Vol. 4-641
`
`UNITED STATES DISTRICT COURT
`SOUTHERN DISTRICT OF INDIANA
`INDIANAPOLIS DIVISION
`
`ELI LILLY AND COMPANY,
`
`Plaintiff,
`
`VS.
`
`)
`) Cause No.
`) I:I0-CV-01376-TWP-DKL
`) Indianapolis, Indiana
`) August 22, 2013
`) 9:04 a.m.
`)
`TEVA PARENTERAL MEDICINES,
`)
`INC., APP PHARMACEUTICALS,
`)
`LLC, PLIVA HRVATSKA D.O.O.,
`)
`TEVA PHARMACEUTICALS USA,
`INC., BARR LABORATORIES, INC.,)
`)
`)
`)
`
`Defendants.
`
`VOLUME IV
`
`Before the Honorable
`TANYA WALTON PRATT
`
`OFFICIAL REPORTER’S TRANSCRIPT OF
`BENCH TRIAL
`
`Court Reporter:
`
`David W. Moxley, RMR, CRR, CMRS
`United States District Court
`46 East Ohio Street, Room 340
`Indianapolis, Indiana 46204
`
`PROCEEDINGS TAKEN BY MACHINE SHORTHAND
`TRANSCRIPT CREATED BY COMPUTER-AIDED TRANSCRIPTION
`
`Sandoz Inc.
`Exhibit 1036-0001
`
`JOINT 1036-0001
`
`
`
`UNITED STATES DISTRICT COURT
`SOUTHERN DISTRICT OF INDIANA
`INDIANAPOLIS DIVISION
`
`ELI LILLY AND COMPANY,
`
`Plaintiff,
`
`VS.
`
`)
`) Cause No.
`) I:I0-CV-01376-TWP-DKL
`) Indianapolis, Indiana
`) August 22, 2013
`) 9:04 a.m.
`)
`TEVA PARENTERAL MEDICINES,
`)
`INC., APP PHARMACEUTICALS,
`)
`LLC, PLIVA HRVATSKA D.O.O.,
`)
`TEVA PHARMACEUTICALS USA,
`INC., BARR LABORATORIES, INC.,)
`)
`)
`)
`
`Defendants.
`
`VOLUME IV
`
`Before the Honorable
`TANYA WALTON PRATT
`
`OFFICIAL REPORTER’S TRANSCRIPT OF
`BENCH TRIAL
`
`Court Reporter:
`
`David W. Moxley, RMR, CRR, CMRS
`United States District Court
`46 East Ohio Street, Room 340
`Indianapolis, Indiana 46204
`
`PROCEEDINGS TAKEN BY MACHINE SHORTHAND
`TRANSCRIPT CREATED BY COMPUTER-AIDED TRANSCRIPTION
`
`Sandoz Inc.
`Exhibit 1036-0001
`
`JOINT 1036-0001
`
`
`
`NIYIKIZA - DIRECT/GENDERSON
`
`Vol. 4-808
`
`i
`
`approving the drug, was saying no. So, it was a tough
`
`2
`
`situation, yeah. We had to act quickly.
`
`3
`
`Q. And during the call, was there a discussion about what the
`
`4
`
`response should be?
`
`5
`
`A. Yes, there was.
`
`6
`
`Q. Can we take a look at Exhibit 2262, please? And let’s
`
`7
`
`pull up i-i. Thank you.
`
`8
`
`9
`
`Is this the letter that Lilly sent back to the FDA the
`
`next day, on December 22nd, Doctor?
`
`i0
`
`A. Yes, it is.
`
`ii
`
`Q. And in the beginning, does the letter just recast what the
`
`12
`
`response was -- what the FDA’s fax said?
`
`13
`
`A. Yes, in the fax of December 21st, late afternoon.
`
`14
`
`Q. And that’s -- the FDA said that the information in the
`
`15
`
`annual report about the toxicities in the trial does not
`
`16
`
`appear to support the addition of vitamins?
`
`17
`
`A. That’s correct.
`
`18
`
`Q. What is the annual report referring to?
`
`19
`
`A. The annual report is now still referring to that
`
`20
`
`September 10th cutoff; and actually, in a sense, it’s probably
`
`21
`
`comprehensible at this time if the FDA reviewer is still
`
`22
`
`referring to this document, because that document didn’t
`
`23
`
`include the deaths -- the sudden deaths we saw post that
`
`24
`
`annual report.
`
`25
`
`Q. Did Lilly in this letter describe those -- that additional
`
`Sandoz Inc.
`Exhibit 1036-0002
`
`JOINT 1036-0002
`
`
`
`NIYIKIZA - DIRECT/GENDERSON
`
`Vol. 4-809
`
`i
`
`information?
`
`2
`
`A. Yeah, we had to right away.
`
`3
`
`Q. Okay. Let’s look at 1-4, still on the first page.
`
`4
`
`5
`
`6
`
`Can you describe what Lilly is telling the FDA here?
`
`A. Yeah. Lilly is telling the FDA that we have actually
`
`additional information on the safety profile that we have seen
`
`7
`
`in addition to what we had as of September 10th.
`
`8
`
`Q. Okay. And then 1-3, please.
`
`9
`
`And then, in the bottom of that page, and onto the
`
`i0
`
`next page, can you explain what Lilly is stating here?
`
`ii
`
`A. Yeah. Here, Lilly is actually updating the FDA that
`
`12
`
`within the time that we’re going back and forth on the
`
`13
`
`reaction, especially from that report, we have seen actually
`
`14
`
`patients dying from drug-related deaths; and that was
`
`15
`
`extremely concerning to us.
`
`16
`
`Q. Can we take a look at 2-3? This is on the second page of
`
`17
`
`the letter. There’s a paragraph.
`
`18
`
`And the paragraph says, "Lilly has consulted a number
`
`19
`
`of oncology experts regarding patients’ safety"; and then it
`
`20
`
`says, "These consultants were in unanimous agreement that
`
`21
`
`intervention was necessary to promote patients’ safety in the
`
`22
`
`pemetrexed trials."
`
`23
`
`Does that accurately reflect what the experts told you
`
`24
`
`on that conference call you had?
`
`25
`
`A. Yes.
`
`Sandoz Inc.
`Exhibit 1036-0003
`
`JOINT 1036-0003
`
`
`
`NIYIKIZA - DIRECT/GENDERSON
`
`Vol. 4-810
`
`i
`
`Q. The next sentence, Doctor, says, "They all further
`
`2
`
`suggested that supplementation with folic acid would offer the
`
`3
`
`best chance of reducing serious toxicity to the broadest
`
`4
`
`patient population."
`
`5
`
`6
`
`Does that accurately reflect what you were told or
`
`what Lilly was told by the experts on that call?
`
`7
`
`A. Yes.
`
`8
`
`9
`
`Q. Then the next sentence says, "These experts felt that
`
`supplementation with low levels of folic acid would not
`
`i0
`
`adversely affect efficacy of pemetrexed."
`
`ii
`
`Does that statement accurately reflect what the
`
`12
`
`experts were saying on the call?
`
`13
`
`A. No, actually not.
`
`14
`
`Q. What were the experts saying about efficacy on the call,
`
`15
`
`Doctor?
`
`16
`
`A. What I understood on the call was that the risk/benefit
`
`17
`
`had shifted towards intervening to protect the patients from
`
`18
`
`the toxicities, and this was warranted by these drug-related
`
`19
`
`deaths now being observed, and that we had --
`
`20
`
`MR. WIESEN: Your Honor, now we’ve gone into hearsay
`
`21
`
`that’s contradicting documents they submitted to the FDA.
`
`22
`
`MR. GENDERSON: Your Honor, this is not hearsay now.
`
`23
`
`It’s not for the truth. It’s for what was stated. And we’re
`
`24
`
`going to explain that the person who wrote this letter wasn’t
`
`25
`
`on the call. All of this happened over a -- literally an
`
`Sandoz Inc.
`Exhibit 1036-0004
`
`JOINT 1036-0004
`
`
`
`Vol. 5-861
`
`UNITED STATES DISTRICT COURT
`SOUTHERN DISTRICT OF INDIANA
`INDIANAPOLIS DIVISION
`
`ELI LILLY AND COMPANY,
`
`Plaintiff,
`
`VS.
`
`TEVA PARENTERAL MEDICINES,
`INC., APP PHARMACEUTICALS,
`LLC, PLIVA HRVATSKA D.O.O.,
`TEVA PHARMACEUTICALS USA,
`INC., BARR LABORATORIES, INC.,
`
`Defendants.
`
`)
`) cause No.
`) I:I0-CV-01376-TWP-DKL
`) Indianapolis, Indiana
`) August 23, 2013
`) 9:06 a.m.
`)
`)
`)
`)
`)
`)
`)
`
`VOLUME V
`
`Before the Honorable
`TANYA WALTON PRATT
`
`OFFICIAL REPORTER’S TRANSCRIPT OF
`BENCH TRIAL
`
`Court Reporter:
`
`David W. Moxley, RMR, CRR, CMRS
`United States District Court
`46 East Ohio Street, Room 340
`Indianapolis, Indiana 46204
`
`PROCEEDINGS TAKEN BY MACHINE SHORTHAND
`TRANSCRIPT CREATED BY COMPUTER-AIDED TRANSCRIPTION
`
`Sandoz Inc.
`Exhibit 1036-0005
`
`JOINT 1036-0005
`
`
`
`NIYIKIZA - CROSS/WIESEN
`
`Vol. 5-874
`
`i
`
`Q. Now, to get that March ist, 2000, meeting --
`
`2
`
`A. Yes.
`
`3
`
`Q. -- Lilly had to make a specific request, right?
`
`4
`
`A. Yes. You have to. At least you have to describe what you
`
`5
`
`6
`
`would like to discuss with them so that the agency has the
`
`right experts in the room on the issues you want discussed.
`
`7
`
`Q. And Lilly made a specific request to the FDA, right?
`
`8
`
`A. What request now?
`
`9
`
`Q. To have a meeting concerning the subject of vitamin
`
`i0
`
`supplementation?
`
`ii
`
`A. Yes. In fact, the previous exhibit that counsel just
`
`12
`
`showed me specifies the three points that Lilly wanted to
`
`13
`
`discuss, and that would be the case.
`
`14
`
`Q. Let me show you what’s been marked as Trial Exhibit 333.
`
`15
`
`A. Thank you.
`
`16
`
`Q. I’m showing you Exhibit -- Trial Exhibit 333. It’s a
`
`17
`
`letter from Lilly to the FDA dated January 25th, 2000, and
`
`18
`
`it’s specifically entitled a "Type A Meeting Request," right?
`
`19
`
`A. Yes.
`
`20
`
`Q. This is actually the formal request for the meeting that
`
`21
`
`ends up happening on March ist, correct?
`
`22
`
`A. Yes. I would expect that to be the case. But, this
`
`23
`
`request was certainly made without my knowledge or
`
`24
`
`consultation, so this is the process. So, it would be
`
`25
`
`something that the regulatory people know how to do.
`
`Sandoz Inc.
`Exhibit 1036-0006
`
`JOINT 1036-0006
`
`
`
`NIYIKIZA - CROSS/WIESEN
`
`Vol. 5-875
`
`i
`
`Q. And when you got the materials to prepare for the
`
`2
`
`March ist meeting, this is another document you would have
`
`3
`
`gotten in the regulatory file; is that right?
`
`4
`
`A. Typically, not for a letter to request a meeting, but I
`
`5
`
`certainly would have probably saw that in the material. But,
`
`6
`
`it didn’t represent something that required my expertise,
`
`7
`
`because these are procedural documents from the regulatory
`
`8
`
`people.
`
`9
`
`Q. And if we look on the very first page of this -- the Bates
`
`i0
`
`No. is ELAPI3452 -- it actually in the first paragraph
`
`ii
`
`references that December 22nd, 1999, letter, correct?
`
`12
`
`A. Yes.
`
`13
`
`Q. If we turn to -- the first few pages are just the forms
`
`14
`
`that go in front of this for an FDA filing to make sure the
`
`15
`
`agency kills as many trees as possible, I guess, right? And
`
`16
`
`then the formal meeting request starts on 13458?
`
`17
`
`A. Yes.
`
`18
`
`Q. And I want to turn to the next page, 13459.
`
`19
`
`A. Yes.
`
`20
`
`Q. And in your experience, Lilly would be careful with a
`
`21
`
`formal meeting request that was going from the head of the
`
`22
`
`regulatory group to the FDA, right?
`
`23
`
`A. That’s certainly always the intent. You have to be -- to
`
`24
`
`provide the information you have to the best of your ability.
`
`25
`
`Q. Right.
`
`Sandoz Inc.
`Exhibit 1036-0007
`
`JOINT 1036-0007
`
`
`
`NIYIKIZA - CROSS/WIESEN
`
`Vol. 5-876
`
`i
`
`A. That’s what I would expect.
`
`2
`
`3
`
`Q. And when you reviewed things for Lilly that were going to
`
`the agency, you were certainly careful to make sure that
`
`4
`
`everything was as accurate as possible, right?
`
`5
`
`6
`
`A. For those that I was asked to review with my expertise,
`
`yes. But, the document contains material that come from
`
`7
`
`completely different experts, and I certainly am not an expert
`
`8
`
`9
`
`in every aspect of it. So that would not be expected to be me
`
`reviewing them. Some of the aspects related to mathematical,
`
`i0
`
`statistics, analysis, and interpretation of what those numbers
`
`ii
`
`are saying; yes, they would consult me.
`
`12
`
`Q. And in this request for a meeting, if we look at the
`
`13
`
`second page of the specific meeting request, ELAPI3459, the
`
`14
`
`second full paragraph --
`
`15
`
`A. Yes.
`
`16
`
`Q. -- Lilly repeats the point that the expert consultants all
`
`17
`
`agreed that adding the folic acid shouldn’t impact efficacy,
`
`18
`
`right?
`
`19
`
`A. They do.
`
`20
`
`Q. They write, "External consultants, including an expert in
`
`21
`
`folate metabolism, were in agreement that this amount of folic
`
`22
`
`acid should be effective in reducing homocysteine levels, but
`
`23
`
`these low levels should not be detrimental to efficacy,"
`
`24
`
`right?
`
`25
`
`A. That’s what the documents say. Again, I’m in disagreement
`
`Sandoz Inc.
`Exhibit 1036-0008
`
`JOINT 1036-0008
`
`
`
`Vol. 7-1193
`
`UNITED STATES DISTRICT COURT
`SOUTHERN DISTRICT OF INDIANA
`INDIANAPOLIS DIVISION
`
`ELI LILLY AND COMPANY,
`
`Plaintiff,
`
`VS.
`
`TEVA PARENTERAL MEDICINES,
`INC., APP PHARMACEUTICALS,
`LLC, PLIVA HRVATSKA D.O.O.,
`TEVA PHARMACEUTICALS USA,
`INC., BARR LABORATORIES, INC.,
`
`Defendants.
`
`)
`) cause No.
`) I:I0-CV-01376-TWP-DKL
`) Indianapolis, Indiana
`) August 27, 2013
`) 9:05 a.m.
`)
`)
`)
`)
`)
`)
`)
`
`VOLUME VII
`
`Before the Honorable
`TANYA WALTON PRATT
`
`OFFICIAL REPORTER’S TRANSCRIPT OF
`BENCH TRIAL
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`i0
`
`ii
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`Court Reporter:
`
`22
`
`23
`
`24
`
`25
`
`David W. Moxley, RMR, CRR, CMRS
`United States District Court
`46 East Ohio Street, Room 340
`Indianapolis, Indiana 46204
`
`PROCEEDINGS TAKEN BY MACHINE SHORTHAND
`TRANSCRIPT CREATED BY COMPUTER-AIDED TRANSCRIPTION
`
`Sandoz Inc.
`Exhibit 1036-0009
`
`JOINT 1036-0009
`
`
`
`CHABNER - CROSS/WIESEN Vo I . 7 - 1216
`
`1
`
`attempt to impeach the doctor with this.
`
`2
`
`3
`
`4
`
`THE WITNESS: So, as I --
`
`THE COURT: Wait for a question.
`
`THE WITNESS: Sorry.
`
`5
`
`BY MR. WIESEN:
`
`6
`
`Q. Dr. Chabner, we’ve handed you what’s been marked as Trial
`
`7
`
`Exhibit 76. Have you ever seen this before?
`
`8
`
`A. I have never seen this before, no.
`
`9
`
`Q. Okay. I’ll represent to you that it’s a document that Eli
`
`i0
`
`Lilly provided to the FDA; and it’s dated February 16th, 2000.
`
`ii
`
`It’s after the priority date that we’re looking at, okay?
`
`12
`
`A. Would this come under the category of unanticipated
`
`13
`
`observations?
`
`14
`
`Q. We can talk about -- the lawyers can argue about what the
`
`15
`
`legally relevant discussion is. I don’t want you to be
`
`16
`
`confused.
`
`This is not prior art, okay?
`
`17
`
`A. Yes.
`
`Well, I thought that I was testifying about prior
`
`18
`
`art.
`
`19
`
`THE COURT: Wait for the question, okay? Stop
`
`20
`
`asking questions.
`
`21
`
`BY MR. WIESEN:
`
`22
`
`Q. If you could turn to page 13769 of this document, and I
`
`23
`
`want to look at the paragraph --
`
`24
`
`A. I’m having trouble finding page --
`
`25
`
`Q. It should be little numbers in the bottom right-hand
`
`Sandoz Inc.
`Exhibit 1036-0010
`
`JOINT 1036-0010
`
`
`
`CHABNER - CROSS/WIESEN
`
`Vo I . 7 - 1217
`
`i
`
`corner.
`
`2
`
`A. Okay, I got it, I got it. Yes.
`
`3
`
`Q. And we’re going to look at the paragraph on "cancer
`
`4
`
`clinical data."
`
`5
`
`A. Yes.
`
`6
`
`Q. And what Lilly wrote here was, "The study of pemetrexed in
`
`7
`
`gastric cancer began in late 1996," right?
`
`8
`
`9
`
`i0
`
`A. Maybe I’m not reading it the same place that you are.
`
`Would you point it out to me?
`
`THE COURT: Look on the screen, Doctor.
`
`ii
`
`A. Okay, got it. Got it. Got it.
`
`12
`
`BY MR. WIESEN:
`
`13
`
`Q. And it indicates that in this trial, as well, there were
`
`14
`
`some deaths, right? And then at that time, the protocol was
`
`15
`
`modified to include folic acid supplementation at 5
`
`16
`
`milligrams per day, two days before, the day of, and two days
`
`17
`
`after the administration of pemetrexed. Do you see that?
`
`18
`
`A. I do.
`
`19
`
`Q. And that’s the same folic acid schedule as in the Hammond
`
`20
`
`abstract, right?
`
`21
`
`A. That’s correct.
`
`22
`
`Q. And this is talking about a Phase 2 trial of gastric
`
`23
`
`cancer, correct?
`
`24
`
`A. I think there’s a difference, though, in that this is a
`
`25
`
`dose of 500 rather than 600, which is what was used in
`
`Sandoz Inc.
`Exhibit 1036-0011
`
`JOINT 1036-0011
`
`
`
`CHABNER - CROSS/WIESEN
`
`Vo I . 7 - 1218
`
`i
`
`Hammond.
`
`2
`
`Q. Right. So there’s no dose escalation. I agree, but there
`
`3
`
`is the folic acid schedule, right?
`
`4
`
`A. The folic acid schedule is the same.
`
`5
`
`6
`
`Q. Right. And it specifically says, "This level of folic
`
`acid supplementation has been shown to be effective in
`
`7
`
`lowering homocysteine levels in a Phase 1 study of
`
`8
`
`pemetrexed and folic acid," right?
`
`9
`
`A. Yes.
`
`i0
`
`Q. And the only Phase 1 study of pemetrexed and folic acid
`
`ii
`
`that you’re aware of is the Hammond study, right?
`
`12
`
`A. That’s correct.
`
`13
`
`MR. WIESEN: You can take that down. I’m just
`
`14
`
`trying to erase the screen.
`
`15
`
`BY MR. WIESEN:
`
`16
`
`Q. Is it your testimony, Dr. Chabner, that people always
`
`17
`
`report efficacy results in Phase 1 trials?
`
`18
`
`A. I only know what I read. And I assume that -- and I don’t
`
`19
`
`know what they’re hiding. I have never heard of an instance
`
`20
`
`where somebody didn’t report responses. But, you know, it’s
`
`21
`
`possible.
`
`22
`
`Q. You’ve worked on some Phase 1 trials, sir?
`
`23
`
`A. I have.
`
`24
`
`Q. You’ve published the results of some Phase 1 trials?
`
`25
`
`A. I have.
`
`Sandoz Inc.
`Exhibit 1036-0012
`
`JOINT 1036-0012
`
`
`
`CHABNER - CROSS/WIESEN
`
`Vo I . 7 - 12 7 8
`
`i
`
`MR. WIESEN: I will try to do it quickly.
`
`2
`
`BY MR. WIESEN:
`
`3
`
`Q. So if you look at --
`
`4
`
`A. May I ask for a clarification? So did you ask me whether
`
`5
`
`I think a person of ordinary skill would use -- consider this
`
`6
`
`reference credible?
`
`7
`
`8
`
`9
`
`i0
`
`THE COURT: He hasn’t asked a question yet.
`
`MR. WIESEN: I don’t think there’s a question
`
`pending, Dr. Chabner.
`
`THE WITNESS: Okay.
`
`ii
`
`BY MR. WIESEN:
`
`12
`
`Q. So if we look at Trial Exhibit 337, this is a letter from
`
`13
`
`Eli Lilly to the FDA on March 20th, 2000, right? Do you see
`
`14
`
`that?
`
`15
`
`A. I’ve never seen it before. I see it now.
`
`16
`
`Q. And if we turn to the page 14741 and we look at the
`
`17
`
`paragraph under page 16, the last sentence, the last sentence
`
`18
`
`of the second paragraph there, it says, "For vitamin BI2,
`
`19
`
`literature searches found no evidence for stimulation of tumor
`
`20
`
`growth by this vitamin." Do you see that?
`
`21
`
`A. I do see it.
`
`22
`
`Q. Do you have a general view whether Lilly would have
`
`23
`
`searched for references before they made that statement to the
`
`24
`
`FDA?
`
`25
`
`A. No. I’m surprised they didn’t find it. I know colleagues
`
`Sandoz Inc.
`Exhibit 1036-0013
`
`JOINT 1036-0013
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