Richard Dorin, M.D.
`
` 1 UNITED STATES PATENT AND TRADEMARK OFFICE
`
` 2 BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
` 3 --------------------------------
`
` 4 AMERIGEN PHARMACEUTICALS LIMITED,
`
` 5 ARGENTUM PHARMACEUTICALS LLC,
`
` 6 Petitioner
`
` 7 v.
`
` 8 JANSSEN ONCOLOGY, INC.
`
` 9 Patent Owner
`
` 10 --------------------------------
`
` 11 Case IPR2016-00286
`
` 12 Patent No. 8,822,438 B2
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` 13 --------------------------------
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` 14
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` 15 VIDEO DEPOSITION OF RICHARD DORIN, M.D.
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` 16
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` 17 Akin Gump Strauss Hauer & Feld, LLP
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` 18 Robert E. Strauss Building
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` 19 1333 New Hampshire Avenue NW
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` 20 Washington, DC 20036
`
` 21 January 19, 2017 9:00 a.m.
`
` 22 Denise D. Vickery, CRR/RMR
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` 23 GOLKOW TECHNOLOGIES, INC.
`
` 877.370.3377 ph | 917.591.5672 fax
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` 24 deps@golkow.com
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`Golkow Technologies, Inc.
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`Page 1 (1)
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`JANSSEN EXHIBIT 2125
`Mylan v. Janssen IPR2016-01332
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`

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`Richard Dorin, M.D.
`Page 2
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`Page 4
` 1 PREVIOUSLY MARKED EXHIBITS REFERENCED
` 2 AMERIGEN 1156 Deletion of a 70
` 3 Phenylalanine in the N-terminal Region of Human
` 4 Cytochrome P-45017a Results in Partial Combined
` 5 17a-Hydroxylase/17,20-Lyase Deficiency,
` 6 Yanase et al.
` 7 AMERIGEN 1027 Two Prevalent CYP17 71
` 8 Mutations and Genotype-Phenotype Correlations
` 9 in 24 Brazilian Patients with 17-Hydroxylase
`10 Deficiency, Costa-Santos et al.
`11 AMERIGEN 1167 Short Reports: 74
`12 Female phenotype in a male child due to
`13 17-a-hydroxylase deficiency
`14 AMERIGEN 1179 A Novel Point Mutation in 76
`15 P450c17 (CYP17) Causing Combined
`16 17a-Hydroxylase/17,20-Lyase Deficiency,
`17 Brooke et al.
`18 AMERIGEN 1155 Differential Inhibition of
`19 17a-Hydroxylase and 17,20-Lyase Activities by
`20 Three Novel Missense CYP17 Mutations Identified
`21 in Patients with P450c17 Deficiency,
`22 Van Den Akker et al.
`
` 1 A P P E A R A N C E S
` 2
` 3 Attorneys for Petitioner:
` 4 McNEELY, HARE & WAR LLP
` 5 5335 Wisconsin Avenue NW
` 6 Suite 440
` 7 Washington, DC 20015
` 8 202.640.1801
` 9 BY: WILLIAM HARE, ESQ.
`10 bill@miplaw.com
`11
`
`12
`13 Attorneys for Patent Owner:
`14 SIDLEY AUSTIN LLP
`15 787 Seventh Avenue
`16 New York, NY 10019
`17 212.839.5696
`18 BY: TODD L. KRAUSE, ESQ.
`19 tkrause@sidley.com
`20
`
`21
`22 Also Present:
`23 Michael Gay, Videographer
`24
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`Page 3
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` 1 I N D E X
` 2 EXAMINATION OF
` 3 RICHARD DORIN, M.D. PAGE
` 4 BY MR. KRAUSE 7
` 5 AFTERNOON SESSION 95
` 6 BY MR. HARE 114
` 7 E X H I B I T S
` 8 PREVIOUSLY MARKED EXHIBITS REFERENCED
` 9 AMERIGEN 1093 Declaration of 9
`10 Dr. Richard I. Dorin
`11 AMERIGEN 1023 Selective blockade of 41
`12 androgenic steroid synthesis by novel lyase
`13 inhibitors as a therapeutic strategy for
`14 treating metastatic prostate cancer,
`15 Attard et al.
`16 AMERIGEN 1005 U.S. Patent No. 5,604,213 41
`17 Barrie et al.
`18 AMERIGEN 1003 Hormonal impact of the 55
`19 17a-hydroxylase/C17,20-lyase inhibitor
`20 abiraterone acetate (CB7630) in patients with
`21 prostate cancer, O'Donnell et al.
`22 AMERIGEN 1154 17a-Hydroxylase/17,20-Lyase 66
`23 Deficiency: From Clinical Investigation to
`24 Molecular Definition, Yanase et al.
`
`23
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`24
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`Page 5
` 1 PREVIOUSLY MARKED EXHIBITS REFERENCED
` 2 AMERIGEN 1173 Use of Prednisone With 104
` 3 Abiraterone Acetate in Metastatic
` 4 Castration-Resistant Prostate Cancer,
` 5 Auchus et al.
` 6 JANSSEN 2014 Phase 1 Clinical Trial 105
` 7 of a Selective Inhibitor of CYP17, Abiraterone
` 8 Acetate, Confirms that Castration-Resistant
` 9 Prostate Cancer Commonly Remains Hormone Drive,
`10 Attard et al.
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`11
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`12
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`13
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`14
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`15
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`16
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`17
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`18
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`19
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`20
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`21
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`22
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`23
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`24
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`Richard Dorin, M.D.
`Page 6
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`Page 8
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` 1 P R O C E E D I N G S
` 2 - - -
` 3 THE VIDEOGRAPHER: We are on the
` 4 record. The time is 9:00 o'clock.
` 5 This marks the beginning of disk
` 6 No. 1 for the videotaped deposition
` 7 testimony of Richard Dorin in the matter
` 8 of Amerigen Pharmaceuticals Limited
` 9 versus Janssen Oncology, Inc. This case
`10 is pending in the United States Patent
`11 and Trademark Office, Case No. IPR
`12 2016-00286.
`13 Today's date is January 19, 2017.
`14 This deposition is being conducted at
`15 1333 New Hampshire Avenue, Northwest,
`16 Washington, DC.
`17 Will all attorneys present please
`18 identify themselves and who they
`19 represent.
`20 MR. KRAUSE: Todd Krause of
`21 Sidley Austin here representing Patent
`22 Owner Janssen.
`23 MR. HARE: I'm Bill Hare,
`24 McNeely, Hare & War representing
`
`Page 7
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` 1 Amerigen.
` 2 THE VIDEOGRAPHER: My name is
` 3 Michael Gay. I'm with Golkow
` 4 Technologies. Our court reporter today
` 5 is Denise Vickery also with Golkow
` 6 Technologies and will now swear in our
` 7 witness.
` 8 - - -
` 9 RICHARD DORIN, M.D.,
`10 called for examination, and, after having been
`11 duly sworn, was examined and testified as
`12 follows:
`13 EXAMINATION
`14 THE VIDEOGRAPHER: You may
`15 proceed.
`16 BY MR. KRAUSE:
`17 Q. Good morning, Dr. Dorin. Can you
`18 please state your name and home address for the
`19 record?
`20 A. Richard Ira Dorin.
`21 Q. Have you ever -- I'm sorry?
`22 A. 2526 Elfego Road -- one word --
`23 E-l-f-e-g-o Road, Northwest, Albuquerque, New
`24 Mexico.
`
` 1 Q. Have you ever been deposed
` 2 before?
` 3 A. I have never been deposed before.
` 4 Q. There are a few points that I'd
` 5 like to review before we get started.
` 6 If I ask a question that's not
` 7 clear or you don't hear me, please let me know
` 8 so I can ask the question again. If you answer,
` 9 I'll assume that you understand and heard my
`10 question. Okay?
`11 A. Yes.
`12 Q. And we have a court reporter
`13 taking down your answers to my questions. So
`14 please try to give verbal answers to my
`15 questions. Okay?
`16 A. Yes.
`17 Q. And we'll try to take breaks
`18 about every hour or so, but please let me know
`19 if you need a break.
`20 A. Thank you.
`21 Q. I'll finish whatever question I'm
`22 asking and then we can take a break. Okay?
`23 A. Great.
`24 Q. Is there any reason you cannot
`
`Page 9
` 1 give complete and accurate testimony here today?
` 2 A. No.
` 3 Q. (Handing document).
` 4 A. Thank you.
` 5 MR. HARE: Thank you.
` 6 MR. KRAUSE: Certainly.
` 7 BY MR. KRAUSE:
` 8 Q. Dr. Dorin, I've handed you a
` 9 document that's been marked Amerigen Exhibit
`10 1093.
`11 Is this your declaration?
`12 A. It is.
`13 Q. And is the declaration an
`14 accurate statement of the opinions that you've
`15 reached in this case?
`16 A. Yes.
`17 Q. And are there any errors in the
`18 declaration or the exhibits that you're aware
`19 of?
`20 A. No.
`21 Q. When were you first asked to
`22 provide opinions on the subject matter in your
`23 declaration?
`24 A. I think in November of 2016.
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`Richard Dorin, M.D.
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` 1 Q. And around that time is that when
` 2 you began working on the opinions that you have
` 3 expressed in your declaration?
` 4 A. Yes.
` 5 Q. And how many hours did you spend
` 6 working on the opinions that you've expressed in
` 7 your declaration?
` 8 A. Oh, perhaps 40 hours.
` 9 Q. How did you gather the
`10 information that you relied on in your
`11 declaration?
`12 A. I -- I reviewed Dr. Auchus's
`13 statement, and I searched the literature that I
`14 thought was relevant in the usual fashion
`15 through PubMed and references in the articles I
`16 had read and looked at all the primary
`17 literature.
`18 Q. And about how many -- how much
`19 time did you spend searching the literature?
`20 A. Long time.
`21 Q. Can you give me a ballpark in
`22 hours?
`23 A. 20 or 30 hours.
`24 Q. And do you recall what topics you
`
`Page 12
` 1 A. Again, I'll give you a number of
` 2 like 20 or 30 hours, but it's quite -- quite an
` 3 intense area to explore, yes.
` 4 Q. And did you thoroughly read each
` 5 reference cover to cover?
` 6 A. Yes.
` 7 Q. Now, did you speak with anyone
` 8 other than Petitioner's counsel in preparing the
` 9 opinions that you've expressed in your
`10 declaration?
`11 A. I'm not sure what you mean speak
`12 to someone.
`13 Q. Well, did you -- did you talk to
`14 anybody other than Petitioner's counsel in
`15 preparing -- in trying to understand the
`16 information or come to the opinions that you've
`17 expressed in your declaration?
`18 Did you ask colleagues, for
`19 example? Did you talk to other experts in this
`20 case?
`21 A. Not about the endocrine aspects.
`22 I did talk to oncologists and urologists.
`23 Q. And about how many oncologists
`24 did you speak with?
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`Page 11
` 1 searched in PubMed when you were trying to get
` 2 an understanding of the literature?
` 3 A. Yes. A variety of topics, but
` 4 including the syndrome of
` 5 17-hydroxylase/17,20-lyase deficiency, the topic
` 6 of prostate cancer, some of the treatments for
` 7 prostate cancer, and of course specifically any
` 8 papers related to abiraterone, both basic
` 9 science and clinical science related to
`10 abiraterone and including the original as well
`11 as current literature.
`12 Q. Were you provided any references
`13 that are cited in your declaration?
`14 A. I was given the references that
`15 were already submitted in -- I guess in previous
`16 depositions. So whatever was in your files
`17 already I was given.
`18 Q. And so did you identify on your
`19 own all of the other references that are cited
`20 in your declaration?
`21 A. Correct.
`22 Q. How much time did you spend
`23 reading the information that's cited in your
`24 declaration?
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`Page 13
`
` 1 A. One.
` 2 Q. And who was that?
` 3 A. Dr. James Lin at my institution,
` 4 the Albuquerque VA Medical Center.
` 5 Q. Okay. And what did Dr. Lin tell
` 6 you?
` 7 A. He told me that they used the
` 8 drug abiraterone in the setting of metastatic
` 9 castration-resistant prostate cancer.
`10 Q. Did he tell you anything else?
`11 A. I really wanted to understand
`12 what they took from the endocrinology and how
`13 sophisticated they were about what the drug
`14 does, and I can tell you my conclusion about
`15 that if you'd like.
`16 Q. Yes.
`17 A. That they're not so
`18 sophisticated. They -- they think of it as
`19 something that blocks cortisol and, therefore,
`20 prednisone is prescribed with it.
`21 Q. Okay. Did Dr. Lin tell you
`22 anything else?
`23 A. No, that was the gist of it.
`24 Q. And I believe you said you also
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`Richard Dorin, M.D.
`Page 14
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` 1 spoke to a urologist?
` 2 A. Yes.
` 3 Q. And who was that?
` 4 A. Dr. Anthony Smith.
` 5 Q. And what did Dr. Smith tell you?
` 6 A. He told me about the life of
` 7 patients who have a diagnosis of metastatic
` 8 castration-resistant prostate cancer.
` 9 Q. And what do you mean telling you
`10 about the life of those patients?
`11 A. What happens between the time of
`12 diagnosis and the time that they die in the
`13 course of a typical patient's life, what they
`14 experience and what sort of complications are
`15 encountered.
`16 Q. And can you tell me what you
`17 recall about what he told you with respect to
`18 those activities?
`19 A. Well, it's -- I came away with
`20 the impression that it's a very unpleasant
`21 wrap-up to a life and that there can be a lot of
`22 bone pain, and there can be complications of
`23 urinary obstruction, and there can be
`24 complications of infectious problems and that
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`Page 15
` 1 problems of -- we use the word inanition
` 2 sometimes. So wasting away due to lack of
` 3 appetite and weight loss are common in the
` 4 course of this disease.
` 5 Q. Anything else?
` 6 A. No.
` 7 Q. And did you speak with anybody
` 8 other than Drs. Lin and Smith in preparing the
` 9 opinions that you've expressed in your
`10 declaration?
`11 A. No.
`12 Q. And you didn't disclose the fact
`13 that you had conversations with Drs. Lin and
`14 Smith in your declaration, did you?
`15 A. I did not. They were informal.
`16 Q. How did you prepare your
`17 declaration?
`18 MR. HARE: And I'll object to the
`19 extent that you shouldn't give, you know,
`20 attorney-client communications. You
`21 can't disclose that, but you can answer
`22 other than that.
`23 THE WITNESS: Okay. I prepared
`24 it in the same way that I would prepare a
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`Page 16
` 1 manuscript of data. So I analyzed the
` 2 data and then wrote it up and edited what
` 3 I wrote and came up with a final
` 4 declaration. I -- I focused the
` 5 declaration on the statement of
` 6 Dr. Auchus.
` 7 BY MR. KRAUSE:
` 8 Q. Okay. So you actually put pen to
` 9 paper or fingers to the -- to the keyboard in
`10 typing it up then; is that correct?
`11 A. Oh, yes.
`12 Q. About how many hours did you
`13 spend drafting your declaration?
`14 A. Around 12 hours.
`15 Q. And about how many hours did you
`16 spend editing your declaration?
`17 A. 12 hours.
`18 Q. And when was your declaration
`19 completed?
`20 A. Same day you received it.
`21 January 16, 2017.
`22 Q. Okay. If I could ask you to turn
`23 to paragraph 7 of your declaration.
`24 Are you with me?
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`Page 17
`
` 1 A. Yes.
` 2 Q. Okay. In paragraph 7, you
` 3 indicate that you relied on your knowledge,
` 4 training, expertise, and the documents cited in
` 5 the declaration, as well as materials discussed
` 6 in the Auchus declaration; is that correct?
` 7 A. Yes.
` 8 Q. Did you rely on any other
` 9 materials?
`10 A. There's -- there's a body of
`11 literature that I'm familiar with through my
`12 research and teaching and that sort of general
`13 information was applied, of course.
`14 Q. Okay. And did you review all of
`15 the materials that were cited by Dr. Auchus?
`16 A. Yes.
`17 Q. And about how much time did you
`18 spend doing that?
`19 A. I'm going to estimate --
`20 Q. Sure.
`21 A. -- at 12 hours.
`22 Q. Okay. If I could ask you to turn
`23 to page 48 of your declaration. The page is
`24 headed "Attachment A, Reference List."
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`Richard Dorin, M.D.
`Page 18
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`Page 20
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` 1 A. Yes.
` 2 Q. Did you rely on all of these
` 3 documents in formulating the opinions that
` 4 you've expressed in your declaration?
` 5 A. (Witness reviewing document).
` 6 Yes.
` 7 Q. And many of these publications
` 8 were published after August 25th of 2006;
` 9 correct?
`10 A. No.
`11 Q. Well, reference number 1 is
`12 published after 2006; correct?
`13 A. See, I was quite selective in the
`14 literature I included in my references, and I
`15 made a point of emphasizing publications that
`16 were published before August 2006, but where I
`17 felt it was relevant, I included literature that
`18 was published after 2006.
`19 I think the majority of these
`20 articles were published before 2006, but to
`21 answer your question, yes, reference number 1
`22 was published in 2012.
`23 Q. And reference number 14 was
`24 published in 2008; right?
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`Page 19
` 1 A. Well, you have to understand that
` 2 reference number 14 is relevant only in the
` 3 definitions, and it provides a perspective of
` 4 some of the terms that are used in here. So it
` 5 really doesn't impact my decision or opinion,
` 6 but you are correct.
` 7 Reference number 14 was published
` 8 in 2008, and it has to do with a change in
` 9 terminology in the definition section of the --
`10 of the declaration.
`11 Q. Well, sir, if you could just
`12 answer the question I've asked. My question is
`13 really quite simple.
`14 Publication number 17 was
`15 published in 2017; correct?
`16 A. Correct.
`17 Q. And publication 19 was published
`18 in 2010; correct?
`19 A. Correct.
`20 Q. Publication 24 was published in
`21 2014; correct?
`22 A. Correct.
`23 Q. And publication 32 was published
`24 in 2016; isn't that right?
`
` 1 A. Correct.
` 2 Q. And is it fair to say that as a
` 3 general matter your declaration doesn't provide
` 4 point cites to the portions of the many
` 5 references that you cite in it?
` 6 A. No.
` 7 Q. Well, can you -- if we go through
` 8 it, for example, isn't it true that more often
` 9 than not references are just cited as a
`10 reference without providing a particular page
`11 number or particular paragraph?
`12 A. Oh, apparently I didn't
`13 understand your question.
`14 Q. I'm sorry.
`15 A. Yeah.
`16 Q. My question was probably unclear.
`17 Well, isn't it true that more
`18 often than not in your declaration you don't
`19 identify a specific page or particular paragraph
`20 or particular figure that you're referring to?
`21 A. When I refer to Auchus's --
`22 Dr. Auchus's declaration, I refer to paragraphs.
`23 When I thought it was important, for example, in
`24 Table 5 of the endocrine review paper
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`Page 21
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` 1 summarizing the clinical syndromes of
` 2 17-hydroxylase deficiency and combined
` 3 17,20-lyase deficiency, I cited a specific
` 4 table. But otherwise I think you're correct
` 5 that I did not give what you refer to as point
` 6 citations. It's not my custom to do so.
` 7 Q. But you would agree with me,
` 8 wouldn't you, that providing point citations
` 9 would allow the reader to get a better
`10 understanding of what in these many references
`11 you're relying on?
`12 A. No, I disagree.
`13 Q. And why is that?
`14 A. Again, it's not customary in my
`15 field to put in point citations, and I think it
`16 would -- it would probably be more cumbersome
`17 and confusing to a reader. The references are
`18 very well-documented and a reader who was going
`19 to take it to that level of detail would know
`20 where to look in the reference.
`21 Q. Can you briefly describe your
`22 college and post-baccalaureate education?
`23 A. Yes. I went to college at
`24 Wesleyan University in Middletown, Connecticut
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`Richard Dorin, M.D.
`Page 22
` 1 and I graduated there with a BA magna cum laude.
` 2 I went to UCLA School of Medicine. I did my
` 3 internal medicine residency at Santa Clara
` 4 Valley Medical Center. My endocrine fellowship
` 5 training was at Stanford University, and I did a
` 6 year of postdoctoral research at University of
` 7 Kyoto in Japan.
` 8 Q. And what was your bachelor's
` 9 degree in? What was your major?
`10 A. Biology/psychology, a combined
`11 major.
`12 Q. And what was the postdoc in?
`13 A. Molecular biology.
`14 Q. Do you have any formal training
`15 in law?
`16 A. Not a bit.
`17 Q. And can you briefly describe your
`18 work experience?
`19 A. Yes. I joined the faculty at the
`20 University of New Mexico in Albuquerque, New
`21 Mexico in January of 1988 and ran the endocrine
`22 division at the Albuquerque VA hospital for most
`23 of my career there and had a research laboratory
`24 at the Albuquerque VA as well, and I am now a
`
` 1 supervision of faculty and fellows.
` 2 Q. And what's the typical age of a
` 3 patient at the VA that you would be taking care
` 4 of? Or is there a range? How does -- if you
` 5 could tell me a little bit about that.
` 6 A. Age ranges from 26 to about 100 I
` 7 would say.
` 8 Q. Okay.
` 9 A. We don't -- we see some active
`10 duty patients at the VA because at the
`11 Albuquerque VA, the Air Force Base and the VA
`12 are combined facilities.
`13 Q. Okay. And what's the gender of
`14 the patients? Is it mixed?
`15 A. It's mixed.
`16 Q. And do you presently treat
`17 patients?
`18 A. I do.
`19 Q. And is there any specialization,
`20 any type of patient that you're more apt to see?
`21 A. I treat every endocrine
`22 condition.
`23 Q. Okay. And how often do you treat
`24 patients?
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`Page 23
` 1 professor of medicine and also biochemistry at
` 2 the University of New Mexico.
` 3 Q. And what was the focus of the
` 4 research in your research lab?
` 5 A. It was -- it was on
` 6 glucocorticoid hormone action and also the
` 7 regulation of the corticotrophin-releasing
` 8 hormone gene, but I also did quite a bit of
` 9 clinical research on the ACTH and adrenal axis.
`10 Q. So would it be fair to say that
`11 most of your research was focused on what's
`12 referred to as basic research and trying to
`13 understand the mechanisms?
`14 A. No, I think it would be better to
`15 characterize my research as basic and clinical
`16 research.
`17 Q. Okay.
`18 A. Both.
`19 Q. And what were the
`20 responsibilities of the endocrine lab or the
`21 endocrinology group that you were in?
`22 A. Providing clinical care for any
`23 endocrine issues for the patients at the VA,
`24 providing consultation service and teaching and
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`Page 25
` 1 A. How often do I have clinic?
` 2 Q. Yes, sir.
` 3 A. I have, I think, clinics six half
` 4 days a week.
` 5 Q. Okay. Have you ever treated a
` 6 patient for cancer?
` 7 A. Yes.
` 8 Q. Can you tell me about that?
` 9 A. Do you mean prostate cancer?
`10 Q. We can start with cancer
`11 generally.
`12 A. Great.
`13 Q. Treating patients for cancer.
`14 Uh-huh.
`15 A. Uh-huh. Well, there's plenty of
`16 cancers --
`17 Q. Okay.
`18 A. -- of endocrine organs. Thyroid
`19 cancer would be the most common.
`20 Q. Okay. Have you ever treated a
`21 patient for prostate cancer?
`22 A. No. I've treated patients with
`23 prostate cancer, but not for the cancer.
`24 Q. Okay. Have you ever prescribed
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`Richard Dorin, M.D.
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` 1 drugs for the treatment of prostate cancer?
` 2 A. I have not. I use some of the
` 3 same drugs for the transgender population.
` 4 Q. Can you tell me a little bit
` 5 about that?
` 6 A. So castration -- medical
` 7 castration for prostate cancer usually involves
` 8 a long-acting drug called an LHRH agonist and we
` 9 sometimes use that same drug in the same dose
`10 and same frequency for treatment of
`11 male-to-female transgenders.
`12 Q. And I believe you testified
`13 earlier that you had never been deposed before;
`14 is that correct?
`15 A. That's correct.
`16 Q. Have you ever provided any expert
`17 testimony or declarations in a legal proceeding?
`18 A. I've consulted on some legal
`19 proceedings, but they have not come to
`20 declaration or testimony.
`21 Q. So it's fair to say, isn't it,
`22 that you're not an expert in the treatment of
`23 prostate cancer?
`24 A. Oh, yes.
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`Page 27
` 1 Q. And you're not an oncologist;
` 2 correct?
` 3 A. For sure.
` 4 Q. Okay. And is it fair to say that
` 5 you have no specialized training in the
` 6 treatment of prostate cancer?
` 7 A. Yes.
` 8 Q. And do you have any publications
` 9 on prostate cancer?
`10 A. No.
`11 Q. And you're not an inventor on any
`12 patents relating to the treatment of prostate
`13 cancer?
`14 A. No.
`15 Q. And you have never prescribed
`16 abiraterone acetate?
`17 A. That's correct. I have not.
`18 Q. And you have never prescribed
`19 ketoconazole; is that correct?
`20 MR. HARE: Object. That's
`21 outside the scope of his -- ketoconazole
`22 is outside the scope of his report.
`23 THE WITNESS: Would you like me
`24 to answer?
`
` 1 BY MR. KRAUSE:
` 2 Q. I would.
` 3 A. I have prescribed ketoconazole.
` 4 Q. And what did you prescribe
` 5 ketoconazole for?
` 6 A. Systemic fungal disease.
` 7 Q. Do you have -- do you have
` 8 experience interacting with oncologists and
` 9 urologists to treat patients with prostate
`10 cancer?
`11 A. Yes.
`12 Q. Can you tell me a little bit
`13 about your experience with that?
`14 A. Well, if I see that patient and
`15 there are endocrine issues, I would talk to
`16 them. They're right down the hall from me and
`17 friends and associates, and so some of the
`18 patients that I've seen for problems other than
`19 prostate cancer have been on abiraterone
`20 acetate.
`21 You know, if there are general
`22 medical issues that come up that are relevant, I
`23 would, of course, contact a urologist if there's
`24 obstruction or some problem like that.
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` 1 Q. Okay. In your expert report, you
` 2 talk about P450c17 deficiency syndromes; is that
` 3 right?
` 4 A. Yes.
` 5 Q. Can you tell me what P450c17 is?
` 6 A. So there's a number of different
` 7 terms that are used to designate this, and the
` 8 one I've chosen here is P450c17. So that refers
` 9 to a gene that encodes the protein that for an
`10 enzyme that has two different activities,
`11 17-hydroxylase and 17,20-lyase.
`12 Q. And have you ever treated a
`13 patient with P450c17 deficiency syndrome?
`14 A. No.
`15 Q. Have you ever published on
`16 P450c17 deficiency syndrome?
`17 A. I have not.
`18 Q. And you don't have any patents
`19 related to P450c17 syndrome?
`20 A. That's correct.
`21 Q. Is it fair to say that you're not
`22 an expert in P450c17 deficiency syndromes?
`23 A. Yes.
`24 Q. Are you a principal investigator
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` 1 on any clinical trials?
` 2 A. No.
` 3 Q. And have you ever been involved
` 4 in clinical trials related to prostate cancer?
` 5 A. No.
` 6 Q. What is the HPA axis?
` 7 A. The
` 8 hypothalamic-pituitary-adrenal axis is the HPA
` 9 axis.
`10 Q. And what does it do?
`11 A. That is a system by which the
`12 brain talks to the pituitary gland and the
`13 pituitary gland communicates with the adrenal
`14 gland and the adrenal talks back to both of
`15 them.
`16 Q. And can the HPA axis be
`17 suppressed?
`18 A. Yes.
`19 Q. And how could the HPA axis be
`20 suppressed?
`21 A. A common way is by exogenous
`22 glucocorticoids at doses and durations that are
`23 sufficient to suppress corticotropin-releasing
`24 hormone and ACTH.
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`Page 31
` 1 Q. And those doses could be as low
` 2 as about 5 to 10 MGs per day; isn't that
` 3 correct?
` 4 A. Yes.
` 5 Q. And what happens when the HPA
` 6 axis is suppressed?
` 7 A. What you can measure is that ACTH
` 8 levels are decreased for any given concentration
` 9 of cortisol and that the cortisol response to
`10 ACTH is subnormal.
`11 Q. Anything else?
`12 A. No.
`13 Q. Can HPA axis suppression result
`14 in adrenal insufficiency?
`15 A. This is a slightly complicated
`16 question. So do you mean adrenal insufficiency
`17 while you're on glucocorticoids or once you stop
`18 the glucocorticoids?
`19 Q. Why don't we take it both ways.
`20 A. Uh-huh. So when you're on
`21 replacement glucocorticoids, it would be unusual
`22 to develop adrenal insufficiency.
`23 Q. And --
`24 A. And --
`
` 1 Q. Sorry.
` 2 A. And if -- if you had suppressed
` 3 the HPA axis and then stopped the exogenous
` 4 glucocorticoids, there would be a risk of
` 5 adrenal insufficiency.
` 6 Q. And can HPA axis suppression lead
` 7 to adrenal crisis?
` 8 A. In the setting of concurrent
` 9 stress, yes.
`10 Q. And is it fair to say that it was
`11 common knowledge in August of 2006 that the
`12 administration of glucocorticoids, including
`13 prednisone, had the potential to cause
`14 significant adverse effects, including the
`15 suppression of the HPA axis?
`16 A. I'm concerned about the dose and
`17 duration issue. Can you restate the question,
`18 please?
`19 Q. Well, why don't you tell me what
`20 your concern is, and then I can try to restate
`21 it to address the issue.
`22 If you have a qualifier, for
`23 example, that a long term your answer would be X
`24 or in short term it would be Y, I'd appreciate
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` 1 it.
` 2 A. So the risks of suppressing the
` 3 HPA axis depend on the dose of prednisone and
` 4 the duration of prednisone use.
` 5 Q. Okay.
` 6 A. So, and there's lots of variation
` 7 in this. So to answer your question simply,
` 8 yes, there is a chance of HPA suppression, and
` 9 that chance would be greater at a higher dose of
`10 prednisone and a longer duration of prednisone
`11 use.
`12 Q. And it's fair to say that that
`13 would have been appreciated in August of 2006?
`14 A. I would think so.
`15 Q. Would it be fair to say that if a
`16 physician was worried about physiological
`17 stress, that addressing those concerns by
`18 coadministering a glucocorticoid could
`19 potentially exacerbate the risk of adrenal
`20 crisis because of suppression of the HPA axis?
`21 A. So you're speaking generally now,
`22 not in the case of a patient treated with
`23 abiraterone acetate?
`24 Q. Yes, I'd like to start generally,
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`Page 34
` 1 and then we can talk about abiraterone acetate.
` 2 A. Uh-huh. Okay. Again, repeat the
` 3 question.
` 4 MR. KRAUSE: Could you read the
` 5 ques