·1· · · ·UNITED STATES PATENT AND TRADEMARK OFFICE
`
`·2· · · · · · · ·___________________________
`
`·3· · · · BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`·4· · · · · · · ___________________________
`
`·5· · MYLAN PHARMACEUTICALS INC., TEVA PHARMACEUTICALS
`· · · · · · · · ·USA, INC. and AKORN INC.,
`·6· · · · · · · · · · · Petitioners,
`
`·7· · · · · · · · · · · · · ·v.
`
`·8· · · · · · · · · · ·ALLERGAN, INC.
`· · · · · · · · · · · ·Patent Owner.
`·9· · · · · · · ·___________________________
`
`10· · · · · ·Case IPR2016-01127 (US 8,685,930 B2)
`· · · · · · ·Case IPR2016-01128 (US 8,629,111 B2)
`11· · · · · ·Case IPR2016-01129 (US 8,624,556 B2)
`· · · · · · ·Case IPR2016-01130 (US 8,633,162 B2)
`12· · · · · ·Case IPR2016-01131 (US 8,648,048 B2)
`· · · · · · ·Case IPR2016-01132 (US 9,248,191 B2)
`13
`
`14
`
`15· · · ·CONFIDENTIAL PURSUANT TO PROTECTIVE ORDER
`
`16· · · · DEPOSITION OF RHETT M. SCHIFFMAN, M.D.
`
`17· · · · · · · · · ·Irvine, California
`
`18· · · · · · · · ·Thursday, June 1, 2017
`
`19· · · · · · · · · · · · Volume I
`
`20
`
`21
`
`22
`
`23· Reported by:
`· · DENISE BARDSLEY
`24· CSR No. 11241
`
`25· Job No. 10033406
`
`MYLAN - EXHIBIT 1035
`Mylan Pharmaceuticals Inc. et al. v. Allergan, Inc.
`IPR2016-01127, -01128, -01129, -01130, -01131, & -01132
`
`PROTECTIVE ORDER MATERIAL
`
`
`
`·2· · · · · · · ·___________________________
`
`·3· · · · BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`·4· · · · · · · ___________________________
`
`·5· · MYLAN PHARMACEUTICALS INC., TEVA PHARMACEUTICALS
`· · · · · · · · ·USA, INC. and AKORN INC.,
`·6· · · · · · · · · · · Petitioners,
`
`·7· · · · · · · · · · · · · ·v.
`
`·8· · · · · · · · · · ·ALLERGAN, INC.
`· · · · · · · · · · · ·Patent Owner.
`·9· · · · · · · ·___________________________
`
`10· · · · · ·Case IPR2016-01127 (US 8,685,930 B2)
`· · · · · · ·Case IPR2016-01128 (US 8,629,111 B2)
`11· · · · · ·Case IPR2016-01129 (US 8,624,556 B2)
`· · · · · · ·Case IPR2016-01130 (US 8,633,162 B2)
`12· · · · · ·Case IPR2016-01131 (US 8,648,048 B2)
`· · · · · · ·Case IPR2016-01132 (US 9,248,191 B2)
`13
`
`14
`
`15· · · ·CONFIDENTIAL PURSUANT TO PROTECTIVE ORDER
`
`16· · · · DEPOSITION OF RHETT M. SCHIFFMAN, M.D.
`
`17· · · · · · · · · ·Irvine, California
`
`18· · · · · · · · ·Thursday, June 1, 2017
`
`19· · · · · · · · · · · · Volume I
`
`20
`
`21
`
`22
`
`23· Reported by:
`· · DENISE BARDSLEY
`24· CSR No. 11241
`
`25· Job No. 10033406
`
`MYLAN - EXHIBIT 1035
`Mylan Pharmaceuticals Inc. et al. v. Allergan, Inc.
`IPR2016-01127, -01128, -01129, -01130, -01131, & -01132
`
`PROTECTIVE ORDER MATERIAL
`
`
`
`·1· · · ·UNITED STATES PATENT AND TRADEMARK OFFICE
`
`·2· · · · · · · ·___________________________
`
`·3· · · · BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`·4· · · · · · · ___________________________
`
`·5· · MYLAN PHARMACEUTICALS INC., TEVA PHARMACEUTICALS
`· · · · · · · · ·USA, INC. and AKORN INC.,
`·6· · · · · · · · · · · Petitioners,
`
`·7· · · · · · · · · · · · · ·v.
`
`·8· · · · · · · · · · ·ALLERGAN, INC.
`· · · · · · · · · · · ·Patent Owner.
`·9· · · · · · · ·___________________________
`
`10· · · · · ·Case IPR2016-01127 (US 8,685,930 B2)
`· · · · · · ·Case IPR2016-01128 (US 8,629,111 B2)
`11· · · · · ·Case IPR2016-01129 (US 8,624,556 B2)
`· · · · · · ·Case IPR2016-01130 (US 8,633,162 B2)
`12· · · · · ·Case IPR2016-01131 (US 8,648,048 B2)
`· · · · · · ·Case IPR2016-01132 (US 9,248,191 B2)
`13
`
`14
`
`15· · · · · ·Deposition of RHETT M. SCHIFFMAN, M.D.,
`
`16· Volume I, taken on behalf of Mylan Inc., at 3161
`
`17· Michelson Drive, Suite 1200, Irvine, California,
`
`18· beginning at 9:03 a.m., and ending at 11:27 a.m.,
`
`19· on Thursday, June 1, 2017, before Denise Bardsley,
`
`20· Certified Shorthand Reporter No. 11241.
`
`21
`
`22
`
`23
`
`24
`
`25
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`PROTECTIVE ORDER MATERIAL
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`
`
`·1· APPEARANCES:
`
`·2
`
`·3· For Patent Owners:
`
`·4· · · ·FISH & RICHARDSON PC
`· · · · ·BY:· SUSAN MORRISON
`·5· · · ·Attorney at Law
`· · · · ·222 Delaware Avenue, 17th Floor
`·6· · · ·Wilmington, Delaware· 19899
`· · · · ·(302) 652-5070
`·7· · · ·coletti@fr.com
`
`·8· · · ·FISH & RICHARDSON PC
`· · · · ·BY:· JONATHAN E. SINGER
`·9· · · ·Attorney at Law
`· · · · ·12390 El Camino Real
`10· · · ·San Diego, California· 92130-2081
`· · · · ·(858) 678-5070
`11· · · ·singer@fr.com
`
`12· For Teva Pharmaceuticals:
`
`13· · · ·CARLSON, CASPERS, VANDENBURGH,
`· · · · ·LINDQUIST & SCHUMAN
`14· · · ·BY:· GARY J. SPEIER
`· · · · ·Attorney at Law
`15· · · ·225 South 6th Street
`· · · · ·Minneapolis, Minnesota· 55042
`16· · · ·(612) 436-9643
`· · · · ·gspeier@carlsoncaspers.com
`17· · · ·(Telephonic appearance.)
`
`18· For Akorn Inc.:
`
`19· · · ·SUGHRUE MION, PLLC
`· · · · ·2100 Pennsylvania Avenue, NW
`20· · · ·Washington, D.C.· 20037
`· · · · ·(202) 293-7060
`21· · · ·(No appearance.)
`
`22
`
`23
`
`24
`
`25
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`PROTECTIVE ORDER MATERIAL
`
`
`
`·1· APPEARANCES (Continued):
`
`·2
`
`·3· For Mylan Inc.:
`
`·4· · · ·WILSON SONSINI GOODRICH & ROSATI
`· · · · ·BY:· WENDY LYNN DEVINE
`·5· · · ·BY:· CHRISTINA E. DASHE
`· · · · ·BY:· JAD A. MILLS
`·6· · · ·Attorneys at Law
`· · · · ·12235 El Camino Real, Suite 200
`·7· · · ·San Diego, California· 92130-3002
`· · · · ·(858) 350-2300
`·8· · · ·wdevine@wsgr.com
`· · · · ·cdashe@wsgr.com
`·9· · · ·jmills@wsgr.com
`
`10· Also Present:
`
`11· · · ·BRIAN ANDERSON
`· · · · ·JACQUELINE ALTMAN
`12
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`13
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`14
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`15
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`16
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`17
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`18
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`19
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`20
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`21
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`22
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`23
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`24
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`25
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`PROTECTIVE ORDER MATERIAL
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`·1· · · · · · · · · · · · ·INDEX
`
`·2· WITNESS· · · · · · · · · · · · · · · · · EXAMINATION
`
`·3· RHETT M. SCHIFFMAN, M.D.
`
`·4· VOLUME I
`
`·5· · · · · · · ·BY MS. DEVINE· · · · · · · · · · · · 7
`
`·6· · · · · · · · · · · · · ·EXHIBITS
`
`·7· EXHIBIT· · · · · · · · ·DESCRIPTION· · · · · · PAGE
`
`·8· Exhibit 1027· ·Allergan Department of· · · · · · 49
`· · · · · · · · · ·Pharmacokinetics and Drug
`·9· · · · · · · · ·Metabolism Departmental
`· · · · · · · · · ·Research Report, Report No:
`10· · · · · · · · ·PK-00-163, Concentrations of
`· · · · · · · · · ·Cyclosporin A in Cornea and
`11· · · · · · · · ·Conjunctiva After a Single
`· · · · · · · · · ·Ophthalmic Dose to New
`12· · · · · · · · ·Zealand White Rabbits:
`· · · · · · · · · ·Evaluation of 7 Ophthalmic
`13· · · · · · · · ·Emulsion Formulations
`
`14· Exhibit 1028· ·Allergan R&D Records· · · · · · · 50
`· · · · · · · · · ·Management, Notebook Number
`15· · · · · · · · ·L-2000-7626
`· · · · · · · · · ·Confidential
`16
`
`17· Exhibit 1029· ·Allergan R&D Records· · · · · · · 51
`· · · · · · · · · ·Management, Notebook Number
`18· · · · · · · · ·L 1998-5709
`· · · · · · · · · ·Confidential
`19
`
`20· Exhibit 1030· ·Allergan R&D Records· · · · · · · 51
`· · · · · · · · · ·Management, Notebook Number
`21· · · · · · · · ·L 1998-5707
`· · · · · · · · · ·Confidential
`22
`
`23· Exhibit 1031· ·Allergan R&D Records· · · · · · · 52
`· · · · · · · · · ·Management, Notebook Number
`24· · · · · · · · ·L-2000-7726
`· · · · · · · · · ·Confidential
`25
`
`PROTECTIVE ORDER MATERIAL
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`
`
`·1· INDEX (Continued):
`
`·2· · · · · · · ·PREVIOUSLY MARKED EXHIBITS
`
`·3· · · · · · · · · · EXHIBIT· · ·PAGE
`
`·4· · · · · · · · · · · 1004· · · ·24
`· · · · · · · · · · · · 1007· · · ·28
`·5· · · · · · · · · · · 1015· · · ·28
`· · · · · · · · · · · · 2027· · · ·49
`·6
`
`·7
`
`·8
`
`·9· · · · · · · ·INSTRUCTION NOT TO ANSWER
`
`10· · · · · · · · · · · ·Page· ·Line
`
`11· · · · · · · · · · · · 10· · ·25
`
`12
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`13
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`14
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`15
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`16
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`17
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`18
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`19
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`20
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`21
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`22
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`23
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`24
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`25
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`PROTECTIVE ORDER MATERIAL
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`
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`·1· · · ·Irvine, California, Thursday, June 1, 2017
`
`·2· · · · · · · · · · · ·9:03 a.m.
`
`·3
`
`·4· · · · · · · ·RHETT M. SCHIFFMAN, M.D.,
`
`·5· having been administered an oath, was examined and
`
`·6· testified as follows:
`
`·7
`
`·8· · · · · · · · · · · EXAMINATION
`
`·9· BY MS. DEVINE:
`
`10· · · ·Q· ·Good morning, Dr. Schiffman.
`
`11· · · ·A· ·Good morning.
`
`12· · · ·Q· ·Would you please state your full name for
`
`13· the record.
`
`14· · · ·A· ·Rhett Mead Schiffman.
`
`15· · · · · ·MS. DEVINE:· I think we're supposed to open
`
`16· my conference line.
`
`17· · · · · ·MR. SINGER:· I was going to ask if people
`
`18· could announce their appearances on the record.
`
`19· · · · · ·MS. DEVINE:· Off the record real quick.
`
`20· · · · · ·(Discussion off the record.)
`
`21· · · · · ·MS. DEVINE:· Okay.· So Wendy Devine of
`
`22· Wilson Sonsini Goodrich & Rosati on behalf of Mylan.
`
`23· With me are my colleagues, Christina Dashe,
`
`24· Jacqueline Altman and Jad Mills.
`
`25· · · · · ·MR. SINGER:· And for patent owner,
`
`PROTECTIVE ORDER MATERIAL
`
`
`
`·1· Allergan, it is Jonathan Singer, Fish & Richardson.
`
`·2· With me is Susan Morrison of Fish & Richardson and
`
`·3· Brian Anderson of Allergan.
`
`·4· BY MS. DEVINE:
`
`·5· · · ·Q· ·Okay.· So just starting all over again,
`
`·6· would you please state your full name for the
`
`·7· record.
`
`·8· · · ·A· ·Rhett Mead Schiffman.
`
`·9· · · ·Q· ·And would you please state your current
`
`10· address.· Work or home is fine.
`
`11· · · ·A· ·1970 Temple Hills Drive, Laguna Beach,
`
`12· California.
`
`13· · · ·Q· ·And, Dr. Schiffman, if you don't understand
`
`14· a question today, will you please let me know?
`
`15· · · ·A· ·Yes, ma'am.
`
`16· · · ·Q· ·And is there any reason why you cannot give
`
`17· truthful testimony today?
`
`18· · · ·A· ·There is not.
`
`19· · · ·Q· ·Okay.· Dr. Schiffman, how much have you
`
`20· been paid by Allergan in connection with your work
`
`21· on this matter?
`
`22· · · ·A· ·I'm paid an hourly rate.
`
`23· · · ·Q· ·And what's your hourly rate?
`
`24· · · ·A· ·$750.
`
`25· · · ·Q· ·And how many hours have you billed?
`
`PROTECTIVE ORDER MATERIAL
`
`
`
`·1· · · ·A· ·All told?
`
`·2· · · ·Q· ·On this matter.
`
`·3· · · ·A· ·On this matter, nothing -- well, just for
`
`·4· preparation yesterday.
`
`·5· · · ·Q· ·And how long did you spend preparing
`
`·6· yesterday?
`
`·7· · · ·A· ·I think four hours or so.
`
`·8· · · ·Q· ·Okay.· Who was present at your preparation
`
`·9· yesterday?
`
`10· · · ·A· ·These three individuals here.
`
`11· · · ·Q· ·Anyone else?
`
`12· · · ·A· ·Someone was on the phone.
`
`13· · · ·Q· ·Do you know who that person was?
`
`14· · · ·A· ·I don't.
`
`15· · · ·Q· ·Do you know if it was a lawyer?
`
`16· · · ·A· ·It was.
`
`17· · · ·Q· ·Was it Allergan counsel?
`
`18· · · ·A· ·I don't know.· I don't know.
`
`19· · · ·Q· ·Okay.· Did you review documents in
`
`20· preparation for your deposition?
`
`21· · · · · ·MR. SINGER:· Objection.· If you lay a
`
`22· foundation, I'll let him answer the question.
`
`23· Otherwise, I instruct not to answer based on
`
`24· privilege.
`
`25· · · · · ·(Instruction not to answer.)
`
`PROTECTIVE ORDER MATERIAL
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`
`
`·1· · · · · ·MS. DEVINE:· Okay.
`
`·2· · · · · ·THE WITNESS:· I did.
`
`·3· BY MS. DEVINE:
`
`·4· · · ·Q· ·You did?· Okay.
`
`·5· · · · · ·Did you review any documents of your
`
`·6· choosing in preparation for your deposition or did
`
`·7· counsel give you all of the documents that you
`
`·8· reviewed --
`
`·9· · · ·A· ·I didn't bring any documents.
`
`10· · · ·Q· ·Okay.· Did you talk to anyone about your
`
`11· deposition today other than counsel?
`
`12· · · ·A· ·I did not.
`
`13· · · ·Q· ·Okay.· Dr. Schiffman, did you work on the
`
`14· clinical trials for Restasis?
`
`15· · · ·A· ·I did.
`
`16· · · ·Q· ·Did you work on the Phase 1 trials?
`
`17· · · ·A· ·I did not.
`
`18· · · ·Q· ·Did you work on the Phase 2 trials?
`
`19· · · ·A· ·I did not.
`
`20· · · ·Q· ·Did you work on the Phase 3 trials?
`
`21· · · ·A· ·I did.
`
`22· · · ·Q· ·Okay.· What was your role in the Phase 3
`
`23· trials?
`
`24· · · ·A· ·I was an investigator for the Phase 3
`
`25· trial.
`
`PROTECTIVE ORDER MATERIAL
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`
`
`·1· · · ·Q· ·Did you play a role in designing any of the
`
`·2· protocols for the Phase 3 trial?
`
`·3· · · ·A· ·I played a role in validating one of the
`
`·4· intended end points.
`
`·5· · · ·Q· ·Which intended end point?
`
`·6· · · ·A· ·The ocular surface disease index.
`
`·7· · · ·Q· ·What's the ocular surface disease index?
`
`·8· · · ·A· ·It's a 12-item questionnaire that's meant
`
`·9· to summarize a patient's symptoms and function
`
`10· related to the effect of dry eye.
`
`11· · · ·Q· ·The effects of dry eye?
`
`12· · · ·A· ·Uh-huh.
`
`13· · · ·Q· ·What's dry eye?
`
`14· · · ·A· ·Well, dry eye is a -- it is what we've now
`
`15· learned to be a very complicated, multi-factorial
`
`16· disease that can involve either excess evaporation
`
`17· or deficient tear production from a whole host of
`
`18· reasons.
`
`19· · · ·Q· ·Is keratoconjunctivitis sicca the same
`
`20· thing as dry eye?
`
`21· · · ·A· ·It is often considered the same thing.
`
`22· · · ·Q· ·By who?
`
`23· · · ·A· ·Experts, even in the literature.· There's
`
`24· usually some overlap or that people refer to them
`
`25· interchangeably.
`
`PROTECTIVE ORDER MATERIAL
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`
`
`·1· · · ·Q· ·What did you do to validate the -- is it
`
`·2· OSDI?
`
`·3· · · ·A· ·Yes.
`
`·4· · · ·Q· ·What did you do?
`
`·5· · · ·A· ·I enrolled, I think, a little more than a
`
`·6· hundred patients who were either normal or had some
`
`·7· severity of dry eye --
`
`·8· · · · · ·MR. SINGER:· Pardon me.
`
`·9· · · · · ·Madam Court Reporter, is there realtime
`
`10· available that counsel is using?
`
`11· · · · · ·THE REPORTER:· Yes.
`
`12· · · · · ·MR. SINGER:· May I please have it?
`
`13· · · · · ·THE REPORTER:· Of course.
`
`14· · · · · ·MS. DEVINE:· Do you want to go off the
`
`15· record?
`
`16· · · · · ·(Whereupon Gary Spier, representing
`
`17· · · · · ·Defendant Teva Pharmaceuticals, joined
`
`18· · · · · ·via telephonic appearance.)
`
`19· BY MS. DEVINE:
`
`20· · · ·Q· ·Dr. Schiffman, I believe you were telling
`
`21· me what you did when you validated OSDI in the
`
`22· context of the Phase 3 study; is that right?
`
`23· · · ·A· ·Prior to the Phase 3 study, yes.
`
`24· · · ·Q· ·Prior to the Phase 3 study you did the
`
`25· validation?
`
`PROTECTIVE ORDER MATERIAL
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`·1· · · ·A· ·Yes.
`
`·2· · · ·Q· ·It was not part of the Phase 3 study?
`
`·3· · · ·A· ·It became part of the Phase 3 study, but it
`
`·4· needed to be validated before it was used in the
`
`·5· Phase 3 study.
`
`·6· · · ·Q· ·Okay.· And so then within the context of
`
`·7· the actual Phase 3 study, what was your role?
`
`·8· · · ·A· ·An investigator.
`
`·9· · · ·Q· ·Okay.· And did you use OSDI as an
`
`10· investigator in the Phase 3 study?
`
`11· · · ·A· ·Everyone did.
`
`12· · · ·Q· ·Okay.· What other end points did you
`
`13· evaluate as an investigator in the Phase 3 study?
`
`14· · · ·A· ·Many.
`
`15· · · ·Q· ·Do you know what they were?
`
`16· · · ·A· ·Corneal staining, conjunctival staining,
`
`17· Schirmer's tear test, a number of symptoms separate
`
`18· and included in the OSDI, adverse events, safety.
`
`19· · · ·Q· ·Anything else?
`
`20· · · ·A· ·Those were the ones that I recall right
`
`21· now, but there were a number of them.· The
`
`22· evaluation took quite a long time to complete.
`
`23· · · ·Q· ·Do you have an understanding of why there
`
`24· were so many end points in the Phase 3 study?
`
`25· · · ·A· ·Let me clarify.· There are a lot of
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`PROTECTIVE ORDER MATERIAL
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`
`
`·1· measures taken, a lot of evaluations done.· Not all
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`·2· of them were end points, per se, or -- but I think
`
`·3· there was one sign and one symptom originally
`
`·4· declared as the sort of primary end points of the
`
`·5· study.
`
`·6· · · ·Q· ·What was that?
`
`·7· · · ·A· ·To the best of my recollection, it had to
`
`·8· do with corneal staining and the OSDI.
`
`·9· · · ·Q· ·Not Schirmer's tear --
`
`10· · · ·A· ·I think that was a key secondary.
`
`11· · · ·Q· ·Do you know why it wasn't a primary?
`
`12· · · ·A· ·I think this was the first dry eye study of
`
`13· any size ever, and so -- and it turned out to be the
`
`14· first approval of a dry eye therapeutic, so we
`
`15· learned a lot along the way and we didn't always
`
`16· know what end point would sort of demonstrate a
`
`17· particular drug's greatest benefit.· I think that
`
`18· end points originally had to do with -- well, just
`
`19· based on what happened in Phase 2.
`
`20· · · ·Q· ·And what was that?· What happened in
`
`21· Phase 2?
`
`22· · · ·A· ·Well, it looked like corneal staining and
`
`23· tear production were sort of the most apparent
`
`24· effects from objective measures.· There were a
`
`25· number of subjective measures that also showed some
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`PROTECTIVE ORDER MATERIAL
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`·1· benefit.
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`·2· · · ·Q· ·Prior to your work on the Phase 3 study for
`
`·3· Restasis, did you ever diagnose a patient with dry
`
`·4· eye?
`
`·5· · · ·A· ·Sure.
`
`·6· · · ·Q· ·How many, roughly?
`
`·7· · · ·A· ·Hundreds.
`
`·8· · · ·Q· ·And how did you go about diagnosing them?
`
`·9· · · ·A· ·A history and an examination.· One of
`
`10· the -- well, I think you're aware that, as I pointed
`
`11· out earlier, there's lots of different kinds of dry
`
`12· eye.· And the kind that has to do with decreased
`
`13· production of tears is usually determined by
`
`14· measuring the amount of tears.· So that's one
`
`15· element.· Examining the surface of the eye is
`
`16· another element.
`
`17· · · ·Q· ·How do you measure the amount of tears?
`
`18· · · ·A· ·There are a number of ways, but the most
`
`19· typical way is by using what's called a Schirmer's
`
`20· test strip, which is placed -- placed in the
`
`21· inferior fornix of the conjunctiva.· It sort of
`
`22· hangs there and it gets wet by wick -- wick action.
`
`23· And it gets -- and it's measured over a five-minute
`
`24· period.· And the amount of wetting of that piece of
`
`25· paper, which is, essentially, a piece of filter
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`PROTECTIVE ORDER MATERIAL
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`·1· paper of a certain intensity, the amount of wetting
`
`·2· that occurs over that period of time is indicative
`
`·3· of the amount of tears that are present.
`
`·4· · · ·Q· ·Do you perform that test -- you,
`
`·5· personally, do you perform that test with
`
`·6· anesthesia?
`
`·7· · · ·A· ·Depending upon what I think I want to know,
`
`·8· I have done it both ways, but I rely on the test
`
`·9· with anesthesia mostly.
`
`10· · · ·Q· ·Okay.· Let's break that down.
`
`11· · · · · ·When you say "both ways," you mean with
`
`12· anesthesia and without anesthesia?
`
`13· · · ·A· ·Yes.
`
`14· · · ·Q· ·And when you say depending on what you
`
`15· think you want to know, how does that differ with
`
`16· anesthesia and without anesthesia?
`
`17· · · ·A· ·If you want some notion of -- well, if you
`
`18· want some notion of sort of a basal steady state
`
`19· production of tears without the influence of what's
`
`20· called reflex tearing, you would want to put
`
`21· aesthetic in the eye so that you sort of block the
`
`22· sensory pathway, so there's no reflex tearing that
`
`23· occurs.
`
`24· · · · · ·So that's why, most of the time, that's the
`
`25· way that I would do it.
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`PROTECTIVE ORDER MATERIAL
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`·1· · · ·Q· ·Why would you do Schirmer testing without
`
`·2· anesthesia?
`
`·3· · · ·A· ·Oversight.· Not really on purpose anymore.
`
`·4· · · · · ·Years ago it was standard to do both and
`
`·5· try to make some inferences about why one was
`
`·6· different from the other, but Schirmer's with
`
`·7· anesthesia was considered to be -- has come to be
`
`·8· considered to be not only an assessment of basal
`
`·9· tear production, which has its own merits, but also
`
`10· least likely to be influenced by unrelated issues or
`
`11· technique.
`
`12· · · ·Q· ·So if you had data on a patient from a
`
`13· Schirmer tear test without anesthesia and then you
`
`14· did a Schirmer tear test with anesthesia, could you
`
`15· compare that two data?
`
`16· · · · · ·MR. SINGER:· Objection to the form of the
`
`17· question, incomplete hypothetical.
`
`18· · · · · ·THE WITNESS:· I think you could make some
`
`19· inferences from both.· But, again, if I wanted what
`
`20· has come to be believed to be the best single
`
`21· measure, I would pick with anesthesia.
`
`22· BY MS. DEVINE:
`
`23· · · ·Q· ·If you had a patient that came to you and
`
`24· you did a Schirmer tear test in January without
`
`25· anesthesia and they came back to you in February and
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`PROTECTIVE ORDER MATERIAL
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`·1· you did one with anesthesia and the results were
`
`·2· lower, would you assume that the patient's disease
`
`·3· had progressed?
`
`·4· · · · · ·MR. SINGER:· Objection to the form of the
`
`·5· question, incomplete hypothetical.
`
`·6· BY MS. DEVINE:
`
`·7· · · ·Q· ·Or that the patient had not gotten better?
`
`·8· · · · · ·MR. SINGER:· Same objection.
`
`·9· · · · · ·THE WITNESS:· Well, I think the way you've
`
`10· asked the question, you sort of appreciate that it
`
`11· is best that you do it the same way.· So if that's
`
`12· all I was given, I would make do.· And I think
`
`13· that if -- well, that's what I -- I would make do.
`
`14· BY MS. DEVINE:
`
`15· · · ·Q· ·Would you feel that you could draw valid
`
`16· conclusions from comparing those two tests?
`
`17· · · ·A· ·I think if they were both quite low, that
`
`18· would -- I could conclude that, but tear production
`
`19· was low.
`
`20· · · ·Q· ·If one was low and one was high, could you
`
`21· draw a conclusion?
`
`22· · · ·A· ·Not if -- not done at the same time.
`
`23· · · ·Q· ·Doctor, were you involved in any of the
`
`24· data analysis from the Phase 3 trials?
`
`25· · · ·A· ·I was.
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`PROTECTIVE ORDER MATERIAL
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`
`
`·1· · · ·Q· ·How were you involved?
`
`·2· · · ·A· ·It was well after -- well after the
`
`·3· original publications and the filing of the NDA.
`
`·4· Really, when I joined Allergan in 2001.
`
`·5· · · ·Q· ·So when you joined Allergan in 2001, the
`
`·6· Phase 3 trials were complete, correct?
`
`·7· · · ·A· ·That's correct.
`
`·8· · · ·Q· ·So in your role as an investigator in the
`
`·9· Phase 3 trials, you did not do any of the data
`
`10· analysis, correct?
`
`11· · · ·A· ·I did not.
`
`12· · · ·Q· ·Are you aware of who did the data analysis
`
`13· for the Phase 3 trials?
`
`14· · · ·A· ·I know -- I know one lady who was a
`
`15· statistician on the project, but I'm sure it was
`
`16· lots of people working on it.
`
`17· · · ·Q· ·What was her name?
`
`18· · · ·A· ·Katherine Stern.
`
`19· · · ·Q· ·So after you came to Allergan, did you some
`
`20· data analysis on the Phase 3 trials?
`
`21· · · ·A· ·Well, I never hit key strokes, if you will,
`
`22· I never sort of did -- generated tables or -- but I
`
`23· certainly was involved in the interpretation of data
`
`24· tables and requesting data tables to be generated
`
`25· looking for certain comparisons.
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`PROTECTIVE ORDER MATERIAL
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`·1· · · ·Q· ·Was that in the context of your declaration
`
`·2· to the patent office?
`
`·3· · · ·A· ·If data weren't existing at the time, it
`
`·4· could have been, yes.
`
`·5· · · ·Q· ·Separate and apart from your declaration to
`
`·6· the patent office, were you involved in any other
`
`·7· data analysis for the Phase 3 trials?
`
`·8· · · ·A· ·Yes.
`
`·9· · · ·Q· ·What was the context?
`
`10· · · ·A· ·Well, we were seeking approval, not only in
`
`11· the United States, but also in various areas of the
`
`12· world, and I was involved in putting together
`
`13· filings to support that -- those submissions.
`
`14· · · ·Q· ·Those regulatory submissions?
`
`15· · · ·A· ·That's correct.
`
`16· · · ·Q· ·Doctor, going back to how you diagnosed dry
`
`17· eye, do you go about diagnosing keratoconjunctivitis
`
`18· sicca differently than how you diagnose dry eye?
`
`19· · · · · ·MR. SINGER:· Objection; outside the scope
`
`20· of prep and cross-examination.
`
`21· · · · · ·Counsel, it is fine to lay a foundation
`
`22· with the witness, I have no problem with that, but
`
`23· this is supposed to be cross-examination on his
`
`24· declaration.
`
`25· · · · · ·How is his diagnosis of KCS related to his
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`PROTECTIVE ORDER MATERIAL
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`
`
`·1· declaration?
`
`·2· · · · · ·MS. DEVINE:· His declaration is about
`
`·3· measurements of symptoms of KCS and dry eye.· So how
`
`·4· it is diagnosed, how those symptoms are measured is
`
`·5· within the scope of his declaration.
`
`·6· · · · · ·MR. SINGER:· I don't think I agree with
`
`·7· that --
`
`·8· · · · · ·MS. DEVINE:· Are you going to tell him not
`
`·9· to answer the question?
`
`10· · · · · ·MR. SINGER:· If you let me finish, I will
`
`11· answer.
`
`12· · · · · ·I don't think I agree with that.· I think I
`
`13· said I think it is proper to lay some foundation if
`
`14· you go on with this, but if you just keep going down
`
`15· this road, I think we're going to have to get on the
`
`16· phone with the board.
`
`17· · · · · ·MS. DEVINE:· Okay.
`
`18· · · · · ·MR. SINGER:· This appears to me to be the
`
`19· design to discover information related to
`
`20· defendant's noninfringement --
`
`21· · · · · ·MS. DEVINE:· I've heard you.· I've heard
`
`22· you.
`
`23· · · · · ·MR. SINGER:· Okay.· Keep on.
`
`24· · · · · ·THE WITNESS:· Again, I say that "KCS" and
`
`25· "dry eye" are often used interchangeably.
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`PROTECTIVE ORDER MATERIAL
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`
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`·1· · · · · ·In more severe forms of dry eye or KCS,
`
`·2· especially when associated with certain systemic
`
`·3· illnesses, you may look for additional things you
`
`·4· would do beyond what you would do in a more typical,
`
`·5· perhaps less severe, case.· That's all I would say.
`
`·6· BY MS. DEVINE:
`
`·7· · · ·Q· ·Do you do a Schirmer tear test on every
`
`·8· patient you evaluate for KCS and dry eye?
`
`·9· · · ·A· ·I do.
`
`10· · · ·Q· ·Were you --
`
`11· · · ·A· ·And, by the way, when I say "I do," it
`
`12· could be me, it could be a technician, it could be
`
`13· overlooked by the time the patient shows up, but for
`
`14· people whose chief problem is around dry eye,
`
`15· Schirmer's testing is a key element of the
`
`16· evaluation.
`
`17· · · ·Q· ·Do you find that there is variability for a
`
`18· given patient in the Schirmer tear test from test to
`
`19· test?
`
`20· · · ·A· ·Yes.· It's -- it's known to be -- can be a
`
`21· variable test and I think, as I mentioned earlier,
`
`22· that's why clinicians, as well as people who do
`
`23· trials in this area, have moved towards Schirmer's
`
`24· with anesthesia for a couple of reasons, but part of
`
`25· that is to try and remove some of the inherent
`
`PROTECTIVE ORDER MATERIAL
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`
`
`·1· variability of the technique itself.
`
`·2· · · ·Q· ·So do you think that the results from
`
`·3· Schirmer's tear test with anesthesia is less
`
`·4· variable than the results from Schirmer's tear test
`
`·5· without anesthesia?
`
`·6· · · ·A· ·I do.
`
`·7· · · ·Q· ·You can tell I have to think about the
`
`·8· words.
`
`·9· · · · · ·May I give you a document that has been
`
`10· marked in IPR 2016-01127 as Exhibit 1027 (sic).· It
`
`11· is an excerpt from that document.
`
`12· · · · · ·And I'm going to ask you --
`
`13· · · · · ·MR. SINGER:· I'm sorry, Counsel.· What's
`
`14· the exhibit number?
`
`15· · · · · ·MS. DEVINE:· It's 1027 from IPR 1127 -- is
`
`16· that wrong?
`
`17· · · · · ·Oh, I'm sorry.· That's the wrong exhibit
`
`18· number.· That is 1004 from IPR 1127.
`
`19· · · · · ·MR. SINGER:· 1004.
`
`20· · · · · ·MS. DEVINE:· From IPR 1127.
`
`21· BY MS. DEVINE:
`
`22· · · ·Q· ·Doctor, do you recognize this document?
`
`23· · · ·A· ·Yes.
`
`24· · · ·Q· ·What is it?
`
`25· · · ·A· ·It appears to be a declaration that I --
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`PROTECTIVE ORDER MATERIAL
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`
`
`·1· from me dated October 2013.
`
`·2· · · ·Q· ·And if you turn to page -204 at the bottom,
`
`·3· is that your signature?
`
`·4· · · ·A· ·Yes.
`
`·5· · · ·Q· ·Did you review this declaration before you
`
`·6· signed it?
`
`·7· · · ·A· ·Yes.
`
`·8· · · ·Q· ·Who wrote this declaration?
`
`·9· · · ·A· ·I don't remember exactly who wrote all the
`
`10· words in here, but it's, but I certainly did review
`
`11· it and I certainly would have made -- had some input
`
`12· into it.
`
`13· · · ·Q· ·Who decided what data to use for this
`
`14· declaration?
`
`15· · · ·A· ·It was ultimately my decision what data to
`
`16· use.
`
`17· · · ·Q· ·Doctor, are you a biostatistician?
`
`18· · · · · ·MR. SINGER:· Objection to the form of the
`
`19· question, actually.
`
`20· · · · · ·THE WITNESS:· I have a master's degree in
`
`21· clinical research design and statistical analysis,
`
`22· so I have some expertise in it.
`
`23· BY MS. DEVINE:
`
`24· · · ·Q· ·Did you consult with a biostatistician on
`
`25· your declaration?
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`PROTECTIVE ORDER MATERIAL
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`
`
`·1· · · ·A· ·So as I said earlier, I don't run the
`
`·2· statistics or generate tables at all.· Everything
`
`·3· that is generated within Allergan is done by
`
`·4· professional biostatisticians and QC'd before they
`
`·5· leave the building.
`
`·6· · · · · ·But I would have asked for certain analyses
`
`·7· to be done and comparisons to be done, sure.
`
`·8· · · ·Q· ·So did you ask for the analyses and
`
`·9· comparisons in your declaration to be done?
`
`10· · · ·A· ·Some of these were preexisting; some of
`
`11· these already existed.· So, actually, I think most
`
`12· of these analyses had been conducted prior to my
`
`13· involvement at all.
`
`14· · · ·Q· ·Most, but not all, correct?
`
`15· · · ·A· ·I think that's right.· I think I would have
`
`16· been involved in some summary analyses of the
`
`17· preexisting data.
`
`18· · · ·Q· ·We'll walk through the exhibits, and as we
`
`19· go through perhaps you could tell me if it was one
`
`20· that was preexisting to your recollection.
`
`21· · · · · ·Does that sound okay?
`
`22· · · ·A· ·Okay.
`
`23· · · ·Q· ·Let's talk about Exhibit B, which is on
`
`24· page -213 and -214.
`
`25· · · ·A· ·Okay.
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`PROTECTIVE ORDER MATERIAL
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`
`
`·1· · · ·Q· ·Okay.· If we look at figures 1 and 2 there
`
`·2· is a title phrase there that says:
`
`·3· · · · · · · ·"Phrase 2 Results - Phase 3
`
`·4· · · · · ·Targets Subpopulation."
`
`·5· · · · · ·Did I read that correctly?
`
`·6· · · ·A· ·Yes, ma'am.
`
`·7· · · ·Q· ·Does that indicate that this was data from
`
`·8· the Phase 2 clinical study?
`
`·9· · · ·A· ·Yes, ma'am.
`
`10· · · ·Q· ·What is the Phase 3 target subpopulation?
`
`11· · · ·A· ·It's the population of patients using the
`
`12· inclusion/exclusion criteria from the Phase 3
`
`13· population.· It's that subset of patients that were
`
`14· enrolled in the Phase 2 study that essentially were
`
`15· like the patients that were to be in the Phase 3
`
`16· program.
`
`17· · · ·Q· ·What were those inclusion and exclusion
`
`18· criteria?
`
`19· · · ·A· ·I don't recall the difference between them.
`
`20· · · ·Q· ·Are they written down somewhere?
`
`21· · · ·A· ·They may be -- well, they're probably
`
`22· described in the -- the key ones are probably
`
`23· described in the papers, the Stevenson and Sall
`
`24· papers --
`
`25· · · ·Q· ·Okay.· Let's look at those.
`
`PROTECTIVE ORDER MATERIAL
`
`
`
`·1· · · ·A· ·-- but I don't recall them.
`
`·2· · · ·Q· ·So I'm going to give you -- these are all
`
`·3· from that same IPR number, 2016-01127.
`
`·4· · · · · ·Exhibit 1015, which is the Stevenson paper,
`
`·5· and Exhibit 1007, which is the Sall paper?
`
`·6· · · · · ·MR. SINGER:· 1015 is Stevenson and 1007 is
`
`·7· Sall?
`
`·8· · · · · ·MS. DEVINE:· 1015 is Stevenson; 1007 is
`
`·9· Sall.
`
`10· · · · · ·MR. SINGER:· Thank you.
`
`11· · · · · ·MS. DEVINE:· Thank you.
`
`12· · · ·Q· ·All right.
`
`13· · · ·A· ·Okay.
`
`14· · · ·Q· ·Do you see the inclusion and exclusion
`
`15· criteria in either Stevenson or Sall?
`
`16· · · ·A· ·I do.
`
`17· · · ·Q· ·Where are they?
`
`18· · · ·A· ·In Stevenson, it is page 968, and in Sall
`
`19· it is page 632.
`
`20· · · ·Q· ·Okay.· Let's start with Stevenson.· Where
`
`21· do you see it on 968?
`
`22· · · ·A· ·Under "Study Population," left side, lower
`
`23· half of the page.
`
`24· · · ·Q· ·Could you tell me exactly where you're
`
`25· looking?
`
`PROTECTIVE ORDER MATERIAL
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`
`
`·1· · · ·A· ·How about this.
`
`·2· · · ·Q· ·That whole paragraph is what you're
`
`·3· referencing?
`
`·4· · · ·A· ·Yes.
`
`·5· · · ·Q· ·That second full paragraph under "Study
`
`·6· Protocol"?
`
`·7· · · ·A· ·That's right.
`
`·8· · · ·Q· ·Okay.· And so does this have the inclusion
`
`·9· and exclusion criteria for Phase 3?
`
`10· · · ·A· ·Well, it absolutely does not have all of
`
`11· them.
`
`12· · · ·Q· ·Okay.· Are you aware of any others that are
`
`13· not listed there?
`
`14· · · ·A· ·Not at this moment.
`
`15· · · ·Q· ·And how about in Sall?
`
`16· · · ·A· ·These are -- under "Materials and Methods,"
`
`17· left side of 632 beginning with the subtitle
`
`18· "Patients."
`
`19· · · ·Q· ·And does that list all the exclusion and
`
`20· inclusion material for Phase 3?
`
`21· · · ·A· ·Unlikely.
`
`22· · · ·Q· ·Going back to Stevenson, is it your
`
`23· understanding that this Stevenson paper reports the
`
`24· results from the Restasis Phase 2 study?
`
`25· · · ·A· ·Yes.· Reports the -- presents some results.
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`PROTECTIVE ORDER MATERIAL
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`
`
`·1· · · ·Q· ·But not all results?
`
`·2· · · ·A· ·No.
`
`·3· · · ·Q· ·What results does it exclude?
`
`·4· · · ·A· ·I don't know for sure, but I mentioned
`
`·5· earlier lots of -- lots of measures were taken and
`
`·6· evaluations done, and this is a portion of that.
`
`·7· · · ·Q· ·If we turn to page 969 --
`
`·8· · · ·A· ·Yes.
`
`·9· · · ·Q· ·-- under "Results," about halfway down the
`
`10· paragraph, do you see a sentence that starts:
`
`11· · · · · · · ·"Moderate-to-severe dry eye"?
`
`12· · · ·A· ·Yes.
`
`13· · · ·Q· ·And it states:
`
`14· · · · · · · ·"Moderate-to-severe dry eye
`
`15· · · · · ·disease was defined as a Schirmer tear
`
`16· · · · · ·test 5 millimeters/5 minutes at
`
`17· · · · · ·baseline in at least one eye and
`
`18· · · · · ·superficial punctate keratitis (pupil
`
`19· · · · · ·and nasal average) of 1.5 averaged
`
`20· · · · · ·over both eyes.· Because these
`
`21· · · · · ·patients represented the greatest
`
`22· · · · · ·therapeutic challenge for any dry eye
`
`23· · · · · ·treatment, the efficacy analysis
`
`24· · · · · ·presented here is confined to the
`
`25· · · · · ·evaluation of this moderate-to-severe
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`PROTECTIVE ORDER MATERIAL
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`
`
`·1· · · · · ·subgroup."
`
`·2· · · · · ·Did I read that correctly?
`
`·3· · · ·A· ·Yes.
`
`·4· · · ·Q· ·Is that the same target subpopulation that
`
`·5· you analyzed in your Exhibit B of your declaration?
`
`·6· · · ·A· ·No.
`
`·7· · · ·Q· ·How are they different?
`
`·8· · · ·A· ·Let me say that I don't believe that's the
`
`·9· same population, because in looking at Sall, you had
`
`10· to have corneal staining of 2 plus and a total of
`
`11· 5 plus, so that's not quite the same as this average
`
`12· of nasal and pupil.
`
`13· · · · · ·And also there was some additional elements
`
`14· of Schirmer's testing where, if you had a score of
`
`15· zero, you had to have at least some production after
`
`16· nasal stimulation.
`
`17· · · · · ·So these are -- this definition is not
`
`18· exactly what I believe was the sort of definition
`
`19· applied in the table that you have -- that you asked
`
`20· me about --
`
`21· · · ·Q· ·Uh-huh.
`
`22· · · ·A· ·-- about the Phase 3 target subpopulation,
`
`23· I think it was modified additionally from this, but
`
`24· I can't be sure.
`
`25· · · ·Q· ·Okay.· If you turn to your declaration,
`
`PROTECTIVE ORDER MATERIAL
`
`
`
`·1· paragraph 8, about halfway down that paragraph you
`
`·2· state:
`
`·3· · · · · · · ·"The data presented in Exhibit B
`
`·4· · · · · ·represents the subpopulation of
`
`·5· · · · · ·mod
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