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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`MODERNA THERAPEUTICS, )
`INC., )
` ) No. IPR019-00554
` Petitioner, )
` ) PATENT NO. 8,058,069
`v. )
` )
`ARBUTUS BIOPHARMA )
`CORPORATION, )
` )
` Patent Owner. )
`_________________________________________________________
`
`VIDEO RECORDED DEPOSITION OF THOMAS J. ANCHORDOQUY, PH.D.
` March 24, 2020
`_________________________________________________________
`
` Page 1
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`YOM: Full Service Court Reporting, A Veritext Company
`800.831.6973
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`Page 1
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`ARBUTUS - EXHIBIT 2043
`Moderna Therapeutics, Inc. v. Arbutus Biopharma Corporation
`IPR2019-00554
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`MODERNA THERAPEUTICS, )
`INC., )
` ) No. IPR019-00554
` Petitioner, )
` ) PATENT NO. 8,058,069
`v. )
` )
`ARBUTUS BIOPHARMA )
`CORPORATION, )
` )
` Patent Owner. )
`_________________________________________________________
`
`VIDEO RECORDED DEPOSITION OF THOMAS J. ANCHORDOQUY, PH.D.
` March 24, 2020
`_________________________________________________________
`
` Page 1
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`YOM: Full Service Court Reporting, A Veritext Company
`800.831.6973
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`Page 1
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`ARBUTUS - EXHIBIT 2043
`Moderna Therapeutics, Inc. v. Arbutus Biopharma Corporation
`IPR2019-00554
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
`APPEARANCES:
`ON BEHALF OF THE PETITIONER (Via videoconference):
` C. MACLAIN WELLS, ESQ.
` Irell & Manella, LLP
` 1800 Avenue of the Stars, Suite 900
` Los Angeles, California 90067
` Phone: 310-277-1010
` Email: mwells@irell.com
`ON BEHALF OF THE PATENT OWNER (Via videoconference):
` MICHAEL T. ROSATO, ESQ.
` NORA M. GREEN, JD, Ph.D.
` Wilson Sonsini Goodrich & Rosati
` 701 Fifth Avenue, Suite 5100
` Seattle, Washington 98104
` Phone: 206-883-2500
` Email: mrosato@wsgr.com
` lgreen@wsgr.com
`Also Present: Megan Young, Esq. (Via videoconference)
` Kyle Hill (Via videoconference)
` Jerry DeBoer, videographer
`
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
` PURSUANT TO WRITTEN NOTICE and the appropriate
`
`Rules of Civil Procedure, the video recorded deposition of
`
`THOMAS J. ANCHORDOQUY, PH.D., called for examination by
`
`the Patent Owner, was taken at the offices of
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`Stevens-Koenig Reporting, 700 Seventeenth Street, Suite
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`1750, Denver, Colorado, commencing at 10:02 a.m. on
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`March 24, 2020, before Bonnie Carpenter Johnshoy, CSR,
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`RPR, CRR, and Notary Public in and for the State of
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`Colorado.
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` Page 3
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
` I N D E X
`EXAMINATION: PAGE
` By Mr. Rosato 7
` By Mr. Wells 77
`EXHIBITS: PAGE
`Exhibit 1001 United States Patent
` 8,058,069 28
`
`Exhibit 1015 United States Patent
` Application Publication
` 2006/0008910 11
`
`Exhibit 1020 Declaration of Thomas J.
` Anchordoquy, Ph.D. in Support
` of Petitioner's Reply to Patent
` Owner's Response 25
`Exhibit 2040 Patent Owner: One-Way
` Particle Variation graph 73
`
`Exhibit 2041 Patisiran N/P Ratio 66
`
`Exhibit 2042 Hypersensitivity and Loss
` of Disease Site Targeting
` Caused by Antibody Responses
` to PEGylated Liposomes 32
`
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
` P R O C E E D I N G S
`
` VIDEOGRAPHER: Good morning. We are going
`
`on the record at 10:02 a.m. on March 24th, 2020.
`
` Please note that microphones are sensitive
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`and may pick up whispering, private conversations, and
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`cellular interference. Please turn off all cellphones or
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`place them away from the microphones, as they can
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`interfere with the deposition audio.
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` Audio and video recording will continue to
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`take place unless all parties agree to go off the record.
`
` This is Media Unit 1 of the video-recorded
`
`deposition of Thomas J. Anchordoquy, Ph.D., taken by
`
`counsel for Patent Owner in the matter of Moderna
`
`Therapeutics, Inc., versus Arbutus Biopharma Corporation,
`
`filed in the United States Patent and Trademark Office
`
`before the Patent Trial and Appeal Board, Case Number
`
`IPR2019-00554.
`
` This deposition is being held at
`
`Stevens-Koenig Reporting, a Veritext company, located at
`
`700 Seventeenth Street, Suite 1750, Denver, Colorado.
`
` My name is Jerry DeBoer from the firm of
`
`Veritext, and I'm the videographer. The court reporter is
`
`Bonnie Carpenter from the firm of Veritext.
`
` I am not related to any party in this
`
`action, nor am I financially interested in the outcome.
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` Page 5
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
` Counsel and all present in the room and
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`everyone attending remotely will now state their
`
`appearances and affiliations for the record. If there are
`
`any objections to proceeding, please state them at the
`
`time of your appearance, beginning with the noticing
`
`attorney.
`
` MR. ROSATO: Mike Rosato on behalf of
`
`Patent Owner.
`
` MS. GREEN: Lora Green on behalf of Patent
`
`Owner.
`
` MR. WELLS: Anybody else on behalf of
`
`Patent Owner, or is that it?
`
` MS. YOUNG: Sorry. Megan Young on behalf
`
`of Patent Owner.
`
` MR. HILL: Kyle Hill on behalf of Patent
`
`Owner.
`
` MR. WELLS: I think that might be it.
`
`Maclain Wells of Irell & Manella on behalf of petitioner,
`
`Moderna.
`
` THE COURT REPORTER: Is that it?
`
` MR. WELLS: Yes.
`
` THOMAS J. ANCHORDOQUY, Ph.D.,
`
`having been first duly sworn, was examined and testified
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`as follows:
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` Page 6
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
` EXAMINATION
`
`BY MR. ROSATO:
`
` Q. Good morning, Dr. Anchordoquy.
`
` A. Good. Anchordoquy. Good morning,
`
`Mr. Rosato.
`
` Q. Have you been deposed before, Doctor?
`
` A. Yeah. I've been deposed twice. It's
`
`listed on my CV. It's been, I'd say, least at least ten
`
`years since I was deposed, but I was deposed twice before.
`
` Q. Have you ever done a deposition by video
`
`conference as we are doing today?
`
` A. No. That's a new one for me.
`
` Q. Okay. It might be a bit of a -- a new
`
`experience in some ways for all of us, so I'm just going
`
`to emphasize a few things that you may already know, but
`
`bear repeating.
`
` But first, you were just sworn in, so you
`
`understand you're providing testimony under oath today and
`
`you're expected to tell the truth?
`
` A. Am I supposed to answer? Yes. Of course,
`
`I understand that, yeah.
`
` Q. Is there any reason you cannot provide
`
`complete and accurate testimony today?
`
` A. Not that I can think of.
`
` Q. Okay. If you don't understand any of my
`
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
`questions or they're unclear, I ask that you let me know
`
`that, rather than asking counsel that's present on your
`
`behalf. Okay?
`
` A. Okay.
`
` Q. Since we're on video conference, it's
`
`particularly important that you provide verbal answers to
`
`questions rather than nodding or shaking your head. Okay?
`
` A. Okay.
`
` Q. And there's a bit of a delay in the feed.
`
`Not bad. But that just means we want to emphasize the
`
`importance of giving a little bit of a pause between
`
`questions and answers, and make sure that you and I don't
`
`speak over each other. Do you understand that?
`
` A. I do.
`
` Q. Okay. And we'll try to take some regular
`
`breaks, about every hour or so. If you get to a point
`
`where you feel like you need a break, you can let me know.
`
`I'd just ask that you answer any pending question before
`
`we move to a break. Okay?
`
` A. Okay.
`
` Q. Are you being compensated for your
`
`testimony in this proceeding?
`
` A. Yes. As stated in my declaration, I'm
`
`getting paid by the hour. 750 an hour. I have a copy of
`
`my declaration here. It's okay to look at it, yeah?
`
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
` Q. Did you bring a copy yourself?
`
` A. Yes.
`
` Q. That's fine. Is there any -- is it a clean
`
`copy, or is there any -- are there any notes or writing on
`
`it?
`
` A. No. It's a clean copy.
`
` Q. Okay. Do you have any financial interest
`
`in Moderna?
`
` A. No.
`
` Q. Other than these IPRs, do you have any
`
`relationship with Moderna?
`
` A. I have consulted with Moderna a few times
`
`in the past several years. But other than that, no.
`
` Q. When was the first consulting arrangement?
`
` A. I'm guessing here. Maybe 2016.
`
` Q. What was the nature of that consulting
`
`agreement?
`
` A. I consulted -- that agreement involved two
`
`trips out there. Two one-day trips. And you know, I gave
`
`a presentation. Kind of a typical consulting trip. They
`
`asked me questions, what I thought about things.
`
` Q. What kind of things were you talking about?
`
` A. Well, the issues they have. You know,
`
`stability. I'm an expert in lyophilization, as well. So
`
`a lot of people want my opinion on that. Freeze drying,
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
`if that's easier for you to follow. As well as delivery
`
`questions.
`
` Q. Was this consultation in relation to any
`
`legal proceeding?
`
` A. No.
`
` Q. You mentioned two consulting instances.
`
`That was one. What was the second one?
`
` A. The second one was about a year ago. I was
`
`out there again for a one-day consulting trip. Again,
`
`talking about delivery and stability issues.
`
` Q. Was that in relation to any legal
`
`proceeding?
`
` A. No.
`
` Q. Did any legal proceedings between Moderna
`
`and Protiva or Arbutus come up in your conversations?
`
` A. I don't believe so, not that I can recall.
`
` Q. Is it accurate that your -- this is the
`
`only case in which you're a witness in a legal proceeding
`
`for Moderna?
`
` A. Correct. Yes.
`
` Q. Have you worked with the Irell law firm at
`
`any time in the past?
`
` A. No. Just over the past, you know, six
`
`weeks or so.
`
` Q. How did you come about being retained as a
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
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`witness in this proceeding?
`
` A. I got a call from Maclain Wells and we
`
`talked about the situation and I signed an agreement. The
`
`situation is rather unfortunate, as you know, with
`
`Dr. Janoff. So ...
`
` Q. When did that conversation with Mr. Wells
`
`occur?
`
` A. I believe it was late January. Mid- to
`
`late January of this year.
`
` Q. Was that the first conversation you had
`
`with anyone regarding this legal proceeding?
`
` A. As far as I can recall, yes.
`
` Q. Have you ever talked with Dr. Janoff about
`
`this proceeding?
`
` A. No. I didn't know Dr. Janoff. I don't
`
`believe I've ever met him.
`
` Q. Okay. I'm going to ask the court reporter
`
`to hand you a copy of Exhibit 1015. Let me know when you
`
`get a copy of that.
`
` A. All right. I have it.
`
` Q. Do you recognize this document?
`
` MR. WELLS: Sorry. Is this one going to
`
`appear in the folder now? This is Maclain Wells. Sorry
`
`to interrupt you. I'm -- I'm looking and I'm not seeing
`
`everything appearing.
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
` MR. ROSATO: That's okay. Why don't we
`
`just give it a minute and we'll try to make that
`
`accessible, as well as email you a copy. Why don't we
`
`just give it a minute. And Maclain, you can let me know
`
`when you get a copy.
`
` MR. WELLS: Sure. I'm keeping both my
`
`email open and the Exhibit Share, so I'll let you know.
`
` Okay. It appears on Exhibit Share. So I
`
`got it.
`
` MR. ROSATO: Okay.
`
` Q. (By Mr. Rosato) Dr. Anchordoquy, do you
`
`recognize this document?
`
` A. Yep. This is the '910 publication I've
`
`referenced in the -- in my declaration.
`
` Q. Okay. I'm also going to refer to it as the
`
`'910 publication going forward. Is that okay with you?
`
` A. Yep.
`
` Q. Please turn to Figure 23 of the '910
`
`publication, and let me know when you're there.
`
` A. Yeah. I'm here.
`
` Q. What is illustrated here in Figure 23?
`
` A. So there are three graphs, essentially,
`
`of -- there are different graphs. Each panel has a
`
`different cationic lipid -- DODAC, DODMA, DLinDMA -- and
`
`there's varying concentrations and percent of control on
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
`the Y axis and siRNA on the X axis.
`
` Q. You mentioned DODAC, DODMA, and DLinDMA; is
`
`that correct?
`
` A. DLinDMA is how I've usually heard it
`
`referred to, but yes.
`
` Q. And DODAC, DODMA, and DLinDMA are the
`
`cationic lipids; is that correct?
`
` A. That's my understanding.
`
` Q. Maybe it'll help to turn to paragraph 44 of
`
`the '910 publication. Let me know when you're there.
`
` A. I'm there. I'm reading it now. Okay.
`
` Q. Does paragraph 44 provide a description of
`
`Figure 23?
`
` A. Yes.
`
` Q. And paragraph 44 states, "Figure 23
`
`illustrates data showing silencing of gene suppression
`
`following in vitro transfection of Neuro2A cells stably
`
`expressing luciferase by SPLP (i.e. SNALP) comprising
`
`DODAC, DODMA, or DLinDMA and encapsulating an
`
`antiluciferase siRNA sequence."
`
` Did I read that correctly?
`
` A. Yes.
`
` Q. Let's turn to example 12 of the '910
`
`publication. That's at paragraph 335 and 336. Let me
`
`know when you're there.
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
` A. Right. I'm here.
`
` Q. This is an in vitro assay; is that correct?
`
` A. Yes. It states in vitro transfection.
`
` Q. Do you see the title of the experiment
`
`here?
`
` A. Yes. You'd like me to read it?
`
` Q. Whoops.
`
` A. Silencing of gene expression following
`
`delivery of siRNA encapsulated --
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` THE COURT REPORTER: Can you slow down?
`
` A. Sorry. Silencing of gene expression
`
`following delivery of siRNA encapsulated in SPLP
`
`comprising cationic lipids.
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` Q. (By Mr. Rosato) The first line of
`
`paragraph 335 states, "This example describes experiments
`
`comprising expression of nucleic acids following in vitro
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`transfection of neuro2A cells with SNALP formulations."
`
` Do you see that?
`
` A. Yep.
`
` Q. Okay. And as we just discussed, this is an
`
`in vitro assay; is that right?
`
` A. Correct.
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` Q. And earlier, you identified the three
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`cationic lipids as DODAC, DODMA, and DLinDMA; is that
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`correct?
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
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` A. Yes.
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` Q. And you mentioned that in example 12, as
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`illustrated in Figure 23, each of those three different
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`cationic lipids were tested at various different
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`concentrations; is that correct?
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` A. Yeah. If I ever find that figure, but
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`yeah. There it is.
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` Q. In the middle of paragraph 335, that
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`identifies those concentrations at 15, 20, 25, 30, 35, or
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`40 percent. Is that correct?
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` A. Right. "The stably transfected cells were
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`then transfected with SNALP comprising" -- right. It's
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`the same -- it's consistent with the figure legend in
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`Figure 23.
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` Q. And the discussion here at Example 12
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`references Figure 23. Do you see that?
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` A. Yes. At the very end.
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` Q. At the bottom of --
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` A. Paragraph.
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` Q. Yeah. At the bottom of paragraph 335.
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` A. Right.
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` Q. Take a look at the second-to-last sentence
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`in paragraph 335. Do you see that?
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` A. Beginning with "luciferase"?
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` Q. Excuse me. Third-to-last.
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
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` A. "The stably transfected"? Let's see.
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`Third-to-last.
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` Q. You had it first -- second -- excuse me.
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`Second-to-last. I apologize.
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` A. So "the stably transfected cells"?
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` Q. Well, it's the sentence that reads, "SNALP
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`comprising 30 percent DLinDMA was more effective in
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`reducing luciferase expression in the neuro2A cells than
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`SNALP comprising DODAC or DODMA were."
`
` Do you see that?
`
` A. I do.
`
` Q. Move forward to Example 14 of the '910
`
`publication, which begins at -- the next page in paragraph
`
`339. And let me know when you're there.
`
` A. Okay.
`
` Q. Do you see the first sentence that states
`
`that "Formulations comprising 15 percent DLinDMA were
`
`tested"?
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` A. It says can be used. Right.
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` Q. The sentence that states, "This example
`
`describes experiments demonstrating in vivo transfection
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`of organs with that SPLP comprising 15 percent DLinDMA."
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` A. Right.
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` Q. That's the sentence I'm referring to. Do
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`you see that?
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
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` A. I do.
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` Q. Turn to Example 15 of the '910 publication,
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`which begins on paragraph 341. Let me know when you're
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`there.
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` A. Yeah. It's right below it.
`
` Q. And the first sentence in paragraph 341
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`references in vivo testing of DLinDMA or DODMA with
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`percentages at 15 percent, 10 percent, 5 percent, or
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`2.5 percent.
`
` Do you see that?
`
` A. Right. Of PEG-C-DMA.
`
` Q. And you indicated previously that DLinDMA
`
`and DODMA are the cationic lipids; correct?
`
` A. Correct.
`
` Q. And Example 15 is testing formulations
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`having 15 percent, 10 percent, 5 percent, or 2.5 percent
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`cationic lipid; is that correct?
`
` A. That's not the way I read this. I think
`
`that these percentages refer to the PEG lipid.
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` Q. Do you see the table that follows --
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` A. Right.
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` Q. -- in paragraph 341?
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` A. Yeah. A through G?
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` Q. Yes. What -- what concentration of
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`cationic lipid is listed as having been tested in this
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
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`table?
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` A. Okay. So -- that's the last number. So
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`15 percent. All of them are 15 percent cationic lipid.
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` Q. Let's look at Example 16 of the '9
`
`publication that begins at paragraph 343. Let me know
`
`when you're there.
`
` A. I'm here.
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` Q. What cationic lipid concentrations are
`
`listed in the table provided in Example 16?
`
` A. Cationic lipid. There's 30, 20, and 15.
`
` Q. The table in paragraph 343 lists
`
`formulations comprising 30, 20, and 15 molar percent
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`cationic lipid. Did I get that right?
`
` A. Correct.
`
` Q. Let's look at the next example, Example 17
`
`of the '910 publication. And that begins at paragraph
`
`345.
`
` A. Right.
`
` Q. Let me know when you're there.
`
` A. I'm there.
`
` Q. Do you see the table listed in Example 17?
`
` A. Yep.
`
` Q. What cationic lipid concentrations are
`
`listed in that table?
`
` A. 30, 20, and 15.
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
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` Q. Let's look at the next example, Example 18
`
`of the '910 publication. And let me know when you're
`
`there.
`
` A. I'm here.
`
` Q. What are the cationic lipid concentrations
`
`listed in the table just above paragraph 349 in Example
`
`18?
`
` A. 30, 20, and 15.
`
` Q. Let's look at the next example, Example 19
`
`of the '910 publication. And let me know when you're
`
`there.
`
` A. I'm here.
`
` Q. What are the cationic lipid concentrations
`
`listed in the table just above paragraph 351 in Example
`
`19?
`
` A. They are all 30 percent. 30 mol percent.
`
` Q. Okay. Let's look at the last example,
`
`Example 20 of the '910 publication. And let me know when
`
`you're there.
`
` A. Yep. I'm here.
`
` Q. What are the cationic lipid concentrations
`
`listed in the table just above paragraph 353 in Example
`
`20?
`
` A. 30 mol percent.
`
` Q. Are you familiar with in vitro screens as
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
`described in Example 12, which we discussed about -- we
`
`discussed previously?
`
` A. Yes.
`
` MR. WELLS: Objection to form.
`
` A. Yes. I'm familiar with these.
`
` Q. (By Mr. Rosato) What is the benefit of
`
`doing an in vitro screen of a number of different
`
`formulations?
`
` A. Well --
`
` MR. WELLS: Objection to form.
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` A. The -- I think many people would argue that
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`there is minimal benefit to these in vitro studies, but
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`the benefit is that they are cheap and they're easy to
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`perform. That's -- people use them as an initial
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`screening tool for formulations.
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` Q. (By Mr. Rosato) As an initial screening
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`tool, is it fair to say that gives some information about
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`the formulation tested?
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` MR. WELLS: Objection to form.
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` A. It certainly provides some information.
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`The question is whether that information is useful or
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`predictive at all of in vivo performance.
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` Q. (By Mr. Rosato) Would you say in vivo
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`testing provides more useful information than an in vitro
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`assay?
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
` MR. WELLS: Objection to form.
`
` A. If the goal is to go in vivo -- i.e. in the
`
`clinic -- then the in vivo testing is more relevant.
`
` Q. (By Mr. Rosato) How -- how do you
`
`interpret the situation where a researcher first does an
`
`in vitro screen of a number of compounds and then proceeds
`
`to in vivo screening with a subset of those tested
`
`compounds?
`
` MR. WELLS: Objection to form. Scope.
`
` A. Can you ask that question again? I'm not
`
`sure I understand what you're getting at.
`
` Q. (By Mr. Rosato) Well, we just confirmed
`
`that Example 12 in paragraph 335 is conducting an in vitro
`
`assay; right?
`
` A. Yes.
`
` Q. And we also confirmed that the subsequent
`
`examples report testing of some formulations, but not all
`
`of the formulations that were screened in the in vitro
`
`assay; correct?
`
` MR. WELLS: Objection. Misstates the
`
`document. Objection to form.
`
` A. That's my understanding, yes.
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` Q. (By Mr. Rosato) Isn't it fair to say under
`
`those circumstances, the investigators were more
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`interested in the formulation they proceeded to test in
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
`vivo?
`
` MR. WELLS: Objection to form. Scope.
`
` A. I'm -- I'm not sure I understand your
`
`question. I don't know how I would know what they were
`
`interested in.
`
` Q. (By Mr. Rosato) If they -- if they then
`
`proceed to conduct multiple additional in vivo tests on a
`
`given compound, is it fair to conclude that they're
`
`interested in that compound they're further screening?
`
` MR. WELLS: Objection to form. Scope.
`
` A. They're interested -- presumably, they're
`
`doing the experiment because they're interested in
`
`assessing that. Many people at this time were developing
`
`in vitro reagents, as well, so it's unclear what their
`
`ultimate goal was.
`
` Q. (By Mr. Rosato) If a researcher does an in
`
`vitro screen on a number of compounds and then proceeds to
`
`never test one of those compounds again, how do you
`
`interpret that inactivity?
`
` MR. WELLS: Objection to form. Scope.
`
` A. The inactivity -- so can you rephrase that?
`
` Q. (By Mr. Rosato) Is there any logical
`
`progression in moving from an in vitro screen to an in
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`vivo screen?
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` MR. WELLS: Objection to form.
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
`
` A. It was -- I don't know if I'd characterize
`
`it as a logical progression, but it was something that
`
`people did and still do. They test in vitro first and
`
`then move to in vivo. I think what the field has shown
`
`decidedly many times is that, oftentimes, in vitro is a
`
`poor predictor of in vivo performance. And that was well
`
`known in the field prior to the time of this patent.
`
` Q. (By Mr. Rosato) If a compound performs
`
`poorly in vitro, would it make sense to not proceed with
`
`in vivo testing?
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` MR. WELLS: Objection to form. Scope.
`
` A. In this case, I think that's -- that's what
`
`people often did and probably still do. I can tell you
`
`that I've been to conferences -- oh, back in the late
`
`nineties where a company stood up and showed that the in
`
`vitro performance was exactly opposite of the in vivo
`
`performance. The -- the parameters there are so
`
`different.
`
` All right. You have -- well, I'll leave it
`
`at that. You can ask me more if you'd like.
`
` Q. (By Mr. Rosato) If a compound performs
`
`well in an in vitro screen, is it fair to say you don't
`
`know whether it's going to similarly perform well in an in
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`vivo test?
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` MR. WELLS: Objection to form.
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
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` A. Yeah. I -- as I -- I think I stated a
`
`minute ago, the in vitro test in this case, certainly,
`
`is -- in the case of delivering nucleic acids with lipid
`
`particles, it's been shown that there's a very poor
`
`correlation between in vitro and in vitro vivo. So in
`
`vitro is not very predictive. And many people have
`
`concluded that and published on it.
`
` Q. (By Mr. Rosato) Can in vitro screens help
`
`focus a researcher's priorities of subsequent in vivo
`
`testing?
`
` MR. WELLS: Objection to form. Scope.
`
` A. I think that is often how they're
`
`interpreted, but the argument that many people would make,
`
`including myself, is that that is a -- a poor way to
`
`proceed. That is, again, the in vitro results -- whether
`
`they're good or bad -- do not predict in vivo success very
`
`well. Again, the parameters are very different.
`
` Q. (By Mr. Rosato) Understood. But I think
`
`you would agree that that was an approach researchers
`
`took? That is, they first conducted an in vitro screen
`
`and then, based on the results of the in vitro screen,
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`decided which compounds to proceed with for in vivo
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`testing; is that right?
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` MR. WELLS: Objection -- objection. Asked
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`and answered.
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`Thomas J. Anchordoquy , Ph.D. - March 24, 2020
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` A. Yeah. I -- I think that that was a -- a
`
`process or a protocol that people used. Again, I think
`
`that it's been shown many times to be a flawed process or
`
`way to interpret the data.
`
` Q. (By Mr. Rosato) But researchers took that
`
`approach nevertheless?
`
` A. Yes.
`
` MR. WELLS: Objection. Asked and answered.
`
` A. Yes.
`
` Q. (By Mr. Rosato) Hand you a copy of Exhibit
`
`2020, which is your declaration. And actually, I believe
`
`you indica
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