101
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` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`-----------------------------x
`ILLUMINA, INC.,
`Petitioner,
`
` vs.
`PATENT OF THE TRUSTEES
`OF COLUMBIA UNIVERSITY IN
`THE CITY OF NEW YORK
`Patent Owner.
`-----------------------------x
`VOLUME II
`VIDEOTAPED DEPOSITION OF DR. GEORGE TRAINOR
`Wednesday, September 4, 2013
`New York, New York
`3:56 p.m.
`
`Reported by:
`Maureen Ratto, RPR, CCR, CLR
`Job No: 31222-B
`
`Illumina Ex. 1058
`IPR Petition - USP 10,435,742
`
`
`
` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`-----------------------------x
`ILLUMINA, INC.,
`Petitioner,
`
` vs.
`PATENT OF THE TRUSTEES
`OF COLUMBIA UNIVERSITY IN
`THE CITY OF NEW YORK
`Patent Owner.
`-----------------------------x
`VOLUME II
`VIDEOTAPED DEPOSITION OF DR. GEORGE TRAINOR
`Wednesday, September 4, 2013
`New York, New York
`3:56 p.m.
`
`Reported by:
`Maureen Ratto, RPR, CCR, CLR
`Job No: 31222-B
`
`Illumina Ex. 1058
`IPR Petition - USP 10,435,742
`
`
`
`* * *
`
`102
`
`Videotaped deposition of DR. GEORGE L.
`TRAINOR, held at the offices of Fitzpatrick
`Cella Harper & Scinto, LLP, 1290 Avenue of
`the Americas New York, New York,
`10104-3800, pursuant to notice, before
`Maureen Ratto, Registered Professional
`Reporter, License No. 817125, and Notary
`Public.
`
`* * *
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`DAVID FELDMAN WORLDWIDE, INC.
`450 Seventh Avenue - Ste 500, New York, NY 10123 1.800.642.1099
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` A P P E A R A N C E S:
`
` Counsel for the Petitioner:
` FOLEY & LARDNER, LLP
` 777 East Wisconsin Avenue
` Milwaukee, WI 53202-5306
` 414-297-5782
` BY: JEFFREY N. COSTAKOS, ESQ.
` jcostakos@foley.com
`
` REINHART BOERNER VAN DEUREN, S.C.
` 22 East Mifflin Street, Suite 600
` Madison WI, 53703
` 608-229-2219
` BY: ROBERT A. LAWLER, ESQ.
` rlawler@reinhartlaw.com
`
` Counsel for the Patent Owner:
` COOPER & DUNHAM, LLP
` 30 Rockefeller Plaza
` New York, New York, 10112
` 212-278-0400
` BY: JOHN P. WHITE, ESQ.
` jwhite@cooperdunham.com
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` A P P E A R A N C E S, continued:
`
` Fitzpatrick Cella Harper & Scinto, LLP
` 1290 Avenue of the Americas
` New York, NY 10104-3800
` 212-218-2100
` BY: ROBERT S. SCHWARTZ, ESQ.
` rschwartz@fchs.com
` SIEW YEN CHONG, ESQ.
` schong@fchs.com
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` ALSO PRESENT:
` Marcus Burch, Esq.
` Illumina Senior Patent Counsel
` Manuel Abreu, Videographer
` Kevin Burgess, Texas A&M University
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` G E O R G E L. T R A I N O R, having
` previously sworn, resumes testifying as
` follows:
` CROSS-EXAMINATION BY MR. COSTAKOS:
` VIDEOGRAPHER: The time is
` 3:56 p.m., and we're back on the
` record.
` MR. COSTAKOS: I think we were
` just going to announce for the record
` that John White is now sitting in the
` -- the catbird seat, as it were.
` Q. All right. So when we took our
` break, we were looking at page 27 of
` Tsien.
` Okay. Dr. Trainor, if you look
` at the bottom of page 27 of Tsien, you
` see it refers to an embodiment that has
` a 3'-blocked dNTP, do you see it -- I'm
` sorry. Let me start over again.
` So at the bottom of page 27, the
` very last line, do you see there is a
` reference to a "3'-block dNTP analog
` containing a label, such as a
` fluorescent group coupled to a remote
` position such as the base."
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` Do you see that?
` A. Yes.
` Q. Okay. So Tsien discloses a dNTP
` analog that is 3'-blocked and has a
` fluorescent label coupled to the base.
` A. Yes. In a general sense, yes,
` in a general notion of that. It's not
` a chemical structure at that point,
` yeah.
` Q. But it says it in words, and you
` agree with that?
` A. Yes. I'll agree with that.
` Q. If you look at page 21 of Tsien,
` actually beginning at page 20 of Tsien,
` which is Exhibit 1002, there is a
` section entitled "Blocking Groups and
` Methods for Incorporation."
` Do you see that?
` A. Yes.
` Q. Okay. And then on page 21, at
` line 12, it says, "The most common
` 3'-hydroxyl blocking groups are esters
` and ethers."
` Do you see that?
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` A. Yes.
` Q. Okay. And so it expresses
` esters and ethers blocking groups,
` right?
` A. Yes. In a general sense, yes.
` Along with other things, yes.
` Q. And you agree those are small,
` right?
` A. I don't know. They could be
` large or small. It doesn't specify.
` Q. And allyls are small we already
` talked about that, right?
` A. Yeah, relatively small, right.
` Q. Okay. And if you look at page
` 24, beginning at line 24, there is a
` reference to "a wide variety of
` hydroxyl blocking groups." Do you see
` that?
` A. "A wide variety," I don't see
` those words.
` Q. Okay. So at line 24 of page 24
` --
` A. Of page 24 --
` Q. -- it says, "a wide variety of
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` TRAINOR
` hydroxyl blocking groups."
` A. Oh, down at the bottom.
` Q. Do you see that?
` A. Yes.
` Q. Okay. And then in the same
` paragraph it refers to "allyl ethers"
` at line 29. Do you see that?
` A. Among other larger groups as
` well, so...
` Q. Okay. But you agree that it --
` it specifically discloses in words, the
` idea of using allyl ethers as blocking
` groups?
` A. Yes.
` Q. And allyl ethers we talked about
` before are small?
` A. A-hum.
` Q. Yes?
` A. Yes.
` Q. Okay.
` A. And I should point out that in
` doing this he's also -- he has not
` specified the combination of those
` groups in this section with
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` TRAINOR
` specifically with a base label or
` cleavable base label. He's simply
` saying, "blocking groups," with the
` implication if you put it on the 3' and
` be blocked there or other -- other
` options but it's not specific to that
` context.
` MR. COSTAKOS: Move to strike as
` non-responsive.
` Q. Okay. So if we look at page 21
` of Tsien, at line 20, you see it refers
` to "presently preferred embodiments."
` Do you see that?
` A. Yes.
` Q. And it says, "Presently
` preferred embodiments focus on the
` ester-blocking groups such as lower (1
` to 4 carbon alkalinuric acid), et
` cetera, et cetera."
` Do you see that?
` A. Yes.
` Q. Okay.
` A. It's a long list.
` Q. And one to four carbons would be
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` small, right?
` A. Again, this is --
` Q. "Yes" or "no"?
` A. -- this is one of a list.
` Q. "Yes" or "no"?
` A. Yes, but one of a list. I can
` -- I believe I can answer the questions
` as I feel. I mean, I --
` Q. No, you really can't, actually.
` A. -- I don't believe I -- I'm
` required to give you a "yes" or "no"
` answer --
` Q. Okay.
` A. -- but sometimes a qualified yes
` is the appropriate answer.
` Q. No. What I --
` MR. WHITE: You can answer the
` questions the way you think are
` appropriate.
` Q. Well, I -- here -- here is the
` way it's supposed to work. You answer
` my questions.
` A. A-hum.
` Q. And then if he has questions,
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` Mr. White has questions for you later,
` then he can ask you those questions.
` A. No.
` Q. Okay.
` A. That -- it was my -- my
` understanding --
` Q. A-hum.
` A. -- that I -- I can give an
` answer that I believe answers your
` question.
` Q. Okay.
` A. Because sometimes a simple "yes"
` or "no" is not the appropriate answer.
` Q. Okay. But my question was: One
` to four carbon is small?
` A. Yes.
` Q. Okay. Now, if we go back to
` page 24, of Tsien, Exhibit 1002, it
` refers to on line 5, "Removal of
` ester-blocking groups from the
` 3'-hydroxyl functions is usually
` achieved by base hydrolysis."
` Do you see that?
` A. Yes.
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` Q. Okay. And so the blocking
` groups can be a -- are removable,
` right?
` A. A-hum.
` Q. Yes?
` A. That's their assertion here.
` Q. Okay. And where we were looking
` down before on line 29, of page 24 it
` says, "Allyl ethers are cleaved by
` treatment with Mercury 2 in
` acetone/water," and it cites to a
` reference.
` Do you see that?
` A. Yes, I see that.
` Q. Okay. So it discloses that
` allyl ethers, as blocking groups, can
` be removable, right?
` A. It doesn't specify whether
` they're removable without other
` reactions going on that would destroy
` the ability of the nucleotide to work,
` which is important to perform this
` invention.
` Q. Okay.
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` MR. COSTAKOS: I move to strike
` as none responsive.
` Q. The allyl ethers are disclosed
` in the reference as being "cleaved by
` treatment with Mercury 2 and acetone
` water," on lines 29 and 30?
` A. Yes.
` Q. Am I right?
` A. Those are the words.
` THE REPORTER: Those are the --
` THE WITNESS: -- words.
` Q. Now, if we look at page 28,
` beginning at line 5, Tsien discusses "a
` method that uses a fluorescent tag
` attached to the base moiety."
` Do you see that?
` A. Yes.
` Q. Okay. So in one of the
` embodiments of Tsien it talks about
` using a fluorescent tag that is
` attached on the base. Fair?
` A. Yes.
` Q. And -- and right after that
` sentence that I -- I just read it says,
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` "the tag may be chemically cleaved."
` Do you see that?
` A. Yes.
` Q. Okay. And if you look at line
` 27, of page 28, it discloses that "the
` cleavable linkage can be an allyl
` ether," agreed?
` A. No. It says, "allyls can be
` cleaved," it doesn't say -- it -- maybe
` it says it somewhere else but it says,
` "allyls are cleavable by Mercury."
` Q. Okay. Let -- let's just go by
` point.
` A. A-hum.
` Q. Okay. Let's look a few lines
` above that at line 23 and it says,
` "there are several" -- "several
` cleavable ethers that permitted
` removing the fluorescent group before
` the next successive nucleotide is
` added."
` Do you see that?
` A. Yes.
` Q. Okay. And then it says, "for
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` example," and it lists three
` possibilities, one of which is allyl
` ethers, right?
` A. Correct.
` Q. And it says, "allyl ethers" --
` strike that.
` So it says that allyl ethers can
` be cleavable linkers, agreed?
` A. That is the implication, yes.
` Q. It also says that "a silo ether
` can be a cleavable linker on are
` tether," right?
` A. It appears to, yes.
` Q. I'll hand you what's been
` previously marked as Exhibit 1008, the
` Stemple reference.
` THE REPORTER: The which
` reference?
` MR. COSTAKOS: The Stemple.
` THE REPORTER: Stemple.
` MR. COSTAKOS: Yeah.
` (Whereupon, the Deponent reviews
` the document.)
` Q. I think it's known to us as the
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` Stemple 3 reference even.
` MR. COSTAKOS: But for the
` record, it is Patent No. 7,270,951.
` Q. And you're familiar with this
` reference, right?
` A. Yes, I am.
` Q. In column 10 of the -- well,
` strike that.
` Stemple discloses a detachable
` blocking group, doesn't it?
` A. I have to take a look.
` Q. Okay.
` A. I talk about that in my
` declaration as well.
` Q. Well, let -- let's look at
` column 10?
` A. I -- I have to go to my
` declaration, because there is a lot of
` material here and a lot of references.
` Q. Okay. Well, can you also turn
` to column 10 while you're looking?
` A. Yeah. Yes. I got it open.
` Q. Okay. So if you look at column
` 10 of Stemple, at line 8, it refers to
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` "a detachable blocking group is 3'-O2
` nitrile benzyl."
` Do you see that?
` A. Yes, I do.
` Q. And if you look, the two lines
` that are above that, so beginning at
` line 7, column 10, or excuse me,
` beginning at line 6, it says, "in a
` preferred embodiment the detachable
` labeling group is a label, e.g., a
` fluorophore linked to the base of the
` nucleotide" --
` A. Sure.
` Q. -- "i.e, by a 2-nitrile benzyl
` group."
` Do you see that?
` A. Yes.
` Q. So that discloses a fluorophore
` that is attached to the base by a
` cleavable linker, right?
` A. By a photocleavable linker, yes.
` Q. Okay. The linker that is in
` column 10 is cleavable by light?
` A. That's correct.
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` Q. I'll hand you what's been
` previously marked as Exhibit 1005.
` Let's just quickly go off the record,
` here. Sorry about that.
` VIDEOGRAPHER: The time is
` 4:08 p.m., and we're going off the
` record.
` (Whereupon, a discussion is held
` off the record.)
` VIDEOGRAPHER: The time is
` 4:09 p.m., and we're back on the
` record.
` Q. So I've handed you what's been
` marked previously as Exhibit 1005 which
` is the Dower Patent --
` A. Yes.
` Q. -- US Patent No. 5,547,839.
` A. Yes.
` Q. And you're familiar with that
` reference, right?
` A. Yes, I am.
` Q. Okay. And so, if you turn to
` column 25 of Dower, if you look at line
` 35, beginning at line 35 --
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` A. A-hum.
` Q. -- it says, "A fluorophore is
` placed in a position, other than the
` 3'-OH of the nucleoside and a different
` group 3'-OH on the dNTPs to function as
` a chain terminator."
` Do you see that?
` A. Yes.
` Q. Okay. And so, that --
` A. So put it somewhere else is what
` they're saying, you can put it
` somewhere other than 3'.
` Q. Yes. Someplace other than 3',
` yes.
` A. Yes.
` Q. And have a blocking group on the
` OH?
` A. Yes.
` Q. Okay. And if you look at figure
` 9 of Dower, figure 9 shows the
` attachment of FMOC to the base, right?
` A. Yes. In a -- in a -- yes.
` Somehow it would imply it has a B, and
` I'm guessing that is the base and it's
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` TRAINOR
` an FMOC.
` Q. And FMOC is a type of
` fluorophore, isn't it?
` A. FMOC is fluorescent. I don't
` know that it's ever been used as a
` label. I don't think that's been
` established.
` Q. But it is fluorescent?
` A. Yes, it is.
` Q. Now, if you look at column 15 of
` Dower, beginning at line 52, it says
` that "one important functional property
` of the monomers is that the label be
` removable."
` Do you see that?
` A. A-huh.
` Q. Yes?
` A. Yes.
` Q. Okay. So it does disclose the
` use of a removable label in Dower?
` A. I -- I don't see anywhere where
` he asserts that the FMOC is removable.
` It might be but I don't know that he
` discusses that.
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` Q. Okay. But you agree here he
` talks about in the -- in 52, in line 52
` and 53, he refers to the label being
` removable, do you agree with that?
` A. A label, but I don't think that
` flows from that figure.
` Q. Okay.
` A. These are two statements they --
` it makes.
` Q. And if you look at column 18 --
` A. A-hum.
` Q. -- and down at the bottom there,
` there is a line 64 and there is a
` reference to "Figure 9"?
` A. A-hum.
` Q. Yes?
` A. Yup.
` Q. And it says, "a suitable
` nucleotide is labeled with FMOC
` fluorescently detectible label by
` reaction," et cetera.
` Do you see that?
` A. Could you give me the line
` again, please he is?
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` Q. Sure. Beginning at line 64,
` there is a reference to "Figure 9," and
` then the very next line --
` A. Right.
` Q. -- it says, "a suitable
` nucleotide is labeled with the FMOC
` fluorescently detectible label."
` Do you see that?
` A. Yes. Well, actually, that is
` not a nucleotide. It's incorrect. It's
` a nucleoside.
` Q. It's a nucleoside.
` A. It's not a nucleotide. And
` that's an important distinction because
` the -- all of the -- all of the
` nucleotides of interest in Dr. Ju's
` invention has a phosphorus and this
` doesn't have a phosphate on it, it has
` photocapable protecting group on 5',
` and that's a major distinction.
` Q. Okay. So -- but it does say
` that the molecule that is in Figure 9
` is labeled with -- and which you say is
` a nucleoside, is labeled with the FMOC
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` fluorescent -- fluorescently detectible
` label, right?
` A. Well, he claims that it's
` detectible but I -- I'm struggling to
` see what that nucleotide has anything
` to do with the DNA sequencing. It
` can't be used for DNA sequencing.
` Q. Okay. Well, let -- let me --
` A. Even a person of ordinary skill
` in the art would say this has to do
` with DNA synthesis not with polymerase
` substratability there is no
` triphosphate.
` Q. Okay.
` MR. COSTAKOS: Move to strike as
` non-responsive.
` Q. So my -- this -- the questions
` I'm asking you here really go to your
` point that you made earlier as to
` whether FMOC is is a label.
` So isn't it accurate that Dower
` characterizes FMOC as a fluorescently
` detectable label?
` A. He appears to do that. I'm not
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` sure I agree with him, and I -- but I'm
` not sure a person of ordinary skill in
` the art reading the literature would
` see that FMOC was a useful label for
` the purpose.
` Q. FMOC groups are removable by a
` base. Is that right?
` A. A relatively strong base, yes.
` Q. Let's turn to paragraph 71 of
` your declaration as refers to the '698
` patent.
` A. '697 or '698?
` Q. '698, paragraph 71 of '698.
` A. Okay.
` Q. I'm just waiting for your
` counsel to get to that page.
` A. Yeah.
` MR. COSTAKOS: Are you all set?
` MR. WHITE: I just wanted to
` make sure that we got the right one.
` A. And -- and '698?
` Q. Yeah.
` Okay. In paragraph 71 of your
` declaration as it relates to the '698
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` patent you are referring to some
` aspects of original Claim 11.
` A. Yes.
` Q. And you say here that
` "Dr. Weinstock testified that he
` understood that Claim 11, now
` substitute Claim 25, describes the
` product of original Claim 5, i.e." --
` A. I'll need to see the claims.
` Q. Okay.
` A. I have a claims' sheet. I don't
` know if you want to give me one or I --
` I have a list of the claims. I can't
` answer your questions unless I'm --
` Q. Well, I -- I'm not done with my
` questions.
` A. Yeah.
` Q. Well, why don't we do this --
` A. Finish your question and then I
` -- I'll -- fine.
` Q. We -- we'll do it one better,
` I'll give you the patent then I'll
` re-ask the question.
` A. Excellent.
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` Q. Assuming I can find the patent.
` A. Okay.
` Q. Okay. Here's a copy of it.
` A. And this, of course, doesn't
` have the substitute claim on it, so I
` will need to -- I believe that might be
` in the back?
` Q. Well, this question really goes
` to original Claim 11 anyway.
` A. Okay.
` Q. Let -- let me re-ask the
` question now.
` You say in paragraph 71 of your
` '698 declaration that Dr. Weinstock
` "testified that he understood that
` Claim 11, now substitute Claim 25" --
` well, let me start over again.
` You say in paragraph 71 of your
` '698 declaration that, quote,
` Dr. Weinstock testified that he
` understood that Claim 11 (now
` substitute Claim 25) describes the
` product of original Claim 5; i.e., the
` product of attaching a plurality of
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` different nucleic acid templates to a
` solid surface, end quote.
` A. Right.
` Q. Do you see that in your
` declaration?
` A. Yes, I do.
` Q. Okay. And you cite there to his
` transcript, Exhibit 1034, page 79 and
` 80. Do you see that?
` A. Yes, and if you are going to ask
` me questions about it, then I'll need
` to see that as well.
` Q. My question right now is that is
` what you cited to, right?
` A. Yes. That's correct.
` Q. Is -- is that your opinion?
` A. Yes. I wrote it.
` Q. Okay. And is that -- that an
` opinion that you came up with on your
` own?
` A. All the opinions were -- were
` worked on between myself and the
` attorneys.
` Q. Okay.
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` A. Because there are certain points
` of law that I'm -- I'm not qualified to
` -- that were explained to me and I used
` them in my judgment of these things.
` Q. Is this one of those or is this
` one of those that you came up with on
` your own?
` A. I don't know about that at all.
` Certainly, all of this, I was advised
` by the attorneys, the set of attorneys
` that I'm working with on all of these
` the entire declaration.
` Q. I -- I guess that the -- the
` question I'm asking and maybe I'm
` asking it inartfully is: Is -- is this
` your opinion as -- as a scientist or
` were you provided this opinion as sort
` of a matter of law by your attorneys?
` A. The attorneys -- I -- I didn't
` get into claim construction. The
` attorneys explained to me what that
` claim means and how I should interpret
` that and then I -- I, as an expert
` witness and as a scientist and applying
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` sort of the standard of being of
` ordinary skill in the art, how would I
` read Dr. Weinstock's testimony in
` relation to the -- to the claim.
` Q. Okay. So the opinion about what
` -- what Dr. Weinstock testified about,
` that is your opinion?
` A. Yes, it is.
` Q. Okay. Now, you understand that
` original Claim 11 didn't actually have
` the word "different" in it, right?
` A. That's correct.
` Q. Okay. But you -- you say that
` what you characterize as
` Dr. Weinstock's understanding is
` consistent with your understanding?
` A. Yeah.
` Q. Right?
` A. So I'd like to --
` Q. So you see --
` A. -- I would like to see his
` deposition, if we're going to have a
` discussion about this point.
` Q. We are, but first we're going to
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` have a discussion just about your --
` your conclusion as relates to Claim 11.
` A. Okay.
` Q. Okay? So, you said that it --
` it was consistent with your conclusion
` that the word "different" --
` A. Right.
` Q. -- should be part of Claim 11?
` A. Right.
` Q. So you think that as you read
` Claim 11, original Claim 11, the word
` "different" should be in the claim
` where it says "a plurality of nucleic
` acid templates," you read that to mean
` a plurality of different nucleic acid
` templates?
` A. I think that -- that, my
` understanding, I -- I didn't rewrite
` the claim, they were represented to me
` as amended claims.
` My understanding was that change
` was meant to clarify the claim and
` certainly to broaden the claim, that's
` for sure.
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` And I believe the, and I have to
` see -- refer to Dr. Weinstock's
` deposition, but I believe that
` Dr. Weinstock understood that the
` original meaning of that claim is as --
` as written and unamended was different,
` you know, different and we said --
` said -- and I think the decision of the
` attorneys must have been to say let's
` clarify that claim so there is no
` question as to what we mean.
` Q. Sure. My question is: When you
` read the claim, the original Claim 11,
` you understood the language "a
` plurality of nucleic acid templates,"
` to mean a plurality of different
` nucleic acid templates?
` A. Absolutely. The title of the
` patent is "Massive Parallel Method of
` Decoding DNA and RNA." There would be
` no point if you are -- were just
` sequencing the many copies of the same
` thing. So the intent of the entire
` patent is a technology that allows you
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` to parallel -- to do many different
` nucleic acids in parallel.
` Q. Okay. DNA sequencing wouldn't
` really make much sense -- strike that.
` It wouldn't -- strike that.
` It wouldn't make sense to talk
` about sequencing short DNA segments
` unless the templates were different?
` A. Yeah. And I -- I think that
` Dr. Weinstock -- and my -- my
` recollection and I -- I'll be happy to
` go back to the deposition, but my
` recollection was he says, "sure," and
` we all the agree that -- well, I agree
` with that, and that it -- that these
` are different.
` Q. And the invention in the context
` of DNA sequencing wouldn't make any
` sense if the templates were all the
` same?
` A. Well, certainly, there are
` certain -- in other words, I don't
` believe the claims restrict to
` massively parallel sequencing. That's
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` -- that is what you like to do
` commercially but the claims speak to
` doing it to a single sequencing
` reaction, which is an element of the
` larger invention but they're a
` legitimate -- a legitimate invention.
` Q. A-hum.
` A. So I mean there is a difference
` here between what a claim says and what
` the intent of the larger invention in
` the commercial realm is, so I think
` that all along you're looking to do
` this many times in parallel but you got
` to do it once --
` Q. Right.
` A. -- the right way, period, before
` you can do it many times in parallel.
` Q. Right. But I thought you said
` when you read Claim 11 in its original
` form where it says, "the plurality of
` nucleic acid templates," you understood
` it to mean a plurality because in the
` context of DNA sequencing it wouldn't
` really make sense for them all to be
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