724
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 1 of 82 PageID #: 2973
`
`IN THE UNITED STATES DISTRICT COURT.
`IN AND FOR THE DISTRICT OF DELAWARE
`- - -
`
`))
`
`))
`
`)
`- - -
`
`)C.A. No. 15-1159 (GMS)(SRF)
`)
`)CONSOLIDATED
`)
`
`ALCON RESEARCH, LTD.,
`Plaintiff,
`
`v.
`WATSON LABORATORIES, INC.,
`Defendant.
`
`ALCON RESEARCH, LTD.,
`Plaintiff,
`
`v.
`LUPIN LTD. and LUPIN
`PHARMACEUTICALS, INC.,
`Defendants.
`
`))
`
`))
`
`))
`
`)
`
`))
`
`)
`- - -
`Wilmington, Delaware
`Thursday, October 5, 2017
`9:00 a.m.
`Bench Trial - Day 4
`- - -
`BEFORE: HONORABLE GREGORY M. SLEET, Senior Judge, U.S.
`District Court of DE
`
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`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 1 of 82 PageID #: 2973
`
`IN THE UNITED STATES DISTRICT COURT.
`IN AND FOR THE DISTRICT OF DELAWARE
`- - -
`
`))
`
`))
`
`)
`- - -
`
`)C.A. No. 15-1159 (GMS)(SRF)
`)
`)CONSOLIDATED
`)
`
`ALCON RESEARCH, LTD.,
`Plaintiff,
`
`v.
`WATSON LABORATORIES, INC.,
`Defendant.
`
`ALCON RESEARCH, LTD.,
`Plaintiff,
`
`v.
`LUPIN LTD. and LUPIN
`PHARMACEUTICALS, INC.,
`Defendants.
`
`))
`
`))
`
`))
`
`)
`
`))
`
`)
`- - -
`Wilmington, Delaware
`Thursday, October 5, 2017
`9:00 a.m.
`Bench Trial - Day 4
`- - -
`BEFORE: HONORABLE GREGORY M. SLEET, Senior Judge, U.S.
`District Court of DE
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`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`725
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 2 of 82 PageID #: 2974
`
`APPEARANCES:
`MARYELLEN NOREIKA, ESQ.
`Morris Nichols Arsht & Tunnell LLP
`-and-
`CHRISTOPHER J. MANDERNACH, ESQ., and
`ADAM PERLMAN, ESQ.,
`JOELLE JUSTUS, ESQ., and
`CHRISTOPHER SUAREZ, ESQ.
`Williams & Connolly LLP
`(Washington, DC)
`Counsel for Plaintiff
`Alcon Research, Ltd.
`MELANIE K. SHARP, ESQ., and
`ROBERT VRANA, ESQ.
`Young Conaway Stargatt & Taylor LLP
`-and-
`MARK D. SCHUMAN, ESQ.,
`TODD S. WERNER, ESQ.,
`JENELL C. BILEK, ESQ.,
`SHELLEAHA JONAS, ESQ., and
`CAROLINE R. MARSILI, ESQ.
`Carlson Caspers
`(Minneapolis, MN)
`
`Counsel for Defendant
`Watson Laboratories, Inc.
`DOMINICK GATTUSO, ESQ.
`Heyman Enerio Gattuso & Hirzel LLP
`-and-
`IMRON T. ALY, ESQ.,
`JOHN K. HSU, ESQ., and
`CHRISTINE WILSON FELLER, ESQ.
`Schiff Hardin
`(Chicago, IL and New York, NY)
`Counsel for Lupin Limited and
`Lupin Pharmaceuticals, Inc.
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`09:03:34
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`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`726
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 3 of 82 PageID #: 2975
`
`THE COURT: Good morning. Please, take your
`seats, ladies and gentlemen.
`Mr. Schuman.
`MR. SCHUMAN: Good morning, Your Honor.
`I understand the videos are now fixed. We have
`a 28-minute video of Dr. Wheeler for you.
`THE COURT: Okay. Thank you.
`(Video played as follows.)
`"Question: Good morning, Dr. Wheeler.
`"Answer: Good morning.
`"Question: I would like to start by discussing
`your education. Could you identify where you went to
`college and what your degree was?
`"Answer: My undergraduate degree is in
`biochemistry and I went to the University of Rochester. I
`have a Ph.D. in pharmacology from the University of Alabama
`at Birmingham.
`"Question: When did you get your Bachelor's
`
`degree?
`
`"Answer: I graduated in 1992.
`"Question: And did you go straight to graduate
`school at that point?
`"Answer: Yes.
`"Question: And when did you obtain your Ph.D.
`in pharmacology?
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`09:04:35
`
`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`727
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 4 of 82 PageID #: 2976
`Wheeler - depo.
`"Answer: That was, I believe, in December of
`
`1997.
`
`"Question: What did you do after your post-doc?
`"Answer: I obtained the position in in vivo
`technology at Alcon.
`"Question: How long did you hold that position?
`"Answer: For approximately eight years.
`"Question: So what year does that bring us up
`to at that point?
`"Answer: About 2009.
`"Question: So up until 2009 at Alcon you were
`focused on in-vivo toxicology?
`"Answer: Correct, various roles within that
`organization.
`"Question: Were you involved with olopatadine?
`"Answer: Yes.
`"Question: Were your responsibilities directed
`to the development side?
`"Answer: Yes.
`"Question: Did you do preclinical work or --
`"Answer: Yes, I did.
`"Question: What position did you assume in
`
`2009?
`
`"Answer: After being in the toxicology
`organization, I transferred to what was known as a project
`
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`09:05:42
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`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`728
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 5 of 82 PageID #: 2977
`Wheeler - depo.
`head role, so it was strictly development.
`"Question: When did you first get involved with
`the high-dose olopatadine project?
`"Answer: I believe it was -- well, back up. As
`a toxicologist in 2008 and '09, I had exposure to the
`high-dose olopatadine project. And then when I transitioned
`to the project head role in 2009, I became the project
`leader of that project.
`"Question: I've handed you Exhibit 105. Do you
`recognize that document?
`"Answer: I have reviewed several documents
`prior to -- as part of the preparation for this, and I
`believe this was one of the documents I may have seen during
`that review.
`
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`"Question: Do you know if you would have been
`at the meeting where this was presented?
`"Answer: I'm fairly certain I was not.
`"Question: If you could turn to Page 727. I've
`seen this acronym TPP a number of places. What does that
`mean?
`
`"Answer: Stands for target product profile.
`"Question: And what is the target product
`
`profile?
`
`"Answer: So it's essentially the goalpost for
`the product in terms of what could be marketable.
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`09:07:10
`
`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`729
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 6 of 82 PageID #: 2978
`Wheeler - depo.
`"Question: And it looks like you typically have
`a base case and then an upside or aspirational case; is that
`correct?
`
`"Answer: That's correct, yes.
`"Question: And so the base case is sort of the
`minimum you want to be able to achieve; is that correct?
`"Answer: Yes.
`"Question: And then the upside or aspirational
`case would be the best-case scenario?
`Maybe just an upside scenario as opposed to best
`
`case.
`
`"Answer: I would -- yeah, I would prefer to
`term it that because there may be something even better that
`we hadn't thought of at the time. Yes, that's correct.
`"Question: I'm wondering what -- why it would
`be -- why you considered it more desirable to have an
`indication for the treatment of signs and symptoms of
`seasonal parenteral conjunctivitis versus the treatment of
`ocular itch due to seasonal parenteral allergic
`conjunctivitis?
`"Answer: It's simply a wider indication, so
`signs and symptoms include both signs and symptoms, whereas
`ocular itch is narrower.
`"Question: Do you know what signs and symptoms
`encompasses beyond ocular itch?
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`09:08:24
`
`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`730
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 7 of 82 PageID #: 2979
`Wheeler - depo.
`"Answer: Yeah. Signs and symptoms includes --
`there is a variety of endpoints we put into the studies, so
`it's both redness, chemosis, swelling, and tearing are I
`think four additional signs and symptoms that we measure in
`those studies.
`"Question: So if you could get the signs and
`symptoms indication, you could market your product for
`treating all of those symptoms as opposed to just itching?
`"Answer: Correct.
`"Question: And in the upside case you identify
`superiority to Pataday; is that correct?
`"Answer: Correct.
`"Question: So you were hoping to be able to
`market it -- market the -- the HD olopatadine product as
`being superior to Pataday; is that correct?
`"Answer: That would be the upside case, yes.
`"Question: So to get the product reg -- to get
`the HD olopatadine product registered, was it necessary to
`demonstrate superiority to earlier products?
`"Answer: No.
`"Question: You just had to demonstrate safety
`and efficacy relative to vehicle?
`"Answer: That's correct.
`"Question: Did you know -- or did you have a
`goal in mind when you set out on this development project in
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`
`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`731
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 8 of 82 PageID #: 2980
`Wheeler - depo.
`terms of what endpoints you hoped to -- to demonstrate
`superiority of for HD olopatadine relative to earlier
`products?
`
`"Answer: I think our -- at this stage of
`development, we would have taken any of the signs and
`symptoms superiority. It wasn't necessarily clear what we
`could achieve at this time.
`"Question: You have been handed Exhibit 137.
`Is this -- this one actually is a PPPM presentation. What
`is a PPPM presentation?
`"Answer: The acronym PPPM, I do not recall the
`exact makeup of it. It has pharmaceutical product --
`project, but I can't remember what it meant.
`"Question: What is the difference between this
`meeting and a PRM meeting?
`"Answer: This meeting -- the PPPM meeting was
`merely a pre-read screening and did not -- the committee did
`not contain the same decision-making members as PRM. It was
`not an official decision-making meeting.
`"Question: If you turn Slide 868, there is a
`reference to an FDA meeting. I'm just wondering, did you
`attend -- personally attend FDA meetings?
`"Answer: Yes.
`"Question: All right. Were you responsible for
`feeding any Q and A with the agency at these meetings?
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`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`732
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 9 of 82 PageID #: 2981
`Wheeler - depo.
`"Answer: Yes.
`"Question: Was that regularly the case or was
`that atypical where you would be answering questions?
`"Answer: I would say it's -- in general, I -- I
`was involved in the discussion, but didn't answer every
`question and wasn't always involved in every question.
`"Question: If you turn to Page 887, this
`concerns CAC Study C-10-126; is that correct?
`"Answer: Yes.
`"Question: And is this the first clinical study
`performed for Pazeo.
`"Phase III clinical study?
`"Answer: This is the first Phase III study
`conducted with the final formulation that eventually became
`Pazeo.
`
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`"Question: Okay. And under the objectives
`there is a references to statistical all caps, and, end all
`caps, clinical superiority. Do you see that?
`"Answer: Yes.
`"Question: What is the difference between
`statistical and clinical superiority?
`"Answer: Statistical superiority is merely a
`numerical empowered difference in terms of the statistical
`difference between two numbers. The clinical superiority is
`based on an interpretation of the magnitude of effect.
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`09:12:56
`
`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`733
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 10 of 82 PageID #: 2982
`Wheeler - depo.
`"Question: A statistically significant
`difference is an indication that an observed difference is
`not just by chance; correct? It's an actual difference.
`"Is that a fair statement?
`"Answer: That's the definition of a statistical
`difference, yes.
`"Question: And then the reference here to
`clinical superiority would be an assessment of the clinical
`meaning -- the clinical significance of that observed
`difference; is that correct?
`"Answer: I would agree with that
`interpretation.
`"Question: Did Alcon ever seek guidance from
`the FDA about what they would need to do in order to
`demonstrate clinical superiority of .7 percent olopatadine
`to -- relative to Pataday?
`"Answer: We had an FDA meeting where we asked
`what would be necessary for us to show the data with Pazeo
`versus Pataday in the label.
`"Question: What was their response?
`"Answer: The response was fairly expected, to
`well controlled clinical trials and with both the active in
`both trials and the ability to put it in the label would be
`a review issue.
`"Question: Did you ever ask them, 'them' being
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`09:14:12
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`09:14:16
`
`09:14:18
`
`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`734
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 11 of 82 PageID #: 2983
`Wheeler - depo.
`the FDA, what you would need to do in order to make any
`statements about clinical superiority of .7 percent relative
`to Pataday?
`
`"Answer: I do not recall exactly discussions
`about clinical superiority, and the reason being, we
`generally avoided that discussion because that's an
`interpretation that we did not want to have to come up with
`a number, and we didn't know what the number was going to
`be.
`
`"Question: So what was that -- in other words,
`was that a -- was there a risk to asking that in the event
`you wouldn't be able to satisfy it?
`"Answer: That's a risk, yes.
`"Question: You have been handed Exhibit 139.
`Do you recognize that document?
`"Answer: I can't say I'm familiar with this
`document, no.
`"Question: As a general matter, are you
`familiar with this type of document?
`"Answer: This appears to be a -- a formulation
`technical report, and I have seen these before.
`"Question: Do you know why these technical
`reports are prepared?
`"Answer: In general they're prepared because we
`want to learn from basically the studies that were done, we
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`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`735
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 12 of 82 PageID #: 2984
`Wheeler - depo.
`want to compile all the data together into one place so we
`can easily find it and then carry it forward for other
`projects or for the existing project.
`"Question: Were you involved in the preparation
`of technical reports during the HD olopatadine project?
`"Answer: Define 'involved.'
`"Question: Did you review them or provide any
`
`input?
`
`reports.
`
`"Answer: I would occasionally review technical
`
`"Question: Turning now to the CAC studies in
`support of the Pazeo NDA, those are the -- at least the
`clinical data in the patent is derived from one of those
`studies; correct?
`"Answer: Yes, that's correct.
`"Question: And that's the first -- the first of
`the two CAC studies performed?
`"Answer: That's correct.
`"Question: With respect to the first clinical
`trial, how did you decide upon the primary endpoints, you
`being Alcon? And just to confirm for the record, this
`was -- we're in the 30(b)(6) topics right now.
`"Answer: So the objective of the study was to
`obtain registration, so the endpoints are fairly set by the
`agency in terms of comparisons to vehicle, and itching being
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`09:16:55
`
`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`736
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 13 of 82 PageID #: 2985
`Wheeler - depo.
`a primary endpoint if we want to obtain the base case
`approval that was in the target product profile.
`"Question: Is there another metric besides
`itching that Alcon could have analyzed in order to
`demonstrate efficacy sufficient to secure registration?
`"Answer: All of the endpoints that are
`considered signs and symptoms of allergic conjunctivitis are
`options to demonstrate efficacy in my interpretation of the
`agency's view on that subject.
`"Question: And why did Alcon choose to focus on
`itching as its endpoint for primary -- its primary endpoint?
`"Answer: It had the highest probability of
`success in terms of being able to achieve the FDA's
`requirements.
`"Question: Do you know if itching is considered
`a more significant endpoint from a clinical or patient
`perspective than the other symptoms of ocular allergic
`conjunctivitis?
`"Answer: Can you define 'more significant?'
`"Question: If that's considered a bigger
`concern to patients than the other endpoints? The other
`symptoms, I should say?
`"Answer: The surveys we conducted in terms of
`what patients view as the most, let's say, burdensome signs
`and symptoms, itching is number one.
`
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`09:18:37
`
`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`737
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 14 of 82 PageID #: 2986
`Wheeler - depo.
`"Question: How was redness assessed in the
`first and second clinical studies?
`"Answer: So redness is assessed by an observer,
`so an observer such as a trained individual has a scale by
`which -- a standardized scale of pictures by which they then
`view the patient with those pictures and select the score
`based on how they correspond the picture to the patient s
`current -- how they look.
`"Question: Were the observers given training or
`are they physicians or just average Joes?
`"Answer: The observers are trained individuals.
`"Question: You measured a few different forms
`of redness; is that correct?
`"Answer: That is correct.
`"Question: What is conjunctival redness?
`"Answer: Conjunctival redness has to do with
`the location of the redness, so there is conjunctiva -- the
`three forms of redness are conjunctive, ciliary and
`episcleral.
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`"Ciliary is captured around the iris, so that's
`the redness directly around the -- the injection around the
`eye. Conjunctival is in the conjunctival bed. Episcleral
`is below that layer of vessels that are just below the
`conjunctiva.
`
`"Question: And then a visual observer can look
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`09:20:01
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`09:20:02
`
`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`738
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 15 of 82 PageID #: 2987
`Wheeler - depo.
`at the eye and separately assess conjunctival, ciliary and
`episcleral redness?
`"Answer: Yes. A trained individual can do
`
`that, yes.
`
`"Question: Do you know if Alcon is -- has done
`what is necessary in order to promote Pazeo as being
`superior relative to Pataday?
`"What was the purpose of having any comparisons
`between .7 and .2 percent olopatadine in the CAC trials?
`"Answer: Well, I mean, we were trying to
`satisfy an unmet medical need, so the idea was we had to
`improve over the existing product that was out there. We
`felt that our product, Pataday, at the time was the best
`product and that comparison made logical sense because
`without being superior to the existing product, it didn't
`have any value. It didn't have the value that, you know, we
`wanted.
`
`"Question: Do you know if Alcon is -- has done
`what is necessary in order to promote Pazeo as being
`superior relative to Pataday?
`"Answer: We have demonstrated that we are
`superior at 24 hours and that is in our label, and then we
`use that in our marketing campaign.
`"Question: Superior at 24 hours with respect to
`what endpoints?
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`09:21:35
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`09:21:38
`
`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`739
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 16 of 82 PageID #: 2988
`Wheeler - depo.
`"Answer: Itching and versus Pataday.
`"Question: What about redness?
`"Answer: We do not make any claims in the
`marketing material on redness.
`"Question: I've handed you Exhibit 140. Do you
`recognize this to be an e-mail with an attached
`presentation?
`"Answer: Yes.
`"Question: And this presentation is another
`PPPM meeting; is that correct?
`"Answer: Yes.
`"Question: On page -- Slide No. 6, assessments
`and endpoints --
`"Answer: Yes.
`"Question: -- we have talked about, I believe,
`primary and secondary efficacy. There is also a category
`called supportive efficacy. Do you see that?
`"Answer: Yes.
`"Question: What's the difference between
`supportive efficacy and secondary efficacy?
`"Answer: The world of statistics. These are
`just three different categories, so your primary is the
`endpoint that you feel, I guess, is the most important in
`terms of being able to demonstrate your difference --
`differences.
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`09:22:49
`
`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`740
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 17 of 82 PageID #: 2989
`Wheeler - depo.
`"Secondary is kind of next in line, and then
`supportive efficacy is generally where you're -- you're --
`you might say hypothesis generating, I want to see what
`happens with these endpoints, and if I see something, then I
`might, you know, try to repeat it in another study as a
`primary or secondary.
`"Question: All right. You have been handed a
`revised Exhibit 141. This one bears Production No.
`150470-509. Do you recognize this document?
`"Answer: Yes.
`"Question: And is this a presentation you gave
`to the PRM after you had completed the second clinical
`trial?
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`"Answer: Yes, it's noted as first interpretable
`results, and that was a -- a typical type of presentation
`the team would give to PRM at that time.
`"Question: Did you prepare this presentation
`with the team?
`"Answer: Similar, yes, similar. The team would
`present -- put together the presentation and we present it
`together.
`
`"Question: Okay. If you could turn to Page
`506, there is a chart on this page. What is this -- what is
`this chart?
`
`"Answer: In order to rank a portfolio, in other
`
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`09:24:10
`
`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`741
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 18 of 82 PageID #: 2990
`Wheeler - depo.
`words, a number of projects or programs that are ongoing,
`they use a scorecard -- Alcon used a scorecard to try to
`compare the projects in terms of their value.
`"Question: So according to this scorecard, the
`project group believed that high-dose olopatadine
`represented under market attractiveness an incremental
`improvement in efficacy, safety or performance; is that
`correct?
`
`"Answer: That's correct.
`"Question: And that is assigned a value of 3;
`
`correct?
`
`"Answer: Yes.
`"Question: And a value of 4 would have been
`assigned if they had perceived a high-dose olopatadine to
`represent a large unmet need related to efficacy or
`performance; correct?
`"Answer: That's correct.
`"Question: I've handed you Exhibit 142. Do you
`recognize that document?
`"Answer: Yes.
`"Question: What is it?
`"Answer: This is a white paper that was
`generated by Dr. Abelson's group at Ora in support of the
`Pazeo product and its benefit to Pataday.
`"Question: Ora was the company that performed
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`09:25:17
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`09:25:27
`
`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`742
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 19 of 82 PageID #: 2991
`Wheeler - depo.
`the clinical studies; is that correct?
`"Answer: That's right.
`"Question: Had they performed clinical studies
`for Alcon before this trial?
`"Answer: Yes.
`"Question: What was the purpose of this white
`
`paper?
`
`"Answer: The purpose of this white paper was to
`try to influence the FDA in terms of demonstrating the
`clinical benefit of Pazeo over Pataday by putting together
`all of the data, not necessarily just the primary and
`secondary, you know, also talking about the supportive
`endpoints that we talked about earlier and compiling them
`into one paper so that they could view a different viewpoint
`of interpreting the data.
`"Question: Was -- did Alcon ask Dr. Abelson to
`prepare this white paper?
`"Answer: Yes.
`"Question: Did they have a role in preparing
`this white paper?
`"Answer: We were reviewers.
`"Question: Did you have -- did Alcon have an
`opportunity to provide feedback and potential changes to the
`white paper?
`
`"Answer: Yes, we did.
`
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`09:26:42
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`09:26:43
`
`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`743
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 20 of 82 PageID #: 2992
`Wheeler - depo.
`"Question: And did you exchange drafts of the
`
`white paper?
`
`"Answer: Yes, we did.
`"Question: How was Dr. Abelson compensated for
`the white paper?
`"Answer: I believe there was a contract set up
`for drafting it and there was payment upon, you know,
`completion.
`
`"Question: Was this something that was part of
`the clinical trial agreement or is it something that's
`separate from the clinical trials?
`"Answer: Separate from the clinical trial
`
`agreement.
`
`"Question: Alcon thought it would be a good
`idea to entrust its support for the superiority of .7 to .2
`percent olopatadine?
`"Answer: Yes, with -- by using the white paper.
`"Question: If you could turn to Page 710 of the
`white paper, there is a section concerning the .2 percent
`olopatadine solution. Do you see that?
`"Answer: Yes.
`"Question: The first sentence refers to
`preclinical data. Do you see that?
`"Answer: Which paragraph are you referring to?
`"Question: Right under olopatadine .2 percent,
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`09:27:42
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`09:27:42
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`09:27:44
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`09:27:49
`
`09:27:57
`
`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`744
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 21 of 82 PageID #: 2993
`Wheeler - depo.
`it refers to preclinical inhibitory concentrations and
`duration.
`
`"Answer: Yes.
`"Question: The full sentence says, 'The broad
`safety profile of olopatadine coupled with the fact that its
`preclinical inhibitory concentration and duration had not
`yet been fully exploited, led to the development of
`olopatadine 0.2 percent (Pataday.)'
`"Is that correct?
`"Answer: That's correct.
`"Question: If you could turn to Page 720, on
`the first section at Page 4.1.2.2, 'Itching Results'?
`"Answer: Uh-huh.
`"Question: And then later on in the third
`paragraph under that heading, Dr. Abelson states that
`'Ocular itching is considered by most clinicians as the key
`issue facing patients in control of symptoms and quality of
`life.'
`
`"Do you see that?
`"Answer: Yes.
`"Question: That was consistent with the survey
`that Alcon had performed that you referenced earlier today;
`correct?
`
`"Answer: That's correct, yes.
`"Question: So redness was a secondary issue to
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`09:29:00
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`09:29:01
`
`09:29:02
`
`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`745
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 22 of 82 PageID #: 2994
`Wheeler - depo.
`
`itching?
`
`"Answer: In the opinion of the patients who
`took that survey, yes.
`"Question: Again, if you could turn to Page
`746. Does this table summarize the results of the secondary
`endpoints?
`
`"I guess primary and secondary endpoints?
`"Answer: This is a summary of both the primary
`and secondary endpoints I think for the trial number one,
`yes, and support as well.
`"Question: And are the values on the right
`column the difference in the mean values for Pazeo and
`Pataday at the referenced time point?
`"Answer: Yes, that is correct.
`"Question: And so if we were testing relative
`to vehicle, that note value would have to be greater than 1
`in order to qualify as clinically significant; correct?
`"Answer: In the FDA's opinion, yes.
`"Question: I've handed you Exhibit 143. Do you
`recognize that document?
`"Answer: Yes.
`"Question: What is this document?
`"Answer: This is a memo or letter from Dr. Neal
`Barney regarding his interpretation of the data that was --
`that was going to be presented to the agency, the FDA.
`
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`Novartis AG Exhibit 2008
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`
`
`746
`Case 1:15-cv-01159-GMS-SRF Document 148 Filed 10/07/17 Page 23 of 82 PageID #: 2995
`Wheeler - depo.
`"Question: Who is Dr. Barney?
`"Answer: Dr. Barney is an ophthalmologist who
`was recommended by Ora's potential outside third-party
`reviewer of the data, an independent viewer of the data.
`"Question: What was the purpose of this paper?
`"Answer: The purpose of this letter was to give
`his opinion of the data, and then that this would be, you
`know, potentially, if it wa
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