`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 IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`
`
`
`____________
`
`Record of Oral Hearing
`Held: March 5, 2019
`____________
`
`Before JAMES A. WORTH, MICHELLE N. ANKENBRAND, and BRIAN
`D. RANGE, Administrative Patent Judges.
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`APPEARANCES:
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`ON BEHALF OF THE PETITIONER:
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`WILLIAM R. ZIMMERMAN, ESQUIRE
`Knobbe Martens
`1717 Pennsylvania Avenue
`Suite 900
`Washington, D.C. 20006
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`
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`KERRY S. TAYLOR, Ph.D., ESQUIRE
`NATHANAEL R. LUMAN, Ph.D., ESQUIRE
`Knobbe Martens
`12790 El Camino Real
`Suite 100
`San Diego, CA 92130
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`ON BEHALF OF THE PATENT OWNER:
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`The above-entitled matter came on for hearing on Tuesday, March 5,
`
`2019, commencing at 9:01 a.m., at the U.S. Patent and Trademark Office,
`600 Dulany Street, Alexandria, Virginia.
`
`
`JOHN D. MURNANE, ESQUIRE
`ROBERT S. SCHWARTZ, Ph.D., ESQUIRE
`Venable Fitzpatrick
`1290 Avenue of the Americas
`20th Floor
`New York, NY 10104
`
`JOHN P. WHITE, ESQUIRE
`Cooper & Dunham LLP
`30 Rockefeller Plaza
`New York, NY 10112
`
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`2
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`P R O C E E D I N G S
`- - - - -
` JUDGE ANKENBRAND: Good morning, you may be seated. Just
`give us a minute here. Is the court reporter ready? All right. Let’s go on the
`record. Good morning, everybody. Today we have our final hearing in IPR
`numbers 2018-00291, 318, 322, 385 and 797. Between petitioner Illumina
`Inc,. and patent owner, The Trustees of Columbia University in the City of
`New York.
`I’m JUDGE ANKENBRAND. I’m joined today by Judge Worth who
`is sitting to my left and Judge Range who is appearing remotely from our
`Dallas hearing room.
`Counsel, can you please introduce yourselves and let us know who
`will be making the arguments today? We will start with petitioner, Illumina.
`
`MR. ZIMMERMAN: Good morning, Your Honor. Bill Zimmerman
`of Knobbe Martens, Holston and Bear on behalf of petitioner Illumina. I
`will be making the argument today. With me are my partners Kerry Taylor
`and Nate Luman, also of Knobbe Martens and Roland Schwillinsky and
`Marcus Burch of Illumina.
`
`JUDGE ANKENBRAND: All right. Good morning, everyone. And
`for the patent owner, who do we have today?
`
`MR. WHITE: John White from Cooper and Dunham. Presentation
`will be made by Mr. John Murnane of Venable and he is sitting right here.
`And with us are also from Venable, Justin Oliver, Robert Schwartz, and
`Zachary Garrett. And we have a number of people from Columbia, as well
`as the inventor, Dr. Ju, present.
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`
`JUDGE ANKENBRAND: All right. Good morning, everyone.
`Thank you, welcome. It is good to have everyone here.
`We set forth the procedures for today’s hearing in our trial order but
`I’ll just remind everyone a little bit about the way this will work today.
`Each party will have 60 minutes of total time to present their arguments.
`Petitioner, since you have the burden of showing unpatentability,
`you’ll go first and then that will be followed by patent owner’s presentation.
`Also both parties may reserve some brief time for rebuttal.
`One thing I’ll say is that one of our goals it to keep the hearing
`running smoothly and focused on the merits so we ask that everybody
`refrain from objecting during an opposing -- an opponent’s presentation. If
`you do have an objection you can make that objection during your
`presentation time.
`One more thing before we begin. Judge Range will not be able to
`view anything that you project on the screen in the room here. So when you
`refer to an exhibit on the screen, please state for the record the exhibit and
`page number or if it’s a demonstrative, the slide number to which you are
`referring so that Judge Range can follow along with us. It is also important
`to do so for the clarity and accuracy of our transcript.
`Also, our microphones do have limitations so Judge Range will be
`unable to hear you if you stray too far from the podium. So just keep that in
`mind as you are making your arguments. I will ty to give each counsel a
`warning when you are reaching the end of argument time. Does anyone
`have any questions or concerns at this point? Mr. Zimmerman?
`
`MR. ZIMMERMAN: No, Your Honor, thank you.
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`
`JUDGE ANKENBRAND: Okay. Mr. White?
`
`MR. WHITE: No. No, Your Honor.
`
`JUDGE ANKENBRAND: All right. So we will start with Mr.
`Zimmerman. And I guess the first thing I will ask is would you like to
`reserve any time for rebuttal?
`
`MR. ZIMMERMAN: Yes, Your Honor, I would like to reserve 15
`minutes.
`
`JUDGE ANKENBRAND: Okay.
`
`MR. ZIMMERMAN: And I have copies of petitioner's
`demonstratives. I know they were already submitted. If you’d like a bound
`copy we have them.
`
`JUDGE ANKENBRAND: Sure, you can pass them up.
`
`JUDGE WORTH: Have you given one to the patent owner?
`
`MR. ZIMMERMAN: Yes, patent owner already has a copy. We
`talked to them earlier.
`
`JUDGE ANKENBRAND: Thank you. All right. We are ready to
`begin whenever you are.
`
`MR. ZIMMERMAN: May it please the Board. Illumina has
`challenged four Columbia patents that claim 3ʹ-O protected labeled
`nucleotides and one patent that claims a method of sequencing using any of
`those nucleotides. These patents share the same specification and the same
`or similar claim limitations to patents that were previously cancelled by the
`Board in IPR and affirmed by the Federal Circuit.
`I would like to start with the issues common to all five patents, then
`address one issue unique to the method patent relating to claim construction,
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`and then address the judicial estoppel and preclusion issues.
`If we could go to Slide 2. The party’s disputes focus on two claim
`limitations. And they relate to R, the 3ʹ capping group. The first that it be
`small and chemically cleavable, the second one that it not interfere with
`recognition of the analogue as a substrate by DNA polymerase. And that’s
`basically an incorporation requirement
`
`JUDGE WORTH: Does this claim require multiple rounds of
`polymerization?
`
`MR. ZIMMERMAN: that is the issue unique to the method case and I
`will go directly to that. If we could go to slide --
`
`
`JUDGE WORTH: So you’re conceding or you’re arguing --
`
`MR. ZIMMERMAN: It is Illumina's position that none of the claims
`require multiple rounds of sequencing. And if we go to the method case,
`which is the easiest one to address that, it's Slide 54.
`The method claim recites a method for sequencing a nucleic acid
`which comprises detecting the identity of a nucleotide analogue incorporated
`into the end of a growing strand of DNA in a polymerase reaction.
`The remainder of the claim set forth a full method of detecting so the
`preamble doesn’t give life and meaning go the claim.
`And the best way to illustrate that is if we go to Slide 55. The patent
`sets out a 9 step process for sequencing. Step 8 is the deprotecting step at
`the 3ʹ position and step 9 is repeating the steps. The claim stops at step 5
`which is the detecting step.
`So there is nothing in the claim language that requires repeating the
`steps, deprotecting at the 3ʹ position, much less sequencing a particular
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`number of bases.
`There is absolutely nothing in the claim language that says 20 bases,
`10,000 bases, even though Columbia would like to read that into the claim.
`There is just no claim language that would support that.
`And in fact, the patent itself contains no sequencing data showing any
`particular number of sequences.
`
`JUDGE WORTH: Going back to the product claims.
`
`MR. ZIMMERMAN: Yes.
`
`JUDGE WORTH: When it says chemically cleavable, why would it
`be cleavable if you’re not repeating it?
`
`MR. ZIMMERMAN: It is cleavable so that it can be used in the
`method and you -- the entire SBS process is designed to be repeated but
`there is nothing in the claim language that actually requires multiple steps in
`the claims as written.
`And so you need it to be cleavable for an SBS process but in order to
`infringe the claim, you don’t have to actually cleave it.
`
`JUDGE WORTH: So you’re saying that the purpose is for repetition
`but it’s not required.
`
`MR. ZIMMERMAN: Exactly. And they could have amended the
`claims. They could have written in the steps that require repeating the
`process. They knew how to do that in Slide 55 where they set out the full
`process but there is nothing in the claim language that actually requires
`repeating the process.
`
`JUDGE WORTH: I mean, what is unusual about this case is if you
`look at the arguments, that there is a lot of arguments about what is mild,
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`what is aqueous. Where is that in the claim?
`
`MR. ZIMMERMAN: The claim itself does not actually recite mild
`conditions, aqueous conditions. It recites cleavable and that it be chemically
`cleavable.
`Now if you’re using that with a DNA process, both Tsien and the
`Columbia patents have the same requirements for their method.
`And if we go to Slide 17, and so it goes more to motivation, Your
`Honor, than an actual claim requirement. The Tsien reference says you need
`efficient incorporation for the SBS method. And then it says need mild
`conditions for rapid and quantitative deblocking.
`Those are the conditions you need to run this process multiple times.
`and Columbia’s patent then gives you four fundamental requirements and
`they're the same.
`And Dr. Menchen, the expert for Columbia, on the next slide, Slide 18
`admitted that they're the same requirements in Tsien's method and the
`Columbia patents.
`
`JUDGE WORTH: Well, in your briefs, do you say anywhere that
`SBS is not required and that these thing that are being argued by patent
`owner are not required? You know, where is this in your brief?
`
`MR. ZIMMERMAN: These conditions, Your Honor?
`
`JUDGE WORTH: What we just talked about. I’m --
`
`MR. ZIMMERMAN: The --
`
`JUDGE WORTH: -- incorporating the whole prior discussion we just
`had about --
`
`MR. ZIMMERMAN: Okay.
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`
`JUDGE WORTH: -- is SBS required by any of the five claims and --
`
`MR. ZIMMERMAN: There is no dispute among the parties that both
`Tsien, Dower and the Columbia patents are all directed to SBS. And a
`person of skill in the art would have known that these are the requirements if
`you’re going to make a commercial SBS system.
`But if you look at the claims as written, none of the nucleotide claims
`actually require a step of deprotecting the 3ʹ-OH. And none of the method
`claims say you have to deprotect the 3ʹ-OH or repeat the cycles for any
`number of sequences.
`
`JUDGE WORTH: Did you say that in your brief?
`
`MR. ZIMMERMAN: Which part?
`
`JUDGE WORTH: What you just said?
`
`MR. ZIMMERMAN: We did.
`
`JUDGE WORTH: You did. And where is that?
`
`MR. ZIMMERMAN: In the petitioner reply, we made clear, there’s a
`section on claim construction relating to the method claims. And it is
`specifically at let me see, the reply at page 4.
`Now the interesting piece of this is you have the Tsien patent, which
`has no data, no actual sequencing data. And the Columbia patents none of
`which contain any actual sequencing data.
`And so I think it is important that you understand the timeframe we
`are dealing with. When Tsien's method comes out in '91, his patent says
`here is the method but there is no data. And he tells the skilled artisan use
`allyl, allyl has advantages. And if we look at slide --
`
`JUDGE WORTH: Sorry, before we move on so you were just
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`referring to the reply brief in the 797 case.
`
`MR. ZIMMERMAN: Yes.
`
`JUDGE WORTH: So in the product claim cases, did you put in a
`claim construction that multiple rounds of SBS are not required for this
`product?
`
`MR. ZIMMERMAN: We did not argue that in the petitions and there
`was no argument in the nucleotide cases from patent owner that multiple
`rounds were required. That issue only came up in the context of the method
`claim in the 797 IPR.
`
`JUDGE WORTH: Okay. Please proceed.
`
`MR. ZIMMERMAN: Okay. So we are in a state of the art where
`Tsien is in '91. It sets forth an SBS method but it has no data. And so it
`directs you to the allyl capping group.
`And if we look at Slide 4, it specifically discloses allyl ethers as the 3ʹ
`blocking group. But Tsien does more than that. It gives you a reason to use
`the allyl ethers along with the other specified ones that these capping groups
`are stable during the sequencing steps and they have some advantages.
`And the advantage is that deblocking occurs only when specific
`reagents are present and premature deblocking during incorporation is
`minimized. You then have --
`
`JUDGE WORTH: Well, --
`
`MR. ZIMMERMAN: Go ahead, Your Honor
`
`JUDGE WORTH: Please proceed.
`
`MR. ZIMMERMAN: Okay. Dr. Menchen, Columbia's expert, agrees
`if we look at Slide 5 that a person of ordinary skill in the art would have
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`recognized the advantages of Tsien's allyl.
`
`JUDGE WORTH: What do you make of the argument that mercury
`denatures DNA?
`
`MR. ZIMMERMAN: Mercury would denature DNA and I think what
`you have to do is look at Tsien's reaction conditions which is the mercury 2
`and then you have to look at what is actually in the patent and that is at Slide
`32.
`
`In the patent, they tell you that it is known that MOM and allyl groups
`can be used to cap an OH group and can be cleaved chemically with high
`yield, cites to Kamal.
`Then if we go to Slide 32 --
`JUDGE WORTH: Isn’t that hindsight
`
`MR. ZIMMERMAN: No. The patent itself is telling you use
`
`Kamal’s conditions. And it tells you on Slide 32 that Kamal is mild, doesn’t
`denature the DNA, rapid 3 minutes, and 93 percent.
`Kamal is in the prior art and now Columbia says Tsien’s conditions
`don’t work. Kamal’s conditions don’t work. They’ve admitted in their
`specification that Kamal provides cleavage conditions. And now they’re
`denigrating those conditions.
`And what we really have is, I don’t think the cite in the patent to
`Kamal is saying use Kamal exactly. And I don’t think Tsien is saying use
`Gigg and Warren’s method exactly. I think they're pointing out represented
`-- representative chemistries and that a person of skill in the art would have
`known how to adjust these chemistries to work with SBS systems.
`
`JUDGE WORTH: So your first argument is that the chemistries don’t
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`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`matter because you don’t need multiple rounds of SBS. That’s your first
`argument.
`
`MR. ZIMMERMAN: Yes.
`
`JUDGE WORTH: And then your second argument is that Kamal is
`mentioned and that a person of ordinary skill would know how to adapt
`Kamal so that it would work with multiple rounds?
`
`MR. ZIMMERMAN: Let me be very clear because I don’t want there
`to be any confusion and I might not have been clear. The patent says Kamal
`provides cleavage conditions.
`And there are no other cleavage conditions in the Columbia patents.
`The only cleavage conditions are the cite to Kamal. And so they're now in
`this strange positon of saying we cited Kamal in our patent, it is the only
`cleavage conditions but those don’t work. And I don’t think that can be
`right.
`I think we have to take the patent at its face value that Kamal provides
`conditions. But I think what they were really trying to teach is the skilled
`artisan knew of other conditions that would work.
`And in our petition, Dr. Romesberg, if we go to Slide 35, he explained
`that it was known in the art that the allyl group could be removed chemically
`with high yield using palladium chemistry. And he said this could be done
`in aqueous conditions and that’s at Exhibit 1012 at paragraph 64.
`And so the state of the art he cites the Qian reference, the Boss
`reference. He cites to Kamal which comes out of the patent. And so you
`have this situation of this palladium chemistry was known in the art.
`Columbia comes back and says individually Tsien doesn’t work. The
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`Kamal conditions in our patent don’t work by themselves. Qian’s conditions
`don’t work individually. Boss doesn't work individually.
`But they miss the collective state of the art that this palladium
`chemistry was known to people of skill in the art and they would have been
`able to use that in an SBS compatible way.
`And when they raise this challenge based on each one individually
`rather than the whole of the art we came back and said okay, look at Exhibits
`1094, 1114, 1115. These are papers by Genet.
`And if we bring up Slide 38, Genet shows palladium based chemistry
`in aqueous media that’s rapid. And the title even says aqueous media.
`
`JUDGE WORTH: Are these the esters -- you're -- this is the where
`you're relying on esters for ether chemistry?
`
`MR. ZIMMERMAN: This is alloc is what is shown in the Genet
`papers.
`
`JUDGE WORTH: Okay. And so patent owner’s argument is that
`alloc is different than an allyl group?
`
`MR. ZIMMERMAN: Yes. And I will address that directly. If we go
`to Slide 39, Columbia’s expert admitted that the chemistry of Genet, this
`palladium chemistry was well known.
`Then if we go to Slide 41, Ju's lab, one of his thesis advisees publishes
`a paper in 2006 and I know that’s not prior art, but he says in the paper in the
`past decades.
`So going back into the prior art, chemists have developed efficient
`catalysts to cleave groups from allyl ethers. And he cites to Genet. So their
`own lab, Dr. Ju's own lab, makes clear that the Genet chemistry isn’t limited
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`to allyl alloc. It covers allyl ethers as well.
`He goes on to say that the -- it happens in aqueous media, its rapid, it's
`efficient and the conditions were mild and complete in 15 minutes. That’s at
`Exhibit 116 page 164.
`
`JUDGE WORTH: So what you’re saying is that you’re relying on
`that reference not for a claim limitation but for the knowledge of -- to inform
`what the knowledge of a person of ordinary skill would have been before the
`critical date?
`
`MR. ZIMMERMAN: Yes. And if you look at the claims, I believe
`they just claim the nucleotide. Now whether that 3ʹ group is cleavable is a
`latent property of allyl. So you shouldn’t have to demonstrate cleavage
`conditions.
`The allyl group is cleavable, that’s just a property that’s inseparable
`from the compound. But to the extent you need to show cleavage
`conditions, because that is our burden, the prior art has palladium based allyl
`cleavage conditions that are rapid, aqueous, efficient and meet all the
`requirements.
`And the real question is if Kamal which is cited in the patents doesn’t
`work, and their position is that the skilled artisan wouldn't have known, then
`what are they relying on for disclosure in the patents? What supports this
`cleavability if it's not Kamal, which is the only thing cited?
`So they would have a real problem if that’s truly their position. I
`don’t believe it is. I believe although they're attacking each reference
`individually, that they will admit that palladium based chemistry of Genet
`was known in the art and would cleave allyl, especially in view of Dr. Ju's
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`own lab admitting it.
`
`JUDGE WORTH: Are you relying only on an allyl group?
`
`MR. ZIMMERMAN: So --
`
`JUDGE WORTH: From the 3ʹ blocking group or are you relying in
`your petition or somewhere else for something other than an allyl group?
`
`MR. ZIMMERMAN: The petition was based on the allyl group of
`Tsien and the Dower based ground using the allyl group of Metzger 94. So
`both Ground 1 and Ground 2 rely on an allyl group.
`And the patent owner admitted during prosecution that allyl was small
`so there is no need for a claim construction of small. There is no dispute that
`allyl is small and satisfies that requirement.
`
`JUDGE WORTH: Can you walk us through the argument and the
`evidence and specifically where is this in your briefs about Dr. Menchen's
`patents? It seems like you’re relying on maybe deposition testimony but
`then you’re talking about Dr. Menchen’s own patents.
`
`MR. ZIMMERMAN: Yes. So there was an argument raised by
`Columbia that you have the Tsien article, Tsien patent, and then Metzger
`which discloses specific data with allyl and that nobody then did it until
`Columbia. That allyl was essentially abandoned as a capping group.
`And Dr. Menchen’s patents respond directly to that argument. If we
`look at Slide 12, Dr. Menchen has a 1998 patent that talks about capping at
`the 2ʹ or 3ʹ position and he uses allyloxy, which everybody has admitted in
`this proceeding is the 3ʹ-O allyl.
`So the idea that nobody used allyl as a 3ʹ blocking group is undercut
`by their own expert.
`
`
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`
`JUDGE WORTH: So you’re talking about Exhibit 1119?
`
`MR. ZIMMERMAN: Exhibit 1091 is the mentioned patent. Exhibit
`1119 is Dr. Romesberg's testimony that 3ʹ-O allyl is the same as 3ʹ allyloxy.
`
`JUDGE WORTH: Okay. And then there is a notation here. Is this in
`your -- what exactly is in your reply brief? And which case is this in?
`
`MR. ZIMMERMAN: This is in the reply brief in all five cases. And
`this simply responds to the argument that nobody used allyl as a capping
`group. And the suggestion seems to be that Metzger’s data would have
`pushed people away from allyl as a capping group. Then if we go to Slide
`13 --
`JUDGE RANGE: This is Judge Range in Dallas. Isn’t Menchen’s
`
`patent, is that an SBS process?
`
`MR. ZIMMERMAN: It is not an SBS process but it’s still in the
`DNA polymerase context.
`
`JUDGE RANGE: Okay.
`
`MR. ZIMMERMAN: And the cap, the use of a capping group it
`spans more than just SBS, Your Honor.
`And then if we look at Slide 13 Dr. Menchen in his 1999 patent again
`cites to allyloxy as a capping group but this time he specifically cites the '94
`Metzger article for reversible nucleotide terminators.
`So it's the exact article that discloses the data for the 3ʹ allyl group as a
`capping group.
`And then on Slide 15, Dr. Menchen was asked well, why did you still
`identify the allyl group and he says because that’s what Metzger calls it. He
`cites Metzger in his patent and admits that his disclosure of the allyl is based
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`on Metzger so it’s to refute this idea that nobody looked at allyl from the
`time of Metzger to the time of the Columbia patents.
`
`JUDGE WORTH: So you may have a claim presentation but I did
`want to take you to a different tack right now, which is and I, you know, you
`can tell me if this is in your briefing. But let’s say according to your first
`argument that we discussed that there is no multiple rounds required.
`Does that change the lens through which we would look at the
`effectiveness of let’s say the completeness of the termination? So in the
`primary Metzger reference, it's with an asterisk and that means its
`incomplete termination at a certain concentration.
`And let’s just say hypothetically that you don’t have to have multiple
`rounds of polymerization. Does that affect the way you look at whether it is
`desirable to have complete termination or not? Or not desirable and is this
`briefed?
`
`MR. ZIMMERMAN: Your Honor, it -- the -- what Metzger shows
`and teaches with respect to incorporation is briefed. But I think the better
`way for me to explain it is in context of what happened in the actual world.
`So Tsien has this method and says use allyl, it has advantages but
`there is no data. Then Metzger in '94 tests eight different nucleotides,
`different 3ʹ capping groups, one of which is allyl. And in that he says there
`is incorporation.
`And I know it's termination star but Metzger’s actual conclusion in
`that article and its Exhibit 1016 at page 4265. The protecting groups
`containing ether linkages of the 3ʹ position, compounds 1, 3, 4, 7 and 8 were
`incorporated by some of the polymerases.
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`And that’s his conclusion and compound 3 is the allyl. So he says it is
`incorporated. And so you have this period where Tsien gives you a method,
`says use allyl, it has advantages and then Metzger comes along with data
`that shows incorporation. And we can debate whether it’s full incorporation
`or partial incorruption but incorporation of some nucleotides.
`So five nucleotides that show actual incorporation and then you get to
`the Columbia patents in 2000, there’s no other data. The parties agree that
`there is no other data on allyl and that the patents in suit have no sequencing
`data on allyl.
`So Metzger’s data would have been promising to a skilled artisan
`because Tsien says use allyl, then Metzger comes along and gives you actual
`incorporation data whether its partial or incomplete versus totally complete.
`That would have told a skilled artisan you’re at a good starting point. Go
`ahead.
`
`JUDGE WORTH: I would like to try the hypothetical one more time.
`
`MR. ZIMMERMAN: Okay.
`
`JUDGE WORTH: And it sounds like you’re pursuing the argument
`that at a higher concentration a person of ordinary skill would have believed
`that there was either complete incorporation or complete enough
`incorporation.
`And that’s based on multiple rounds of polymerization and you might
`be arguing that based on Tsien because that’s when Tsien is talking about.
`So this is a hypothetical. So let’s say hypothetically that the claim does not
`require multiple rounds of polymerization.
`
`MR. ZIMMERMAN: Okay.
`
`
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`Case IPR2018-00291 (Patent 9,718,852 B2)
`Case IPR2018-00318 (Patent 9,719,139 B2)
`Case IPR2018-00322 (Patent 9,708,358 B2)
`Case IPR2018-00385 (Patent 9,725,480 B2)
`Case IPR2018-00797 (Patent 9,868,985 B2)
`
`JUDGE WORTH: And let’s just say that at that concentration,
`hypothetically, that that star means that it’s incomplete at that concentration.
`Is there anything in your briefing or evidence about whether that
`might actually be desirable if you’re not doing multiple rounds of?
`
`MR. ZIMMERMAN: It wasn’t briefed separately of not doing
`multiple rounds still being appealing. What you do have is Dr. Romesberg
`explained that even if it was incomplete termination, a person of skill in the
`art would have still found the data favorable.
`But I think under your hypothetical, our case only gets better.
`Because if you don’t need multiple rounds of sequencing, you just ended one
`incorporation, Metzger showed you some incorporation.
`Like there is no dispute that Metzger showed incorporation. The
`question is whether it was complete and absolute.
`
`JUDGE WORTH: And I guess what I’m asking you is where you
`think is, you can show me some testimony or if this is in your briefing?
`Because, you know, we are not going to build that part of the case out of
`here.
`
`MR. ZIMMERMAN: No, you -- the case was really addressed as to
`whether a person of skill in the art would have been motivated by Metzger’s
`data as it stood. Not in the context of whether the claim required one round
`or multiple rounds. It wasn’t addressed at that level of granularity.
`
`JUDGE WORTH: Well it --
`
`JUDGE RANGE: This is -- can I jump in? This is Judge Range in
`Dal
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