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` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
` __________________________________________
`
` BRECKENRIDGE PHARMACEUTICAL, INC.
` AND WEST-WARD PHARMACEUTICALS
` INTERNATIONAL, LIMITED,
`
` Petitioner,
`
` vs.
`
` NOVARTIS PHARMACEUTICALS
` CORPORATION,
`
` Case No. IPR2017-01592
` Patent No. 8,410,131
`
` Patent Owner.
` __________________________________________
`
` DEPOSITION OF : DR. HOWARD A. BURRIS, III
`
` DATE
`
` TIME
`
` : MAY 24, 2018
`
` : 8:25 A.M.
`
` LOCATION
`
` : NASHVILLE, TENNESSEE
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`1
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` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
` __________________________________________
`
` BRECKENRIDGE PHARMACEUTICAL, INC.
` AND WEST-WARD PHARMACEUTICALS
` INTERNATIONAL, LIMITED,
`
` Petitioner,
`
` vs.
`
` NOVARTIS PHARMACEUTICALS
` CORPORATION,
`
` Case No. IPR2017-01592
` Patent No. 8,410,131
`
` Patent Owner.
` __________________________________________
`
` DEPOSITION OF : DR. HOWARD A. BURRIS, III
`
` DATE
`
` TIME
`
` : MAY 24, 2018
`
` : 8:25 A.M.
`
` LOCATION
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` : NASHVILLE, TENNESSEE
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`NorthStar Deposition Services
`(877) 544-3377
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`2
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` 1
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` 2
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` 3 The Deposition of DR. HOWARD A. BURRIS, III,
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` 4 taken on behalf of the Petitioner, pursuant to Notice
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` 5 on May 24, 2018, beginning at approximately 8:25 a.m.
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` 6 in the offices of Sarah Cannon Cancer Institute, 1100
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` 7 Charlotte Avenue, Nashville, Tennessee, 37203.
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` 8 This deposition is taken in accordance with
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` 9 the terms and provisions of the Federal Rules of
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`10 Civil Procedure. All objections are reserved except
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`11 as to form.
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`12 The signature of the witness was waived.
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`3
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` 1 APPEARANCES
`
`
`
` 2
` For the Petitioner:
` 3
` DANIEL R. EVANS
` 4 Attorney at Law
` MERCHANT & GOULD
` 5 191 Peachtree Street NE, Suite 3800
` Atlanta, GA 30303
` 6 404.954.5100
` devans@merchantgould.com
` 7
`
` 8
` For the Patent Owner:
` 9
` CHARLOTTE JACOBSEN
`10 JARED L. STRINGHAM
` Attorneys at Law
`11 FITZPATRICK, CELLA, HARPER & SCINTO
` 1290 Avenue of the Americas
`12 New York, NY 10104-3800
` 212.218.2523
`13 cjacobsen@fchs.com
`
`14
`
`15 Also Present:
`
`16 ALLAN PANTUCK
`
`17
`
`18 Reported By:
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`19 PATRICIA A. NILSEN, RMR, CRR, CRC
` TN Certified Court Reporter
`20 (877) 544-337
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`4
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` 1 DR. HOWARD A. BURRIS, III MAY 29, 2018
`
`
`
` 2 C O N T E N T S
`
` 3 Stipulations Page 2
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` 4
`
` 5 Appearances Page 3
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` 6
`
` 7 Exhibit Index Page 5
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` 8
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` 9 Examination by Mr. Evans Page 6
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`10 Examination by Ms. Jacobsen Page 249
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`11
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`12 Certification Page 257
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`13
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`14 Word Index Page 258
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` 1 DR. HOWARD A. BURRIS, III MAY 29, 2018
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`
`
` 2 E X H I B I T S
`
` 3 NUMBER DESCRIPTION PAGE
`
` 4 1121 Summary of results of 26
` Weckbecker in vivo assay
` 5
` 1122 Reference in the Journal of 106
` 6 Clinical Oncology, volume 26,
` number 10, dated April 1, 2008,
` 7 entitled Phase I Pharmacokinetic
` and Pharmacodynamic Study of the
` 8 Oral Mammalian Target of Rapamycin
` Inhibitor Everolimus in Patients
` 9 with Advanced Solid Tumors
`
`10 1123 Cover page for meeting of 110
` the 93rd Annual Meeting of the
`11 American Association for Cancer
` Research
`12
` 1124 First page of the Zhu '973 173
`13 patent
`
`14 1125 Provisional application for 173
` Zhu patent
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`Dr. Howard A. Burris, III
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`6
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` D R. H O W A R D A. B U R R I S, III,
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` having been first duly sworn, was examined and
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` testified as follows:
`
` EXAMINATION
`
` BY MR. EVANS:
`
`Q.
`
`Good morning, Dr. Burris. Thank you for
`
` taking the time to meet with us today. You and I
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` have not met before, but I've been thinking about
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` you. I've been reading your writings for quite
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` some time, so I'm grateful to have the opportunity
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` to chat with you. I know that you've done several
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` depositions in the past, correct?
`
`A.
`
`Q.
`
`Yes, I have.
`
`And so you understand the fundamental
`
` ground rules, correct? In other words, I will ask
`
` you a question, and then you wait and give your
`
` counsel an opportunity to object. And unless your
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` counsel tells you not to answer, you have to answer
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` the question. Do you understand, sir?
`
`A.
`
`Q.
`
`Yes.
`
`Okay. And I'm going to try to speak
`
` clearly and ask questions slowly. If you don't
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` understand, please ask me to rephrase the question.
`
`A.
`
`Q.
`
`Okay.
`
`And if you don't ask me to rephrase the
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`NorthStar Deposition Services
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`Dr. Howard A. Burris, III
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`7
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` 1 question, I'll just understand that you understand
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` 2 what I'm saying. Is that a fair assumption?
`
` 3 A. Yes.
`
` 4 Q. All right. So I have for you -- and this
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` 5 is so many documents. I've got a document for you
`
` 6 and counsel.
`
` 7 MS. JACOBSEN: Thank you.
`
` 8 MR. EVANS: And this document is Novartis
`
` 9 Exhibit 2092. And it's entitled Corrected Expert
`
`10 Declaration of Dr. Howard A. Burris, III.
`
`11 And I have another document I'm going
`
`12 to hand to you, this is Novartis Exhibit 2001,
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`13 Expert Declaration of Dr. Howard A. Burris,
`
`14 III. And we're going to have to refer to
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`15 several of these documents.
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`16 And I apologize, Jared. I didn't
`
`17 bring you an extra copy.
`
`18 MR. STRINGHAM: No worries.
`
`19 MR. EVANS: And then I have a third
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`20 document. This is Breckenridge Exhibit 1010. This
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`21 is Dr. Pantuck's declaration. And I'm going to
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`22 hand you that copy.
`
`23 And then I'm going to put those away.
`
`24 Okay.
`
`25 BY MR. EVANS:
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`NorthStar Deposition Services
`(877) 544-3377
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`Dr. Howard A. Burris, III
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`8
`
`
` 1 Q. So, Doctor, I've put before you three
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` 2 documents. Do you recognize these documents, sir?
`
` 3 A. Yes, I do.
`
` 4 Q. Okay. And so these -- the first document,
`
` 5 which is 2001, the smaller document, you understand
`
` 6 that that was the first declaration that you
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` 7 submitted and corresponds to Novartis's -- the
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` 8 preliminary patent owner's response?
`
` 9 A. Yes.
`
`10 Q. Or patent owner's preliminary response.
`
`11 Now, you have a second document there,
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`12 2092, that's your corrected declaration. And you
`
`13 recognize that document. And that was filed in
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`14 conjunction with patent owner's response, was filed
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`15 early in April, right?
`
`16 A. Correct.
`
`17 Q. And of course you recognize Dr. Pantuck's
`
`18 declaration. And so with that said, I would ask
`
`19 you to turn to your corrected declaration. And
`
`20 that's Exhibit 2092. And if you would, please,
`
`21 sir, turn to paragraph one at page one.
`
`22 And just for the record, there are Bates
`
`23 numbers on the lower right-hand corner. This is
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`24 Bates number 41 of 218.
`
`25 So, Doctor, if you would please read
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`NorthStar Deposition Services
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`Dr. Howard A. Burris, III
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`9
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` 1 paragraph one for the record.
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` 2 A. "Challenged claims 1 to 3 and 5 to 9 of US
`
` 3 patent number 8,410,131 (the ''131 patent') relate
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` 4 to methods for inhibiting growth of solid excretory
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` 5 system tumors in a subject, consisting of
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` 6 administering a therapeutically effective amount of
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` 7 everolimus."
`
` 8 Q. Thank you, sir.
`
` 9 And so your understanding, then, Doctor,
`
`10 is that the challenged claims 1 through 3 and 5
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`11 through 9 relate to methods for inhibiting growth
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`12 of solid excretory tumors in a subject, correct?
`
`13 A. Correct.
`
`14 Q. Thank you, sir.
`
`15 So I am going to hand you another document
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`16 which you have considered extensively. This is an
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`17 exhibit numbered 1021. A document -- Doctor, do
`
`18 you recognize this document?
`
`19 A. Yes, I do.
`
`20 Q. It may have been also referred to as
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`21 Weckbecker. So, Doctor, you realize if you look in
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`22 the upper left-hand -- upper right-hand corner,
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`23 pardon, this is a PCT document, WO 97/47317.
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`24 A. Yes, I do.
`
`25 Q. Okay. Thank you.
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`NorthStar Deposition Services
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`Dr. Howard A. Burris, III
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`10
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`
` 1 And you see that it was published on 18
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` 2 December, 1997?
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` 3 A. Yes, I do.
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` 4 Q. Okay. And if you look on the left-hand
`
` 5 corner, it's an INID code 71, the left-hand margin.
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` 6 It says "the applicant"? Do you see where it says
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` 7 "Novartis AG"?
`
` 8 A. Yes, I do.
`
` 9 Q. Okay. And then 75, you see the inventor
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`10 applicant is Weckbecker?
`
`11 A. Yes, I do.
`
`12 Q. Okay, sir. Thank you.
`
`13 And INID code 21 at the top, where it says
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`14 "International Application Number PCT/EP97/03036."
`
`15 Do you see that, Doctor?
`
`16 A. Yes, I do.
`
`17 Q. Okay. Thank you.
`
`18 And you understand from the abstract that
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`19 the document here refers to a combination of a
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`20 compound of the somatostatin class and a rapamycin
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`21 macrolide, and it states, "is useful for the
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`22 prevention or treatment of cell
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`23 hyperproliferation."
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`24 A. Yes, I see that.
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`25 Q. Okay. Thank you, sir.
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`NorthStar Deposition Services
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`Dr. Howard A. Burris, III
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`11
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`
` 1 So if you would, please, I'd like you to
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` 2 turn to page 14. And when I refer to page 14, I'm
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` 3 referring to the native page number. And it's at
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` 4 the top, but it's also the Bates number in the
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` 5 lower right-hand corner, page 0016. And you see in
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` 6 Section A there it refers to an in vitro assay?
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` 7 Do you see that, Doctor?
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` 8 A. Yes, I do.
`
` 9 Q. Okay. Thank you.
`
`10 And so it refers there to AR42J cell
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`11 cultures. Doctor, are you aware what the AR42J
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`12 cell cultures, what cancer that represents?
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`13 A. If I could, could I go to my report --
`
`14 Q. Sure. Please.
`
`15 A. -- and just refresh my memory on this
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`16 particular section.
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`17 Q. And I will try to assist you. I believe
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`18 it's at page 81. Pardon. Page 86. Paragraph 163.
`
`19 A. Yes, I do. I see that.
`
`20 Q. Okay.
`
`21 A. Yes, I do. I see that. Yes.
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`22 Q. Okay. And so the question was: Do you
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`23 see the AR42J cell cultures?
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`24 A. Yes, I do.
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`25 Q. Do you understand what type of cell
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`NorthStar Deposition Services
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`Dr. Howard A. Burris, III
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`12
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` 1 culture that is, sir?
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` 2 A. Yes. That's a pancreatic tumor cell.
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` 3 Q. Is that a solid tumor, as you understand
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` 4 the term?
`
` 5 A. Yes, it is.
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` 6 Q. Okay. It's not a liquid tumor?
`
` 7 A. No, it's not.
`
` 8 Q. Okay. So if you look at this experiment
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` 9 -- and this experiment kind of runs pages, native
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`10 pages 14 through 15 -- and they refer to exposing
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`11 these various cell lines, these AR42J solid
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`12 pancreatic tumor cell lines, to a certain amount of
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`13 either octreotide -- do you see that, sir, the
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`14 table on the right?
`
`15 A. Yes, I do.
`
`16 Q. Okay. And then there's compound B.
`
`17 Do you understand what compound B is, sir?
`
`18 A. Yes, I do.
`
`19 Q. Okay. So if you refer to -- for the
`
`20 record, this is at page 12 of Exhibit 1021,
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`21 left-hand side. It says a preferred compound is
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`22 40-O-(2-hydroxy)ethyl-rapamycin?
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`23 A. Yes, I do, sir.
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`24 Q. Referred thereafter as compound B?
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`25 A. Yes, I do.
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`Dr. Howard A. Burris, III
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`13
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` 1 Q. And Dr. Burris, you understand this
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` 2 compound to be everolimus?
`
` 3 A. Yes, I do.
`
` 4 Q. Thank you, sir.
`
` 5 So if you look at this table here, Doctor,
`
` 6 you see that an octreotide concentration of 1.2
`
` 7 nanomolar. The Weckbecker reference describes a
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` 8 certain cell growth represented by a delta OD.
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` 9 A. Yes, I see that.
`
`10 Q. And you understand what the OD is?
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`11 They're looking at the absorbance difference,
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`12 difference in absorbance; do you understand that,
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`13 sir?
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`14 A. Yes, I do.
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`15 Q. Thank you.
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`16 And you see that compound B is at 12
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`17 nanomolar concentration?
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`18 A. Yes, I do.
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`19 Q. Okay. And then the reports say cell
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`20 growth delta OD percent of 420. And there's
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`21 standard error plus or minus 12. And then, of
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`22 course, the octreotide is 39 -- 397 plus or minus
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`23 60.
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`24 So do you see those values, Doctor?
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`25 A. Yes, I do see those.
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`NorthStar Deposition Services
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`Dr. Howard A. Burris, III
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`14
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` 1 Q. Okay. And you see that just above that
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` 2 they have results for a control. And the cell
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` 3 growth delta OD percent is 664 plus or minus 9.
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` 4 A. Yes, I do see that.
`
` 5 Q. Okay. Thank you, sir.
`
` 6 And so would you agree, then, that this
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` 7 data shows that compound B and octreotide both
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` 8 inhibit growth of this AR42J solid cancer cell
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` 9 line, sir?
`
`10 MS. JACOBSEN: Object to the form.
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`11 Mischaracterizes the document.
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`12 A. Well, I think that, as I've written in my
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`13 report here, there -- and taken in context from
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`14 what's described here, it doesn't clearly show that
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`15 with the overlap that there's substantial
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`16 inhibition as shown here. I've written on my
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`17 report, as in paragraph 165, just beginning at the
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`18 beginning, "additionally, Weckbecker tested only
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`19 one tumor cell line in both in vitro and in vivo
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`20 assays: A pancreatic tumor cell line."
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`21 Q. Okay.
`
`22 A. "I disagree with Dr. Pantuck that
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`23 Weckbecker disclosed that everolimus alone,
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`24 exhibited in vivo antitumor activity against solid
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`25 pancreatic tumors." The results are summarized
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`Dr. Howard A. Burris, III
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`15
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` 1 there below with the tumor volumes and the standard
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` 2 error.
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` 3 And if you go to the table on the top of
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` 4 page 89, one can see that "A POSA would recognize
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` 5 there is no statistical difference in tumor volume
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` 6 between the control group, which received no drug,
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` 7 and the everolimus group. Even taking into
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` 8 consideration the fact that the control group data
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` 9 was taken at the third week and the other data at
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`10 the fourth week, these data would not have
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`11 suggested to a POSA that everolimus alone had
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`12 antitumor activity against the cell line. And
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`13 because this experiment was conducted in vivo in
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`14 mice, a POSA would have considered the data more
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`15 informative than the in vitro data in Weckbecker."
`
`16 Q. Thank you, sir. That's a remarkable
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`17 answer, but can you answer the question? I was
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`18 asking about the in vitro data.
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`19 MS. JACOBSEN: Objection to form.
`
`20 Q. And you realize that what you explained to
`
`21 me was the in vivo data?
`
`22 A. Yes.
`
`23 Q. I was asking about the in vitro data.
`
`24 If you would please turn to paragraph 168,
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`25 page 90 of your report.
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`Dr. Howard A. Burris, III
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`16
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` 1 A. Yes.
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` 2 Q. And so my question to you, sir, is related
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` 3 to your parenthetical on the third and fourth line.
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` 4 A. So, "Furthermore, in both the in vitro and
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` 5 in vivo assay, the results with everolimus alone
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` 6 clearly were inferior compared to the combination
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` 7 of everolimus with the somatostatin analog.
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` 8 Exhibit 1021, Weckbecker at 15, 16, showing that in
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` 9 vitro tumor cell growth was 63.3 percent of the
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`10 control with everolimus alone and 15.6 percent of
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`11 the control with everolimus in combination with
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`12 octreotide, and showing that in vivo the tumor
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`13 volume after treatment with everolimus alone was
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`14 3,685, plus or minus 263 cubic millimeters. While
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`15 the combination of everolimus and octreotide --"
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`16 Q. Thank you, sir.
`
`17 A. "-- resulted in a tumor volume of 130
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`18 cubic millimeters plus or minus 75 cubic
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`19 millimeters."
`
`20 Q. Thank you, sir.
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`21 So in this passage that you just read, you
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`22 stated that tumor cell growth was 63.3 percent of
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`23 the control with everolimus alone. Would you agree
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`24 with that statement, sir, which relates to the
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`25 original question that was outstanding?
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`Dr. Howard A. Burris, III
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`17
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` 1 MS. JACOBSEN: Objection to form.
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` 2 A. I agree with that statement that I read
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` 3 there, yes.
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` 4 Q. Okay. Thank you, sir.
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` 5 So let's go back to page 15 of the
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` 6 Weckbecker reference.
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` 7 A. Okay.
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` 8 Q. And do you see the in vitro results,
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` 9 octreotide plus compound B?
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`10 A. Yes.
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`11 Q. And do you see, sir, that the
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`12 concentrations of octreotide and compound B are at
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`13 1.2 and 12 nanomolar respectively?
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`14 A. Yes, I do.
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`15 Q. And do you see that the cell growth delta
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`16 OD percent is 103, plus or minus 5 percent, sir?
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`17 A. Yes, I do see that.
`
`18 Q. Thank you.
`
`19 And if you go up to this top paragraph,
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`20 Weckbecker here -- do you see the sentence where it
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`21 says "Chou and Talalay," and then it goes on to the
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`22 next line, it says, "if the measured cell growth"?
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`23 A. If -- correct, I see that sentence.
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`24 Q. Okay. Thank you.
`
`25 And it says, "if the measured cell growth,
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`Dr. Howard A. Burris, III
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`18
`
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` 1 percent of control, is less than to the calculated
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` 2 cell growth, this shows evidence for a synergistic
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` 3 effect."
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` 4 Do you see that, Doctor?
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` 5 A. Yes, I do.
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` 6 Q. Okay. And if you go to the next
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` 7 paragraph, they refer to in this assay -- and I'm
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` 8 quoting -- "the following results are obtained with
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` 9 octreotide alone, compound B alone, and a
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`10 combination of octreotide and compound B."
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`11 Do you see that, Doctor?
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`12 A. Yes, I do.
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`13 Q. And do you see where it says, "the synergy
`
`14 according to the Webb method is confirmed by using
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`15 the Chou-Talalay method"?
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`16 A. Yes, I do see that.
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`17 Q. So then you would agree that Weckbecker
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`18 here states that the combination of everolimus and
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`19 octreotide at the stated concentrations against
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`20 this in vitro solid pancreatic cell tumor line
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`21 exhibits synergy?
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`22 MS. JACOBSEN: Objection to form.
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`23 A. The data in this chart and the calculated
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`24 method utilized demonstrate mathematically that the
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`25 two drugs together are better than either drug
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`19
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` 1 alone.
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` 2 But there's a number of factors that could
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` 3 enter in this to why that sort of effect would take
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` 4 place.
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` 5 Q. Sure. Sure. Understood. Thank you,
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` 6 Doctor.
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` 7 So in the bottom of the page here, where
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` 8 it refers to the in vivo assay --
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` 9 A. Yes.
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`10 Q. Do you see that, sir?
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`11 A. Yes, I do.
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`12 Q. So again, Weckbecker is using this same
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`13 pancreatic tumor cell line, the AR42J?
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`14 A. Yes.
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`15 Q. And you see that, if you would please turn
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`16 to page 16, where they identify that they inject
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`17 the cell lines -- or this cell line, pardon -- into
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`18 the female nude mice nu/nu Balbc-A.
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`19 Do you see that, sir?
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`20 A. Yes, I do see that.
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`21 Q. Then it refers to the cages -- they talk
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`22 about the experiment. I just want to go through
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`23 this with you, sir, to make sure that we're on the
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`24 same page.
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`25 It says, "the cages are placed in
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`20
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` 1 ventilated cabinets that are maintained at a
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` 2 certain temperature, and the animals have free
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` 3 access to drinking water," and it says, "to
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` 4 initiate tumors" -- do you see that, sir, from
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` 5 cultured cells?
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` 6 A. Yes.
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` 7 Q. It says, "AR42J cells are trypsinized and
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` 8 ten times ten to the sixth tumor cells (in 0.2
`
` 9 mils) are injected subcutaneously into both flanks
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`10 of nude mice."
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`11 Do you see that, sir?
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`12 A. Yes, I do.
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`13 Q. And it says, further, "when tumors have
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`14 reached a volume of .03 centimeters cubed, animals
`
`15 are randomized into control and treatment groups."
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`16 And do you understand, sir, that .03
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`17 centimeters cubed is 30 millimeters cubed?
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`18 A. Yes, I do.
`
`19 Q. Thank you.
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`20 And it says here that "control animals
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`21 receive placebo. Animals are treated as indicated
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`22 below for three weeks with single agents or the
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`23 drug combination."
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`24 Do you see that, sir?
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`25 A. Yes, I do.
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`21
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` 1 Q. And it refers to "the somatostatin analog
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` 2 is given as a single injection of a slow release
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` 3 form at 30 mg per kilogram subcutaneous."
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` 4 Do you see that, sir?
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` 5 A. Yes, I do.
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` 6 Q. And it further says, "the size of the
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` 7 tumors is determined with a caliper. To calculate
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` 8 the tumor volume in mils" -- which of course is the
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` 9 same thing as cubic centimeters, correct?
`
`10 A. Correct.
`
`11 Q. Thank you.
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`12 Then, "the equation 'volume" -- and that's
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`13 in quotes -- "(ellipsoid) equal length times depth
`
`14 times height times .52' was used."
`
`15 And you see that, sir?
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`16 A. Yes, I do.
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`17 Q. All right. So I apologize for doing that.
`
`18 I just wanted to make sure that we understood what
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`19 type of experiment was performed here.
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`20 So we have two different groups: We have
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`21 a treatment group and we have a control group.
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`22 Correct?
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`23 MS. JACOBSEN: Objection to form.
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`24 A. Correct.
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`25 Q. Okay. And so in the control group they
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`Dr. Howard A. Burris, III
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`22
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` 1 receive a placebo, correct?
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` 2 A. Correct.
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` 3 Q. And then for -- we have four different --
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` 4 pardon me, five different experiments that are
`
` 5 identified as A, which is compound B; B, which is
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` 6 rapamycin; C, which is octreotide pamoate.
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` 7 Do you see those, sir?
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` 8 A. Yes, I do.
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` 9 Q. Okay. And so on the next page, or page
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`10 17, do you see where it says "compound B plus
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`11 octreotide, C." So -- do you see that, sir?
`
`12 A. Yes, I do.
`
`13 Q. And do you understand that to be that both
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`14 compound B and octreotide pamoate were administered
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`15 to the mice that were referred to?
`
`16 A. Yes, I do.
`
`17 Q. Thank you, sir.
`
`18 And then finally, there's a rapamycin plus
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`19 octreotide. So you would agree, then, that in both
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`20 of these two examples -- meaning the examples at
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`21 the top of page 17: The compound B plus
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`22 octreotide, and then the rapamycin plus octreotide
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`23 -- those are the combination experiments, correct?
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`24 A. Yes.
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`25 Q. Okay. So then Weckbecker identifies tumor
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`Dr. Howard A. Burris, III
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`23
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` 1 volumes, ones that they were measured with the
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` 2 caliper. And you see that there is control value
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` 3 of 4,020, and then on the right-hand side it has
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` 4 SE.
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` 5 Do you understand that to be the standard
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` 6 error, sir?
`
` 7 A. Yes, I do.
`
` 8 Q. Okay. And, Doctor, did you consult with
`
` 9 Novartis at the time this publication was prepared,
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`10 1997?
`
`11 A. In 1997 I don't believe I had any ongoing
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`12 consultation with Novartis.
`
`13 Q. So prior to this proceeding or -- you
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`14 know, let's say prior to 2001, you weren't aware of
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`15 this data; would that be a fair assessment, sir?
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`16 A. I don't know that I could say that for a
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`17 fact. I had done some work with octreotide during
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`18 the '90s.
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`19 Q. Okay.
`
`20 A. During the time when Novartis was known as
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`21 Sandoz and other companies, before it became known
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`22 as Novartis.
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`23 Q. Okay.
`
`24 A. But I don't remember being familiar with
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`25 this information.
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`24
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` 1 Q. Okay. Fair enough. Thank you, sir.
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` 2 And so I would refer to your declaration
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` 3 again. Let's set Weckbecker aside. And this is on
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` 4 page 88. And you've identified what we referred to
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` 5 on pages 16, 17, the treatment groups and the
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` 6 control groups. And then you've identified the
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` 7 tumor volumes in cubic millimeters, and then you've
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` 8 identified the standard errors.
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` 9 A. Correct.
`
`10 Q. And I see that you've added here what's
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`11 commonly referred to as tumor volume range. And I
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`12 don't see that you explained what that means in
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`13 your declaration, sir.
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`14 Can you please explain what that means?
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`15 A. So the tumor volume range is taking the
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`16 tumor volume -- for example, the control at 4,020,
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`17 and with the standard error ranging at 579 cubic
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`18 millimeters, subtracted 579 from 4,020 and added
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`19 579 to 4,020 to get the potential range that could
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`20 have occurred.
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`21 Q. I see. So this range is not in
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`22 Weckbecker; this is a range that you calculated and
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`23 included in your declaration, correct?
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`24 MS. JACOBSEN: Objection. Form.
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`25 A. Well, it's -- the data to create this
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`Dr. Howard A. Burris, III
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`25
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` 1 table is contained in Weckbecker. One would
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` 2 understand that that's how that would be
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` 3 calculated.
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` 4 Q. Okay. So -- but I don't see that you've,
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` 5 in your table here, identified the percent
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` 6 shrinkage of the tumors for each of the control
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` 7 everolimus group, rapamycin, octreotide, everolimus
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` 8 plus octreotide, and rapamycin plus octreotide.
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` 9 MS. JACOBSEN: Objection to form.
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`10 A. So the -- I just took the data -- directly
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`11 extrapolating from the data that was available in
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`12 Weckbecker to look at how the standard errors would
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`13 affect the tumor volume. And then with the graphic
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`14 shown on the top of page 89 demonstrating the
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`15 overlapping confidence intervals or standard of
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`16 error bars for the various combinations and the
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`17 single agents.
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`18 Q. And so you actually haven't calculated the
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`19 percent shrinkage for each of the treatment groups
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`20 from Weckbecker, have you?
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`21 MS. JACOBSEN: Objection to form.
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`22 A. No, I have not made that calculation.
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`23 Q. Okay. Sir, I have.
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`24 MR. EVANS: And I would like to mark as
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`25 Petitioner's Exhibit 1021 -- I'm going to hand this
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`Dr. Howard A. Burris, III
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`26
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` 1 out, and please bear with me while I make sure I
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` 2 have the --
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` 3 MS. JACOBSEN: What is this being marked,
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` 4 1021?
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` 5 MR. EVANS: One moment, please. I'm
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` 6 looking for the -- sorry, 1121.
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` 7 (EXHIBIT NO. 1121, summary of results
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` 8 of Weckbecker in vivo assay, was marked for
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` 9 identification and attached hereto.)
`
`10 A. Yes.
`
`11 BY MR. EVANS:
`
`12 Q. Thank you, sir.
`
`13
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