July 2, 2019
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`Page 1
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`Ronald A. Thisted
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`- - - - - - - - - - - - - - x
`MYLAN PHARMACEUTICALS INC., :
` Petitioner, : Case Number
` vs. : IPR2018-01403
`BIOGEN MA INC., :
` Patent Owner. :
`- - - - - - - - - - - - - - x
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` VIDEOTAPED DEPOSITION OF RONALD A. THISTED
`
` Washington, DC
` Tuesday, July 2, 2019
`
`REPORTED BY:
` CARMEN SMITH
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`MYLAN PHARMS. INC. EXHIBIT 1133 PAGE 1
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`Page 1
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`Ronald A. Thisted
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`- - - - - - - - - - - - - - x
`MYLAN PHARMACEUTICALS INC., :
` Petitioner, : Case Number
` vs. : IPR2018-01403
`BIOGEN MA INC., :
` Patent Owner. :
`- - - - - - - - - - - - - - x
`
` VIDEOTAPED DEPOSITION OF RONALD A. THISTED
`
` Washington, DC
` Tuesday, July 2, 2019
`
`REPORTED BY:
` CARMEN SMITH
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`MYLAN PHARMS. INC. EXHIBIT 1133 PAGE 1
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`July 2, 2019
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`Page 2
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`Ronald A. Thisted
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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` Videotaped deposition of RONALD A. THISTED,
`called for examination pursuant to notice of
`deposition, on Tuesday, July 2, 2019, in Washington,
`DC, at the offices of Finnegan, Henderson, Farabow,
`Garrett & Dunner, LLP, 901 New York Avenue NW, at
`9:08 a.m., before CARMEN SMITH, a Notary Public
`within and for the District of Columbia, when were
`present on behalf of the respective parties:
`
` MICHAEL CHAJON, ESQ.
` BRANDON WHITE, ESQ.
` Perkins Coie LLP
` 700 13th Street NW, Suite 600
` Washington, DC 20005-3960
` 202.654.6200
` mchajon@perkinscoie.com
` On behalf of Petitioner
`
` -- continued --
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`MYLAN PHARMS. INC. EXHIBIT 1133 PAGE 2
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`July 2, 2019
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`Ronald A. Thisted
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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`APPEARANCES (Continued):
`
` MARK J. FELDSTEIN, PhD, ESQ.
` LAURA P. MASUROVSKY, ESQ.
` PIER D. DE ROO, ESQ.
` Finnegan, Henderson, Farabow, Garrett &
` Dunner, LLP
` 901 New York Avenue, NW
` Washington, DC 20001-4413
` 202.408.4000
` mark.feldstein@finnegan.com
` On behalf of Patent Owner
`
`ALSO PRESENT: Wendy Plotkin, Esq.
` Larry Flowers, video operator
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`MYLAN PHARMS. INC. EXHIBIT 1133 PAGE 3
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`Ronald A. Thisted
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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` P R O C E E D I N G S
` VIDEO OPERATOR: Good morning. We are now
`on the record. Please note that the microphones are
`sensitive and may pick up whispering and private
`conversations. Please turn off all cell phones and
`place them away from the microphones as they may
`interfere with deposition audio. Recording will
`continue until all parties agree to go off the
`record.
` This is the deposition of Dr. Ronald
`Thisted in The Matter of Mylan Pharmaceuticals Inc.,
`Petitioner, versus Biogen, Patent Owner, Patent
`8,399,514, before the United States Patent and
`Trademark Office.
` This deposition is being held at the
`offices of Finnegan, Henderson, 901 New York Avenue,
`Northwest, Washington, D.C.
` The time is approximately 9:08 a.m.
` The date today is July 2, 2019. The court
`reporter is Carmen Smith with the firm of
`Ace-Federal Reporters, Inc., I am the video
`operator, Larry Flowers, also with Ace-Federal, 555
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`MYLAN PHARMS. INC. EXHIBIT 1133 PAGE 4
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`Ronald A. Thisted
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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`12th Street, Northwest, Washington, D.C.
` Will all counsel identify themselves and
`who they represent.
` MR. CHAJON: Michael Chajon from Perkins
`Coie on behalf of Mylan.
` MR. WHITE: Brandon White from Perkins
`Coie on behalf of Mylan.
` MR. FELDSTEIN: Mark Feldstein from
`Finnegan, Henderson on behalf of Patent Owner
`Biogen. With me is Pier DeRoo and Laura Masurovsky
`from Finnegan and Wendy Plotkin from Biogen.
`Whereupon,
` RONALD A. THISTED
`was called as a witness and, having first been duly
`sworn, was examined and testified as follows:
` EXAMINATION
` BY MR. CHAJON:
` Q Good morning. Please state and spell your
`name for the record.
` A Ronald Thisted. The last name is spelled
`T-h-i-s-t-e-d.
` Q Dr. Thisted, where are you employed?
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`MYLAN PHARMS. INC. EXHIBIT 1133 PAGE 5
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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` A I am currently retired from the University
`of Chicago, although I still am doing some work
`there.
` Q And you've had your deposition taken
`before; correct?
` A Yes, I have.
` Q So this should all be familiar to you, but
`I will quickly go through it so we're on the same
`page. I'll ask you questions today, and your
`counsel might object. Your counsel may also
`instruct you not to answer.
` If your counsel objects with no further
`instruction, you must answer the question.
` Will you answer my questions today if your
`counsel objects but gives no further instruction?
` A I will attempt to do so.
` Q The court reporter is taking down
`everything we say for the transcript, so it's
`important that we talk one at a time. Will you wait
`until I finish my question before answering?
` A I'll do my best.
` Q Thanks. And if I cut you off today, it
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`MYLAN PHARMS. INC. EXHIBIT 1133 PAGE 6
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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`will be by accident. Please let me know and I'll be
`happy to let you finish your answer.
` Will you let me know if you need to finish
`an answer?
` A Yes.
` Q And also, to help the court reporter, you
`will need to give spoken answers to my questions, so
`not a head nod or pointing to something.
` Will you provide spoken answers to my
`questions today?
` A Yes.
` Q If you don't understand a question, please
`let me know and I'll try to clarify. Will you let
`me know if you don't understand any of my questions?
` MR. FELDSTEIN: I'm going to object to
`that.
` BY MR. CHAJON:
` Q You can answer.
` A I have forgotten the question.
` Q Will you let me know if you don't
`understand any of my questions?
` MR. FELDSTEIN: Objection.
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`MYLAN PHARMS. INC. EXHIBIT 1133 PAGE 7
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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` THE WITNESS: I will try to make it clear
`if -- if I don't understand.
` BY MR. CHAJON:
` Q Thank you. And I'm happy to take a break
`if you need one at any point today. But if a
`question is pending, you should answer it before we
`take the break. Will you let me know if you need a
`break at any point?
` A Yes.
` Q And will you answer any pending question
`before we take the break?
` A As long as it doesn't involve a question
`of potential privilege, yes.
` Q Is there anything preventing you from
`giving truthful testimony today?
` A No.
` Q What did you do to prepare for your
`deposition today?
` A I met with counsel.
` Q For how long?
` A For most of yesterday.
` Q And I see you have a document in front of
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`MYLAN PHARMS. INC. EXHIBIT 1133 PAGE 8
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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`you. You submitted a declaration in this IPR
`proceeding; correct?
` A Yes, I did.
` Q Is that -- is that what you have a copy
`of?
` A This is a copy of my "DECLARATION" in this
`proceeding.
` Q Okay. And it's been marked as Exhibit
`2060?
` A Yes.
` (Biogen Exhibit 2060 previously
`identified.)
` BY MR. CHAJON:
` Q Did you -- so Appendix B of your
`declaration, I'm pretty sure, is the materials
`considered?
` A Yes, it is.
` Q "Documents Considered, Appendix B." It's
`on page 76 of 77.
` Did you review any documents yesterday
`that were not on this list?
` MR. FELDSTEIN: Objection.
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`MYLAN PHARMS. INC. EXHIBIT 1133 PAGE 9
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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` I'm going to direct you not to answer,
`Dr. Thisted.
` BY MR. CHAJON:
` Q Did you review any documents yesterday to
`prepare for today?
` A Yes.
` Q What documents did you review?
` MR. FELDSTEIN: Objection.
` Direct you not to answer, Dr. Thisted.
` BY MR. CHAJON:
` Q Did you review any deposition transcripts
`yesterday?
` MR. FELDSTEIN: Direct you not to answer,
`Dr. Thisted.
` BY MR. CHAJON:
` Q Just to make the record clear, you're
`instructing him not to answer on the basis of
`attorney-client privilege?
` MR. FELDSTEIN: Work product.
` BY MR. CHAJON:
` Q Work product. We can move on.
` For this proceeding, you also reviewed a
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`MYLAN PHARMS. INC. EXHIBIT 1133 PAGE 10
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`Ronald A. Thisted
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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`declaration from one of Mylan's experts, correct,
`Dr. Leslie Benet?
` A Yes.
` Q And that declaration was marked Exhibit
`1003, and I have a copy of it -- I have copies of it
`if you ever need to take a look.
` In your declaration, you critiqued certain
`analyses that Dr. Benet did on data from Biogen's
`Phase II clinical trial for dimethyl fumarate;
`correct?
` A I critiqued calculations that Dr. Benet
`performed. I'm not sure I would characterize them
`as analyses.
` Q Calculations. Why wouldn't you
`characterize them as analyses?
` A Because for the reasons that you outline
`in my declaration, they are -- they're not reliable,
`they are not standard analyses of the -- for the
`purpose that Dr. Benet purports to use them, and
`there are substantial flaws both in the logic and in
`the interpretation of those calculations.
` Q Okay. Just to make our record today
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`MYLAN PHARMS. INC. EXHIBIT 1133 PAGE 11
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`clear, dimethyl fumarate, I'll refer to it as DMF.
`Is that okay?
` A That's okay.
` Q And it's also your understanding that
`Biogen refers to DMF as BG12; correct?
` A My understanding is that BG12 is -- the
`active ingredient is DMF.
` Q And Biogen's Phase II clinical trial for
`DMF, data on that Phase II trial was disclosed in a
`document you reviewed, it's been marked as Exhibit
`1046. And you refer to it in your declaration as
`the "Kappos Presentation." I'll hand you a copy.
` MR. FELDSTEIN: I'm sorry, what's the
`question?
` MR. CHAJON: There isn't a question yet.
` (Mylan Exhibit 1046 previously
`identified.)
` BY MR. CHAJON:
` Q Data about Biogen's Phase II clinical
`trial for DMF was disclosed in Exhibit 1046;
`correct?
` A Preliminary data from study C1900 is
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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`contained in the presentation slides.
` Q And study C1900 was the Phase II clinical
`trial for DMF; correct?
` MR. FELDSTEIN: Objection; foundation.
` THE WITNESS: It's my understanding that
`C1900 was a Phase II clinical trial.
` BY MR. CHAJON:
` Q In paragraph 39 of your declaration, which
`is on page 18, you discuss the data presented in the
`Kappos presentation, correct, in Exhibit 1046?
` A Let me just review paragraph 39 here.
` Would you repeat the question, please?
` Q In paragraph 39 of your declaration, you
`discuss Exhibit 1046; correct?
` A This is, I believe, one of the points in
`my declaration at which I discuss aspects of Exhibit
`1046.
` Q And you said, "First, the Kappos
`Presentation does not indicate any discrepancy in
`outcomes associated with the reported mean number of
`baseline lesions across study arms."
` Right?
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`MYLAN PHARMS. INC. EXHIBIT 1133 PAGE 13
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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` A Yes, I did say that.
` Q But the Kappos presentation does disclose
`variations in the baseline lesions across placebo
`and the study dosing arms; correct?
` A It indicates variation across the study
`arms in all of the baseline measurements, including
`Gd+ lesions.
` Q Please turn to page 17 of Exhibit 1046,
`the Kappos presentation.
` A Page 17?
` Q Yes.
` A Yes. I am there.
` Q The bottom row in this table gives, "No.
`of Gd+ lesions," "mean" and standard deviation;
`correct?
` A It does.
` Q The number of Gd+ lesions for the placebo
`group had a mean of 0.8; correct?
` A That's what the slide says.
` Q For the 120-milligram qd Treatment Group,
`the number of Gd+ lesions had a mean of 1.2; right?
` A Again, that's what this slide says, and
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`the reason I'm saying that is that other reports on
`this clinical trial give different numbers for these
`means. But the slide says 1.2 for the 120 milligram
`per day group.
` Q Okay. And it also says -- so slide 30 --
`or let's say page 17 of Exhibit 1046 says that for
`the 120 mg, tid Treatment Group, the number of Gd+
`lesions had a mean of 2.5; right?
` A Yes, it says that.
` Q And for the 240-milligram tid Treatment
`Group, the number of Gd+ lesions had a mean of 1.2;
`right?
` MR. FELDSTEIN: Objection.
` THE WITNESS: Again, this slide says that
`the mean number of Gd+ lesions for the 240 milligram
`group three times a day is 1.2.
` BY MR. CHAJON:
` Q And the authors of this presentation, of
`the Kappos presentation, chose to list the number of
`Gd+ enhancing lesions on the slide; correct?
` MR. FELDSTEIN: Objection; foundation.
` THE WITNESS: Yes, they did, along with
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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`the mean EDSS, which was the other inclusion
`criterion for the study.
` BY MR. CHAJON:
` Q The mean number of Gd+ lesions for the
`120-milligram tid Treatment Group was higher than
`all the other treatment groups; right?
` A It was the highest one, yes.
` Q The mean number of Gd+ lesions for the
`120-milligram tid group was over three times higher
`than placebo; right?
` MR. FELDSTEIN: Objection.
` THE WITNESS: In this version of the data
`set, yes. 2.5 is slightly more than three times
`0.8.
` BY MR. CHAJON:
` Q That's considered a discrepancy; right?
` A Not necessarily. The question is whether
`it is discrepant relative to what one would expect
`in this context with this kind of data. And the
`authors didn't flag it or comment on it.
` Q They did include it on this slide, though;
`right?
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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` A They included the numbers on the slide,
`just like they included the numbers for the other
`inclusion criterion, the EDSS score, which was
`highest in the 240 milligram three times a day
`group.
` Q For the primary endpoint of the -- of this
`Phase II study, the C1900 study, the treatment group
`was compared to placebo to determine whether it was
`statistically significantly effective; correct?
` A The -- with respect to the primary
`endpoint, each of the three treatment groups was
`compared to placebo to determine whether there were
`statistically significant differences in effect,
`specifically effect on the primary endpoint.
` Q Right. So the comparison between the mean
`number of baseline Gd+ lesions in the treatment
`groups versus the number of mean Gd+ lesions in the
`placebo group would be relevant because that
`comparison directly relates to the primary endpoint;
`correct?
` A I'm not sure I followed your question.
` Q The mean number of baseline lesions in the
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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`treatment groups, so for example, the 2.5 for the
`120-milligram tid group, the comparison to that
`number versus the one for the placebo group, which
`is 0.8, that's relevant because that's how the --
`those figures play into, if you will, the endpoint
`results?
` MR. FELDSTEIN: Objection.
` THE WITNESS: The number of Gd+ lesions at
`baseline don't -- don't figure in the analyses of
`the primary endpoint that are shown on page 19 of
`the exhibit.
` BY MR. CHAJON:
` Q In your opinion, the mean number of
`baseline Gd+ lesions do not relate to the primary
`endpoint?
` A I'm not sure what you mean by "relate."
`The primary endpoint is based on new Gd+ lesions,
`not the lesions that were existing at baseline. And
`the lesions that were existing at baseline wouldn't
`be included in the calculation of the primary
`endpoint.
` Q Is it your understanding that the mean
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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`number of baseline Gd+ lesions for the 120-milligram
`tid group, whether that's statistically
`significantly different from the mean number of
`baseline lesions for the placebo group?
` A It's my understanding that if one compares
`the highest group here to the lowest group here, at
`baseline, the difference is statistically
`significant, which is -- well, it is statistically
`significant.
` Q Did you perform the necessary calculation
`to determine whether the mean number of baseline Gd+
`lesions for the 120-milligram tid group was
`statistically significantly different from the mean
`number for the placebo group?
` A I did do that calculation.
` Q Is that calculation in your declaration?
` A No.
` Q I'm handing you what's been marked as
`Exhibit 1036 in this proceeding.
` (Mylan Exhibit 1036 previously
`identified.)
` MR. FELDSTEIN: Thank you.
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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` BY MR. CHAJON:
` Q Exhibit 1036 is a chapter written by, if
`you turn to page 3, it's a book chapter written by
`Robert J. Fox and Ralf Gold in the book "Multiple
`Sclerosis Therapeutics"; right?
` A Yes.
` Q And you reviewed Exhibit 1036?
` A Yes, I did.
` Q Do you consider Drs. Fox and Gold to be
`skilled artisans?
` A I haven't considered that question.
` Q Starting on page 389, which is page 5 of
`the exhibit, the authors discuss the Phase II
`clinical trial for BG12; right?
` A Yes.
` Q On the next page, page 390, page 6 of
`Exhibit 1036.
` A Yes.
` Q The paragraph that starts "The study met
`its primary outcome" in the left-hand column.
` Do you see that?
` A I'm sorry, say that again, please.
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`Ronald A. Thisted
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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` Q The paragraph in the left-hand column that
`starts, "The study met its primary outcome."
` Do you see that?
` A Yes.
` Q Towards the middle it says, "however" --
`it says, "However, the middle (240 mg/d) dose group
`had a 76% higher mean number of Gd-enhancing lesions
`at baseline, which may have obscured a treatment
`effect"; correct?
` A I see that.
` Q So Drs. Fox and Drs. Gold -- Drs. Fox and
`Gold recognized that there was a discrepancy with
`the mean number of Gd-enhancing lesions at baseline
`for the 360 milligram per day treatment group;
`correct?
` MR. FELDSTEIN: Objection to form.
` THE WITNESS: I don't see Drs. Fox and
`Gold drawing that conclusion drawing that conclusion
`from this statement.
` BY MR. CHAJON:
` Q By saying that the mean number of
`Gd-enhancing lesions at baseline was 76 percent
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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`higher for the 240-milligram-per-day dose group --
` MR. FELDSTEIN: I'm sorry, what's the
`question?
` MR. CHAJON: I haven't finished it yet.
` BY MR. CHAJON:
` Q All right. By saying that the mean number
`of Gd-enhancing lesions at baseline for the
`240-milligram-per-day dose group was 76 percent
`higher, the authors of Exhibit 1036 noted variation
`in those baseline figures; correct?
` A They noted a variation in the context of
`looking at the overall results from the study, in
`light of their knowledge that another study had
`already shown that 480 -- 480 milligrams per day was
`effective. And the result here is indicating that
`the highest dose showed statistically significant
`differences from placebo, but the other two doses
`didn't. And so they are, in effect, exploring and
`raising a possibility that -- that the treatment
`effect for one of the groups may have been affected
`by this observation.
` Q You have no question -- you have no reason
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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`to question their belief that the treatment effect
`for the 240-milligram-per-day dose group may have
`been obscured; correct?
` MR. FELDSTEIN: Objection.
` THE WITNESS: They don't express a belief
`that it was obscured. They are raising the
`possibility that in hindsight, it may have been
`obscured. But they don't investigate that
`possibility any further, and they don't assess what
`effect that might have had, if any, on whether that
`dose -- the 360 dosing group was statistically
`significantly different from placebo.
` BY MR. CHAJON:
` Q But you have no reason to question their
`opinion that the treatment effect might have been
`obscured by the number of baseline lesions for the
`240 milligram per day group; correct?
` A I -- it's an observation which is a
`possibility. And that I think is all that it is
`here. They are expressing a possibility. They are
`not expressing an opinion that that possibility is a
`fact.
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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` Q At the end of that paragraph, it says, "if
`the primary outcome is re-displayed as % reduction
`from each group's baseline enhancing lesion
`activity, a dose-response becomes more apparent."
` Correct?
` A Yes, they do say that.
` Q So in their discussion, the authors of
`Exhibit 1036, the authors of Fox 2011, corrected for
`baseline lesion discrepancy; right?
` MR. FELDSTEIN: Objection.
` THE WITNESS: No, that is not a correction
`for baseline lesion activity. It would be
`inappropriate as -- it would not be an appropriate
`statistical correction.
` BY MR. CHAJON:
` Q So in your opinion, Drs. Fox and Gold
`performed an inappropriate statistical correction in
`their book chapter in "Multiple Sclerosis
`Therapeutics"?
` MR. FELDSTEIN: Objection.
` THE WITNESS: First of all, they don't
`characterize this as a statistical correction. They
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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`characterize this as a hypothesis based on a rough
`calculation that, in effect, treats everyone in the
`360 milligram per day dosing group in exactly the
`same way. Each -- the result for each individual is
`essentially divided by 2.5 lesions per day,
`regardless of how many lesions they had at baseline.
`A statistical correction would take into account
`each individual's baseline lesion count, and this
`analysis doesn't and cannot do that.
` Consequently, individuals who had one
`lesion at baseline in the placebo group is treated
`differently in this analysis than patients who had
`one lesion at baseline in the 360 milligram per day
`treatment group.
` And so when you start treating patients in
`different treatment groups differently, you've lost
`the basis for a fair statistical comparison.
` Q But the authors of Fox 2011, Drs. Fox and
`Gold, they redisplayed the primary outcome as
`percent reduction for each treatment group's
`baseline enhancing lesion activity; right?
` A The second figure, 30 -- Figure B of
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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`Figure 31.4 displayed the mean number of new Gd+
`lesions divided by the number, on average, at
`baseline in each group. And that's not a -- as I
`indicated, that's not an analysis per patient, it's
`not a statistical adjustment. In fact, Fox and Gold
`had all of the individual patient data available to
`them, I presume, and did not do such an analysis,
`although they do report other analyses based on
`individual patient data that do make adjustments in
`other variables.
` So I just don't see them following up on
`this conjecture in a statistically appropriate way.
` Q So even though the Drs. Fox and Gold had
`the individual data?
` A Actually, I'm not sure whether they did
`have the individual data. I'm not sure who had
`that.
` (Mylan Exhibit 1037 previously
`identified.)
` BY MR. CHAJON:
` Q I'm handing you what's been marked as
`Exhibit 1037 in this proceeding.
`
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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` MR. FELDSTEIN: Thank you.
` MR. CHAJON:
` Q It's the "European Medicines Agency
`Assessment report" for "Tecfidera." You reviewed
`Exhibit 1037; right?
` A Yes, I did.
` Q Starting at the bottom of page 33 of
`Exhibit 1037, there's a discussion of the Phase II
`"Dose response study" for BG12; correct?
` A Yes.
` Q On page 34, the last paragraph, it says,
`"There were considerable imbalances at baseline for
`the mean number of Gd-enhancing lesions across the
`groups (notably in the 120 mg TID group which
`presented patients with higher disease activity i.e.
`higher number of Gd enhancing lesions). To further
`interpret the MRI results, subgroup analyses were
`added to the protocol after database lock by the
`applicant and additional sensitivity analyses were
`requested by the CHMP during the evaluation. In the
`CHMP requested analyses using the number of baseline
`GD-enhancing lesions as covariates, BG00012 120 mg
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`TID also provided statistically significant results
`for the primary endpoint (p=0.009)"; correct?
` A Yes, it does say that.
` Q So in the Assessment report for Tecfidera,
`the EMA recognized there was an imbalance of
`baseline lesions for the 360 milligram per day
`treatment group; correct?
` MR. FELDSTEIN: Objection; foundation.
` THE WITNESS: I would say this paragraph
`indicates that they noticed that there were
`differences and they sought to determine whether
`those differences could affect the outcomes, which
`was the purpose for the multiple analyses that they
`requested to be done, again in light of the full
`clinical trials experience, including the Phase III
`results, which was the primary focus of this
`evaluation for the EMA.
` BY MR. CHAJON:
` Q Right. So the EMA requested correction
`for the baseline lesion discrepancy in this
`assessment report for Tecfidera; right?
` A No --
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`Mylan Pharmaceuticals Inc. v. Biogen MA Inc.
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` MR. FELDSTEIN: Objection.
` Go ahead.
` THE WITNESS: No, they did not request
`correction. They asked for analyses that would
`investigate the potential effects of that.
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