Thran, Ph.D., Moritz
`
`Case IPR2017-02194
`CONFIDENTIAL
`
`October 2, 2018
`
`1
`
` 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
` ____________________
` CONFIDENTIAL TRANSCRIPT
` DEPOSITION OF
` MORITZ THRAN, Ph.D.
` Washington, D.C.
` Tuesday, October 2, 2018
` 9:05 a.m.
`Job No. 44198
`Reported By: Donna A. Peterson
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`MTX1069
`ModernaTX, Inc. v. CureVac AG
`IPR2017-02194
`
`1
`
`

`

`Thran, Ph.D., Moritz
`
`Case IPR2017-02194
`CONFIDENTIAL
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`2
` The Deposition of MORITZ THRAN, 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
` DAVID W. ROADCAP, 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
` droadcap@sternekessler.com
`
` ON BEHALF OF PATENT OWNER, CUREVAC AG:
` SHANNON LENTZ, ATTORNEY at LAW
` DEBORAH H. YELLIN, 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
` dyellin@crowell.com
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`October 2, 2018
`2 (Pages 2 to 5)
`4
` A P P E A R A N C E S C O N T I N U E D
`
` ALSO PRESENT: Marshall P. Byrd, Ph.D.,
` ParkerHighlander
` Dr. Anita Buck, CureVac
`
` C O N T E N T S
`EXAMINATION OF MORITZ THRAN, Ph.D. PAGE
` By Ms. Ellison 6
`
`5
`
` E X H I B I T S
` PREVIOUSLY MARKED EXHIBITS
`EXHIBIT DESCRIPTION PAGE
`Exhibit MTX 1004 U.S. Patent No. 6,567,133 72
`Exhibit MTX 1005 Journal article, Rigid 72
` polymerics: the future of
` oligonucleotide analysis and
` purification, Lloyd, et al.,
` Journal of Chromatography A,
` 1009(2003) 223-230
`Exhibit CureVac 2013 Declaration of
` Moritz Thran, Ph.D. 10
`Exhibit CureVac 2018 Curriculum Vitae, 10
` Dr. rer. nat. Moritz Thran
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`2
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`

`

`Thran, Ph.D., Moritz
`
`Case IPR2017-02194
`CONFIDENTIAL
`
`October 2, 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,
` MORITZ THRAN, 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:
` MS. ELLISON: Good morning.
` Let's start with a roll call. I'm Eldora
`Ellison, from Sterne, Kessler, Goldstein and Fox, and
`I represent Moderna Therapeutics. Here with me today
`is my colleague, David Roadcap, who also represents
`Moderna.
` MS. LENTZ: I'm Shannon Lentz, on behalf
`of CureVac, from Crowell and Moring. And with me is
`Debbie Yellin, from Crowell and Moring, also on
`behalf of CureVac. And Marshall Byrd, from
`ParkerHighland -- Highlander, and Anita Buck, from
`CureVac.
` EXAMINATION BY COUNSEL FOR PETITIONER, MODERNATX
`BY MS. ELLISON:
` Q. Good morning, Dr. Thran.
`
`7
`
` Did I pronounce your name correctly?
` A. Yes.
` Q. Will you please state your full name, for
`the record.
` A. My name is Moritz Thran.
` Q. Thank you.
` Have you ever been deposed before?
` A. To?
` Q. Have you ever been deposed before?
` A. No.
` Q. I'm going to go over some of the ground
`rules for today's deposition. So in general, it's my
`job today to ask you questions and it's your job
`today to answer my questions. As you can see,
`there's a court reporter here who is transcribing
`everything that you say and everything that I say.
`So it's important that you answer my questions out
`loud, so that she can write down what you say.
` Okay?
` A. Okay.
` Q. Thank you.
` If you have any questions about any
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`question that I ask, if anything's unclear to you,
`please ask me for clarification, rather than counsel
`for CureVac.
` Do you understand that?
` A. Yes.
` Q. Okay. And do you agree to abide by that?
` A. Yes.
` Q. Okay. Now that this deposition has begun,
`the rules of the Patent Office prevent you from
`speaking with counsel for CureVac during the
`cross-examination. So while we're on breaks, you're
`not allowed to speak with them about the substance
`your testimony today or about the case.
` Do you understand that?
` A. Yes.
` Q. Okay. And do you agree to abide by that?
` A. Yes.
` Q. Thank you.
` Is there any reason why you might be
`unable to testify truthfully and accurately today,
`like any medical condition or anything like that?
` A. No.
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`9
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` Q. Okay. So do you agree to abide -- to
`testify truthfully and to the best of your ability
`accurately today?
` A. Yes.
` Q. Thank you.
` We'll take a number of breaks today, but
`if at any point you'd like a break, just ask for one
`and I'll try to accommodate your request. But if
`there's a question pending, then I will ask that you
`answer the question before we take a break, okay?
` A. Okay.
` Q. Thank you.
` There may be times today when counsel for
`CureVac objects to one of my questions, but unless
`she instructs you not to answer, you, nonetheless,
`have to answer my question.
` Do you understand that?
` A. Yes.
` Q. Okay. And do you agree to follow that?
` A. Yes.
` Q. Thank you.
` I'm going to hand you a copy of what has
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`3
`
`

`

`Thran, Ph.D., Moritz
`
`Case IPR2017-02194
`CONFIDENTIAL
`
`October 2, 2018
`4 (Pages 10 to 13)
`12
`
`10
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`been marked as CureVac Exhibit 2013.
` Do you recognize the document that I just
`gave you as Exhibit 20 -- marked as Exhibit 2013?
` A. Yes.
` Q. What is it?
` A. It's my declaration in this patent
`deposition.
` Q. Okay. And I'm gonna ask you to turn to
`page 11 of the declaration.
` Is that your signature at page 11 of
`Exhibit 2013?
` A. Yes, it is my signature.
` Q. I'm also going to hand you a copy of your
`CV, which has been marked as Exhibit 2018. Actually
`David is going to hand you Exhibit 2018.
` Do you recognize Exhibit 2018?
` A. Yes.
` Q. And what is it?
` A. It's my CV.
` Q. Did you prepare this CV?
` A. Yes.
` Q. Is your CV accurate?
`
`11
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` A. Yes.
` Q. Is your CV complete?
` A. Yes.
` Q. Can you tell me what you were doing
`between 1999 and 2008?
` A. I was a student at the University of
`Erlangen-Nuremberg in Germany, and I studied biology
`and finished with a diploma degree.
` Q. When did you receive your diploma degree?
` A. In 2008.
` And I think I have to clarify, might be
`mistaken. The CV is not correct, now that I look at
`it. So for correction, between '99 and 2002, I was
`at school. From 2002 until 2008, I studied biology
`at the University of Erlangen-Nuremberg in Germany.
`And from 2008 and 2012, as it is stated, I did a
`doctoral degree at the division of biochemistry at
`the University of Erlangen-Nuremberg in Germany.
` Q. So are you saying you were a student from
`2002 to 2008?
` A. At the university, yes.
` Q. And what were you studying between 2002
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`and 2008?
` A. Biology.
` Q. Did you obtain a degree as a result of
`your studies from 2002 to 2008?
` A. It was a diploma degree.
` Q. Do you have more than one diploma degree?
` A. No.
` Q. So on your CV, where it says "diploma in
`biology, 1994 to 1999," is that correct?
` A. That information is not correct.
` Q. What were you doing between 1994 and 1999?
` A. I was a student at the school.
` Q. At what school?
` A. It was -- in Germany, we call it
`gymnasium, which --
` Q. It's like our high school?
` A. It's like a high school, yes. And it was
`in Hohenschwangau in Germany.
` Q. So then what were you doing between 1999
`and 2002?
` Strike that question, let me ask you this.
` What year did you finish gymnasium?
`
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` A. In 2002.
` Q. So then after gymnasium, you started your
`studies for the diploma in biology, is that correct?
` A. Since I was a little bit off track because
`of this mistake, I forgot I have to correct myself.
` Between 2002 and 2003, I was doing civil
`rights service in Munich at the Lebenshilfe, in
`Munich. And in 2003, I started studying biology at
`the University of Erlangen-Nuremberg. I think now I
`got it.
` Q. Okay. So is it correct to say that from
`1994 to 1999, you were in gymnasium?
` A. Yes. But 1994 is -- let me calculate. I
`think I started in 1992. So 1994 is not the correct
`year.
` Q. Okay. So is it --
` A. From 1992 to 2002, I was at the gymnasium.
` Q. Okay. So from 1992 to 2002, you were at
`the gymnasium, correct?
` A. Yes.
` Q. And then from 2002 to 2003, you were doing
`civil rights service?
`
`202-220-4158
`
`Henderson Legal Services, Inc.
`www.hendersonlegalservices.com
`
`4
`
`

`

`Thran, Ph.D., Moritz
`
`Case IPR2017-02194
`CONFIDENTIAL
`
`October 2, 2018
`5 (Pages 14 to 17)
`16
`
`14
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` A. (Nods.) Yes.
` Q. Thank you.
` And then from 2003 to 2008, you were
`obtaining your diploma in biology, is that correct?
` A. Yes.
` Q. Okay. And then from 2008 until 2012, you
`were obtaining your doctoral degree, is that correct?
` A. Yes.
` Q. What did your doctoral degree research
`encompass?
` A. The research was on mRNA metabolism in
`plants.
` Q. What kind of experiments did you conduct
`as part of your doctoral degree research?
` MS. LENTZ: Objection to form.
` THE WITNESS: Can you repeat and specify
`your question?
`BY MS. ELLISON:
` Q. Did you understand the question?
` A. Not entirely.
` Q. What was unclear about my question?
` A. I think there are more than one answer to
`
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`that question.
` Q. What are the multiple answers to my
`question, then?
` A. To -- can you please repeat it because --
`can you please --
` Q. As part of your doctoral research, what
`kind of experiments were you conducting?
` A. Okay.
` MS. LENTZ: Same objection.
` THE WITNESS: I would start to define
`fields within these experiments that have been done.
`If you want to specify the experiments themselves, I
`can do that in the next question. So the field I
`comprise, that are comprised in my doctoral thesis,
`were mostly molecule of biology, biochemistry and
`genetics.
`BY MS. ELLISON:
` Q. As part of your Ph.D. research, did you
`purify RNA?
` A. Yes.
` Q. Using what techniques?
` A. I used cellular messenger RNA from -- from
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`plant extracts, using commercial kits but also
`in-house, and solutions with chemical reagents, in
`order to isolate the messenger RNA from the crude
`extract.
` Q. Did you purify RNA using HPLC as part of
`your Ph.D. research?
` A. No.
` Q. What commercial kits did you use as part
`of your doctoral research to purify mRNA?
` A. The Qiagen RNeasy extraction kit.
` Q. Q-I-A-G-E-N, correct? Did I spell it
`correctly?
` A. Yes.
` Q. Did you use any other commercial kits to
`purify RNA as part of your Ph.D. research?
` A. Not that I recall.
` Q. And what in-house solutions did you use to
`purify RNA as part of your doctoral research?
` A. TRIzol.
` Q. Can you spell that, please?
` A. T-R-I-TSET-O-L.
` Q. Okay. Did you use any other in-house
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`solutions to purify RNA as part of your doctoral
`research?
` A. Yes.
` Q. What else?
` A. The extraction buffer contained
`guanidinium hydrochloride. G-U-A-N-I-D-I-N-E
`H-Y-D-R-O-C-H-L-O-R-I-D-E.
` Q. It's a spelling test.
` A. I passed.
` Q. Okay. Did your doctoral research use any
`other in-house solutions for purifying RNA?
` A. No.
` Q. In preparing your declaration, did you
`review any documents that are not identified in your
`declaration?
` A. No.
` Q. In reviewing -- in preparing your
`declaration, did you carry out any searches of the
`scientific literature?
` A. No.
` Q. In preparing your declaration, did you
`carry out any searches of the patent literature?
`
`202-220-4158
`
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`
`5
`
`

`

`Thran, Ph.D., Moritz
`
`Case IPR2017-02194
`CONFIDENTIAL
`
`October 2, 2018
`6 (Pages 18 to 21)
`20
`
`18
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` A. No.
` Q. In preparing your declaration, did you
`read the '340 patent?
` A. No.
` Q. Do you know what I'm referring to when I
`say the "'340 patent"?
` A. I know there is this '340 patent, but I
`haven't read it.
` Q. Is it your understanding that the '340
`patent is the patent that's being challenged in this
`proceeding, legal proceeding?
` A. Yes.
` Q. In preparing your declaration, did you
`rely upon any information that's not identified in
`your declaration?
` A. Could you repeat the question, please.
` Q. In preparing your declaration, did you
`rely upon any information that is not identified in
`your declaration?
` A. No.
` Q. In -- in your work in connection with this
`proceeding, have you carried out any experiments that
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`are not identified in your declaration?
` A. Can -- can you please repeat it?
` Q. You realize that you're here today for a
`deposition involving a legal proceeding known as an
`inter partes review, correct?
` A. Yes.
` Q. Okay. So in your work in connection with
`this inter partes review, did you carry out any
`experiments that are not discussed in your
`declaration?
` A. I haven't done any other experiments in --
`related to this proceeding, but I do experiments for
`different projects every day --
` Q. Okay.
` A. -- which are not related to this case.
` Q. Okay. In your work in connection with
`this inter partes review proceeding, did you carry
`out any RNA purification experiments that are not
`discussed in your declaration?
` A. No.
` Q. Let's look back at your CV, which is
`Exhibit 2018.
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` Does your CV contain a complete list of
`your publications?
` A. Yes.
` Q. Let's look at paragraph six of your
`declaration. I'm going to focus on the part that
`appears on page four. In the last sentence of
`paragraph six of your declaration, you state "as a
`postdoctoral fellow"..."I evaluated the contribution
`of mRNA degrading protein complexes on the half-life
`of mRNA," correct?
` A. Yes.
` Q. Which mRNA degrading protein complexes did
`you study?
` A. I studied the decapping complex.
` Q. I'm sorry, could you say that again,
`please.
` A. Studies were on the decapping protein
`complex. D-E-C-A-P-P-I-N-G.
` Q. And can you briefly explain what a
`decapping complex is.
` A. The decapping complex removes the five
`prime cap structure of the mRNA before it undergoes
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`the final degradation step.
` Q. And your studies on the contribution of
`mRNA degrading protein complexes on the half-life of
`mRNA, were those in vivo studies?
` A. These were studies done in human
`intracellular cell culture.
` Q. So they were not in vivo studies, correct?
` A. Can you explain "in vivo"?
` Q. What's your understanding of what the word
`"in vivo" means?
` A. There is different meanings of "in vivo."
`Some people understand living animals; others do
`understand cell culture, as well.
` Q. What's your understanding of the term "in
`vivo"?
` A. Animal research.
` Q. Okay. So the experiments you did were not
`conducted in animals for your postdoctoral
`fellowship, correct?
` A. Correct.
` Q. And when were you a postdoctoral fellow?
` A. Between 2013 and 2015.
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`202-220-4158
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`6
`
`

`

`Thran, Ph.D., Moritz
`
`Case IPR2017-02194
`CONFIDENTIAL
`
`October 2, 2018
`7 (Pages 22 to 25)
`24
`
`22
`
` Q. So let's look at paragraph nine of your
`declaration that appears on page four. In paragraph
`nine, you state, among other things, "For this
`purpose I planned the experiments together with
`technicians who subsequently carried out the
`experiments."
` Do you see that?
` A. Yes.
` Q. Who were the technicians to whom you refer
`in that sentence in paragraph nine of your
`declaration?
` A. There were two technicians I was working
`together with.
` Q. Who are they?
` A. Their names are Axel Teegler, A-X-E-L
`T-E-E-G-L-E-R, a male. And a female, she was called
`Arbea Betten, A-R-B-E-A B-E-T-T-E-N.
` Q. Does Mr. Teegler work for CureVac?
` A. Yes.
` Q. Does Ms. Betten work for CureVac?
` A. Yes.
` Q. Does Mr. Teegler have a doctoral degree?
`
`23
`
` A. No.
` Q. Does Ms. Betten have a doctoral degree?
` A. No.
` Q. In paragraph nine, you also say, "I
`analyzed the results together with the technicians
`who conducted the experiments."
` In the sentence that I just read where you
`refer to the technicians who conducted the
`experiments, are you referring again to Mr. Teegler
`and Ms. Betten?
` A. Yes.
` Q. And you state in paragraph nine that you
`planned the experiments together with the
`technicians.
` What contributions did Mr. Teegler make to
`planning the experiments?
` A. Mr. Teegler prepared the protocol based on
`standard operating procedure documents we have at
`CureVac.
` Q. What contributions did Ms. Betten make
`towards planning the experiments?
` A. Ms. Betten was involved in the planning of
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`the overall schedule involving the schedule for
`practical work.
` Q. Are the standard operating procedures to
`which you referred provided in your declaration or in
`any appendix to your declaration?
` A. Can you please explain -- repeat the
`question.
` Q. You said that Mr. Teegler prepared a
`protocol based on standard operating procedures
`documents that you have at CureVac, correct?
` A. Yes.
` Q. Okay. Are those standing operating
`procedure documents included in your declaration or
`in any appendix to your declaration?
` A. No.
` Q. What were the standing operating procedure
`documents -- what -- what do the standard operating
`procedure documents relate to?
` A. These, short-term, SOP's relate to
`transfection of cells, measurement of antibody
`titers.
` Q. Anything else?
`
`25
`
` A. I don't know the answer.
` Q. And what is the standard operating
`procedure for trans -- transfection of cells?
` A. Sorry?
` Q. What is the standard operating procedure
`for transfection of cells?
` A. This SOP defines what reagents are being
`used and in which order they are added to the -- to
`the mRNA before it is transfected into cells.
` Q. And so what do the standard operating
`procedures specify regarding which reagents are used
`and the order in which they're used for transfection
`into cells?
` A. These SOP's define that the cells are to
`be transfected with Lipofectamine2000, and as a
`additional low serum-containing medium Opti-MEM is
`required.
` Q. Why is the low serum-containing medium
`required?
` A. It is required in order to product the
`mRNA against early degradation.
` Q. And what was the name of the low
`
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`
`7
`
`

`

`Thran, Ph.D., Moritz
`
`Case IPR2017-02194
`CONFIDENTIAL
`
`October 2, 2018
`8 (Pages 26 to 29)
`28
`
`26
`
`serum-containing medium that you mentioned?
` A. Opti-MEM. O-P-T-I dash M-E-M.
` Q. And why is Lipofectamine used?
` A. Because the Lipofectamine is a standard
`transfection reagent at CureVac and we have used it a
`lot in the past and, therefore, we rely on this
`transfection reagent.
` Q. What is the function of Lipofectamine2000
`as a transfection reagent?
` A. Lipofectamine encapsulates the mRNA and,
`to my understanding, it forms particles that can be
`taken up by the cells and then the particles release
`the mRNA into the cytoplasm.
` Q. What is the purpose of using
`Lipofectamine2000?
` A. The purpose is to efficiently bring the
`mRNA into the cytoplasm.
` Q. What happens if Lipofectamine2000 is not
`used in the transfection experiment?
` A. The messenger RNA will hardly be able to
`enter the cytoplasm.
` Q. What happens if the messenger RNA is
`
`27
`
`hardly able to enter the cytoplasm?
` A. The cells won't be transfected
`efficiently.
` Q. Prior to carrying out the experiments
`disclosed in your declaration, had you worked with
`Mr. Teegler or Ms. Betten?
` A. I planned ex -- other unrelated
`experiments, similar experiments, and these
`experiments were also performed by these two
`technicians.
` Q. How long have you worked with Mr. Teegler?
` A. For -- I have worked with Mr. Teegler for
`three years and four months.
` Q. What percentage of your time is spent
`working on a project with Mr. Teegler?
` A. Ten percent.
` Q. How long have you worked with Ms. Betten?
` A. I have worked with Ms. Betten three years
`and four months.
` Q. And roughly what percentage of your time
`is spent working on projects with Ms. Betten?
` A. Ten percent.
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` Q. You mentioned standard operating
`procedures for measurement of antibody titers.
` What do the standard operating procedures
`for the measurement of antibody titers encompass?
` A. They encompass the material and the
`reagents that have to be used in order to carry out
`this method.
` Q. Which materials and reagents have to be
`used to carry out this method?
` A. You -- one needs microtiter plates,
`specific buffer solutions for capturing antibodies,
`for washing steps, for detection antibodies, and for
`substrate solutions.
` Q. Do the standard operating procedures for
`measurement of antibody titers encompass anything
`else?
` A. I don't recall that.
` Q. Do the standard operating procedures for
`measurement of antibody titers encompass any
`particular antibodies?
` A. I am not sure. I don't recall.
` Q. Do the standard operating procedures for
`
`29
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`measurement of antibody titers encompass any
`particular detection methods?
` A. I don't know whether it's a particular
`detection method, so I don't know.
` Q. Can you tell me what buffer solutions are
`encompassed within the standards operating procedures
`for measurement of antibody titers?
` A. I don't know the exact ingredients of the
`buffer, but I can tell you the different names of the
`buffers and for which purpose they serve.
` Q. Okay. What are they?
` A. So there is a buffer for the capture
`antibody. There is a buffer for a washing, for the
`washing steps. There is a blocking buffer required
`for the detection antibody. There is a blocking
`buffer for the blocking step. There is the blocking
`buffer for the -- for a reagent called Streptavidin
`HRP. Then there is -- but it's not a buffer, it's a
`substrate solution, TMB substrate solution. And
`there is sulfuric acid.
` Q. Did you say TMB?
` A. TMB.
`
`202-220-4158
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`
`8
`
`

`

`Thran, Ph.D., Moritz
`
`Case IPR2017-02194
`CONFIDENTIAL
`
`October 2, 2018
`9 (Pages 30 to 33)
`32
`
`30
`
` Q. What is TMB substrate solution?
` A. I think it's tetramethylbenzidine, but I'm
`not hundred percent sure.
` Q. Can you tell me anything else about what
`the standard operating procedures for the measurement
`of antibody titers encompass?
` A. They provide information on the duration
`of the incubation steps and also on how many times
`the plates used in the measurement needs to be washed
`during the incubation steps.
` Q. Can you tell me anything else?
` A. I think -- I don't think there's anything
`else.
` Q. What do the standard operating procedures
`specify regarding the duration of incubation in
`measuring antibody titers?
` A. The duration of the capture antibody can
`be done overnight, and that's what we have always
`done. The duration -- sorry, let me correct.
` The capture antibody is incubated on the
`microtiter plate for four -- between four and five
`hours at 37 degrees, and the blocking is done
`
`31
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`overnight at four degrees. After that the samples,
`or the unknown samples, as well as the internal
`protein standards, are incubated for two hours. The
`detection antibody solution is incubated for one
`hour. The Streptavidin HRP is incubated for 30
`minutes. And the substrate solution S depends on the
`time of the reaction.
` The reaction is a color change and this
`can vary. But based on our knowledge, it typically
`takes roughly two minutes. And then the sulfuric
`acid, the 20 per -- the sulfuric acid is added at 20
`percent, and this is then finally added to finalize
`the protocol.
` Q. What do the standard operating procedures
`specify regarding how many times the washes are
`carried out?
` A. There are three washes following the
`capturing. There are three washes following the
`blocking. There are three washes following the
`detection antibody. And there are four washes
`following the Streptavidin HRP.
` Q. Let's look at paragraph 11 of your
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`declaration. Paragraph 11 begins, "mRNA was
`synthesized as follows:"
` Do you see that?
` A. Yes.
` Q. Who synthesized the mRNA that's mentioned
`in paragraph 11 of your declaration?
` A. The mRNA was synthesized at CureVac in the
`production facility.
` Q. Who synthesized it?
` A. I cannot answer this because the
`production facility consists of several production
`members. In order to answer your question, I would
`need to look into their protocols.
` Q. Can you tell me who the members of the
`production facility are?
` A. I don't know all the names, so I cannot
`tell you.
` Q. Can you tell me how many members there are
`in the production facility?
` A. This production facility roughly consists
`of 20 to 30 members.
` Q. Later in that paragraph, it states, "For
`
`33
`capping of the RNA, m7G cotranslational" -- excuse
`me, "cotranscriptional capping was used."
` Do you see that?
` A. Yes.
` Q. Did the production facility carry out the
`cotranscriptional capping?
` A. Yes.
` Q. Then it states, "After in vitro
`transcription, the samples described as being HPLC
`purified were purified by reversed-phase
`chromatography" --
` Who carried out the reversed-phase
`chromatography described in paragraph 11 of your
`declaration?
` A. The production facility.
` Q. Can you tell me who in the production
`facility carried out the reversed-phase
`chromatography?
` A. No. I don't know.
` Q. Were you present when the mRNA was
`synthesized as described in paragraph 11 of your
`declaration?
`
`202-220-4158
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`
`9
`
`

`

`Thran, Ph.D., Moritz
`
`Case IPR2017-02194
`CONFIDENTIAL
`
`October 2, 2018
`10 (Pages 34 to 37)
`36
`
`34
`
` A. No.
` Q. Were you present when the HPLC
`purification was carried out as described in
`paragraph 11 of your declaration?
` A. No.
` Q. Was Mr. Teegler present for the mRNA
`synthesis described in paragraph 11 of your
`declaration?
` A. No.
` Q. Was Ms. Betten present for the mRNA
`synthesis described in paragraph 11 of your
`declaration?
` A. No.
` Q. Was Mr. Teegler present for the
`reverse-phase chromatography described in paragraph
`11 of your declaration?
` A. No.
` Q. Was Ms. Betten present for the
`reverse-phase chromatography described in paragraph
`11 of your declaration?
` A. No.
` Q. At the end of paragraph 11 of your
`
`35
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`declaration, it says, "The mRNA was complexed with
`Lipofectamine2000 according to the manufacturer's
`instructions," the citation is in Thermo Fisher
`Scientific, do you see that?
` A. Yes.
` Q. Who complexed the mRNA with
`Lipofectamine2000?
` A. Axel Teegler.
` Q. Were you present when Mr. Teegler
`complexed the mRNA with Lipofectamine2000?
` A. No.
` Q. Can you tell me what the manufacturer's
`instructions are for complexing mRNA with
`Lipofectamine2000?
` A. They define the amount -- or a range of
`amount of microliter Lipofectamine2000 per microgram
`messenger RNA and how long the complexes need to form
`before they can be added to its cells.
` Q. What do the manufacturer's instructions
`specify regarding the amount of Lipofectamine per
`microgram of mRNA?
` A. I don't know the entire range, but we use
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`one of one ratio that is comprised in this range,
`which is 1.5 microliter per microgram mRNA.
` Q. What do the manufacturer's instructions
`spe