Švec, Ph.D., František
`
`Case IPR2017-02194
`
`September 26, 2018
`
`1
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` UNITED STATES PATENT AND TRADEMARK OFFICE
` __________________
`
` BEFORE THE PATENT TRIAL APPEAL BOARD
` __________________
` MODERNATX, INC.,
` Petitioner,
` vs.
` CUREVAC AG,
` Petitioner.
` ___________________
` Case IPR2017-02194
` Patent No. 8,383,340
` ____________________
` DEPOSITION OF
` FRANTIŠEK ŠVEC, Ph.D.
` Washington, D.C.
` Wednesday, September 26, 2018
` 9:08 a.m.
`Job No. 44197
`Reported By: Donna A. Peterson
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`MTX1058
`ModernaTX, Inc. v. CureVac AG
`IPR2017-02194
`
`1
`
`

`

`Švec, Ph.D., František
`
`Case IPR2017-02194
`
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`2
` The Deposition of FRANTIŠEK ŠVEC, Ph.D.,
`taken at the law offices of:
`
` CROWELL & MORING, LLP
` 11th Floor
` 1001 Pennsylvania Avenue, N.W.
` Washington, D.C. 20004-2595
`
` Pursuant to Notice, before Donna A.
`Peterson, Notary Public in and for the District of
`Columbia.
`
`3
`
` A P P E A R A N C E S
`
` ON BEHALF OF PETITIONERS, MODERNATX, INC.:
` ELDORA LYNN ELLISON, Ph.D., ATTORNEY at LAW
` OLGA A. PARTINGTON, Ph.D., ATTORNEY at LAW
` STERNE, KESSLER, GOLDSTEIN & FOX, PLLC
` 1100 New York Avenue, N.W.
` Washington, D.C. 20005
` Telephone: (202) 772-8508
` eellison@skgf.com
` opartington@sternekessler.com
`
` ON BEHALF OF PATENT OWNER, CUREVAC AG:
` SHANNON LENTZ, ATTORNEY at LAW
` CROWELL & MORING, LLP
` 11th Floor, 1001 Pennsylvania Avenue, N.W.
` Washington, D.C. 20004-2595
` Telephone: (202) 624-2500
` slentz@crowell.com
`
` ALSO PRESENT: MARSHALL P. BYRD, Ph.D.,
` ParkerHighlander
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`September 26, 2018
`2 (Pages 2 to 5)
`4
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` C O N T E N T S
`EXAMINATION OF FRANTIŠEK ŠVEC, Ph.D. PAGE
` By Ms. Ellison 6
`
` E X H I B I T S
`EXHIBIT DESCRIPTION PAGE
`MTX1054 Molecular Cloning, A Laboratory 60
` Manual, Third Edition, Sambrook,
` Russell, 2001
` PREVIOUSLY MARKED EXHIBITS
`MTX1001 U.S. Patent No. 8,383,340 22
`MTX1004 U.S. Patent No. 6,576,133 56
`MTX1008 RNA analysis by ion-pair 72
` Reversed-phase high performance
` liquid chromatography, Azarani,
` Hecker, Nucleic Acids Research,
` 2000, Vol. 29, No. 2 e7 pp. 1-9
`MTX1023 Use of high-performance liquid 66
` chromatographic fractionation of
` large molecules in the assay of
` group I intron ribozyme activity,
` Georgopoulos, Leibowitz, Journal
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` E X H I B I T S C O N T I N U E D
`EXHIBIT DESCRIPTION PAGE
` Of Chromatography A, A. 868(2000)
` 109-114, pp. 1-8
`CUREVAC 2001 Declaration of František 11
` Švec, Ph.D.
`CUREVAC 2016 Second Declaration Of František 12
` Švec, Ph.D.
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`2
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`

`

`Švec, Ph.D., František
`
`Case IPR2017-02194
`
`September 26, 2018
`3 (Pages 6 to 9)
`8
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`6
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` P R O C E E D I N G S
`Thereupon,
` FRANTIŠEK ŠVEC, Ph.D.,
`was called as a witness by counsel for Petitioner,
`Moderna Therapeutics, and having been duly sworn by
`the Notary Public, was examined and testified as
`follows:
` EXAMINATION BY COUNSEL FOR PETITIONER, MODERNATX
`BY MS. ELLISON:
` Q. Good morning.
` A. Good morning.
` Q. We're going to start with a roll call,
`just for the record. I'm Eldora Ellison from Sterne,
`Kessler, Goldstein and Fox, and I represent Moderna
`Therapeutics, and here today with me is my colleague
`Olga Partington, also from Sterne Kessler.
` MS. LENTZ: I'm Shannon Lentz, from
`Crowell & Moring, on behalf of CureVac.
` MR. BYRD: I'm Marshall Byrd, from
`ParkerHighlander, PLLC, on behalf of CureVac.
` THE WITNESS: Do I need to introduce
`myself?
`
`7
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` MS. ELLISON: That was going to be my
`first question for you, Dr. Švec.
` THE WITNESS: Okay. You obviously know my
`name, obviously. My name is František Švec,
`F-R-A-N-T-I-S-E-K, Švek, S-V-E-C. And I am expert
`witness for -- for this.
` Q. Thank you.
` Have you ever been deposed before,
`Dr. Švek?
` A. Yes.
` Q. How many times?
` A. One or two times, long time ago.
` Q. Okay. And in what kind of case were you
`deposed? Was it a patent case, for instance?
` A. Yes.
` Q. And who are the parties to that case?
` A. I don't think I will tell you. It was a
`long time ago and -- is that necessary?
` Q. Actually yes, it is. So your job today is
`to answer the questions that I ask.
` A. Okay. So --
` Q. So let me just explain a few ground rules.
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`So unless your counsel instructs you not to answer,
`you have to answer the question I ask.
` A. Okay. So it was Dow Chemicals --
` Q. Okay.
` A. -- versus -- I don't remember, really.
` Q. And were you testifying on behalf of Dow
`Chemicals in that case?
` A. Yes.
` Q. Okay. And just very generally, what did
`that case relate to?
` A. It was about the production of macroporous
`materials.
` Q. And is that the only case in which you've
`been deposed before?
` A. Yes.
` Q. Have you served as an expert witness in
`any other case before?
` A. No, I don't think so.
` Q. Okay. Have you ever submitted written
`testimony in a case before this one or the Dow case
`that you mentioned?
` A. Testimony?
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` Q. Yes.
` A. I don't think so. The only documentation
`that I submitted was part of -- of the proceedings.
` Q. Okay. But excluding the Dow case and this
`case --
` A. Well, for the Dow case, yes, it was very
`similar to this case.
` Q. Okay. And have you submitted testimony in
`any case other than --
` A. No.
` Q. -- the Dow case?
` A. No.
` Q. One of the things I'm going to ask you to
`do today is to let me finish my questions and so we
`can try not to talk over each other.
` A. Of course, yes.
` Q. If we talk over each other, it makes it
`difficult for the court reporter.
` A. I understand.
` Q. Okay, thank you.
` Let me also just go over some of the
`basics of a deposition. Under the rules that apply
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`202-220-4158
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`

`

`Švec, Ph.D., František
`
`Case IPR2017-02194
`
`September 26, 2018
`4 (Pages 10 to 13)
`12
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`10
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`to this case, now that this deposition has begun,
`you're not allowed to speak with counsel for CureVac
`about the substance of the deposition or about the
`substance of your testimony before the deposition
`ends. Do you understand that?
` A. Yes.
` Q. So on breaks, you're not permitted to ask
`them questions about the deposition or -- or the
`case. Do you understand that?
` A. I understand.
` Q. Okay. And do you agree to abide by that
`rule?
` A. I do.
` Q. Okay, thank you.
` We'll take a number of breaks today. If,
`at any point in time, you'd like a break, please just
`let me know and I'll try to take a break shortly
`after any request that you have. If there's a
`question pending, I will ask that you answer the
`question before we take a break. But otherwise, I
`will try to accommodate your request for a break.
`Okay?
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` A. Okay.
` Q. As I mentioned earlier, my job today is to
`ask you -- ask you questions and your job today is to
`answer them. Your counsel may object to the
`question, but, unless she instructs you not to answer
`the question, you do need to answer my questions,
`okay?
` A. I understand.
` Q. Okay. If -- if there's anything that you
`find unclear about my question, please feel free to
`ask me for clarification, and you need to ask me, not
`your counsel, for clarification.
` A. I will.
` Q. Thank you.
` Will it be fair for me to assume that if
`you don't ask for clarification, would it be fair for
`me to assume that you understood the question?
` A. I think so.
` Q. Thank you.
` I'm going to hand you a copy of what's
`been marked as Exhibit 2001. Actually Olga is going
`to hand you a copy of what's been marked as Exhibit
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`2001.
` Do you recognize this document?
` A. Yes. It's my Declaration.
` Q. This is your first Declaration, correct?
` A. Yes.
` Q. If you turn to the last page, is that your
`signature at page 63?
` A. Yes, it is my signature.
` Q. Are there any errors in your Declaration
`that we have provided as Exhibit 2001?
` A. Yes, there are some typos.
` Q. Okay. Other than typographical errors,
`are there any substantive errors in your Declaration?
` A. I don't think so.
` Q. Okay. So do you stand by the testimony --
` A. Yes.
` Q. -- in your Declaration? Thank you.
` And then I'm going to hand you a copy of
`what has been marked as Exhibit 2016.
` Do you recognize Exhibit 2016?
` A. Yes, I do.
` Q. And what is Exhibit 2016?
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` A. It is my Second Declaration.
` Q. And is that your signature on page 41 of
`Exhibit 2016?
` A. Yes, it is.
` Q. Okay. Are there any errors in your
`Exhibit that's -- in your -- excuse me, let me try
`that again.
` Are there any errors in your Second
`Declaration which has been provided as Exhibit 2016?
` A. Yes, there might be some typos, again.
` Q. Okay. Are there any substantive errors
`in --
` A. No.
` Q. -- that -- okay. Let me finish my
`questions, please.
` A. (Nods.)
` Q. All right. So there are no substantive
`errors in your Second Declaration, correct?
` A. Correct.
` Q. Thank you.
` And do you stand by the testimony that's
`in your Second Declaration?
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`4
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`

`

`Švec, Ph.D., František
`
`Case IPR2017-02194
`
`September 26, 2018
`5 (Pages 14 to 17)
`16
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` A. Yes.
` Q. Does your Second Declaration accurately
`describe how you carried out your analysis in
`formulating the opinions set forth in your Second
`Declaration?
` A. Yes.
` Q. And does your first Declaration accurately
`set forth how you carried out your analysis in
`formulating the opinions in your first Declaration?
` A. Yes.
` Q. Are you being compensated for your time in
`working on this case?
` A. Yes.
` Q. How much?
` A. I am getting $400 per hour being here.
` Q. Okay. And were you compensated for your
`time spent in preparing your declarations?
` A. Yes.
` Q. And how much?
` A. It was three hundred and fifty.
` Q. So $350 per hour?
` A. By hour.
`
`15
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` Q. Okay. And approximately how much time
`have you spent working on this case overall?
` A. Overall, maybe 40 hours, maybe 50. I -- I
`didn't count exactly how much. We can do it, but it
`was in the range of 40, 50 hours.
` Q. Okay, thank you.
` What did you do to prepare for today's
`deposition?
` MS. LENTZ: I'll just caution the witness
`not to disclose any communications that we had.
` MS. ELLISON: Yes. I don't want to know
`the substance of any communications you had.
` THE WITNESS: We had a meeting on Monday
`and Tuesday.
`BY MS. ELLISON:
` Q. And with whom did you meet?
` A. I met with the team working on this case.
` Q. And can you identify those people for me,
`please.
` A. Well, it was Debbie Yellin, Shannon and
`Marshall.
` Q. Okay. Did you meet with anyone else in
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`preparation for today's deposition?
` A. No.
` Q. And how long did you meet for?
` A. We met for about seven hours on Monday and
`six hours yesterday.
` Q. Okay. So earlier when you estimated that
`you've spent approximately 40 to 50 hours working on
`this case, did that include the time that you met
`with counsel yesterday and the day before?
` A. No.
` Q. So would it be fair to say that the total
`amount of time that you spent working on this case
`was approximately 40 to 50 hours plus the time that
`you met with counsel --
` A. Yes.
` Q. -- yesterday and the day before?
` A. Yes.
` Q. Okay, thank you.
` In formulating the opinions set forth in
`your declarations, did you rely upon any documents
`that are not identified in your declarations?
` A. No. Actually I certainly relied on my own
`
`17
`knowledge. But the declaration concerns only those
`documents that are mentioned in the declaration.
` Q. Okay. And in doing your work on this
`case, did you carry out any searches of the
`literature?
` A. Yes, I did.
` Q. How did you carry out those searches?
` Actually let me ask first, did you carry
`out more than one search of the literature in your
`work in connection with this case?
` A. Well, you know, being a scientist, I
`typically do the following if I have a question and I
`don't have any answer to that and I do believe that
`the answer is somewhere in the literature. I go and
`look in the literature, anyway. So each time I need
`to get that information, I open the database and look
`in the database for publications, books, whatever is
`available related to the specific topic. And then I
`receive this information from -- today, it is easy
`because we can get it from the internet.
` You know, I have my own database in --
`that I formulated during the last, I don't know, 20
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`

`

`Švec, Ph.D., František
`
`Case IPR2017-02194
`
`September 26, 2018
`6 (Pages 18 to 21)
`20
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`years or so, and obviously there are a number of
`scientific databases available for me because I'm
`still affiliated with the university and the
`national -- and the national laboratory.
` Q. Okay. Can you tell me what searches of
`the literature you carried out in connection with
`your work on this case?
` A. Well, I -- as I said, it was several
`searches. And, again, I just looked at a specific
`type of information I wanted to know. For example, I
`looked at the issues that are related to the nucleic
`acids.
` Q. Which issues are you referring to?
` A. Well, general knowledge of nucleic acids.
`I am a polymer chemist and analytical chemist, so my
`knowledge of biochemistry, I mean, is limited to the
`basics, and if I need to get a little bit deeper, I
`have to have a look in the literature, which I had.
` Q. Okay. And with respect to nucleic acids,
`what did you search the literature for?
` A. Well, I don't really recall exactly what I
`was looking at. For example -- oops, excuse me.
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` For example, I looked at the newest
`developments in the application of nucleic acids in
`the medicine because I think this is very pertinent
`to this case. This is one of those things that I
`looked at and I remember that very vividly.
` Q. Okay. Can you identify for me any other
`issues that you searched the literature for in -- in
`carrying out your work in connection with this case?
` A. Well, I said it's a little bit difficult
`because I didn't go for anything, any large piece of
`information. It was bit and pieces just to get
`assured perhaps that what I think is really correct,
`you know. So obviously it was mostly related to the
`case we are discussing today.
` Q. Do you recall any key words that you used
`when searching the literature?
` A. Yes. Probably oligonucleotides, RNA, DNA,
`this type of key words.
` Q. Did you search for "RNA," just that key
`word by itself?
` A. Actually yes. But the number of hits is
`enormous. I understand your point.
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` Q. That was going to be my next question.
` A. Well, this was just to -- for example, I
`looked at the RNA in Wikipedia --
` Q. Okay.
` A. Now -- which was on the top, as always.
` Q. Uh-huh.
` A. So it says essentially nothing I didn't
`know, you know.
` Q. Okay.
` A. But just to start somewhere because even
`in Wikipedia, you always have some literature at the
`end of -- of the text. So the literature could be
`another direction where one can go to get more
`information about a specific topic concerned within
`the Wikipedia article.
` Q. So other than searching the literature to
`find information relating to how nucleic acids are
`used in medicine, I guess what you said earlier --
` A. Yeah.
` Q. -- were there any other topics that you
`searched the literature to find information about?
` A. Yes. For example, I searched through the
`
`21
`web site of Moderna because one of the hits -- and I
`knew from the case that Moderna is certainly working
`in the field of pharmaceuticals based on RNA. They
`also have, based on the information from the web
`site, they have some potential pharmaceuticals that
`can be used. This information is open for public,
`they have a few of them in the phase I testing, just
`very little in the Phase II testing. It's
`interesting to see what areas, what -- let's say
`illnesses they are shooting for. From that, I could
`get some information about the company.
` Q. Okay. Did any of that information that
`you found about the company impact your opinions set
`forth in your declarations?
` A. No.
` Q. Okay. Can you tell me what databases you
`searched?
` A. As I said, mostly just using Google, you
`know. I can go in the American Chemical Society
`database, which is really huge and covers almost
`everything, and I have access to that. And I used my
`own database, as well.
`
`202-220-4158
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`6
`
`

`

`Švec, Ph.D., František
`
`Case IPR2017-02194
`
`22
`
` Just for your information, my database is
`about ten -- ten thousand entries.
` Q. Okay.
` A. So it's really big.
` Q. Outside of your work on this case, have
`you ever had any other relationship with CureVac?
` A. No.
` Q. Have you ever had a professional
`relationship with Moderna?
` A. No.
` Q. I'm going to hand you a copy of what's
`been marked as Exhibit 1001, which is the '340
`patent.
` Do you recognize Exhibit 1001, Dr. Švek?
` A. Yes, I do.
` Q. Do you know Thomas Ketterer, who's named
`as an inventor on the '340 patent?
` A. No.
` Q. Do you know Florian Von Der Mulbe, another
`inventor on the '340 patent?
` A. No.
` Q. Do you know Ladislaus Reidel, another
`
`23
`
`inventor on the '340 patent?
` A. No.
` Q. And do you know Thursten Mutzke, another
`inventor on the '340 patent?
` A. No.
` Q. Have you ever purified nucleic acids using
`HPLC?
` A. Yes.
` Q. Have you purified DNA using ion-pair
`reverse-phase HPLC?
` A. Yes.
` Q. And what kind of DNA did you purify when
`you purified it using ion -- ion-pair reverse-phase
`HPLC?
` A. It was oligonucleotides. DNA
`oligonucleotides.
` Q. Precisely what was the size of those DNA
`oligonucleotides?
` A. It was, I think, up to about 30 base
`pairs.
` Q. And what media did you use in purifying
`oligonucleotides using ion-pair reverse-phase HPLC?
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`September 26, 2018
`7 (Pages 22 to 25)
`24
` A. Can you specify "media"? Meaning the --
`the stationary phase or the -- the liquid, the mobile
`phase?
` Q. Let's talk about both.
` What stationary phase did you use?
` A. The stationary phase was a monolithic
`stationary phase.
` Q. Made from what?
` A. Made from, in this case, it was
`polyglycidyl methacrylate and ethylene
`dimethacrylate, modified with diethylamine.
` Q. Okay. And what was the mobile phase?
` A. The mobile phase in this case was a
`solution of -- buffer solution of acetonitrile as a
`solution A and salt solution in that solution A as
`the solution B.
` Q. Okay. And was that stationary phase
`medium, was that a porous or a nonporous medium?
` MS. LENTZ: Objection to form.
` MS. ELLISON: You can answer the question.
` THE WITNESS: Well, it was monolithic
`structure that was most likely nonporous.
`
`25
`
`BY MS. ELLISON:
` Q. Why do you say "most likely"?
` A. Because we didn't measure the porosity.
`We know that it was monolithic material that was
`permeable for liquids.
` Q. And when did you carry out this DNA
`purification using ion-pair reverse-phase HPLC?
` A. I think it was in 1999.
` Q. And how many times did you carry out DNA
`purification using ion-pair reverse-phase HPLC?
` A. Not too many times. We eventually
`published the results in a single paper.
` Q. Which paper was that?
` A. It's a paper in the Journal of
`Chromatography.
` Q. Is the paper listed on your CV?
` A. Yes.
` Q. Can you point me to it, please. Your CV
`is attached to your Second Declaration, it seems.
` A. Actually I may have missed it. This was
`not reverse-phase separation, it was ionic exchange
`separation.
`
`202-220-4158
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`
`7
`
`

`

`Švec, Ph.D., František
`
`Case IPR2017-02194
`
`September 26, 2018
`8 (Pages 26 to 29)
`28
`
`26
`
` Q. Ion exchange separation?
` A. Yes. I'm sorry, I made a mistake.
` Q. That's okay. Which -- which paper are you
`referring to?
` A. It's paper 235.
` Q. So I'll ask the question I asked earlier,
`then, again, just for clarity.
` Have you ever purified DNA using ion-pair
`reverse-phase HPLC?
` A. No.
` Q. Have you ever purified RNA using ion-pair
`reverse-phase HPLC?
` A. No.
` Q. Have you ever purified DNA using any kind
`of reverse-phase HPLC?
` A. No.
` Q. Okay. Would the answer be the same for
`RNA?
` A. Yes.
` Q. Thank you.
` Are you familiar with various types of RNA
`that exists?
`
`27
`
` A. Yes.
` Q. Can you identify for me different types of
`RNA that exist.
` MS. LENTZ: Objection, vague.
` MS. ELLISON: Again, that's actually not
`one of the permissible objections under the PTAB
`rules. You can't say that, not vague.
` MS. LENTZ: We've always -- okay.
`Understood.
` THE WITNESS: Okay. For example,
`messenger RNA, the short interfering RNA. There are
`some other types of RNA available.
`BY MS. ELLISON:
` Q. What other types of RNA?
` A. Well, for example, the cyclic RNA's you
`know, the -- and so on. You know, I don't recall all
`of them.
` Q. Do you know what tRNA is?
` A. tRNA?
` Q. tRNA.
` A. No, I don't remember.
` Q. Do you know what rRNA is?
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` A. The restriction RNA?
` Q. Lower case "r" capital "RNA"?
` A. Say it again.
` Q. Are you familiar with the term "rRNA,"
`with a lower case "r" and capital "RNA"?
` A. I said that time, I thought it was the
`restriction RNA.
` Q. Okay. Can you tell me approximately how
`long short interfering RNA's are in nucleotides?
` A. They are typically in the range of 20, 20
`NT's.
` Q. Okay. So 20 nucleotides?
` A. Nucleotides, yes.
` Q. And what's the approximate size of the
`cyclic RNA's to which you referred earlier?
` A. The cyclics can be larger. It can go up
`to, I don't know, 50 nucleotides. We also have the
`hairpin types of RNA's that are also larger, simply
`because when they are short, they cannot do this.
` Q. And what's the approximate size of the
`hairpin RNA's to which you've just referred?
` A. This is again between 30-50 nucleotides.
`
`29
`
` Q. Can you tell me what a ribozyme is?
` A. Ribozyme is -- well, that's the ribosomal
`RNA, that's another one. That's the "r" probably.
`This is part of the cell where the RNA directs
`formation of proteins.
` Q. Just so I'm clear, to what -- to what are
`you referring right now, to what type of RNA are you
`referring?
` A. The ribosomal.
` Q. Ribosomal?
` A. Ribosomal.
` Q. Actually my question was about ribozymes.
`Can you tell me what a ribozyme is?
` A. Ribozyme is part of the cell where the
`proteins are formed.
` Q. So just so the record's clear, I'm
`referring to the word R-I-B-O-Z-Y-M-E, ribozyme.
` A. I think this is -- this is what I'm
`talking about.
` Q. Okay, thank you.
` So can you tell me whether a ribozyme is?
`I just want you to finish your answer, if you weren't
`
`202-220-4158
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`
`8
`
`

`

`Švec, Ph.D., František
`
`Case IPR2017-02194
`
`September 26, 2018
`9 (Pages 30 to 33)
`32
`
`30
`
`finished.
` A. Well, I am not sure I know exactly what
`the ribozyme is, but as I said, it is part of the
`cell where some chemical reactions are occurring
`during the -- the living phase of the cell.
` Q. What kind of chemical reactions?
` A. It's the creation or formation of
`proteins.
` Q. And what is the role of a ribozyme in the
`formation of proteins?
` A. It includes the enzymes that are being
`directed to create the sequences of amino acids that
`form eventually the desired proteins.
` Q. Can you tell me what ribosomal,
`R-I-B-O-S-O-M-A-L, RNA is?
` A. That's one type of RNA that directs the
`formation of proteins that is a -- well, blueprint
`for the creation of -- of the proteins.
` Q. So is it your testimony that ribosomal RNA
`is the blueprint for the formation of proteins?
` A. Yes.
` Q. Is it fair to say that ribosomal RNA
`
`31
`
`encodes proteins?
` A. I don't think so because the encoding is
`in the messenger RNA.
` Q. Okay. So when you say that ribosomal RNA
`is the blueprint for proteins, what do you mean by
`"blueprint"?
` A. I -- I would say this is essentially
`the -- how to say that? Probably this way: The
`ribosomal RNA is really directed -- directing
`directly which -- which amino acid should be attached
`to the growing protein, while the information how
`this should happen is in the messenger RNA.
` Q. Is it fair to say that messenger RNA
`encodes proteins?
` A. Yes, it is.
` Q. But ribosomal RNA does not encode
`proteins, is that --
` A. No.
` Q. Just so I'm clear, it's your testimony
`that ribosomal RNA does not encode proteins, correct?
` A. Yes.
` Q. Okay. Can you tell me what the size of
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`ribosomal RNA is in nucleotides?
` A. I don't know.
` Q. Can you give me any approximate estimation
`of the size of ribosomal RNA in nucleotides?
` A. Well, I really don't know, so any
`estimation would be probably wrong. I don't know.
` Q. Is it more than a hundred nucleotides
`long?
` A. I don't know.
` Q. Okay. So earlier, you mentioned short
`interfering RNA's. Do short interfering RNA's encode
`proteins?
` A. No.
` Q. And you mentioned hairpin RNA's. Do
`hairpin RNA's encode proteins?
` A. No, not as the hairpin.
` Q. Can you tell me what a transfer RNA is?
` A. The tRNA you mentioned earlier.
` Q. Yes. Can you tell me what the function of
`transfer RNA is?
` A. No, I don't know.
` Q. Can you tell me the approximate size and
`
`33
`
`nucleotides of the transfer RNA?
` A. No.
` Q. Do transfer RNA's encode proteins?
` A. I don't know.
` Q. Can you tell me what whole cell RNA is?
` A. Whole cell RNA?
` Q. Yes, sir.
` A. Well, just by the name, it must be RNA
`that is included in the whole cell.
` Q. Before 2006, could RNA be synthesized in
`vitro?
` A. Probably yes.
` Q. Do you know whether RNA could be
`synthesized in vitro before 2006?
` A. I think it was synthesized in vitro and it
`was certainly synthesized chemically at that time.
` Q. Okay. Can you tell me what chemical
`synthesis methods existed before 2006 for
`synthesizing RNA?
` A. Well, these methods were developed for the
`synthesis of poly -- oligo and polynucleotides. The
`synthesis is carried out in a hardware that enables
`
`202-220-4158
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`9
`
`

`

`Švec, Ph.D., František
`
`Case IPR2017-02194
`
`September 26, 2018
`10 (Pages 34 to 37)
`36
`
`34
`synthesis of defined sequences that are directed by a
`computer, so it's fully automatic. The same
`instrument is used -- can you used for both DNA and
`RNA. And the synthesis is relatively tedious because
`it goes one nucleotide after another. So typically
`this type of synthesis is not used for long sequences
`because it would be too long to make them, and the
`longer the sequence, the higher the danger of failed
`sequences. So the purity decreases with the length.
` Q. So when you say typically it would not be
`used for long sequences, what do you mean by "long"
`in that context?
` A. Well, I think this is certainly well
`suitable for sequences that are in the range maybe
`20, maybe 30 nucleotides. The longer can be
`prepared. As I said, you know, there is essentially
`no limit how many of these can be connected together
`using this instrument and this chemistry, but the
`longer the -- the worse is the yield. So I would
`estimate that going up to about 20, maybe 25, is a
`very good -- a very good length of the sequence.
` Q. Okay. Before 2006, did methods exist for
`
`35
`
`in vi -- in vitro transcribing RNA?
` A. I think the transcription existed before
`2006.
` Q. And before 2006, what method -- what
`methods existed -- I'm sorry, strike that question.
` Before 2006, what lengths of RNA's could
`be produced using in vitro transcription?
` A. I don't know. I -- this is not my field,
`so I don't know how long the sequence could be using
`transcription.
` Q. Can you describe for me how in vitro
`transcription wo