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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
`) Patent No. 9,364,435
`)
`)
`)
`)
`Patent Owner. )
`________________________________________________________
`DEPOSITION UPON ORAL EXAMINATION
`OF
`DAVID H. THOMPSON, PhD - VOLUME II
`________________________________________________________
`
`v.
`PROTIVA BIOTHERAPEUTICS,
`INC.,
`
`Taken at 701 Fifth Avenue, Suite 5100
`Seattle, Washington
`DATE TAKEN: February 5, 2019
`
`REPORTED BY: KATHLEEN HAMILTON, RPR, CRR, CCR 1917
`JOB NO: 154633
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`A P P E A R A N C E S
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`FOR THE PETITIONER:
`
`MACLAIN WELLS, ESQ.
`Irell & Manella
`1800 Avenue of the Stars
`Los Angeles, CA 90067
`
`FOR THE PATENT OWNER:
`
`MICHAEL ROSATO, ESQ.
`SONJA GERRARD, ESQ.
`Wilson Sonsini Goodrich & Rosati
`701 Fifth Avenue
`Seattle, WA 98104
`
`ALSO PRESENT:
`
`ANDREW JANOFF, PhD
`
`* * * * *
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`DEPOSITION OF DAVID H. THOMPSON, PhD
`EXAMINATION INDEX
`
`PAGE
`EXAMINATION BY
`MR. WELLS................................................ 213
`MR. ROSATO............................................... 403
`MR. WELLS................................................ 413
`
`EXHIBIT INDEX
`EXHIBITS FOR IDENTIFICATION
`Exhibit 10 United States Patent Application
`Publication US 2006/0240554 A1
`Exhibit 11 Three-Dimensional Imaging of Lipid
`Gene-Carriers: Membrane Charge Density
`Controls Universal Transfection Behavior
`in Lamellar Cationic Liposome-DNA
`Complexes
`Exhibit 12 New multivalent cationic lipids reveal
`bell curve for transfection efficiency
`versus membrane charge density: Lipid-DNA
`complexes for gene delivery
`Exhibit 13 United States Patent Application
`Publication US 2007/0042031 A1
`Exhibit 14 United States Patent No. 8,058,069 B2
`Exhibit 15 Rational design of cationic lipids for
`siRNA delivery
`Exhibit 16 Liposome Drug Products Chemistry,
`Manufacturing, and Controls; Human
`Pharmacokinetics and Bioavailability; and
`Labeling Documentation Guidance for
`Industry
`Exhibit 17 Diffusible-PEG-Lipid Stabilized Plasmid
`Lipid Particles
`Exhibit 18 United States Patent No. 8,236,943 B2
`Exhibit 19 United States Patent Application
`Publication US 2013/0116307 A1
`
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` DAVID H. THOMPSON, PhD
` SEATTLE, WASHINGTON; FEBRUARY 5, 2019
` 8:54?a.m.
` -o0o-
`
` E X A M I N A T I O N
`BY MR. WELLS:
` Q. You understand that you're still under oath that
`you gave yesterday to tell the truth and the whole
`truth?
` A. Yes.
` Q. And during the breaks yesterday or yesterday
`evening, did you discuss your deposition testimony here
`today with anybody?
` A. No.
` Q. With regard to the `435 patent, do you
`understand that one of the grounds involves the 054
`reference? Do you recall that?
` MR. ROSATO: Objection. Form.
` THE WITNESS: 054?
`BY MR. WELLS:
` Q. Oh, actually I should have said `554. I
`apologize. That was my error. Let's try that again.
` A. Yeah.
` Q. With regard to the `435 patent, do you recall
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`one of the references cited was the `554 patent?
` A. Correct. Yes, I recall.
` Q. Okay. And I'll give you a copy of the `554
`patent should you need it. It was previously marked as
`Exhibit 1004 to the `435 IPR.
` (Exhibit 10 marked.)
`BY MR. WELLS:
` Q. Now, the `554 publication has a formulation
`called the LO54 formulation. Do you recall that?
` A. Yes, I do recall.
` Q. And the cationic lipid used in the LO54 lipid
`mixture is a DMOBA, do you recall that?
` A. I recall the structure. I don't... The acronym
`I would have to look back and refamiliarize myself, but
`it's a -- an aerial ether dimethylamino -- benzyl
`dimethylamino lipid.
` Q. And if you look at paragraph 122 of your `435
`declaration, that has a discussion where you identify
`DMOBA as the acronym.
` A. Paragraph...?
` Q. 122.
` A. 122. Yes; okay I see it.
` Q. And do you know whether DMOBA is an ionizable
`cationic lipid?
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` A. As a tertiary -- pardon me. Yes, as a tertiary
`amine, it is going to be protonatable.
` Q. And do you know whether DMOBA is charge neutral
`at physiological pH?
` A. I have not -- I have not worked with this
`material. Couldn't speculate.
` Q. And when I say "physiological pH," you
`understand that to be --
` A. pH 7.4.
` Q. Okay.
` A. Ionic strength of roughly 200 milliosmole.
` Q. Now, in your declaration you point out that in
`your opinion the LO54 formulation would not be suitable
`for systemic administration; is that right?
` A. Yes.
` Q. And is suitability for systemic administration a
`requirement of the claims of the claim 1 of the `435
`patent?
` MR. ROSATO: Objection. Form.
` THE WITNESS: As was discussed yesterday,
`the only reason to be concerned with any of these or --
`in my opinion, any of these developments is to get them
`into humans. And so that's a critical filter in my
`opinion.
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`BY MR. WELLS:
` Q. Now, the -- are you familiar with the term ex
`vivo?
` A. Yes.
` Q. And what does ex vivo refer to?
` A. Typically taking tissues out of the body or
`cells out of the body, treating them externally and then
`possibly reintroducing them into the body.
` Q. And are you familiar with anybody in the field
`doing work with carrier formulations for nucleic acids
`using an ex vivo approach?
` MR. ROSATO: Objection. Form. Foundation.
`Scope.
` THE WITNESS: I read a lot of literature. I
`believe I've encountered that, but I don't -- I don't
`recall the details.
`BY MR. WELLS:
` Q. Would the same issues regarding systemic
`administration arise at an ex vivo application?
` A. Absolutely it could.
` MR. ROSATO: Objection. Form.
` THE WITNESS: Absolutely it could arise,
`because the way those cells are kept alive is by feeding
`them serum. And if you have serum present, if it's not
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`a serum stable formulation, and one that actually
`performs in the presence of serum, game over.
`BY MR. WELLS:
` Q. And would the cells -- I'm sorry, would the
`systemic stability issues be the same for ex vivo
`applications for as for systemic administration or would
`they be different?
` A. They would be different.
` Q. And how would they be different?
` A. It's much more challenging. It's a much higher
`bar for in vivo, so you're not only encountering just
`the physical processes in a -- in an ex vivo or in vitro
`situation where essentially you have a -- you have a
`contained compartment that you are adding, you control
`the composition of. Once you go in vivo, you're
`wrestling a live alligator. There are many more
`biologic challenges that you have to encounter and
`survive.
` Q. Now, the LO54 formulation disclosed in the `554
`patent was tested for in vitro, was tested in vitro;
`correct?
` A. Yes.
` Q. And it actually showed efficacy; correct?
` MR. ROSATO: Objection. Form.
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` THE WITNESS: It showed in vitro
`performance.
`BY MR. WELLS:
` Q. It didn't kill the cells outright; correct?
` MR. ROSATO: Objection. Form.
` THE WITNESS: There was no reliable measure
`of that.
`BY MR. WELLS:
` Q. Except there was some activity; right, so not
`all the cells were dead?
` A. Depending upon when you do your readout, those
`that manage to survive can expand. So you actually,
`it's a -- it's an -- the details matter. So an
`experiment showing some activity, there's no measure of
`cytotoxicity shown. I take that with a grain of salt.
`It's a shallow analysis.
` Q. But you would agree that at least some of those
`cells had to survive for them to measure activity?
` A. Those that survived had demonstrated activity.
` Q. And in paragraph 126 you talk about some of the
`disclosures of the ranges in the `554 publication. And
`ranges are given for the cationic lipid, a neutral lipid
`and the PEG conjugate. Do you see that?
` A. Mm-hm, yes I see.
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` Q. You would agree that those ranges overlap with
`the claimed ranges in the claim 1 of the `435 patent?
` MR. ROSATO: Objection. Form.
` THE WITNESS: The -- the ranges that are
`described there are -- overlap in -- in some of the --
`broadly speaking, in some of the ranges.
`BY MR. WELLS:
` Q. And one of the points you raise in your
`declaration is that the `554 patent for the LO54
`formulation I think you use the term bookends the 50
`percent and the 2 -- cationic lipid of the 2 percent PEG
`are at the lower and upper ends of the claimed ranges in
`the `435 patent; is that correct?
` MR. ROSATO: Objection. Form.
` THE WITNESS: What paragraph are you
`referring to?
`BY MR. WELLS:
` Q. Let's see if I can find it. I believe paragraph
`1 15.
` A. (Reviews exhibit.)
` The bookend statement is your language. I'm
`speaking about the likelihood that the composition of
`the final formulation may be different.
` Q. Right. And you say actually it -- presumably
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`the particles as formulated would be outside the scope
`of the challenged claims. Do you see that?
` A. Yes, I see that statement.
` Q. And do you stand by that statement?
` A. I stand by that statement given the way in which
`these particles were formulated.
` Q. Now, when particles are formulated, they don't
`all have -- they're not homogenous with regard to their
`lipid compositions in the population of particles, are
`they?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: As we discussed extensively
`yesterday, the method of formulation, the composition
`and the method of production of the particles matters
`greatly in terms of the polydispersity, size, all the
`lipid-to-drug ratio, serum stability, all of those
`physical features are impacted by the formulation.
`BY MR. WELLS:
` Q. And the particles when they're formulated, you
`end up with a bell curve of what their lipid percentages
`are for any given lipid; is that accurate?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: That's I would say a first
`approximation. There are -- it again, depends on the
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`formulation method and whether it's -- what sort of
`statistical distribution it is and how broad that
`distribution is. That's what is -- that's how we use
`the polydispersity measure as kind of a guide of how
`uniform the formulation is.
`BY MR. WELLS:
` Q. But you would --
` A. It says nothing -- actually, the embedded
`assumption in those -- typically those measurements are
`made by light scattering that relies on the Stokes
`Einstein equation which relies on assumed spherical
`geometry.
` Well, there may be rodlike particles in there
`and guess what? That assumption breaks down. And so
`that means that your size and polydispersity are
`impacted.
` So what you're proposing is... What I'm saying
`is that the measures that we use in the laboratory are
`approximations at what actually exists in the
`dispersion.
` Q. Right. But in the dispersion you would expect
`there actually to be a dispersion, you wouldn't expect
`all the particles to have exactly the same lipid
`components in a particle population?
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` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: Depending upon the level of
`control that you have in your process and these days
`building in process analytical tools, they actually tell
`you how your production run is going, you have much
`narrower distributions than the methods that were being
`used at -- at the time of -- of this of the `554 --
`BY MR. WELLS:
` Q. So at the time --
` A. 00 filing.
` Q. So at the time of the `554 you'd expect a
`broader distribution of particle lipid compositions in
`the resulting formulations?
` A. I --
` MR. ROSATO: Objection. Form.
` THE WITNESS: Okay.
` I would expect given the methods that are
`reported in this -- and there are -- it's not clear
`actually exactly how they're being formulated. It
`describes a set of different fabrication methods, one of
`which is detergent dialysis, that will certainly give
`you a broad distribution.
`BY MR. WELLS:
` Q. And if you have a broad distribution of
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`resulting particles, would some of those particles be
`accepted -- expected to have greater than 50 percent
`cationic lipid for the L54 formulation?
` MR. ROSATO: Objection. Form.
` THE WITNESS: The -- in a distribution of
`particles, there -- there may be a distribution of
`compositions. Something that would require -- to answer
`the question you're raising would require a separation,
`a fractionation of the particles. That's tough to do.
`But to answer your question precisely would require a
`analysis.
`BY MR. WELLS:
` Q. So you don't know whether the particles in the
`054 formulation would exist in that particle population
`that have greater than 50 percent without looking?
` A. I don't know any more than the authors of this
`document know what's in their composition. I can tell
`you based on my experience and understanding of
`self-assembly that it's likely that -- very likely that
`these particles are outside the range.
` Q. And would you hypothesize because you're
`hypothesizing that these particles are outside the
`range, right, you didn't test that; right?
` MR. ROSATO: Objection. Form. Foundation.
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` THE WITNESS: I believe I answered that
`question already that I've not worked with this
`material.
`BY MR. WELLS:
` Q. So would you have also hypothesize that some of
`the particles in the dispersion would have greater than
`50 percent cationic lipid?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: In a population of particles,
`there may be a X percent of particles that fall within
`the range. Are those the functional particles that give
`rise to the modest function that's reported? Who knows.
`The experiment was not done in a rigorous way. So
`it's -- it's not an answerable question with any
`precision.
` You know, I can -- just as the authors
`opine, I opine as well that the -- that the particles
`that are being produced here are -- are, have a much
`broader distribution than -- than particles produced by
`other more controlled methodologies.
`BY MR. WELLS:
` Q. And we've been talking about the greater than 50
`percent requirement from claim 1 of the `435 patent.
`With regard to the 2 percent conjugated lipid
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`requirement in the `435 patent, would you expect that
`some of the particles created by the L54 formulation
`would fall within the 2 percent under the 2 percent
`threshold --
` MR. ROSATO: Objection.
`BY MR. WELLS:
` Q. -- for conjugated lipid?
` MR. ROSATO: Excuse me. Objection to form.
` THE WITNESS: The -- the -- let me go back
`and look at what else is with 054. Can you direct me to
`the table that that formulation --
`BY MR. WELLS:
` Q. It's in the back of the patent. I believe it's
`table 4.
` A. Those are the structures. Here we are. Yeah,
`so...
` (Reviews exhibit.)
` The most at risk elements of this, of controlled
`formulation are going to be the cholesterol and the...
` (Reviews exhibit.)
` The cholesterol is what I would expect to be
`most difficult to control. Cholesterol content.
` Q. Okay. So back to my question. Would you expect
`some of the particles from the resulting particle
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`population for the L5 -- LO54 formulation to result in
`particles that have less than 2 percent PEG?
` A. Well --
` THE VIDEOGRAPHER: Objection. Form. Asked,
`answered.
` THE WITNESS: If one is losing cholesterol,
`the composition of the other components is the
`proportions are going to change. If we have lower
`cholesterol, that conjugate lipid concentration is going
`up, not down.
`BY MR. WELLS:
` Q. Okay. So that's expert, it's your opinion that
`in a population of particles produced by the LO54
`formulation process, none of those particles would have
`less than 2 percent PEG?
` MR. ROSATO: Objection. Form. Asked and
`answered.
` THE WITNESS: I -- I'm not taking the bait
`on that one. The point is clear. The composition will
`change as a -- in a -- can change, I should be precise
`here. The composition can change as a function of the
`formulation process.
`BY MR. WELLS:
` Q. Oh, I have no problem with that. I'm just --
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`but I'm asking a specific question. In your expert
`opinion --
` A. Mm-hm.
` Q. -- do you hypothesize that none of the particles
`resulting from the LO54 formulation will have less than
`2 percent PEG?
` MR. ROSATO: Objection. Form. Asked and
`answered.
` THE WITNESS: In a population of particles,
`you may -- there will be likely especially as a function
`of the formulation, there's likely to be minor -- a
`range of compositions on a particle-by-particle basis.
`And how broad that range is is something that is likely
`formulation dependent.
`BY MR. WELLS:
` Q. Sure. So you can't say one way or the other
`whether or not the particles in the resulting -- any
`particles in the resulting population have 2 percent PEG
`as formulated or less than 2 percent PEG?
` MR. ROSATO: Objection. Form. Asked and
`answered.
` THE WITNESS: Based on my experience that
`the -- that you're focused on the peak at the
`distribution, not some distant wings of the bell-shaped
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` DAVID H. THOMPSON, PhD
`curve if we're using that analogy, we're not really
`worried about that, because often those get removed by a
`post-processing step whether filtration or some other
`integral, centrifugal step to clean up the population.
` So usually you're not focused on those minor
`components of the distribution. It's the heart of the
`distribution that you're, that is -- that's where your
`drug is, that's where your activity most likely lies.
`BY MR. WELLS:
` Q. And in your analysis you focused on that heart
`of the distribution curve?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: In my analysis I was
`considering largely the method of formulation and the
`likelihood that that method of formulation would deliver
`the particles of specified composition, and it's my
`opinion that that is the wrong technique and unreliable
`in producing particles of a -- with controlled
`composition.
`BY MR. WELLS:
` Q. And so your -- in your opinion you hypothesize
`that using the LO54 formulation, none of the particles
`would have -- resulting particles would have greater
`than 50 percent cationic lipid and less than 2 percent
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`conjugated lipid; is that right?
` MR. ROSATO: Objection. Form. Foundation.
`Asked and answered.
` THE WITNESS: What paragraph are we
`referring to?
`BY MR. WELLS:
` Q. I'm asking whether that's your opinion. In your
`opinion do you hypothesize that none of the particles
`resulting from the LO54 formulation would have greater
`than 50 percent cationic lipid and less than 2 percent
`conjugated lipid?
` MR. ROSATO: Same objection.
` THE WITNESS: It is -- it's a -- an
`expectation that they will -- that the composition will
`not be reflective of the nominal concentration, whether
`there is parts per million level, so one particle out of
`a million that fall within the regime, it's possible.
`BY MR. WELLS:
` Q. Now, let's go ahead and mark the next exhibit,
`which has previously been marked Exhibit 1005 to the
``435 IPR.
` (Exhibit 11 marked.)
`BY MR. WELLS:
` Q. Do you recognize the exhibit that's just been
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` DAVID H. THOMPSON, PhD
`handed to you?
` A. Yes.
` Q. And you've reviewed the Lin paper; correct?
` A. Yes.
` Q. Now, in the Lin paper, if you could turn to
`figure 4A which I believe is the heart of our discussion
`today.
` A. Yeah.
` Q. And for your reference, in your declaration I
`believe you're talking about this in the 100 range of
`your report, if you need to refer to it. Now, looking
`at paragraph 101 of your report, you state that, "Lin
`discloses that transfection efficiency for lipoplexes
`varies dramatically depending on which cationic lipid
`and non-cationic lipid are used." Do you see that?
` A. Give me a moment to find that statement.
` Q. I think it's the last full sentence on the page,
`41.
` A. (Reviews exhibit.)
` Yes, I see that statement.
` Q. And is it your experience that the same holds
`true in carrier formulations, that if you vary the
`cationic lipid or the non-cationic lipid, the
`transfection efficiency for the carrier formulation can
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`vary dramatically?
` MR. ROSATO: Objection. Form. I'm going to
`state a standing objection to anything in this document
`that is referring to content not cited in the petition,
`which I think is the vast majority of the document.
` THE WITNESS: So the -- this set of
`experiments is for plasmid DNA. You can tell from
`figure 5 the fact that you see the particles in an
`optical microscope means that these are microns in size.
`These are large, these are boulders, completely
`different both in terms of composition, not only in
`terms of cationic lipid and the non-cationic lipid
`composition, how they were fabricated this series of
`experiments was locked in on a single N-to-P ratio;
`right. So it didn't -- it's not even searching
`parameter space in terms of ratio of cationic lipid to
`cargo. So this is just a single slice through a
`mountain range of -- of possible maxima in minima in
`performance. So this -- that's the perspective I bring
`to this dataset.
`BY MR. WELLS:
` Q. Sure. And we'll get into that data in a minute,
`but I'm just trying to figure out whether for the
`nucleic acid lipid carrier formulations described in the
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` DAVID H. THOMPSON, PhD
``435 patent, whether in your opinion varying the
`cationic lipid and the non-cationic lipids used could
`dramatically affect the transfection efficiency.
` MR. ROSATO: Objection. Form. Foundation.
`Scope.
` THE WITNESS: The... So what I'm -- what
`I'm understanding is being asked is does the composition
`affect transition -- pardon me, transfection
`performance. And the answer is yes.
`BY MR. WELLS:
` Q. Now, looking at Lin and Ahmad, and if we go to
`figure 4A, which I believe is...
` A. Mm-hm.
` Q. There's a series of formulations depicted there;
`is that right?
` MR. ROSATO: Objection. Form. Foundation.
`Sorry, question. Have we -- you've mentioned Ahmad.
`Have we introduced that reference?
` MR. WELLS: We haven't.
` MR. ROSATO: Okay. Sorry. Just managing my
`documents.
` THE WITNESS: So 4A shows three different
`cationic lipids using the same non-cationic lipid at a
`2.8 N-to-P ratio. That's what's uniform throughout this
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` DAVID H. THOMPSON, PhD
`entire set of experiments.
`BY MR. WELLS:
` Q. And the N-to-P ratio, is that related to the
`charge density?
` MR. ROSATO: Objection. Form. Foundation.
`I state a standing objection to any questions on Ahmad
`as well to the extent that they're discussing material
`not cited in the petition, which again is the vast
`majority of the document.
` THE WITNESS: So the -- the DOTAP structure
`I'm familiar with, that's a hard charge, that's in other
`words a quaternary ammonia compound. The other three
`I'd have to refamiliarize myself whether they are
`protonatable or not.
`BY MR. WELLS:
` Q. So sitting here today you don't know whether
`DOSPA is an ionizable cationic lipid?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: That's a -- what's of interest
`to me is the performance. And the behavior of the
`material. And whether it happens to be ionizable or not
`is, I believe, a link to a hypothesis that may or may
`not be correct.
`BY MR. WELLS:
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` DAVID H. THOMPSON, PhD
` Q. But you sitting here today you don't know
`whether DOSPA is ionizable; correct?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: If that's important to answer,
`I can go look the structure up and answer that question
`directly and be specific.
`BY MR. WELLS:
` Q. Okay. Well, sitting here right now without
`doing further research, you don't know one way or the
`other whether it's ionizable; correct?
` MR. ROSATO: Objection. Form. Foundation.
`Asked and answered.
` THE WITNESS: Let's see if there are actual
`chemical names here.
` (Reviews exhibit.)
` So DMRIE is a protonatable species.
`DOSPA...
` (Reviews exhibit.)
` DOSPA also appears to be protonatable.
`BY MR. WELLS:
` Q. And now looking at figure 4A on the top it says,
`"Mole fraction of DOPC." Do you see that?
` MR. ROSATO: Objection. Form. Foundation.
` THE WITNESS: X axis is mole fraction. DOPC
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` DAVID H. THOMPSON, PhD
`Y axis is the luciferase expression.
`BY MR. WELLS:
` Q. Right. And so the X axis because DOPC is
`increasing there and that's the -- one of the components
`of the carriers presented, the other portion of the
`carrier is the cationic lipid; correct?
` MR. ROSATO: Objection. Form.
` THE WITNESS: (Reviews exhibit.)
` The -- the way I read the formulation, so
`they're putting specified -- or they're controlling
`composition at the level of mixing the lipids in
`chloroform, chloroform methanol, evaporating the
`solvent, and then adding aqueous solution AND vortexing.
` So how representative that the particles
`formed by that are representing the actual composition
`that was added is -- there's no analysis here of what
`those particles actually contain. So there is, I would
`expect, experimental variation. But ultimately what
`is -- what's being reported here is tied to that nominal
`composition.
`BY MR. WELLS:
` Q. Sure. And so if we look at the mole fraction of
`DOPC indicated at 0.2, at least the nominal percentage
`of cationic lipid there would be 80 percent; correct?
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` DAVID H. THOMPSON, PhD
` A. That is at the nominal concentrations, that's
`right, that's what the mole fraction means. It's 20
`percent DOPC, 80 percent cationic lipid, one of the
`three cationic lipids listed.
` Q. Right. And then as the mole fraction of
`cationic lipid -- well, let's talk about them
`individually here. For DOTAP, DOPC as the cationic
`lipid percentage increases, does the trans -- reported
`transfection efficiency increase?
` MR. ROSATO: Objection. Form.
` THE WITNESS: If I understand the question
`correctly, does the transfection efficiency increase
`when the cationic lipid concentration increases.
`BY MR. WELLS:
` Q. Correct.
` A. And the answer is there's no -- in this
`experiment, there's no apparent difference in any of the
`cationic lipids from 0 to .2, their performance appears
`to be similar.
` Q. Right. But so I think you were referring to the
`0.2 as the mole fraction of DOPC.
` A. Mm-hm.
` Q. So what you're saying is between 80 and 100
`percent cationic lipid there doesn't appear to be a
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