`
`Transcript of Szilard Kiss, M.D,
`Volume 2
`
`Date: May 13, 2022
`Case: Regeneron -v- Novartis (PTAB)
`
`Planet Depos
`Phone: 888.433.3767
`Email: transcripts@planetdepos.com
`www.planetdepos.com
`
`WORLDWIDE COURT REPORTING & LITIGATION TECHNOLOGY
`
`Novartis Exhibit 2345.001
`Regeneron v. Novartis, IPR2021-00816
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`REDACTED VERSION
`
`
`
` UNITED STATES PATENT AND TRADEMARK OFFICE
` ___________________________
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
` __________________________
`
` REGENERON PHARMACEUTICALS, INC.,
` Petitioner
` v.
` NOVARTIS PHARMA AG,
` NOVARTIS TECHNOLOGY LLC,
` NOVARTIS PHARMACEUTICALS CORPORATION,
` Patent Owners
` ____________________________
` Case IPR2021-00816
` Patent No. 9,220,631
` ___________________________
`
` Remote Zoom Deposition of
` SZILARD KISS, taken on
` May 13, 2022 at 8:04 a.m.
` ____________________________
` CONFIDENTIAL
`Job No. 448259
`Pages 80-122
`Reported by: Lisa M. Barrett, RPR, CRR, CRC, CSR
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`Regeneron v. Novartis, IPR2021-00816
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`REDACTED VERSION
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`
`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
` REMOTE DEPOSITION OF SZILARD KISS held
`virtually via Zoom videoconferencing,
`
` Before Lisa M Barrett, Certified Relatime
`Court Reporter Reporter, and Notary Public of the
`State of Maryland.
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`Regeneron v. Novartis, IPR2021-00816
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`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`A P P E A R A N C E S:
`ON BEHALF OF PETITIONER REGENERON PHARMACEUTICALS,
`INC.:
` Andrew Peter Gesior, Esquire
` Anish R. Desai, Esquire
` Weil, Gotshal & Manges LLP
` 767 Fifth Avenue
` New York, New York 10153-0119
` PHONE: +1 (212) 310-8244
` E-MAIL:andrew.gesior@weil.com
` E-MAIL: Anish.desai@weil.com
`
`ON BEHALF OF PETITIONER REGENERON PHARMACEUTICALS,
`INC.:
` Petra Scamborova, PhD, JD
` Regeneron Pharmaceuticals, Inc.
` 777 Old Saw Mill River Road
` Tarrytown, New York 10591
` PHONE: +1 (914) 847-7611
` E-MAIL: Petra.scamborova@regeneron.com
`
`ON BEHALF OF THE PATENT OWNERS:
` Elizabeth J. Holland, Esquire
` Allen & Overy LLP
` 1221 Avenue of the Americas
` New York, New York 10020
` PHONE: +1 (212) 610 6365
` E-MAIL: Elizabeth.Holland@allenovery.com
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`Novartis Exhibit 2345.004
`Regeneron v. Novartis, IPR2021-00816
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`REDACTED VERSION
`
`
`
`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`A P P E A R A N C E S (CONT'D)
`(Via Zoom Videoconferencing):
`ON BEHALF OF PETITIONER REGENERON PHARMACEUTICALS,
`INC.:
` Petra Scamborova, PhD, JD
` Regeneron Pharmaceuticals, Inc.
` 777 Old Saw Mill River Road
` Tarrytown, New York 10591
` PHONE: +1 (914) 847-7611
` E-MAIL: Petra.scamborova@regeneron.com
`
`Also present: Rachel Carrick, PD Remote Technician
` Isha Agarwal
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`Novartis Exhibit 2345.005
`Regeneron v. Novartis, IPR2021-00816
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`REDACTED VERSION
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`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
` C O N T E N T S
`EXAMINATION OF SZILARD KISS PAGE
`By Ms. Holland 85
` E X H I B I T S
` PAGE
` (Presented pre-marked exhibits)
` (Attached to the Transcript)
`
`Exhibit 1106 Reply declaration of 85
` Szilard Kiss, M.D.
` Bates No. IPR2021-00816,
` pages 1106.01 to 1106.035
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`Novartis Exhibit 2345.006
`Regeneron v. Novartis, IPR2021-00816
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`REDACTED VERSION
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`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`--- Commencing at 8:04 a.m.
` (Remote Technician read on.)
` SZILARD KISS, M.D. having been duly
` sworn testified as follows:
` EXAMINATION
`BY MS. HOLLAND:
` Q Good morning, Dr. Kiss.
` A Good morning.
` Q In the packet of materials you got
`yesterday should be your reply declaration which
`is Exhibit 1106. Could you take that out, please?
` A Yes, I see it here.
` A Just give me within second here. Yes.
` Q Okay, about five lines down, you say
`that:
` "Ophthalmologists as of 2012
`administered drugs that provided benefits to
`patients, even though the drug and/or drug
`delivery mechanism were known to present a risk of
`side effects and/or adverse reactions to the
`patient." [As read.]
` Do you see that?
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`Novartis Exhibit 2345.007
`Regeneron v. Novartis, IPR2021-00816
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`REDACTED VERSION
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`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
` A I do, yes.
` Q If you were designing a drug or drug
`delivery mechanism, is it fair to say that you
`would want to reduce the risks, if possible?
` MR. GESIOR: Objection, form.
` THE WITNESS: I think you'd want to
`maximize the benefit and minimize the risk.
`BY MS. HOLLAND:
` Q Okay, so for example, the drugs that
`you say were administered as of 2012, even though
`they had known risk of side effects, ideally you
`would like to minimize those side effects and
`risks, if possible; is that right?
` MR. GESIOR: Objection, form.
` THE WITNESS: So any time we administer
`any medication to a patient there's a
`benefit-to-risk ratio and we weigh that
`benefit-to-risk ratio and that's how we, you know,
`administer any medication or go forward with any
`treatment.
`BY MS. HOLLAND:
` Q But if it wasn't going to sacrifice the
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`Novartis Exhibit 2345.008
`Regeneron v. Novartis, IPR2021-00816
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`REDACTED VERSION
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`
`
`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`benefit, you would like to minimize the risks; is
`that fair?
` A Maximize the benefit; minimize the
`risk.
` Q If you had a benefit to the patient
`that wasn't going to be effected by minimizing the
`risk, do you agree that if you were designing a
`drug product, you would like to minimize that
`risk?
` MR. GESIOR: Objection, form.
` THE WITNESS: So, as an
`ophthalmologist, you know, I am a member of a team
`who designs drug products so in my personal, sort
`of, non-expert opinion, I always want to minimize
`risk and maximize benefit.
`BY MS. HOLLAND:
` Q What do you mean by "In your non-expert
`opinion"?
` A So, I think that when you think about
`the question that you asked, you asked about
`designing a drug product and one person does not
`design a drug product.
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`Novartis Exhibit 2345.009
`Regeneron v. Novartis, IPR2021-00816
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`
`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
` I'm an ophthalmologist, retina
`specialist, and as a retina specialist and
`ophthalmologist, part of designing a drug product,
`I would be part of that team. And so as a person
`who takes care of patients, I would want to
`minimize the risk and maximize the benefit.
` There's more than just an
`ophthalmologist, when designing a drug product.
`So, you know, there's all sorts of people.
` Q All right. But you agree that you
`would be an expert on the team who was providing
`input from the ophthalmology perspective, right?
` A Yes, that's correct.
` Q And as that expert on the team, your
`input would be to try to minimize the risks and
`maximize the benefits; is that right?
` A Yes.
` Q Now you mention Avastin in that
`paragraph.
` You do not administer Avastin, correct?
` A So since we last talked I've been
`forced by insurance companies to administer
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`Regeneron v. Novartis, IPR2021-00816
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`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`Avastin.
` So, it was correct as of about, you
`know, a week or two ago or, you know, insurance
`companies now are putting a lot of pressure on
`what I can and can't do. And there are some who
`say you have to administer Avastin so since we
`last talked, I've been forced to administer
`Avastin to prevent the risk of vision loss.
` Q And how recent is this?
` A This is in the last, like, two to three
`weeks. I, you know -- I don't know the exact
`date, but it's been sort of the bane of my
`existence as administrators are telling me how to
`practice medicine.
` Q So from 2009 until two to three weeks
`ago you did not administer Avastin; is that fair?
` A Yes, that's a fair statement, yeah.
` Q Okay, and the reason that you did not
`administer Avastin to patients was because you
`believe it posed a risk to patients; is that
`right?
` MR. GESIOR: Objection, form.
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`Novartis Exhibit 2345.011
`Regeneron v. Novartis, IPR2021-00816
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`REDACTED VERSION
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`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
` THE WITNESS: So the reason I did not
`administer it, is the benefit-to-risk ratio when
`compared to alternatives: Lucentis, Eylea and
`such, Macugen, were greater with administering
`Avastin, versus administering the other ones.
`BY MS. HOLLAND:
` Q All right. And one of the risks that
`you mentioned in paragraph 8 is the risk of
`injecting silicone oil into a patient's eye when
`using Avastin, correct?
` A Can you point that out?
` Q I can. It's about five lines up from
`the bottom on page 4.
` A Oh, yes, yes, yes. Thank you, sorry I
`just couldn't -- yes, that's correct --
` -- (overspeaking) --
` Q But when I --
` -- (overspeaking) --
` I'm sorry, did you have something to
`say?
` A As I point out there, it's due to the
`syringes that are being used, so I think there's
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`Regeneron v. Novartis, IPR2021-00816
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`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`several issues that you are bringing up here, drug
`product, syringe and such.
` Q All right. But when you said that
`there was a -- you looked at the risk benefits for
`Avastin, one of the risks for Avastin that you've
`identified is the risk of injecting silicone oil
`into a patient's eye, correct?
` A That is correct, yes.
` Q And when you perform your risk benefit
`analysis, is that one of the reasons that would
`fall on the side of you not wanting to give
`patients Avastin injections?
` MR. GESIOR: Objection, form.
` THE WITNESS: So if there are
`alternatives available, yes but you know,
`unfortunately when one is forced to choose between
`blindness and Avastin, the Avastin is the lesser
`of the risk versus blindness, but yes.
`BY MS. HOLLAND:
` Q All right. If you turn to paragraph 12
`of your reply declaration, Exhibit 1106.
` (Whereupon, Exhibit 1106 was
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`Regeneron v. Novartis, IPR2021-00816
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`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`presented.)
` THE WITNESS: Give me one moment.
`BY MS. HOLLAND:
` Q It's on page 8.
` A There we go. Okay.
` Q In that paragraph you talk about the
`use of Parylene C; do you see that?
` A I do, yes.
` Q Is it correct that you don't have an
`independent opinion on whether Parylene C would be
`unsafe, toxic or unacceptable?
` A I'm not an expert in toxicology so, you
`know, toxicology, Parylene C is not something that
`I can opine on.
` Q All right. Did you review
`Dr. Dilberger's declaration?
` A The relevant sections here, as cited.
` Q I don't see a cite to Dr. Dilberger.
`That's why I'm asking you.
` A Oh, I'm sorry. I'm sorry,
`Dr. Dilberger -- I don't know who Dr. Dilberger --
`sorry, all the names get -- Dr. Cohen's
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`Regeneron v. Novartis, IPR2021-00816
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`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`declaration, I cited. I don't think I recall who
`Dr. Dilberger is.
` Q Oh, okay. So Dr. Cohen responded to
`Dr. Dilberger, who was a toxicologist that
`submitted a declaration on behalf of Novartis.
`Did you read that declaration?
` A No, I did not.
` Q Let's turn to paragraph 13.
` A Yes.
` Q In that paragraph you discuss break
`loose and slide forces; do you see that?
` A I do, yes.
` Q In the last sentence, you say:
` "... Dr. Calman, however, Dr. Wolfe does not
`quantify what magnitude of forces and variations
`... would have been acceptable or unacceptable for
`intravitreal injection." [As read.]
` Do you see that?
` A I do, yes.
` Q Do you agree that there is some
`magnitude of force that would be unacceptable for
`an intravitreal injection?
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`Regeneron v. Novartis, IPR2021-00816
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`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
` A Yes.
` Q Can you quantify what that is?
` A What I can say is that the syringes
`that I've used: Macugen, Trivaris, the
`Aflibercept, as well as the ranibizumab PFS all
`have, you know, magnitudes of force that are
`acceptable. So I can't quantify -- I've never had
`it too high or too low, you know, so those seem
`all to be workable.
` Q Would you also agree that there would
`be some variation in force of a syringe over time
`that would be unacceptable to a physician like
`yourself?
` MR. GESIOR: Objection, form.
` THE WITNESS: You know, I've thought
`about as I'm doing injections what the break loose
`force or slide force may be something that I
`haven't really thought about in this much depth or
`never thought I would think about. And it all
`seems the same to me and, you know, maybe I'm an
`odd one, but I think that when I'm injecting, you
`know, the Ranibizumab PFS, the Aflibercept PFS
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`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`and, you know, I don't recall injecting the
`Macugen PFS and the Trivaris, they are all about
`the same.
` I don't see -- I don't feel any
`variation. My patients haven't told me that you
`know, oh my gosh, you are using a different
`injection for a site; something is different.
`BY MS. HOLLAND:
` Q So, my question's a little different, I
`guess. Set aside the ones that are actually on
`the market, do you agree that if a syringe would
`come out in the market hand had very variable
`forces, that that is something that could
`potentially be unacceptable to you as an
`ophthalmologist?
` MR. GESIOR: Objection, form.
` THE WITNESS: Yeah, I mean I want
`something to work, you know. And I'm assuming if
`it's on my shelf and, you know, the FDA has looked
`at it, it works.
`BY MS. HOLLAND:
` Q When you say you want something to
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`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`work, do you mean you want it to have acceptable
`forces for you to administer the injection to the
`patient?
` A It works as well as the Eylea and the
`Lucentis and the Macugen PFS, then, yeah, it would
`be acceptable to me.
` Q And something that worked differently
`than those not as well in terms of forces, might
`not be acceptable; is that right?
` MR. GESIOR: Objection, form.
` THE WITNESS: If it doesn't work, yeah,
`I wouldn't want to use it. Absolutely.
`BY MS. HOLLAND:
` Q I'm just focusing in on work there.
` When you say it doesn't work, what did
`you mean by that?
` A So if I can pick something up and put
`the needle in the patient's eye and I can put it
`in the eye, that's sort of, you know, having it
`work, and not sort of think about that process,
`you know, and I know we're focusing on the PFS
`here, but there's other injections that we do, and
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`Novartis Exhibit 2345.018
`Regeneron v. Novartis, IPR2021-00816
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`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
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`they all sort of just have, you know, I guess what
`we're calling a break loose force and a glide
`force that, that, I don't have to think about,
`right, so I don't have to -- so I, you know, if
`it's so so low that, you know, it sort of slips
`out of my hand or it's so so high that I'm jamming
`it into the patient's eye, then, yeah, it would
`not be acceptable, but I can't quantify that.
` Q Do you agree, Dr. Kiss, that prior to
`2012 there was not one single PFS on the market
`for intravitreal injection with a VEGF antagonist
`that had had all the attributes claimed in the
`'631 Patent?
` MR. GESIOR: Objection, form.
` THE WITNESS: So, in terms of the '631
`Patent, I've opined on what, you know, the
`specific sections that I've opined on.
` I think 24 through 26 and what I can
`agree to is that the Macugen syringe which I used,
`you know, was acceptable and what I gathered from
`referring sections of, you know, other
`declarations, that that syringe and, you know, the
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`Regeneron v. Novartis, IPR2021-00816
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`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`Trivaris, but Macugen specifically, had some of
`the attributes, if not all of them of the patent,
`but that's --
`BY MS. HOLLAND:
` Q Okay but --
` A -- I haven't reviewed the whole patent;
`I've reviewed the relevant sections.
` Q But you understand that Macugen had
`more silicone oil than what was claimed in the
`'631 Patent, right?
` MR. GESIOR: Objection, form.
` THE WITNESS: So I think, you know,
`what I'm concerned about is how much silicone oil
`gets into the patient's eye, right, in terms of
`the dynamics of the silicone oil and how much is
`in the syringe, as long as it doesn't get into the
`eye, would be relevant to me.
`BY MS. HOLLAND:
` Q Why don't you look at page 11, footnote
`3 of your reply declaration, Exhibit 1106.
` A Mm-hmm.
` Q So there you say:
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`Novartis Exhibit 2345.020
`Regeneron v. Novartis, IPR2021-00816
`
`REDACTED VERSION
`
`
`
`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
` "I understand that the Macugen PFS had
`silicone oil applied to the syringe barrel and
`quantities greater than those claimed in the '631
`Patent." [As read.]
` Do you see that?
` A I do, yes.
` Q So you do understand it had more
`silicone oil, right?
` A Yes.
` Q And you also know that the Macugen PFS
`sometimes resulted in silicone oil contamination
`in patients because of the intravitreal injection.
` MR. GESIOR: Objection, form.
`BY MS. HOLLAND:
` Q Let me restate that: Is it correct
`that there were reports of silicone oil
`contamination in patient's eyes that were caused
`by the Macugen PFS?
` A Yes, as footnote number 3 on page 11
`states that there were reports of silicone oil,
`yes.
` Q Okay, but you don't -- you don't
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`Novartis Exhibit 2345.021
`Regeneron v. Novartis, IPR2021-00816
`
`REDACTED VERSION
`
`
`
`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`believe that the cause of the silicone oil in the
`patient's eyes was the amount of silicone oil in
`the syringe barrel?
` MR. GESIOR: Objection, form.
` THE WITNESS: I think -- I think, you
`know, it's not that I don't believe it. I'm not
`an expert in making syringes and so I think that
`what my concern -- when I use a syringe is how
`much oil -- silicone oil actually gets into the
`solution that I inject into the eye.
` How that silicone oil gets in and the
`process of making sure it doesn't, I don't
`understand and I can't opine on, but yeah...
` -- (overspeaking) --
`BY MS. HOLLAND:
` Q But however the silicone oil got into
`the solution, you agree that the Macugen PFS had
`too much silicone oil, such that it caused
`silicone oil contamination in patient's eyes?
` MR. GESIOR: Objection, form.
` THE WITNESS: No, what I agree is that
`there was silicone oil that got into the solution
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`Novartis Exhibit 2345.022
`Regeneron v. Novartis, IPR2021-00816
`
`REDACTED VERSION
`
`
`
`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`that I injected in patient's eyes. How much
`silicone oil was actually in the syringe I don't
`know how that relates to how much silicone oil
`actually gets into the solution.
` MS. HOLLAND: I'm sorry, just one
`second. (Pause) sorry about that.
` THE WITNESS: It's all right.
`BY MS. HOLLAND:
` Q I'm sorry, I'm going to have to look up
`your last answer.
` Is it correct that as of 2012, the only
`syringe -- withdrawn.
` Is it correct that as of 2012, the only
`PFS on the market for administration of a VEGF
`antagonist was Macugen?
` A I think so. I would have to check, you
`know, when the ranibizumab PFS was approved. It's
`not on the tip of my tongue. Maybe you know when
`the ranibizumab PFS was approved. Was it after
`2012?
` Q Yes.
` A So, yes, that's correct. Maybe a
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`Novartis Exhibit 2345.023
`Regeneron v. Novartis, IPR2021-00816
`
`REDACTED VERSION
`
`
`
`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`brain -- senior moment, but Macugen was on the
`market, yeah.
` Q So now we've discussed that Macugen had
`more silicone oil in it than claimed in the '631
`Patent and that it was the only PFS on the market
`that you could use.
` So with that background, do you agree
`that there was no single PFS for intravitreal
`injection on the market that had all the
`attributes claimed in the '631 Patent?
` MR. GESIOR: Objection, form.
` THE WITNESS: So, let me just follow
`your logic, so can you state the sentence again.
`So there's Macugen was the only PFS on the market,
`okay.
`BY MS. HOLLAND:
` Q And we've agreed it had more silicone
`oil than the '631 Patent.
` A That's correct.
` Q So therefore there was no single device
`PFS for intravitreal injection on the market that
`had the attributes claimed in '631 Patent?
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`
`Novartis Exhibit 2345.024
`Regeneron v. Novartis, IPR2021-00816
`
`REDACTED VERSION
`
`
`
`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
` MR. GESIOR: Objection, form.
` THE WITNESS: So I'm trying to think of
`24 through 26 and I think, you know, what sort
`of -- within my lane in terms of an
`ophthalmologist, I don't want to agree to it
`because I've not read the entire patent, so I
`don't want to perjure myself by agreeing to
`something that may or may not have been in the
`patent.
` I agree that Macugen was the only one
`and I agree that there was more silicone oil than
`what was stated, you know, in that patent. But,
`you know, there may be other things in that patent
`that I have not read so, you know, I can't give
`you a "yes" or "no" answer.
`BY MS. HOLLAND:
` Q Dr. Kiss, for the same active
`ingredient, for example, ranibizumab, you agree
`that physicians prefers a PFS presentation to a
`vial presentation, right?
` A Yes, that seems to be correct. So for
`the same drug, a PFS is preferred over vial.
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`
`Novartis Exhibit 2345.025
`Regeneron v. Novartis, IPR2021-00816
`
`REDACTED VERSION
`
`
`
`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
` Q Okay, and that's true for Aflibercept,
`as well; correct?
` A Yes, that's correct.
` Q And you switched completely to the use
`of Lucentis PFS when it came on the market, right?
` A Completely, no. I mean, you know, I
`switched from the Lucentis vial to the Lucentis
`PFS, still using a lot of Eylea.
` Q Okay, fair enough. I think my question
`wasn't accurate enough. Let me ask you this:
`When Lucentis PFS came on the market, you switched
`all your patients who are on Lucentis vial to
`Lucentis PFS; is that right?
` A Yes, that's correct, you know, as the
`PFS became more and more available, absolutely.
` Q And is it correct that you also
`switched your patients who were on Eylea vial to
`Eylea PFS, when that came on the market?
` A Yes, yes, that's correct.
` Q Do you recall when Eylea PFS came on
`the market?
` A Yeah, I don't know why I'm having
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`Novartis Exhibit 2345.026
`Regeneron v. Novartis, IPR2021-00816
`
`REDACTED VERSION
`
`
`
`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`trouble with dates this morning. It was a long
`day yesterday. If you can you remind me, please.
`I don't remember.
` Q Does December 2019 sound right to you?
` A It sounds right. I mean, I can look it
`up. It think it may be in my original
`declaration, but that may sound correct. I'm
`(indiscernible) that you are going to tell me the
`right answer.
` Q But you agree that it was years after
`Lucentis PFS came on the market; is that right?
` A Yes, it was after the Lucentis PFS,
`yes, absolutely.
` Q Do you agree that Lucentis and Eylea
`PFS were an improvement over Macugen in terms of
`the amount of silicone oil that was injected into
`patient's eyes?
` MR. GESIOR: Objection, form.
` THE WITNESS: Not in my experience. I
`think it was a tremendous improvement over the
`drug product. Macugen like, you know barely
`worked. It worked better than nothing, but I
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`Novartis Exhibit 2345.027
`Regeneron v. Novartis, IPR2021-00816
`
`REDACTED VERSION
`
`
`
`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`think, you know, Eylea and Lucentis, what was in
`the PFS was the greatest improvement, not the PFS
`difference itself.
`BY MS. HOLLAND:
` Q I was asking a very specific question
`about the amount of silicone oil that's injected
`into the eye.
` A Mm-hmm.
` Q Just in that one respect, are Lucentis
`and Eylea an improvement over Macugen?
` MR. GESIOR: Objection, form.
` THE WITNESS: Not in my experience. I
`was fine with the Macugen PFS.
`BY MS. HOLLAND:
` Q You were fine with the silicone oil
`being injected in patients' eyes?
` A No. There were reports and, you know,
`there are reports of, you know, inflammation after
`one injection and another and the reports of that.
` I never saw, in my experience, silicone
`oil for Macugen. We didn't use it long, but we
`used it and so, you know, I think that the biggest
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`Novartis Exhibit 2345.028
`Regeneron v. Novartis, IPR2021-00816
`
`REDACTED VERSION
`
`
`
`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`improvement was what was in the vial.
` If somebody gave me Eylea in a Macugen
`PFS, I would use that.
` Q If someone gave you Eylea in a Macugen
`PFS are you saying that that would be just as good
`as giving it to you in an Eylea PFS?
` MR. GESIOR: Objection, form.
` THE WITNESS: Yeah.
`BY MS. HOLLAND:
` Q Even though there were reports of
`silicone oil being injected into patient's eyes
`with the Macugen PFS?
` MR. GESIOR: Objection, form.
` THE WITNESS: Yes. One report does not
`make for evidence of a difference, you know, and
`so, you know, I think what -- with the PFSs that
`were available and FDA approved, the most
`important choice that I would make is what's
`inside it, not the difference among the various
`PFSs.
` Q I understand that, doctor. So there is
`the difference in the active, which you say is the
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`Novartis Exhibit 2345.029
`Regeneron v. Novartis, IPR2021-00816
`
`REDACTED VERSION
`
`
`
`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`most important.
` A Mm-hmm.
` Q And then there could also be decisions
`based on the presentation, right, like a PFS over
`a vial, for example?
` A Sure.
` Q Okay, and you are not saying there was
`one report about Macugen resulting in silicone oil
`in patient's eyes, right?
` MR. GESIOR: Objection, form.
` THE WITNESS: There were reports.
`There were reports.
`BY MS. HOLLAND:
` Q So, I understand that, doctor, so there
`is a difference in the active, which you say is
`the most important.
` A Hm-hmm.
` Q And then there could also be decisions
`based on the presentation, right, like a PFS over
`a vial, for example?
` A Sure.
` Q And you're not saying that there was
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`Novartis Exhibit 2345.030
`Regeneron v. Novartis, IPR2021-00816
`
`REDACTED VERSION
`
`
`
`Transcript of Szilard Kiss, M.D, Volume 2
`Conducted on May 13, 2022
`
`one report about Macugen resulting in silicone oil
`in patient's eyes, right?
` MR. GESIOR: Objection, form.
` THE WITNESS: There were reports,
`right. There were reports, I mean, of
`inflammation following, you know, Aflibercept
`injections, and we continued to use it, continued
`to monitor it and it petered out and so, you know,
`I think, you look at the overwhelming evidence,
`you not just reports.
`BY MS. HOLLAND:
` Q What do you mean by the "overwhelming
`evidence?
` A So, like for Beovu, for example, you
`know, just to let you through, through my train of
`thought. So with Beovu there were reports here
`and there of something going on with inflammation.
` We, as a field, continued to use it and
`then we, as a field, aggregated those reports and
`realized the, you know, the
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