`
`U.S. PATENT AND TRADEMARK OFFICE
`__________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________
`
`ModernaTX, Inc.,
`Petitioner
`
`v.
`
`CureVac AG,
`Patent Owner.
`
`__________
`
`Case IPR2017-02194
`Patent 8,383,340 B2
`__________
`
`Record of Oral Hearing
`Held: February 7, 2019
`__________
`
`Before JAMES T. MOORE, SUSAN L. C. MITCHELL, KRISTI L.
`R. SAWERT, Administrative Patent Judges.
`
`
`
`
`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER:
`
`ELDORA ELLISON, Ph.D.
`DAVID W. ROADCAP, Ph.D.
`OLGA PARTINGTON, Ph.D.
`of: Sterne, Kessler, Goldstein & Fox, PLLC
`1100 New York Avenue, N.W.
`Suite 600
`Washington, D.C. 20005
`(202) 371-2600
`eellison@sternekessler.com
`
`
`ON BEHALF OF THE PATENT OWNER:
`
`DEBORAH YELLIN, ESQ.
`TERESA S. REA, ESQ.
`SHANNON LENTZ, ESQ.
`of: Crowell & Moring, LLP
`1001 Pennsylvania Avenue, N.W.
`Washington, D.C. 20004
`(202) 624-2500
`dyellin@crowell.com
`trea@crowell.com
`
`DAVID L. PARKER, Ph.D.
`MARSHALL P. BYRD, Ph.D.
`of: Parker Highlander, PLLC
`1120 S. Capital of Texas Highway
`Building One, Suite 200
`Austin, TX 78746
`(512) 334-2900
`dparker@phiplaw.com
`mbyrd@phiplaw.com
`
`The above-entitled matter came on for hearing on Thursday, February
`7, 2019 commencing at 1:00 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
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`1:02 p.m.
`JUDGE SAWERT: Good afternoon, everyone. We have
`this afternoon our final hearing in IPR 2017-02194 between Petitioner
`ModernaTX and Patent Owner CureVac.
`I'm Judge Sawert and I'm joined today by Judges Moore and
`Mitchell.
`So let's start with the introductions. We'll start with
`Petitioner. Counsel, will you please introduce yourselves and let us
`know who will be presenting today?
`DR. ELLISON: Good afternoon, Your Honor. I'm Eldora
`Ellison from Sterne, Kessler, Goldstein, and Fox. I will be making
`the argument this afternoon. I have here with me backup counsel
`Olga Partington and backup counsel David Roadcap.
`JUDGE SAWERT: Thank you and welcome. And for
`Patent Owner, who do we have today?
`MS. YELLIN: Hello, Your Honor. I'm Deborah Yelling of
`Crowell and Moring and I'll be making the presentation today, and
`with me also of Crowell is Shannon Lentz and Teresa Stanek Rea.
`JUDGE SAWERT: Okay, thank you. Welcome. So we
`set forth today's procedure in our Trial Order which was Paper 38 in
`this case. Please remember that each side has 60 minutes of total
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`time to present arguments, and that includes the pending motions to
`exclude if you wish to talk about those today.
`Petitioner, you will go first, and you may reserve time for
`rebuttal on the main case and on your Motion to Exclude. And
`Patent Owner, you will then go after Petitioner and you may also
`reserve time for rebuttal on your Motion to Exclude if you so wish.
`Please remember that you are not allowed to interrupt the
`other party, and please save any objections you have to your own
`argument time or to the, or before we adjourn.
`Okay, I know there's a Motion to Seal pending in this case. I
`don't think it's relevant to what we're going to be talking about today,
`but if it is, please save it to the end so we can clear the courtroom.
`I'm not sure if there's anyone here that would need to leave, but just in
`case.
`
`So do we have any questions or concerns from Petitioner or
`from Patent Owner? Okay, so, no. With that, we're going to be
`ready to start here in a moment.
`JUDGE MOORE: Just one quick question. Are the three
`folks in the back affiliated with any party?
`PARTICIPANT: Back up counsel.
`JUDGE MOORE: All of you?
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`DR. ELLISON: Your Honor, this is in-house counsel from
`Moderna Therapeutics and then we have backup counsel David
`Roadcap.
`JUDGE MOORE: Okay.
`JUDGE SAWERT: Okay, so Ms. Ellison, correct?
`DR. ELLISON: Yes, Your Honor.
`JUDGE SAWERT: Okay, let's begin. Can you tell me do
`you wish to reserve any time for rebuttal?
`DR. ELLISON: Yes, I'd like to reserve 10 minutes for
`rebuttal.
`JUDGE SAWERT: I have your clock set at 50 minutes, and
`so whenever you're ready to begin, please do so.
`DR. ELLISON: Your Honor, is there a countdown clock in
`this room somewhere? Or I can just use the wall clock, I guess.
`JUDGE MOORE: Just not one by numbers, but.
`DR. ELLISON: Okay, thank you. May it please the court,
`I'm Eldora Ellison on behalf of Petitioner Moderna Therapeutics.
`We submit that the evidence in this record demonstrates that all of
`CureVac's 340 patent claims are unpatentable as anticipated and are
`obvious over the cited art, and I'd like to start with our obviousness
`grounds, in particular, ground two. If we could see slide three,
`please?
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`The 340 patent broadly claims a method for purifying RNA
`using, for example, HPLC, and it specifies using a porous reversed-
`phase medium, and the porous reversed-phase medium is known as
`polystyrene-divinylbenzene or PSDVB. This type of purification is
`also referred to as ion-pair reversed-phase HPLC or IP RP HPLC.
`There can be no dispute that by 2006, a person of skill in the
`art would have been motivated to purify large quantities of RNA, for
`example, for use in preclinical investigations and clinical trials
`involving antisense therapies for instance. Examples of such types
`of antisense therapies include siRNAs, short-interfering RNAs,
`ribozymes and oligonucleotides.
`JUDGE SAWERT: Can you speak for one moment about
`the RNAs that are disclosed in, I believe it's Zhang?
`DR. ELLISON: Yes.
`JUDGE SAWERT: Could you remind me what exhibit that
`
`is?
`
`DR. ELLISON: The Zhang exhibit is Exhibit 1005.
`JUDGE SAWERT: Okay.
`DR. ELLISON: And Zhang mentions siRNAs, ribozymes --
`JUDGE SAWERT: Okay, I think that's Lloyd.
`DR. ELLISON: I'm sorry, 1038, my apologies. Zhang
`mentions in its abstract, for instance, antisense oligonucleotides,
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`small-interfering RNAs. I believe ribozymes are mentioned in the
`abstract as well. I'm just looking for that, but it mentions those,
`several types of antisense RNAs, including ribozymes.
`JUDGE SAWERT: Can you respond to Patent Owner's
`argument that Zhang's antisense oligonucleotides are actually DNAs?
`I don't know what small-interfering RNAs are, but could you speak to
`how Zhang discloses those and how that's relevant to the ground you
`have when you combine this with Lloyd?
`DR. ELLISON: Certainly, Your Honor. By 2006, a person
`of ordinary skill in the art who reads a disclosure relating to antisense
`therapies, which is something that's mentioned not only in Zhang, but
`also in Lloyd, would have understood that such antisense therapies
`included short-RNAs, including RNA oligonucleotides, and RNAs,
`including RNA oligonucleotides had been known in the art. This is
`part of the general knowledge in the art.
`So for instance, the Greene reference, which is Exhibit 1042,
`mentions that antisense was known to include RNAs since at least
`1986, and more generally, the term oligonucleotides is understood to
`encompass both DNA and RNA. Even Dr. Svec acknowledges that
`this term can encompass both DNA and RNA, Dr. Svec, CureVac's
`expert.
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`And so there's no reason why a person of ordinary skill in the
`art would have read Lloyd and Zhang so narrowly in combination by
`2006 to exclude RNA oligonucleotides when RNAs were known to be
`useful to antisense therapies.
`SiRNAs, by the way, just stands for short-interfering RNAs,
`so that's all they are is they actually are an RNA oligonucleotide since
`they're short-interfering RNAs, interfering referring to how they
`function.
`So the Patent Owner takes an overly narrow view of the art
`when they make the argument that a person would have read Lloyd as
`limited to DNA. That's not how a person of ordinary skill in the art
`would have understood Lloyd given that antisense RNAs were known,
`well known by 2006, and there were plenty of reasons to purify large
`quantities of antisense RNAs such as for clinical trials.
`Indeed actually, the Lloyd reference cites to several RNA
`papers such as references five and reference 12, and so these
`references must be considered together, Lloyd and Zhang.
`JUDGE SAWERT: Are those in the record?
`DR. ELLISON: Yes, yes, Your Honor. Exhibit 5 is, excuse
`me, reference five from Lloyd is Exhibit 1030, and reference 12 from
`Lloyd is Exhibit 1037. And if you look at just the abstracts of each
`of those references, you can see they talk about RNA.
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`So a person of skill in the art who would consider Zhang's
`discussion of a need for RNA for antisense therapies together with
`Zhang's discussion of a need to purify RNA for antisense therapies
`would arrive at the claimed invention as we've discussed in our briefs.
`Indeed, CureVac cannot credibly deny that the Lloyd
`reference was focused on preparative purification using IP RP HPLC
`for preparing oligonucleotides for antisense therapies since it
`mentions various RNA papers.
`And I'll note also that general knowledge in the art such as
`shown in various references that we cited like Sullenger, Exhibit
`1039, Kiefth, Exhibit 1041, and Deshmukh, Exhibit 1047, also would
`have impacted how a person of skill in the art reads the cited
`references. Each of those references --
`JUDGE SAWERT: I'm confused about all of those extra
`references that you're using. My understanding is that none of those
`references disclose porous reversed-phase. Is that correct?
`DR. ELLISON: So let me just try to clarify one thing. The
`references I just mentioned, I was pointing to them because they
`explain why or they're further evidence that a person of ordinary skill
`in the art would have been motivated to purify RNA on a preparative
`scale.
`
`JUDGE SAWERT: Okay.
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`DR. ELLISON: But with respect to porous, Patent Owner
`criticizes certain references that we've cited on the ground that they do
`not disclose a porous resin, but I'll note first Lloyd itself uses a porous
`resin. Lloyd uses the exact same resin that's used in the 340 patent.
`It's known as PLRP-S and that's a porous resin.
`And so she explains that the use of her resin would have been
`an obvious choice. The use of reserve-phase ion-pair HPLC would
`have been an obvious choice. Those are her own words that we can
`see on slide 12 --
`JUDGE SAWERT: Right.
`DR. ELLISON: -- if we can look at that quickly. But with
`respect to other references that Patent Owner has criticized, some of
`those references do use nonporous resins if we can turn to slide 16 for
`instance. I'm sorry, let's go to 17, slide 17.
`So Patent Owner criticizes these references that we've shown
`here on the ground that they use a nonporous resin, but again, Patent
`Owner is not viewing the art from the perspective of a person of
`ordinary skill in the art who would understand that the literature
`shows that persons of skill in the art reasonably expected reverse-
`phase ion-pair HPLC methods to be useful for purifying RNA.
`So Patent Owner throws out some theories about why these
`are allegedly irrelevant references and they say things such as the
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`RNA has to enter the pores, but as you can see from the claims, the
`claims don't require the RNA to enter the pores. They say that --
`JUDGE SAWERT: Can I -- I'm sorry to interrupt you.
`DR. ELLISON: That's okay.
`JUDGE SAWERT: So for me, for this case, the obviousness
`case, I see this as a very strong motivation because Lloyd expressly
`says that this would be the obvious choice for oligonucleotide
`purification. My issue in this case is reasonable expectation of
`success. And to the extent that you're using these references for
`reasonable expectation of success, I'm unsure how they help you
`because they are not directed to porous in regards to phase
`chromatography. So could you speak to that, please?
`DR. ELLISON: Sure, so these are not the only references we
`rely upon. In particular, we also rely upon the Polymer Labs
`Catalogue which in and of itself says that its resin, the same PLRP-S,
`can be used to purify both DNA and RNA and that scale-up is easy
`per the words in the Polymer Labs Catalogue, but with respect to --
`JUDGE SAWERT: Do we know when it says easy scale-up,
`do you know the amount to scale-up? Do you have testimony or
`something on that?
`DR. ELLISON: The Polymer Labs Catalogue, slide 16, says
`it's preparative, and that's all that the claim requires is preparative.
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`So the catalogue, the very catalogue that sells the resin that Lloyd
`used, and it's the same resin that's used in the 340 patent, says that this
`is easy scale-up for preparative uses.
`JUDGE SAWERT: Can I ask you a question here? Then
`why wasn't this an anticipation rejection? What am I missing here?
`DR. ELLISON: In our view, this could have been an
`anticipation rejection, but we chose to use the Lloyd reference and the
`Zhang reference in part because they address certain dependent claims
`like -- they address more of the limitations, I think, that appear across
`the full scope of the claims, of the various types of claims.
`But Polymer Labs in and of itself says preparative easy scale-
`up, and on a different slide, I believe it's, I want to say it's slide seven,
`the Polymer Labs Catalogue makes it clear that its method can be used
`for both DNA and RNA.
`But I'd like to address your question about porous media if
`you could just bear with me just one second. So as I mentioned, the
`Lloyd reference -- I'm looking at slide 12. The Lloyd reference in
`particular tested various pore size and said that her method was
`effective in separating nucleic acids with various pore sizes.
`JUDGE SAWERT: So the issue with Lloyd though is that
`although I think it's fair to say that there's a clear motivation, would
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`somebody of ordinary skill in the art have had, would have had a
`reasonable expectation of success with RNA?
`DR. ELLISON: Yes, so let's look at claim 17, or, excuse me,
`slide 17 for just a second. So these are some of the other references
`about which you were asking me earlier, and what these references
`show is that persons of skill in the art were well aware of differences
`between DNA and RNA when the authors of these references made
`statements explaining that they expected, and in many cases
`demonstrated, RP IP HPLC methods that had been developed for
`DNA to work with RNA.
`The Patent Owner speculates that such methods would not
`work with RNA because there are minor structural differences
`between DNA and RNA, but my point is the persons of skill in the art
`were well aware of those structural differences when they stated that
`these types of methods could work for both DNA and RNA.
`And their criticisms of nonporous references go to issues such
`as entry into the pores, but again, that's not a claim limitation.
`They're making arguments that are un-moored from the claims if we
`could look at slide 24 for instance.
`So they criticize such nonporous media by saying the
`nonporous media do not allow RNA entry into the pores, but they're
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`wrong because the claims simply don't require entry into the pores,
`and they also say --
`JUDGE SAWERT: I'm not sure I exactly understand that
`since isn't that the way a porous reversed-phase works is by entering
`the pores, because otherwise it wouldn't be a porous chromatography
`method?
`DR. ELLISON: There's no per se requirement that the RNA
`enter the pores, and that's certainly not a requirement of the claimed
`invention.
`JUDGE SAWERT: Is there anything in the spec that would
`support a reading that -- because by saying -- my understanding is by
`saying you don't require the RNA to enter into the pores, that you're
`reading porous as basically functioning as nonporous.
`DR. ELLISON: I would not say that, Your Honor. I would
`not go that far. So the claims simply recite porous media, which
`simply means that the media is characterized by pores, but the claims
`do not and the specification does not require entry into the pores, and
`indeed, if we could skip to almost the end where we have the slide on
`RP IP HPLC --
`JUDGE SAWERT: Do you have anything in the
`specification that says, or some sort of chromatography that
`encompassed or mentioned in the specification that would provide
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`evidence that not only are they talking about, is this method directed
`to a method where the RNA enters the pores, but it also encompasses
`other types of chromatography methods where it's literally flowing
`through the, I believe that's the stationary phase?
`DR. ELLISON: Yeah, I'd like to show you a schematic that
`we have at slide 47 which explains how ion-pair reverse-phase HPLC
`works, and as you can see in this schematic, it works by adsorption of
`the nucleic acid onto the reverse-phase. So in this drawing, the ion
`pairing agent is shown on the right-hand side of the first figure.
`I don't even know how to describe that figure, but the top
`figure shown on the right-hand side, and you can see that the ion-
`pairing agent allows the nucleic acid to adsorb to the outside of the
`reserve-phase, to the reverse-phase.
`JUDGE SAWERT: Okay, so I see -- so the specification
`lists ion-pair reverse-phase HPLC as a type of HPLC that is
`encompassed by the invention, correct?
`DR. ELLISON: Right.
`JUDGE SAWERT: And then the way that ion-pair works,
`it's not actually flowing into the pore. It's actually just adsorbing -
`DR. ELLISON: Adsorb.
`JUDGE SAWERT: -- onto the surface.
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`DR. ELLISON: Yes, the ion-pairing agent enables the
`nucleic acid to be adsorbed onto the surface of the reverse-phase.
`JUDGE SAWERT: Okay.
`DR. ELLISON: Entry into the pores is not required by these
`claims.
`JUDGE SAWERT: If we could, I'd like to talk about
`reasonable expectation of success. When I look at Dr. Hornsby, I
`believe --
`DR. ELLISON: Hornby.
`JUDGE SAWERT: -- Hornby, his first declaration, I see the
`reasonable expectation of success section is really just a few
`paragraphs long, and then when Patent Owner came back, Patent
`Owner found a lot of examples were merely three years after 2006.
`Dr. Hornby published many papers saying that the art of RNA
`chromatography is unpredictable, that you can't expect DNA and
`RNA to act the same in a chromatography column.
`And I'm struggling what to do with this because these quotes
`really undermine the credibility of your expert, what you expect
`somebody skilled in the art would understand in 2006. And so I
`want you to point me to something in the record, to examples in the
`record where Dr. Hornby, why -- point me to something in the record
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`showing that these statements that he makes are not applicable to the
`type of chromatography that he speaks of in his first declaration.
`DR. ELLISON: Sure, let's turn to slide 48. You're there
`already. So Patent Owner has pointed to Exhibit 2024, which is a
`2009 publication from Dr. Hornby, and Exhibit 2025, which again is a
`2009 publication from Dr. Hornby.
`I think to understand Dr. Hornby's comments, it's important to
`understand some differences between the preferences of persons of
`ordinary skill in the art when it comes to preparative purification
`versus analytical purification back in 2006.
`And what the art showed, and even Dr. Svec acknowledged, is
`that persons of ordinary skill in the art had a preference for using
`nonporous resins, nonporous media when doing analytical
`separations. I think that's in slide 13. We have a quote from Dr.
`Svec saying nonporous is only preferred for analytical separation.
`Porous media, on the other hand, as Lloyd explained, were
`preferred for doing preparative purification because they could better
`withstand the operating pressures and have better loading capacity.
`And so we submit that CureVac has taken Dr. Hornby's statements out
`of context because Dr. Hornby was referring to analytical separation,
`and that's what he explains here on slide 48.
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`So to the extent that he mentions that there was any preference
`for nonporous, he was referring to an analytical context, and to the
`extent that he acknowledged that nonporous media had been used to
`purify RNA, well, that's a fact.
`We don't dispute that nonporous media can be used to purify
`RNA, but other references like the Lloyd reference makes it clear that
`the porous media were an obvious choice for preparing antisense
`oligonucleotides for impending preclinical and clinical investigations,
`so Dr. Hornby's statements don't undermine the obviousness case
`here.
`
`But to the extent that Dr. Hornby talked about issues with
`extracting RNA, if we could go to that slide, please, David? He was
`simply stating a well-known fact which is that there are some
`differences between DNA and RNA, but persons of skill in the art
`knew how to deal with them.
`For example, when he talked about extraction, he mentioned
`nucleases that may exist. You just went past the slide on molecular
`cloning. But persons of skill in the art by 2006 knew how to deal
`with RNA and its potential to be degraded by nucleases.
`And so even though Dr. Hornby acknowledged that RNA may
`be more sensitive to degradation than DNA, that doesn't undermine
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`the fact that a person of ordinary skill in the art knew how to deal with
`that difference.
`And what we point to, the Molecular Cloning Handbook that's
`here on slide 19, is an example of a basic laboratory manual. It's an
`iconic laboratory manual from Sambrook that was well known and
`used widely in the field by molecular biologists to figure out how to
`deal with RNAs, and that's what's highlighted in the lower left-hand
`corner there.
`And so persons of skill in the art knew how to deal with this
`basic difference between DNA and RNA and to mitigate it, and none
`of the evidence that the Patent Owner has put on in this case
`establishes that the differences between DNA and RNA are so
`significant that it would undermine any expectation of success in
`using RNA. And with --
`JUDGE SAWERT: Sorry, let me just ask one more question
`on that. The difficulty I have is that these statements seem very
`general and I'm looking for something very specific as to this type of
`chromatography, that these statements don't apply to this case.
`DR. ELLISON: Well, I'll --
`JUDGE SAWERT: I mean, I understand that people knew
`about RNAs and people have ways to try to deal with it, and I
`understand the differences between RNA and DNA, but these are still
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`very general statements, so I have a general statement and another
`general statement. Do you have something specific from Dr.
`Hornby?
`DR. ELLISON: Specific from Dr. Hornby about? Let me
`make sure I understand your question. You're looking for something
`specific, specifically from Dr. Hornby about the use of --
`JUDGE SAWERT: Why you would have had a reasonable
`expectation of success in this case for this chromatography because
`you see the position I'm in. I have what I would characterize as a
`very general statement about reasonable expectation of success in Dr.
`Hornby's first declaration. Then I have many, many general
`statements from Dr. Hornby that he made just a few years later saying
`that RNA purification was very unpredictable, etcetera, etcetera.
`I'm looking for, if you have it -- you know, so now I have
`these general statements. I'm trying to figure out how to weigh them
`against each other, and the best way to overcome those statements
`would be if you had something specific as to why this particular
`system would have been, somebody would have thought that this
`would have been successful.
`DR. ELLISON: Well, first I would submit that Dr. Hornby's
`statements were all backed up by specific citations to the literature,
`including citation to the Polymer Labs Catalogue that specifies and
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`makes it clear that its resin, which is useful, it's PSDVB resin, the
`same resin that's used in the 340 patent, can be used for both DNA
`and RNA, and we see that here on slide seven.
`And this is a porous resin, which again, you can see from the
`first quote on slide seven, so the Polymer Labs Catalogue, which is
`one of the references Dr. Hornby relied upon, demonstrates that this
`was expected to work for RNA, for purification of RNA.
`And not just on an analytical scale, but as we see from slide 16
`that we looked at previously, the Polymer Labs Catalogue makes it
`clear that this resin is suitably for preparative scale-up and that said
`scale-up would be easy.
`Also on slide 16, we have other statements from others in the
`art, and Dr. Hornby has pointed to these as evidence of what a person
`of ordinary skill in the art would have thought in 2006.
`So he cites, for instance, to the Swiderski reference which says
`there's no obvious reasons why IP RP HPLC can't be scaled up, as
`well as the Gelhaus reference which explains that IP RP HPLC offers
`the same resolution when used in the analytical scale as for
`preparative scale.
`So these are, there are numerous statements in the art in
`addition to the Lloyd reference which Dr. Hornby has cited as
`evidence of what a person of ordinary skill in the art would have
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`thought back in 2006 at the time the first patent application was filed
`here.
`
`JUDGE SAWERT: Let me ask you one more follow-up
`question about that. I know in your brief, you said that what Dr.
`Hornby said in 2009 would not inform what someone skilled in the art
`would expect in 2006, and I'm wondering do you have a case for that?
`Do you have a case for that general proposition that references
`that come out after the date at issue, the effective filing date, are
`irrelevant for determining whether or not there would have been
`motivation and reasonable expectation of success as to the earlier
`date?
`
`DR. ELLISON: I'll try to cite a case to you when I come
`back on rebuttal, but you can understand, I think, the general principle
`that even if by 2006, one had a different view, the real issue is what
`did one think as of -- excuse me. Even if by 2009, one had a certain
`view, the real issue is what did one think as of 2006?
`And what the references we've cited, the numerous references
`we've cited show, the expectations of a person of ordinary skill in the
`art, they expected these methods that were developed for DNA to also
`work for RNA, and in numerous instances, they demonstrated that the
`methods developed for DNA also worked for RNA.
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`So the citations and discussions that are in the prior art
`references that we've cited are significantly more probative of this
`issue than Dr. Hornby's personal statements, individual statements
`made in 2009.
`And as I've explained, those statements from Dr. Hornby in
`2009 don't relate to preparative purification. They relate to
`analytical purification and highlight a preference for nonporous over
`porous just for analytical, but not preparative.
`JUDGE SAWERT: For those later statements, can you
`explain a little more why the fact that they're directed to analytical
`versus preparative, why that makes a difference as to the relevance?
`DR. ELLISON: So in our ground two, we argued that a
`person of skill in the art would have been motivated to use Lloyd's
`methods for carrying out RNA purification on a preparative scale, and
`one of the differences technically between carrying out purification on
`a preparative scale versus analytical scale is this issue, two issues of
`loading capacity and high speed, the need for high speed.
`So as Dr. Svec acknowledged, the nonporous supports were
`just preferred for high-speed separations of various types of
`molecules, including nucleic acids on an analytical scale, but Dr.
`Hornby's statements, to the extent he expressed a preference for
`nonporous, was limited to analytical scale and does not undermine the
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`obviousness of using Lloyd's porous PSDVB resin in preparative scale
`purification of RNAs.
`The Patent Owner -- let's look at slide 15. In an effort to
`save its case, the Patent Owner repeatedly focuses on what was
`actually experimentally demonstrated rather than what the art would
`have suggested to a person of ordinary skill in the art.
`For example, on slide 15, we have Lloyd's statements showing
`again why a person of skill would have had a reasonable expectation
`of success, and she says from her data, which used the same resin that
`she used in the 340 patent, it's clear that ion-pair reverse-phase HPLC
`can be used for the analysis and purification of oligonucleotides, and
`one would not have viewed that statement as being narrowly limited
`to DNA for all of the reasons that I discussed before.
`The Patent Owner tries to discredit these data by criticizing
`the peaks that you see on the chromatograms on the right-hand side.
`They posit that a person of skill in the art wouldn't even look to the
`Lloyd reference because one would want narrow and tall peaks and
`symmetrical peaks that are not overlapping peaks, but none of these
`characteristics are required by the claims, and so Patent Owner's
`arguments in this regard should be disregarded.
`As their own expert, Dr. Svec, admitted, obviously if you see
`different peaks in a run, you've got separation, and that's all that the
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`claims require is some degree of purification, and he further
`acknowledged that the methods on Lloyd tell a person of skill in the
`art which molecules can be separated.
`Let's look at the next slide.
`JUDGE MOORE: You're about a half-hour in.
`DR. ELLISON: Okay, so I have --
`JUDGE MOORE: 20 minutes, total minutes.
`DR. ELLISON: 20 more minutes. Thank you.
`JUDGE MOORE: Ten in this section though.
`DR. ELLISON: Thank you, Your Honor. I'll also note that
`Dr. Svec's criticisms of Lloyd re
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