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`
`IN THE UNITED STATES DISTRICT COURT
`IN AND FOR THE DISTRICT OF DELAWARE
`- - -
`PFIZER INC., PHARMACIA & UPJOHN
`)
`COMPANY, PHARMACIA & UPJOHN
`)
`COMPANY LLC, SUGEN INC., C.P.
`)
`PHARMACEUTICALS INTERNATIONAL
`)
`C.V., PFIZER PHARMACEUTICALS LLC, )
`and PF PRISM C.V.,
`Plaintiffs,
`
`))
`
`))
`
`Civil Action
`
`No. 10-528-GMS
`
`))
`
`))
`
`)
`
`v.
`MYLAN PHARMACEUTICALS INC.,
`Defendant.
`
`- - -
`Wilmington, Delaware
`Thursday, November 29, 2012
`8:30 a.m.
`Trial Day 4
`- - -
`BEFORE: HONORABLE GREGORY M. SLEET, Chief Judge
`APPEARANCES:
`MARYELLEN NOREIKA, ESQ.
`Morris Nichols Arsht & Tunnell, LLP
`-and-
`THOMAS H.L. SELBY, ESQ.,
`WILLIAM E. McDANIELS, ESQ.,
`STANLEY E. FISHER, ESQ.,
`JESSAMYN A. BERNIKER, ESQ.,
`SCOTT DASOVICH, ESQ., and
`JESSICA STOLL, ESQ.
`Williams & Connolly LLP
`(Washington, D.C.)
`
`Counsel for Plaintiffs
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`Ex. 1095-0001
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`
`Case 1:10-cv-00528-GMS Document 151 Filed 02/05/13 Page 1 of 287 PageID #: 3659
`
`IN THE UNITED STATES DISTRICT COURT
`IN AND FOR THE DISTRICT OF DELAWARE
`- - -
`PFIZER INC., PHARMACIA & UPJOHN
`)
`COMPANY, PHARMACIA & UPJOHN
`)
`COMPANY LLC, SUGEN INC., C.P.
`)
`PHARMACEUTICALS INTERNATIONAL
`)
`C.V., PFIZER PHARMACEUTICALS LLC, )
`and PF PRISM C.V.,
`Plaintiffs,
`
`))
`
`))
`
`Civil Action
`
`No. 10-528-GMS
`
`))
`
`))
`
`)
`
`v.
`MYLAN PHARMACEUTICALS INC.,
`Defendant.
`
`- - -
`Wilmington, Delaware
`Thursday, November 29, 2012
`8:30 a.m.
`Trial Day 4
`- - -
`BEFORE: HONORABLE GREGORY M. SLEET, Chief Judge
`APPEARANCES:
`MARYELLEN NOREIKA, ESQ.
`Morris Nichols Arsht & Tunnell, LLP
`-and-
`THOMAS H.L. SELBY, ESQ.,
`WILLIAM E. McDANIELS, ESQ.,
`STANLEY E. FISHER, ESQ.,
`JESSAMYN A. BERNIKER, ESQ.,
`SCOTT DASOVICH, ESQ., and
`JESSICA STOLL, ESQ.
`Williams & Connolly LLP
`(Washington, D.C.)
`
`Counsel for Plaintiffs
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`Ex. 1095-0001
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`APPEARANCES CONTINUED:
`PHILIP A. ROVNER, ESQ.
`Potter Anderson & Corroon, LLP
`-and-
`DOUGLAS H. CARSTEN, ESQ., and
`JOSH A. MACK, ESQ., and
`BOBBY DELAFIELD, ESQ.
`Wilson Sonsini Goodrich & Rosati
`(San Diego, CA)
`
`Counsel for Defendant
`
`- - -
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`Ex. 1095-0002
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`Case 1:10-cv-00528-GMS Document 151 Filed 02/05/13 Page 3 of 287 PageID #: 3661
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`THE COURT: Good morning.
`Please, take your seats.
`(Counsel respond "Good morning.")
`THE COURT: Let's resume.
`MR. SELBY: Thank you, Your Honor.
`A couple of housekeeping matters. First, we had
`this demonstrative that was up yesterday. And the parties
`have conferred and agreed that it can be marked as
`Plaintiffs' Exhibit 640 and admitted, if Your Honor will
`accept it.
`
`MR. CARSTEN: That is correct, Your Honor.
`THE COURT: That is fine.
`(Plaintiffs' Exhibit No. 640 received in
`
`evidence.)
`
`MR. SELBY: Second, Your Honor, we have, on
`behalf of Pfizer -- we are going to present speedy testimony
`from three witnesses today. We did put the outlines to the
`chopping block last night. I think we are going to move
`through them fairly quickly. The second two witnesses
`address economic issues that may involve current proprietary
`and sensitive financial information of Pfizer.
`We have tried to limit the extent to which any
`of that is discussed in their testimony. But, of course,
`the cross-examination may wander into that. And counsel has
`been kind enough to advise me that, in fact, without giving
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`away his outline, they do intend to address some of those
`issues.
`
`So there may be a point at which today we will
`ask if the Court will be willing to close the courtroom.
`THE COURT: I don't favor that. We will cross
`the bridge if we come to it. I am decidedly opposed to
`closing an American courtroom.
`MR. SELBY: I appreciate that, Your Honor. We
`don't ask lightly.
`There are a few exhibits that will be discussed
`along with that testimony, and ultimately we would like to
`ask that those be sealed as well.
`THE COURT: We will cross the bridge when we
`
`come to it.
`
`MR. SELBY: Thank you, Your Honor.
`MS. STOLL: Good morning, Your Honor. Jessica
`Stoll of Williams & Connolly on behalf of plaintiffs. At
`this time plaintiffs call Dr. Matthew Kulke.
`... MATTHEW KULKE, having been duly sworn as a
`witness, was examined and testified as follows ...
`THE COURT: You may proceed, counsel.
`DIRECT EXAMINATION
`
`BY MS. STOLL:
`Dr. Kulke, would you please introduce yourself to the
`Q.
`Court?
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`Ex. 1095-0004
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`Case 1:10-cv-00528-GMS Document 151 Filed 02/05/13 Page 5 of 287 PageID #: 3663
`
`My name is Matthew Kulke. I am a medical oncologist.
`A.
`I practice at Dana Farber Cancer Institute. And I have a
`special interest in neuroendocrine tumors.
`When did you start focusing your practice in treating
`Q.
`patients with neuroendocrine tumors?
`I started my focus right after completing my
`A.
`fellowship in 1997. At that time I was seeing patients with
`neuroendocrine tumors. I wrote an initial review article on
`carcinoid tumors, which is a subtype of neuroendocrine
`tumors. That was published in the New England Journal of
`Medicine in 1999.
`What clinical positions do you currently hold?
`Q.
`I am an attending physician at Dana Farber Institute.
`A.
`I also direct the program in neuroendocrine and carcinoid
`tumors at Dana Farber.
`On average, how many patients with pancreatic
`Q.
`neuroendocrine tumors do you personally treat each year?
`In my practice, I will see about 150 neuroendocrine
`A.
`tumor patients. About a third of those will have pancreatic
`neuroendocrine tumors. So it would be about 50 new patients
`a year. Many of those patients will also then subsequently
`stay for treatment.
`Roughly how many other physicians in the United States
`Q.
`see that many patients with this disease each year?
`In speaking to my colleagues, I think I am in the top
`A.
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`Ex. 1095-0005
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`
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`783
`Case 1:10-cv-00528-GMS Document 151 Filed 02/05/13 Page 6 of 287 PageID #: 3664
`Kulke - direct
`five if not the top three physicians with regard to the
`number of patients with neuroendocrine tumors I see.
`Have you participated in clinical trials investigating
`Q.
`treatments for pancreatic neuroendocrine tumors?
`I have participated in trials. I have also helped
`A.
`develop a number of clinical trials of new agents and new
`drugs for the treatment of these patients.
`Do you currently hold any academic positions?
`Q.
`I do. I am an associate professor of medicine at
`A.
`Harvard Medical School.
`Have you published in this field?
`Q.
`I have published in this field. I have over a hundred
`A.
`peer-reviewed articles, the majority of which focus on
`neuroendocrine tumors.
`Can we please put up JTX-130. Dr. Kulke, what is this
`Q.
`document?
`This is a copy of my CV.
`A.
`MS. STOLL: We offer Dr. Kulke as an expert in
`the treatment of pancreatic neuroendocrine tumors and the
`clinical development and treatment of these diseases.
`MR. MACK: No objection, Your Honor.
`THE COURT: He is accepted.
`BY MS. STOLL:
`Dr. Kulke, do you understand you will be giving
`Q.
`opinions today from the perspective of a person of ordinary
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`Ex. 1095-0006
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`Case 1:10-cv-00528-GMS Document 151 Filed 02/05/13 Page 7 of 287 PageID #: 3665
`Kulke - direct
`skill in the art as the parties have defined that term?
`Yes.
`A.
`Briefly, what are some of the key features of
`Q.
`pancreatic neuroendocrine tumors?
`Neuroendocrine tumors generally are tumors that we
`A.
`think start from the endocrine cells in our body which are
`distributed throughout our body. Pancreatic neuroendocrine
`tumors start from the endocrine cells, also called the islet
`cells in the pancreas. These are the cells that secrete
`hormones like insulin. And some pancreatic neuroendocrine
`tumors will secrete hormones, just like insulin.
`When they grow, if they are caught early enough
`in the pancreas, they can be removed by a surgeon and
`patients can be cured. Unfortunately, in many cases, they
`metastasize, just like any other cancer. And at that point,
`they are really not curable.
`Most people, before a few years ago, hadn't
`really heard of neuroendocrine tumors. They recently have
`been in the news. It turned out Steve Jobes died of a
`metastatic pancreatic neuroendocrine tumor.
`In October 2000, were you treating patients with this
`Q.
`disease?
`Yes, I was.
`A.
`I want to ask you a few questions now about how
`Q.
`patients with this disease were treated before October 2000.
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`Case 1:10-cv-00528-GMS Document 151 Filed 02/05/13 Page 8 of 287 PageID #: 3666
`Kulke - direct
`What were the treatment options available at that time?
`There were not very many treatment options. There was
`A.
`one drug that had been approved in the early 1980s. This
`was a drug called streptozocin. It was an old style
`chemotherapy drug. It was administered intravenously.
`Patients had to come into the clinic or even be admitted to
`the hospital for five days in a row to receive the
`chemotherapy. It was also associated with a number of side
`effects.
`Were patients often enrolled in clinical trials at
`Q.
`that time?
`They were. There was enough doubt about using
`A.
`streptozocin that it was not at all uncommon for patients to
`come into the clinic looking for new and better drugs that
`might be more effective or more tolerable in treating the
`tumor.
`What were the side effects associated with
`Q.
`streptozocin?
`It had several of the standard side effects that you
`A.
`think about when you hear about chemotherapy. There was
`nausea and vomiting. It would also suppress the white blood
`cell count, the immune system, so patients would be prone to
`infection.
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`It had a somewhat more unique toxicity in that
`it could cause kidney damage. Particularly over time, as
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`Ex. 1095-0008
`
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`Case 1:10-cv-00528-GMS Document 151 Filed 02/05/13 Page 9 of 287 PageID #: 3667
`Kulke - direct
`patients received repeated cycles of streptozocin, kidney
`function could decrease and we would have to stop treatment.
`How long did patients generally stay on streptozocin?
`Q.
`It didn't work in every patient. If it wasn't working
`A.
`we would stop treatment after just a month or two. In some
`patients it did work. In those cases, we could keep
`patients on treatment for maybe about six months before the
`cumulative toxicity prevented us from giving further
`treatment.
`Did any of the clinical trials that patients were
`Q.
`being enrolled in at that time yield effective reasonably
`tolerable treatments?
`At that time, there really were no other good options.
`A.
`People had tried looking at other drugs. But those trials
`really were not particularly successful.
`In October of 2000 was there a need for better
`Q.
`treatments for pancreatic neuroendocrine tumors?
`Yes, there was a clear and obvious need for better
`A.
`treatments.
`Please describe that need?
`Q.
`Well, we had at that time an old drug, streptozocin,
`A.
`which was associated with toxicity. We were not
`particularly eager to prescribe it for our patients, to
`treat our patients with that. We really didn't have
`anything else to treat our patients with.
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`Can we please pull up PTX-489. Dr. Kulke, what is
`Q.
`this document?
`This is an example of a clinical trial that was
`A.
`published in 1993, looking at a new drug combination for the
`treatment of neuroendocrine tumors.
`Can we please go to Page 4. Does this article say
`Q.
`anything about the need you described?
`This article does describe the need, if you look at
`A.
`the final sentence of the manuscript here, it says that, The
`results of treatment with chemotherapy remain unsatisfactory
`in these diseases, and additional investigational trials of
`new agents and new combinations of agents remain a high
`priority.
`Can we please pull up PTX-329?
`Q.
`What is this document?
`This document is an example of another clinical trial
`A.
`that was performed at that time. This is a trial of a drug
`that was being commonly used and worked in other conditions,
`a drug called taxol or paclitaxel. It was used and worked
`in diseases like breast cancer or ovarian cancer. And the
`investigators here were looking at paclitaxel not just at
`standard dose but at a high dose to see if it might have
`some efficacy in treating neuroendocrine tumor patients.
`Did it have efficacy in treating these patients?
`Q.
`Unfortunately, it didn't. Even giving it at a high
`A.
`
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`dose here, there was not any clinical activity seen.
`Does this article say anything about the need in the
`Q.
`field?
`This article also describes that exact same need, the
`A.
`very first sentence in the background states that, New
`agents with antitumor activity in patients with
`neuroendocrine tumors are sorely needed.
`Would the person of ordinary skill in the art, in
`Q.
`October 2000, have expected sunitinib to treat pancreatic
`neuroendocrine tumors?
`No, they would not. As we have just seen, the history
`A.
`here was of taking new drugs and trying them and seeing if
`they worked in neuroendocrine tumors. And they weren't
`working. So there really was not that expectation.
`What would the person of skill in the art have
`Q.
`expected?
`Unfortunately, the expectation would have been that
`A.
`any new drug that you were going to test in this disease
`that was perceived as very refractory to most treatments
`would not work.
`Had any new effective and tolerable treatments emerged
`Q.
`by the time sunitinib reached clinical trials?
`No, they had not.
`A.
`Can we please pull up PTX-379?
`Q.
`Dr. Kulke, what is this document?
`
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`This document is a manuscript that describes the Phase
`A.
`I, the early Phase I trial of sunitinib in patients with a
`variety of different cancers.
`Were patients with neuroendocrine tumors enrolled in
`Q.
`this study?
`They were. There were patients with a number of
`A.
`different cancers enrolled in this study. And as it turned
`out, there were four patients with neuroendocrine tumors
`that enrolled in this study.
`And what were the results for those patients?
`Q.
`The results were surprising. Of the four patients,
`A.
`there was one patient that was treated with sunitinib that
`had a significant response, a partial response, a more than
`30-percent shrinkage of the tumor. There was a second
`patient with a neuroendocrine tumor that had a somewhat
`smaller amount of shrinkage but it looked like the disease
`had stabilized. So it really looked like something was
`happening here.
`How were those results interpreted by specialists in
`Q.
`the field?
`There was, first of all, tremendous excitement. There
`A.
`was also a sense of disbelief. I would say that when we
`heard about these results, we were obviously thinking about
`moving forward with another Phase II clinical study. We had
`a hard time believing that these patients really did have
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`Kulke - direct
`neuroendocrine tumors. We went back to the company and
`asked them just to confirm the pathology, confirm that these
`really were neuroendocrine tumors that appeared to be
`responding to the drug.
`And were they?
`Q.
`They were.
`A.
`Can we please put up PTX-487.
`Q.
`Dr. Kulke, what is this document?
`This document is the manuscript that describes the
`A.
`subsequent study. This was the registration study of
`sunitinib in patients with advanced pancreatic
`neuroendocrine tumors that led to the FDA approval for this
`indication.
`And what was the comparator in this study?
`Q.
`This was a study that was designed where patients were
`A.
`randomized to receive either treatment with sunitinib, or,
`in this case, treatment with placebo.
`I would note that the choice of using a placebo
`as the control arm in this study is interesting. It
`reflects, in many ways, some of the ambivalence that people
`had about using streptozocin for this indication. People
`just weren't real interested in comparing it to
`streptozocin.
`Can you summarize the results of this Phase III study?
`Q.
`This Phase III study clearly showed that sunitinib had
`A.
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`Kulke - direct
`activity in advanced pancreatic neuroendocrine tumors. The
`end point of the study was progression free survival.
`The median for progression free survival for a
`patient to receive sunitinib was 11.4 months, and the
`patients who were receiving placebo was only 5.5 months.
`How did these results compare to what we have seen
`Q.
`earlier with streptozocin?
`The progression free survival here was clearly better
`A.
`in the sunitinib arm. Sunitinib was also really much better
`tolerated. Streptozocin is an old I.V. drug with
`significant toxicities.
`Sunitinib is a pill. It was fairly well
`tolerated by patients. So there was a clearly difference.
`It's almost like apples and oranges.
`How did the medical community receive Sutent?
`Q.
`There was great excitement when this data came out.
`A.
`For the first time, there was a drug that was easy to give,
`easy to prescribe, and a drug that doctors could have
`confidence would work for treating patients with metastatic
`neuroendocrine tumors.
`How are patients with these tumors generally treated
`Q.
`today?
`So, for the most part, patients with metastatic
`A.
`pancreatic neuroendocrine tumors will be treated with
`targeted therapies.
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`Kulke - direct
`So, sunitinib is a targeted therapy that targets
`the VEGF receptor. At almost exactly the same time, it was
`discussed at the same FDA meeting, there was a second
`targeted therapy that also had became available, a drug
`called Afinitor, which targets another molecule called mTOR.
`Are Sutent and Afinitor interchangeable?
`Q.
`They are not. They target different targets.
`A.
`Sunitinib targets the VEGF receptor. Afinitor targets mTOR.
`And the way that most people now are using these drugs is
`that you will see a patient, and one might initially
`prescribe sunitinib for that patient. Over time, the tumors
`ultimately will continue to grow and then you might change
`and treat them with Afinitor. In another situation, one
`might start with Afinitor. If the tumors over time start to
`grow, you will then treat them with sunitinib.
`About how many of your patients receive sunitinib at
`Q.
`some point during their treatment?
`The majority of patients will receive sunitinib. I
`A.
`feel bad if they had not had the opportunity to receive an
`active drug.
`In your opinion, did Sutent meet the need from October
`Q.
`of 2000 that you discussed earlier?
`I think it clearly met the need for a new drug for
`A.
`pancreatic neuroendocrine tumors.
`Isn't there still a need for better treatments for
`Q.
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`Kulke - direct
`
`this disease?
`There is still a need. Sunitinib is not a cure, and,
`A.
`ultimately, patients will have tumor progression and we need
`to find other drugs. And one of the things I am still doing
`is trying to identify new drugs for this disease.
`It's important, though, to remember that this
`represents a huge paradigm shift. We went from having an
`old toxic chemotherapy drug to a drug that a patient can now
`come in, I can write a prescription, and I can have fairly
`good confidence that it will work.
`I think we can only hope that we will see a
`similar paradigm shift like that over the next few years or
`even decades.
`MS. STOLL: Thank you, Dr. Kulke.
`THE COURT: Thank you.
`Mr. Mack, you may cross-examine.
`MR. MACK: May I approach?
`THE COURT: Yes, you may, Mr. Mack.
`MR. MACK: May I approach the witness?
`THE COURT: Yes.
`MR. MACK: Thank you.
`May I proceed?
`THE COURT: Yes, sir.
`CROSS-EXAMINATION
`
`BY MR. MACK:
`
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`Ex. 1095-0016
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`
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`794
`Case 1:10-cv-00528-GMS Document 151 Filed 02/05/13 Page 17 of 287 PageID #: 3675
`Kulke - cross
`Good morning, Dr. Kulke.
`Q.
`Good morning.
`A.
`Now, during your direct examination, you discussed a
`Q.
`number of drugs that were previous treatments for pancreatic
`neuroendocrine tumors. Do you recall that?
`Yes.
`A.
`And I believe you discussed paclitaxel, interferon,
`Q.
`and streptozocin. Is that correct?
`That's my recollection.
`A.
`Did you discuss any other drugs?
`Q.
`I would have to go back and look. I do remember
`A.
`discussing those.
`And none of these drugs were -- none of those previous
`Q.
`drugs were angiogenesis RTK inhibitors. Is that correct?
`Yes. Those three drugs were not perceived as
`A.
`angiogenesis inhibitors.
`I'd like to talk about sunitinib and Afinitor that you
`Q.
`mentioned on your direct.
`Now, Afinitor is also known as everolimus. Is
`that correct?
`That's correct.
`A.
`In your own practice, you prescribe both sunitinib and
`Q.
`everolimus. Is that correct?
`Yes, I do.
`A.
`And everolimus is effective at treating pancreatic
`Q.
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`Ex. 1095-0017
`
`
`
`795
`Case 1:10-cv-00528-GMS Document 151 Filed 02/05/13 Page 18 of 287 PageID #: 3676
`Kulke - cross
`neuroendocrine tumors. Is that correct?
`Yes, it is.
`A.
`And as it pertains to sunitinib and everolimus, you do
`Q.
`not have a general preference for one over the other. Is
`that correct?
`That's correct.
`A.
`And in your practice, you prescribe everolimus just as
`Q.
`often as you prescribe sunitinib. Is that correct?
`In my practice, I -- I have patients who are not on
`A.
`clinical trials and I have patients who are on clinical
`trials. So if I enroll them in a study, that will affect my
`prescribing decision. But apart from a clinical trial, I
`really have no specific preference over one or the other.
`So excluding clinical trials, you have -- you
`Q.
`prescribe everolimus just as often as you prescribe
`sunitinib. Is that correct?
`That would be my sense, yes.
`A.
`And there is no -- and you are aware of no
`Q.
`head-to-head study comparing sunitinib to everolimus. Is
`that correct?
`In pancreatic neuroendocrine tumors, there has been no
`A.
`head-to-head study comparing those two.
`And there would need to be a head-to-head start --
`Q.
`sorry. Let me start again.
`There would need to be a head-to-head comparison
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`Ex. 1095-0018
`
`
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`796
`Case 1:10-cv-00528-GMS Document 151 Filed 02/05/13 Page 19 of 287 PageID #: 3677
`Kulke - cross
`of everolimus to sunitinib in order to decide which one was
`more effective. Is that correct?
`That is correct. I would add that something that is
`A.
`provocative is going to be discussed a lot in the community.
`It's interesting that there has not been a tremendous desire
`to pursue such a study, the thinking being that most of
`these patients ultimately will have the ability to be
`exposed to both drugs, so the whole sense of which one might
`be a little bit better than the other hasn't gained a whole
`lot of traction.
`I'd like to discuss the subject of long-felt need.
`Q.
`First I'd like to turn to PTX-329.
`And if you could look at the date on this. This
`is -- this study is after the priority date. Is that
`correct?
`The publication of this study was, I believe, a few
`A.
`months after the priority date. This study, itself, would
`have been performed well prior to the priority date that's
`been discussed here.
`And -- but it was published after the priority date.
`Q.
`Is that correct?
`The -- the formal publication was after priority date.
`A.
`I believe that results from the study would have been
`available and people would have known about it before then.
`And how would someone have known about the results of
`Q.
`
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`Ex. 1095-0019
`
`
`
`797
`Case 1:10-cv-00528-GMS Document 151 Filed 02/05/13 Page 20 of 287 PageID #: 3678
`Kulke - cross
`the study before that, before it was published?
`Through abstracts that were discussed.
`A.
`And are you relying on the abstracts or discussions
`Q.
`for your opinions here?
`I -- I do not have a specific abstract.
`A.
`And, to your knowledge, sunitinib has never cured a
`Q.
`pancreatic neuroendocrine tumor patient. Is that correct?
`That is correct.
`A.
`And as of the priority date, there was a long-felt
`Q.
`need for treatment to which pancreatic neuroendocrine tumors
`would not ultimately become refractory. Is that correct?
`Could you restate that -- that question?
`A.
`So, as of the priority date, is it your opinion that
`Q.
`there was a long-felt need for a treatment for pancreatic
`neuroendocrine tumors that would -- that would -- let me
`start again.
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`So, pancreatic neuroendocrine tumors can become
`refractory to cytotoxic chemotherapy agents. Is that
`correct?
`Yes, they can.
`A.
`And as of the priority date, is it your opinion -- let
`Q.
`me start again.
`As of the priority date, it is your opinion that
`there was a long-felt need for a treatment for pancreatic
`neuroendocrine tumors that would not cause the tumors to
`
`Ex. 1095-0020
`
`
`
`798
`Case 1:10-cv-00528-GMS Document 151 Filed 02/05/13 Page 21 of 287 PageID #: 3679
`Kulke - cross
`ultimately become refractory. Is that correct?
`I think the need was a little different from that.
`A.
`Actually, what we were looking for is a -- is a drug that we
`could treat our patients with that would work and that
`patients could tolerate. So it's even one step before that.
`It would be great to have a drug that patients never become
`refractory to that you could treat them for the rest of
`their lives. But at that point, it was a much more basic
`need just to have something that we could treat our patients
`with that would work.
`THE COURT: Doctor, when a patient becomes
`refractory, what does that mean?
`THE WITNESS: So, with -- with -- with virtually
`any treatment now, you give a chemotherapy drug or a
`targeted agent to a patient with cancer, and that treatment
`may result in tumor shrinkage or may stop the cancer from
`growing. But over time, the cancer becomes resistant.
`Essentially, the cells figure out a way to get around the
`treatment. And, so, over time, the tumors will start to
`gradually grow. And then you have to look for another type
`of therapy.
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`THE COURT: Thank you.
`
`BY MR. MACK:
`And there still exists a need for treatment where
`Q.
`pancreatic neuroendocrine tumors do not ultimately become
`
`Ex. 1095-0021
`
`
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`799
`Case 1:10-cv-00528-GMS Document 151 Filed 02/05/13 Page 22 of 287 PageID #: 3680
`Kulke - cross
`refractory. Is that correct?
`That is true.
`A.
`And there still exists a need for new treatment
`Q.
`options for pancreatic neuroendocrine tumors. Is that
`correct?
`There is -- there is still that need. I -- I think,
`A.
`as I said before, that should not necessarily overshadow
`what has really been a big transformation in the field with
`the development of these new therapies.
`And everolimus has met a need for a treatment that --
`Q.
`that would demonstrate efficacy against pancreatic
`neuroendocrine tumors. Is that correct?
`Everolimus has also been part of this -- this big
`A.
`transformation where we are now able to treat our patients
`with pills with targeted therapies that are very different
`from the old style chemotherapy.
`Everolimus and sunitinib have been both approved by
`Q.
`the FDA for pancreatic neuroendocrine tumors. Is that
`correct?
`That's correct.
`A.
`And everolimus was approved first for pancreatic
`Q.
`neuroendocrine tumors. Is that correct?
`They were -- I see them as being approved at the same
`A.
`time. They were reviewed by the FDA at the ODAC (phonetic)
`meeting on exactly the same day, and the approvals I believe
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`Ex. 1095-0022
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`Case 1:10-cv-00528-GMS Document 151 Filed 02/05/13 Page 23 of 287 PageID #: 3681
`Kulke - cross
`came out within just a few weeks of each other. I don't
`recall which was first or second, actually.
`MR. MACK: I have no further questions.
`THE COURT: Any redirect?
`MS. STOLL: No redirect.
`THE COURT: Thank you.
`(Witness excused.)
`MR. McDANIELS: Our next witness, Your Honor, is
`Anne Marie Robinson. She is outside.
`... ANNE MARIE ROBERTSON, having been duly sworn
`as a witness, was examined and testified as follows ...
`DIRECT EXAMINATION
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`BY MR. McDANIELS:
`Good morning, Ms. Robertson.
`Q.
`THE COURT: Any handouts?
`MR. McDANIELS: They look large, but we are
`going to move through them very quickly.
`BY MR. McDANIELS:
`Would you please introduce yourself to Chief Judge
`Q.
`Sleet?
`A.
`Q.
`
`Anne Marie Robertson.
`You may have to get a little closer to the microphone.
`Could you tell me, please, where you are
`
`employed?
`I work for Pfizer.
`A.
`
`Ex. 1095-0023
`
`
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