`
` 1 IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
` 2 BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
` 3 **************************************
`
` 4 MYLAN PHARMACEUTICALS INCORPORATED,
`
` 5 Petitioner
`
` 6 vs.
`
` 7 JANSSEN ONCOLOGY, INC.,
`
` 8 Patent Owner
`
` 9 **************************************
`
` 10 CASE IPR2016-01332
`
` 11 U.S. Patent No. 8,822,438
`
` 12 **************************************
`
` 13
`
` 14 VIDEOTAPED DEPOSITION of MARC B. GARNICK, M.D.
`
` 15 Thursday, February 16, 2017
`
` 16
`
` 17
`
` 18 .
`
` 19
`
` 20 9:02 a.m.
`
` 21 Held at: Eliot Hotel
`
` 22 360 Commonwealth Avenue
`
` 23 Boston, Massachusetts
`
` 24 Megan M. Castro, RPR, Court Reporter
`
`Golkow Technologies, Inc.
`
`Page 1 (1)
`
`JANSSEN EXHIBIT 2126
`Mylan v. Janssen IPR2016-01332
`
`
`
`Marc B. Garnick, M.D.
`Page 2
`
`Page 4
`
` 1 APPEARANCES:
`
` 2 PERKINS COIE
`
` 3 Bryan D. Beel, Ph.D.
`
` 4 Shannon M. Bloodworth, Esquire - VIA TELECONFERENCE
`
` 5 1120 NW Couch Street
`
` 6 10th Floor
`
` 7 Portland, Oregon 97209-4128
`
` 8 503-727-2116
`
` 9 bbeel@perkinscoie.com
`
`10 sbloodworth@perkinscoie.com
`
`11 on behalf of the Petitioner
`
`12
`
`13 SIDLEY AUSTIN, LLP
`
`14 Todd L. Krause, Esquire
`
`15 787 Seventh Avenue
`
`16 New York, New York 10019
`
`17 212-839-5696
`
`18 tkrause@sidley.com
`
`19 on behalf of the Patent Owner
`
`20
`
`21
`
`22
`
`23
`
`24
`
`Page 3
` 1 APPEARING VIA TELECONFERENCE:
` 2 WINSTON & STRAWN, LLP
` 3 Ryan B. Hauer, Esquire
` 4 35 W. Wacker Drive
` 5 Chicago, Illinois 60601-9703
` 6 312-558-8116
` 7 rhauer@winston.com
` 8 on behalf of Apotex, Inc.
` 9
`10 ALSO PRESENT:
`11 Marissa DeMonte, videographer
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
` 1 I N D E X
` 2 Witness Page
` 3 MARC B. GARNICK, M.D.
` 4 Direct Examination by Mr. Krause 5
` 5
` 6 E X H I B I T S
` 7 Number Description Page
` Exhibit JSN2009 Article entitled 104
` 8 "Eligibility and
` Response Guidelines for
` 9 Phase II Clinical
` Trials in
`10 Androgen-Independent
` Prostate Cancer:
`11 Recommendations From
` the Prostrate-Specific
`12 Antigen Working Group"
` by Glenn J. Bubley, et
`13 al.
`14 Exhibit JSN2010 Declaration of Scott R. 109
` Serels, M.D.
`
`15
`
` Exhibit JSN2011 Two-page document from 184
`16 The Journal of Urology
` dated December 1991
`
`17
`18
`19
`20
`21
`22
`23
`24
`
`Page 5
`
` 1 P R O C E E D I N G S
` 2 - - -
` 3 THE VIDEOGRAPHER: We are now on the
` 4 record. My name is Marissa DeMonte, and I am a
` 5 videographer for Golkow Technologies.
` 6 Today's date is February 16, 2017, and
` 7 the time is 9:02 a.m. This video deposition is
` 8 being held in Boston, Massachusetts, in the
` 9 matter of Mylan Pharmaceuticals Incorporated
`10 versus Janssen Oncology, Inc., for the United
`11 States Patent and Trademark Office, before the
`12 Patent Trial and Appeal Board.
`13 The deponent is Marc B. Garnick, M.D.
`14 Counsel will be noted on the stenographic record.
`15 The court reporter is Megan Castro. She will now
`16 swear in the witness and we can proceed.
`17 - - -
`18 MARC B. GARNICK, M.D., first having been
`19 satisfactorily identified by the production of
`20 his driver's license and duly sworn by the Notary
`21 Public, testified under oath as follows in answer
`22 to direct examination by MR. KRAUSE:
`23 - - -
`24 Q. Good morning, sir. Can you please state
`
`Golkow Technologies, Inc.
`
`Page 2 (2 - 5)
`
`
`
`Page 8
`
`Marc B. Garnick, M.D.
`Page 6
` 1 your name and home address for the record?
` 2 A. Marc Bennett Garnick, G-A-R-N-I-C-K,
` 3 289 Marlborough Street, Boston, Massachusetts
` 4 02116.
` 5 Q. There are a few points I would like to
` 6 review before we get started. If I ask a
` 7 question that is not clear or you didn't hear me,
` 8 please let me know so I can ask the question
` 9 again. If you answer, I will assume you
`10 understood and heard my question. Okay?
`11 A. Yes.
`12 Q. And we have a court reporter taking down
`13 your answers to my questions, so please try to
`14 give verbal answers to my questions. Okay?
`15 A. Yes.
`16 Q. We will try to take breaks about every
`17 hour or so, but please let me know if you need a
`18 break, and I will finish whatever question I am
`19 on and we can take a break.
`20 Is there any reason you cannot give
`21 complete and accurate testimony here today?
`22 A. No.
`23 (Handing document to the witness.)
`24 Q. I have handed you a document that has
`
` 1 A. This basically represents the steroid
` 2 pathway from cholesterol to various other
` 3 steroids, such as cortisol, aldosterone, and the
` 4 sex steroids.
` 5 Q. And the biosynthesis of all steroids
` 6 begins with the cleavage of the side chain of
` 7 cholesterol to form pregnenolone; is that
` 8 correct?
` 9 MR. BEEL: Objection to form.
`10 A. Yes.
`11 BY MR. KRAUSE:
`12 Q. So if the conversion of cholesterol to
`13 pregnenolone is blocked, so is the biosynthesis
`14 of all the steroids; is that correct?
`15 A. It would have to be a complete block, I
`16 would assume.
`17 Q. But if one had a complete block, that
`18 would block the production of all of the steroids
`19 in the pathways; correct?
`20 MR. BEEL: Objection. Foundation.
`21 A. I would assume so.
`22 BY MR. KRAUSE:
`23 Q. Some arrows in the diagram have the word
`24 "CYP17" over them. What is CYP17?
`
`Page 7
` 1 been marked as Mylan Exhibit 1002. Is this your
` 2 declaration?
` 3 (Witness viewing document.)
` 4 A. Yes, it is.
` 5 Q. Is that your signature on the last page
` 6 of the declaration?
` 7 A. Yes, it is, page 57.
` 8 Q. Yes, sir. Thank you.
` 9 Is the declaration marked as Mylan 1002
`10 an accurate statement of the opinions that you
`11 have reached in this case?
`12 A. Yes, it is.
`13 Q. We will be talking about a person of
`14 ordinary skill in the art a lot today. When I
`15 refer to a person of ordinary skill in the art,
`16 will you understand that I am referring to a
`17 person's knowledge as of -- that person's
`18 knowledge as of August 25, 2006?
`19 A. Yes.
`20 MR. BEEL: Objection to form.
`21 BY MR. KRAUSE:
`22 Q. Please turn to the diagram following
`23 paragraph 37 in your declaration. What does this
`24 represent?
`
`Page 9
`
` 1 A. It is -- my understanding is that is an
` 2 enzyme complex that includes 17 alpha-hydroxylase
` 3 and 17,20-lyase, part of the cytochrome P450
` 4 system.
` 5 Q. Is it fair to say that these two
` 6 activities are represented in the diagram but not
` 7 specifically labeled?
` 8 A. I would assume so, yes.
` 9 Q. And paragraph 38 of your declaration
`10 notes the 17 alpha-hydroxylase activities as a
`11 hydroxyl group, OH, to pregnenolone and
`12 progesterone at carbon 17 of the steroid D ring,
`13 converting both to their 17-hydroxy forms. This
`14 is represented in the horizontal arrows between
`15 the first and second columns of the diagram; is
`16 that correct?
`17 A. Yes.
`18 Q. Can you please circle those arrows for me
`19 in your declaration and label them
`20 "17 alpha-hydroxylase"?
`21 (Witness marking document.)
`22 A. They are not on the diagram.
`23 Q. There are horizontal arrows between
`24 pregnenolone and 17-hydroxy pregnenolone, as well
`
`Golkow Technologies, Inc.
`
`Page 3 (6 - 9)
`
`
`
`Page 12
`
`Marc B. Garnick, M.D.
`Page 10
` 1 as progesterone and 17-hydroxy progesterone?
` 2 A. Correct.
` 3 Q. And don't those -- I believe you just
` 4 testified that those horizontal arrows represent
` 5 the 17 alpha-hydroxylase activity; is that
` 6 correct?
` 7 A. My understanding is that it is
` 8 incorporated into the CYP17 nomenclature,
` 9 C-Y-P 17.
`10 Q. So the activity that is being represented
`11 by those arrows is the 17 alpha-hydroxylase
`12 activity of CYP17; is that correct?
`13 A. Yes.
`14 Q. Could you circle those arrows and label
`15 them "17 alpha-hydroxylase" for me?
`16 MR. BEEL: Objection to form and
`17 foundation.
`18 A. I am not sure I understand what you want
`19 me to do.
`20 BY MR. KRAUSE:
`21 Q. I am trying to identify the activity in
`22 this diagram that is associated with the
`23 17-hydroxylase activity.
`24 A. It is incorporated into the CYP17.
`
` 1 MR. BEEL: Objection to form and
` 2 foundation.
` 3 THE WITNESS: Should I hear your
` 4 objection before I answer?
` 5 MR. BEEL: If you can pause for a second.
` 6 THE WITNESS: Okay.
` 7 BY MR. KRAUSE:
` 8 Q. And can you please label those arrows
` 9 "17,20-lyase"?
`10 MR. BEEL: Objection to form and
`11 foundation.
`12 (Witness marking document.)
`13 BY MR. KRAUSE:
`14 Q. Let's talk first about the 17-hydroxylase
`15 activity of CYP17. What does that do?
`16 A. My understanding is it adds a hydroxy
`17 group to pregnenolone.
`18 Q. So if you completely block the
`19 17-hydroxylase, you do not get any production of
`20 cortisol or testosterone; is that correct?
`21 MR. BEEL: Objection to form.
`22 A. I would assume that you have to have
`23 complete blockage to have that.
`24 BY MR. KRAUSE:
`
`Page 11
`
` 1 Q. Correct.
` 2 A. Okay.
` 3 Q. And that is represented by these
` 4 horizontal arrows between the first and second
` 5 columns in the diagram; is that correct?
` 6 A. Yes, correct.
` 7 Q. So I am simply trying to ask you --
` 8 A. Want me to put 17 alpha-hydroxylase
` 9 there?
`10 Q. Yes, sir. And just circle the arrows
`11 that are correlated with that.
`12 MR. BEEL: Objection to form and
`13 foundation.
`14 (Witness marking document.)
`15 BY MR. KRAUSE:
`16 Q. And I believe in your declaration,
`17 paragraph 38, you note that 17,20-lyase activity
`18 splits the side chain off of 17-hydroxy
`19 progesterone and 17-hydroxy pregnenolone?
`20 A. Yes.
`21 Q. This is represented by the horizontal
`22 arrows between the second and third columns of
`23 the diagram; is that correct?
`24 A. Yes.
`
`Page 13
` 1 Q. So if one has complete blockage, is it
` 2 true that you would not get any production of
` 3 cortisol and testosterone?
` 4 A. That is a question for basically an
` 5 endocrine biochemist or enzymologist. That is
` 6 not an expertise that I have, whether it is
` 7 completely blocked or incompletely blocked, to
` 8 answer your question accurately.
` 9 Q. But my question was with reference to a
`10 complete blockage. If one completely blocks that
`11 activity, that is, the 17-hydroxylase activity,
`12 one does not get any production of cortisol or
`13 testosterone; is that correct?
`14 MR. BEEL: Objection to form and
`15 foundation.
`16 A. I don't really know what you mean by
`17 "completely blocked."
`18 BY MR. KRAUSE:
`19 Q. If there is a total absence of
`20 17-hydroxylase activity, cortisol and
`21 testosterone are not produced; is that correct?
`22 MR. BEEL: Same objection.
`23 A. Of 17-hydroxylase?
`24 BY MR. KRAUSE:
`
`Golkow Technologies, Inc.
`
`Page 4 (10 - 13)
`
`
`
`Marc B. Garnick, M.D.
`Page 14
`
`Page 16
`
` 1 Q. Yes, sir.
` 2 A. I am not sure that is correct.
` 3 Q. And if you get some but not complete
` 4 blocking of 17-hydroxylase, one could get some
` 5 cortisol and testosterone, but it would be less
` 6 than if it were completely blocked; is that
` 7 correct?
` 8 A. You are asking questions that are really
` 9 better addressed to a steroid biochemist or a
`10 steroid enzymologist, in terms of the degree of
`11 blockage, complete blockage versus incomplete
`12 blockage. I am not really equipped to answer
`13 those questions because I really don't know what
`14 complete "blockage means" and what "incomplete
`15 blockage" means.
`16 Q. Okay. Now let's talk about 17,20-lyase
`17 activity. What does 17,20-lyase do?
`18 MR. BEEL: Objection. Foundation.
`19 A. My understanding is that it basically is
`20 involved in the pathway going to the sex
`21 steroids.
`22 BY MR. KRAUSE:
`23 Q. And if one completely blocks the
`24 17,20-lyase activity, no testosterone is
`
`Page 15
` 1 produced, but cortisol could be produced; is that
` 2 correct?
` 3 MR. BEEL: Objection to form and
` 4 foundation.
` 5 A. That would be incorrect because
` 6 testosterone is produced other places as well.
` 7 BY MR. KRAUSE:
` 8 Q. Well, with respect to the pathway that we
` 9 have in front of us, isn't it true that if
`10 one blocks the 17,20-lyase activity, the
`11 production of testosterone would be blocked?
`12 A. I guess my best answer to that question
`13 is you are asking terms that I am really not
`14 terribly familiar with. When you say "complete
`15 block," "incomplete block," those questions are
`16 really better addressed to an enzymologist.
`17 Q. So is it fair to say you don't know the
`18 answer to those questions?
`19 A. I don't know what the term "blockage"
`20 means. In strict enzymology, I don't understand
`21 what that term means, complete versus incomplete
`22 blockage.
`23 Q. Okay. The diagram also has the word
`24 "CYP11B1" near a couple of arrows. What is that?
`
` 1 MR. BEEL: Objection to form.
` 2 A. That is another enzyme involved in
` 3 steroid synthesis.
` 4 BY MR. KRAUSE:
` 5 Q. What does that do?
` 6 MR. BEEL: Objection. Foundation.
` 7 A. It takes it from DOC to corticosterone,
` 8 from deoxy-corticosterone to corticosterone.
` 9 BY MR. KRAUSE:
`10 Q. So is it true that if there is no
`11 11-beta-hydroxylase activity, cortisol would not
`12 be produced?
`13 MR. BEEL: Objection to form and
`14 foundation.
`15 A. My answer is the same answer that I have
`16 given you previously to the other quantitative
`17 analyses of blockage or inhibition.
`18 BY MR. KRAUSE:
`19 Q. So is it your testimony that you have no
`20 opinion with respect to a relative degree of
`21 blockage of any of the enzymatic activities
`22 represented on this diagram?
`23 MR. BEEL: Objection to form.
`24 A. I definitely have opinions on that.
`
`Page 17
`
` 1 BY MR. KRAUSE:
` 2 Q. Well, what are your views with respect to
` 3 the relative degrees of blockage and the
` 4 potential production of steroids in light of
` 5 those relative degrees?
` 6 A. So I have been asked to be an expert
` 7 on -- and provide expert testimony on this
` 8 related to the clinical understanding of the way
` 9 in which pharmaceuticals are utilized in the
`10 management of patients with prostate cancer that
`11 affects steroid synthesis and sex steroid
`12 synthesis.
`13 So my opinions on agents that block
`14 either 17-hydroxylase activity or 17,20-lyase
`15 activity are agents which are commonly used --
`16 which I commonly use in my day-to-day practice of
`17 medicine, and the sequelae of those activities of
`18 these particular enzymes relate -- result in
`19 clinical activities and clinical sequelae that I
`20 understand and treat.
`21 So that is my understanding of the
`22 opinions. I am not an expert in providing for
`23 you specific enzymatic characteristics,
`24 equilibrium characteristics. That would be
`
`Golkow Technologies, Inc.
`
`Page 5 (14 - 17)
`
`
`
`Marc B. Garnick, M.D.
`Page 18
` 1 better suited for a biochemical enzymologist.
` 2 Q. In your answer, you just referred to
` 3 block. What degree of blockage were you
` 4 referring to?
` 5 A. If I said "block," I meant inhibition or
` 6 anything that decreases the production of
` 7 cortisol, mineralocorticoids, or sex steroids.
` 8 Q. So what degree of inhibition are you
` 9 referring to?
`10 A. Inhibition that results in a clinical
`11 result or a clinical sequelae. And,
`12 quantitatively, I can't tell you that, the degree
`13 of that inhibition.
`14 Q. But there could be different degrees of
`15 inhibition; is that fair to say?
`16 A. I would say so, yes.
`17 Q. But you are not prepared to discuss any
`18 particular degree of inhibition?
`19 A. I am not qualified to discuss the degree
`20 of inhibition.
`21 Q. Is it fair to say that the steroids
`22 synthesis pathway is very complex?
`23 MR. BEEL: Objection to form.
`24 A. That is an unanswerable question.
`
`Page 20
` 1 Q. And the inhibition of different enzymes
` 2 in the pathways can affect the production of
` 3 different reaction products downstream; is that
` 4 correct?
` 5 A. In general, yes.
` 6 Q. And the action of any given enzyme in the
` 7 pathways can be affected by other enzymes and
` 8 components in the pathways?
` 9 A. Yes. In general, yes.
`10 Q. And the pathways and the effects of
`11 enzyme inhibition can also be affected by the
`12 expression and inactivity of individual enzymes
`13 as well as by environmental factors, which can
`14 vary between individuals; is that correct?
`15 MR. BEEL: Objection to form, foundation.
`16 A. That is an all-encompassing question. I
`17 didn't get all of the details of the question.
`18 BY MR. KRAUSE:
`19 Q. Sure. I will be happy to ask it again.
`20 Isn't it true that the pathways and
`21 effects of enzyme inhibition can also be affected
`22 by the expression and activity of individual
`23 enzymes as well as environmental factors, which
`24 can vary between individuals?
`
`Page 19
`
`Page 21
`
` 1 BY MR. KRAUSE:
` 2 Q. Why?
` 3 A. Well, if you were a steroid biochemist
` 4 and studied enzyme machinology -- mechanisms,
` 5 that would probably be something that is
` 6 understandable and something that someone does.
` 7 The word "complex" is a very far-reaching and
` 8 all-encompassing word.
` 9 Q. Would a POSA view the steroid synthesis
`10 pathway as complex?
`11 MR. KRAUSE: Sorry. Strike that.
`12 BY MR. KRAUSE:
`13 Q. Would a person of ordinary skill in the
`14 art view the steroid synthesis pathway as very
`15 complex?
`16 MR. BEEL: Objection to form.
`17 A. Qualitatively, yes. Quantitatively,
`18 probably not.
`19 BY MR. KRAUSE:
`20 Q. And is it true that enzymes operate at
`21 various steps in the biochemical pathways to
`22 regulate the step-by-step biosynthesis of
`23 steroids?
`24 A. In general, yes.
`
` 1 MR. BEEL: Objection to form and
` 2 foundation.
` 3 A. Again, I can't answer that question
` 4 because I don't know what you mean by
` 5 "environmental factors."
` 6 BY MR. KRAUSE:
` 7 Q. Well, isn't it true that environmental --
` 8 that drugs or other agents in the environment can
` 9 impact enzymatic activity?
`10 A. Again, I can't answer your question
`11 because when you say drugs or other factors in
`12 the environment, you would have to be more
`13 specific. Clearly, if a patient is taking
`14 another drug -- preferably, it wasn't in the
`15 environment but it was given as a pharmaceutical,
`16 as a pharmaceutical to the patient -- that could
`17 potentially influence these things.
`18 Q. Can diet affect enzymatic activity?
`19 MR. BEEL: Objection to form and
`20 formation.
`21 A. I think I would have to know the
`22 particular component of the diet that you are
`23 referring to.
`24 BY MR. KRAUSE:
`
`Golkow Technologies, Inc.
`
`Page 6 (18 - 21)
`
`
`
`Page 24
`
`Marc B. Garnick, M.D.
`Page 22
` 1 Q. In general, to your knowledge, can diet
` 2 in any way affect enzymatic activity?
` 3 MR. BEEL: Objection to form.
` 4 A. In the case of abiraterone, for example,
` 5 my assumption is that the enzymatic activity is
` 6 influenced by food because there is strict
` 7 instructions that the drug should be taken on an
` 8 empty stomach.
` 9 So under those circumstances, given the
`10 activity of abiraterone clinically, my
`11 understanding is that the activity is definitely
`12 different if food is ingested with a product as
`13 opposed to on an empty stomach. So to that
`14 matter, I would say yes.
`15 BY MR. KRAUSE:
`16 Q. And is it true that a number of steroids
`17 have overlapping functions that can compensate
`18 for one another?
`19 MR. BEEL: Objection to form.
`20 A. That is an unanswerable question in its
`21 current form.
`22 BY MR. KRAUSE:
`23 Q. Why is that?
`24 A. Which particular steroids are you
`
` 1 inhibitor of?
` 2 A. I am very happy to answer your question,
` 3 but I need a little bit more precision in your
` 4 question.
` 5 Q. Okay. Well, is it true that a person of
` 6 ordinary skill in the art knew that ketoconazole
` 7 was a nonspecific inhibitor of
` 8 17 alpha-hydroxylase?
` 9 A. I would assume that a person that used
`10 ketoconazole would know that, yes.
`11 Q. And among other things, a person of
`12 ordinary skill would also have known that
`13 ketoconazole was known to inhibit the conversion
`14 of cholesterol to pregnenolone; is that correct?
`15 MR. BEEL: Objection to form.
`16 A. A person may or may not have known that.
`17 BY MR. KRAUSE:
`18 Q. And what is the basis for whether the
`19 person may or may not have known that?
`20 A. A person would know that ketoconazole
`21 when used as an anticancer agent inhibited the
`22 production of steroids. And I think
`23 17 alpha-hydroxylase and the 17,20-lyase, to me,
`24 were the things that were probably best known.
`
`Page 23
`
` 1 referring to?
` 2 Q. Well, I am just asking in the general
` 3 sense, in your view.
` 4 A. I can't -- I can't answer that question.
` 5 If you give me a specific steroid, I will say
` 6 yes, it can, or it can't, or I don't know.
` 7 Q. For example, cortisol had some weak
` 8 mineralocorticoid activity, and corticosterone,
` 9 which is a weak mineralocorticoid, had some
`10 glucocorticoid activity?
`11 A. In general, I would agree with that, yes.
`12 Q. So isn't it true that one could
`13 compensate for the other to a certain degree?
`14 MR. BEEL: Objection to form.
`15 A. I don't know.
`16 BY MR. KRAUSE:
`17 Q. Your declaration discusses ketoconazole;
`18 is that right?
`19 A. Yes, it does.
`20 Q. And a person of ordinary skill knew that
`21 ketoconazole was a nonspecific inhibitor; is that
`22 right?
`23 A. An inhibitor of what?
`24 Q. Well, can you tell me what it was an
`
`Page 25
` 1 Q. Well, isn't it true that ketoconazole was
` 2 known to inhibit the biosynthesis of all
` 3 steroids?
` 4 MR. BEEL: Objection to form and
` 5 foundation.
` 6 A. Of all?
` 7 BY MR. KRAUSE:
` 8 Q. Steroids.
` 9 A. Of all steroids?
`10 Q. Yes, sir.
`11 A. Of all steroids? I don't know.
`12 A person skilled in the art who utilized
`13 ketoconazole for fungal disease would be one set
`14 of experiences, and the person skilled in the art
`15 that used ketoconazole for the management of
`16 patients with prostate cancer would probably have
`17 another set of knowledge that would allow that
`18 person to use that drug.
`19 Q. So you are saying that there are
`20 different persons of ordinary skill in the art
`21 that would have different sets of knowledge?
`22 A. It depends on the indication that
`23 ketoconazole was being used in.
`24 Q. Well, I think the person of ordinary
`
`Golkow Technologies, Inc.
`
`Page 7 (22 - 25)
`
`
`
`Page 28
`
`Marc B. Garnick, M.D.
`Page 26
` 1 skill in the art that we are talking about here
` 2 today is with respect to the patent in the
` 3 lawsuit.
` 4 A. Okay.
` 5 Q. And you have provided opinions with
` 6 respect to the knowledge of that person; is that
` 7 correct?
` 8 A. That's correct, yes.
` 9 Q. And just so I understand, are you
`10 testifying that there could be people within your
`11 definition of a person of ordinary skill that
`12 would have different skill sets or different sets
`13 of knowledge?
`14 MR. BEEL: Objection to form.
`15 A. I think a person skilled in the art that
`16 used ketoconazole for the treatment of patients
`17 with prostate cancer would have the following
`18 knowledge: They would know that it inhibits
`19 steroid production; they would know that it
`20 inhibits sex steroid production.
`21 And in so doing, a person skilled in the
`22 art that utilized ketoconazole would know that
`23 there was an obligation to replace
`24 glucocorticoids when ketoconazole is used for the
`
` 1 A. Yes.
` 2 Q. Would a person of ordinary skill in the
` 3 art have been familiar with O'Donnell?
` 4 A. In what year?
` 5 Q. As of August 25, 2006.
` 6 (Handing document to the witness.)
` 7 A. Well, a person in 2006, since abiraterone
` 8 was -- since this paper deals with abiraterone,
` 9 would not have access to abiraterone. So a
`10 person skilled in the art in 2006 would probably
`11 not be familiar with the O'Donnell paper.
`12 Q. Let me ask you to turn to -- well, I have
`13 handed you a document that bears the label
`14 Amerigen 1003, which is an exhibit.
`15 A. Yes, okay.
`16 Q. And this is O'Donnell; correct?
`17 MR. BEEL: Objection to form.
`18 Did you say Amerigen 1003?
`19 BY MR. KRAUSE:
`20 Q. Sorry. I meant Mylan 1003. I apologize.
`21 This exhibit is marked Mylan 1003;
`22 correct?
`23 A. Yes.
`24 Q. And this is the O'Donnell reference?
`
`Page 27
` 1 treatment of patients with prostate cancer. That
` 2 is what a person skilled in the art would know.
` 3 BY MR. KRAUSE:
` 4 Q. Well, a person of ordinary skill in the
` 5 art as you have defined it would be familiar with
` 6 the references that you referred to in your
` 7 declaration; is that correct?
` 8 A. A person skilled in the art would know of
` 9 publications that identified the utility of
`10 ketoconazole.
`11 Q. I am not sure what you are trying to
`12 parse. My question was: A person with ordinary
`13 skill in the art as you have defined it would be
`14 familiar with the references that you cited in
`15 your declaration; is that correct?
`16 MR. BEEL: Objection to form.
`17 A. I think a person skilled in the art,
`18 i.e., a practicing physician who treated patients
`19 with ketoconazole, would know some but not
`20 necessarily all of the references in my
`21 declaration.
`22 BY MR. KRAUSE:
`23 Q. One of the key references in your
`24 declaration was O'Donnell; is that correct?
`
`Page 29
`
` 1 A. Yes, it is.
` 2 Q. And this is one of the key references in
` 3 your declaration; correct?
` 4 A. That's correct, yes.
` 5 Q. Can I ask you to turn to page 2318? Look
` 6 in the left column, the first full paragraph,
` 7 second line. There is a statement, "Ketoconazole
` 8 is relatively unselective, inhibiting both
` 9 cholesterol side chain cleavage and
`10 11-beta-hydroxylation."
`11 Do you see that?
`12 A. Yes, I do.
`13 Q. Would that statement be consistent with
`14 how a person of ordinary skill in the art would
`15 view ketoconazole's activity?
`16 MR. BEEL: Objection to form.
`17 A. I don't know.
`18 BY MR. KRAUSE:
`19 Q. Do you believe that this statement in
`20 O'Donnell would inform a person of ordinary skill
`21 in the art's knowledge about the activity of
`22 ketoconazole?
`23 A. In 2006 or when?
`24 Q. In 2006.
`
`Golkow Technologies, Inc.
`
`Page 8 (26 - 29)
`
`
`
`Marc B. Garnick, M.D.
`Page 30
` 1 A. I believe a person skilled in the art in
` 2 2006 would probably not have access -- would
` 3 not -- a person skilled in the art who is
` 4 utilizing ketoconazole for the management of
` 5 patients with prostate cancer would probably not
` 6 be aware of this paper.
` 7 Q. Would a person of ordinary skill in the
` 8 art in 2006 have any reason to doubt that
` 9 ketoconazole inhibited cholesterol side chain
`10 cleavage?
`11 A. No, there would be no reason why they
`12 would think that.
`13 Q. And cholesterol side chain cleavage, as I
`14 believe we discussed earlier, is the cleavage
`15 that occurs on the side chain from cholesterol
`16 that produces pregnenolone; is that correct?
`17 A. Yes.
`18 (Handing document to the witness.)
`19 Q. And I handed you another document. This
`20 one is marked Mylan Exhibit 1004. Do you
`21 recognize this document?
`22 (Witness viewing document.)
`23 A. Yes, I do.
`24 Q. And is this the Gerber reference that you
`
`Page 32
` 1 Q. Well, I am asking you how a person of
` 2 ordinary skill in the art would view that
` 3 statement.
` 4 A. A person of ordinary skill in the art
` 5 would say, okay, ketoconazole for the use in
` 6 patients with prostate cancer inhibits gonadal,
` 7 which would be testosterone as a steroid, and
` 8 adrenal steroid synthesis. That could be
` 9 mineralocorticoids; it could be glucocorticoids;
`10 it could be a variety of other things. Your term
`11 was "all."
`12 Q. Is it fair to say that this could be
`13 referring to the fact that it blocks any or all
`14 of the steroids?
`15 MR. BEEL: Objection to form and
`16 foundation.
`17 A. Any or all? No, okay. As opposed to
`18 all. So that is what a person skilled in the
`19 art -- a person that would understand who is
`20 using ketoconazole.
`21 BY MR. KRAUSE:
`22 Q. And would a person of ordinary skill in
`23 the art as of August 25, 2006, be aware of this
`24 reference?
`
`Page 31
`
` 1 talk about in your declaration?
` 2 A. Yes, it is.
` 3 Q. If I could ask you to look in the first
` 4 paragraph under the abstract on the left column.
` 5 And the first couple of sentences there, it
` 6 indicates that ketoconazole is a potent inhibitor
` 7 of gonadal and adrenocortical steroid synthesis;
` 8 is that correct?
` 9 A. Yes.
`10 Q. So a person of ordinary skill in the art
`11 would understand from that statement that
`12 ketoconazole blocks the synthesis of all
`13 steroids; correct?
`14 MR. BEEL: Objection to form.
`15 A. No. What the article says is the drug is
`16 a potent inhibitor of gonadal and adrenocortical
`17 steroid synthesis. It doesn't say all steroids.
`18 That is what a person skilled in -- of ordinary
`19 skill in the art would know, would understand.
`20 Exactly.
`21 BY MR. KRAUSE:
`22 Q. But that statement doesn't exclude any
`23 types of steroids, does it?
`24 A. I have no idea.
`
`Page 33
` 1 A. I would assume, yes. I would assume so,
` 2 absolutely.
` 3 (Handing document to the witness.)
` 4 Q. I have handed you another document,
` 5 Exhibit 1020. Do you recognize this document?
` 6 A. Yes, I do.
` 7 Q. This is the Harris reference?
` 8 A. Yes, it is.
` 9 Q. And this reference is referred to in your
`10 declaration; is that correct?
`11 A. Correct.
`12 Q. Would a person of ordinary skill in the
`13 art be familiar with this reference?
`14 A. Yes.
`15 Q. If I could ask you to look at page 544
`16 and the right-hand column, the first full
`17 paragraph. There the paper says, "Ketoconazole
`18 is a substituted imidazole that suppresses
`19 testicular and adrenal steroidogenesis by
`20 inhibition of the conversion of cholesterol to
`21 pregnenolone. Because ketoconazole is a potent
`22 inhibitor of all adrenal steroid synthetic
`23 pathways, replacement doses of hydrocortisone may
`24 be required."
`
`Golkow Technologies, Inc.
`
`Page 9 (30 - 33)
`
`
`
`Marc B. Garnick, M.D.
`Page 34
`
` 1 Do you see that?
` 2 A. Yes.
` 3 Q. So would a person of ordinary skill in
` 4 the art understand from this statement that
` 5 ketoconazole blocks the production of all adrenal
` 6 steroid synthetic pathways?
` 7 A. Yes.
` 8 Q. Would a person of ordinary skill in the
` 9 art have any reason to believe that this is not a
`10 true statement?
`11 A. No.
`12 MR. BEEL: Objection to form on the last
`13 two.
`14 MR. KRAUSE: I will wait to let you go
`15 first.
`16 BY MR. KRAUSE:
`17 Q. So would a person of ordinary skill
`18 understand ketoconazole to block the biosynthesis
`19 of mineralocorticoids, glucocorticoids, and
`20 androgens?
`21 MR. BEEL: Objection to form and
`22 foundation.
`23 A. A person skilled in the art who utilized
`24 ketoconazole would know that ketoconazole
`
`Page 36
` 1 ketoconazole inhibited steroid production,
` 2 including sex steroids and glucocorticoids, and,
` 3 in so doing, needed to replace the glucocorticoid
` 4 with another glucocorticoid. That is what a
` 5 person skilled in the art would know.
` 6 BY MR. KRAUSE:
` 7 Q. Is it your testimony, Doctor, that a
` 8 person of ordinary skill in the art would be
` 9 ignorant of the