LEON SHARGELLEON SHARGEL
`
`LUPIN vs. POZENLUPIN vs. POZEN
`
`·1· · · · · UNITED STATES PATENT AND TRADEMARK OFFICE
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`·2· · · · · BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`Page 1
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`·3
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`· · LUPIN, LTD. AND LUPIN· · · ·)
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`·4· PHARMACEUTICALS, INC.,· · · )
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`· · · · · · · · · · · · · · · · )
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`·5· · · · · · Petitioners,· · · )
`
`· · · · · · · · · · · · · · · · )
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`·6· VS.· · · · · · · · · · · · ·)· · Case IPR2015-01773
`
`· · · · · · · · · · · · · · · · )· · Patent 8,858,996 B2
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`·7· POZEN, INC.,· · · · · · · · )
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`· · · · · · · · · · · · · · · · )
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`·8· · · · · · Patent owner.· · ·)
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`·9
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`10· · · · · · ------------------------------------
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`11· · · · · · · ORAL AND VIDEOTAPED DEPOSITION OF
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`12· · · · · · · · · · · · LEON SHARGEL
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`13· · · · · · · · · · · · MAY 25, 2016
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`14· · · · · · ------------------------------------
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`15
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`16· · · · · · ORAL AND VIDEOTAPED DEPOSITION of LEON
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`17· SHARGEL, a witness produced at the instance of Horizon
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`18· Pharma, taken in the above-styled and numbered cause on
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`19· the 25th day of May, 2016, from 9:00 a.m. to 10:02 a.m.,
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`20· before Stacy L. Jordan, a CSR in and for the State of
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`21· Texas, Registered Professional Reporter and Certified
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`22· Realtime Reporter, taken in the offices of Wick
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`23· Phillips, 3131 McKinney Avenue, Suite 100, Dallas, Texas
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`24· 75204, in accordance with the Federal Rules of Civil
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`25· Procedure.
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`May 25, 2016May 25, 2016
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`1–4
`Page 3
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`·1· · · · · · · · · · · · · I N D E X
`·2· · · · · · · · · · · · · · · · · · · · · · · · ·PAGE
`·3· Appearances...................................... 2
`·4· Stipulations.................................... 34
`·5· LEON SHARGEL
`·6· · · ·Examination by Mr. Rodriguez................ 5
`·7· Changes and Signature........................ 35-36
`· · Reporter's Certificate....................... 37-38
`·8
`·9
`10
`· · · · · · · · · · · · ·E X H I B I T S
`11
`· · NO.· · · · ·DESCRIPTION· · · · · · · · · · PAGE MARKED
`12
`· · Exhibit 1· ·Shargel Declaration................. 24
`13
`· · Exhibit 2· ·Ulcer Prevention in Long-Term Users
`14· · · · · · · of Nonsteroidal Anti-Inflammatory
`· · · · · · · · Drugs............................... 24
`15
`· · Exhibit 3· ·Ulcer Recurrence in High-Risk
`16· · · · · · · Patients Receiving Nonsterodial
`· · · · · · · · Anti-Inflammatory Drugs Plus
`17· · · · · · · Low-Dose Aspirin:· Results of a
`· · · · · · · · Post Hoc Subanalysis................ 24
`18
`19
`20
`21
`22
`23
`24
`25
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`Page 2
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`Page 4
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`·1· · · · · · · · · · A P P E A R A N C E S
`·2
`·3· FOR THE PETITIONER COALITION FOR AFFORDABLE DRUGS:
`·4· · · ·Ms. Amy E. LaValle
`· · · · ·Mr. Jerry C. Harris, Jr.
`·5· · · ·WICK PHILLIPS
`· · · · ·3131 McKinney Avenue, Suite 100
`·6· · · ·Dallas, Texas· 75204
`· · · · ·Phone:· · (214) 692-6200
`·7· · · ·Fax:· · · (214) 692-6255
`· · · · ·E-mail:· ·amy.lavalle@wickphillips.com
`·8· · · · · · · · ·jerry.harris@wickphillips.com
`·9
`· · FOR POZEN, INC.:
`10
`· · · · ·Mr. Stephen M. Hash
`11· · · ·BAKER BOTTS
`· · · · ·98 San Jacinto Boulevard, Suite 1500
`12· · · ·Austin, Texas· 78701
`· · · · ·Phone:· · (512) 322-2587
`13· · · ·Fax:· · · (512) 322-3687
`· · · · ·E-mail:· ·stephen.hash@bakerbotts.com
`14
`15· FOR HORIZON PHARMA:
`16· · · ·Mr. Ricardo Rodriguez
`· · · · ·Ms. Susan Krumplitsch
`17· · · ·COOLEY, LLP
`· · · · ·3175 Hanover Street
`18· · · ·Palo Alto, California· 94304
`· · · · ·Phone:· · (650) 843-5046
`19· · · ·Fax:· · · (650) 849-7400
`· · · · ·E-mail:· ·rr@cooley.com
`20· · · · · · · · ·skrumplitsch@cooley.com
`21
`· · ALSO PRESENT:
`22
`· · · · ·Ms. Lauren Stevens
`23· · · ·HORIZON PHARMA
`24· · · ·Mr. Cody Modro, videographer
`25
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`·1· · · · · · · · · · P R O C E E D I N G S
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`·2· · · · · · · · ·(May 25, 2016, 9:00 a.m.)
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`·3· · · · · · · · ·THE VIDEOGRAPHER:· This is the videotaped
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`·4· deposition of Dr. Shargel, held in Dallas, Texas.· The
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`·5· time is now 9:00 a.m., May 25th, 2016.· We are now on
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`·6· record.
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`·7· · · · · · · · ·At this time, will the counsel please
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`·8· introduce themselves and whom they represent, and the
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`·9· witness will then be sworn in.
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`10· · · · · · · · ·MR. RODRIGUEZ:· Ricardo Rodriguez from
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`11· Cooley, LLP, on behalf of Horizon.
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`12· · · · · · · · ·MS. KRUMPLITSCH:· Susan Krumplitsch, also
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`13· from Cool- -- Cooley, LLP, also representing Horizon.
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`14· · · · · · · · ·MR. HASH:· Stephen Hash, from Baker
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`15· Botts, on behalf of Pozen.
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`16· · · · · · · · ·MS. STEVENS:· Lauren Stevens from Horizon
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`17· Pharma.
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`18· · · · · · · · ·MS. LaVALLE:· Amy LaValle from Wick
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`19· Phillips on behalf of the Petitioner Coalition for
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`20· Affordable Drugs.
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`21· · · · · · · · ·MR. HARRIS:· Jerry Harris from Wick
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`22· Phillips on behalf of Petitioner Coalition for
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`23· Affordable Drugs.
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`24· · · · · · · · · · · · LEON SHARGEL,
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`25· having been first duly sworn, testified as follows:
`
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`Page 1 of 10
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`Patent Owner Ex. 2020
`CFAD v. Pozen
`IPR2015-01718
`
`

`
`
`LEON SHARGELLEON SHARGEL
`
`LUPIN vs. POZENLUPIN vs. POZEN
`
`·1· · · · · · · · · · · · ·EXAMINATION
`
`·2· BY MR. RODRIGUEZ:
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`May 25, 2016May 25, 2016
`
`5–8
`Page 7
`·1· There's Simmons & Simmons, out of London, whom I've
`
`Page 5
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`·2· never met, actually.· We've done everything by
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`·3· · · ·Q.· ·Good morning.· Would you please state your
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`·3· teleconference.
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`·4· name and address for the record.
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`·4· · · ·Q.· ·Are you working as an expert for or in
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`·5· · · ·A.· ·Leon Shargel, at 1535 Caraleigh Mills Court,
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`·5· connection with Wick Phillips for any matter other than
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`·6· Raleigh, North Carolina 27603.
`
`·6· this one?
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`·7· · · ·Q.· ·Have you previously worked as an expert for
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`·7· · · ·A.· ·No.
`
`·8· any litigation or patent office proceeding?
`
`·8· · · ·Q.· ·How did you get in contact with Wick Phillips?
`
`·9· · · ·A.· ·I did one case many years ago, when I was
`
`·9· · · ·A.· ·I was contacted, actually, by lawyers for
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`10· employed by Sandoz, in which there was a patent case in
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`10· Conley Rose and -- in which case I initially got
`
`11· which I was deposed.· Sandoz is a generic arm of
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`11· involved in several of these patents, including the '907
`
`12· Novartis, in which case they were being sued -- I don't
`
`12· patent.
`
`13· recall the drug, actually; it was several years ago --
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`13· · · ·Q.· ·How did they identify you?
`
`14· for a particular patent.
`
`14· · · ·A.· ·Actually, I --
`
`15· · · ·Q.· ·Were you deposed as an expert or an employee?
`
`15· · · · · · · · ·MS. LaVALLE:· Objection, form.
`
`16· · · ·A.· ·I was an employee, but I -- I guess -- I was a
`
`16· · · ·A.· ·I -- I got a call.
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`17· vice president of biopharmaceutics.· I ran the studies
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`17· · · ·Q.· ·(BY MR. RODRIGUEZ)· Do you know where they got
`
`18· for the company.
`
`19· · · ·Q.· ·Have you done any prior expert work?
`
`18· your -- your name?
`
`19· · · ·A.· ·No, I didn't.
`
`20· · · ·A.· ·Yes.
`
`21· · · ·Q.· ·For litigation?
`
`20· · · ·Q.· ·Do you know now how they got your name?
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`21· · · ·A.· ·I'm not clear how they got my name.
`
`22· · · ·A.· ·I have looked at patents in which I have made
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`22· · · ·Q.· ·Can you give me an overview of your clinical
`
`23· my general expert opinion, but these have never
`
`23· trial experience?
`
`24· really -- they've been settled before going to court.
`
`24· · · ·A.· ·In -- in terms of what context?
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`25· · · ·Q.· ·Can you identify those?
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`25· · · ·Q.· ·Any context.
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`Page 6
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`Page 8
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`·1· · · ·A.· ·I don't really recall.· They were several --
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`·1· · · ·A.· ·Well, in -- I would have to start very early.
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`·2· some years ago, but -- I -- I don't recall all the
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`·2· In 1969, when I completed my degree, I started at
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`·3· exact -- one was -- I remember was a Cialis-type
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`·3· Sterling Winthrop.· Then I was involved in drug
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`·4· product --
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`·4· metabolism in the areas of looking at blood levels of
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`·5· · · · · · · · ·THE REPORTER:· I'm sorry.· "Was a"?
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`·5· drugs involved in some clinical trials.· So that goes
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`·6· · · · · · · · ·THE WITNESS:· C-i-a-l-i-s.
`
`·6· back many years ago.
`
`·7· · · ·A.· ·-- for erectile dysfunction.· So that one, of
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`·7· · · · · · · · ·At Forest Labs, I also was in charge of
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`·8· course, I remember a little bit more, perhaps.· But
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`·8· running mainly generic company -- or generic products
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`·9· there were several others that I don't recall.· They
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`·9· dealing with bioequivalence and looking at
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`10· were, generally, formulation-associated or
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`10· pharmacokinetics absorption studies.· We looked at a few
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`11· biopharmaceutic-associated issues.
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`11· new drug applications, what we called 505(b)(2)s, which
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`12· · · ·Q.· ·(BY MR. RODRIGUEZ)· Were you deposed in any of
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`12· are old drugs in new carrier systems, new drug products.
`
`13· those cases?
`
`14· · · ·A.· ·No.
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`13· · · · · · · · ·In my last job, I was vice president of
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`14· Sandoz in biopharmaceutics and re- -- responsible for
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`15· · · ·Q.· ·Did you write expert declarations in any of
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`15· other generic clinical studies, leading to generic
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`16· those cases?
`
`16· approval.
`
`17· · · ·A.· ·On -- a couple of times, I did; and other
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`17· · · ·Q.· ·Have you been involved in clinical trials for
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`18· times, it was mostly oral, by teleconference and
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`18· new drugs?
`
`19· discussions of the patent.
`
`19· · · ·A.· ·On occasion, where there is a drug
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`20· · · ·Q.· ·Do you recall the law firms that you worked
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`20· interaction, absorption/pharmacokinetic issue, blood
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`21· with?
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`21· level related to pharmacodynamic effect.
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`22· · · ·A.· ·One that I worked with was Rakoczy -- I forgot
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`22· · · ·Q.· ·What has been the nature of your involvement
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`23· their last name -- in Chicago.· There was Steptoe in --
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`23· in clinical trials?
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`24· I just remember the first names -- in -- they're in
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`24· · · ·A.· ·Again, it's in the area of pharmacokinetics
`
`25· Washington, D.C.· And there's a couple other ones.
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`25· and biopharmaceutical aspects of the drug.
`
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`Page 2 of 10
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`Patent Owner Ex. 2020
`CFAD v. Pozen
`IPR2015-01718
`
`

`
`
`LEON SHARGELLEON SHARGEL
`
`LUPIN vs. POZENLUPIN vs. POZEN
`
`·1· · · ·Q.· ·Can you be more specific?
`
`May 25, 2016May 25, 2016
`
`9–12
`Page 11
`·1· involved, has your role ever included the identification
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`Page 9
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`·2· · · ·A.· ·Biopharmaceutics deals with how the drug gets
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`·2· of the patients who are to be studied?
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`·3· out of a tablet or a capsule into the body, and we're
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`·3· · · ·A.· ·May I ask:· What do you mean by
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`·4· looking at absorption of the drug from said tablet into
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`·4· "identification"?
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`·5· the body.· And then we would give different doses and
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`·5· · · ·Q.· ·Determining whether or not a particular
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`·6· you look at how -- the doses and the amount of drug
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`·6· patient should be part of the study.
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`·7· coming in.· So if you have 10 milligrams, how much drug
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`·7· · · ·A.· ·When a study is put together, a protocol is
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`·8· comes in the body.· A 10 -- if you have a 20-milligram,
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`·8· written, which is sort of the operating idea of the
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`·9· how much does that -- and you build up a dosage regimen
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`·9· study, and you include what is called "inclusion" and
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`10· response for the new drug.
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`10· "exclusion factors" so that if you're looking for a
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`11· · · ·Q.· ·Can you identify the drugs?
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`11· particular set of patients -- you may not want smokers;
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`12· · · ·A.· ·I worked on many of them, particularly in the
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`12· you may not want women of childbearing age, or you may
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`13· generic areas, from Claritin to -- actually, you have
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`13· include women if they're on birth control or something
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`14· Naproxen, diclofenac.· I have to re-think of many of
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`14· of this sort.· So there is criteria for inclusion or
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`15· these.· I'm sorry.· I don't have all of the drugs
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`15· exclusion of subjects, depending upon the study.
`
`16· that -- we usually worked on -- we had 20 different
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`16· · · ·Q.· ·Can you describe for me your experience in
`
`17· products a year or more.
`
`17· identifying the inclusion or exclusion criteria?
`
`18· · · ·Q.· ·Any others you can think of?
`
`18· · · ·A.· ·I have audited the generic studies and
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`19· · · ·A.· ·Metaxalone was one, which is Skelaxin.· Xanax,
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`19· reviewed the case report forms, which is the people who
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`20· another one.· Several -- those are called
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`20· have been in a study, and looked to see whether they met
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`21· benzodiazepines, things similar to Valium, because I --
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`21· the inclusion and exclusion criteria.
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`22· I worked on several different ones of those series, but
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`22· · · ·Q.· ·Other than the auditing, do you have any
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`23· I don't recall all of the drugs.
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`23· experience in identifying the inclusion or exclusion
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`24· · · ·Q.· ·And these are all generic forms of the drugs
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`24· criteria?
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`25· that you've mentioned?
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`25· · · ·A.· ·Your -- your term "identifying," I -- I would
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`·1· · · ·A.· ·No.· In some cases, they were branded.· At
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`Page 10
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`Page 12
`·1· look at it as recruitment.· Is that what you mean?· When
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`·2· Forest Labs, which is now part of Actavis, they had both
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`·2· you recruit, you advertise or you look for a patient in
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`·3· a brand and generic side.· So we had several on the
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`·3· a study and you put in the characteristics that they
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`·4· brand side that we did blood-level work and -- and such.
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`·4· must be this way or that way within an age group.· We
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`·5· As I mentioned, pharmacokinetics.
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`·5· don't identify as an identifier.· I'm not sure of your
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`·6· · · ·Q.· ·For the branded side, which are the ones that
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`·6· question.
`
`·7· you can remember?
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`·7· · · ·Q.· ·Yeah, maybe we're just not using the -- the
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`·8· · · ·A.· ·I'm trying to think.· No, I don't recall.
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`·8· same terminology.· Somebody has to write out what the
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`·9· There was one for Alzheimer's, but I don't recall the
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`·9· inclusion criteria is; is that correct?
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`10· name of the drug.
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`11· · · ·Q.· ·Was it with Forest?
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`10· · · ·A.· ·Yes.· That's done by a medical committee.
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`11· · · ·Q.· ·And somebody has to write out what the
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`12· · · ·A.· ·Forest Labs, which is now bought out by
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`12· exclusion criteria is; is that correct?
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`13· Actavis.
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`13· · · ·A.· ·By the same committee.
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`14· · · ·Q.· ·Was that Namenda?
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`14· · · ·Q.· ·And have you ever been involved in that?
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`15· · · ·A.· ·They bought that after the fact.· They were --
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`15· · · ·A.· ·Yes.
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`16· Forest Labs had an interest in the Alzheimer's drugs,
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`16· · · ·Q.· ·Can you describe your involvement?
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`17· and they licensed out Namenda, but I didn't work on that
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`17· · · ·A.· ·In putting together -- let's -- let's take a
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`18· particular product.
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`18· straightforward study.· We can pick on a generic product
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`19· · · ·Q.· ·For the branded Alzheimer's drug where you did
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`19· that we want to look at.· And in this case, the
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`20· do work in a clinical trial, what was your involvement?
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`20· criteria, which is often given by FDA, that the study
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`21· · · ·A.· ·The involvement was look at blood levels and
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`21· must be -- be done in normal, healthy patients or
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`22· pharmacokinetics and how the drugs are absorbed and the
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`22· subjects.· And we may add they may be between a certain
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`23· relationship with the blood level to a clinical end
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`23· age group.· So 18 through 55 years of age, who are
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`24· point.
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`24· otherwise healthy by standard clinical tests and things
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`25· · · ·Q.· ·For the clinical trials in which you have been
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`25· of that sort.· So we -- we put that.· If they are
`
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`Page 3 of 10
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`Patent Owner Ex. 2020
`CFAD v. Pozen
`IPR2015-01718
`
`

`
`
`LEON SHARGELLEON SHARGEL
`
`LUPIN vs. POZENLUPIN vs. POZEN
`
`Page 13
`·1· smokers, use drugs -- we do a drug test on these
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`May 25, 2016May 25, 2016
`
`13–16
`Page 15
`·1· Parkinson's or Alzheimer's or any of these other kinds
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`·2· subjects as they come in -- they're excluded.· So we --
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`·2· of things.· So we would -- it's a criteria.· According
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`·3· we put together inclusion criteria and we put together
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`·3· to hypothesis, is the estrogen patch equivalent to, say,
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`·4· exclusion criteria.
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`·4· Estraderm, which might be the brand name.
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`·5· · · ·Q.· ·And the inclusion and exclusion criteria is
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`·5· · · ·Q.· ·Now, in addition to determining inclusion and
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`·6· determined at the outset of the study; is that correct?
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`·6· exclusion criteria, there is also a determination made
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`·7· · · ·A.· ·Every protocol is put together as clear as
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`·7· of what factors or criteria will be tracked in a study;
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`·8· possible, including an informed-consent form, and goes
`
`·8· is that correct?
`
`·9· to an institutional review board for that particular
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`·9· · · ·A.· ·That is part of the hypothesis, yes.
`
`10· hospital or clinic in which the study is going to be
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`10· · · ·Q.· ·And how is that determined?
`
`11· done.· The institutional review board is an ethics
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`11· · · ·A.· ·The determination is always:· What is the
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`12· committee, and they will review the inclusion/exclusion
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`12· objective of the study?
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`13· as well as all the other observations that would be done
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`13· · · · · · · · ·And once you have a clear-cut idea of what
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`14· on the subjects in the protocol.
`
`14· the objective is, then you can have other objectives.
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`15· · · ·Q.· ·Approximately how many medical -- medical
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`15· For example, again, going back to my bioequivalents, is
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`16· committees have you been on that have identified the
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`16· the product bio- -- we'll pick on Estraderm, since I
`
`17· inclusion and exclusion criteria?
`
`17· used that as an example -- is the estrogen patch made by
`
`18· · · ·A.· ·In terms of being on an IRB, which it's
`
`18· Sandoz equivalent to Estraderm?· That would be our
`
`19· called, the institutional review board, I was on the
`
`19· hypothesis.
`
`20· institutional review board for the National Institute of
`
`20· · · · · · · · ·We may look at other factors, such:· Does
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`21· Drug Abuse in Baltimore.· I was involved at
`
`21· the patch on the skin irritate the skin, as an adhesive?
`
`22· Massachusetts College of Pharmacy on the IRB.· In the
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`22· Does the patch fall off from the skin or does it stay on
`
`23· other cases, I am involved in putting the protocol
`
`23· for seven days?· Say it's a seven-day patch.· So input
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`24· together, so I am putting the protocol -- which will be
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`24· on that.· Do women who have this complain of headaches
`
`25· then submitted to the IRB.· So in one case, I'm on the
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`25· or anything else?
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`Page 14
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`·1· board for certain products; in the other case, I'm --
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`Page 16
`·1· · · · · · · · ·So we would put other observations.· But
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`·2· I'm the person who's involved in submitting the
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`·2· our main hypothesis still remains:· Is the drug
`
`·3· protocol.
`
`·3· bioequivalent?· That's the first hypothesis.· But we're
`
`·4· · · ·Q.· ·And approximately how many products?
`
`·4· also going to look at safety, adverse events, and other
`
`·5· · · ·A.· ·Hundreds.
`
`·5· issues that may occur.
`
`·6· · · ·Q.· ·What is the methodology by which the inclusion
`
`·6· · · ·Q.· ·The issues that you're interested in looking
`
`·7· and exclusion criteria is determined?
`
`·7· at as the study goes forward, how are those tracked?
`
`·8· · · ·A.· ·The first part of any study is to have a
`
`·8· · · ·A.· ·Well, we can start at the beginning of the
`
`·9· hypothesis and -- so the scientific method.· So what are
`
`·9· study, in which case -- if we go back to my estrogen
`
`10· you trying to prove?· And in this case, in the generic,
`
`10· patch example, there would be -- this was done in
`
`11· you're trying to prove that the generic product is what
`
`11· Florida, with a contract research organization.· And
`
`12· we call a "bioequivalent" to the brand-name products.
`
`12· they would advertise for women in terms of who would
`
`13· So that is our hypothesis.· It is either equivalent or
`
`13· meet the minimum criteria, being otherwise healthy,
`
`14· it is not equivalent.
`
`14· being postmenopausal, and -- and within an age group
`
`15· · · · · · · · ·Then we have to have some methodology in
`
`15· specified.
`
`16· terms of determining that, in terms of subjects, in
`
`16· · · · · · · · ·Now, they got that information from the
`
`17· terms of the healthy subjects.· Are we going to use
`
`17· protocol.· This is -- and -- and the protocol hadn't
`
`18· patients that have a disease entity?· Are we going to
`
`18· been approved.· So advertising is done first.· There
`
`19· use women?· Are we going to use -- I did, for example,
`
`19· will be women who will come in and will be initially
`
`20· an estrogen patch that was, obviously, going to be done
`
`20· recruited if they meet the criteria.· If they're
`
`21· in women, and it was done in postmenopausal women.· So
`
`21· alcoholic or a drug problem or such, they will,
`
`22· in that particular case, they were normal, healthy --
`
`22· obviously, be refused in the study.
`
`23· you wouldn't want to say a postmenopausal woman is
`
`23· · · · · · · · ·At that point in time, they will enter the
`
`24· unhealthy, but we wanted to put criteria to be sure that
`
`24· clinic at a specified day or time, receive the
`
`25· she otherwise had no other particular problems, such as
`
`25· appropriate treatment.· They will be housed, usually, at
`
`
`800.211.DEPO (3376)800.211.DEPO (3376)
`
`EsquireSolutions.comEsquireSolutions.comYVer1f
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`Page 4 of 10
`
`Patent Owner Ex. 2020
`CFAD v. Pozen
`IPR2015-01718
`
`

`
`
`LEON SHARGELLEON SHARGEL
`
`LUPIN vs. POZENLUPIN vs. POZEN
`
`Page 17
`·1· least for 24 hours, and blood samples will be taken; the
`
`·1· patients or is this going to be patients that are
`
`May 25, 2016May 25, 2016
`
`17–20
`Page 19
`
`·2· protocol will be followed.· There will be a physician,
`
`·2· brought in and then sent out, after certain training, to
`
`·3· nurses, phlebotomists, quality-assurance people.
`
`·3· be on their own.· So we would have to determine what we
`
`·4· · · ·Q.· ·How does that procedure work in the case of
`
`·4· have, as far as a protocol, and what is our objectives.
`
`·5· a -- of a drug that is taken orally?
`
`·5· · · ·Q.· ·What are the possibilities?
`
`·6· · · ·A.· ·The same procedure, except you don't put it on
`
`·6· · · ·A.· ·Possibilities for what, sir?
`
`·7· the skin; you swallow the drug.
`
`·7· · · ·Q.· ·For tracking that.
`
`·8· · · ·Q.· ·Are they housed, as well, the patients?
`
`·8· · · ·A.· ·I'll come back to the hypothesis of the
`
`·9· · · ·A.· ·Yes.
`
`·9· question -- I mean, of the study.· If we have an
`
`10· · · ·Q.· ·Would it be atypical not to house the
`
`10· in-house study, we have it monitored very well.
`
`11· patients?
`
`11· · · ·Q.· ·And if it's not?
`
`12· · · ·A.· ·I don't quite understand the question.· If you
`
`12· · · ·A.· ·The subjects are monitored.· They initially
`
`13· don't have the patients, you wouldn't have the study,
`
`13· have a training period, and then they will be monitored
`
`14· which, apparently -- maybe I'm reading your question
`
`14· during the period of time -- over a period of time.
`
`15· wrong.
`
`15· · · ·Q.· ·How would they be monitored?
`
`16· · · ·Q.· ·Are there studies where the patients are not
`
`16· · · ·A.· ·They may come in to the clinic each day.· They
`
`17· housed, where they are provided with the drug and then
`
`17· will be called.· There will be a pill count at -- at a
`
`18· they just go home?
`
`19· · · ·A.· ·That --
`
`18· certain time to see what they have not taken.· It can be
`
`19· done a number of different ways.
`
`20· · · · · · · · ·MS. LaVALLE:· Objection, form.
`
`20· · · ·Q.· ·What records are kept?
`
`21· · · ·A.· ·That, again, depends upon the hypothesis of
`
`21· · · ·A.· ·They keep all records of all contact, all
`
`22· the study.· If your hypothesis is going to be a
`
`22· e-mails, all phone calls, all measurements of bodily
`
`23· longer-time treatment, it may be necessary to give
`
`23· functions, such as blood pressures and whatever else is
`
`24· instructions and then the patients understand that they
`
`24· needed.
`
`25· carry a diary; they're responsible for self-medication.
`
`25· · · ·Q.· ·What records are kept with respect to the
`
`Page 18
`·1· And there are some controls about counting the number of
`
`·1· exclusion criteria?
`
`Page 20
`
`·2· pills they've taken at any specific time, and they may
`
`·2· · · ·A.· ·When the patients are initially recruited,
`
`·3· be calling in.· There will be something in the protocol
`
`·3· they're first checked whether they meet the recruit- --
`
`·4· to track them, even though they are ambulatory and on
`
`·4· exclusion criteria.· And if they don't meet it, they're
`
`·5· their own.
`
`·5· rejected from the study.
`
`·6· · · ·Q.· ·(BY MR. RODRIGUEZ)· Okay.· And you've answered
`
`·6· · · ·Q.· ·And thereafter?
`
`·7· part of this with your response right now, but can you
`
`·7· · · ·A.· ·This is -- what we try to do is track the
`
`·8· identify for me the steps that are taken to make sure
`
`·8· patients.· If they're not in-house, they're -- and I
`
`·9· that each patient receives the right amount of drug at
`
`·9· assume -- well, I never assume, but is that what you're
`
`10· the right time?
`
`11· · · · · · · · ·MS. LaVALLE:· Objection, form.
`
`10· asking --
`
`11· · · ·Q.· ·Yes.
`
`12· · · ·A.· ·Again, it depends upon the study that we're
`
`12· · · ·A.· ·-- if they're --
`
`13· doing.· If we're doing an in-house study, a nurse or a
`
`13· · · ·Q.· ·Not in-house.
`
`14· nurse-practitioner will administer the drug.· It could
`
`14· · · ·A.· ·-- not in-house?
`
`15· be some specialized medical assistant to administer the
`
`15· · · · · · · · ·So if they're not in-house, we'll have to
`
`16· drugs that the person is taking at a specified time
`
`16· track by phone calls, by having them come in
`
`17· under specified conditions.
`
`17· periodically.· They may have to be -- certain testing
`
`18· · · ·Q.· ·(BY MR. RODRIGUEZ)· You mentioned before that
`
`18· done periodically, in which case you can do a drug test.
`
`19· a couple of common exclusion criteria are drugs and
`
`19· · · ·Q.· ·And there are records kept of all of these
`
`20· alcohol.· How is that monitored to make sure that,
`
`20· testings?
`
`21· initially, they may not have been involved with either
`
`21· · · ·A.· ·It's mandatory.
`
`22· of those, but later, during the study, they might?
`
`22· · · ·Q.· ·You mentioned a diary before.· How does a
`
`23· · · ·A.· ·Well, you have it open-ended in terms of
`
`23· diary -- diary work in connection with one of these
`
`24· study.· Again, we have to go back to what is the study
`
`24· studies?
`
`25· hypothesis, and is this going to be an -- in-house
`
`25· · · ·A.· ·It will go back to what -- what -- the kind of
`
`
`800.211.DEPO (3376)800.211.DEPO (3376)
`
`EsquireSolutions.comEsquireSolutions.comYVer1f
`
`Page 5 of 10
`
`Patent Owner Ex. 2020
`CFAD v. Pozen
`IPR2015-01718
`
`

`
`
`LEON SHARGELLEON SHARGEL
`
`LUPIN vs. POZENLUPIN vs. POZEN
`
`Page 21
`·1· study you're doing and if they're on their own, as they
`
`·1· hear --
`
`May 25, 2016May 25, 2016
`
`21–24
`Page 23
`
`·2· seem to go, then we want to be sure that the patient is
`
`·2· · · ·Q.· ·When did you first learn of misoprostol?
`
`·3· taking the medication as instructed.· So they may write
`
`·3· · · ·A.· ·I am a registered pharmacist in 1963.· It's
`
`·4· down the time -- each time they take the medication, any
`
`·4· been around for a long time.· I'm -- don't recall the
`
`·5· kind of feeling, if they feel they've got a headache,
`
`·5· exact moment in time, but it's many, many years ago.
`
`·6· whether it was drug-related or not, any -- any
`
`·6· It's been used -- I guess it's been used since the '70s.
`
`·7· complaints or adverse events.· They will keep a diary.
`
`·7· · · ·Q.· ·So you've --
`
`·8· · · ·Q.· ·And the -- the diaries are kept, as well?
`
`·8· · · ·A.· ·That's, more or less, a grounded thing, but
`
`·9· · · ·A.· ·Yes.
`
`·9· it's been around for a long time, this product.
`
`10· · · ·Q.· ·Now, in terms of the reporting of the studies,
`
`10· · · ·Q.· ·You first learned of it before this matter?
`
`11· what information is provided in the reports?
`
`11· · · ·A.· ·Yes.
`
`12· · · ·A.· ·The report, basically, is a complete dossier
`
`12· · · ·Q.· ·Are you familiar with proton pump inhibitors?
`
`13· of -- all the tests are summarized, usually
`
`13· · · ·A.· ·Yes.
`
`14· statistically evaluated, and eventually a summary of the
`
`14· · · ·Q.· ·When did you first learn of those?
`
`15· entire study is also sent to the institutional review
`
`15· · · ·A.· ·They first came out in the '80s, 1980s,
`
`16· board, as well.
`
`16· sometime in that period.
`
`17· · · ·Q.· ·Do the reports indicate or identify the
`
`17· · · ·Q.· ·Can you describe how they function?
`
`18· criteria for inclusion or exclusion of patients?
`
`18· · · ·A.· ·They work on what is called an atpA system,
`
`19· · · ·A.· ·That's in the original protocol.
`
`19· which -- a proton, which is a hydrogen, goes into the --
`
`20· · · ·Q.· ·And do the reports identify the criteria that
`
`20· what we're interested in here is the gastric area -- and
`
`21· is tracked over the course of the study?
`
`21· increases acidity.· So what the proton pump inhibitor
`
`22· · · ·A.· ·That's in the protocol.
`
`22· does, it literally inhibits that proton from going into
`
`23· · · ·Q.· ·Can you give me an overview of your experience
`
`23· the stomach by inhibiting the atpA system, which is an
`
`24· in statistics?
`
`24· energy system that moves -- shuttles protons and
`
`25· · · ·A.· ·I had minimum statistics.· I have understood
`
`25· potassium.
`
`Page 22
`·1· how statistics are run, but I go to a statistician when
`
`Page 24
`·1· · · ·Q.· ·Is it your understanding that the mechanism of
`
`·2· I need complicated statistics such as in large clinical
`
`·2· action of misoprostol is different from a proton pump
`
`·3· trials.
`
`·3· inhibitor?
`
`·4· · · ·Q.· ·Have you prescribed medication for anyone?
`
`·4· · · ·A.· ·Yes.
`
`·5· · · ·A.· ·No.· I'm not legally allowed to prescribe any
`
`·5· · · ·Q.· ·What are all the differences that you can
`
`·6· medication.
`
`·6· identify?
`
`·7· · · ·Q.· ·Have you treated any patients for any medical
`
`·7· · · ·A.· ·I don't recall exactly how the prostaglandin
`
`·8· conditions?
`
`·8· works on a molecular basis.
`
`·9· · · ·A.· ·I am not a physician.
`
`·9· · · · · · · · ·MR. RODRIGUEZ:· Can we just take a short
`
`10· · · ·Q.· ·Are you familiar with misoprostol?
`
`10· break?
`
`11· · · ·A.· ·Somewhat, yes.
`
`11· · · · · · · · ·THE VIDEOGRAPHER:· The time is now
`
`12· · · ·Q.· ·What is your understanding?
`
`12· 9:30 a.m.· We are now off the record.
`
`13· · · ·A.· ·It's a prostaglandin known as Cytotec.· It is
`
`13· · · · · · · · ·(Recess taken from 9:31 to 9:44 a.m.)
`
`14· both a -- a proton-inhibitor, as well as coats the --
`
`14· · · · · · · · ·THE VIDEOGRAPHER:· The time is 9:44 a.m.
`
`15· protects the linings of the gastric mucosa.
`
`15· We are now on record.
`
`16· · · · · · · · ·THE REPORTER:· I'm sorry?· The lining --
`
`16· · · · · · · · ·MS. KRUMPLITSCH:· Can we go off the
`
`17· I'm sorry.· You're turned --
`
`17· record for one second?
`
`18· · · · · · · · ·THE WITNESS:· The lin- --
`
`18· · · · · · · · ·THE VIDEOGRAPHER:· The time is now
`
`19· · · · · · · · ·THE REPORTER:· -- away from me.
`
`19· 9:44 a.m.· We are now off record.
`
`20· · · · · · · · ·THE WITNESS:· I'm sorry.· Linings of the
`
`20· · · · · · · · ·(Recess taken from 9:44 to 9:46 a.m.)
`
`21· gastric mucosa.
`
`21· · · · · · · · ·(Exhibits 1-3 marked.)
`
`22· · · ·A.· ·And also inhibits acid in the stomach.
`
`22· · · · · · · · ·THE VIDEOGRAPHER:· The time is now
`
`23· · · ·Q.· ·(BY MR. RODRIGUEZ)· When did you first learn
`
`23· 9:46 a.m.· We are now on record.
`
`24· of misoprostol?
`
`24· · · ·Q.· ·(BY MR. RODRIGUEZ)· I've handed you what is
`
`25· · · ·A.· ·I'm sorry.· Could you repeat that?· I didn't
`
`25· marked as Exhibit 1.· Would you please take a look at
`
`
`800.211.DEPO (3376)800.211.DEPO (3376)
`
`EsquireSolutions.comEsquireSolutions.comYVer1f
`
`Page 6 of 10
`
`Patent Owner Ex. 2020
`CFAD v. Pozen
`IPR2015-01718
`
`

`
`
`LEON SHARGELLEON SHARGEL
`
`LUPIN vs. POZENLUPIN vs. POZEN
`
`·1· Exhibit 1 and tell me if you recognize it?
`
`·2· · · ·A.· ·Yes.· It's my declaration.
`
`Page 25
`
`·1· know?
`
`·2· · · ·A.· ·No.
`
`May 25, 2016May 25, 2016
`
`25–28
`Page 27
`
`·3· · · ·Q.· ·And I have handed you what is marked as
`
`·3· · · ·Q.· ·Can you give any examples?
`
`·4· Exhibit 2.· Would you please take a look at that and
`
`·4· · · ·A.· ·Branded?· Well, Burroughs Wellcome used to
`
`·5· tell me if you recognize it?
`
`·6· · · ·A.· ·Yes.
`
`·7· · · ·Q.· ·What is Exhibit 2?
`
`·5· make an empirin compound.
`
`·6· · · · · · · · ·THE REPORTER:· I'm sorry --
`
`·7· · · ·A.· ·There's aspirin --
`
`·8· · · ·A.· ·Exhibit 2 is an article, by David Graham and
`
`·8· · · · · · · · ·THE REPORTER:· I'm sorry --
`
`·9· others, entitled:· Ulcer Prevention in Long-Term Users
`
`·9· · · ·A.· ·Okay.· I'm thinking.· As- -- there are some
`
`10· of Nonsteroidal Anti-Inflammatory Drugs.
`
`10· aspirin/caffeine or acetaminophen combinations, but I
`
`11· · · ·Q.· ·And is Exhibit 2 one of the references that
`
`11· don't recall the names at this point.
`
`12· you discuss in your declaration, Exhibit 1?
`
`12· · · ·Q.· ·(BY MR. RODRIGUEZ)· Would you say that there
`
`13· · · ·A.· ·Yes.
`
`13· are more than 25 different aspirin combinations?
`
`14· · · ·Q.· ·Can you tell me how you identified or learned
`
`14· · · ·A.· ·I would rather not put a number on it.
`
`15· of Exhibit 2, the