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` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`--------------------------------)
`PAR PHARMACEUTICAL, INC., )
`BRECKENRIDGE PHARMACEUTICAL, )
`INC., and ROXANE LABORATORIES, )
`INC., )
` )
` Petitioners, )
` )
` vs. ) Case IPR2016-00084
` ) U.S. Patent No.
`NOVARTIS AG, ) 5,665,772
` )
` Patent Owner. )
`--------------------------------)
`
` DEPOSITION OF HOWARD A. BURRIS, III, M.D.
` New York, New York
` November 11, 2016
`
`Reported by: BONNIE PRUSZYNSKI, RMR, RPR, CLR
`JOB NO. 115232
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`Ex. 1035-0001
`
`
`
` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`--------------------------------)
`PAR PHARMACEUTICAL, INC., )
`BRECKENRIDGE PHARMACEUTICAL, )
`INC., and ROXANE LABORATORIES, )
`INC., )
` )
` Petitioners, )
` )
` vs. ) Case IPR2016-00084
` ) U.S. Patent No.
`NOVARTIS AG, ) 5,665,772
` )
` Patent Owner. )
`--------------------------------)
`
` DEPOSITION OF HOWARD A. BURRIS, III, M.D.
` New York, New York
` November 11, 2016
`
`Reported by: BONNIE PRUSZYNSKI, RMR, RPR, CLR
`JOB NO. 115232
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`Ex. 1035-0001
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`Page 2
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` November 11, 2016
` 9:00 A.M.
`
` DEPOSITION OF HOWARD A. BURRIS,
` III, M.D., held at the offices of Fitzpatrick,
` Cella, Harper & Scinto, 1290 Avenue of the
` Americas, New York, New York, before Bonnie
` Pruszynski, a Registered Professional Reporter,
` Registered Merit Reporter, Certified Livenote
` Reporter, and Notary Public of the State of New
` York.
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`Ex. 1035-0002
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`Page 3
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`A P P E A R A N C E S:
`
`FITZPATRICK CELLA HARPER & SCINTO
`Attorneys for Patent Owner
` 1290 Avenue of the Americas
` New York, New York
`BY: SUSANNE FLANDERS, ESQ.
` CHARLOTTE JACOBSEN, ESQ.
`
`LATHAM & WATKINS
`Attorneys for Par Pharmaceuticals
` 330 North Wabash Avenue
` Chicago, Illinois 60611
`BY: BRENDA DANEK, ESQ.
` JONATHAN STRANG, ESQ. (telephonic appearance)
`
`MERCHANT & GOULD
`Attorneys for Breckenridge Pharmaceutical, Inc.
` 1900 Duke Street
` Alexandria, VA 22314
`BY: MARY BRAM, ESQ. (telephonic appearance)
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`Ex. 1035-0003
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`Page 4
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` H. Burris
` HOWARD A. BURRIS, III, M.D.,
` called as a witness, having been first
` duly sworn, was examined and testified
` as follows:
`EXAMINATION
`BY MS. DANEK:
` Q. Good morning, Dr. Burris.
` A. Good morning.
` Q. We met previously at your other 09:00
` deposition in the District Court litigation.
` A. Yes.
` Q. I'm Brenda Danek. I'm from
` Latham & Watkins, and I'm representing Par in
` this proceeding before the Patent Office. 09:00
` A. Okay.
` MS. FLANDERS: Susanne Flanders
` from Fitzpatrick Cella here with my
` colleague Charlotte Jacobsen on behalf of
` patent owner, Novartis. 09:00
` Q. Dr. Burris, I have placed before
` you an exhibit that's been previously
` marked as Exhibit 2095, and this is a copy
` of the expert declaration of Dr. Howard A.
` Burris, III. 09:00
`
`Ex. 1035-0004
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`Page 5
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` H. Burris
` Do you recognize this exhibit?
` A. Yes, I do.
` Q. What is it?
` A. This is my declaration as it 09:01
` relates to this particular issue.
` Q. And the issue is the validity of
` U.S. Patent Number 5,665,772?
` A. Yes, it is.
` Q. I'm going to refer to that as the 09:01
` '772 patent. Is that okay?
` A. Yes, it is.
` Q. If you would please turn to
` paragraph 13 of your declaration. It's on
` page five. 09:01
` A. Yes.
` Q. And this is the paragraph in which
` you identified the level of a person of
` ordinary skill; is that correct?
` A. Yes, it is. 09:01
` Q. And a person of ordinary skill, as
` you have used in your report, is someone that
` has a Ph.D. in medicinal or organic
` chemistry; is that correct?
` A. Yes, that is correct. 09:01
`
`Ex. 1035-0005
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`
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`Page 6
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` Q. Or alternatively, this person could
` have had a bachelor's or master's degree in
` medicinal or organic chemistry with practical
` experience in the field? 09:02
` A. Yes, that is correct.
` Q. And is the field the field of drug
` discovery and drug design?
` A. Yes, it is.
` Q. Do you have a Ph.D. in medicinal or 09:02
` organic chemistry?
` A. No, I do not.
` Q. Do you have a master's or
` bachelor's degree in medicinal or organic
` chemistry? 09:02
` A. No, I do not.
` Q. Do you have practical experience in
` the field of drug discovery or drug design?
` A. Yes. I have practical experience
` in the clinical trials of drug discovery. 09:02
` Q. Do you have practical experience in
` any preclinical assessment in drug discovery
` or drug design?
` A. I, early in my career, late '80s,
` early '90s, conducted some preclinical 09:02
`
`Ex. 1035-0006
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` H. Burris
` experiments as part of my training and
` initial career.
` Q. What did your experience in the
` preclinical assessment include in the late 09:02
` '80s or '90s?
` A. Focused on the use of human tumor
` colony assays, so taking human tumors into
` Petri dishes or plates and testing various
` anticancer compounds against those cells. 09:03
` Q. Were any of those anticancer
` compounds rapamycin or rapamycin derivatives?
` A. No, they were not.
` Q. Have you ever assessed any
` rapamycin or rapamycin derivatives in any 09:03
` preclinical assays?
` A. No, I have not.
` Q. And you would agree with me that
` you are not a person of ordinary skill in the
` art? 09:03
` A. Correct. I am not a person of
` ordinary skill in the art.
` Q. You are not an immunologist; right?
` A. No, I am not.
` Q. And you do not have experience in 09:03
`
`Ex. 1035-0007
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`Page 8
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` the development or assessment of
` immunosuppressive compounds?
` A. No, I do not.
` Q. You don't have any expertise or 09:03
` experience in analyzing the activity of
` immunosuppressive drugs in immunological
` assays; is that right?
` A. That is correct.
` Q. So, for example, you do not have 09:04
` any experience or expertise in determining
` whether drugs have immunosuppressive activity
` based on the mixed lymphocyte reaction or
` MLR; is that correct?
` A. That is correct. 09:04
` Q. And you do not have any experience
` or expertise in determining whether drugs
` have immunosuppressive activity based on the
` IL-6 mediated proliferation assay; is that
` correct? 09:04
` A. That is also correct.
` Q. Or any other preclinical assay of
` immunosuppressive activity?
` MS. FLANDERS: Objection to form.
` A. That would be correct. 09:04
`
`Ex. 1035-0008
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`Page 9
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` Q. And you don't have -- we have
` already talked about that.
` The only experience that you have
` concerning rapamycin is your clinical 09:04
` experience on everolimus; is that correct?
` A. Yes. I have clinical experience
` with everolimus and temsirolimus, and through
` the years other investigational compounds
` that have similar characteristics. 09:04
` Q. To rapamycin?
` A. Yes.
` Q. That is all clinical experience;
` correct?
` A. Yes. 09:05
` Q. You don't have any experience in
` assessing rapamycin or any of its derivatives
` in macrophilin binding assays; is that
` correct?
` A. That is correct. 09:05
` Q. And you do not consider yourself an
` expert in treating pancreatic neuroendocrine
` tumors or neuroendocrine tumors; is that
` correct?
` A. That is not an area of my 09:05
`
`Ex. 1035-0009
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`Page 10
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` H. Burris
` expertise. I have treated a number of
` patients with neuroendocrine tumors,
` including those patients that would be
` classified as PNET. 09:05
` Q. But you don't consider yourself an
` expert in that area?
` A. Correct.
` Q. And you don't have any expertise in
` treating, let me just call them SEGA in 09:05
` patients with TSC; is that correct?
` A. That's also correct.
` Q. And you don't have any expertise in
` treating renal angiomyolipomas in patients
` with TSC; is that correct? 09:05
` A. That is also correct.
` Q. Your expertise, as it's detailed in
` your declaration, centers on treating breast
` cancer and renal cell carcinoma; is that
` correct? 09:06
` MS. FLANDERS: Objection to form.
` A. My expertise is -- pertains to both
` of those disease areas, breast and renal cell
` cancer, as well as having conducted many of
` the clinical trials with everolimus. 09:06
`
`Ex. 1035-0010
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`Page 11
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` H. Burris
` Q. In breast cancer and renal cell
` cancer?
` MS. FLANDERS: Objection, form.
` A. My experience includes trials that 09:06
` were specific to breast and renal cell
` cancer, but also phase one clinical trials
` with the drug as well.
` Q. And what phase one clinical trials
` with rapamycin or rapamycin derivatives have 09:06
` you conducted?
` MS. FLANDERS: Objection, form.
` A. I was -- I have conducted -- I was
` an investigator on the phase one studies of
` everolimus, two different phase one trials of 09:06
` everolimus, determining its best dosing
` schedule.
` Q. And in that phase one study, did
` you assess the clinical activity of
` everolimus in a particular tumor type? 09:07
` MS. FLANDERS: Objection, form.
` A. Those phase one trials were classic
` phase one trials. The compound was
` everolimus, at that time known as RAD001, and
` the trial took on all types of patients with 09:07
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`Ex. 1035-0011
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`Page 12
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` H. Burris
` the primary endpoint of determining the best
` schedule and the best dose of administration
` of everolimus.
` Q. Did you make any determinations in 09:07
` any of the phase one trials that you were
` involved in where everolimus was administered
` to cancer patients regarding the clinical
` activity of everolimus in any particular
` cancer type? 09:07
` MS. FLANDERS: Objection, form.
` A. No. That was not an endpoint for
` those studies.
` Q. Can you turn to paragraph 15 of
` Exhibit 2095? 09:08
` A. Yes.
` Q. And here you outline the legal
` standard that you understood and applied in
` forming your opinions in this case; is that
` correct? 09:08
` MS. FLANDERS: Objection, form.
` A. Yes.
` Q. And in paragraph 15 of the report,
` the bottom of the paragraph, you state that
` "the board will consider whether there would 09:08
`
`Ex. 1035-0012
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` H. Burris
` have been a reasonable expectation of
` achieving the unique combination of
` properties possessed by the chemical
` compound." 09:08
` Do you see that?
` MS. FLANDERS: Objection, form.
` A. I do see that.
` Q. And is this the standard that you
` used in arriving at your opinions related to 09:08
` reasonable expectation of success?
` A. Yes. I'm -- this is correct, and I
` was asked to look at what was known about the
` art as of October 1992, and compared what we
` know about everolimus today with that. 09:09
` Q. And so, you looked at the
` information known about everolimus today and
` compared that to the art in October 1992, in
` forming your opinions related to reasonable
` expectation of success? 09:09
` A. No. Let me clarify. With regard
` to reasonable expectation of success, I
` looked at what was known about the art in
` October 1992. And then I guess I was going
` to the next part about the predictability of 09:09
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`Ex. 1035-0013
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` H. Burris
` the results, and then for looking at other
` aspects, unexpected results, looked at where
` we stood today.
` Q. Okay. Just to make sure we 09:09
` understand, your opinions related to
` reasonable expectation of success looked only
` at the information available on everolimus
` and rapamycin in October 1992?
` MS. FLANDERS: Objection, form. 09:10
` A. I looked at what was available and
` what was known about the prior art as of
` October 1992, which consisted of what we knew
` about rapamycin at that time.
` Q. And what did you look at with 09:10
` respect to everolimus in forming your
` opinions on reasonable expectation of
` success?
` A. For reasonable expectation of
` success, I didn't look at everolimus at that 09:10
` time.
` Q. And your opinions related to
` reasonable expectation of success include the
` unique combination of properties possessed by
` the chemical compound; is that correct? 09:10
`
`Ex. 1035-0014
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`Page 15
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` H. Burris
` MS. FLANDERS: Objection, form.
` A. Yes.
` Q. And the unique combination of
` properties include the confirmed clinical 09:10
` efficacy of everolimus in the approved
` indications; is that correct?
` A. The success of everolimus, yeah,
` the combination of approvals was part of the
` success of everolimus that I looked at. 09:11
` Q. And in forming your opinion about
` the reasonable expectation of success, you
` looked at the confirmed clinical efficacy in
` the approved indications for everolimus; is
` that correct? 09:11
` A. Would you clarify? I'm not sure I
` understand exactly what you are asking.
` Q. Right. I just want to understand.
` You testified that the success of
` everolimus, the combination of approvals was 09:11
` part of the success of everolimus, and I am
` trying to understand how that success that
` you have just defined there relates to your
` opinions on the reasonable expectation of
` success that you have offered. 09:12
`
`Ex. 1035-0015
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`Page 16
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` MS. FLANDERS: Objection, form.
` A. I assessed reasonable expectation
` of success by looking at what was known about
` the art in October 1992, and the data at that 09:12
` time that was available was what I was able
` to find about rapamycin.
` Q. Okay. And is it your opinion that
` a person of ordinary skill in the art in
` October 1992 would have been modifying 09:12
` rapamycin to try to make a compound that
` would achieve confirmed clinical efficacy in
` the approved indications of everolimus?
` MS. FLANDERS: Objection, form,
` outside the scope. 09:12
` A. I was not asked to consider whether
` a person of ordinary skill in the art would
` have modified such a compound.
` Q. So, in forming your opinions on
` reasonable expectation of success, you 09:12
` weren't asked to consider what motivation the
` person of ordinary skill in the art in
` October 1992 would have had in modifying
` rapamycin?
` MS. FLANDERS: Objection, form. 09:13
`
`Ex. 1035-0016
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`Page 17
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` Outside the scope.
` A. I was asked to consider whether
` there would have been a reasonable
` expectation of success based on what was 09:13
` known about rapamycin in October 1992. So, I
` looked at the information that I referred to
` in this report with regard to what was
` published and known about preclinical work.
` Q. I guess I am trying to understand 09:13
` where the expectation comes from. What was
` the expectation that you were asked to
` consider in forming your opinions on
` reasonable expectation of success?
` MS. FLANDERS: Objection, form. 09:13
` A. I was asked to consider and I
` looked at whether there would have been a
` reasonable expectation of success for
` everolimus for the '772 patent based on --
` with regard to the later findings with regard 09:14
` to what was known at that time, as of
` October 1992, which consisted of the
` preclinical data that was available and the
` other data that hadn't yet been produced.
` Q. But you weren't asked to assume 09:14
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`Ex. 1035-0017
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`Page 18
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` that a person of ordinary skill in the art
` would have been motivated to make a
` derivative of rapamycin to achieve the
` confirmed clinical efficacy in these approved 09:14
` indications; is that correct?
` MS. FLANDERS: Objection, form.
` Outside the scope.
` A. As I state at the beginning of
` paragraph 15, I understand that the board 09:14
` will consider whether a POSA would have
` selected the asserted prior art compound as a
` lead compound or starting point for further
` development and chemical modification.
` A POSA would have done that. I 09:15
` wasn't asked to consider whether I would have
` selected the lead compound.
` Q. Okay. And then in the next
` sentence you state that "the board will next
` consider whether the prior art would have 09:15
` supplied a POSA with a reason or motivation
` to modify a lead compound to make the claimed
` compound with a reasonable expectation of
` success."
` And so, what I am trying to 09:15
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`Ex. 1035-0018
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`Page 19
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` understand is: What motivation did you
` understand a person of ordinary skill in the
` art would have used to modify the lead
` compound that sets the -- whether or not the 09:15
` expectation of success was reasonable?
` MS. FLANDERS: Objection. Form.
` Outside the scope.
` A. I certainly don't mean to be
` argumentative. I don't -- I was asked to not 09:15
` make a judgment with regard to the lead
` compound or what the motivation would have
` been for a POSA to have modified or worked
` with such a compound.
` I was simply asked to look at the 09:16
` data that was available in October 1992, with
` my expertise, as to whether there would have
` been a reasonable expectation of success.
` Q. Okay. So, you didn't consider --
` you didn't consider a motivation in coming to 09:16
` your conclusions on whether or not a person
` of ordinary skill in the art would have had a
` reasonable expectation of success?
` A. Correct.
` Q. Okay. And you have used the term 09:16
`
`Ex. 1035-0019
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`Page 20
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` H. Burris
` "confirmed clinical efficacy" in your
` declaration; is that right?
` A. Yes.
` Q. And in your opinion, confirmed 09:16
` clinical efficacy requires positive results
` from a placebo-controlled, double-blind phase
` three clinical study; is that right?
` MS. FLANDERS: Objection, form.
` A. Certainly the results of a 09:16
` well-controlled, double-blind,
` placebo-controlled phase three trial would be
` one example of confirmed clinical efficacy.
` Q. What other examples of -- would
` establish confirmed clinical efficacy? 09:17
` MS. FLANDERS: Objection, form.
` Outside the scope.
` A. I mean, in terms of confirmed
` clinical efficacy for drugs in the treatment
` of cancer, depending on the state of the drug 09:17
` and the state of the disease being assessed,
` one would not necessarily have to have a
` placebo control. I mean, a trial could be
` compared to another standard of care in that
` setting. 09:17
`
`Ex. 1035-0020
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`
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`Page 21
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` H. Burris
` So, I do think that the confirmed
` clinical efficacy does come routinely from
` randomized phase three trials.
` Q. And in your opinion, a person of 09:17
` ordinary skill would not have had a -- would
` not have reasonably expected that everolimus
` would have confirmed clinical efficacy in its
` antitumor indications; is that right?
` MS. FLANDERS: Objection, form. 09:18
` A. I would not think it would be a
` reasonable expectation, that a POSA would
` have reasonably expected that result.
` Q. Okay. And the approved antitumor
` indications includes efficacy in HR-positive 09:18
` HER2-negative breast cancer in combination
` with exemestane after failure with letrozole
` or anastrozole; is that correct?
` A. That's correct.
` Q. Was exemestane approved as a 09:18
` treatment for breast cancer in October of
` 1992?
` A. No, it was not.
` Q. Was letrozole approved as a
` treatment for breast cancer in 1992? 09:18
`
`Ex. 1035-0021
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`Page 22
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` H. Burris
` A. No, it was not.
` Q. Was anastrozole approved as a
` treatment for breast cancer in 1992?
` A. No, it was not. 09:18
` Q. And then the unique combination of
` properties that you rely on for your
` reasonable expectation of success opinions
` include confirmed clinical efficacy in renal
` cell carcinoma after failure of treatment 09:18
` with sunitinib or sorafenib; is that correct?
` MS. FLANDERS: Objection, form.
` A. Yes, that is correct.
` Q. Was sunitinib approved as a
` treatment for RCC in October of 1992? 09:19
` A. No, it was not.
` Q. Was sunitinib a compound that was
` known in the art in October 1992?
` A. No, it was not.
` Q. Was sorafenib approved as a 09:19
` treatment for RCC in October of 1992?
` A. No, it was not.
` Q. Was sorafenib a compound that was
` known in the art in October 1992?
` A. No, it was not. 09:19
`
`Ex. 1035-0022
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`Page 23
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` H. Burris
` Q. And then the unique combination of
` properties that you rely on in forming your
` opinions on reasonable expectation of success
` also includes confirmed clinical efficacy in 09:19
` PNET or NET of the lung or GI tract origin;
` is that correct?
` MS. FLANDERS: Objection, form.
` A. Yes, it is.
` Q. And the unique combination of 09:19
` properties that you rely on in your opinions
` for reasonable expectation of success include
` confirmed clinical efficacy in renal
` angiomyolipomas and TSC; is that correct?
` MS. FLANDERS: Objection to form. 09:20
` A. Yes, that is correct.
` Q. And the unique combination of
` properties that you rely on in forming your
` opinions related to reasonable expectation of
` success includes confirmed clinical efficacy 09:20
` in patients with TSC who have SEGA; is that
` correct?
` MS. FLANDERS: Objection, form.
` A. Yes, that's correct.
` Q. Okay. Part of your opinion that a 09:20
`
`Ex. 1035-0023
`
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`Page 24
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`
` H. Burris
` person of ordinary skill in the art would not
` have a reasonable expectation that everolimus
` would have this unique combination of
` confirmed clinical efficacies is, you have 09:20
` offered opinions about the antitumor activity
` of rapamycin was unpredictable in
` October 1992; is that correct?
` A. Yes, that is correct.
` Q. I believe you have this discussion 09:20
` starting at paragraph 78 in your -- in your
` declaration, Exhibit 2095. Let's start
` there.
` Are you with me here, Dr. Burris?
` A. Yes. Yes, I am. 09:21
` Q. And in October 1992, you agree that
` the antitumor activity of rapamycin had been
` tested and reported; is that right?
` MS. FLANDERS: Objection, form.
` A. As of October 1992, there was a 09:21
` number of publications that included
` rapamycin among drugs studied in preclinical
` cancer models.
` Q. And you indicate that rapamycin was
` not unique in the National Cancer Institute 09:21
`
`Ex. 1035-0024
`
`
`
`Page 25
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`
` H. Burris
` or the NCI testing of antitumor activity; is
` that right?
` MS. FLANDERS: Objection, form.
` Q. This is in paragraph 79. 09:21
` A. Yes. I refer there to the fact
` that it was one of thousands of compounds
` that were being assessed.
` Q. Right. And you indicate actually
` that the NCI had screened 180,000 different 09:22
` culture filtrates for antitumor activity; is
` that right?
` A. Yes, that is a true statement.
` Q. And the culture filtrates, they're
` solutions in which microorganisms are 09:22
` cultured and secrete compounds; is that
` right?
` MS. FLANDERS: Objection, form.
` A. Yes. They secrete proteins and --
` which then can be utilized as compounds to 09:22
` test.
` Q. Proteins and also small molecules;
` isn't that right?
` MS. FLANDERS: Objection, form.
` A. Yes. You know, certainly the 09:22
`
`Ex. 1035-0025
`
`
`
`Page 26
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` H. Burris
` definition of a small molecule is broad, but
` that would be within that range.
` Q. So, these culture filtrates, they
` don't just include proteins, but there are 09:22
` chemical compounds smaller than proteins that
` are assessed in these culture filtrate
` screenings?
` MS. FLANDERS: Objection, form.
` A. Yes. 09:23
` Q. And rapamycin was one of the
` culture filtrates that were screened for
` anticancer activity?
` A. Yes.
` Q. And in paragraph 79 and 80, you 09:23
` cite Exhibit 2155, a paper by Douros. Is
` that correct?
` A. That is correct.
` Q. Let me hand you a copy of Douros.
` MS. DANEK: Is that all right, if I 09:23
` keep this?
` MS. JACOBSEN: Yes, of course.
` Q. Do you recognize Exhibit 2155,
` Dr. Burris?
` A. Yes, I do. 09:24
`
`Ex. 1035-0026
`
`
`
`Page 27
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` H. Burris
` Q. Is this the exhibit that you cite
` in support of your discussion of rapamycin
` screening for anticancer activity by the
` National Cancer Institute? 09:24
` MS. FLANDERS: Objection, form.
` A. This is one of the papers to which
` I refer.
` Q. And then at page 63, in the sort of
` middle of the introduction, there's a 09:24
` sentence that says, "Since the inception of
` the program, approximately 180,000 culture
` filtrates have been tested in vivo against
` murine tumors."
` Do you see that? 09:24
` A. Yes, I do.
` Q. Is this the source of your 180,000
` figure that you have in paragraph 79?
` A. Yes, it is.
` Q. And the sentence goes on to say 09:24
` that "8.5 percent of these have been found to
` be active."
` Do you see that?
` A. I do see that.
` Q. Okay. And then further, further on 09:24
`
`Ex. 1035-0027
`
`
`
`Page 28
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` H. Burris
` in the paragraph, the next sentence, it says,
` "A marked improvement in in vivo activity in
` recent years has been due to using in vitro
` pre-screen tests." 09:25
` Do you see that?
` A. Yes, I do.
` Q. So, by using an in vitro screen,
` the NCI was able to exclude those compounds
` that did not have antitumor activity before 09:25
` further testing in in vivo screens; is that
` right?
` MS. FLANDERS: Objection, form.
` A. The statement there, I don't know
` that you can draw an absolute from that 09:25
` statement. My interpretation of that was
` that using an in vitro screen helped
` eliminate compounds that were likely to be
` inactive and allow a smaller number to move
` into in vivo testing. 09:26
` Q. Okay. And of the 180,000 culture
` filtrates that the NCI tested, in this
` report, they identified 28 compounds that
` they described the anticancer activity of; is
` that correct? 09:26
`
`Ex. 1035-0028
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`Page 29
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` H. Burris
` MS. FLANDERS: Objection, form.
` Q. And Dr. Burris, I will just refer
` you to Note 98 in your report on page 43.
` A. Yes, that is correct. 09:26
` Q. So, rapamycin was one of 28
` compounds that the NCI selected after
` screening 180,000 culture filtrates to report
` on in this paper.
` MS. FLANDERS: Objection, form. 09:26
` Outside the scope.
` A. Yes. They report on 28 compounds.
` You know, the math, eight-and-a-half percent
` of 180,000 is actually 15,000. So, there is
` substantial scope decrease in terms of what 09:27
` they actually report there, but true that 28
` are included in this report.
` Q. Okay. And then table 21, on the
` top of page 75 of 2155, Exhibit 2155 -- I'm
` sorry, it's at the bottom of page 75. 09:27
` A. Yes.
` Q. And this is the table that you cite
` in paragraph 80 of your report?
` A. Yes, it is.
` Q. Okay. And so, you agree that 09:27
`
`Ex. 1035-0029
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`Page 30
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` H. Burris
` rapamycin was known to be active as an
` antitumor agent in the colon 38 mouse colon
` carcinoma assay?
` MS. FLANDERS: Objection, form. 09:28
` A. I have reported and listed in this
` table active or inactive based on the
` definition set up by the investigators
` interpreted from table 21, the criterion
` meant to be considered active within this 09:28
` assay.
` Q. And you didn't disagree in your
` declaration that rapamycin was reported to be
` active in this cancer model?
` MS. FLANDERS: Objection, form. 09:28
` A. Correct. I had no data to refute
` what the authors declared as active.
` Q. And similarly, you didn't in your
` declaration disagree that rapamycin had been
` reported to be active in the CX-1 human colon 09:28
` carcinoma model?
` MS. FLANDERS: Objection, form.
` A. Agree, yes. Again, no data to
` refute that the authors determined that the
` CX-1 human colon carcinoma showed activity 09:28
`
`Ex. 1035-0030
`
`
`
`Pag
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