Trials@uspto.gov
`571-272-7822
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` Paper 136
`Entered: February10, 2014
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`RECORD OF ORAL HEARING
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`ILLUMINA, INC.
`Petitioner,
`V.
`
`THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF
`NEW YORK
`Patent Owner.
`
`_________
`
`Case IPR2012-00007
`U.S. Patent 7,790,869
`_________
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`Oral Hearing Held December 17, 2013
`_________
`
`
`
`
`
`Before SALLY GARDNER LANE, RICHARD M. LEBOVITZ, and
`DEBORAH KATZ, Administrative Patent Judges.
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`LANE, Administrative Patent Judge.
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`571-272-7822
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`
`
`
`
`
`
`
` Paper 136
`Entered: February10, 2014
`
`
`
`RECORD OF ORAL HEARING
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`ILLUMINA, INC.
`Petitioner,
`V.
`
`THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF
`NEW YORK
`Patent Owner.
`
`_________
`
`Case IPR2012-00007
`U.S. Patent 7,790,869
`_________
`
`Oral Hearing Held December 17, 2013
`_________
`
`
`
`
`
`Before SALLY GARDNER LANE, RICHARD M. LEBOVITZ, and
`DEBORAH KATZ, Administrative Patent Judges.
`
`LANE, Administrative Patent Judge.
`
`
`
`
`
`
`
`
`Case IPR2012-00007
`U.S. Patent 7,790,869
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`APPEARANCES:
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`On Behalf of Petitioner:
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`Jeffrey N. Costakos
`FOLEY & LARDNER, LLP
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`
`Robert Lawler
`REINHART BOERNER VAN DEUREN S.C.
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`Marcus Burch
`Roland Schwillinski
`ILLUMINA, INC.
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`On Behalf of Patent Owner:
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`Jon White
`COOPER & DUNHAM LLP
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`Anthony Zupcic
`Robert Schwartz
`Donald Curry
`FITZPATRICK, CELLA, HARPER & SCINTO
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`P R O C E E D I N G S
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`JUDGE LANE: Let's go on the record, please.
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`We're here today in three related IPRs. The parties are the Petitioner, Micron
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`Technology Inc., the Patent Owner, the Board of Trustees of the -- I'm sorry. Sorry.
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`Wrong one. Let me try that again.
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`The parties are the Petitioner, Illumina, Inc.; and the Patent Owner, the
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`Trustees of Columbia University in the City of New York. The IPR numbers are
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`2012-00006, 2012-00007, and IPR 2013-00011.
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`What we'll do is start out and have the Petitioner, Illumina, introduce
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`yourself and who you brought with you.
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`MR. COSTAKOS: Yes, Your Honor. My name is Jeff Costakos, of Foley
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`& Lardner, representing Illumina. With me today is Robert Lawler from the
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`Reinhart firm and Marcus Burch is also at counsel table. And behind me is Roland
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`Schwillinski, also with Illumina.
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`JUDGE LANE: Welcome.
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`And who is for Patent Owner?
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`MR. WHITE: John White.
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`JUDGE LANE: Mr. White.
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`MR. WHITE: John White, Your Honor. I'm here for the Patent Owner,
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`Columbia University.
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`With me is Anthony Zupcic from the Fitzpatrick firm, who is the back-up
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`counsel in the case; and Robert Schwartz from the Fitzpatrick firm; and Donald
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`Curry who is from the Fitzpatrick firm. And he will be participating this morning
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`on the one part about the objective indicia in our presentation.
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`JUDGE LANE: Okay. Welcome.
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`All right. So each side will have an hour to present your arguments. We'll
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`begin with the Petitioner.
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`The Petitioner and Patent Owner as well may reserve time for rebuttal.
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`When you get up, let me know how much of your one hour you would like to
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`reserve for rebuttal. So, we'll go Petitioner, Patent Owner, Petitioner, Patent
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`Owner, in that order.
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`Would you like to go ahead and get started?
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`MR. COSTAKOS: Yes, Your Honor. I would like to reserve 20 minutes for
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`rebuttal.
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`JUDGE LANE: 20 minutes? Okay.
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`MR. COSTAKOS: Thank you, Your Honor.
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`May it please the Board, as I indicated, my name is Jeff Costakos, and I
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`represent Illumina.
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`The claims at issue in this IPR are all invalid, and I think this first slide,
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`which is for the record slide number 2.
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`JUDGE LANE: I'm sorry. Did you bring copies of your demo?
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`MR. COSTAKOS: Oh, yes, I did.
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` (Whereupon, there was a pause in the proceedings.)
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`MR. COSTAKOS: As I indicated, this slide, which, for the record, is slide
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`number 2 of our invalidity demonstrative, I think it does a good job of illustrating
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`exactly why the Columbia claims that are at issue in this lawsuit are invalid.
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`The original independent claims of the Ju patents and the Columbia patents
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`are claims, for the most part, a method of doing DNA sequencing where a label
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`was attached to the base, a cleavable label is in most instances in the claim, and
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`where a capping group was at the 3'-OH position, removable capping group.
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`As the Board previously found, and as shown in this slide, the Tsien
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`reference actually shows each one of those limitations that were in the independent
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`claims. As we'll talk about in a few moments, Tsien shows examples where it has
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`a label attached to the base, cleavable labels specifically, and where there is a
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`removable cap improvement at the 3'-OH position. And it does it for the DNA
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`sequencing purposes.
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`So as the Board found in its order initiating the trial, the Tsien reference
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`discloses each and every element of the independent -- original independent claims
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`of the Columbia patents.
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`And I think the correctness of the Board's original decision was shown by
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`the fact that Columbia cancelled all of its original independent claims and has
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`really made no attempt in this IPR to defend the validity of those independent
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`claims.
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`JUDGE LEBOVITZ: So you're only -- will be addressing the claims as a
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`mass -- you are only addressing the claims as amended?
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`MR. COSTAKOS: Well, we did address sort of the -- because they're a
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`subset of the broader claims, we addressed every element of the claims, which
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`would include in instances where there was a dependent claim written over an
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`independent form. Naturally, we addressed every element. But I will be
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`addressing the claims that are still at issue in this litigation.
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`It is our position, and I think their pleadings have been clear, that they
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`cancelled the original independent claims. It was not a contingent cancellation.
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`Instead what they did was they proposed substitute claims. So that's what the focus
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`has been since their motion to amend was filed, and that's what I'm going to focus
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`my comments on here today.
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`JUDGE LANE: Now, why is the motion to amend not contingent?
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`MR. COSTAKOS: Well, because for one thing, it didn't say that it was
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`contingent. And the Idle Free decision makes it clear, I think on page 10 of that
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`decision, that it needs to make an expressed claim of what is contingent and what's
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`not contingent and express what the contingency is. So they didn't express any
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`contingency. And I think a substantive point of view, they made no attempt, after
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`the motion to amend was filed, to defend the validity of those cancelled
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`independent claims.
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`So it's not as though there was just a procedural failure where they forgot to
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`say it's contingent. As a matter of fact, after that motion to amend was filed, they
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`didn't say, "Oh, by the way, these original independent claims are still valid for
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`these reasons." They just didn't do that. They only addressed the amended claims
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`after their motion to amend was filed.
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`JUDGE LANE: So then we will still have to make a determination that their
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`original claims are unpatentable?
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`MR. COSTAKOS: That's right. And I think we did carry that burden in our
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`legal position and as I mentioned by virtue of explaining the invalidity of the
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`amended claims, we also showed that the independent claims -- the original
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`independent claims were also invalid. I think by virtue of their failure to defend
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`those claims and the evidence that we put in the record, it's indisputable that the
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`original independent claims should be invalid in this.
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`So, as I was saying, what Columbia did was instead to amend its claims.
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`And what it did, for the most part, was to amend the claims all to add the
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`limitations where instead of the label being attached just to the base, the label was
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`attached to a base that was a Deaza Purine.
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`Unfortunately, however, this is also shown in the prior art. And, in fact, in
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`our original petition, we demonstrated the invalidity of just this very amendment,
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`because Tsien points to Prober, which expressly discloses the use of a deaza purine
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`as the label attachment.
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`JUDGE LEBOVITZ: I think in that case, I think it was pointed out by
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`Columbia at some point that Prober talked about the deaza being on a dideoxy, so
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`where the 3' was blocked, is that correct?
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`MR. COSTAKOS: It was a dideoxy certainly in Prober, that's right. But
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`Tsien said you can use the nucleotides that are in Prober and Tsien specifically
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`shows in it -- in a pyrimidine form. Make sure I point that out. But Tsien shows
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`when it incorporates the analogues from Prober, it shows them in a deoxyuridine
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`type form not of dideoxyuridine.
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`JUDGE LEBOVITZ: Where does Tsien show that?
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`MR. COSTAKOS: On page 30. It has some examples where it shows the
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`molecules that it said would be formed by what's in the Prober. And those are
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`deoxy nucleotides, not dideoxyuridine.
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`So Prober specifically says use a 7-deaza purine as your attachment when
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`you're doing purines. And that's the only kind of purine attachment that Prober
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`discloses. It discloses attachment at a 5 position of a pyrimidine and the 7 position
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`of a deazapurine.
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`But Columbia's pleadings sort of talk as though time stops in 1991 when
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`Tsien was published. When, in fact, as we've demonstrated in our papers and as
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`this slide shows, there was an evolution of the technology and a solidification, I
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`think, of the notion that it would have been obvious to attach the label not just to
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`the base but to the deaza, to a deazapurine.
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`And in particular, the -- I should also say, I think this is an important point.
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`Prober not only says attached a 7-deaza position, but Prober also says why. Prober
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`says it's advantageous, because it has a stable linker arm attachment. So it wasn't
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`as though this was just some random attachment point, Prober actually explains the
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`reasoning behind it. And what happened then after the Tsien patent was published
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`in 1991, is that the technology that's in the Prober article -- this is technology that
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`was described by Prober and Columbia's expert Trainor and a doctor by the name
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`of Hobbs as well. That was commercialized by Applied Bio-Systems. Applied
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`Bio-Systems became the dominant player in the DNA sequencing market during
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`the '90s for signer sequencing. It was their sequencing technology and this type of
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`sequencing technology that was used in the human genome project during the
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`1990s. And by the end of the 1990s, this particular type of sequencing using labels
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`that were attached to the 7-deaza position was the dominant form of attachment for
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`DNA sequencing. It was ubiquitous. It was the way that all attachment was done
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`by the end of the 1990s.
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` And it wasn't --
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`JUDGE LEBOVITZ: Well, it seems that you're talking about prior art that
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`is not in front of us. Because what's in front of us -- primarily the Tsien reference,
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`Stemple reference, Dower, Prober and Anazawa. So I understand there may have
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`been later developments, but it's not really helping the case to know what the later
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`developments are when we have certain objections in front of us.
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`MR. COSTAKOS: Well, I think what it goes to is it shows the motivation of
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`people skilled in the art to make this modification. It's pointed to specifically in
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`Prober. It's pointed to specifically in Hobbs. It's pointed to in Stemple and the
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`other references that were mentioned. And there is evidence in the record, in the
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`original petition, Dr. Weinstock said that this was a common type of technology.
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`Dr. Trainor conceded it in this deposition that this was the common way of
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`making attachments by the time of the --
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`JUDGE LEBOVITZ: Well, we've read the briefs and we understand the
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`position on that point.
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`MR. COSTAKOS: Right. But my point is that this isn't a new piece of prior
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`art that we're trying to make a new combination. What we're showing is the
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`motivation that existed in the art to make this particular modification. And that
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`any argument that one would never have made this modification is simply contrary
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`to the facts, because the facts show that this was the way that attachment was done
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`by the end of the 2000s.
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`And, Dr. Trainor pointed out that -- in his testimony, that this modification
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`wasn't done because it was is easier. It was more difficult to synthesize a
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`deazapurine. It was more cumbersome. It took more steps. But nonetheless,
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`Applied Bio-Systems marketed its products with attachments of the --
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`JUDGE LEBOVITZ: Where is that evidence of Applied Bio-Systems?
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`MR. COSTAKOS: In Dr. Burgess's declaration, I believe, at paragraphs --
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`JUDGE LEBOVITZ: He's not -- okay.
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`MR. COSTAKOS: In Dr. Burgess's declaration he explained this very thing.
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`JUDGE LEBOVITZ: Okay.
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`MR. COSTAKOS: As I said, Dr. Trainor conceded that it was the dominant
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`form of attachment. And he also conceded in his deposition, which he had to
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`because it's in his patents as well that it was a better way of attaching, better than
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`attaching a D position.
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`So, by the conclusion of the 1990s, this technology was ubiquitous in the art
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`for attachment of labels.
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`And parallel with this, there were -- there was work that was being done in
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`the sequencing and biosynthesis fields and particularly by a group of scientists,
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`Welch, Burgess and Metzner. And what they were trying to do was to attach labels
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`at the 3' --
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`JUDGE LEBOVITZ: I understand you're trying to tell a story, but we
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`understand that. And we would like to get to more of your rejections. Like why
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`you think the claims are obvious based on this prior art that is actually in front of
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`us.
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`MR. COSTAKOS: Okay. Well, maybe --
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`JUDGE LEBOVITZ: Because, you know, we've instituted, so we clearly
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`understand what's, you know, what's going on. And I'm unclear at this point
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`whether you're talking about, you know, developments that occurred after the filing
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`date or before the filing date, so it gets a little confusing that way.
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`MR. COSTAKOS: Well, as I illustrated on the slide, all those developments
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`with the exception of the filing of the Barnes application, the Illumina application,
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`preceded the filing date of the -- of the Ju patent application here.
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`And this is all in the record. This goes to the argument that Columbia has
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`made that, number one, no one would have ever attached at the 7-deaza position.
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`So that's the argument. That goes to every claim that's at issue here, which -- where
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`the rejection is based on Tsien plus Prober. Tsien plus Prober is a rejection to every
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`claim at issue in this IPR.
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`And their argument primarily is that it wouldn't have been obvious to make
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`that modification. Well, my point is, and I think the evidence shows, that by the
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`time the patent was filed in 2000, not only would it have been obvious, everyone
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`was doing it that way. And they were doing it because it was the best way to
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`attach. There was -- there were work -- groups that were working to show exactly
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`why attaching at the 7-deaza position was advantageous over attaching at the C-8
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`position. That was Ramzaeva, Seela, Ward among others demonstrate specifically
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`why it was a better place to attach. And that's because when you attach the label, it
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`tends to stick out into open space when you attach it to the 7 position. And
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`therefore it doesn't interfere with the ability of the nucleotide to be incorporated.
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`JUDGE LEBOVITZ: And what declaration of yours lays that case out more
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`clearly? Is that in the original Weinstock declaration?
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`MR. COSTAKOS: Well, there are two declarations at issue here, right.
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`So Weinstock's declaration he explains that the advantages of attaching at
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`the 7-deaza position, and he points to Prober and Hobbs.
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` He also points to references by Williams. There are two separate Williams.
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`There is a Pete Williams and a Jay Williams. That they were attaching the 7-deaza
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`position after Tsien and referenced by Kinnard as well. So he makes that case.
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` And then also that it was common by the time of the filing of the
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`application.
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`And then in the Burgess declaration, he lays out in rebuttal to the arguments
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`that Columbia made, the fact that by the time 2000 rolled around, attachment of the
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`7-deaza position was common and was well accepted in the art as the most
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`effective way to make the attachment.
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`But the other argument that Columbia has made is that it wouldn't have been
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`obvious to attach at a base at all. A base -- strike that.
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`That it wouldn't have been obvious to attach the label to a base at all.
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`Obviously Tsien showed that very thing, so that's a little bit beside the point. But,
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`they make sort of a starting-point argument.
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`And I think this slide again, slide 2, shows graphically why that's not the
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`case.
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`What happened is, as I was indicating before, is there was this group of
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`Welch, Burgess and Metzner. They were trying to attach the label at the 3'-OH
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`position, which is the further embodiment in Tsien. What they found after years of
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`trying was that it didn't really work. What they said was -- and they published this
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`in an article that was published in 1999, attaching a label to the 3'-OH position
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`tends to be too big to fit, and so it interferes with the incorporation of fluoros and --
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`JUDGE LEBOVITZ: It sounds like you're trying to bolster your prima facie
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`case.
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`MR. COSTAKOS: No, I don't think so, Your Honor. Because, well, for one
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`thing, attachment at the base is already a given, because that was disclosed in
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`Tsien.
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`So is this an argument in response to their starting-point argument.
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`We already showed that Tsien doesn't just suggest it, but actually says attach
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`the label at the base. So that's in the prior art, and I don't really think that that's
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`disputed. What we're pointing out is that by the time -- and we're pointing out that
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`contemporaneously with the publication of this Welch article, a number of people
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`arrived at exactly the same conclusion.
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`JUDGE LEBOVITZ: So where's Tsien? Can we go to Tsien? Where does
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`Tsien show you put the label on the base using a cleavable linker?
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`MR. COSTAKOS: Sure. Let's get to that.
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`Okay.
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`So Tsien discloses in a number of places attachment of the label to the base.
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`At the -- here on page 26 -- excuse me, on page 27, he says that you can use
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`a label such as a fluorescent group which is coupled to a remote position such as a
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`base.
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`JUDGE LANE: And you're on slide five of your exhibit?
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`MR. COSTAKOS: Yes, thank you, Your Honor, I'm on slide five.
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`There are a number of other places as well that demonstrates the very same
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`thing, including on page 30 where it actually shows some examples of attaching at
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`the base.
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`Dr. Trainor agreed that Tsien shows an embodiment where a fluorescent
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`label is on the base and there is a 3'-blocked OH.
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`Tsien also discloses -- I'm looking now at slide 6 of our demonstratives a
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`cleavable 3'-blocking group. And this is a reference to page 20 of Tsien. This is
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`line 28 through page 21, line 3.
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`There is a section in Tsien that talks about blocking groups and has a
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`number of different types of blocking groups that can be used. And, in fact, Tsien
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`discloses the very blocking group that is used in the Columbia patent, an allyl
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`blocking group. And he discloses that on page 24, at lines 24 through 30.
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`JUDGE LEBOVITZ: What kind of sequencing scheme was Tsien using?
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`Was he using deoxy, dideoxy sequencing or was he doing sequencing by
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`synthesis?
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`MR. COSTAKOS: Sequencing by synthesis. That was the whole point of
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`Tsien was to do sequencing by synthesis as an improvement over Sanger's
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`sequencing. That's exactly what he said.
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`JUDGE LEBOVITZ: So in sequencing by synthesis, you would necessarily
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`want a blocking group on the 3-prime end, right?
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`MR. COSTAKOS: Certainly that's the most common way of doing
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`sequencing.
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`JUDGE LEBOVITZ: So that was known. And that's shown in Tsien, having
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`blocking groups on the 3' end?
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`MR. COSTAKOS: That's right, yes. And what it shows here is a small
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`3'-blocking group, a cleable one. And he shows an allyl blocking group, as I
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`mentioned, as the very type of blocking group that is shown in the Columbia
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`patent. The only blocking -- well, there are two blocking groups, but that's one of
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`the two is shown in the Columbia patent.
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`Looking at slide 7, Tsien also discloses a cleavable linker.
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`Tsien says that there could be a tether, which attaches the label to the remote
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`position such as the base. The tether can be cleavable. And he gives some
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`examples of types of linkers that can be used that are cleavable, and specifically
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`says they can be cleavable by chemical means.
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`JUDGE LEBOVITZ: Right. But the claims or some of the claims require
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`that the groove of the group is on the base that connects the label to the base. I
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`don't see Tsien saying that.
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`MR. COSTAKOS: Well, this part right here is talking about a label that's
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`attached to the base.
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`JUDGE LEBOVITZ: It just says attached to the nucleotide.
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`MR. COSTAKOS: Well, if you look immediately before it -- maybe I can
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`get Tsien here.
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`(Whereupon, there was a pause in the proceedings.)
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`MR. COSTAKOS: I'm not sure if I can work this exactly like I would like
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`to.
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`JUDGE LANE: You can just tell us.
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`MR. COSTAKOS: Maybe I'm tell you. It's easier.
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`JUDGE LANE: I think it's the figure in 1002, is that --
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`MR. COSTAKOS: Yes, this is Exhibit 1002 and I was attempting to put on
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`the Elmo a portion of page 28 which, beginning at page 27, around line 33, starts
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`talking about alternatives to labeling at the 3'-OH position. And it says, which we
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`went through before, there are a number of alternatives. Particularly you can use a
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`label such as a fluorescent group coupled to a remote position such as a base. And
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`then it says -- it talks about one method of -- involves use of a fluorescent tag
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`attached to the base nucleotide, and it talks about it in a irreversible form. And this
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`is at page 28, beginning at line five.
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`JUDGE LEBOVITZ: And you're reading from what reference?
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`MR. COSTAKOS: The Tsien reference, Exhibit 1002.
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`JUDGE LEBOVITZ: Thank you.
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`MR. COSTAKOS: Okay. So Tsien, Exhibit 1002, page 28, beginning at
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`line 5, talks about one type of labeling using a fluorescent tag, tag on the base.
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`And then it says that can be irreversible. And then beginning at line 19, it talks
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`about another type of labeling and it says, "What did you do there?" And that what
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`I have up in front of you on slide 7. It's the use of a cleavable linker.
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`So you can, instead of having a label that doesn't come off, as an alternative,
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`you can have a label that does come off. And it specifically says that.
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`This section here is all about labeling of the base. Beginning at page 27 and
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`continuing through page 30.
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`Okay?
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`JUDGE LEBOVITZ: So what about, now, most of the claims also have the
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`deaza on it, so where does the deaza come from? How do we get to there?
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`MR. COSTAKOS: Sure. Tsien specifically points to the Prober reference.
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`And Prober, as I indicated before, discloses attachment at a 7-deaza position for the
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`purine. And that's the only type of attachment that is shown in Prober.
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`JUDGE LEBOVITZ: Do you have testimony on that, that's the only type of
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`attachment shown in Prober? Is there evidence of that?
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`MR. COSTAKOS: I'm pretty confident we do. I'm not sure I can cite it right
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`here in front of you, but if you look at Prober, there are only I think three places in
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`Prober where there is reference to attachment at the purine. And each time it says
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`7-deazapurine. It is a relatively short reference and that's all that it's about.
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`JUDGE LEBOVITZ: Well, I think you would have to establish that fact, but
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`I do think that it's in the Burgess declaration.
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`MR. COSTAKOS: I'm pretty sure that we've said it as the type attachment
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`that's shown in Prober.
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`In addition, as I indicated, attachment at the 7-deaza position became even
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`more common after Tsien and Prober were published. I went through that earlier
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`with reference to slide 2.
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`JUDGE LEBOVITZ: Does Columbia agree or disagree with you about the
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`deaza in Tsien?
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`MR. COSTAKOS: Well, they don't dispute that Prober teaches a deaza,
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`sure.
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`JUDGE LEBOVITZ: Sure. But what about Tsien, do they dispute that?
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`MR. COSTAKOS: Their argument, as I understand it, as it relates to Tsien,
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`is that Tsien points to attachment at the C-8 position for a purine and that it points
`
`to Prober for attachment with a purine. That's their argument.
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`And the point I was making earlier when I was talking about the evolution of
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`the technology, was that not only does Prober say what the advantages of attaching
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`at the C-7 position, not the C-8, but after Prober there was even more in the art that
`
`explained why a C-7 was a better attachment position than a C-8 position.
`
`So, while the C-7 was a harder and the 7-deaza was a harder period to
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`synthesis, as a matter of fact it turned out that it worked better. And so, that was
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`the reason that by 2000 it became the dominant way of attaching labels to bases for
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`DNA sequencing.
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`JUDGE LEBOVITZ: You're making that argument based on other reference
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`that are not part of the original prima facie case that you -- excuse me, the
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`patentability challenge?
`
`MR. COSTAKOS: Well, what I would say is that we're making that both
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`based on the references that were part of the original filing and argument -- and
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`references that were added after, yes.
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`JUDGE LEBOVITZ: Right.
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`But that sounds like you're trying to bolster your prima facie case.
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`MR. COSTAKOS: No, I wouldn't put it that way. I'm sorry?
`
`JUDGE LEBOVITZ: I hadn't finished.
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`MR. COSTAKOS: I apologize. I thought you were done. But I wouldn't
`
`say it that way. What we're doing is we're responding to specific arguments that
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`Columbia has made about why it would not, they think, have been obvious to make
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`this modification. And I think that's entirely permissible for us to do in our
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`response to their papers.
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`They are the ones -- they amended the claims after all to focus on this deaza
`
`limitation. We established in our original papers, and pointed you to a Weinstock
`
`declaration and some of these other references that show that 7-deaza was an
`
`attachment point that was used in the art. And then in response to their specific
`
`arguments about why that wouldn't have been a good idea, we have cited
`
`additional references to show that in fact that was the predominant way of
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`attachment by the time 2000 rolled around.
`
`I think it's worth pointing out -- this was in the slide that we were looking at
`
`in the beginning. I mentioned how the contemporaneous invention by others
`
`argument that we've made, that once Welch came out with his publication saying
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`labels are too big to fit at the 3'-OH position position, at least four other groups
`
`happened upon the exact same solution to that problem. Stemple, Amersham or
`
`Odedra, Ju and Barns/Illumina/Solexa all said, you know what, if it's too big to fit
`
`at the 3'-OH position, we're going to attach it at the base.
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`But not only that, because of course Tsien had already disclosed that very
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`thing, not only did they say we're going to attach it at the base, they said we're
`
`going to attach it at the 7-deaza position. This is in 1990. This is a
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`contemporaneous invention by others that I think that the law is clear tends to
`
`show obviousness.
`
`JUDGE LANE: Did you make this argument in your brief?
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`MR. COSTAKOS: This was an argument that was made in our reply. This is
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`an objective indicia of obviousness that was included in our reply not in our
`
`original petition.
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`JUDGE LEBOVITZ: And you were citing Stemple, Ju, Barnes, Welch, and
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`what was the other reference I heard?
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`MR. COSTAKOS: Odedra.
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`JUDGE LEBOVITZ: Spell that.
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`MR. COSTAKOS: O-D-E-D-R-A, which is Exhibit 1048. Odedra
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`sometimes is referred to as Amersham in the papers, because that was the
`
`inventive --
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`JUDGE LEBOVITZ: In all of these references your position will show an
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`attachment at the fluorescein base -- of the fluorescein tag to the base at the 7'
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`position?
`
`MR. COSTAKOS: At the 7-deaza position, yes.
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`JUDGE LEBOVITZ: Are these -- are all five of these references prior art to
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`Columbia?
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`MR. COSTAKOS: No. They are not.
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`JUDGE LEBOVITZ: Which ones are?
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`MR. COSTAKOS: Of those, obviously one of them is Columbia, so that's
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`not --
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`JUDGE LEBOVITZ: Stemple is.
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`MR. COSTAKOS: Stemple is and the other two are not. So Odedra is not
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`prior art and the Barnes reference is not.
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`JUDGE LEBOVITZ: All right. Welch?
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`MR. COSTAKOS: Welch doesn't show -- I'm sorry, maybe I should clarify
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`my previous comment.
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`Welch doesn't show attachment at the 7-deaza position. Welch is the one
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`that says the label is too big to fit at the 3'-OH. Welch didn't propose a specific
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`solution. My point was that once Welch came out with his article saying it was too
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`big to fit, everybody else came up with the same solution at about the same time.
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`Which is attachment at the base and attach at the 7-deaza position.
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`JUDGE LANE: To be clear, this argument is not part of your prima facie
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`case, it's part of your reply?
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`MR. COSTAKOS: The contemporaneous invention by others argument is
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`part of the reply, yes.
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`(Whereupon, there was a pause in the proceedings.)
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`MR. COSTAKOS: Okay. As I indicated, some of these we have already
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`gone over.
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`JUDGE LEBOVITZ: I think we understand that.
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`MR. COSTAKOS: Fair enough.
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`Now, as I indicated, Prober explains why 7-deazapurines are advantageous,
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`but so are the Hobbs' reference, which was in our original petition and was cited
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`for this very proposition. Hobbs is an invention by Hobbs, Prober and Trainor.
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`And Hobbs explains in detail why this was better and explains synthetic routes to
`
`synthesize the particular molecules that are at issue here.
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`JUDGE LEBOVITZ: So Hobbs is prior art, but it was not cited in your
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`petition, and you're now relying on it to establish why you would use deazapurine
`
`to attach the fluorescent tag?
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`MR. COSTAKOS: No. Hobbs was cited in our petition. You're right, it is
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`prior art. It was cited as a grounds of rejection by us, by Illumina, in the petition. It
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`was found by the Board to be redundant.
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`JUDGE LEBOVITZ: Okay. Right.
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`MR. COSTAKOS: The point though, again this goes to the motivation, this
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`is an attempt at a new obviousness --
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`JUDGE LEBOVITZ: First evidence of the advantage of using a 7-deaza?
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`MR. COSTAKOS: Right. Exactly. And Hobbs has great detail on exactly
`
`how to make nucleotide analogues, deaza nucleotide analogues. And, in fact, the
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`patent that is at issue here points only to Hobbs and Prober for its teaching of how
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`to synthesize a 7-deaza nucleotide to be used in its invention. So there's an
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`argument that's been made by Columbia that, well, none of them really know how
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`to synthesize this particular molecule. But Hobbs has great detail on that.
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`The Ju patents point to Hobbs and Hobbs and Prober only as support for
`
`how to do the synthesis of the very molecules that they're attempting to patent.
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`JUDGE LEBOVITZ: Prober does not? Is that --
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`MR. COSTAKOS: Prober says -- Prober is an article. It's much shorter than
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`Hobbs. But it has a paragraph that says here is a highly convergent and general
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`approach, and it explains how to make a -- I think it's a dideoxy-T. I think it
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`explains how to make the T version. It doesn't exp
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