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`UNITED STATES PATENT AND TRADEMARK OFFICE
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`______________________________________________________
`
` MODERNA THERAPEUTICS, )
` INC., )
`)
`Petitioner, )
`) NO. IPR2019-00554
`vs. )
`) PATENT NO. 8,058,069
` ARBUTUS BIOPHARMA )
` CORPORATION, )
`)
`Patent Owner. )
`)
`______________________________________________________
`
`DEPOSITION UPON ORAL EXAMINATION OF
`DAVID H. THOMPSON, Ph.D.
`______________________________________________________
`WEDNESDAY, JANUARY 15, 2020
`9:04 A.M.
`701 5TH AVENUE, SUITE 5100
`SEATTLE, WASHINGTON
`
`REPORTED BY: VICKY L. PINSON, RPR-CCR Washington 2559
`California No. 9845; Oregon No. 16-0442
`JOB NO. 3835178
`PAGES 1 - 211
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` A P P E A R A N C E S
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`F O R T H E P E T I T I O N E R :
` C . M A C L A I N W E L L S
` I r e l l & M a n e l l a , L L P
` 1 8 0 0 A v e n u e o f t h e S t a r s , S u i t e 9 0 0
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` 3 1 0 . 2 7 7 . 1 0 1 0
` m w e l l s @ i r e l l . c o m
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`F O R T H E P A T E N T O W N E R :
`
` M I C H A E L T . R O S A T O
` L O R A M . G R E E N , J D , P h . D .
` W i l s o n S o n s i n i G o o d r i c h & R o s a t i
` 7 0 1 5 t h A v e n u e , S u i t e 5 1 0 0
` S e a t t l e , W A 9 8 1 0 4
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` l g r e e n @ w s g r . c o m
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` I N D E X
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`EXAMINATION BY PAGE
` Mr. Wells 4
` Mr. Rosato 203
`
`EXHIBITS FOR IDENTIFICATION PAGE
`Exhibit 1 Declaration of David H. 5
` Thompson, Ph.D.
`
`Exhibit 2 Curriculum Vitae of David H. 5
` Thompson
`Exhibit 3 US Patent 8,058,069 B2 31
`Exhibit 4 Publication '196 107
`Exhibit 5 US Patent Application 112
` Publication 2006/0134189 A1
`
`Exhibit 6 Excerpt from the Prosecution 158
` History
`Exhibit 7 US Patent Application 160
` Publication 2006/0008910 A1
`
`Exhibit 8 US Patent Application 191
` Publication 2006/0240554 A1
`Exhibit 9 Article: 197
` Diffusible-PEG-Lipid
` Stabilized Plasmid Lipid
` Particles
`
`Exhibit 10 Orange Book: Approved Drug 201
` Products with Therapeutic
` Equivalence Evaluations
`
`Exhibit 11 Deposition of David H. 207
` Thompson, Ph.D. - 02-04-2019
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` Seattle, Washington; January 15, 2020
`
` 9:04 a.m.
`
` * * *
`
` DAVID H. THOMPSON, Ph.D.,
`
`sworn as a witness by the Certified Court Reporter,
`
`testified as follows:
`
` EXAMINATION
`
`BY MR. WELLS:
`
` Q. Good morning, Dr. Thompson. Welcome back.
`
`We've been through this a couple of times. Do you
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`remember the general rules of a deposition?
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` A. Yes.
`
` Q. You understand that you're under oath and
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`obligated to tell the truth and the whole truth?
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` A. Yes.
`
` Q. And if you'll allow me to finish my questions
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`before you answer, I'll try to make sure that you can
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`finish your answers before I begin the next question
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`and make sure we don't talk over each other.
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` A. Yes.
`
` Q. And if you don't understand any of my
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`questions, I'll see if I can clarify them. Any reason
`
`you can't give your best testimony here today?
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` A. No.
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` Q. Now, you submitted a declaration in the IPR
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`relating to the '069 Patent. Is that correct?
`
` A. Yes.
`
` Q. And when I said '069 Patent, you understand
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`that I'm referring to U.S. Patent No. 8.058,069?
`
` A. Yes.
`
` MR. WELLS: And so let's go ahead and mark
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`as Exhibit 1 a copy of your Declaration.
`
` (Exhibit 1 was marked for identification.)
`
` MR. ROSATO: It's Exhibit 23 already
`
`entered.
`
` MR. WELLS: And let's go ahead and mark as
`
`Exhibit 2 to your deposition, which is Exhibit 2032 to
`
`the IPR, a copy of your CV.
`
` (Exhibit 2 was marked for identification.)
`
` Q. Okay. And is your CV current and up-to-date?
`
` A. I'm just checking that. Yes.
`
` Q. Now, when I was looking through your CV, I
`
`think I noticed that you had published nine additional
`
`articles since you had provided testimony previously in
`
`the IPR relating to the '435 and the '127 patents.
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`Does that sound right?
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` A. Let me get the timeline here. I'm sorry,
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`could you repeat the question? I want to make sure I
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`have it.
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` Q. When I was looking through your CV, it
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`appeared that you had published nine additional
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`articles since we had previously spoken at your
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`deposition in the '435 and '127 IPRs. Does that sound
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`right to you?
`
` A. So my recollection is that the last time we
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`had spoken was in January of 2019, and so it would have
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`been, by that time it would be publications of 146. So
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`by my account that would be two, four, five
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`publications that appeared. There are a number that
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`are still in process that are described here as in
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`preparation.
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` Q. And do these additional publications relate to
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`your work with polymer carrier chemicals?
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` A. These are -- one of those five is dealing with
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`polymer carrier particles, yes.
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` Q. Do any of those five additional publications
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`deal with cationic lipid carrier particles?
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` A. Since our last meeting these five that have
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`appeared are focused on high throughputs. This is high
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`throughputs screening machine learning. And the
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`development of a polymer carrier system. So none of
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`these that have yet, that have appeared are actually
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`describing the use of cationic lipids.
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` Q. And so regarding your publications, you
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`haven't published on cationic lipid -- cationic LNPs.
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`Correct?
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` A. That actually is incorrect. I have published
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`on cationic lipid particles. Just not since our last,
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`since our last meeting.
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` Q. And do you have any additional patents that
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`you've obtained since our last meeting?
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` A. So on page 15 the item that is listed No. 8,
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`that actually is now issued, and that would be the only
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`change.
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` Q. And does your patent work -- since our last
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`meeting, do any of those patents relate to cationic
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`LNPs?
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` A. The patents that are listed here are focused
`
`on polymer carriers for delivery. Both synthetic
`
`polymer and biopolymer, trying to advance the field of
`
`beyond cationic lipid particles.
`
` Q. And the focus of your work is on polymer lipid
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`carrier particles. Correct?
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` A. At present our focus is on polymer carriers.
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`At the time of the '069, we were very actively involved
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`in lipid particle, specifically bioresponsive lipid
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`particles that would degrade in a program manner. But
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`that is a theory that at present we typically use lipid
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`nanoparticles more or less as a benchmark for comparing
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`our polymer carrier systems.
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` Q. And regarding your prior work at the time of
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`the '069 Patent, just so we're clear as to the time
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`we're talking about, what time frame are you referring
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`to?
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` A. So this would be in, with respect to our work
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`beginning in 1994 and extending actually actively in
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`the lipid delivery area through the citation 110. So
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`2014 is where our, where the heart of the paper, the
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`subject is focused on cationic lipid formulation.
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` Q. Did you say Publication 110?
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` A. Yes. Actually, yes, 110, entitled
`
`"DNA-Epitope Vaccine Provided Efficient Protection to
`
`Mice Against Lethal Dose of Influenza A Virus H1N1."
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`So that's a paper describing a cationic lipid that we
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`had developed that was degradable, and we were
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`evaluating it as a potential vaccine in a mouse model.
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` Q. Now, I think that you mentioned earlier that
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`you had done some research relating to degradable lipid
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`particles. Correct?
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` A. Yes.
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` Q. Were those all cationic lipid particles or --
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` A. Not all cationic. There were some degradable
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`phospholipids, actually natural products, so-called
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`plasmid coating lipids that are found predominantly in
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`brain sarcoplasm as only malate (phonetic) source. It
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`was kind of a natural choice because being natural
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`products, they would have an intrinsic metabolic
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`pathway, not only for their synthesis, but also for
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`their degradation. And so it seemed like a natural
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`family of materials to explore for nucleic acid
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`delivery applications, since it got right to the heart
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`of what the problem was from the very first cationic
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`lipid publication, was their toxicity.
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` So that was really where we first established
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`our efforts. We then -- so that's for phospholipid.
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`That work, as I mentioned, the first publication
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`appeared in '92, actually. That would be in the
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`citation or publication listed here on page 3, Nos. 16
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`and 17, plasmalogen liposomes, and then extending into
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`the mid 2000s where we were essentially using the same
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`platform -- or I should say the same chemistry, to be
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`more precise, the same phenyl ether, also called vinyl
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`ether chemistry. But repositioning it to the position
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`between a polyethylene glycol and a lipid anchoring
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`group.
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` And so it, from a chemical reaction point of
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`view it displayed the same kinds of reactivity
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`profiles. But it was, instead, a non-cationic
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`non-phospholipid. So a lipid that was formulated with
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`other fusogenic lipids. So a slightly different
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`strategy to promote, and to some, escape into nucleic
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`acid. So that work continued, as I say, into the
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`2000s.
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` Q. Well, let's start with you described
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`Publications 15 and 16 that relates to liposomes. Is
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`that right?
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` A. 16 and 17.
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` Q. Oh, I'm sorry. I think you said 15 and 16.
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` A. I mis -- my apologies, I misspoke. So it's
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`16, "Photoinduced Morphology Changes in Plasmalogen
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`Liposomes Using Visible Light." And 17, "Triggered
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`Release of Hydrophilic Agents From Plasmalogen
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`Liposomes Using Visible Light Or Acid."
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` Q. And did either of those publications involve
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`cationic LNPs?
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` A. These are focused on hydrophilic agents.
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`They're actually, structurally they were different
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`compounds than nucleic acids.
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` Q. And, in fact, you've offered opinions that
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`liposomes are different than LNPs. Correct?
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` MR. ROSATO: Objection to form.
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`Foundation.
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` A. The use of liposome is conveying that there's
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`an aqueous compartment where a cargo -- in this case
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`it's, in '92 it was a model cargo. Later that cargo
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`evolved to active compounds like siRNA and plasma DNA.
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` Q. When did you actually first work with cationic
`
`LNPs?
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` MR. ROSATO: Objection to form.
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` A. So the first publication of working with a
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`nucleic acid is Publication 48. So that's 2002.
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`"Formation of Plasmid-Plasmid-Based Transfection
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`Complexes With an Acid-Labile Cationic Diplasmenyl
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`Lipid: In Vitro and in Vivo Gene Transfer."
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`Pharmaceutical Research 2002, Volume 19, pages 1289 to
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`1298.
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` Q. And would you consider the transform mechanism
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`that you developed to be a cationic LNP as described in
`
`that paper?
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` MR. ROSATO: Objection to form.
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` A. Please restate the question. I'm not clear
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`exactly what you're asking.
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` Q. I'm asking whether you actually developed
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`cationic LNPs as part of your work as subscribed in
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`that paper.
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` MR. ROSATO: Objection to form.
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`Foundation.
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` A. This paper is describing the development of
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`cationic lipid referred to as BCAT. Or at least that's
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`the acronym that we gave to it. That's referring to
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`bis vinyl ether plasmalogen lipid. And our own
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`control, where the vinyl ether was reduced. So, in
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`other words, unreactive. And using it or comparing it
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`to the standard cationic lipid in the field at the
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`time.
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` Q. And do you recall what the standard cationic
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`lipid in the field at the time was?
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` A. I would actually have to review that to be
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`certain.
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` Q. So this paper, you didn't actually make
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`cationic lipid nanoparticles as part of your research
`
`in this paper. Is that right?
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` MR. ROSATO: Objection to form and
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`foundation.
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` A. That's incorrect. As I said, this is a lipid
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`formulation with nucleic acid.
`
` Q. Okay. I just want to make sure that I'm
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`clear. So in your publication that you list as
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`Publication 48 in your CV, it's your testimony that the
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`particles described therein are cationic lipid
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`nanoparticles?
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` MR. ROSATO: Objection to form.
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`Foundation.
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` A. Publication 48 is "Formation of Plasmid-Based
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`Transfection Complexes with an Acid-Labile Cationic
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`Diplasmenyl Lipid." That lipid is what we synthesized.
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`That synthetic lipid was formulated with plasma, and
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`tested both in vitro and in vivo.
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` Q. Okay. And is the plasmid-based transfection
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`complex a cationic LNP in your opinion?
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` MR. ROSATO: Objection to form and
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`foundation.
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` A. The, at the time of this Publication and the
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`way these were prepared, and based on the structural
`
`information that's in that paper, these are more
`
`appropriately described as polyplex -- or pardon me,
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`lipoplex.
`
` Q. And you've offered opinions that lipoplexes
`
`are different than cationic LNPs. Correct?
`
` MR. ROSATO: Objection to form.
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`Foundation.
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` A. As we discussed last time we met, there are
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`substantial differences between a stabilized nucleic
`
`acid lipid particles, so-called SNALP, and lipoplex
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`with regard to, really, many different properties.
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` Q. I've been using the term cationic LNP, but I'm
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`happy to use the term "SNALP," if you prefer. Do you
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`have a preference?
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` MR. ROSATO: Objection to form.
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` A. Actually, as a scientist I much prefer, like,
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`a real description rather than a brand name. So, like
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`a particle that has a identifiable property, a size, a
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`composition, a well-established composition, a
`
`resistant nuclease degradation, a particular shape is
`
`what is more -- is the way scientists communicate to
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`one another. The other is just branding.
`
` Q. So Publication 48 dealt with what you would
`
`call lipoplexes. Correct?
`
` A. Um-hmm.
`
` Q. When was the first time that you worked with
`
`actual cationic LNP as you understand that term?
`
` MR. ROSATO: Objection to form.
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` A. So the, what is it that -- so that I can
`
`answer the question precisely, what is it that you're
`
`referring to as cationic LNP.
`
` Q. You're the expert. You've read the '069
`
`Patent. Correct?
`
` A. Yes.
`
` Q. And you have an understanding that that's
`
`directed towards carrier particles that are sometimes
`
`referred to in the industry as cationic LNPs?
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` MR. ROSATO: Objection. Form and
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`foundation.
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` A. I understand what the '069 is describing. So
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`what's your question?
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` Q. Do you have an understanding of what a
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`cationic LNP is, in the context of the '069 Patent?
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` MR. ROSATO: Objection to form and
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`foundation.
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` A. I have an understanding of what the authors of
`
`this patent are describing. The '069 Patent.
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` Q. In the '069 Patent what is your understanding
`
`of what a cationic LNP is?
`
` MR. ROSATO: Objection to form.
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` A. So this is my definition. It is referring to
`
`a stabilized nucleic acid lipid particle. Nucleic acid
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`is protected by a lipid coating, and stabilized,
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`meaning both colloidally stabilized due to the presence
`
`of polyethylene glycol on the surface, and stabilized
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`from the prospective of serum stability. That the
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`cargo remains intact when exposed to nuclease.
`
` Q. And using your understanding of what a CLNP --
`
`or a cationic LNP is in the context of the '069 Patent,
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`when did you first work with a cationic lipid
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`nanoparticle?
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` MR. ROSATO: Objection to form and
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`foundation.
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` A. So it would be Publication 56 of 2003,
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`"Intracellular Delivery of DNA and Proteins Using Vinyl
`
`Ether-Based Drug Delivery Vehicles."
`
` Q. And were the vinyl ether-based drug delivery
`
`vehicles described therein what you would consider to
`
`be cationic LNPs?
`
` MR. ROSATO: Objection to form.
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`Foundation.
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` A. This publication is describing the expanded
`
`application of the BCAT lipids that we had developed,
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`and their more-controlled formulation to give better
`
`particle-sized distribution.
`
` Q. And so were the formulations of the delivery
`
`vehicles that you developed cationic LNPs based upon
`
`your understanding of what that term means in the
`
`context of the '069 Patent?
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` MR. ROSATO: Objection to form.
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`Foundation. Asked and answered.
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` A. The particles are -- this paper is describing
`
`the formulation and delivery efficacy and the
`
`morphology of the particles. So at the time of this
`
`publication, it's what was understood as a nucleic acid
`
`lipid particle.
`
` Q. And to be more clear, it was what you
`
`considered to be a nucleic acid lipid nanoparticle?
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` MR. ROSATO: Objection to form.
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`Foundation.
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` A. The work at this time did establish that
`
`these, that it was a distribution of particles. Some
`
`of those particles, most of those particles actually
`
`were in the, in the nanometer size range. Submicron
`
`size range. So what we refer to as in the nanometer or
`
`nano size range.
`
` Q. So just looking at No. 56 in your list of
`
`publications from 2003, you developed cationic lipid
`
`nanoparticles in your work that led to that
`
`publication. Is that right?
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` MR. ROSATO: Objection to form.
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`Foundation.
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` A. This work is describing the use of a synthetic
`
`cationic lipid that we had developed and were testing
`
`its formulation with nucleic acids and proteins for
`
`delivery purposes. And the particles formed were in
`
`the submicron size range of well-controlled submicron
`
`size range.
`
` Q. And so you would consider those to be cationic
`
`lipid nanoparticles. Correct?
`
` MR. ROSATO: Objection to form.
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`Foundation. Asked and answered.
`
` A. As I described, the particles are in the
`
`nanometer size range, and they're lipid-based. They're
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`nucleic acid. Contain nucleic acid cargo. So they
`
`satisfy the criterion of nucleic acid lipid particle of
`
`nanometer dimension.
`
` Q. And were these -- earlier you talked about
`
`your understanding of CLNPs in the context of the '069
`
`Patent, including that they were stable and that the
`
`payload was encapsulated. Do you recall that
`
`discussion?
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` MR. ROSATO: Objection to form.
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`Misstates.
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` A. What I recall speaking about is stability is
`
`one of the key criteria.
`
` Q. And using those criteria, your understanding
`
`of what a CLNP is in the context of the '069 Patent,
`
`would you consider the carrier particles developed as
`
`described in No. 56 of your list of publications to
`
`meet those criteria?
`
` MR. ROSATO: Objection to form. Asked and
`
`answered.
`
` A. So I am unclear what you mean by "CLNP," so I
`
`would need some precision on that before I could answer
`
`the same question that you've been asking.
`
` Q. I'm using your explanation of CLNP as
`
`described in the context of the '069 Patent where you
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`said it was a stable nucleic acid lipid particle.
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` MR. ROSATO: Objection to form.
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` A. I did not use the term "CLNP." That's your
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`mutation. As I said earlier, I don't -- the
`
`imprecision of the, of the cartoons that we draw on our
`
`papers and the kinds of labels that we give lack
`
`precision. And so I speak by -- as a scientist, I
`
`speak in terms of measurable properties. That's the
`
`preferred way.
`
` So 56 is referring to a cationic lipid that
`
`has been formulated into a nucleic acid particle, and
`
`it's testing for its delivery characteristic.
`
` Q. And because that particle was in the submicron
`
`size, you consider it to be a cationic lipid
`
`nanoparticle. Certain of the particles.
`
` MR. ROSATO: Objection to form. Asked and
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`answered.
`
` A. I, I have nothing to add to what I've already
`
`said.
`
` Q. I just want to make sure that I have a clear
`
`understanding. So my understanding is that the
`
`particles described in Paragraph 56 had a cationic
`
`lipid and were formed into nucleic acid particles, and
`
`that certain of those particles had a submicron size,
`
`and, hence, you would consider them to be cationic
`
`lipid nanoparticles. Correct?
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` MR. ROSATO: Objection to form. Asked and
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`answered.
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` A. The paper describes the use of a cationic
`
`lipid to form lipid nucleic acid nanoparticles and
`
`their testing. The last part of your statement is
`
`not -- is yours. Not what I'm saying.
`
` Q. After Publication 56, what was the next work
`
`that you did with cationic lipid nanoparticles?
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` MR. ROSATO: Objection to form.
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`Foundation.
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` A. So Citation 94 on page 9, "Effective Targeted
`
`Gene Delivery to Dendritic Cells Via Synergistic
`
`Interaction of Mannosylated Lipid with DOPE and BCAT,"
`
`Biomacromolecules 2012. The paper is a publication
`
`describing the use of the degradable cationic lipid
`
`that we have been developing and trying to target it to
`
`dendritic cells as a potential vaccine.
`
` Q. And when you say the degradable cationic
`
`lipid, are you talking about BCAT?
`
` A. Yes, that's in the title "Effective Targeted
`
`Gene Delivery to Dendritic Cells Via Synergistic
`
`Interaction of Mannosylated Lipid with DOPE and BCAT."
`
`So BCAT is that cationic lipid that we had developed.
`
` Q. Do you recall whether BCAT was an itemizable
`
`cationic lipid?
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` A. BCAT was a, or is a fixed-charge lipid that is
`
`designed to lose its charge by a hydrolytic mechanism.
`
`So decrease the toxicity of the lipid through a
`
`different pathway than was used at the time.
`
` Q. So for BCAT, the charge would decrease over
`
`time, and hence the toxicity would decrease. Is that
`
`right?
`
` MR. ROSATO: Objection to form and
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`foundation.
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` A. The design of BCAT was to actually shed the
`
`cationic group from the lipid scaffold so that it would
`
`be a water-soluble excretable fragment.
`
` Q. So by shedding the cationic group that would
`
`decrease the charge of the BCAT. Is that right?
`
` A. Actually, that is not quite right. The BCAT
`
`is the intact molecule. And when it's formulated with
`
`the nucleic acid, you have an electrostatic complex.
`
`And that complex is held together in any lipid nucleic
`
`acid nanoparticle. It's held together by lipid
`
`hydrophobic interaction. So the design of this lipid
`
`is to actually remove the cationic segment of BCAT so
`
`it's no longer BCAT, but it's a small, cationic,
`
`excretable fragment that allows the complex to
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`decomplex.
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` Q. And the delivery particles that are described
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`in entry 94 of the publications list in your CV, in
`
`your opinion, were cationic lipid nanoparticles. Is
`
`that right?
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` MR. ROSATO: Objection to form.
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`Foundation.
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` A. These were complexes with, where we were
`
`testing different ratios of mannosylated lipid, DOPE,
`
`and BCAT, to evaluate their efficacy towards dendritic
`
`cell transfection.
`
` Q. And were the carrier particles that you
`
`developed cationic lipid nanoparticles, based upon your
`
`understanding?
`
` MR. ROSATO: Objection to form. Asked and
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`answered.
`
` A. These were targeted lipid nucleic acid
`
`complexes in a size range that could be internalized by
`
`cells. So in that submicron size range.
`
` Q. And so would you consider that to be cationic
`
`lipid nanoparticles?
`
` MR. ROSATO: Objection to form. Asked and
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`answered.
`
` A. As I've said before, that is, that is -- lacks
`
`the kinds of specificity that I prefer. This is a
`
`plasmid degradable cationic lipid complex that is
`
`targeted, fusogenic, and tested for transfection
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`efficiency.
`
` Q. Was a conjugated lipid in the delivery
`
`particles that you developed that are described in
`
`entry 94?
`
` A. It's been some time since this work was done,
`
`so I'd actually have to review that detail. So I want
`
`to, I guess, leave it at that. I would have to review
`
`the document to be certain.
`
` Q. And after paragraph 94, when was the next time
`
`that you worked with cationic LNPs?
`
` MR. ROSATO: Objection to form and
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`foundation.
`
` A. So Publication 98 on page 10, also same year.
`
`It's also describing a delivery of nucleic acid. This
`
`focused on specifically the H1N1 swine influenza virus
`
`with the target of -- since water fowl, swine and
`
`humans share a common set of epitomes, they shuffle
`
`epitomes, which is why we struggle constantly with an
`
`influenza. Because there's epitomes moving from those
`
`species.
`
` This is aiming to -- since we have a hard time
`
`getting humans to be vaccinated, the idea was to
`
`vaccinate a swine with an influenza virus that
`
`presumably that population you can treat uniformly. So
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`this is a nucleic acid formulated, even though it's not
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`specified in the title, this is also using BCAT in the
`
`formulation and testing for the cytacon response in
`
`cells. So it's using cationic lipid, has a nucleic
`
`acid, and is formulated to be in the sub-nanometer --
`
`pardon me -- submicron-sized regime.
`
` Q. And do you recall whether or not a conjugated
`
`lipid was included in those carrier particles?
`
` A. I'd have to look at the Viral Immunology 2012
`
`paper to be, to be certain to answer with certainty
`
`your question.
`
` Q. Do you recall whether a phospholipid was
`
`included in those carrier particles?
`
` A. My recollection of this body of work is that
`
`we were using a phospholipid. We were blending in
`
`di-oleyl phosphatidyl ethanolamine, an unknown fusogen,
`
`or sometimes referred to in the literature as a helper
`
`lipid, to help promote into some escape and delivery of
`
`the nucleic acid into the cytosol cell. So these
`
`formulations were using mannos to actually engage the
`
`dendritic cell population that helps with the, or I
`
`should say is the primary target for this particular
`
`vaccine. So it's a mannosylated lipid, a DOPE, and
`
`either a BCAT or a benchmark cationic lipid.
`
` Q. What was the function of the mannosylated
`
`lipid?
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` A. That is serving as the targeting agent. So
`
`that's many infectious agents have mannos on their
`
`surface. And that's what's recognized. That's what
`
`generates the immune recognition. In this case the
`
`dendritic cells are using that as a clue that those
`
`particles are to be internalized.
`
` Q. The SNALPs that are described in the '069
`
`Patent don't involve using a mannosylated lipid.
`
`Correct?
`
` MR. ROSATO: Objection to form and
`
`foundation.
`
` A. The '069 Patent does not specify a
`
`mannosylated lipid. The mannosylated lipid we are
`
`using in this study is non-ionic. It has a stealth
`
`character in the sense that it can be functionally
`
`viewed as a conjugated lipid, providing that same kind
`
`of protective function. So it is, well --
`
` Q. Okay. So the '069 Patent, the SNALPs
`
`described therein don't use -- or don't describe using
`
`the mannosylated lipid, but a mannosylated lipid could
`
`be equated to the conjugated lipid that's described.
`
`Is that fair?
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` MR. ROSATO: Objection to form.
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`Foundation.
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` A. What I was attempting to say is that the
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`mannosylated lipid is a component of