throbber
Page 1
`
` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`MYLAN PHARMACEUTICALS INC. *
`and AMNEAL PHARMACEUTICALS *
`LLC, *
` * Case No. IPR2015-00643
` Petitioners, * (8,232,250 B2)
` *
`VS. * Case No. IPR2015-00644
` * (8,399,413 B2)
`YEDA RESEARCH AND *
`DEVELOPMENT CO. LTD., * Case No. IPR2015-00830
` * (8,969,302 B2)
` Patent Owner. *
`
` *******************************************
` ORAL AND VIDEOTAPED DEPOSITION OF
` EDWARD J. FOX, MD
` JANUARY 26, 2016
` *******************************************
`
` ORAL AND VIDEOTAPED DEPOSITION OF EDWARD
`J. FOX, MD, produced as a witness at the instance of
`the Petitioner Mylan Pharmaceuticals Inc. and duly
`sworn, was taken in the above-styled and numbered cause
`on the 26th day of January, 2016, from 9:22 a.m. to
`4:30 p.m., before Marsha Yarberry, Certified Shorthand
`Reporter in and for the State of Texas, reported by
`machine shorthand, at the offices of Wilson Sonsini
`Goodrich & Rosati, 900 South Capital of Texas Highway,
`Las Cimas IV, 5th Floor, Austin, Texas.
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`1
`
`2 3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`Page 1 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
` APPEARANCES
`
`Page 2
`
`FOR THE PETITIONER MYLAN PHARMACEUTICALS INC.:
`
` MR. DAVID L. ANSTAETT
` Perkins Coie
` One East Main Street, Suite 201
` Madison, Wisconsin 53703-5118
` 608-663-5408
` DAnstaett@perkinscoie.com
` --and--
` MS. COURTNEY M. PROCHNOW
` Perkins Coie
` 1888 Century Park East, Suite 1700
` Los Angeles, California 90067-1721
` 310-788-3284
` CProchnow@perkinscoie.com
`
` --and--
`
` MS. SHANNON BLOODWORTH (Via Telephone)
` MR. ROBERT SWANSON (Via Telephone)
` Perkins Coie
` 700 13th Street, NW, Suite 600
` Washington, DC 20005-3960
` 202-654-6200
` --and--
` MS. LORELEI P. WESTIN
` Wilson Sonsini Goodrich & Rosati
` 12235 El Camino Real, Suite 200
` San Diego, California 92130
` 858-350-2300
` lwestin@wsgr.com
`
` Veritext Legal Solutions
` Mid-Atlantic Region
` 1250 Eye Street NW - Suite 1201
` Washington, D.C. 20005
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`1
`
`2 3
`
`4
`
`5
`
`6
`
`7
`8
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`17
`18
`
`19
`
`20
`
`21
`22
`
`23
`24
`25
`
`Page 2 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`2
`
`3
`
`4
`
`5
`
`6
`7
`
`8
`
`9
`
`10
`
`11
`12
`13
`
`14
`
`15
`
`16
`17
`
`18
`
`19
`
`20
`21
`22
`23
`24
`25
`
`Page 3
`
` APPEARANCES (cont'd)
`
`FOR THE PETITIONER AMNEAL PHARMACEUTICALS LLC:
`
` MR. VINCENT L. CAPUANO
` Duane Morris LLP
` 100 High Street, Suite 2400
` Boston, Massachusetts 02110-1724
` 857-488-4250
` vcapuano@duanemorris.com
`
`FOR THE PATENT OWNER:
`
` MR. JOHN T. BENNETT
` Goodwin Procter
` Exchange Place
` Boston, Massachusetts 02109
` 617-570-1000
` jbennett@goodwinprocter.com
` --and--
` MR. ANDREW E. RILEY
` Goodwin Procter
` The New York Times Building
` 620 8th Avenue
` New York, New York 10018-1405
` 212-813-8800
` ariley@goodwinprocter.com
`
`ALSO PRESENT:
`
` Mr. Matthew Greinert, Mylan in-house counsel
` Ms. Lori Wolfe, Teva in-house counsel
` Mr. Jason Lemley, Videographer
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 3 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`Page 4
`
` INDEX
` PAGE
`
`Appearances..................................... 2
`
`EDWARD J. FOX, MD
` Examination by Mr. Anstaett................. 7
` Examination by Mr. Bennett.................. 211
` Further Examination by Mr. Anstaett......... 213
`Changes and Corrections......................... 215
`Signature....................................... 216
`Reporter's Certificate.......................... 217
`
` EXHIBITS
`
`NO. DESCRIPTION PAGE/LINE REFERENCED
`
`Exhibit 1005.................................... 192/15
` PCT application
`Exhibit 1006.................................... 131/8
` Article titled Randomized, Double-Blind,
` Dose-Comparison Study of Glatiramer Acetate
` in Relapsing-Remitting MS
`
`Exhibit 1008.................................... 43/13
` Article titled Copolymer 1 (Glatiramer
` Acetate) in Relapsing Forms of Multiple
` Sclerosis: Open Multicenter Study of
` Alternate-Day Administration
`
`Exhibit 1010.................................... 27/1
` Study by Dr. Omar Khan
`Exhibit 1011.................................... 41/25
` Study comparing daily injections of
` 20 milligrams of glatiramer acetate with
` every-other-day 20-milligram glatiramer
` acetate injections
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`1
`
`2
`
`3 4
`
`5
`
`6
`7
`8
`9
`10
`11
`12
`13
`14
`
`15
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`23
`
`24
`
`25
`
`Page 4 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`Page 5
`
` EXHIBITS (cont'd)
`
`NO. DESCRIPTION PAGE/LINE REFERENCED
`
`Exhibit 1067.................................... 9/10
` Petitioners' Notice of Deposition of
` Dr. Edward J. Fox
`Exhibit 1068.................................... 86/14
` Abstract
`
`Exhibit 1069.................................... 102/4
` Abstract
`Exhibit 1070.................................... 123/22
` Article titled Glatiramer Acetate:
` Successful Desensitization For Treatment of
` Multiple Sclerosis
`
`Exhibit 1071.................................... 151/6
` Article titled Gray Matter Atrophy in
` Multiple Sclerosis: A Longitudinal Study
`
`Exhibit 1072.................................... 161/3
` Fourth Declaration of Edward J. Fox, M.D.,
` PH.D.
`
`Exhibit 1073.................................... 181/2
` Article titled Tolerability and Safety of
` Novel Half Milliliter Formulation of
` Glatiramer Acetate For Subcutaneous
` Injection: An Open-Label Multicenter,
` Randomized Comparative Study
`Exhibit 1074.................................... 203/11
` Article titled Exorbitant Drug Costs May
` Price Out Patients
`Exhibit 2028.................................... 135/10
` Slide presentation
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`1
`2
`
`3 4
`
`5
`6
`
`7
`
`8
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`19
`
`20
`21
`
`22
`23
`24
`25
`
`Page 5 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`Page 6
`
` EXHIBITS (cont'd)
`
`NO. DESCRIPTION PAGE/LINE REFERENCED
`
`Exhibit 2029.................................... 59/22
` Article titled GLACIER: An Open-Label,
` Randomized, Multicenter Study to Assess the
` Safety and Tolerability of Glatiramer
` Acetate 40 mg Three Times Weekly Versus 20 mg
` Daily in Patients with Relapsing-Remitting
` Multiple Sclerosis
`Exhibit 2054.................................... 96/19
` Shalit abstract
`
`Exhibit 2091.................................... 121/11
` Katz abstract
`Exhibit 2093.................................... 114/20
` Article titled Rapid Desensitization For
` Hypersensitivity Reactions to Medications
`Exhibit 2095.................................... 110/13
` Article titled Responsiveness of Human Skin
` Mast Cells to Repeated Activation: An In
` Vitro Study
`
`Exhibit 2100.................................... 194/4
` Curriculum Vitae
`Exhibit 2129.................................... 12/4
` Declarations of Edward J. Fox, M.D., Ph.D. in
` Support of Patent Owner Yeda's Response to
` Institution of Inter Partes Review
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`1
`2
`
`3 4
`
`5
`
`6
`
`7
`8
`
`9
`
`10
`11
`
`12
`13
`
`14
`
`15
`
`16
`17
`
`18
`
`19
`20
`21
`22
`23
`24
`25
`
`Page 6 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Page 7
`
` THE VIDEOGRAPHER: Good morning. We are
`
`on the record at 9:22 a.m. on January 26, 2016. This
`
`is the video recorded deposition of Dr. Edward Fox. My
`
`name is Jason Lemley, here with our court reporter,
`
`Marsha Yarberry. We are here from Veritext Legal
`
`Solutions at the request of counsel for the plaintiff.
`
` This deposition is being held at 900
`
`South Capital of Texas Highway in Austin, Texas. The
`
`caption of this case is Mylan Pharmaceuticals Inc.
`
`versus Yeda Research and Development Company Ltd.
`
` At this time will counsel and all present
`
`identify themselves for the record?
`
` MR. ANSTAETT: This is David Anstaett of
`
`Perkins Coie on behalf of Mylan, and we have several
`
`people here as well, and I'm going to let them make
`
`their own introductions.
`
` MS. PROCHNOW: Courtney Prochnow from
`
`Perkins Coie on behalf of Mylan.
`
` MS. WESTIN: Lori Westin, Wilson Sonsini
`
`Goodrich & Rosati on behalf of Mylan.
`
` MR. GREINERT: Matthew Greinert
`
`representing Mylan.
`
` MR. CAPUANO: Vincent Capuano with Duane
`
`Morris on behalf of Petitioner Amneal.
`
` MR. BENNETT: John Bennett, Goodwin
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 7 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Page 8
`
`Procter, Boston, representing the patent owner. With
`
`me is my colleague, Andy Riley, and we also have
`
`Lori Wolfe, counsel from Teva Pharmaceuticals.
`
` THE VIDEOGRAPHER: Thank you. The
`
`witness will be sworn in and counsel may begin the
`
`examination.
`
` (Witness sworn)
`
` MR. BENNETT: Before we begin, David, I'm
`
`going to lodge an objection to the presence of the
`
`videographer. Petitioners should have filed a motion
`
`for permission to video the deposition. There was no
`
`agreement between the parties that video would occur,
`
`and in our view the presence of the videographer is
`
`objectionable. We will reserve all rights to oppose
`
`any entry of a video record onto the record should
`
`Mylan decide to later do so. That being said, we are
`
`going to go ahead and proceed subject to my objection
`
`today.
`
` MR. ANSTAETT: Okay. And I understand
`
`the objection. Our understanding of the requirements
`
`of 37 CFR 42.53(a) are different than those you just
`
`articulated. We do understand that to submit a
`
`videotape to the Board we would need to move for
`
`permission to do that, and I will note for the record
`
`and I'm going to mark as an exhibit just so it is in
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 8 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Page 9
`
`record the deposition notice that was served for
`
`Dr. Fox which specifically noted that the testimony
`
`would be recorded by stenographic and videographic
`
`means, and we received no objection from patent owner
`
`to the deposition notice. But with that understanding,
`
`I think we can proceed.
`
` And let me give Madam Court Reporter a
`
`copy of the deposition notice so we can mark that as an
`
`exhibit.
`
` (Exhibit 1067 marked)
`
` MR. ANSTAETT: Do you want a copy of
`
`that, John? Or --
`
` MR. BENNETT: That's fine.
`
` EDWARD J. FOX, MD,
`
`having been first duly sworn, testified as follows:
`
` EXAMINATION
`
`QUESTIONS BY MR. ANSTAETT:
`
` Q. Good morning, Dr. Fox.
`
` A. Good morning.
`
` Q. I'm going to ask you to please state and spell
`
`your name for the record.
`
` A. First name Edward, E-d-w-a-r-d, middle initial
`
`J, last name Fox, F-o-x, MD, PhD.
`
` Q. Dr. Fox, have you ever had your deposition
`
`taken before?
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 9 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Page 10
`
` A. I have.
`
` Q. How many times?
`
` A. Approximately five.
`
` Q. Can you tell me in chronological order what
`
`those depositions involved to the best of your
`
`recollection?
`
` A. I have been a fact witness in several personal
`
`injury cases, and I have given one instance of expert
`
`testimony, again in a malpractice case.
`
` Q. Okay. But the -- so the expert testimony was
`
`in the context of a malpractice case?
`
` A. Correct.
`
` Q. Okay. Have you ever served as an expert in a
`
`patent litigation?
`
` A. I have not.
`
` Q. Okay. The medical malpractice case that you
`
`served as an expert in, did that involve multiple
`
`sclerosis?
`
` A. No, it did not.
`
` Q. Okay. What did it involve?
`
` A. It involved a postoperative injury that was
`
`immune in nature.
`
` Q. Okay. Do you recall when that testimony was
`
`given? Just the expert testimony.
`
` A. It may have been ten years ago.
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 10 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Page 11
`
` Q. Okay. Okay. I want to -- you've been through
`
`this before, so you probably know the drill, but I do
`
`want to remind you that you're under oath, so the
`
`testimony you give today has the same force and effect
`
`as if it were given in a court of law. If you don't
`
`understand a question that I ask today, please stop me
`
`and ask me to explain and I'll do my best to do so.
`
` Your counsel may object to questions that
`
`I ask from time to time, which he's perfectly entitled
`
`to do, but notwithstanding that, unless he instructs
`
`you not to answer the question, you may go ahead and
`
`answer the question. It's important that we try not to
`
`talk over one another today because it makes the court
`
`reporter's life very difficult if we do that, so I'll
`
`do my best not to interrupt any answer you're giving,
`
`and if you'll just let me complete my questions, that
`
`will make everybody's life easier.
`
` And if you want to take a break at any
`
`point, just let me know. I just ask you to answer any
`
`question that's pending at the time. But please feel
`
`free if you need to take a break to just let me know.
`
`Okay?
`
` A. Yes.
`
` Q. Sound good?
`
` A. Yes.
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 11 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Page 12
`
` Q. All right. Let me do some kind of
`
`housekeeping here first. I'm going to give you some
`
`exhibits which I think you'll recognize. The first one
`
`is Exhibit 2129 in IPR2015-643, which relates to Patent
`
`No. 8,232,250. Let me hand that to you.
`
` MR. BENNETT: David, if you could just
`
`give me a copy.
`
` MR. ANSTAETT: Oh, yeah. Sorry, John.
`
` Q. (By Mr. Anstaett) The second exhibit I'm
`
`going to hand you is also Exhibit No. 2129, but that is
`
`in IPR2015-00644, which relates to U.S. Patent No.
`
`8,399,413. And the third I'm handing you is also
`
`Exhibit No. 2129. This is in IPR No. 2015-00 -- it
`
`says on the cover 6830. I believe it's 830. And that
`
`relates to Patent No. 8,969,302.
`
` And what I would like you to do is -- and
`
`please feel free to take all the time you need. Just
`
`look through those. These are your declarations in
`
`the -- in the three IPRs, and just if you could look
`
`through those and verify that they are indeed your
`
`declarations, I would appreciate that.
`
` A. Yes, I agree that these are the documents.
`
` Q. Okay. Thank you. As I ask you questions
`
`today I'll generally be referring to the first of those
`
`documents, which is the declaration that relates to
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 12 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Page 13
`
`U.S. Patent No. 8,232,250, which I'll call the '250
`
`patent I'm sure from time to time, but if you -- in
`
`answering any question, if you want to look through any
`
`of the other declarations, please feel free to do so.
`
`And with that, let me ask you in the '250 declaration
`
`to turn to paragraph 14.
`
` A. Yes, sir.
`
` Q. In paragraph 14 you describe the person of
`
`ordinary skill in the art; is that correct?
`
` A. It is correct.
`
` Q. All right. And you say in paragraph 14 that a
`
`person of ordinary skill in the art would have
`
`knowledge and experience of the pathophysiology of
`
`multiple sclerosis. What do you mean by
`
`pathophysiology?
`
` A. Pathology is the damage that takes place
`
`within the organ systems within the human body in the
`
`case of multiple sclerosis.
`
` Q. And so that's -- when you use pathophysiology,
`
`that's kind of the definition that I should understand.
`
`Is that fair to say? Is there any other component to
`
`that, or is it just person of ordinary skill in the art
`
`would have an understanding of the kind of damage that
`
`takes place as a result of multiple sclerosis?
`
` MR. BENNETT: Objection to the form.
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 13 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Page 14
`
` THE WITNESS: I would agree that a person
`
`of ordinary skill in the art would understand the
`
`nature of the disease to the extent that damage is
`
`occurring to the central nervous system and to the body
`
`as a whole in multiple sclerosis.
`
` Q. (By Mr. Anstaett) Okay. All right. Fair
`
`enough. Okay. If you'd turn to paragraphs 34 and 35
`
`of your declaration. You acknowledge, I think, in
`
`those paragraphs that as of 2009 it was well-known that
`
`some patients had difficulty with daily injections of
`
`glatiramer acetate as a result of pain and other
`
`symptoms associated with injection site reactions,
`
`correct?
`
` MR. BENNETT: Objection to form.
`
` THE WITNESS: If you're referring to the
`
`statement, "Understandably, many patients had
`
`difficulty with daily injections," that's the
`
`terminology that I used in my declaration.
`
` Q. (By Mr. Anstaett) Right. And that's -- you
`
`agree with that some -- it was known in the art in 2009
`
`that patients had difficulty with daily injections of
`
`glatiramer acetate, correct?
`
` A. I would not use the words you've used.
`
` Q. What words would you use?
`
` A. Many patients. You said patients. I would
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 14 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Page 15
`
`say many patients.
`
` Q. Fair enough. Many patients. It was
`
`well-known in the art in 2009 that many patients taking
`
`daily injections of glatiramer acetate had difficulty
`
`with those injections, correct?
`
` A. Correct.
`
` Q. And that that was -- further perhaps other
`
`reasons, but certainly one of the reasons was because
`
`of injection site reactions?
`
` MR. BENNETT: Objection to the form.
`
` THE WITNESS: Injection site reactions as
`
`defined here was an aspect of the difficulty with the
`
`administration of the drug.
`
` Q. (By Mr. Anstaett) Okay. And you would agree
`
`that skilled artisans in 2009 knew that daily dosing of
`
`glatiramer acetate posed challenges from a patient
`
`tolerability perspective. Is that fair to say?
`
` A. I would disagree with the wording of that.
`
` Q. How so?
`
` A. Can you restate the question?
`
` Q. Would it help if I said many patients? Would
`
`you agree that it was known in the art in 2009 that
`
`daily dosing of glatiramer acetate posed challenges for
`
`many patients from a tolerability perspective?
`
` MR. BENNETT: Objection to the form.
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 15 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Page 16
`
` THE WITNESS: Dosing of injections at all
`
`were an issue with the administration of the medicine.
`
` Q. (By Mr. Anstaett) Of glatiramer acetate?
`
` A. Yes.
`
` Q. And they were a tolerability issue for
`
`patients, correct?
`
` A. Injections are a tolerability issue.
`
` Q. Okay. And you'd also agree that skilled
`
`artisans in 2009 knew that daily dosing of glatiramer
`
`acetate posed challenges from a patient compliance
`
`perspective. Is that fair to say?
`
` A. Again, that's not the wording that I used.
`
` Q. Well, how would you word it?
`
` A. The dosing of the medication itself had
`
`implications in terms of the tolerability of the
`
`medication.
`
` Q. Correct. And that's because it was dosed as a
`
`daily subcutaneous injection, correct?
`
` MR. BENNETT: Objection.
`
` THE WITNESS: The patients that were
`
`using glatiramer acetate 20 milligrams daily had
`
`issues with injections. All injectable medicines have
`
`issues.
`
` Q. (By Mr. Anstaett) And glatiramer acetate is
`
`no exception in that regard?
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 16 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
` A. Correct.
`
` Q. And that was known by skilled artisans in
`
`Page 17
`
`2009?
`
` A. That is correct.
`
` Q. All right. And those same issues with daily
`
`subcutaneous injections also posed compliance problems
`
`with patients on glatiramer acetate, correct?
`
` A. All medicines have compliance issues.
`
` Q. Right. But glatiramer acetate, daily
`
`subcutaneous injections had patient compliance issues
`
`and skilled artisans knew that in 2009, correct?
`
` MR. BENNETT: Objection to the form.
`
` THE WITNESS: All patients on injectable
`
`medicines, including glatiramer acetate 20 milligrams
`
`daily, had issues with regards to adherence.
`
` Q. (By Mr. Anstaett) And how would you define
`
`adherence?
`
` A. Adherence is a very complicated term. There
`
`have been many definitions given to it. Do you want a
`
`specific definition as given by a specific agency?
`
` Q. I'd like to know what you mean by adherence in
`
`the context of daily 20-milligram injections of
`
`glatiramer acetate and the problems they posed with
`
`adherence.
`
` A. Adherence is keeping to a schedule that had
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 17 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Page 18
`
`been defined ahead of time, and a lack of adherence can
`
`be in many different forms but is expected to be less
`
`than adequate dosing of a medication.
`
` Q. All right. And that was a known problem in
`
`the art with daily 20-milligram injections of
`
`glatiramer acetate in 2009, correct?
`
` MR. BENNETT: Objection.
`
` THE WITNESS: I think I need you to
`
`restate that question because it was overly broad for
`
`me to say whether this was a specific problem to
`
`glatiramer acetate.
`
` Q. (By Mr. Anstaett) I'm asking you if it was a
`
`problem that was known in the art with glatiramer
`
`acetate in 2009. You're free to tell me if you think
`
`it was a problem with other medicines as well, but
`
`certainly I think we can agree that daily dosing of
`
`20 milligrams of glatiramer acetate in 2009 was known
`
`by skilled artisans to cause adherence problems as
`
`you've defined that.
`
` A. What I agree with was that dosing of
`
`glatiramer acetate as of 2009 had issues with regards
`
`to adherence.
`
` Q. All right. And skilled artisans knew that in
`
`2009?
`
` A. Agreed.
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 18 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Page 19
`
` Q. Okay. Those issues with tolerability and
`
`adherence motivated skilled artisans in 2009 to explore
`
`dosing regimens for glatiramer acetate that were less
`
`frequent than daily dosing, correct?
`
` MR. BENNETT: Objection.
`
` THE WITNESS: I would disagree with that
`
`statement.
`
` Q. (By Mr. Anstaett) All right. Could you look
`
`at paragraph 35 of your declaration?
`
` A. Yes.
`
` Q. And in that paragraph you say, "Because of the
`
`difficulty that many patients experience with daily GA
`
`injections, a few small studies exploring alternate day
`
`injections were described in the literature as of
`
`2009," correct?
`
` A. Correct.
`
` Q. And you would agree with that, right?
`
` A. I would agree with that statement.
`
` Q. Okay. And you'd also agree with me, would you
`
`not, that prior to August of 2009 there were at least a
`
`few studies exploring alternate day injections of GA
`
`that were described in the literature, correct?
`
` A. That is this statement I have here in 35.
`
` Q. Okay. All right. And one of the studies --
`
`you cite a couple of those studies in your declaration,
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 19 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Page 20
`
`correct?
`
` A. I do.
`
` Q. All right. And one of those studies of less
`
`frequent than daily dosing of glatiramer acetate as of
`
`2009 was conducted by Dr. Omar Khan, correct?
`
` A. Correct.
`
` Q. All right. Do you know Dr. Khan?
`
` A. I do.
`
` Q. How do you know him?
`
` A. We have been a colleague for many years.
`
` Q. Okay. What is Dr. Khan's reputation in the
`
`field, in your field?
`
` MR. BENNETT: Objection; vague.
`
` THE WITNESS: I cannot speak to his
`
`overall reputation. His reputation from my standpoint
`
`is positive.
`
` Q. (By Mr. Anstaett) Okay. He's a reputable
`
`scientist in your estimation?
`
` A. In my estimation he is.
`
` Q. Okay. Now, in paragraph 35 you say that none
`
`of those studies with less frequent than daily dosing
`
`in the art in 2009 changed the standard of care
`
`concerning glatiramer acetate as of 2009, correct?
`
` A. Correct.
`
` Q. All right. What does it take to change the
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 20 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Page 21
`
`standard of care for a disease-modifying therapy in
`
`multiple sclerosis?
`
` A. A number of factors are involved in changing a
`
`standard of care, the most principal being that there
`
`is solid scientific evidence that a change in solid
`
`[sic] of care is in the best clinical interest of the
`
`patient.
`
` Q. Okay. You said there were a number of
`
`factors. Are there others?
`
` A. Feasibility of change in care would include
`
`access to medication, whether the patient would, in
`
`fact, be able to get the product and administer it as
`
`being suggested.
`
` Q. All right. So to change the standard of care
`
`or the -- the different dosing regimen would have to be
`
`available to patients. Is that --
`
` A. Correct.
`
` MR. BENNETT: Objection.
`
` Q. (By Mr. Anstaett) Okay. And you said there
`
`has to be solid scientific evidence that a change in
`
`care is in the best clinical interest of the patient.
`
`What would, in your estimation, constitute solid
`
`scientific evidence sufficient to change the standard
`
`of care for dosing a disease-modifying therapy in
`
`multiple sclerosis?
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 21 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Page 22
`
` A. There would have to be a consensus of the
`
`persons of ordinary skill in the art that this was the
`
`correct move and that this consensus was made public.
`
` Q. Okay. How -- on what -- in your experience,
`
`what would be required for there to be consensus on
`
`that topic?
`
` A. At meetings there would have to be discussions
`
`and agreement on the subject, and the critical data
`
`would be presented and peer reviewed.
`
` Q. Okay. And is this a consensus that must exist
`
`amongst all or a substantial portion of skilled
`
`artisans?
`
` MR. BENNETT: Objection to the form.
`
` THE WITNESS: I would agree that a
`
`substantial proportion of the involved parties would
`
`have to be in agreement.
`
` Q. (By Mr. Anstaett) Okay. And you said
`
`critical data would have to be presented and peer
`
`reviewed. What did you mean by "critical data"?
`
` A. Either large, well-controlled clinical trials
`
`or a substantial number of independent smaller trials
`
`that could be analyzed in a meta-analysis that would
`
`give clinically meaningful information.
`
` Q. Okay. You say in paragraph 15 to 18 of your
`
`declaration that you've been informed about certain
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 22 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`legal principles concerning obviousness. Do you see
`
`Page 23
`
`that?
`
` A. Yes, I do.
`
` Q. All right. According to your understanding,
`
`does information in the prior art have to change the
`
`standard of care concerning glatiramer acetate in order
`
`to be relevant to the issue of obviousness?
`
` MR. BENNETT: Objection to the form,
`
`calls for a legal conclusion.
`
` THE WITNESS: The definition of
`
`obviousness includes the scope and content of the prior
`
`art. As a medical person, when I think of scope and
`
`content, it is what I've been referring to as to the
`
`quality of the research, the size of the research, and
`
`the importance of the research.
`
` Q. (By Mr. Anstaett) Okay. So quality of the
`
`research, size of the research, important of the
`
`research are three factors; is that correct?
`
` A. Among others.
`
` Q. Okay. And those are principles I assume
`
`you've applied in selecting the references which you
`
`rely on in your declaration. Is that fair to say?
`
` A. I would not have thought to say it that way.
`
` Q. Okay. You make a number of -- you have a
`
`number of opinions that you express in your declaration
`
`Veritext Legal Solutions
`215-241-1000 ~ 610-434-8588 ~ 302-571-0510 ~ 202-803-8830
`
`Page 23 of 258
`
`YEDA EXHIBIT NO. 2146
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Page 24
`
`about what a person of ordinary skill in the art would
`
`have expected with respect to less frequent dosing of
`
`glatiramer acetate in 2009, correct?
`
` A. I would not say expected at all. I would say
`
`that we had a number of prior arts that were listed as
`
`meaningful data points for the support of the
`
`statements that I make in m

This document is available on Docket Alarm but you must sign up to view it.


Or .

Accessing this document will incur an additional charge of $.

After purchase, you can access this document again without charge.

Accept $ Charge
throbber

Still Working On It

This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.

Give it another minute or two to complete, and then try the refresh button.

throbber

A few More Minutes ... Still Working

It can take up to 5 minutes for us to download a document if the court servers are running slowly.

Thank you for your continued patience.

This document could not be displayed.

We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.

Your account does not support viewing this document.

You need a Paid Account to view this document. Click here to change your account type.

Your account does not support viewing this document.

Set your membership status to view this document.

With a Docket Alarm membership, you'll get a whole lot more, including:

  • Up-to-date information for this case.
  • Email alerts whenever there is an update.
  • Full text search for other cases.
  • Get email alerts whenever a new case matches your search.

Become a Member

One Moment Please

The filing “” is large (MB) and is being downloaded.

Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.

Your document is on its way!

If you do not receive the document in five minutes, contact support at support@docketalarm.com.

Sealed Document

We are unable to display this document, it may be under a court ordered seal.

If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.


Access Government Site

We are redirecting you
to a mobile optimized page.





Document Unreadable or Corrupt

Refresh this Document
Go to the Docket

We are unable to display this document.

Refresh this Document
Go to the Docket