Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
`1
`
` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`----------------------------------------x
`SANDOZ INC.,
` Petitioner,
` -against-
`PHARMACYCLICS LLC,
` Patent Owner.
`----------------------------------------x
`
` Case IPR2019-00865
` U.S. Patent No. 9,795,604
`
` STENOGRAPHIC DEPOSITION OF:
` JAMES L. FERRARA, M.D., DSC
` Thursday, December 5, 2019
` New York, New York
` 9:03 a.m. - 5:13 p.m.
`
` Reported in stenotype by:
` Rich Germosen,
` CCR, CRCR, CRR, RDR, NYACR, NYRCR
` NCRA/NJ/NY/CA Certified Realtime Reporter
` NCRA Realtime Systems Administrator
` Job No. 48052
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`IPR2019-00865
`
`December 5, 2019
`
`1
`
` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`----------------------------------------x
`SANDOZ INC.,
` Petitioner,
` -against-
`PHARMACYCLICS LLC,
` Patent Owner.
`----------------------------------------x
`
` Case IPR2019-00865
` U.S. Patent No. 9,795,604
`
` STENOGRAPHIC DEPOSITION OF:
` JAMES L. FERRARA, M.D., DSC
` Thursday, December 5, 2019
` New York, New York
` 9:03 a.m. - 5:13 p.m.
`
` Reported in stenotype by:
` Rich Germosen,
` CCR, CRCR, CRR, RDR, NYACR, NYRCR
` NCRA/NJ/NY/CA Certified Realtime Reporter
` NCRA Realtime Systems Administrator
` Job No. 48052
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
`2
`
` STENOGRAPHIC DEPOSITION of JAMES L. FERRARA,
`M.D., DSC, taken in the above-entitled matter before
`RICH GERMOSEN, Certified Court Reporter, (License No.
`30XI00184700), Certified Realtime Court Reporter-NJ,
`(License No. 30XR00016800), NCRA/NY/CA Certified
`Realtime Reporter, NCRA Registered Diplomate Reporter,
`New York Association Certified Reporter, NCRA Realtime
`Systems Administrator, taken ALSTON & BIRD LLP, 90 Park
`Avenue, New York, New York 10016, on Thursday, December
`5, 2019, commencing at 9:03 a.m.
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`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
`3
`
`A P P E A R A N C E S:
`
`ALSTON & BIRD LLP
`BY: KIRK T. BRADLEY, ESQ.
`Bank of America Plaza
`101 South Tyron Street
`Suite 4000
`Charlotte, North Carolina 28280
`(704) 444.1000 / (704) 444.1730 (FAX)
`kirk.bradley@alston.com
`Attorneys for the Petitioner
`
`ALSTON & BIRD LLP
`BY: CHRISTOPHER L. McARDLE, ESQ.
`90 Park Avenue
`New York, New York 10016
`(212) 210.9542 / (212) 922.3843 (FAX)
`chris.mcardle@alston.com
`Attorneys for the Petitioner
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`www.hendersonlegalservices.com
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`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
`4
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`A P P E A R A N C E S: (CONT'D.)
`
`FINNEGAN HENDERSON FARABOW GARRETT & DUNNER LLP
`BY: WILLIAM B. RAICH, Ph.D., ESQ.
` -and-
`BY: YOONJIN LEE, Ph.D.
`901 New York Avenue, N.W.
`Washington, D.C. 20001-4413
`(202) 408.4000 / (202 408.4400 (FAX)
`william.raich@finnegan.com
`yoonjin.lee@finnegan.com
`Attorneys for the Patent Owner
`
`ALSO PRESENT:
`IRENA ROYZMAN, Ph.D., ESQ., Kramer Levin
`POOPAK BANKY, Sandoz, (telephonic a.m. only)
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`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
`5
`
` I N D E X
`WITNESS EXAMINATION
`JAMES L. FERRARA, M.D., DSC
` BY MR. RAICH 12
` BY MR. BRADLEY 224
`
` E X H I B I T S
`EXHIBIT NO. DESCRIPTION PAGE
`Exhibit 1006 document entitled: 18
` Declaration of James L.
` Ferrara, M.D.
`
`Exhibit 2043 document entitled: Test 29
` predicts response to
` treatment for complication of
` leukemia stem cell treatment
`
`Exhibit 2044 document entitled: ibrutinib 32
` approval expanded to include
` chronic GvHD
`
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`202-220-4158
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`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
`6
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` E X H I B I T S (CONT'D.)
`EXHIBIT NO. DESCRIPTION PAGE
`Exhibit 2045 document entitled: FDA 36
` approves Imbruvica as first
` therapy for chronic
` graft-versus-host disease
`
`Exhibit 2046 document entitled: GVHD 38
` management improves, but
` questions remain about risk
` stratification, prophylaxis
`
`Exhibit 2002 document entitled: 45
` Pathogenesis and management
` of Graft-versus-host disease
`
`Exhibit 2047 document entitled: National 63
` Institutes of Health
` consensus development project
` on criteria for clinical
` trials in chronic
` Graft-versus-host disease: 1
` diagnosis and staging working
` group report
`
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`202-220-4158
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`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
`7
`
` E X H I B I T S (CONT'D.)
`EXHIBIT NO. DESCRIPTION PAGE
`Exhibit 2048 document entitled: Measuring 72
` therapeutic response in
` chronic Graft-versus-host
` disease: National Institutes
` of Health consensus
` development project on
` criteria for clinical trials
` in chronic Graft-versus-host
` disease: IV, response
` criteria working group report
`
`Exhibit 2049 document entitled: 79
` Therapeutic targets and
` emerging treatment options in
` gastrointestinal acute
` Graft-versus-host disease
`
`Exhibit 2005 document entitled: Advances 83
` in Stem Cell Research
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`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
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`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
`8
`
` E X H I B I T S (CONT'D.)
`EXHIBIT NO. DESCRIPTION PAGE
`Exhibit 2050 document entitled: Consensus 108
` conference on clinical
` practice in chronic GvHD:
` Second-line treatment of
` chronic Graft-versus-host
` disease
`
`Exhibit 2001 document entitled: Diagnosis 112
` and management of chronic
` Graft-versus-host disease
`
`Exhibit 2006 document entitled: Treatment 116
` of chronic Graft-versus-host
` disease past, present and
` future
`
`Exhibit 2051 document entitled: Acute 120
` Graft-versus-host disease:
` Pathophysiology, risk
` factors, and prevention
` strategies
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`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
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`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
`9
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` E X H I B I T S (CONT'D.)
`EXHIBIT NO. DESCRIPTION PAGE
`Exhibit 1003 Shimabukuro reference 126
`
`Exhibit 2052 document entitled: Efficacy 134
` of rituximab in the setting
` of steroid-refractory chronic
` Graft-versus-host disease: A
` systematic review and
` meta-analysis
`
`Exhibit 2053 document entitled: Lack of 144
` efficacy of rituximab in
` refractory sclerodermatous
` chronic GvHD
`
`Exhibit 2054 document entitled: Mouse 148
` models of Graft-versus-host
` disease
`
`Exhibit 1005 Uckun reference 157
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`www.hendersonlegalservices.com
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`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
`10
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` E X H I B I T S (CONT'D.)
`EXHIBIT NO. DESCRIPTION PAGE
`Exhibit 1012 document entitled: Dual 158
` targeting of Bruton's
` tyrosine kinase and Janus
` kinase 3 with rationally
` designed inhibitors prevents
` Graft-versus-host disease
` (GvHD) in a murine allogeneic
` bone marrow
`
`Exhibit 2033 document entitled: The Btk 166
` inhibitor LFM-A13 is a potent
` inhibitor of Jak2 kinase
` activity
`
`Exhibit 2034 document entitled: Bruton's 168
` tyrosine kinase is
` dispensable for the Toll-like
` receptor-mediated activation
` of mast cells
`
`Exhibit 1004 document entitled Blood, 173
` v.117, no. 23, June 9, 2011
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`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
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`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
`11
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` E X H I B I T S (CONT'D.)
`EXHIBIT NO. DESCRIPTION PAGE
`Exhibit 1002 '085 patent 179
`
`Exhibit 1001 '604 patent 193
`
`Exhibit 1023 James Lawrence Michael 224
` Ferrara Curriculum Vitae
`**original exhibits returned with original transcript
`by HENDERSON LEGAL SERVICES to FINNEGAN HENDERSON
`FARABOW GARRETT & DUNNER LLP
`(exhibit index concluded)
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`www.hendersonlegalservices.com
`
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`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
`12
`
`--------------------------------------------------
` P R O C E E D I N G S
` 9:03 a.m.
` New York, New York
`--------------------------------------------------
` (Whereupon, the Certified Realtime
`Stenographer administered the oath to the witness.)
`
`J A M E S L. F E R R A R A, M.D., DSC,
`having been first duly sworn or affirmed, was
`examined and testified as follows:
`EXAMINATION BY MR. RAICH:
`BY MR. RAICH:
` Q. Good morning, Doctor.
` A. Good morning.
` Q. Could you please state your name for
`the record.
` A. James Ferrara.
` Q. And can you please state the city and
`state where you reside for the record.
` A. New York, New York.
` Q. I'll be taking your deposition today.
`My name is Bill Raich. You understand that you're
`testifying in IPR 201900865 before the United States
`Patent and Trademark Office?
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`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
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` A. I do.
` Q. You understand that your testimony
`today will be transcribed and made public in these
`proceedings?
` A. I do.
` Q. You understand that your answers
`today are under oath?
` A. I do.
` Q. And your counsel may from time to
`time object to my questions, but you still need to
`answer the question, unless you are specifically
`instructed not to.
` Do you understand that?
` A. I do.
` Q. If at any time you're unclear about a
`question, please let me know and I'll do my best to
`rephrase. If you answer one of my questions, I'm
`going to assume that you understood the question.
`Is that fair?
` A. I understand.
` Q. We'll plan to take breaks
`approximately every hour or so, but if you need a
`break, please just let me know. All I'd ask if
`there is a question pending, that you answer that
`question before taking a break.
`
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`09:04:53
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
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` A. Understood.
` Q. We have a court reporter transcribing
`your deposition today, so you need to give audible
`answers to my questions, okay?
` A. I'll do my best.
` Q. We can also help the court reporter
`by not talking over each other during the
`deposition. So can we agree to try to do that?
` A. Yes, we can agree.
` Q. Is there any reason you cannot
`provide full and truthful testimony today?
` A. None to my knowledge.
` Q. And will you provide full and
`truthful testimony today?
` A. I will.
` Q. Doctor, have you ever been deposed
`before?
` A. I have.
` Q. And were you deposed before in a
`patent case?
` A. No.
` Q. And could you give me, generally, the
`subject matter for the cases where you were
`previously deposed?
` A. Sure. Should I -- someone has just
`
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`09:05:48
`09:05:50
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
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`come into the room. Does that matter?
` MR. RAICH: Not really. We can
`continue.
` A. Fine.
` Q. This is counsel who is joining us.
` A. Fine.
` Could you repeat the question,
`please.
` Q. How many times have you previously
`been deposed? Let's start there.
` A. I've been deposed twice.
` Q. And what were the nature of the cases
`in which you were previously deposed?
` A. Both were malpractice lawsuits.
` Q. And were you testifying as an expert?
` A. In one of them I was an expert and in
`one of them I was a defendant.
` Q. Did either of the cases involve
`Graft-versus-host disease?
` A. Yes.
` Q. And did you give any testimony
`regarding Graft-versus-host disease?
` A. I gave a deposition. Does that count
`as testimony?
` Q. Yes, it does.
`
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`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
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` Did you testify live at trial also?
` A. I did not.
` Q. Have you ever testified at a trial?
` A. Yes.
` Q. And what was the context for that
`testimony?
` A. That was the other case in which I
`gave a deposition in which I was a defendant and I
`testified live at that trial.
` Q. Did any of the cases involve
`ibrutinib?
` A. No.
` Q. Was any of your previous testimony
`related in any way to the subject matter of this
`case?
` A. No.
` MR. BRADLEY: Objection. Form.
` A. May I just ask a process question?
` Q. You may.
` A. You asked a question. I started to
`answer before he objected. I didn't mean to speak
`over him. Should I be waiting for him to finish
`before I answer? Just tell me how that should work.
` Q. You can answer my questions and he
`can make objections, if he sees fit.
`
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`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
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` MR. BRADLEY: It's certainly better
`if you give me a moment to object.
` THE WITNESS: Fine.
` Q. Doctor, steroids are the first-line
`therapy for patients with chronic Graft-versus-host
`disease; correct?
` A. That is correct. Steroids are the
`first-line treatment for both acute
`Graft-versus-host disease and chronic
`Graft-versus-host disease.
` Q. And steroids have been the first-line
`therapy for patients with Graft-versus-host disease
`for about 50 years; is that right?
` A. Correct. Steroids are the first-line
`therapy, but I believe I speak to this in my
`deposition. May I see my deposition to just ensure
`that I'm giving the correct answer in context?
` Q. Do you mean your written declaration?
` A. My declaration. My declaration.
` Q. We'll get to the declaration in a
`minute; is that okay? Can you just answer my
`questions in the meantime?
` A. Well, I can, but are you saying that
`I'm not allowed to see my declaration?
` Q. If there is any question that I ask
`
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`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
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`where you think you need to see your declaration,
`let me know and --
` A. I've just asked to see whether I
`could have my declaration.
` Q. We'll provide the declaration.
` (Whereupon, document entitled:
`Declaration of James L. Ferrara, M.D., is received
`and marked as Exhibit 1006 for Identification.)
`BY MR. RAICH:
` Q. Doctor, I'm handing you what was
`previously marked as Sandoz exhibit 1006, the
`declaration of James L. Ferrara.
` A. Great. Thank you.
` Q. Now, when a patient suffering from
`chronic Graft-versus-host disease does not respond
`to steroid treatment, that patient has
`steroid-resistant chronic GvHD or refractory GvHD;
`is that correct?
` A. I'm reviewing -- I'd like to take a
`moment to just review my declaration for a second.
` So as I say here, on page -- by the
`way, if I'm reading from this, how would you like me
`to refer to it? The page or the number?
` Q. It's up to you, Doctor.
` A. Okay. So on page 11, number 32:
`
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`09:10:40
`09:10:41
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
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`Acute and chronic GvHD are closely related.
`Physicians commonly prescribe a number of the same
`treatments to patients with acute GvHD and to
`patients with chronic GvHD, for example,
`glucocorticoids, a type of steroid, such as
`prednisone, with --
` (Reporter clarification.)
` A. For example, glucocorticoids, a type
`of steroid, such as prednisone, with or without a
`calcineurin inhibitor, such as cyclosporin, are the
`standard regimen as primary treatment for both acute
`and chronic GvHD.
` Q. Doctor, that didn't answer my
`question. Do you recall my question?
` A. I don't. Would you repeat your
`question, please?
` Q. When a patient is suffering from
`chronic GvHD and does not respond to steroid
`treatment, the patient has steroid-resistant or
`refractory chronic GvHD; correct?
` A. When a patient does not respond to
`steroid treatment, that patient has
`steroid-refractory GvHD, that is correct.
` Q. Do steroids produce any notable
`adverse effects in chronic GvHD patients?
`
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`09:11:46
`09:11:49
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
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` MR. BRADLEY: Objection. Form.
` A. Steroids have a number of effects in
`chronic GvHD patients. They produce hypertension.
`They can produce diabetes. They can produce
`avascular necrosis of the femoral heads of the bone,
`so yes, they do produce a number of side effects.
` Q. Any other side effects produced by
`steroids in chronic GvHD patients other than
`hypertension, diabetes, and a vascular nephrosis?
` A. There are probably others, but those
`are the principal ones that are -- for example,
`glaucoma or cataracts, but I believe those are the
`principal ones.
` Q. Can steroids cause severe
`immunosuppression in chronic GvHD patients?
` A. Yes, they do -- they do also cause --
`because they are an immunosuppressant, they cause
`immunosuppression.
` That's -- it is correct. Steroids
`cause immunosuppression in chronic GvHD patients.
` Q. Could that lead to an increased risk
`of opportunistic infections?
` A. I'd like to review where I speak
`about this because I believe I do speak about this.
` Well, I can't find where I speak to
`
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`09:13:09
`09:13:14
`09:13:15
`09:14:05
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
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`immunosuppression specifically by steroids, but yes,
`chronic steroid use does cause immunosuppression in
`chronic GvHD patients.
` Q. And does immunosuppression increase
`the risk of opportunistic infections?
` A. Immunosuppression does increase the
`risk of opportunistic infections.
` Q. And what are the other consequences
`of immunosuppression in patients with chronic GvHD?
` A. The primary -- the primary risk
`factor or the primary effect of immunosuppression
`would be an increased risk of infections, although
`there may be other issues in patients with chronic
`GvHD, such as a loss of a Graft-versus-Leukemia
`effect and increased risk of relapse.
` Q. Doctor, you referred to steroids as
`Stone Age drugs for treating Graft-versus-host
`disease patients?
` A. I'm sorry, I just didn't hear you.
` Q. You referred to steroids as Stone Age
`drugs for treating Graft-versus-host disease
`patents; correct? You've referred to steroids as
`Stone Age drugs for treating Graft-versus-host
`disease patients; correct?
` A. Can you remind me where I say that?
`
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`09:15:31
`09:15:32
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
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` Q. I saw that online on several videos.
`Do you recall saying that?
` A. It sounds like something that I might
`say. I don't recall specifically saying that, but
`it sounds like something I might say in another
`context, yes.
` Q. Could you explain what you meant by
`that?
` MR. BRADLEY: Objection. Foundation
`and vague.
` A. If I -- when I've said -- let's
`assume for the moment that I have said steroids are
`like Stone Age medicine, it means that the -- they
`are very blunt. They do not have -- they have many
`mechanisms of action and they have many kinds of
`effects, both deleterious effects, as well as
`antiinflammatory effects, which is why we usually
`use steroids and, therefore, they are like stone
`tools as opposed to lasers.
` Q. Approximately what portion of
`patients with chronic GvHD fail to respond to
`steroids?
` A. I would say that approximately 40 to
`50 percent of patients who -- with chronic GvHD fail
`to respond to steroids.
`
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`09:16:59
`09:17:04
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
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` Q. Would you agree that as of October
`2013, there was an unmet need for alternative
`therapies of chronic Graft-versus-host disease?
` A. I would agree that there was an unmet
`need for alternative therapies in October 2013. I
`believe there still is.
` Q. And would you agree that there was an
`unmet need specifically for patients with chronic
`Graft-versus-host disease who failed to respond to
`steroids as of October 2013?
` A. There was an unmet need for patients
`with chronic GvHD who failed to respond to steroids
`at that time, that is correct.
` Q. As of October 2013, which specific
`drugs had you tried for treating patients with
`steroid-resistant chronic Graft-versus-host disease?
` A. I had tried as of October 2013, to
`the best of my recollection, extracorporeal
`photopheresis; rituximab; alemtuzumab; possibly
`antithymocyte globulin. I'm now scanning way back.
`So there may well be others, but certainly those
`four, rituximab, extracorporeal photopheresis,
`antithymocyte globulin, and -- can you repeat what
`the fourth one was? I've now forgotten what the
`fourth --
`
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`09:19:00
`09:19:02
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
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`
` THE WITNESS: Can you just read that
`back to me?
` Q. ECP, rituximab, alemtuzumab and
`antithymocyte globulin.
` A. Those are the four, right.
` Q. None of those drugs that you just
`recited were approved for steroid-refractory cGvHD
`as of October 2013; correct?
` A. As of October 2013, no drug had been
`approved for any form of Graft-versus-host disease.
` Q. Is it fair to say that as of October
`2013, patients suffering from steroid-refractory
`chronic Graft-versus-host disease were treated with
`drugs that lacked established safety and efficacy as
`evaluated and endorsed by the FDA?
` A. As endorsed by the FDA, there were no
`FDA approved drugs for the treatment of
`steroid-resistant chronic Graft-versus-host disease
`as of October 2013. That did not stop us from using
`drugs for these patients obviously. I just recited
`four that were not FDA approved and, in fact, all of
`the drugs as of October 2013 that we used to treat
`patients with Graft-versus-host disease, every
`single one did not have FDA approval because none
`had been approved.
`
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`09:20:35
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
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`
` Q. Now, you have prescribed ibrutinib to
`patients with chronic Graft-versus-host disease;
`correct?
` A. I have.
` Q. And ibrutinib is the active agent in
`the commercial product known as Imbruvica?
` A. Yes, that is correct.
` Q. And Imbruvica is approved by FDA for
`treating chronic GvHD patients who failed one or
`more lines of systemic therapy; correct?
` A. That is correct.
` Q. Imbruvica is the only FDA-approved
`drug for treating chronic Graft-versus-host disease;
`correct?
` A. As of today, it is the only FDA
`approved drug for treating steroid-resistant chronic
`GvHD. There is now another drug that is approved
`for treating steroid-resistant acute
`Graft-versus-host disease, which is ruxolitinib.
` Q. Approximately how many patients have
`you treated with Imbruvica?
` A. I would say a half a dozen perhaps.
` Q. And when you treated those patients
`with Imbruvica, did you use the recommended dosing
`regimen?
`
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`09:21:46
`09:21:50
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
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` A. I believe I did.
` Q. And the recommended dosing regimen is
`420 milligrams per day?
` A. That is my recollection.
` Q. Now, of the patients that you
`treated, how many of them -- let me strike that.
` Of the patients that you treated, how
`many of those patients with chronic
`Graft-versus-host disease experienced a complete
`response following treatment with Imbruvica?
` A. None.
` Q. How many achieved a partial response?
` A. Two.
` Q. How many of them, patients that you
`treated, experienced a lessen severity of chronic
`Graft-versus-host disease following treatment with
`Imbruvica?
` A. A lessening of the severity of the
`disease is the same as a partial response, so that
`would be two.
` Q. Okay. And that's how you define a
`lessening of severity --
` A. That is -- that is -- that is a
`common definition. There are more complicated
`definitions, but that's a common definition of
`
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`09:23:00
`09:23:04
`09:23:06
`09:23:08
`09:23:12
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`
`
`Ferrara, James L.
`
`IPR2019-00865
`
`December 5, 2019
`
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`partial response. It's not a complete response, but
`a lessening of severity.
` Was my answer clear there?
` Q. Yes. Thank you.
` You would agree that the recommended
`dose of Imbruvica does not necessarily treat chronic
`Graft-versus-host disease in each and every patient?
` A. I would agree with that. It does not
`necessarily treat all patients.
` Sorry. I would agree that -- I'm not
`sure that that's actually what I meant. Would you
`repeat your question, please?
` Q. You would agree that the recommended
`dose of Imbruvica does not necessarily treat chronic
`Graft-versus-host disease in each and every patient?
` A. I would agree that the recommended
`dose of Imbruvica does not produce either a partial
`or a complete resolution of all GvHD symptoms in
`every patient.
` Q. Imbruvica was approved for treating
`chronic Graft-versus-host disease in 2017; correct?
` MR. BRADLEY: Objection. Scope.
` A. I believe the date of FDA approval of
`Imbruvica was in 2017. Did you say Octob
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