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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`
`NUEVOLUTION A/S,
`Petitioner,
`
`v.
`
`CHEMGENE HOLDING APS,
`Patent Owner.
`____________
`
`Case IPR2017-01598 (Patent 8,168,381 B2)
`Case IPR2017-01599 (Patent 8,168,381 B2)
`Case IPR2017-01603 (Patent 8,951,728 B2)
`____________
`
`Record of Oral Hearing
`Held: September 18, 2018
`____________
`
`
`
`
`Before SUSAN L. C. MITCHELL, ROBERT A. POLLOCK, and
`TIMOTHY G. MAJORS, Administrative Patent Judges.
`
`
`

`

`Case IPR2017-01598 (Patent 8,168,381 B2)
`Case IPR2017-01599 (Patent 8,168,381 B2)
`Case IPR2017-01603 (Patent 8,951,728 B2)
`
`
`
`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER:
`
`
`ANDREW LARSEN, ESQUIRE
`CHRISTOPHER J. SORENSON, ESQUIRE
`Merchant & Gould
`767 Third Avenue
`23rd Floor
`New York, New York 10017-2023
`
`
`
`
`The above-entitled matter came on for hearing on Tuesday, September
`
`18, 2018, commencing at 1:02 p.m., at the U.S. Patent and Trademark
`Office, 600 Dulany Street, Alexandria, Virginia.
`
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`
`P R O C E E D I N G S
`- - - - -
`JUDGE MAJORS: Good afternoon. We’re here today for an
`oral hearing in IPR 2017-01598, 01599, and 01603. Here Judge Majors, and
`with me Judges Mitchell and Pollock. Counsel for Petitioner, will you
`please introduce yourselves for the record?
`
`
`MR. LARSEN: Yes, my name is Andrew Larsen, lead counsel
`for Petitioner, Nuevolution.
`
`
`MR. SORENSON: Good afternoon. My name is Chris
`Sorenson, backup counsel for Petitioner, Nuevolution.
`
`
`JUDGE MAJORS: Nice to meet you finally. We’ve talked
`several times on the phone, I know.
`
`
`MR. LARSEN: Yes.
`
`
`JUDGE MAJORS: I’ll just briefly mention that there was an
`exchange of correspondence and orders from last week, and just for
`purposes of the record, Patent Owner has elected to cede its time for oral
`hearing today and further has elected not to appear for the oral hearing. So
`absent anything unusual happening, the Patent Owner is not making an
`appearance today.
`
`
`So, Counsel, we’re familiar with the record. We’re going to
`give you 60 minutes’ time. I’m not sure rebuttal time is going to be
`necessary today. And you may begin your presentation when ready.
`
`
`MR. LARSEN: Okay, thank you, Your Honor. Just one point
`of note, we did prepare more of a consolidated presentation of the
`demonstratives that we shared with you last week. And we’ve presented that
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`as our oral argument presentation, and just ask if you’d like -- each like a
`copy of what will be the final presentation, which removes some of the
`demonstrative slides that we shared with you previously.
`
`
`JUDGE MAJORS: So this is just a truncated version of the one
`that was sent around last week?
`
`
`MR. LARSEN: Yes, primarily.
`
`
`JUDGE MAJORS: Have you sent a copy to Patent Owner’s
`counsel?
`MR. LARSEN: No, we have not.
`
`
`JUDGE MAJORS: Yeah, you can go ahead and present it, but
`
`
`I would -- you need to send that to Patent Owner’s counsel, and we’ll accept
`your representation that it’s the same but a shortened number of slides, no
`further changes to the content.
`
`
`MR. LARSEN: Okay. Yes, Your Honor, there’s just one slide
`in the beginning that presents the invalidity grounds in each proceeding, just
`as part of our opening statement, but the rest of the content is identical, just
`removing some of the demonstrative slides.
`
`
`JUDGE MAJORS: Okay, you can proceed.
`
`
`MR. LARSEN: Okay. Would you like a copy, or just reserve
`that?
`
`
`
`
`
`
`JUDGE MAJORS: You can send a copy to the trials email.
`MR. LARSEN: Sure.
`JUDGE MAJORS: And we’ll see it here today.
`MR. LARSEN: Okay, thank you.
`JUDGE MAJORS: Would you like a hard copy?
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`JUDGE MITCHELL: I would. Sorry, I like a hard copy.
`
`
`JUDGE MAJORS: Okay.
`
`
`JUDGE MITCHELL: I’m old school.
`
`
`JUDGE MAJORS: Change of plan.
`
`
`JUDGE POLLOCK: I’ll take a copy, please.
`
`
`JUDGE MAJORS: Do you have hard copies for each of us?
`
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`MR. LARSEN: Yes.
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`JUDGE MAJORS: Okay.
`
`
`MR. LARSEN: And we will send an email with a copy to
`
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`opposing counsel right after this hearing.
`
`
`JUDGE MAJORS: Okay.
`
`
`MR. LARSEN: All right, thank you, Judge Majors, Judge
`Mitchell, and Judge Pollock. My name, as I said earlier, is Andrew Larsen,
`and I am lead counsel for Petitioner, Nuevolution, in these three inter parte
`review proceedings. With me today is Chris Sorenson, and we are both from
`the law firm of Merchant & Gould
`
`
`As a first matter, Nuevolution would like to thank the Board for
`its time and attention to these proceedings. There is a voluminous record
`with several claims under review, and we certainly appreciate your efforts in
`reviewing and considering all the parties’ briefings, as well as some
`uncharacteristically long prior art disclosures. And, of course, we thank you
`for granting us this oral argument, even though the Patent Owner,
`Chemgene, has decided not to appear today. We hope to be helpful and
`informative and to summarize the key issues in dispute here, and of course
`to answer any questions the Board may have.
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`Now, this oral hearing relates to three separate IPR proceedings
`
`
`involving two patents from the same family. The first is the ‘381 patent,
`which contains 46 total claims, each directed to methods for synthesizing
`encoded molecules employing a combination of split and mix synthesis, or
`stage 1 carrier synthesis, with template directed synthesis, or stage 2
`synthesis. The second is the ‘728 patent, a grandchild of the ‘381 patent,
`with one claim having a similar scope to Claim 1 of the ‘381 patent.
`
`
`Since both the ‘381 patent and the ‘728 patent have a common
`specification, unless we state otherwise on this record, Nuevolution intends
`for its argument today to be applicable to all three pending matters. We will
`focus on the ‘381 patent, but the ‘728 patent has the same specification. So
`all references to the ‘381 patent should be considered as relevant to the ‘728
`patent as well.
`
`
`Now, given the large number of claims in the ‘381 patent,
`Nuevolution decided at the outset to submit two separate petitions for inter
`partes review. The first is the 1598 petition, which contains 11 grounds and
`is directed to a subset of the claims that embrace a single round of stage 1
`carrier synthesis prior to a template hybridization step in stage 2. The 1599
`petition contains seven grounds and is directed to a different subset of claims
`that require multiple rounds of stage 1 carrier synthesis prior to the template
`hybridization step.
`
`
`Then the 1603 petition is directed to the ‘728 patent and its
`single claim. It contains 14 grounds, and those 14 grounds are essentially
`the same invalidity grounds as are set forth in the combination of the 1598
`and 1599 petitions.
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`Now, the Board initially granted institution of all three petitions
`
`
`based solely on obviousness over Freskgard, which is WO ‘825, alone and in
`combination with other secondary references. And those grounds are shown
`here in the blue boxes.
`
`
`Thereafter, the Supreme Court decision in SAS v. Iancu issued,
`and the Board instituted review on all grounds in each of the three petitions.
`This is shown now in green, the added grounds after the Supreme Court
`decision.
`With the newly instituted grounds now under review, we
`
`
`thought it was particularly important to appear here today. A lot has
`changed since the -- a lot has changed since the original institution decisions
`were issued. And we would like to discuss three central points today. The
`first, the Patent Owner’s disclosure in the ‘381 specification. The second
`will be the term “reaction well” and its application in the ‘381 specification
`and its application to the prior art. And the third is that in Petitioner’s view,
`Petitioner’s burden is met by a preponderance of the evidence here.
`
`
`Now, on point one, the specification of the ‘381 and ‘72 [sic]
`patents describe and enable combinations of well-known methods for split
`and mix synthesis with well-known methods for template directed synthesis
`to allegedly provide an improvement in the generation of oligonucleotide
`encoded chemical libraries.
`
`
`Your Honors, these patents have never been directed to,
`described as, or claimed as a new method for conducting stage one split and
`mix synthesis in a single-reaction vessel as the Patent Owner’s papers would
`have you believe. Before these proceedings began, Petition Owner [sic] did
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`not once hint in the specifications or during prosecution, as it has in these
`proceedings, that its central point of novelty was the discovery of a new and
`more efficient way to conduct stage 1 split and mix synthesis in a single-
`reaction vessel, such as the well in a microtiter plate or an individual
`Eppendorf tube.
`
`
`Quite to the contrary, the specific enablements and concrete
`examples, which establish the written description of Patent Owner’s alleged
`invention, explicitly rely on preexisting prior art stage 1 and stage 2
`methods, such as those described in Freskgard, Pedersen, and other prior art
`publications of Nuevolution, the Petitioner here.
`
`
`On to the second point. While the Board’s construction of the
`term “well” appearing in the independent claims of the ‘381 and ‘728
`patents is correct, it is, indeed, a physical containment of molecule
`fragments, reagents, et cetera in a localized space. The Board’s application
`of that meaning in the context of the clause “each of said reaction wells”
`should respectfully be reconsidered in the full context of the evidence now
`of record. While “each of said reaction wells” certainly encompasses the
`possibility of stage 1 carrier synthesis in the same reaction vessel, the proper
`construction of said reaction well is significantly broader than that.
`
`
`Your Honors, a well as used in the ‘381 and ‘728 patent claims
`need only facilitate the function of containment to the extent that separation
`of different compositions of bifunctional molecules is as desired. Petitioner
`submits that so long as the components for making one type of bifunctional
`molecule are kept separate from the components for making other types of
`bifunctional molecules during the stage 1 carrier synthesis, each different
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`bifunctional molecule is prepared in its own physical containment in a
`localized space, and thus within its own reaction well.
`
`
`JUDGE MITCHELL: Well, what would be the physical
`containment? Because I’m assuming you’re talking about two reactions in
`one well.
`MR. LARSEN: Right.
`
`
`JUDGE MITCHELL: You know, one physical well.
`
`
`MR. LARSEN: Yes.
`
`
`JUDGE MITCHELL: So what’s the physical containment
`
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`within that well that would keep the reaction separate?
`
`
`MR. LARSEN: Well, in the definition of the well that appears
`on Column 4 of the ‘381 patent, there’s the broad definition that’s Patent
`Owner’s lexicography that it’s a physical containment in a localized space.
`And then after that, we see the explanation that a well includes the well in a
`microtiter plate. Now, that could be -- that can be a vessel. It could also
`include any container and a reagent. Those are types of vessels.
`
`
`But then it goes further and it speaks to a bead, which -- to
`which these, you know, components can be attached. And it speaks to a
`nanocompartment, which is simply a hybridization event. Petitioner’s
`position here is that the definition says that including all of those, it can also
`include any other well that separates the components from making
`bifunctional molecules as desired.
`
`
`Our position is that a physical containment in a localized space
`can be anything that allows a process to occur almost like an assembly line.
`So if you have a linker molecule that’s added to a well in step a), and you
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`have three different reaction wells that you’re going to be performing the
`synthesis of bifunctional molecules, the point of the well is actually the
`function of separating the synthesis of bifunctional molecule 1 from
`bifunctional molecule 2 from bifunctional molecule 3.
`
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`If you don’t separate those three synthetic schemes into
`separate physical containments in a localized space, then you’re going to get
`scrambling between a molecule fragment and the oligonucleotide tag that’s
`intended to be connected to it through the linker. So Nuevolution’s position
`here is that the physical containment in a localized space is actually broader
`than a single vessel and could incorporate more than one actual reaction
`vessel through which a process flows to get to the final bifunctional
`molecule product, as long as the components for making that specific
`bifunctional molecule are kept separate from the components for making a
`different bifunctional molecule.
`
`
`JUDGE MAJORS: So, Mr. Larsen, would you agree with -- if I
`characterize Petitioner’s position on claim construction as in effect as long
`as you get the reactions that you want to form the molecule, it does not
`matter how many specific physical -- to use Petitioner’s term -- vessels that
`those molecules will transfer between in the process ultimately of getting the
`bifunctional molecule that you want?
`
`
`MR. LARSEN: That would be Petitioner’s position, and
`another way to think about this, and our expert, Dr. Winssinger, has
`explained in his second declaration in that claim construction is that a well in
`the art of split and mix synthesis is -- can also be considered a compartment.
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`And a compartment is an area in which different bifunctional molecules are
`being synthesized.
`
`
`So if you take a linker molecule, you could separate it into
`different compartments, so the same linker molecule goes into these three
`separate areas, and only to area one do you add the molecule fragment one.
`Only in area two do you add the molecule fragment two, et cetera. And then
`only to that compartment number one would you add the oligonucleotide
`identifier one that is intended to be attached through the linker to molecule
`fragment one.
`
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`The purpose of the process, as explained by our expert, Dr.
`Winssinger, is to prevent mismatching between an oligonucleotide identifier
`and the molecule fragment it’s intended to identify so you get proper
`formation of your bifunctional molecules in this split. You split, you
`synthesize, and then once you have covalent linkages between your
`molecule fragment and the identifiers through the linker, now you have
`proper identification of your molecule fragments with the appropriate
`oligonucleotide.
`
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`Now when you mix them together, they’re not going to come
`apart. The covalent linkages have been formed between these molecules.
`You mix them together; now they’re in a mixture, an add mixture, as
`required by the claims of bifunctional molecules, and those identifiers are
`going to stay attached to their appropriate molecule fragments. Then you
`can split them again and you have mixtures -- a mixture from the first round
`of the split and mix synthesis. You can then split them again into new
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`reaction wells, and that’s actually what’s called for in the optional steps f)
`and g) of Claim 1.
`
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`New reaction wells. These are new physical containments in a
`localized space. To each of those separate physical containments of
`localized -- in a localized space, you again add a specific molecule fragment
`to containment one, containment two, containment three. And only to
`containment one are you adding the specific identifier for the molecule
`fragment added to that containment.
`
`
`JUDGE MAJORS: I think the difficulty, in part, is
`understanding where to draw those lines. If I understand you correctly, in
`one instance, one might say that a particular linker molecule itself is the
`compartment or the well or even subsections of the linker that have a
`particular reactive group.
`
`
`MR. LARSEN: Mm-hmm.
`
`
`JUDGE MAJORS: And you’re correct that the definition
`points to nanocompartments, but in our decision on institution, we reflected
`and we said, well, that may be true that it could be this particular portion of a
`linker or a nanocompartment, but it’s got to be the same thing --
`
`
`MR. LARSEN: Right.
`
`
`JUDGE MAJORS: -- to which the oligonucleotide identifier
`and the molecule fragment -- and, so, then the question becomes where do
`we draw that line. On the one hand, is it this linker? On the other hand, is it
`a physical Eppendorf tube? Is it a room? A lab?
`
`
`MR. LARSEN: Right.
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`JUDGE MAJORS: On the floor of a building? And you start
`
`
`to -- it starts to in some ways, and I’ll use the word unclear, recognizing that
`that’s a loaded term, but to understand for a particular reaction where does
`that line get drawn. And it seems to me, we can talk more about the claim
`construction, but it seems to me that Petitioner’s position is, well, regardless
`if you adopt the broader interpretation that Petitioner is offering, which we
`rejected at the institution phase, or the construction that the Patent Owner
`offered, which is narrower, that either way Petitioner should prevail here
`because of the cited teachings of at least Freskgard.
`
`
`MR. LARSEN: Again, that’s correct, Your Honor. And as we
`presented in our petition and in our reply and as we’re prepared to discuss
`here today, both the figures in Freskgard and the examples in Freskgard
`react the necessary components for the bifunctional molecules, and
`according to Patent Owner’s lexicography in the same physical containment
`in a localized space.
`
`
`JUDGE MAJORS: Now, just a couple more points. Petitioner
`did not request reconsideration of the decision on institution, in effect
`saying, Board, we see what you said, but you got the construction wrong.
`
`
`MR. LARSEN: Well, Petitioner’s position, Judge Majors,
`would not be that you got the claim construction wrong. In fact, you did
`correctly identify that the claim construction for the term “well” is a physical
`containment in a localized space according to Patent Owner’s lexicography.
`Petitioner’s position here is only asking that you reconsider the application
`of that broad terminology to how it’s being used in the patent specification
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`and how it’s being applied to the prior art in our initial petitions and in our
`responsive arguments in our reply.
`
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`JUDGE MAJORS: I think as a practical matter, let’s say that
`we agreed with you, though, at this stage. All the briefing in the entire
`proceeding has now been driven around this concept of the -- I’ll call it the
`narrower interpretation. And, so, if I’m looking at it from Patent Owner’s
`perspective and we were to -- let’s say we agree with Petitioner at this phase
`and we said, okay, claim construction needs to be revisited --
`
`
`MR. LARSEN: Mm-hmm.
`
`
`JUDGE MAJORS: -- all the briefing in these proceedings has
`now proceeded along a certain path, and now as a practical matter, we have
`to reach a final decision, and we don’t have briefing on a different claim
`construction. So that goes back to my question about the rehearing request,
`which could have been made at a time when the briefing could have
`proceeded and folks could have addressed a reconsidered claim construction
`at the time.
`MR. LARSEN: Okay.
`
`
`JUDGE MAJORS: I’m not sure that’s a question. I’m just
`
`
`saying as a practical matter, how do we as a Board, even if we were inclined
`to agree that Petitioner’s assertions of a broader claim interpretation are
`correct, how do we proceed as a Board to now make a record on a different
`claim construction?
`
`
`MR. LARSEN: Well, again, Petitioner’s position is that we’re
`not asking the Board to make any kind of different claim construction.
`We’re simply asking the Board to reconsider the application of that broad
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`terminology. But as a second point, as you recognized earlier and pointed
`out, our position is regardless of the -- how the claim interpretation, the
`proper claim construction is applied to the prior art, whether that be a single
`vessel as proposed by the Patent Owner here, or as a broader physical
`containment in a localized space that really just needs to keep the molecule
`fragments, linker, and identifier together so there’s no mismatching and
`scrambling of molecule fragments and tags.
`
`
`Regardless of that interpretation, the figures in Freskgard and
`the examples in Freskgard meet that limitation under both circumstances,
`and we would simply ask for you, based on that, to revisit these previously
`denied grounds and the examples that are presented in those previously
`denied grounds so that you can see that each different bifunctional molecule
`that’s being provided in those examples in the previously denied grounds,
`such as Pedersen, Gouliaev ‘627, Franch ‘427, Gouliaev ‘994, all of those
`are preparing these different bifunctional molecules in different physical
`containments in a localized space.
`
`
`But, also, if you look at the examples, there’s nothing in these
`examples, and our expert in his second declaration has confirmed, that
`there’s nothing in these examples that say that when you’ve finished one
`step of that two-step process that you put it into a different reaction vessel
`and, therefore, under Patent Owner’s construction or interpretation, a
`different reaction well, but to do the next step of the process, all of those
`components are being held separately until the covalent linkage has been
`made between the molecule fragment, the linker, and the identifier. And
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`only then can you mix in step e) before you optionally do another round of
`the split and mix synthesis.
`
`
`JUDGE MAJORS: Let’s say that we agree with you that
`Freskgard renders obvious the claims under the narrower interpretation.
`Why, then, would Petitioner -- we understand you may disagree with aspects
`of the claim construction, but would Petitioner then still contest the decision
`here? I mean, it seems to me on one hand if the decision on institution is
`maintained now through trial and having the evidence and the claim is
`obvious, even under a narrower interpretation the claim or claims would still
`be found unpatentable.
`
`
`MR. LARSEN: Petitioner certainly is not looking to contest the
`institution decision in terms of how the Board reviewed and characterized
`the Freskgard disclosure. The Board had said that at least Figures 12 and 13
`that occur in the Freskgard reference are, you know, disclosed; the steps a)
`through d), including the same reaction well.
`
`
`Petitioner would only ask the Board to revisit the examples that
`were initially, you know, discarded from the analysis as disclosing synthesis
`in the same reaction well and to consider Petitioner’s reply arguments in
`response to Patent Owner’s contention regarding different reaction vessels
`and to see if those examples also disclose those steps.
`
`
`JUDGE MAJORS: Okay.
`
`
`MR. LARSEN: Moreover, the Petitioner would respectfully
`request the Board to reconsider in view of that re-review of the examples
`that at least Claim 5, which does not include this -- what we call the region
`limitation in the fourth “wherein” clause, it does not require hybridization of
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`the region of the identifier that actually identifies the molecule fragment to
`the template.
`
`
`With that limitation not being a part of Claim 5, we would
`simply ask you to revisit the anticipatory disclosure of Claim 7 -- Example 7
`from Freskgard itself in meeting each and every one of those limitations.
`And also to reconsider to the extent that we’ve presented in our position any
`claim that depends from Claim 5 that doesn’t incorporate any region
`hybridization requirement, to reconsider the anticipatory arguments for that.
`
`
`JUDGE MAJORS: Because Petitioner’s allegation is that those
`claims are -- split and mix are the stage 1, sometimes called -- it’s not a
`combination of templating and split and mix synthesis?
`
`
`MR. LARSEN: Well, it is a -- it is a combination of split and
`mix and templated synthesis, but it’s a combination of split and mix
`synthesis followed by a template directed step. The -- and that can be
`contrasted with a split and mix synthesis combined with a template encoded
`step, like you would see for the combination of the bifunctional molecules
`made by Example 7, combined with this assembly platform embodiment in
`Figure 7 of Freskgard.
`
`
`And it would be different than the combination of bifunctional
`molecules prepared by split and mix from any embodiment in Freskgard
`with the template encoded techniques that are disclosed in Pedersen and
`Gouliaev ‘427 and -- the ‘627, excuse me, and the other template-specific art
`that we used in combination with Freskgard.
`
`
`JUDGE MAJORS: Okay. Thank you for that clarification, and
`if I understand you correctly, the claim construction position primarily
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`relates to asking the Board to reconsider some of the examples that were
`cited, both in Freskgard -- the working examples -- as well as the examples
`that I think you said discarded but that the Board did not find the petition
`itself had made a sufficient case that those were being conducted in the same
`well, so interpreted, and in that respect reach the alternative grounds that
`were added post-SAS. Correct?
`
`
`MR. LARSEN: Yes, that’s correct. Petitioner’s position is is
`that if you review the procedures that are being used in the Freskgard
`examples there’s -- there are some striking similarities between how
`Example 7, for example, prepares bifunctional molecules in these separate
`physical containments in a localized space and how the examples in the
`previously denied grounds makes those bifunctional molecules in the
`examples in, for example -- for example, in the Pedersen reference. We’ve
`pointed out throughout the analysis an Example 108 from that reference.
`And Example 108 from that reference is a templated synthesis, a template
`encoded synthesis for making a library containing 64 members.
`
`
`Now, as part of that template encoded synthesis, the first thing
`that you need to do is to prepare your bifunctional molecules that are going
`to be hybridized to that template. In Example 108 of Pedersen, you prepare
`12 different bifunctional molecules. Those molecules have a molecule
`fragment, and each one of them, as shown in that example, has a specific
`oligonucleotide identifier attached to it through a linker. And this is N-
`hydroxymaleimide that we refer to as the linker in those examples.
`
`
`You need to make those 12 different bifunctional molecules,
`and you need to make them separately. But you make them all from the
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`same N-hydroxymaleimide linker. So what you do is you take that linker
`and you separate it out into 12 different processes; and then you can attach
`your molecule fragment; and then you can attach your oligonucleotide
`identifier. What happens after that is you mix them together, and that’s step
`e) of Claim 1 and step c) of Claim 5 of the ‘381 patent.
`
`
`The next steps are optional, steps f) and g). You don’t need to
`repeat split and mix synthesis. So what you do is you take that add mixture
`or a smaller subset of add mixture of that 12 bifunctional molecules, and you
`hybridize that with the template disclosed in Pedersen Example 108.
`Thereafter, and this relates really only to some of the dependent claims, once
`those different bifunctional molecules are hybridized to the same template,
`they can react. And that is stage 2 synthesis. That’s templated synthesis.
`It’s template directed synthesis, which Petitioner submits the ‘381
`specification is really limited to, and it’s also template encoded synthesis
`because the sequence of the oligonucleotide in the building block is 100
`percent complementary to the sequence of the template encoding region for
`that building block. And that’s also why the fourth “wherein” clause of
`Claims 1 and 4, the region limitation, is met by Pedersen Example 108.
`
`
`A similar analysis, without going into the details of this, can be
`applied to each and every example that we relied upon in these previously
`denied grounds. And just for example, as I was -- introduced this concept,
`Pedersen Example 108, that example all by itself contains the disclosure of
`the stage 1 split and mix synthesis in a single-reaction round. Freskgard
`comes into play because Freskgard is disclosing more of a true split and mix
`process where you split the linker, you do one round, and then you mix it
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`back together, and then you split it into new wells and do a second round.
`That creates