Trials@uspto.gov
`571-272-7822
`
`
`
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`Paper No. 101
`Entered: March 18, 2021
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
`
`
`LABORATOIRE FRANCAIS DU FRACTIONNEMENT ET DES
`BIOTECHNOLOGIES S.A.,
`Petitioner,
`
`v.
`
`NOVO NORDISK HEALTHCARE AG,
`Patent Owner.
`_____________
`
`IPR2017-00028
`Patent 9,102,762 B2
`_____________
`
`Record of Supplemental Oral Hearing
`Held: February 6, 2019
`_____________
`
`
`
`Before ERICA A. FRANKLIN, SUSAN L. C, MITCHELL, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`
`
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`
`
`
`
`
`571-272-7822
`
`
`
`
`Paper No. 101
`Entered: March 18, 2021
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
`
`
`LABORATOIRE FRANCAIS DU FRACTIONNEMENT ET DES
`BIOTECHNOLOGIES S.A.,
`Petitioner,
`
`v.
`
`NOVO NORDISK HEALTHCARE AG,
`Patent Owner.
`_____________
`
`IPR2017-00028
`Patent 9,102,762 B2
`_____________
`
`Record of Supplemental Oral Hearing
`Held: February 6, 2019
`_____________
`
`
`
`Before ERICA A. FRANKLIN, SUSAN L. C, MITCHELL, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`
`
`
`
`
`
`
`
`
`
`
`IPR2017-00028
`Patent 9,102,762 B2
`
`
`
`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER:
`
`
`GEORGE E. QUILLIN, ESQ.
`JASON N. MOCK, Ph.D., ESQ.
`Foley & Lardner LLP
`Washington Harbour
`3000 K Street, N.W., Suite 600
`Washington, DC 20007
`202-672-5413 (Quillin)
`gquillin@foley.com
`
`
`
`ON BEHALF OF THE PATENT OWNER:
`
`
`JEFF OELKE, ESQ.
`CATHERINE H. MCCORD, ESQ.
`Fenwick & West LLP
`902 Broadway, Suite 14
`New York, NY 10010
`212-430-2747 (Oelke)
`joelke@fenwick.com
`
`
`
`
`The above-entitled matter came on for hearing on Wednesday,
`
`February 6, 2019, commencing at 1:00 p.m. at the U.S. Patent and
`Trademark Office, 600 Dulany Street, Alexandria, Virginia.
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`IPR2017-00028
`Patent 9,102,762 B2
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`
`P R O C E E D I N G S
`- - - - -
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`
`
`(1:00 p.m.)
`JUDGE PAULRAJ: Good afternoon. This is the supplemental oral
`hearing for IPR2017-00028. I am Judge Paulraj and to my left is Judge
`Mitchell and to my right is Judge Franklin.
`Let's start with the appearances, Petitioner's counsel first and then
`Patent Owner's counsel.
`MR. QUILLIN: Good day, Your Honor. I am George Quillin from
`Foley & Lardner representing Petitioner LFB, and with me at counsel table
`is my colleague Jason Mock who will be presenting most of the
`technological arguments.
`JUDGE PAULRAJ: All right. Thank you, Mr. Quillin, Mr. Mock.
`Patent Owner's counsel?
`MR. OELKE: Good afternoon, Your Honor. Jeff Oelke from
`Fenwick & West on behalf of the Patent Owner, Novo Nordisk Healthcare
`AG, and with me is my colleague Catherine McCord, whose pro hac is
`pending for this proceeding.
`JUDGE PAULRAJ: I did want to actually address that as a
`preliminary matter. So we are granting Ms. McCord's pro hac vice and there
`will be an order issued. So to the extent that she wants to participate in this
`hearing consider her admission granted.
`MR. OELKE: Thank you, Your Honor, although I will be
`presenting.
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`IPR2017-00028
`Patent 9,102,762 B2
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`
`JUDGE PAULRAJ: All right. Thank you, Mr. Oelke. As per the
`hearing order that we issued last week, each side will have 30 minutes to
`present arguments limited to the scope of this hearing -- proceeding.
`So I do want to emphasize again that as we did in prior orders that
`this oral hearing will not be used as an opportunity to re-argue on
`patentability grounds that were decided in our final written decision from
`April.
`
`So with that let's start with Petitioner's counsel. Actually, are there
`any other preliminary matters we need to address before we start the
`arguments?
`MR. QUILLIN: Aside from reserving rebuttal time if you want to
`do that, Your Honor.
`JUDGE PAULRAJ: Okay.
`MR. QUILLIN: There is nothing that -- I don't believe there is
`anything else from Petitioner's side.
`JUDGE PAULRAJ: Okay.
`MR. OELKE: Your Honor, we did file a Motion to Exclude some of
`the exhibits they filed in their supplemental reply.
`JUDGE PAULRAJ: Okay. And we will consider those in due
`course. We are not going to be addressing that at this point.
`MR. OELKE: Okay. Thank you, Your Honor.
`JUDGE PAULRAJ: All right. Mr. Mock, if you are ready --
`whenever you are ready.
`MR. QUILLIN: George Quillin, Your Honor, just some preliminary
`remarks. We would like to reserve 15 minutes of our time for rebuttal.
`JUDGE PAULRAJ: Okay.
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`IPR2017-00028
`Patent 9,102,762 B2
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`
`MR. QUILLIN: So just the big picture, we have asserted that Novo
`is not entitled to the benefit of its priority applications. We say that they
`waived that in their initial -- the first Patent Owner response by not
`addressing it, even in this supplement hearing, although they did address it,
`we say there is no evidence.
`It is their burden, they didn't carry it, they are not entitled. That is
`important for a couple of reasons. One, it bears on the state of the art. It
`goes to the Graham factors for example, the scope and content of the prior
`art, differences between the art, and the claim did mention it.
`It also goes, Your Honor, to the credibility of the Patent Owner's
`expert witnesses who don't address the state of the art after their asserted
`benefit date, so they are in that sense blind to a whole year's worth of
`progress in the art.
`Second, big picture, the claims, as you know, are directed to a
`method of filtering a liquid composition. Of course there is no claim to the
`filter itself -- that's old, that's in the art. There is also no claim to the liquid
`composition itself -- that's old, that's in the art.
`So the claims, big picture, are to run a known liquid through a
`known filter and what do you get? What happens when you run a liquid
`through a filter? The big stuff is retained and the small stuff goes through.
`Here are the big stuff, the virus is retained -- the small stuff, the
`protein goes through. That's what you expect when you run a liquid through
`a filter. So in our view it's very straightforward and I will turn it over to Mr.
`Mock to address our specific arguments on the technology.
`JUDGE PAULRAJ: All right. Thank you.
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`IPR2017-00028
`Patent 9,102,762 B2
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`
`MR. MOCK: Thank you, Your Honors. My name is Jason Mock.
`If you are okay with this I will start out with claim construction since that
`issue permeates the rest of the issues that we'll be talking about today.
`So Novo and LFB both agree that the term Factor VII polypeptides
`should be construed as it is defined in the PCT application. So this includes
`Factor VII variants, conjugates, and derivatives.
`Conjugates and derivatives, of course, as you have read in our briefs,
`are species or embodiments, different types of compositions that were added
`only as of the PCT application. The PCT application includes numerous
`examples of variants, conjugates, and derivatives that all should fall within
`the scope of the claim and as acknowledged by Dr. Krishnaswamy during
`his second deposition, this includes peptides that have increased proteolytic
`stability.
`It also includes conjugates that are linked to activation site inhibitors
`as disclosed in U.S. 2003-0211094, and the variants would reduce sensitivity
`to proteolytic degradation as disclosed in WIPO Publication 2003-093465.
`So for the purposes of considerations of the grounds at issue the
`claims should not be limited just to wild-type Factor VII polypeptides --
`Factor VII and Factor VIIa. They should include variants, conjugates, and
`derivatives that have been expressly designed to limit degradation.
`So turning to the first ground that will be discussed today, our Tolo
`anticipation ground. In Novo's supplemental response they have stated that
`it would be impossible to define the claimed method from Tolo's disclosure,
`but that is actually far from the truth.
`The only thing that has to be done in order to meet every single
`limitation of the claims is to substitute Factor VII alpha for interferon -- the
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`IPR2017-00028
`Patent 9,102,762 B2
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`Factor VIIa for interferon alpha in Example 3 that will bring you to a
`method of nanofiltering a biologically active protein through the proper size
`filter at the appropriate concentration and the appropriate percent activation.
`Tolo not only gives express instructions for this as feasible, it
`recommends using Factor VII among a handful of other proteins. While
`Novo would let the Board believe that Tolo should be read solely as related
`to interferon alpha, I believe we all know that that's not the law.
`On Page 6 of Tolo this reference says that stabilization and filtration
`of interferon alpha is a preferred embodiment, but references aren't read to
`be limited to their preferred embodiments. They are read for everything that
`is included therein.
`And here every part of Tolo belies Novo's position that it has to be
`related solely to interferon alpha. The title is a method for preparing virus
`safe pharmaceutical compositions, not virus safe interferon alpha
`compositions.
`JUDGE PAULRAJ: So, Mr. Mock, so as I'm sure you are well
`aware that this ground is going to be limited to only the anticipation ground
`based on Tolo.
`MR. MOCK: Sure.
`JUDGE PAULRAJ: So why do you think we should read Tolo to be
`an anticipatory reference when we certainly considered it in terms of
`obviousness and didn't find that Petitioner made it showing as to
`obviousness based on Tolo?
`MR. MOCK: So the only two disputed limitations, the only two that
`Novo alleges are not present in the reference, are the concentration and the
`percent activation. The other limitations are recited in Example 3.
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`IPR2017-00028
`Patent 9,102,762 B2
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`
`For our purposes we believe the concentration is there and
`application to Factor VII and Factor VIIa as well as interferon alpha
`because as we have noted in our briefs, there is plenty of case law that says a
`reference can be anticipatory even if it doesn't expressly spell out the
`limitations, so long as the elements that are there can be arranged in a way
`that would be -- that a person of ordinary skill in the art could envisage the
`claimed invention and that --
`JUDGE PAULRAJ: Right. So on that point then, so how do you
`propose that a skilled artist in reading Example 3, which is what you want us
`to look at for the concentration limitation, and that example is specifically
`limited to IFN-alpha, and read that to suggest or at least at once envisage the
`same concentration for Factor VIIa?
`MR. MOCK: I think you have to look at Example 3 in the context of
`disclosure as a whole because the rest of the disclosure refers to biologically
`active proteins in general, not just interferon alpha.
`It says that interferon alpha is solely one embodiment, but the rest of
`the specification relates to how to formulate a biologically active protein
`generally -- the nanofilters that can be used, therefore, generally, and this is
`all in the context of the paragraph at the beginning of the detailed description
`that expressly lists Factor VII and activated Factor VII as proteins that are
`suitable for these methods.
`The reason that a person with skill in the art would presume or infer
`that the 0.04 mg per mL concentration that is used in Example 3 is because
`this is a much lower concentration than even known forms of activated
`Factor VII.
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`IPR2017-00028
`Patent 9,102,762 B2
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`
`For instance, we point out in our reply brief that NovoSeven, the
`FDA approved formulation of activated Factor VII that had been approved
`for several years as of that point, is a concentration of 0.60 mg per mL, so 15
`times more than that.
`JUDGE PAULRAJ: So why should the skilled artisan have looked
`at what the FDA approved version of Factor VIIa is in reading Tolo's
`disclosure?
`MR. MOCK: Well that actually relates not only to the concentration
`but also the activation limitation. Tolo talks about using therapeutically-
`used proteins and here there is really no dispute that activated Factor VII is
`the therapeutically-used protein.
`That is something that our declarant, Dr. Chtourou said in his initial
`declaration. That is something that Dr. Krishnaswamy confirmed in his
`latest deposition saying that NovoSeven is almost 100 percent Factor VII.
`So if you are looking for a therapeutically-used version of Factor
`VIIa you would be looking at that time frame at NovoSeven. Furthermore, a
`concentration of 0.04 mg per mL is not a highly concentrated composition,
`as Novo has alleged throughout the course of this proceeding, but Dr.
`Krishnaswamy said again during his cross deposition that 0.02 mg per mL is
`a small scale experiment when you are talking about protein filtration and he
`even said that 0.10 mg per mL is what you would consider an intermediate
`scale experiment.
`So we're not talking about just blasting a filter with highly
`concentrated protein, this is something that a person with skill in the art
`would be able to look at, and taking into everything that they know, infer I
`could substitute Factor VIIa in for interferon alpha and this would work.
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`IPR2017-00028
`Patent 9,102,762 B2
`
`
`JUDGE PAULRAJ: All right. Just a preliminary question on your
`anticipation grounds, so I mean Patent Owner I think they have a point here
`that the anticipation grounds that were actually set forth in the petition is
`almost limited to just a single sentence and the way I read that sentence it
`almost seems like it's just limited to Claim 1.
`Is that your understanding as well, that the petition limited the
`anticipation grounds for a total up to just Claim 1 or any other claims?
`MR. MOCK: No, it would not just be Claim 1. Tolo discloses at
`least the independent claims, which differ only in terms of the size of the
`filter being used -- the size of the pore of the filter being used, and I think it's
`Claim 12 that includes a detergent which is also --
`JUDGE PAULRAJ: But before you start making those types of
`arguments I would like you to point to me where in the petition, since the
`petition does govern the scope of this proceeding as per SAS, you have
`made any anticipation arguments beyond Claim 1.
`MR. MOCK: I don't know that I can point to something expressly at
`this time, Your Honor, in the interest of time.
`JUDGE PAULRAJ: That's fine. And I will say for the record that I
`haven't found anything either. So to my knowledge, and correct me again if
`you are aware of anything to the contrary, the only indication -- or only
`reference to an anticipation argument with Tolo is on Page 35 of your
`petition, and I'll read that sentence.
`Nevertheless, Tolo anticipates Claim 1 because Tolo discloses all
`limitations in a matter that a POSITA would immediately recognize and
`acknowledge as an anticipatory embodiment.
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`Patent 9,102,762 B2
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`
`MR. MOCK: Again, Your Honor, I am not sure if I would be able to
`point to a section right now with my time dwindling. We'll move on if that's
`all right.
`JUDGE PAULRAJ: All right. Thank you.
`MR. MOCK: So in the interest of time we will go ahead and switch
`to the Eibl ground, our other ground that is at issue here. And in this
`situation Eibl teaches all of the limitations for its claims except for the
`claimed concentration range.
`There is an argument in Novo's supplemental response that the
`activation percentage is also not present, but that's such a strained reading of
`this reference that it borders on implausible. Eibl discusses both Factor VII
`and Factor VIIa.
`It says that formulations included therein can include one or two, one
`or the other. It's apparent that the authors -- the inventors there, appreciate
`the difference between Factor VII and Factor VIIa and there is no sentence
`or remarks within Eibl that say those terms are going to be used
`interchangeably.
`So to read Example 7 of Eibl, which nanofilters Factor VIIa, and
`uses the term Factor VIIa as maybe just a Factor VIIa, maybe it's Factor VII,
`is just an illogical interpretation of the reference that is clearly shown that it
`knows how to distinguish between Factor VII and Factor VIIa.
`JUDGE PAULRAJ: So in Example 7 of Tolo, Factor VIIa is
`identified as an activator substance?
`MR. MOCK: Yes.
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`IPR2017-00028
`Patent 9,102,762 B2
`
`
`JUDGE PAULRAJ: So that Factor VIIa is different than the Factor
`VIIa that may be present in the prothrombin complex that is also disclosed in
`Eibl?
`
`MR. MOCK: No, it wouldn't be distinct from it. In fact, the rest of
`Example 7 goes on to articulate that after that mixture of Factor IX or Factor
`VIIa that is part of this activator substance is nanofiltered, it is then -- can be
`diluted to appropriate concentrations to be added to, for example, the
`mixture of clotting factors that was prepared in Example 3 and Example 4
`above. So that activation substance can ultimately end up in the
`prothrombin complex after it has been nanofiltered.
`That actually provides a segue to another point that I think is worth
`making here and that is that LFB has not argued that the increase in
`concentration that would be required for Eibl to meet the claimed limitations
`would indicate that we are increasing the concentration of Factor VIIa in
`isolation from the other coagulation factors in a prothrombin complex.
`I see I am running out of time here. If you would allow me to finish
`this point.
`JUDGE PAULRAJ: Sure.
`MR. MOCK: So that is really a construct of Novo's design here
`because reading through Example 7, as I just noted, Factor VII and Factor
`IX are nanofiltered independently and then they are mixed with these other
`coagulation factors to get the prothrombin complex that is disclosed in that
`reference.
`So when -- If you were to increase the concentration in order to meet
`the claimed limitations at issue here, you are still going to go through these
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`IPR2017-00028
`Patent 9,102,762 B2
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`subsequent steps of diluting Factor VIIa to the appropriate levels before it's
`mixed with the other coagulation factors.
`There has never been an argument on LFB's case that Factor VIIa
`can just be increased without any consideration in the ultimate product, just
`that for the purposes of preparing this activation substance it could be
`increased in a commercial context.
`JUDGE PAULRAJ: All right. Thank you, counsel.
`MR. MOCK: Thanks.
`MR. OELKE: Your Honor, I have some slides. Can I pass them
`
`out?
`
`JUDGE PAULRAJ: Sure. Thank you.
`(Pause.)
`MR. OELKE: Your Honor, I'd like to reserve five minutes.
`JUDGE PAULRAJ: Okay. Whenever you are ready.
`MR. OELKE: Okay. Your Honors, this proceeding is supposed to
`be limited to the grounds that were not instituted in the DI that the court --
`the Board, issued at the beginning of this case. And yet what we find in this
`proceeding is time and again what LFB has tried to do is to bring in new
`arguments that either are parts of the arguments from the final written
`decision, or entirely new arguments as if they want to file yet another
`petition as to the '762 Patent.
`If you look at the one paper that they filed in this re-hearing
`proceeding, it's 21 pages. They don't talk about Eibl until Page 16. They
`talk about Tolo for the first time on Page 11. The first 10 pages are talking
`about this new scope and content of the art being reviewed as of 2004.
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`Patent 9,102,762 B2
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`
`But if you look at the petition, which is what should be controlling
`here, and the declaration from Dr. Chtourou, it's all talking about 2003. Dr.
`Chtourou in his declaration actually says, if I am going to talk about 2004 I
`will say so expressly, and then never does so anywhere in his declaration.
`So his entire declaration is the state of the art as of 2003.
`The petition is grounded in the same way except for the Eibl
`reference. Other than that, there is no difference as to 2003 or 2004 as to the
`petition. So these are all new arguments that are raised for the first time in
`this supplemental reply.
`They took the deposition of Dr. Krishnaswamy who put in a
`declaration in this supplemental proceeding. It went for seven hours. They
`didn't mark Tolo, they didn't mark Eibl, they didn't ask a question about
`Eibl, they didn't ask a question about Tolo. It didn't even come up for seven
`hours.
`
`This is not what the supplemental proceeding is supposed to be about
`and it is improper for a SAS re-hearing to be opening up all of these new
`issues that we have heard about today, and in their papers.
`Now if you do look at the proper grounds for this re-hearing
`proceeding I think it is important to look at the claims of the '762 Patent, and
`specifically Claim 1. Two limitations that are important here on Slide 2 are
`the concentration, which requires a range of 0.10 to 5 mg per mL and it also
`requires and activation level of 50 to 100 percent.
`And in some of the subsequent claims those percentages are higher,
`and in the concentration range for Claim 11 the lower range is 0.05. That is
`important to keep in mind for these particular grounds, and these particular
`grounds are what this re-hearing is supposed to be about.
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`Patent 9,102,762 B2
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`
`As you pointed out, Tolo has an anticipatory reference. It is
`mentioned once in the petition. So we're doing a lot of talking about
`something that started out as really one sentence. If you look at Slide 3, here
`is Tolo. Tolo is about interferon alpha. It's not about Factor VII or activated
`Factor VII.
`There is a single sentence mentioning Factor VII, but let's look at
`what is actually described, what the disclosure is in Tolo. It's all about
`interferon. They had a problem with interferon. The Tolo inventors had a
`problem.
`Their interferon alpha, which is what they were working with, was
`sticking to filters, it was sticking to vessels, they were having to get rid of
`vessels, they were having to replace things, and so they were looking for a
`new way to solve that problem and so they added polysorbate as a detergent
`to their interferon solutions, and that's what these examples are about.
`That's what Example 3 is about. They are comparing polysorbate-
`containing interferon solutions to albumin-containing interferon solutions,
`which is what they have used prior to polysorbate, and they determined
`which one worked better.
`That's what Tolo is about. That is what the experimental data shows.
`It's not about Factor VII. And, in fact, this Board found in the decision back
`in April of last year, the final written decision, that there is a difference
`between interferon alpha and Factor VII and it is important.
`The molecular weight is different. Factor VII is more than twice the
`size. They have completely different types of structures. With respect to
`interferon it's compact and globular. With respect to Factor VII it's
`asymmetric, it's elongated, it has different domains. None of that is
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`IPR2017-00028
`Patent 9,102,762 B2
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`applicable to interferon and most importantly interferon has nothing to do
`with the zymogen activated dichotomy that you have with respect to Factor
`VII.
`
`All this is put forward in our response and with Dr. Krishnaswamy's
`declaration at Paragraphs 59 to 60. LFB in their supplemental reply put it in
`no evidence on this point. As I said Tolo mentions Factor VII once.
`This here is Slide 5 where it is mentioned. That is an aspirational
`list. It's basically all proteins. That's not a teaching as to each of these
`proteins which is what LFB would have you believe with respect to Tolo.
`JUDGE PAULRAJ: So Tolo is dated in 1999. Is there any evidence
`of record as to what was publicly known of NovoSeven or any other
`commercial version of Factor VIIa at the time?
`MR. OELKE: There was -- Factor VIIa was available before 2003
`and it was activated and it was a high level of activation, but that part of the
`record that had to do with the fact that Factor VIIa in NovoSeven was never
`nanofiltered.
`It was the first time that Nova Nordisk nanofiltered NovoSeven was
`many years later. So that is part of the record in the file history, but this is
`basically a new argument and that's why they are adding this new
`specification about NovoSeven into their supplemental reply brief.
`But there is nothing in Tolo about NovoSeven. There is nothing in
`Tolo that would suggest, oh, you look at specific forms of Factor VII that are
`on the marketplace or any of these other proteins. The concentration
`disclosure is specific to interferon alpha -- that was clear, it was made clear
`in the final written decision from this Board, and nothing that was put in by
`LFB in these papers has changed that.
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`There are also is no teaching as to the percent of activation. They
`want to argue, well, if it has an "A" behind it then it's 100 percent, but there
`is nothing to say that just because it's activated it's a 100 percent activated.
`There has to be a disclosure that actually teaches that and there is
`nothing like that in Tolo. If we go on to Eibl the first thing to talk about Eibl
`before we talk about the disclosure is Eibl prior art and really that issue
`comes down to the initial Danish application did not include the term
`"derivative," it did not include the term "conjugate." That was added in the
`PCT in 2004.
`But it did, the Danish application did use the term "variant" and it
`made clear that variant was without limitation. And, in fact, it is defined
`there from the beginning of 2003 that a variant is one in which biological
`activity has been substantially modified or somewhat reduced relative to the
`activity of wild-type Factor VIIa.
`That would qualify those derivatives and conjugates that are
`specifically those two terms that are added in 2004 would fall within that
`definition. And, again, Dr. Krishnaswamy put in his declaration that it was
`his opinion that a variant in 2003 would be understood to include a
`derivative and a conjugate.
`But even if we assume Eibl is a prior art what you have to remember
`about Eibl is it's a prothrombin complex, and what is a prothrombin
`complex, prothrombin complex basically has a trace amount of Factor VIIa
`in it, a trace amount.
`It came up during prosecution and there were references cited during
`prosecution and it was made clear that these concentration requirements in
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`the claims distinguish these prothrombin complexes that have many things
`in them, and the amount, 20 nanograms, that's 500 times less than 0.01.
`So when they say 0.01 is not that high of a concentration, well it's
`500 times higher than the reference they want to rely on. If you look at Slide
`8 Eibl is silent as to the level of activation. There is no indication that they
`have tested the Factor VIIa for the level of activation in this disclosure.
`They, again, want to argue, well, if it says VIIa it's 100 percent.
`There is nothing in this disclosure that says that. So the problem for Eibl
`from the beginning, and this is really what was found by this Board in the
`decision, on the DI, was the concentration is so low that there has to be some
`other teaching for it to be in any way relevant.
`And so where do they look? They argue, well, you pull in Mollerup.
`But you have to remember Mollerup has already been considered by this
`Board as well and the final written decision said this teaching on
`concentration in Mollerup is talking about a VIIa just sitting there in storage.
`There is nothing about passing it through filters, it's sitting there.
`And what did they say about it in Mollerup? They actually said, well, under
`these static conditions you still need to control time and concentration, and
`that's what this Board found in April.
`So the reasons that are put forward for why you would combine Eibl
`and Mollerup in the petition would there be a need to increase the rate of
`purification or there would be a need to increase throughput.
`But think about this, these prothrombin complexes require minute
`amounts of VIIa. There is no reason to be increasing them. You need to
`keep them to their scant amounts that are already in the complex.
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`Finally, and this is all, again, put in by Dr. Krishnaswamy in this
`declaration, which was un-rebutted by LFB. In their reply there was nothing
`rebutting this. They did not put in a counter-declaration on these points.
`And, finally, Dr. Krishnaswamy in Paragraph 94 talked about it
`would likely fail if you did try to combine these. There is no reason you
`would combine them but if you did there is a reason it would be a bad idea,
`and that bad idea is in Slide 11, and that's the Josic reference.
`And Josic is talking about what happens when they found
`thrombogenic events from prothrombin. So prothrombin had been used in
`these patients and these patients have a lot of difficulties. You know, they
`have bleeding events, but when you try to stop a bleeding event the concern
`you have is that you over clot the patient and that leads to these
`thrombogenic events such as strokes, and so that's what Josic is talking
`about.
`
`They were looking at what were causing these thrombogenic events
`and what did they find, it was ones where they had substantially higher
`potencies of activated Factor VII, meaning a higher concentration.
`So here is Josic telling you you don't want to increase concentration
`in prothrombin of Factor VIIa. It's going to lead to really bad results and so
`they said as a consequence of these observations a PCC, that's a prothrombin
`complex concentrate, meeting the criteria of low, presumed low
`thrombogenicity was developed.
`And what did they require? A very low proteolytic and Factor VIIa
`activity. They wanted to keep it to those minor, minor amounts that are in
`prothrombin. And that's what the Josic reference states. There is no
`reference stating otherwise.
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`IPR2017-00028
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`So in the end LFB's efforts here are to either try to re-argue that final
`written decision or to bring forward all new arguments so it's just an all-new
`petition. None of this was in their original petition.
`It should be rejected as not proper in this re-hearing proceeding.
`This proceeding was about the SAS grounds alone, which is Tolo and the
`Eibl obviousness grounds and there is a reason those grounds, that you did
`not institute on those grounds in the first place is because Tolo and Eibl have
`tangential connection at best to Factor VIIa.
`And LFB in this proceeding set forth no evidence to change that
`conclusion in the decision on institution. So, therefore, we respectfully
`submit the '762 claims should again be found patentable over those grounds
`for Tolo and for Eibl. Thank you.
`JUDGE PAULRAJ: Thank you, counsel. Whenever you are ready,
`counsel.
`MR. MOCK: Okay. So just for one point of clarification for the
`purpose of the record before we go any further, when Mr. Oelke started and
`characterized the claims he had said that the claims are cited at concentration
`of 0.10 to 5 mg per mL, it's actually 0.01 mg per mL, so it is a much larger
`span of concentration.
`Taking some of his points in turn though, one of the arguments that
`has been repeated throughout Novo's responses is that interferon alpha and
`Factor VIIa are different proteins. But the important thing is they are not
`diffe
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