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` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________________________________________________
`MODERNA THERAPEUTICS, INC., )
` ) Case No. IPR2018-00680
` Petitioner, ) Case No. IPR2018-00739
` ) Patent No. 9,404,127
`v. ) Patent No. 9,364,435
` )
`PROTIVA BIOTHERAPEUTICS, )
`INC., )
` )
` Patent Owner. )
`________________________________________________________
` DEPOSITION UPON ORAL EXAMINATION
` OF
` DAVID H. THOMPSON, PhD - VOLUME I
`________________________________________________________
`
` Taken at 701 Fifth Avenue, Suite 5100
`
` Seattle, Washington
`
`Job No: 154632
`DATE TAKEN: February 4, 2019
`REPORTED BY: KATHLEEN HAMILTON, RPR, CRR, CCR 1917
`
`TSG Reporting - Worldwide - 877-702-9580
`
`ARBUTUS - EXHIBIT 2005
`Moderna Therapeutics, Inc. v. Arbutus Biopharma Corporation
`IPR2019-00554
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`Page 1
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` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________________________________________________
`MODERNA THERAPEUTICS, INC., )
` ) Case No. IPR2018-00680
` Petitioner, ) Case No. IPR2018-00739
` ) Patent No. 9,404,127
`v. ) Patent No. 9,364,435
` )
`PROTIVA BIOTHERAPEUTICS, )
`INC., )
` )
` Patent Owner. )
`________________________________________________________
` DEPOSITION UPON ORAL EXAMINATION
` OF
` DAVID H. THOMPSON, PhD - VOLUME I
`________________________________________________________
`
` Taken at 701 Fifth Avenue, Suite 5100
`
` Seattle, Washington
`
`Job No: 154632
`DATE TAKEN: February 4, 2019
`REPORTED BY: KATHLEEN HAMILTON, RPR, CRR, CCR 1917
`
`TSG Reporting - Worldwide - 877-702-9580
`
`ARBUTUS - EXHIBIT 2005
`Moderna Therapeutics, Inc. v. Arbutus Biopharma Corporation
`IPR2019-00554
`
`
`
`Page 2
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` A P P E A R A N C E S
`
` FOR THE PETITIONER:
`
` MACLAIN WELLS, ESQ.
` Irell & Manella
` 1800 Avenue of the Stars
` Los Angeles, California
` 90067
`
` FOR THE PATENT OWNER:
` MICHAEL ROSATO, ESQ.
` SONJA GERRARD, ESQ.
` Wilson Sonsini Goodrich &
` Rosati
` 701 Fifth Avenue
` Seattle, Washington 98104
`
` ALSO PRESENT:
`
` ANDREW JANOFF, PhD
`
` * * * * *
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` DEPOSITION OF DAVID H. THOMPSON, PhD
` EXAMINATION INDEX
` EXAMINATION BY PAGE
` MR. WELLS................................................ 4
`
`Page 3
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` EXHIBIT INDEX
` EXHIBITS FOR IDENTIFICATION PAGE
` Exhibit 1 David H. Thompson curriculum vitae 11
` Exhibit 2 Declaration of David H. Thompson, Ph.D. 43
` Exhibit 3 Corrected Declaration of David H. 43
` Thompson, Ph.D. in Support of Patent
` Owner's Contingent Motion to Amend
` Exhibit 4 Declaration of David H. Thompson, Ph.D. 44
` Exhibit 5 United States Patent 9,364,435 B2 78
` Exhibit 6 United States Patent 9,404,127 B2 78
` Exhibit 7 Declaration of Andrew S. Janoff, Ph.D. 80
` in Support of Moderna Therapeutics
` Inc.'s Petition for Inter Partes Review
` of U.S. Patent No. 9,364,435
` Exhibit 8 WO 2005/007196 A2 190
` Exhibit 9 United States Patent Application 190
` Publication US 2006/0134189 A1
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` DAVID H. THOMPSON, PhD
` SEATTLE, WASHINGTON; FEBRUARY 4, 2019
` 10:54 a.m.
` -o0o-
`
`Page 4
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` DAVID H. THOMPSON, PhD, witness herein, having been
` first duly sworn on oath,
` was examined and testified
` as follows:
`
` E X A M I N A T I O N
` BY MR. WELLS:
` Q. And for the record, I am counsel for petitioner
` Moderna, and with me is Dr. Andrew Janoff.
` Can you state your name and your home address
` for the record, please?
` A. Sure. David H. Thompson. 230 Spring Valley
` Lane, West Lafayette, Indiana 47906.
` Q. And have you been deposed before?
` A. Yes.
` Q. How many times?
` A. Once.
` Q. Once.
` And was that a case where you were retained as
` an expert?
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` DAVID H. THOMPSON, PhD
` A. Yes.
` Q. And generally, I don't want you to get into the
` specifics of the technology, but generally what did that
` case involve?
` A. PEGylation of lipid -- PEGylation of liposomes.
` MR. ROSATO: Counsel, do you want us to just
` announce ourselves for the record real quick?
` MR. WELLS: Sure.
` MR. ROSATO: Mike Rosato on behalf of
` Arbutus, Protiva. And I have Sonja Gerrard with me as
` well both from Wilson Sonsini.
` BY MR. WELLS:
` Q. And who was involved in that lawsuit? Do you
` remember the parties?
` A. It was ALZA and PolyMask.
` Q. And was that a federal district court case, a
` lawsuit or was that a patent hearing, do you recall?
` A. It was, the -- it was, what 16, 17 years ago.
` So the details are a little bit fuzzy other than the
` technical issues. So I don't... As I recall, that was
` an infringement case.
` Q. And do you recall whether you were opining about
` the validity of the patents that were at issue in that
` case?
`
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` A. I was looking at formulation and the chemistries
` that were used and stability data, pharmacokinetic data.
` That -- that's what I can recall.
` Q. Sure. And I think you said -- you just said the
` formulation. Are you talking about the formulation of
` the liposomes?
` A. Yes.
` Q. And do you recall what the payload was for the
` liposomes in that case?
` A. I -- there were different payloads as I recall,
` so they were small molecule payloads.
` Q. So siRNA? Was that an example?
` A. Let's see. 17 years, 16, 17 years ago, we were
` just learning about siRNA, so no.
` Q. Do you recall what type of small molecules were
` involved?
` A. As I recall, it was doxorubicin and that's --
` that's as far as I feel comfortable going with my
` memory.
` Q. I appreciate 16 or 17 years is a long time.
` And you mentioned that that involved liposomal
` structures as opposed to -- well, let's just start
` there.
` A. Yeah.
`
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` Q. When you say liposome, just so we have our
` context correct --
` A. Yeah.
` Q. -- what are we talking about?
` A. At essence it was the distinction between
` chemically synthesizing polyethylene glycol modified
` lipids that were then added into a lipid mixture and
` fabrication of the liposomes from that mixture, which
` was the ALZA approach. And PolyMask, as I recall, was
` grafting on to, so they had a chemically activated
` liposome and they were trying to react the polyethylene
` glycol to that activated liposome surface.
` So it essentially boiled down to a topology
` issue; where's the pay, how much, how much can you
` control the resultant structures.
` Q. And just generally, what's your understanding of
` what a liposome is?
` A. It is --
` MR. ROSATO: Objection. Form.
` THE WITNESS: A liposome is a -- is
` understood to be a lipid bilayer that encloses an
` aqueous compartment.
` BY MR. WELLS:
` Q. I know we have a lot of these terms that we're
`
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` DAVID H. THOMPSON, PhD
` going to be throwing around today, so it helps to get
` some idea of those. And I'll get back to that in a
` minute, but let me just go through a little bit of my
` admonition since it's been a while since you've had your
` deposition taken.
` You understand that you're under oath today;
` correct?
` A. Mm-hm.
` Q. And this is with the same force that if you were
` testifying in a court of law, you're required to give
` the truth and the whole truth. Do you understand that?
` A. Mm-hm.
` Q. Is there anything preventing you from giving
` your best testimony here today?
` A. No.
` Q. If at any point you need a break today, please
` let me know. We can take a break. If I have a question
` pending though, I will request that you answer that
` question unless you have a question regarding the
` privilege in which case make that known and we can
` figure out how to deal with that should it arise. I
` don't imagine that's going to be much of an issue.
` A. What does "privilege" mean?
` Q. I don't -- it would be attorney/client
`
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` DAVID H. THOMPSON, PhD
` communications --
` A. Oh, okay.
` Q. -- or work product communications with your
` attorney and in certain instances that could be
` protected.
` A. Okay.
` Q. If you don't understand one of my questions, ask
` me to clarify and I'll try to clarify it for you so that
` we can get on the same page.
` A. Okay.
` Q. Did you do anything to prepare for your
` deposition here today?
` A. I read a series of documents, the petition, the
` one -- the two patents that are in question or under
` discussion, and Dr. Janoff's declaration. Some other
` associated patent documents.
` Q. And there's actually two petitions that we're
` going to be covering over the course of the next two
` days. One relates to the `127 patent. Do you recall
` that patent?
` A. Yes.
` Q. And are you comfortable with me referring to it
` as the `127 patent?
` A. Yes.
`
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` DAVID H. THOMPSON, PhD
` Q. And then the petition relates to the ?435
` patent. Are you comfortable with me referring to that
` as the `435 patent?
` A. Yes.
` Q. Did you meet with counsel to prepare for your
` deposition here today?
` A. Yes.
` Q. And who did you meet with?
` A. I met with the two individuals to my left.
` Q. And how long did you meet?
` A. Hours, not days.
` Q. A full day? Like eight hours or...?
` A. In sum, eight hours.
` Q. And how many meetings was that spread across?
` A. There were three meetings.
` Q. And when did those take place?
` A. The first meeting was October I guess, sometime
` late October. The second meeting was on Friday. And
` the third meeting was yesterday.
` Q. Other than your counsel, did you speak to
` anybody else to prepare for your deposition here today?
` A. No.
` Q. Let's go ahead and mark Thompson Exhibit 1, your
` CV.
`
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` DAVID H. THOMPSON, PhD
` (Exhibit 1 marked.)
` BY MR. WELLS:
` Q. Now, before we get into the details of your
` prior work, going back to liposomes and all of the other
` terms we're going to be talking about today, in your
` declaration you mention the term lipoplex as well. Is
` that -- do you recall that?
` A. Yes.
` Q. And do you have an understanding of what a
` lipoplex is?
` A. Yes.
` Q. And what is that understanding?
` A. It is typically referring to a liposome
` cationic -- often a liposome with cationic lipid content
` that has been admixed with a nucleic acid, most
` typically plasmid DNA is where that language primarily
` lives.
` Q. And when you say that it has been mixed with a
` nucleic acid, is the nucleic acid and lipoplexes
` typically in the aqueous space on the interior of the
` particle or is it somewhere else?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: The... So there are two
` questions. What is -- I'm hearing so could you --
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` BY MR. WELLS:
` Q. Sure, why don't I try --
` A. -- restate?
` Q. I'm glad to. Do lipoplexes have an aqueous
` space?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: Typically lipoplex are
` heterogeneous enough that some areas contain water, are
` aqueous and some areas are not.
` BY MR. WELLS:
` Q. And where is the nucleic acid in a lipoplex
` typically found?
` MR. ROSATO: Same objection.
` THE WITNESS: It is because they're
` heterogeneous, some portions are, can be protected.
` Other portions are exposed to that aqueous environment.
` BY MR. WELLS:
` Q. And when you say "protected," what are you
` referring to there?
` MR. ROSATO: Same objection.
` THE WITNESS: Protected from what I'll call
` exchange or accessibility to the aqueous milieu.
` BY MR. WELLS:
` Q. And is that both the aqueous milieu on the
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` internal of the particle as well as the external of the
` particle or are you differentiating?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: The aqueous milieu that the
` particle, at least the initial formulation is often what
` is associated with the complex. But where the nucleic
` acid is exposed, now it depends on the environment that
` that lipoplex is introduced into. So it's a, it depends
` on the conditions of the experiment and what the
` experimentalist is trying to achieve.
` BY MR. WELLS:
` Q. And I believe when we began this discussion you
` said that typically lipoplexes have this form; is that
` correct?
` A. Yes.
` Q. And why did you use the term "typically"?
` A. Because the -- at the time that lipoplex were --
` that that term was created, our understanding was pretty
` primitive about how to properly form complexes and to
` control their composition, morphology, function,
` performance. And so in some cases the complexes were
` formed by nothing more than vortexing, so dumping two
` solutions together and vortexing. And the particles
` were very -- produced that way are very heterogeneous.
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` So again, it is I would say to be or trying to
` be precise, it depends when and the technology or the
` experiment was done and the specifics of how the
` experiment were executed.
` Q. And you said at the time that lipoplexes were
` being developed for these purposes. Do you recall the
` general timeframe that that would have been?
` A. Yes, so this -- this would have been -- really
` began in the late '80s with the -- with essentially the
` first publication of cationic lipid literature and
` evolved from there. If memory serves, 1987 FEBS letter
` paper.
` Q. And have you ever heard the abbreviation LNP?
` A. LN -- LNP. Yeah, that's one of several
` fashions.
` Q. Have you ever heard -- I'm sorry, I didn't mean
` to interrupt you.
` A. Yeah.
` Q. Have you ever heard that abbreviation in the
` context of lipid nucleic acid particles?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: Lipid nucleic acid particles,
` that... I guess the... On reflection I may or may not
` have heard that term. The... When you're active in a
`
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` research field, there is -- there's a tension of people
` who want to try to create a fashion around their --
` around their technology so they create names. And I
` tend to ignore the names and look at the experiment and
` the data.
` BY MR. WELLS:
` Q. So is it fair to say in the field of lipid
` carrier poly- -- carrier particles that there are
` numerous names for these particles and they vary over
` time and with the researchers that are using them?
` MR. ROSATO: Objection. Form.
` THE WITNESS: You can draw your own
` conclusion. What I'm saying is that what matters are
` the details, and that is what you get and its
` performance is tied to the details.
` BY MR. WELLS:
` Q. Are you familiar with the term SNALP?
` A. Yes.
` Q. And what is a SNALP?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: The acronym I believe stands
` for stabilized nucleic acid-lipid particle.
` BY MR. WELLS:
` Q. And in the industry are you familiar with that
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` term or strictly from the patents that we've been
` discussing?
` MR. ROSATO: Objection. Form.
` THE WITNESS: I've been aware of it in the
` literature, so I was -- it was not an unfamiliar term.
` BY MR. WELLS:
` Q. And in your experience with SNALPs from the
` literature, what were SNALPs? What were those?
` MR. ROSATO: Objection. Form.
` THE WITNESS: As that name suggests,
` stabilized nucleic acid-lipid particles.
` BY MR. WELLS:
` Q. And in your experience, what were those used
` for?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: It is, SNALP are a type of
` self-assembly that can be used in many different ways.
` So in the same way that liposomes in the previous
` technology can be used for many different applications,
` that's the way I viewed SNALP.
` BY MR. WELLS:
` Q. And --
` A. Depends on what the cargo is.
` Q. And what cargos are you familiar with being used
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` with SNALPs from your experience in the literature?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: There are many targets that --
` so some of the more... So essentially receptor
` knockdowns, enzyme knockdowns, a number of different
` types of applications.
` BY MR. WELLS:
` Q. Other than receptor knockdowns and enzyme
` knockdowns, do you recall any of the purposes of SNALPs
` from your experience with the literature?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: Restate the question, please.
` BY MR. WELLS:
` Q. Sure. Other than the receptor knockdowns and
` enzyme knockdowns that you just mentioned, do you recall
` any other uses of the SNALPs from your experience?
` MR. ROSATO: Same objection.
` THE WITNESS: The -- the -- what's the word
` I'm searching for here? The -- the typical application
` when they appeared were siRNA cargo in all its forms,
` mRNA delivery, other -- and a oligonucleotide delivery.
` So essentially a technology for transporting shorter
` nucleic acid cargos than how the field kind of got
` started in nucleic acid delivery around plasma delivery.
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` BY MR. WELLS:
` Q. And do you recall when siRNA being used with
` SNALPs was being done in the field?
` MR. ROSATO: Objection. Form.
` THE WITNESS: My first recollection was
` presentation at a liposome conference in North Carolina.
` It was early to mid 2000s.
` BY MR. WELLS:
` Q. And do you recall who was presenting?
` A. At that presentation it was Ian MacLachlan who
` was presenting his work on Toll-like receptor
` stimulation. Essentially pointing us in the direction
` that we needed to pay attention to CPG content in -- in
` nucleic acid constructs.
` Q. And what about oligonucleotide delivery, when
` you say oligonucleotide, what are you referring to?
` A. First came plasmid, then came antisense, so
` that's what I'm referring to is ODN or OGN depending
` upon which abbreviation people use, but
` oligonucleotides.
` Q. And then when do you recall first hearing about
` oligonucleotides being used with SNALPs for delivery?
` MR. ROSATO: Objection. Form.
` THE WITNESS: I can't recall in the moment
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` the exact date.
` BY MR. WELLS:
` Q. Do you have a general, was it that early 2000
` time period?
` MR. ROSATO: Objection. Form.
` THE WITNESS: Yeah, I'm... I can't recall
` with precision.
` BY MR. WELLS:
` Q. What about mRNA use with SNALPs, do you recall
` when mRNA use with a SNALP delivery mechanism was first
` introduced into the field?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: As best I can recall it was
` 2007, 2009 kind of timeframe. Again I'm... That's --
` that's the best I can do without having -- looking over
` my records.
` BY MR. WELLS:
` Q. Sure.
` So is it fair to say that the use of SNALPs
` started with plasmid constructs, plasmid payloads at
` first?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: Actually no, I think that
` there -- as I was saying earlier, there's an evolution
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` in terms of the nucleic acid cargo.
` BY MR. WELLS:
` Q. Mm-hm.
` A. And the methods for fabrication of those
` complexes matured. And the -- the acronym SNALP, to my
` recollection, was always focused on or utilized in the
` creation of non plasmid assemblies. So shorter pieces
` of nucleic acid where the, that were more amenable to
` small particle formulation.
` Q. What's -- is there a problem with using SNALP
` technologies with larger nucleic acids like plasmid DNA?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: As a -- it depends on your
` objective. The... If you're trying to deliver a gene,
` a whole gene, at the time you -- we attempted to deliver
` them in the form of a plasmid that would be episomal.
` Today's standards would be delivering a -- essentially
` the CRISPR/Cas technology. And the methods used to
` make -- the process used to make stabilized nucleic
` acid-lipid particles could be applied to any cargo.
` It's up to the experimentalist to make a reasoned choice
` where they think their best odds lie.
` BY MR. WELLS:
` Q. The best odds of it being successful and
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` delivering the therapeutic to the --
` A. Right, being plasma stable. Being serum or
` nuclease stable. Being in a particle sufficiently of a
` size that can be internalized.
` Q. Okay. I want to talk a little bit more about
` that, see if I can get to the heart. There was a lot
` there.
` Okay. So we have SNALP carrier technology and
` it can potentially be used with DNA plasmid payloads.
` Do I have it right thus far?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: I -- I guess I'm -- what I'm
` trying to say is that the SNALP has a specific meaning.
` It's stabilized. It's a serum-stabilized nuclease
` stable. And whether the methods of production, the
` process used to make the particle, you can use that
` process to make lots of different particles. We use
` methods... Actually if I'm going to personalize this,
` we make stabilized nucleic acid particles, but they're
` not lipid particles. We make them out of polymers. But
` it's used -- many of the same ideas are applicable.
` So what I'm getting at is that it's a --
` it's as a process. It's a fabrication method is the way
` I view it.
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` BY MR. WELLS:
` Q. Let me see if I can clean that up. So when we
` talk about SNALPs, SNALPs are formed by a process or a
` fabrication method. Do I have it right thus far?
` A. Mm-hm.
` MR. ROSATO: Objection. Form.
` BY MR. WELLS:
` Q. I think you're going to need to speak orally so
` that the court reporter can --
` A. So repeat the question, please.
` Q. Sure. So when we're talking about SNALPs,
` SNALPs are formed by a process or fabrication method.
` Do I have it right thus far?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: Stabilized lipid nanoparticles
` are what they -- what the name implies. They're stable
` particles to serum and can be made in many ways.
` BY MR. WELLS:
` Q. And when a researcher is trying to determine
` whether or not such particles can be used with a given
` payload, for example plasmid payload, they need to do
` some testing to determine whether or not they are going
` to be stable, whether they are going to be of an
` appropriate size I think are the two variables you
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` identified. Do I have that right?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: Actually, there are, for
` the -- for a therapeutic application, there are many
` more variables than the ones you elucidated that are
` important to focus on. Size is certainly one to deal
` with. Cellular -- pardon me -- the cellular
` internalization machinery is kind of geared towards
` dealing with certain size cargos. The poly dispersity
` of the formulation that has multiple -- can have
` multiple implications. Drug-to-lipid ratio, morphology.
` The protein corona that it attracts that can impact PK
` and BD on the particle. Pharmacokinetics and
` biodistribution. Lots of things to worry about, because
` you're trying to engage a living entity.
` BY MR. WELLS:
` Q. Those are a lot of variables. So is it fair to
` say that researchers when they're evaluating whether
` SNALPs are appropriate for a given payload need to do
` testing to -- regarding a variety of potential variables
` to determine whether SNALPs are an appropriate carrier
` molecule?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: The question one more time,
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` please.
` BY MR. WELLS:
` Q. Sure. Is it fair to say that researchers when
` evaluating whether SNALPs are an appropriate -- are
` appropriate carrier molecule for a given payload need to
` do testing to look at variables such as the ones that
` you're looking that you just mentioned to evaluate
` whether indeed SNALPs are appropriate as the carrier
` molecule?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: So it's any prudent
` investigator would test their formulation for the set of
` variables that's going to impact its performance.
` BY MR. WELLS:
` Q. Because it might or might not actually perform?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: Correct. You are -- there's
` the assurance that the formulation will perform is -- is
` not certain.
` BY MR. WELLS:
` Q. And if I wanted to test whether a given carrier
` molecule formulation will work with a given payload,
` what kind of tests would I run?
` MR. ROSATO: Objection. Form. Foundation.
`
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` THE WITNESS: It -- what kind of tests would
` you run if -- remind me what the first part of the
` question was.
` BY MR. WELLS:
` Q. Sure. If I wanted to evaluate whether a given
` carrier molecule, for example a SNALP, is appropriate
` for a given payload, say DNA.
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: You would -- you would run
` initially size determinations, so typically -- pardon
` me, a light scattering measurement to determine particle
` size, polydispersity. You'd analyze composition. You
` would, to essentially -- and also would measure
` typically for something like a composition that has
` cationic lipid in it or any lipid with a net charge, you
` would measure the zeta potential.
` Some type of morphology analysis would be
` appropriate to determine uniformity and essentially
` its -- its three-dimensional arrangement of components.
` Of course the performance experiments initially, kind of
` the trivial experiment of in vivo -- pardon me, in
` vitro. It's an important correction there. In vitro
` screening which is just standard routine methodology,
` but then most importantly going to the -- the heart of
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` the application, what the -- measuring serum stability
` and performance by whatever measure the active is,
` mechanism of action, the active is utilizing.
` BY MR. WELLS:
` Q. And I gave you the example of DNA as the payload
` for a SNALP, determining whether or not a SNALP is an
` appropriate carrier molecule of the given formulation.
` Would your opinion change if I changed the payload,
` suppose I said is for this siRNA, is this SNALP an
` appropriate carrier molecule, how would you make that
` determination?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: So this discussion is in the
` context of an array of delivery tools. And if one is
` considering the use of the methods to produce SNALP,
` it's just one of the -- one of the tools that you might
` evaluate.
` BY MR. WELLS:
` Q. But you would need to evaluate the tool to
` determine whether the SNALP formulation you're proposing
` works with the given payload; is that right?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: It is... You have a -- as is
` typical in these kinds of experiments, you have a set of
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` compositions as well as formulation choices as well as
` the cargo. So -- which is a huge search space. And so
` the setting for this whole conversation really is
` where -- where do you -- you don't know where the sweet
` spot is. How do you find it. And that is the challenge
` you're always fac
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