pd
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`Planet Depos0
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`
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`We Make It Happen-
`
`pt of Benjamin Greenberg,
`Transcri
`M.D.
`
`Date: February 26, 2024
`
`Case: 1WI Pharmaceuticals, Inc. -v-Merck Serano SA (PTAB)
`
`
`Planet Depos
`
`Phone: 888.433.3767
`Email: transcripts@planetdepos.com
`www.planetdepos.com
`
`Merck 2009
`TWi v Merck
`IPR2023-00050
`
`
`
`WORLDWIDE COURT REPORTING & LITIGATION TECHNOLOGY
`
`
`
`Planet Depos0
`
`
`
`We Make It Happen-
`
`pt of Benjamin Greenberg,
`Transcri
`M.D.
`
`Date: February 26, 2024
`
`Case: 1WI Pharmaceuticals, Inc. -v-Merck Serano SA (PTAB)
`
`
`Planet Depos
`
`Phone: 888.433.3767
`Email: transcripts@planetdepos.com
`www.planetdepos.com
`
`Merck 2009
`TWi v Merck
`IPR2023-00050
`
`
`
`WORLDWIDE COURT REPORTING & LITIGATION TECHNOLOGY
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`TWI PHARMACEUTICALS,
`
`INC.
`
`Petitioner,
`
`V.
`
`MERCK SERONO SA
`
`Patent Owne r.
`
`IPR2023-00049 (Patent 7,713,947 B2)
`
`IPR2023-00050 (Patent 8,377,903 B2)
`
`ORAL DEPOSITION OF
`
`BENJAMIN GREENBERG, M.D.
`
`FEBRUARY 26, 2024
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`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
`
`2
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`ORAL DEPOSITION OF BENJAMIN GREENBERG, M.D., produced
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`as a witness at the instance of the Patent Owner, Merck
`
`Serono SA, and duly sworn, was taken in the above-styled
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`and numbered cause on February 26, 2024, from 9:06 a.m.
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`to 3:28 p.m., before Kim A. Mccann, CSR in and for the
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`State of Texas, reported by machine shorthand, at the
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`offices of Husch Blackwell, 1900 N. Pearl Street, Suite
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`1800, Dallas, Texas, pursuant to the Federal Rules of
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`Civil Procedure.
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`PLANET DEPOS
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`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
`
`3
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`A P P E A R A N C E S
`
`FOR THE PETITIONER:
`
`Philip Segrest, Esq.
`
`HUSCH BLACKWELL, LLP
`
`120 South Riverside Plaza
`
`Suite 2200
`
`Chicago, Illinois 60606
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`(312) 655-1500
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`( 312) 655-1501 fax
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`FOR THE PATENT OWNER MERCK SERONO SA:
`
`Cindy Kan, Esq.
`
`Emily R. Whelan, Esq.
`
`WilmerHale
`
`7 World Trade Center
`
`250 Greenwich Street
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`New York, New York 10007
`
`(212) 295-6470
`
`PLANET DEPOS
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`
`
`
`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
`
`4
`
`I N D E X
`
`Examination by Ms. Kan
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`PAGE
`
`6
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`E X H I B I T S
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`NUMBER
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`DESCRIPTION
`
`PAGE
`
`Exhibit 2004
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`Exhibit 2005
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`Exhibit 2006
`
`Exhibit 2007
`
`Article entitled "Cladribine in
`treatment of chronic
`progressive multiple sclerosis"
`by Sipe
`
`Excerpt from Pharmacology and
`Therapeutics - Principles to
`Practice
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`Article co-authored by Dr.
`Greenberg "Reduction of Disease
`Activity Disability With
`High-Dose Cyclophosphamide in
`Patients With Agressive
`Multiple Sclerosis
`
`Article entitled "Defining
`Success in Multiple Sclerosis,
`Treatment Failures and
`Nonresponders"
`
`Exhibit 2008
`
`Article from "Continuum"
`co-authored by Dr. Greenberg
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`26
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`60
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`96
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`123
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`145
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`P R E V I O U S E X H I B I T S
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`NUMBER
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`DESCRIPTION
`
`Exhibit 1005
`
`IPR 2023-00049
`
`Exhibit 1008
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`Rice study "Cladribine and
`progressive MS: Clinical and
`MRI outcomes of a multicenter
`controlled trial
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`PAGE
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`PLANET DEPOS
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`
`
`
`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
`
`5
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`Exhibit 1016
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`INDEX (Cont.)
`
`Romine study "A Double-Blind,
`Placebo-Controlled, Randomized
`Trial of Cladribine in
`Relapsing-Remitting
`Multiple Sclerosis
`
`Exhibit 1017
`
`Package insert for Novantrone
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`Exhibit 1024
`
`Exhibit 1028
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`Exhibit 1029
`
`Cursiefen article "Escalating
`Immunotherapy with
`mitoxantrone in Patients with
`Very Active
`Relapsing-Remitting or
`Progressive Muscular
`Sclerosis"
`
`Coles article" Campath-lH
`treatment of multiple
`sclerosis: Lessons
`From the bedside for the
`bench"
`Copy of U.S. Patent 7,888,328,
`Bodor, et al.
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`51
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`90
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`PLANET DEPOS
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`
`
`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
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`P R O C E E D I N G S
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`(Witness duly sworn.)
`
`MS. KAN: Good morning. My name
`
`is Cindy Kan.
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`I'm an attorney at the law firm of
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`Wilmer Hale, and with me today is Emily Whelan,
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`also an attorney at Wilmer Hale.
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`MR. SEGREST: And just
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`if we're
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`doing appearances, Philip Segrest of
`
`Husch Blackwell representing the Petitioner, TWi,
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`and the witness, Dr. Greenberg.
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`MS. KAN: And we represent patent
`
`owner, Merck Serono SA.
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`BENJAMIN GREENBERG, M.D.,
`
`Having been first duly sworn, testified as
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`follows:
`
`BY MS. KAN:
`
`EXAMINATION
`
`Q. Good morning.
`
`A. Good morning.
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`Q. Please state your full name for the
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`record.
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`A. Benjamin Greenberg,
`
`G-r-e-e-n-b-e-r-g.
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`Q.
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`Is there any reason that you cannot
`
`provide complete and accurate testimony today?
`
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`
`
`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
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`A. No.
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`Q. Do you understand that y our testimon y
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`here toda y is giv en under oath?
`
`A.
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`Q.
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`A.
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`Q.
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`A.
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`Q.
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`Yes.
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`Have y ou ever been deposed before?
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`Yes.
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`How man y times?
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`Somewhere between four and eight.
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`Have you ever testified in court
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`before?
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`A.
`
`Q.
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`A.
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`Q.
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`Yes.
`
`How many times?
`
`Twice .
`
`And when?
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`A. One was appro ximately 19 years ago,
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`and one was more than 10 years ago.
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`Q. What's --
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`A. And I apologize. A third around
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`about six years ago.
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`Q. What sort of matters did you give
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`testimony in?
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`A. The first case was a vaccine injury
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`compensation case, one was a medical malpractice
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`case where I served as an expert witness, and one
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`was a case relative to a patent.
`
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`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
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`Q. You understand that we are taking
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`today's deposition in two IPR proceedings:
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`IPR
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`2023-00049 and IPR 2023-00050; correct?
`
`A. Yes.
`
`Q. And unless I know otherwise, all
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`exhibits that we use today are being introduced
`
`with the same numbers in both proceedings.
`
`A. Yes.
`
`Q.
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`I'm going to hand you what has
`
`previously been marked as Exhibit 1005 in IPR
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`2023-00049.
`
`MR. SEGREST: Thank you.
`
`Q.
`
`I may refer to IPR 2023-00049 as
`
`the '049 IPR. Okay?
`
`A. Okay.
`
`Q. Do you recognize the document?
`
`A. Yes.
`
`Q. Are you familiar with this document?
`
`A. Yes.
`
`Q. This is your declaration providing
`
`your opinions regarding U.S. Patent 7,713,947;
`
`correct?
`
`MR. SEGREST: Object. Form.
`
`A. Yes.
`
`Q.
`
`I may refer to U.S. Patent 7,713,947
`
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`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
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`as the '947 patent. Okay?
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`A. Okay.
`
`Q. This is also your declaration
`
`providing your opinions regarding U.S. Patent
`
`8,377,903; correct?
`
`A. Yes.
`
`Q.
`
`I ma y refer to U.S. Patent 8,377,903
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`as the '903 patent. Okay?
`
`A. Okay.
`
`Q. Could you confirm that this
`
`declaration which addresses both the '947 and
`
`the '903 patents is the same declaration as was
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`submitted in IPR 2023-00050?
`
`A.
`
`It appears to be so.
`
`Q. Could you turn to page 126 of
`
`Exhibit 1005.
`
`A. Yes.
`
`Q.
`
`Is that your signature on the
`
`declaration?
`
`A. Yes.
`
`Q. And you stand by the opinions you
`
`provided in your declaration?
`
`A. Yes.
`
`Q. Could you turn to page 11 of
`
`Exhibit 1005.
`
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`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
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`A. Okay.
`
`Q. At paragraph 12 you state:
`
`I have
`
`considered the facts and data contained in the
`
`references cited herein, as well as my
`
`experience, education, and training in providing
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`the opinions contained herein. Correct?
`
`A. Yes.
`
`Q. The references cited herein are
`
`limited to exhibits in the '049 IPR; correct?
`
`A. Yes.
`
`Q.
`
`So every time you cite a reference in
`
`your declaration, you provide an exhibit number;
`
`correct?
`
`A.
`
`I believe that to be true.
`
`Q. Are there any materials you
`
`considered in forming your opinions that are not
`
`cited in the declaration?
`
`A. None that I specifically recall at
`
`this moment.
`
`Q.
`
`In forming your opinions for the '049
`
`IPR, did you search for any literature yourself?
`
`A.
`
`I do not recall a specific search.
`
`Q. Your opinion is that the challenged
`
`claims of the '947 and '903 patents are
`
`anticipated by Bodor; correct?
`
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`
`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
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`A. Yes.
`
`Q. Your further opinion is that the
`
`challenged claims of the '947 and '903 patents
`
`would have been obvious over Bodor; correct?
`
`A. Yes.
`
`Q. And your opinion is that the
`
`challenged claims of the '947 and '903 patents
`
`would have been obvious over Bodor and Rice;
`
`right?
`
`A. Yes.
`
`Q. How did you become aware of the Bodor
`
`and Rice references?
`
`A.
`
`So the Bodor reference was made
`
`available to me after I was asked to review the
`
`case. The Rice material may have been familiar
`
`to me in the course of my practice and work as a
`
`neurologist.
`
`I don't specifically recall.
`
`Q. Did you talk to anyone other than
`
`counsel for TWi in forming the opinions that are
`
`in your declaration for the '049 and '050 IPRs?
`
`A. Nobody else than counsel's office or
`
`staff.
`
`Q. Did you do anything to prepare for
`
`today's deposition?
`
`A. Yes.
`
`PLANET DEPOS
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`
`
`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
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`Q. What did you do?
`
`A.
`
`I reviewed my declaration.
`
`I
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`reviewed the '943 and '907 patent -- actually,
`
`'903 and '947 patent and Bodor and Rice, as well
`
`as looking at the IPR decision allowing the case
`
`to move forward.
`
`Q. Did you meet with anyone to prepare
`
`for your deposition?
`
`A. Yes.
`
`Q. Who did you meet with?
`
`A.
`
`I met with counsel from
`
`Husch Blackwell in preparing.
`
`Q. When?
`
`A. Over the last week and a half, there
`
`were a few meetings.
`
`Q. And how long in total do you think
`
`you met with counsel for?
`
`A. Each meeting lasted anywhere from one
`
`to two hours.
`
`Q.
`
`A.
`
`So in total?
`
`In total, up to six hours.
`
`Approximately.
`
`Q. Did you bring any documents with you
`
`to today's deposition?
`
`A. No.
`
`PLANET DEPOS
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`
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`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
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`Q. Did you make -- and you didn't
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`communicate with anyone other than counsel for
`
`TWi to prepare for this deposition; correct?
`
`A. Correct.
`
`Q. And aside from the documents that you
`
`noted earlier, have you reviewed any documents
`
`other than the exhibits in this IPR?
`
`A. Only the exhibits or, for example, if
`
`the patent referred to an article like Rice,
`
`anything contained in the patent.
`
`Q.
`
`I'd like to introduce what has
`
`previously been marked as Exhibit 1028, an
`
`article by Coles.
`
`MR. SEGREST: Thank you.
`
`Q. Do you recognize Exhibit 1028 as a
`
`Coles article you relied on in your declaration?
`
`A. Yes.
`
`Q. Coles describes treatment of multiple
`
`sclerosis patients with Campath-lH; correct?
`
`A. Yes.
`
`THE REPORTER: Can you say that
`
`again?
`
`I'm not familiar with the terminology, so
`
`if you just say that again.
`
`MS. KAN: Coles describes treatment
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`of multiple sclerosis patients with Campath-lH;
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`
`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
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`correct?
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`THE REPORTER: Thank you.
`
`Q. Please turn to page 271 of Coles.
`
`A. Okay.
`
`Q. Please go to the left column, first
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`full paragraph, first sentence.
`
`A. Okay.
`
`Q. Here Coles states: We administered
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`100 milligrams of Campath-lH as five daily doses
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`of 20 milligrams given intravenously over four
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`hours. Correct?
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`A. Correct.
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`Q. The paragraph goes on to say:
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`Subsequently, we offered elective retreatment
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`after 12 to 18 months giving a fixed total dose
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`of 60 milligrams over 3 consecutive days
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`(20 milligrams per day), again premedicated with
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`corticosteroids.
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`9 of 22 of the acute relapsing
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`group have now received a second course of
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`Campath-lH. Correct?
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`A. Yes.
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`Q. Retreatment that is elective means
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`that retreatment is optional; correct?
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`A.
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`I'm not sure that in -- in terms of
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`the word "optional," but elective can be for a
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`variety of reasons. Technically every treatment
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`is always optional, but I'm not sure those are
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`exactly the same.
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`Q. Could a patient decline retreatment?
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`A.
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`It -- a patient can decline any
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`treatment.
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`Q. The patients who received retreatment
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`received a fixed total dose of 60 milligrams of
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`Campath-lH; correct?
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`A. That is what it says.
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`Q. And this fixed total dose of
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`60 milligrams was referred to as a second course
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`of Campath-lH; correct?
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`A.
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`I'm not sure I see the term "second
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`course."
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`I don't disagree that it was a
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`subsequent course, but I don't see that
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`terminology you're referring to, unless I'm
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`missing a piece pointed out.
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`Q.
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`So I had read a sentence that started
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`with, Subsequently we offered elective
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`retreatment.
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`Do you see tha t?
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`A. Yes.
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`Q. And it ends with, 9 of 22 of the
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`acute relapsing group have now received a second
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`course.
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`A. Ah, yes.
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`Q.
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`So the fixed total dose of
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`60 milligrams was referred to as a second course
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`of Campath-lH; correct?
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`A. Yes.
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`Q. And these patients who had received
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`the first course of Campath-lH; correct?
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`A. Yes.
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`Q.
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`So the dose of Campath-lH during
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`retreatment was lower than the initial
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`100-milligram dose of Campath-lH; correct?
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`A. Yes.
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`Q. The second course of Campath-lH was a
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`lower dose than the initial 100-milligram dose of
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`Campath-lH; correct?
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`A. Yes.
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`Q.
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`Some of these patients received
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`retreatment 12 months after receiving the initial
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`dose; correct?
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`A.
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`I believe that's what's stated.
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`Q. And some of these patients received
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`retreatment 18 months after the -- receiving the
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`initial dose; correct?
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`A. Yes.
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`Q. For patients who received
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`retreatment, they did not all receive retreatment
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`at the same time; correct?
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`A. Yes.
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`Q. Please turn to page 270 of Coles.
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`A. Okay.
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`Q. Please go to the right column, bottom
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`paragraph.
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`If you count nine lines from the
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`bottom
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`A. Okay.
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`Q.
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`-- Coles states: Seven patients in
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`this cohort received a second dose of Campath-lH
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`two to four years after the first treatment.
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`Correct?
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`A. Yes.
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`Q. The cohort that the seven patients
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`were in was a progressive cohort; correct?
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`A. Yes.
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`Q. These seven patients in the
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`progressive cohort received a second dose of
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`Campath-lH in order to maintain or increase
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`perceived improvements; correct?
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`A. Could you re-ask that. Sorry.
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`Q. These seven patients in the
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`progressive cohort received a second dose of
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`Campath-lH in order to maintain or increase
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`perceived improvements; correct?
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`MR. SEGREST: Objection. Form.
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`A.
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`I'm not seeing that specific
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`sentence.
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`If you'd like to point it out, I'm
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`happy to address it.
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`Q.
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`If you'd turn to page 271, left
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`column, first full paragraph, four lines in
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`starting with the word "Seven."
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`A.
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`Q.
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`I see it.
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`So these seven patients in the
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`progressive cohort received a second dose of
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`Campath-lH in order to maintain or increase
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`perceived improvements; correct?
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`A. That's what's stated here, yes.
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`Q. Do you agree that these seven
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`patients who received a second dose of Campath-lH
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`received retreatment?
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`A. Yes.
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`Q. For those seven patients, Coles did
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`not specify the amount of the second dose of
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`Campath-lH; correct?
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`A. Could you ask that again.
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`Q. For these seven patients, Coles did
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`not specify the amount of the second dose of
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`Campath-lH; correct?
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`MR. SEGREST: Objection. Foundation.
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`A.
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`Q.
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`It does not appear so.
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`Some of these seven patients received
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`a second dose two years after the first
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`treatment; correct?
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`A. Yes.
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`Q. And some of these seven patients
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`received a second dose four years after the first
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`treatment; correct?
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`A. Yes.
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`Q. For the seven patients that received
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`a second dose, they did not all receive a second
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`dose at the same time; correct?
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`A. Yes.
`
`Q. Let's look at Romine. This is an
`
`exhibit that has been previously marked as
`
`Exhibit 1016.
`
`MR. SEGREST: Thank you.
`
`Do you recognize Exhibit 1016 as
`
`Romine article you relied on in your declaration?
`
`(Brief interruption.)
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`Q.
`
`I'm going to repeat that question.
`
`A. Please do.
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`Q. Do you recognize Exhibit 1016 as a
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`Romine article you relied on in your declaration?
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`A. Yes.
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`Q. Exhibit 1016 is a publication by
`
`Romine from 1999; correct?
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`A. Yes.
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`Q. Please turn to page 35 of Romine.
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`A. Yes.
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`Q. Please go to the abstract. The first
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`two sentences, Romine states: We conducted an
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`18-month, placebo-controlled, double-blind study
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`to evaluate cladribine in the treatment of 52
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`patients with relapsing-remitting multiple
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`sclerosis. Patients received either placebo or
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`cladribine 0.07 milligrams per kilograms per day
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`by subcutaneous injection for five consecutive
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`days as six monthly courses for a total
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`cumulative dose of 2.1 milligrams per kilogram.
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`Correct?
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`A. Yes.
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`Q. Romine's study as disclosed in
`
`Exhibit 1016 was on relapsing-remitting multiple
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`sclerosis patients; correct?
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`A. Yes.
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`Q. These patients received a total dose
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`of 2.1 milligrams per kilogram of cladribine
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`subcutaneously; correct?
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`A. Yes.
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`Q. Please turn to page 43 of Romine.
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`A. Okay.
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`Q. Please go to the right column, three
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`lines down. Here Romine states: The lengthy but
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`permanent duration of effect of cladribine means
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`that retreatment will be necessary if cladribine
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`is to become a practical long-term therapy for
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`MS; correct?
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`A. That is what it says.
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`Q. You rely on this statement in Romine
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`to teach retreatment with cladribine; correct?
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`A.
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`I rely on a variety of sources, as
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`outlined in my declaration, about the notion of
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`retreatment.
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`Q. One of those sources that you rely on
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`is Romine; correct?
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`A. Romine is used for a variety of
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`reasons in forming my opinions, but concept of
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`retreatment is here and elsewhere.
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`Q.
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`So staying at Romine, page 44 -(cid:173)
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`well, page 43, right column, nine lines down,
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`Romine states: Twenty-four patients from our
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`initial study of cladribine in chronic
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`progressive MS have been retreated, 0.07
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`milligrams per kilogram times five days times
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`four courses because of a recurrence of disease
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`worsening. Correct?
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`A. Yes.
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`Q. Romine selected patients for
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`retreatment with cladribine because the y had a
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`recurrence of disease worsening; correct?
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`A.
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`I can't speak to selection criteria.
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`It just states that they were retreated because
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`of recurrence of disease worsening.
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`Q.
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`So Romine treated patients -- strike
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`that.
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`So Romine administered treatment with
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`cladribine of patients because they had a disease
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`worsening; correct?
`
`A. That's what it says.
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`Q. Romine discloses retreatment of
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`chronic progressive MS patients from their
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`initial study of cladribine; correct?
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`A. Yes.
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`Q. Romine does not disclose retreatment
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`of the relapsing-remitting multiple sclerosis
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`patients that we referenced from page 35 earlier
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`of Romine; correct?
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`A.
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`I don't believe so.
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`Q. During retreatment the chronic
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`progressive MS patients received 0.07 milligrams
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`per kilogram for five days for four courses for a
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`total dose of 1.4 milligrams per kilogram
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`cladribine; correct?
`
`A.
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`Q.
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`I believe that math is correct.
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`In forming your opinions regarding
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`retreatment, did you consider the initial
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`treatment dose that was given to the chronic
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`progressive MS patients from Romine's initial
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`study?
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`A. As outlined in my declaration, I rely
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`on a variety of sources to come to the
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`conclusions that I did. Romine plays one role
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`relative to the notion of retreatment and to the
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`effect of cladribine.
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`Q. And with respect to Romine's role in
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`the notion of retreatment with cladribine, in
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`forming your opinions regarding retreatment, did
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`you consider the initial treatment dose that was
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`given to the chronic progressive MS patients from
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`Romine's initial studying?
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`A. Amongst a variety of other features
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`in Romine and articles, it was one piece
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`considered.
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`Q. Your declaration does not address the
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`initial treatment dose; correct?
`
`A.
`
`I'm sorry, the initial treatment dose
`
`referring to?
`
`Q.
`
`So referring to the initial treatment
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`dose of chronic progressive MS treatments from
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`Romine's initial study, your declaration does not
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`address that initial treatment dose; correct?
`
`A.
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`I'd have to look back specifically
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`for it to be confident in my answer.
`
`Q. Staying in the same paragraph in
`
`Romine, the paragraph goes on to say: There were
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`no instances of marrow suppression or
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`thrombocytopenia in these patients, but six
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`(25 percent) developed herpes zoster with a
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`second course of cladribine as compared to 2 of
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`51
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`(4 percent) with the first treatment.
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`Correct?
`
`A. That is what it says.
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`Q. And in that initial study, 2 of 51
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`also developed herpes zoster with the first
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`treatment; correct?
`
`A. Yes.
`
`Q.
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`In Romine's initial study, there were
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`51 patients?
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`A.
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`I believe so.
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`Q. Romine did not give retreatment to
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`all 51 patients in that initial study; correct?
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`A. Correct.
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`Q. Romine only gave retreatment to a
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`subset of the patients included in that study;
`
`correct?
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`A. Correct.
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`Q. Please turn to page 36 of Romine.
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`A. Okay.
`
`Q.
`
`In the right column, first paragraph,
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`full sentence
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`first full paragraph, first
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`sentence, Romine states:
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`In contrast to our
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`earlier study of intravenous cladribine in
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`progressive MS, the drug was administered
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`subcutaneously. Correct?
`
`A. Yes, that is what it says.
`
`Q. Romine cites the reference 5 for
`
`their earlier study of intravenous cladribine in
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`progressive MS; correct?
`
`A. Yes.
`
`Q. Please turn to page 44 of Romine.
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`A. Okay.
`
`Q. Reference 5 is cited as: Sipe JC,
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`Romine JS, Koziol JA, et al. Cladribine in
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`treatment with chronic progressive multiple
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`sclerosis. Lancet 344; 9 to 13, 1994.
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`Correct?
`
`A. Yes.
`
`Q.
`
`So I would like to introduce an
`
`exhibit.
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`I'm going to mark this Exhibit 2004.
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`(Exhibit 2004 was marked.)
`
`A. Sorry. Where
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`Q. Preferably where it's not covering
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`text.
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`A. Okay.
`
`Q. Dr. Greenberg, do you recognize
`
`Exhibit 2004?
`
`A.
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`I believe so.
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`Q. This is a publication listing JC Sipe
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`as a first author; correct?
`
`A. Yes.
`
`Q. This publication is co-authored by
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`Romine; correct?
`
`A. Yes.
`
`Q. The same Romine who was the first
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`author of the study we just discussed; correct?
`
`A.
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`I believe so.
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`Q. The title of Exhibit 2004 is
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`"Cladribine in treatment of chronic progressive
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`multiple sclerosis." Correct?
`
`A. Yes.
`
`Q. The publication is from 1994?
`
`A. Yes.
`
`Q. This is a publication you did not
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`cite in providing your opinions for this IPR;
`
`correct?
`
`A.
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`I don't recall.
`
`Q. Have you reviewed this 1994 Sipe
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`publication before?
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`A. Sitting here today, I don't recall.
`
`Q. You did not discuss Exhibit 2004,
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`this publication by Sipe in your declaration;
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`correct?
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`A. Again, I don't recall.
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`I would need
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`to go through it to give a firm answer.
`
`Q. This 1994 publication is the same
`
`reference that Romine cites to as reference 5 in
`
`Exhibit 1016 that we previously were looking at;
`
`correct?
`
`A. Yes.
`
`Q. Please turn to page 9 of
`
`Exhibit 2004.
`
`A. Okay.
`
`PLANET DEPOS
`888.433.3767 I WWW.PLANETDEPOS.COM
`
`
`
`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
`
`28
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`Q. Please go to the left column, second
`
`paragraph, first sentence. Here Sipe and Romine
`
`state:
`
`51 patients (48 entered as matched pairs)
`
`received four monthly courses of 0.7 milligrams
`
`per kilogram of cladribine or placebo (saline)
`
`given through a surgically implanted central
`
`line. Correct?
`
`A. Correct.
`
`Q. There were 51 patients in this
`
`initial 1994 study of Sipe and Romine; correct?
`
`A. Correct.
`
`Q. These patients in this initial 1994
`
`study of Sipe and Romine were chronic multiple
`
`chronic progressive multiple sclerosis patients;
`
`correct?
`
`A. That appears to be so.
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`Q. The total amount of cladribine
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`administered was four monthly courses of
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`0.7 milligrams of kilograms of cladribine;
`
`correct?
`
`A. That appears to be so.
`
`Q. This corresponds to a total dose of
`
`2.8 milligrams per kilogram; correct?
`
`A.
`
`Q.
`
`I believe so.
`
`If you would please turn to page 11
`
`PLANET DEPOS
`888.433.3767 I WWW.PLANETDEPOS.COM
`
`
`
`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
`
`29
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`of Exhibit 2004.
`
`A. Okay.
`
`Q.
`
`If you go to the right column, last
`
`full paragraph, here you see the beginning of the
`
`Results section of Sipe and Romine's 19 --
`
`1999
`
`excuse me -- 1994 study; correct?
`
`A. Yes.
`
`Q. The Results section continues to the
`
`next page; correct?
`
`A. Yes.
`
`Q.
`
`So at the right column of page 12 is
`
`a subsection within Results entitled
`
`"Side-effects and complications." Correct?
`
`A. On page 12, yes.
`
`Q. And that is a subsection of the
`
`Results section; correct?
`
`A. Yes.
`
`Q. The last paragraph in the
`
`Side-effects and complications states:
`
`2 patients who had received cladribine had mild
`
`episodes of herpes zoster restricted to one or
`
`two dermatomas, and these subsided rapidly on
`
`treatment with oral acyclovir. Correct?
`
`A. Yes.
`
`Q.
`
`So two patients out of Sipe and
`
`PLANET DEPOS
`888.433.3767 I WWW.PLANETDEPOS.COM
`
`
`
`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
`
`30
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`Romine's patients developed herpes zoster;
`
`correct?
`
`A.
`
`It said they had mild symptoms of
`
`herpes zoster.
`
`Q.
`
`If you'd turn to Exhibit 1016, the
`
`Sipe and Romine publication.
`
`A. Yes.
`
`Q. At page 43.
`
`A. Yes.
`
`Q. The right column which we read
`
`earlier and which states:
`
`24 patients from our
`
`initial study of cladribine in chronic
`
`progressive MS have been retreated (0.7
`
`milligrams per kilogram for five days for four
`
`courses) because of a recurrence of disease
`
`worsening. Correct?
`
`A. That's what it says.
`
`Q. The paragraph continued with there
`
`were no instances of marrow suppression or
`
`thrombocytopenia in these patients, but 6
`
`(25 percent) developed herpes zoster with the
`
`second course of cladribine as compared to 2 of
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`51
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`(4 percent) with the first treatment.
`
`Correct?
`
`A. Yes.
`
`PLANET DEPOS
`888.433.3767 I WWW.PLANETDEPOS.COM
`
`
`
`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
`
`31
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`Q. As discussed in Exhibit 1016 Romine's
`
`1999 publication, 2 of 51 patients in Romine's
`
`initial study developed herpes zoster with the
`
`first treatment; correct?
`
`A. Yes.
`
`Q. We saw from Romine and Sipe's 1994
`
`publication on 51 chronic progressive multiple
`
`sclerosis patients, that two patients who had
`
`received cladribine had mild episodes of herpes
`
`zoster; correct?
`
`A. Yes.
`
`Q.
`
`So the initial study referenced in
`
`Romine's 1999 study was the same study reported
`
`and cited in Romine's 1994 publication; correct?
`
`A.
`
`I'm sorry, could you ask that one
`
`more time.
`
`Q. The initial study referenced in
`
`Romine's 1999 study was the same study reported
`
`in Sipe and Romine's 1994 publication; correct?
`
`MR. SEGREST: Objection. Form.
`
`A.
`
`It appears so.
`
`Q. During retreatment the patients
`
`received 0.07 milligrams per kilogram for five
`
`days for four courses for a total of
`
`1.4 milligrams per kilogram of cladribine;
`
`PLANET DEPOS
`888.433.3767 I WWW.PLANETDEPOS.COM
`
`
`
`Transcript of Benjamin Greenberg, M.D.
`Conducted on February 26, 2024
`
`32
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`1
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`12
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