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`Page 1
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` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________________
`BLUEBIRD BIO, INC. ) Case No. IPR2023-00070
` Petitioner, ) Patent No. 7,541,179
`v. )
`SLOAN KETTERING INSTITUTE ) Case No. IPR2023-00074
`FOR CANCER RESEARCH, ) Patent No. 8,058,061
` Patent Owner. )
`__________________________)
`
`
` DEPOSITION OF DR. MICHEL SADELAIN
` Friday, October 20, 2023
` WilmerHale
` 250 Greenwich Street, 45th Floor
` New York, New York
` 9:10 a.m.
`
`
`Reported by:
`Angela M. Shaw-Crockett, CCR, CRR, RMR, CSR
`______________________________________________________
` DIGITAL EVIDENCE GROUP
` 1730 M Street, NW, Suite 812
` Washington, D.C. 20036
` (202) 232-0646
`
`www.DigitalEvidenceGroup.com
`
`Digital Evidence Group C'rt 2023
`
`202-232-0646
`
`BLUEBIRD EXHIBIT 1066
`bluebird v. SKI
`IPR2023-00070
`
`Page 1 of 161
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`bluebird bio, Inc. v. Sloan Kettering Institute for Cancer Research Dr. Michel Sadelain
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` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________________
`BLUEBIRD BIO, INC. ) Case No. IPR2023-00070
` Petitioner, ) Patent No. 7,541,179
`v. )
`SLOAN KETTERING INSTITUTE ) Case No. IPR2023-00074
`FOR CANCER RESEARCH, ) Patent No. 8,058,061
` Patent Owner. )
`__________________________)
`
`
` DEPOSITION OF DR. MICHEL SADELAIN
` Friday, October 20, 2023
` WilmerHale
` 250 Greenwich Street, 45th Floor
` New York, New York
` 9:10 a.m.
`
`
`Reported by:
`Angela M. Shaw-Crockett, CCR, CRR, RMR, CSR
`______________________________________________________
` DIGITAL EVIDENCE GROUP
` 1730 M Street, NW, Suite 812
` Washington, D.C. 20036
` (202) 232-0646
`
`www.DigitalEvidenceGroup.com
`
`Digital Evidence Group C'rt 2023
`
`202-232-0646
`
`BLUEBIRD EXHIBIT 1066
`bluebird v. SKI
`IPR2023-00070
`
`Page 1 of 161
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`A P P E A R A N C E S:
`
`Attorneys for Petitioner
`PAUL HASTINGS LLP
`BY: MAX H. YUSEM, ESQ.
`200 Park Avenue
`New York, New York 10166
`(212) 318-6375
`maxyusem@paulhastings.com
`
`Attorneys for Sloan Kettering
`WilmerHale
`BY: TIMOTHY A. COOK, ESQ.
`60 State Street
`Boston, Massachusetts 02109
`(617) 526-6005
`tim.cook@wilmerhale.com
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`A P P E A R A N C E S CON'T:
`
`Attorneys for San Rocco Therapeutics
`Fox Rothschild LLP
`BY: JOE CHEN, PH.D., ESQ.
`Princeton Pike Corporate Center
`997 Lenox Drive
`Lawrenceville, NJ 08648-2311
`(609) 844-3024
`joechen@foxrothschild.com
` -and-
`Fox Rothschild LLP
`BY: HOWARD S. SUH, ESQ.
`101 Park Avenue, 17th Floor
`New York, New York 10178
`(212) 878-7914
`hsuh@foxrothschild.com
`
`
`
`ALSO PRESENT: Jonathan Juarez, The Videographer
` Hilary Libka, MSK
` In-house Counsel
`
`
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` I N D E X
`Examination by: Page
`MR. YUSEM 6
`MR. YUSEM 104
`
` REFERENCED E X H I B I T S
` Page
`Exhibit 1005 88
`
` PREVIOUSLY MARKED E X H I B I T S
` Page
`
`Exhibit 1001 9
`Exhibit 2006 10
`Exhibit 2033 62
`Exhibit 1006 76
`Exhibit 1022 104
`Exhibit 1015 108
`Exhibit 2003 112
`Exhibit 1032 124
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` THE VIDEOGRAPHER: We're now on the
` record. My name is Jonathan Juarez. I am a
` legal videographer for Digital Evidence Group.
` Today's date is October 20, 2023, and the time
` is 9:10 a.m.
` This deposition is taking place at 250
` Greenwich Street, New York, New York, in the
` matter of bluebird bio, Inc. v. Sloan Kettering
` Institute. The deponent is Dr. Michel
` Sadelain.
` Counsel, please identify yourselves for
` the record.
` MR. YUSEM: Max Yusem from Paul Hastings
` for Petitioner.
` MR. SUH: Howard Suh from the law firm of
` Fox Rothschild. With me is my colleague,
` Dr. Joe Chen, also from Fox Rothschild. And we
` represent San Rocco Therapeutics.
` MR. COOK: Tim Cook, WilmerHale for Sloan
` Kettering and the witness. Later today I'm
` going to be joined by Hilary Libka, who's
` in-house counsel at Sloan Kettering.
` THE VIDEOGRAPHER: The court reporter is
` Angie Shaw-Crockett and will now swear in the
` witness.
`
`Page 5
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` Dr. Michel Sadelain, having been first duly sworn by a
`Notary Public of the State of New York, was examined and
`testified as follows:
`EXAMINATION
`BY MR. YUSEM:
` Q. Good morning, Dr. Sadelain. Is it
`pronounced Sadelain (pronunciation)?
` A. That's very well. Thank you.
` Q. Have you been deposed before?
` A. Yes.
` Q. How many times, roughly?
` A. Twice.
` Q. Okay. And how many of those times --
`withdrawn.
` Were those depositions as a fact witness?
` MR. SUH: Objection to form.
` A. I was -- served twice as a witness, yes.
`BY MR. YUSEM:
` Q. And were you testifying in an expert
`capacity or in a fact witness capacity?
` MR. SUH: Objection, foundation.
` A. I don't know if I'm -- I'm not sure I know
`the difference between those two.
`BY MR. YUSEM:
` Q. What were the matters about?
`
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` A. One was relating to CAR-T cell technology
`and the topic was infringement by a company on MSK's
`technology. It's immunotherapy, and I served as a
`witness there. The other case related to a dispute
`between MSK and EGT about a clinical trial, where I
`also served as a witness.
` Q. And for the first matter, regarding CAR-T,
`was that patent infringement matter -- the patents
`there, were you a named inventor?
` A. Yes.
` Q. And those patents are not the ones that
`we're going to be discussing today that relate to
`the IPR proceeding?
` A. Completely unrelated.
` Q. Okay. And with respect to the second
`matter, the one versus EGT, do you understand that
`EGT has since changed its name to San Rocco
`Therapeutics?
` A. I do. I do.
` Q. And you were deposed once in that action
`with EGT?
` A. That's what I recall at the moment, just
`once.
` Q. And how did you prepare for today's
`deposition?
`
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` A. I met with representation yesterday.
` Q. And did that include the attorneys in this
`room?
` A. Exactly.
` Q. Anyone else that you met with in
`preparation for today's deposition that is not here?
` A. Yesterday, present representing, I guess,
`Hilary Libka, who's not here yet, was her associate,
`I think, Garry Colin, who is not here today.
` Q. Anyone else?
` A. No.
` Q. Did you speak with any other inventors in
`preparation of today's deposition?
` A. No.
` Q. Did you speak with anyone else from MSK in
`preparation for today's deposition?
` A. No.
` Q. Did you review documents in preparation
`for today's deposition?
` A. Some documents, yes.
` Q. Can you tell me which documents those
`were?
` A. Well, mostly my deposition, and to refresh
`my memory I went over the manuscript that was
`published in 2000, an abstract, and also, claims in
`
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`our patent.
` Q. I think you said deposition. Did you mean
`the declaration?
` A. I'm sorry, declaration. I meant
`declaration.
` Q. Not a problem.
` And the manuscript that you referenced, is
`that the one that was published in Nature in 2000?
` A. Yes.
` Q. And the abstract, that was the abstract
`where Dr. May was the lead author published in
`Molecular Therapy?
` A. I forget where it's published, but that's
`the abstract. There's only one.
` Q. All right. We'll take a look at that
`later.
` And the claims that you referred to -- let
`me hand you. I'm going to hand you two previously
`marked exhibits. They're both marked Exhibits 1001.
`The first one is the '179 patent. And the second
`document is also previously marked Exhibit 1001,
`it's the '061 patent.
` A. Thank you.
` Q. Do you have both of those patents in front
`of you?
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` A. Yes.
` Q. The claims that you referred to reading in
`preparation for today's deposition, are those the
`claims of the '179 and '061 patents?
` A. The '179 is what I focused on, yes.
` Q. Anything else that you -- that you
`reviewed in preparation for today's deposition?
` A. No.
` Q. And do you understand that we're here
`today for a deposition relating to two IPR
`proceedings that relate to your patents, the '179
`and '061 patents?
` MR. SUH: Objection to form.
` A. Yeah, I thought it was one, but it's two
`that's -- yes.
`BY MR. YUSEM:
` Q. Yeah, so there's two IPR proceedings. One
`is on the '179 and one is the '061.
` MR. SUH: Objection to form. I'm not sure
` that's a question.
`BY MR. YUSEM:
` Q. Let me hand you previously marked
`Exhibit 2006.
` A. Oh, this is my declaration.
` Q. Dr. Sadelain, can you tell us what is
`
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`Exhibit 2006?
` A. It is my declaration.
` Q. And is this the declaration that you
`prepared for the IPR proceeding that we're here
`today to discuss?
` A. I won't read it, but I'll certainly assume
`so, yes.
` Q. Did you prepare any other declarations for
`the IPR proceedings?
` A. No.
` Q. Okay. Can you tell me generally how you
`prepared this declaration Exhibit 206?
` MR. SUH: Objection, vague.
` And I just want to caution the witness, to
` the extent that that answer reveals
` communications you may have had with counsel, I
` instruct you not to reveal those.
` THE WITNESS: Well, thank you. You're
` right.
` A. I was informed by counsel at MSK, Hilary
`Libka, of this upcoming event of an IPR. And it is
`with her that this document was prepared.
`BY MR. YUSEM:
` Q. Did someone ask you to prepare this
`declaration?
`
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` A. Well, Hilary Libka. Obviously, I needed
`help to structure this document because I'm not
`familiar with this type of document. But yes, she
`asked me to review it with her and work on it with
`her.
` Q. Apart from Hilary, did you work with
`anyone else in preparation of your declaration?
` A. No.
` Q. In preparation for your declaration, did
`you review any documents apart from the documents
`that we discussed you reviewing in preparation for
`today's deposition?
` A. What I recall is I probably verified
`dates, you know, the publication, things that I
`wouldn't memorize. That's about it.
` Q. How did you verify dates?
` A. Oh, if you pull up the manuscript, you see
`the date it's published, things like that.
` Q. Did you, for example, go through your old
`emails to check dates of things that you might have
`emailed to people at certain times to confirm the
`dates were accurate?
` A. I don't recall that that was necessary for
`what was incorporated into this declaration.
` Q. Did you look through any of your old files
`
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`to see whether or not, you know, the dates were
`correct?
` A. Not really. The level that is reflected
`here, I think, my memory was overall adequate to
`provide dates or years, for example.
` Q. Did you speak with any of the other named
`inventors on your patents in preparation for the
`declaration?
` A. No, I did not.
` Q. Did you review anyone else's declaration
`as part of this proceeding?
` A. No.
` Q. So I'd like to take a look at your
`declaration, specifically paragraph 32.
` A. (Witness complies.)
` Q. This is Exhibit 2006.
` Let me know when you're there.
` A. I found it.
` Q. Okay. Five lines up from the bottom, it
`states "It took me 11 years."
` Do you see that?
` A. Yes.
` Q. Okay. You write here in paragraph 32 of
`your declaration "It took me 11 years, from 1989 to
`2000, to succeed in designing a vector meeting those
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`two fundamental criteria, and I continued to test
`and develop that design thereafter."
` Do you see that?
` A. Yes.
` Q. What two fundamental criteria are you
`discussing here?
` A. Okay. As I state here the design of the
`vector was a very challenging task. Globin vectors
`are very different from virtually all other
`therapeutic vectors used for other diseases. In
`particular, they need to express a gene product at a
`very high level, in the right cell type, not
`indiscriminately as most common vectors do.
` That requires, it turns out, the
`incorporation of many more elements than would be
`needed in almost any other vector. The challenges
`are multiple. But I highlight here the two main.
`If you were to distill all of this complexity to two
`main aspects, one is to incorporate an appropriate
`combination of elements to achieve that high-level
`expression. But the more elements you introduce in
`a vector, the more unstable the structure or the
`lesser the gene transfer efficiency.
` Therefore, there are really two parallel
`tasks: To design a vector that provide remarkably
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`high-level expression that also -- that has a stable
`structure and transfers at high efficiency.
` Q. And that vector design that you're
`discussing here in paragraph 32 of your declaration
`that succeeded, was that the TNS9 vector?
` A. That is the combination of, as I sit here,
`many years of research, 11 years for me, and also,
`of the construction and testing of a very large
`number of vectors. If I may, some colleagues
`thought I may hold a Guinness Book of Record --
`saying jokingly -- for the number of vectors we
`tested before we came up with TNS9.
` Q. So the culmination, as you described it,
`of all these years of research was the vector design
`of the TNS9 vector?
` A. It is the vector, and it is in the larger
`picture, the first ever demonstration that you could
`cure a mouse with a globin disorder achieved through
`this vector. If I may say, in the days, some people
`said this study would warrant the Nobel Prize, just
`to give you an idea of what needed to be resolved to
`reach this design.
` Q. When you refer to the study, you're
`talking about the results that are published as part
`of the Nature paper in 2000?
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` A. Yes.
` Q. So --
` A. It is a concept that was demonstrated that
`it is feasible, eventually, to design a vector
`expressing a globin gene at therapeutic levels,
`emphasize "therapeutic."
` Q. And that's what's being described in your
`Nature paper that you published in 2000?
` MR. SUH: Objection to form.
` A. Yeah, depends what you mean by
`"described." As I said, it is the first report ever
`in the literature that you can design a vector
`including the globin gene and treat successfully an
`animal with a thalassemia, thalassemia being one of
`the two major diseases for which this type of vector
`would be indicated.
`BY MR. YUSEM:
` Q. And your evidence of that was published as
`part of the Nature paper; is that right?
` MR. SUH: Objection to form.
` A. Yeah. Depends what you mean by
`"evidence." If you may clarify for me?
`BY MR. YUSEM:
` Q. You described a concept that was
`demonstrated as being feasible to eventually design
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`a vector expressing the globin gene at therapeutic
`levels.
` Is that concept part of the Nature article
`publication in 2000?
` A. Yes. There are multi layers, multiple
`layers, in the concept. The first is, we were
`successful using a lentiviral. For years before, we
`and others had attempted unsuccessfully to reach
`this result with other types of retroviral vectors.
` In fact, by the late '90s, a number of
`groups who were also seeking to achieve such a
`result as we did even abandoned the use of any
`so-called "retroviral vector." A lentiviral vector
`is a type of retroviral vector.
` And so one part of that concept shown in
`this paper is that contrary to what many have begun
`to believe, you could design a stable vector
`encompassing, you know, a fair number of elements
`required to achieve high expression of the globin
`gene in a lentiviral vector.
` That opened up the whole field.
`Subsequently, pretty well every other group in the
`world that I'm aware of followed in the footsteps of
`the concept that was reported in this paper.
` Q. And that concept that you're describing
`
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`is, you said, the lentivirus?
` A. That's part of it. I said there's multi
`layers. Another part of it is what is the
`combination of elements and how you put them
`together, how you assemble them to actually produce,
`to generate, what we call a "transcription unit,"
`meaning a structure that allows for a gene, in this
`case a globin gene, to be expressed at very high
`level in red cells, which are the disease cells in
`these disease, with what we call a "high probability
`of expression."
` This other layer, it's a bit more complex
`to explain. But, essentially, these vectors
`integrate at different positions in different
`chromosomes, and there's variability in how well
`they work in each and every cell. They may silence
`over time. Silence means stop working. And we
`showed that this design addressed these multiple
`challenges -- that's what I'm referring to -- to
`multiple layers underlying the success of this
`concept.
` Q. Apart from the concept of the lentiviral
`vector, the other concept you're describing is the
`actual genetic material that makes up the globin and
`the regulatory elements of the vector?
`
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` MR. SUH: Objection to form.
` A. Yeah. I'm not sure I would separate them
`as distinct concepts. It's all together one thing
`that achieves multiple purposes, overcoming multiple
`challenges, I would say. You can break it down in
`subsets, but it's still, in the end, to me, one
`multilayered concept if you'd like.
`BY MR. YUSEM:
` Q. The multilayer concept being the
`functional globin and the regulatory elements?
` MR. SUH: Objection to form.
` A. Yes, borne by a lentiviral vector.
`BY MR. YUSEM:
` Q. Got it.
` And these concepts -- withdrawn.
` The multilayer concepts that you're
`discussing, functional globin regulatory elements
`borne by the lentiviral vector, these are concepts
`that are a part of your Nature article that you
`published in 2000?
` MR. SUH: Objection to form.
` A. Correct. There's -- yes.
`BY MR. YUSEM:
` Q. And let's turn to paragraph 13 of your
`declaration.
`
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` A. May I add something? When you say "They
`are a part of the manuscript," yes. It doesn't mean
`that all details that one may want to see are
`specified in the manuscript itself, but it clearly
`shows that this approach works.
` Q. Do you believe you provided enough details
`in your Nature manuscript to allow others to --
` A. It's --
` Q. Sorry. I've got to finish my question.
` Do you believe that you provided enough
`details in your Nature manuscript -- withdrawn.
` Do you believe that you provided enough
`details in the Nature article published in 2000 to
`allow others in the industry to understand the
`importance of the discovery that you had made?
` MR. SUH: Objection to form.
` A. It's a complicated long question, but I'll
`do my best to address it.
` First, we provided enough evidence and
`detail to satisfy reviewers of what is arguably the
`most famous and toughest scientific journal in the
`world, Nature. So, obviously, that reflects on the
`sufficiency of the content for anyone in the
`academic setting.
` Secondly, there obviously was enough
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`evidence to support the concept and the approach,
`given that subsequent to this publication, a number
`of groups who had never constructed a vector of this
`kind pursued the design of similar vectors,
`including in the academic and industry setting,
`following in the footsteps of this paper. And
`that -- you know, the history demonstrates that.
`BY MR. YUSEM:
` Q. Let's take a look at paragraph --
` A. Thirdly -- yes.
` Q. Sorry. I just wanted to draw your
`attention to --
` A. Okay. So firstly and secondly. That's
`all.
` Q. Sorry. Yeah.
` So I'd like to draw your attention to
`paragraph 13 of your declaration, Exhibit 2006.
` A. (Witness complies.)
` Yes, I have it.
` Q. You write here "The first step in our
`research that led to the TNS9 vector, and the most
`innovative, was designing the genetic material that
`would be inserted into the patient's cells."
` Do you see that?
` A. Yes.
`
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` Q. The genetic material that you referred to
`here, what does that include?
` A. Everything. All of the foreign DNA that
`is introduced, ultimately, in a patient cell. This
`is not patients, not at this point. It is the
`genetic material. So it encodes -- it comprises a
`vector which, in this case, is a lentiviral vector,
`which harbors with a transcription unit to express
`the gene, and in this case, it's a beta-globin gene.
` And to afford adequate level, an adequate
`pattern of expression, it also comprises a series of
`so-called "regulatory elements."
` Q. The transcription unit, that's the
`functional globin part of the vector?
` MR. SUH: Objection to form.
` A. Yes. You could call it a "transcription
`unit." No, I would refer to the transcription unit
`as the combination of the gene with the elements
`that have been assembled to allow for optimal
`expression of that gene.
`BY MR. YUSEM:
` Q. So that includes the fragments of the LCR?
` A. Yes.
` Q. So the transcription unit is the
`combination of the globin gene as well as the LCR
`
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`fragment?
` A. Yes. That's how I see it. I don't know
`if there's universal agreement on the definition
`of -- it's just a word, but it is the combination of
`the gene and the associated regulatory element.
` Q. Appreciate it. I just wanted to try and
`get an understanding of -- I've only seen these
`things in images and in documents. So it's
`sometimes hard to conceptualize.
` A. And I believe the term "transcription
`unit" wasn't used here, although they're all
`synonyms.
` Q. So to make sure I understand paragraph 13
`then, the most innovative part of TNS9 was the
`genetic material that you just discussed?
` MR. SUH: Objection to form.
` A. No. I concur that this paragraph 13
`emphasizes this part and, indeed, that is what makes
`the gene work, if you like, and be therapeutic. But
`as I said before, the ability to transfer that
`material is obviously of great importance.
`BY MR. YUSEM:
` Q. Right, yeah.
` A. And, therefore, the lentiviral vector is
`also important. But this segment just emphasizes
`
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`the elem
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