)
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`THE COURT: Good morning, everyone.
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`Hello. Welcome back. Let's begin with appearances.
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`And today we are on Helsinn versus Dr. Reddy's, which has
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`docket number 12-2867, having to do with one claim term in the
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`'724 patent.
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`I'll take your appearances. Everyone else please be
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`seated.
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`MR. LIZZA: Good morning, Your Honor. Charles M.
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`Lizza of the Saul Ewing firm for the plaintiffs, Helsinn
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`Healthcare and Roche Palo Alto.
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`MR. O'MALLEY: Good morning, Your Honor. Joe
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`O'Malley, Paul Hastings, also appearing for plaintiffs.
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`MR. DITTMANN: And Eric Dittman, also from Paul
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`Hastings, on behalf of plaintiffs.
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`MR. SENDER: Stewart Sender from Budd Larner for Dr.
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`Reddy's.
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`MR. IMBACUAN: Michael Imbacuan from Budd Larner for
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`Dr. Reddy's.
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`MR. CROWELL: And Ken Crowell from Budd Larner for
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`Dr. Reddy's.
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`THE COURT: Fine. Thank you.
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`All right. And, Mr. Lizza, thank you for your letter,
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`which everybody, I guess, joins in. It was helpful yesterday.
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`United States District Court
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`Trenton, New Jersey
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`Colloquy
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`5
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`And we can begin with the five-minute introduction from
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`plaintiffs.
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`MR. O'MALLEY: Thank you, Your Honor.
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`THE COURT: Yes. Mr. O'Malley?
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`MR. O'MALLEY: I have a couple copies of my intro
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`slides I can hand up.
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`THE COURT: Okay. Thank you. Is somebody going to
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`be time keeper for us, today? Somebody who is not up to bat,
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`so they can just concentrate on that?
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`MR. LIZZA: I can do it, Your Honor.
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`MR. O'MALLEY: Good morning. Again, we want to give
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`about a five-minute overview of the evidence you're going to
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`be hearing today. We're going to introduce you to Dr.
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`Schöneich in a minute, but in summary fashion, we're going to
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`argue that our construction is the long established ordinary
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`and customary meaning of "chelating agent." I don't think
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`there's very serious dispute about that.
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`In order to get to the defendant's construction you
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`have to read in limitations from the patent specification,
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`they say from the context of the patent. We'll argue to you
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`that that law does not permit that, except in rare cases that
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`aren't present here. We'll say once you accept, or if you
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`accepted our constructions, the ordinary and customary
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`meaning, there's nothing in the specification or the
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`prosecution history that evinces a disavowal of any portion of
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`Page 2 of 4
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`

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`Schöneich - Direct - Dittmann
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`Schöneich - Direct - Dittmann
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`THE COURT: Would these be micelles of the API, the
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`active pharmaceutical ingredient, or some other ingredient in
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`a composition?
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`THE WITNESS: So, in this case I think they refer to
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`the API, and that's the reason why I put a positive charge on
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`here, because the API likely carries a positive charge.
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`THE COURT: But "micelle" is sort of a general term
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`when this kind of arrangement happens?
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`THE WITNESS: Yes. Micelles can form with many
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`different molecules.
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`THE COURT: Okay.
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`THE WITNESS: And that's why I like to use this
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`picture here because it is a more traditional view of a
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`micelle.
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`THE COURT: It looks like a wreath. That's pretty.
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`THE WITNESS: So, as I said, we have these polar head
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`groups, the positively-charged head groups, and now EDTA, the
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`chelating agent, comes in. And I purposely gave EDTA the
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`charge negative 2 here. You see that because of electrostatic
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`interactions, the positively-charged head groups, and the
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`negatively-charged molecule, that EDTA can bind to these polar
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`head groups, and that is a binding very similar to what the
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`Brauer reference articulated when EDTA bound to that protein.
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`THE COURT: You said you gave it a negative 2 value
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`to the EDTA. Does that indicate that there are two places
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`And, so, this is, of course, an animation which only
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`illustrates that point. If these polar head groups reorient
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`themselves around EDTA that may suffice to break up the
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`micelle structure.
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`THE COURT: Break up the clumps?
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`THE WITNESS: Yes.
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`THE COURT: Right.
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`BY MR. DITTMANN:
`
`Q.
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`Just to make sure we all understand, Dr. Schöneich, in
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`this scenario postulated by the inventors, the chelating agent
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`is affecting the stability of the system through not binding
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`with metals and not any sort of chelation binding or function;
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`is that correct?
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`A.
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`Q.
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`Very likely not, yes.
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`Now, did you perform a --
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`THE COURT: But it is helping stability?
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`THE WITNESS: Yes.
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`THE COURT: Because it is interfering with clumping
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`in the bottle?
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`THE WITNESS: Yes.
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`THE COURT: Right?
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`MR. DITTMANN: Yes.
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`BY MR. DITTMANN:
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`Q.
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`Did you perform a mechanistic analysis to confirm whether
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`the inventor's micelle theory actually happens in palonosetron
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`Schöneich - Direct - Dittmann
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`Schöneich - Direct - Dittmann
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`where it can bond even to this positively-charged unit?
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`THE WITNESS: No, there are more, but the negative 2
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`is just a net charge of the molecule.
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`THE COURT: So, it is the power?
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`THE WITNESS: It is equivalent to a power, let's say,
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`yes. And this negative charge comes from the fact that EDTA
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`contains functional groups which can exist in different
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`protonation states.
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`THE COURT: It is not chelating, though, when it is
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`doing that kind of binding?
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`THE WITNESS: In this case it is not chelating, no.
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`THE COURT: It is binding to the individual molecule
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`at one point?
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`THE WITNESS: Likely one, but maybe two, and in this
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`case --
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`matter.
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`THE COURT: But not in a chelation type --
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`THE WITNESS: It may be chelating, but it doesn't
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`THE COURT: It doesn't matter. There's no metal?
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`There's no metal, is that what you're saying?
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`THE WITNESS: There's no metal involved in this
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`interaction. And, so, we have this electrostatic interaction,
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`and now we have a different force present. While initially
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`this polar head group interacted like this, and the lipophilic
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`tails interacted like this, they could reorient themselves.
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`solutions?
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`A.
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`Q.
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`A.
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`I did not perform a detailed mechanistic analysis.
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`And why is that?
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`I had no doubt about their theory. It is actually a very
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`credible theory, and for me it was just important at that
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`point to see that it supported my opinion put forward of what
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`a chelating agent is.
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`THE COURT: One moment, Mr. Dittmann. Before
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`cross-examination we will be taking a recess, so nobody is to
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`worry that you just have to roll on right into cross.
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`MR. DITTMANN: Thank you.
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`BY MR. DITTMANN:
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`Q.
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`And, so, again what you gleaned from the micelle theory,
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`the importance of what the inventors said in terms of what
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`they thought the chelating agent was doing, correct?
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`A.
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`Q.
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`Yes.
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`Did you consider the portion of the prosecution history
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`that was relied upon by Dr. Reddy's discussing the '333
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`patent?
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`A.
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`Q.
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`Yes.
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`And is this the May 24th, 2010, appeal brief that is in
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`Tab 14 of your binder?
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`A.
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`Q.
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`Yes.
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`Do you have a slide summarizing your analysis of this
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`document?
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`Page 3 of 4
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`Schöneich - Direct - Dittmann
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`A.
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`Yes. And that's on the next slide.
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`So, in the Berger patent the inventors had included
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`citric acid, and there was no indication in this reference
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`that the citric acid had a function anything else than being a
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`buffer. There was no stability issue with the formulation,
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`and that's why I think it is correct that EDTA -- in this
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`case, basically, citric acid was not functioning as a metal
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`binding agent, but it really was perceived as functioning as a
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`buffer.
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`Q.
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`And those statements were made based on what the '333
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`patent disclosed to a POSA, correct?
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`A.
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`Q.
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`Yes, that is correct.
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`Now, is citric acid a chelating agent under your
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`definition of that term?
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`A.
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`Q.
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`Citric acid is clearly a chelating agent.
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`Can you explain how it is that the inventors were not
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`changing the ordinary meaning of the word "chelating agent"
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`through their discussion of the '333 patent?
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`A.
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`Because to a POSA there was absolutely no indication that
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`citric acid was being used as a chelator in this patent.
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`Q.
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`Dr. Schöneich, could you for the Court just summarize,
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`you know, do the '724 patent claims, the specification, or
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`prosecution history alter in any way the ordinary meaning of
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`"chelating agent" as used in the '724 patent?
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`A.
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`They don't alter the ordinary meaning.
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`Schöneich - Direct - Dittmann
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`molecules present.
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`BY MR. DITTMANN:
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`Q.
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`I'm sorry, you mentioned, also, that Dr. Reddy's
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`construction was vague in your view. Can you explain that?
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`A.
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`Yes. There's vagueness concerning the term "stable"
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`because I don't really understand why the word "stable" has
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`been introduced in this definition. I have no problem with
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`"stable" if it is limited to inherent stability of the bond,
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`but it is not clear whether "stable" has any other meaning in
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`this definition.
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`Q.
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`So, is what you're saying, Dr. Schöneich, that the
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`chelated complexes we see up on this definition has an
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`inherent stability, correct?
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`A.
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`Q.
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`A chelated complex has an inherent stability, yes.
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`So, your point is that by adding the word "stable" in
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`front of that it injects confusion as to what that means?
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`A.
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`Q.
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`A.
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`Q.
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`Yes.
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`Beyond possibly the inherent stability of the bond?
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`Yes.
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`Are there any other portions of Dr. Reddy's proposed
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`construction that is vague in your view?
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`A.
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`In my opinion it is the reference to trace metals because
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`if you set up a definition I think you ought to give at least
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`some specifics as to what you mean with trace metals, and in
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`this case probably also state which metals you mean or if you
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`Schöneich - Direct - Dittmann
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`Schöneich - Direct - Dittmann
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`Q.
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`Do you understand that Dr. Reddy's has proposed a
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`different definition of the word "chelating agent" in this
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`case?
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`A.
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`Q.
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`A.
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`Q.
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`Yes.
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`Is this the proposed construction seen on Slide 36?
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`Yes.
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`And what is your opinion with respect to this proposed
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`construction?
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`A.
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`It is my opinion that this proposed definition is overly
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`restrictive in some aspects and vague in other aspects.
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`Q.
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`And can you explain how Dr. Reddy's definition is overly
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`restrictive in your view?
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`A.
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`Well, that definition contains reference to an aqueous
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`liquid pharmaceutical formulation, and as I hope that I could
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`show you in this presentation, chelation is not restricted to
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`aqueous liquid pharmaceutical formation.
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`There is also the restriction that the multidentate
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`ligand has to form chelates, and I think, as I could show you
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`in this presentation, chelating agents don't always have to
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`form chelated complex in order to have some function.
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`THE COURT: That would be true even if there are
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`metal ions floating around in there?
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`THE WITNESS: Well, there could be some metal ions,
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`and the chelating agent could be bound to some metal ions but
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`still does the other function with other parts of the
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`mean all metals that may be present in the solution.
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`Q.
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`I want to focus just a little bit on that last point you
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`just made. Do certain chelating agents bind only to different
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`metal ions depending on the conditions?
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`A.
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`I understand that this is a very active area of research
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`where synthetic chemists try to build molecules which bind
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`only to certain types of metals. So, it is possible that
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`chelating agents bind only to certain types of metals.
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`Q.
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`And how does this fact impact your opinion with respect
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`to Dr. Reddy's claim construction?
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`A.
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`Well, it really would have -- it really would mean that a
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`POSA at first has to analyze what type of metals are present
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`in a solution and, also, would have to know how much metals
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`are present in the solution, whether it is traces, and I would
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`say even understand what a trace could be.
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`Q.
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`So, Dr. Schöneich, just to conclude, could you please,
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`once again, summarize your opinion regarding --
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`THE COURT: Could I get a question in because it
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`sounds like you might be wrapping up, yes?
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`MR. DITTMANN: Yes.
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`THE COURT: Okay. This patent itself, it is in the
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`abstract. Do you have your copy with you, Doctor?
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`THE WITNESS: Sure. You mean the '333 or the '724?
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`THE COURT: The '724.
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`THE WITNESS: Yes.
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