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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`MYLAN PHARMACEUTICALS,
`Petitioner,
`
`v.
`
`BIOGEN MA INC.,
`Patent Owner.
`____________
`
`Case IPR2018-01403
`Patent 8,399,514 B2
`____________
`
`Record of Oral Hearing
`Held: November 13, 2019
`____________
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`
`
`
`Before SHERIDAN K. SNEDDEN, JENNIFER MEYER CHAGNON, and
`JACQUELINE T. HARLOW, Administrative Patent Judges.
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`Case IPR2018-01403
`Patent 8,399,514 B2
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`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER:
`
`
`NATHAN R. KELLEY, ESQ.
`BRANDON WHITE, ESQ.
`Perkins Coie, LLP
`700 13th Street, NW
`Suite 600
`Washington, D.C. 20005
`
`
`
`ON BEHALF OF THE PATENT OWNER:
`
`
`BARBARA MCCURDY, ESQ.
`Finnegan, Henderson, Farabow, Garrett & Dunner, LLP
`901 New York Avenue, NW
`Washington, D.C. 20001
`
`
`
`
`The above-entitled matter came on for hearing on Wednesday,
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`November 13, 2019, commencing at 1:00 p.m., at the U.S. Patent and
`Trademark Office, 600 Dulany Street, Alexandria, Virginia.
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`Case IPR2018-01403
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`P R O C E E D I N G S
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`BAILIFF: All rise.
`JUDGE SNEDDEN: All right. Please be seated. Thank you. Good
`morning. This is the final hearing in IPR2018-01403. I am Judge Snedden
`and I have with me on the panel Judge Chagnon and Harlow. Let’s begin
`with appearances, starting with petitioner, please stand, introduce yourself
`and who you have with you today.
`MR. WHITE: Good morning, Your Honor. Brandon White, counsel
`for Mylan Pharmaceuticals from Perkins Coie and with me today is Nathan
`Kelley, Courtney Prochnow, Shannon Bloodworth, David Anstaett, Emily
`Greb and Mike Chajon. And from Mylan Pharmaceuticals, Matt Griner and
`Tom Jenkins. Mr. Kelley will be handling the argument today.
`JUDGE SNEDDEN: Thank you, welcome. Patent owner?
`MS. MCCURDY: Good morning, Your Honors. Barbara McCurdy
`for Biogen. With me at counsel table today is Pier DeRoo, Erin Sommers.
`Also with me are Mark Feldstein, Cora Holt, Yoonhee Kim and also for
`Biogen, we have representatives here including the general counsel, Susan
`Alexander and a number of other representatives. I can introduce them all if
`you would like. Okay.
`JUDGE SNEDDEN: That won’t be necessary.
`MS. MCCURDY: Okay, thank you.
`JUDGE SNEDDEN: Thank you. Per our order granting this oral
`hearing, each party will have 60 minutes of total time to present its
`argument. Petitioner will open the hearing presenting its case regarding the
`challenged claims for which we institute a trial and then patent owner will
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`then respond to petitioner’s argument. Each party may reserve rebuttal time
`and patent owner may reserve up to five minutes for rebuttal time per our
`(inaudible) order.
`I also note that Judge Harlow is joining us remotely so I take the
`opportunity to remind the parties to speak the slide number as you go
`through your presentation today for both the benefit of the record and also
`for Judge Harlow. Okay. With that I’ll let petitioner being when you’re
`ready.
`MR. KELLEY: Thank you. Good morning or good afternoon, Your
`Honors. I’d like to reserve 20 minutes for rebuttal.
`JUDGE SNEDDEN: When you’re ready.
`MR. KELLEY: So I’d like to begin with a claim in this case. Claim 1
`of the 514 patent. And this is on Slide 6 of our presentation which we are
`getting up now.
`So Claim 1 and we will wait for the slide to come up but you have the
`slides in front of you. Claim 1 is a simple claim. It’s the only claim in
`dispute and it requires three things. It requires a disease, a drug, and a dose.
`The disease is multiple sclerosis. The drug is dimethyl fumarate and
`the dose is 480 milligrams per day. That’s what’s required by Claim 1.
`Nothing else is required and no other claim is in dispute in this case.
`At the time of the priority date of the 514 patent, the prior art was
`replete with references directing the skilled artisan right towards that subject
`matter. DMF was known to treat MS. The claimed 480 milligrams dose
`was between doses that were known to treat MS in the prior art and GI side
`effects were also well known at that time.
`In the face of that overwhelming evidence, Biogen attempts to side
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`step the evidence by presenting distractions. Biogen attempts to say that
`work by Dr. Kappos was actually work by Dr. O’Neill, that the Kappos
`study was actually O’Neill’s study. That their own press release hasn’t been
`shown to be publicly available when an employee of Westlaw swears it was
`at the time. That a flaw in the Kappos study that everybody -- that many
`people skilled in the art recognized in fact was not there and finally by
`ignoring all the drivers of Tecfidera's commercial success, other than the
`claim subject matter of the 514 patent.
`Now there are four grounds that we presented in our petition and I
`would like to briefly address ground number four. So it’s not displaying but
`the Board has the slides in front of them so I'm just going to go, oh here we
`go. Okay.
`So the fourth ground the Board is familiar with, that’s the ground that
`relies on Kappos 2006, the clinical trial that showed efficacy of 720
`milligram dose as well as an argued efficacy of 360 milligram dose. And
`clinical trials reference as well as Joshi and the ICH guidelines.
`And I would like to start with that because in the previous IPR
`brought by the coalition, the Board already found that those working in the
`art would have had sufficient reason to investigate doses between 720 and
`360 milligrams in hopes of identifying effective doses with fewer side
`effects.
`And moreover, that those working in the art would also have had a
`reasonable expectation of success in determining additional therapeutically
`effective doses.
`Now of course we know what the issue was in that case and we know
`why the final written decision came out the way it was, the way it did, I'm
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`sorry. Was that there were secondary considerations of non-obviousness put
`forward by Biogen and there was no rebuttal at all by the coalition. There
`was no evidence, there was really no argument at all except to say that no,
`there are no secondary considerations and of course that didn’t carry the day.
`JUDGE SNEDDEN: Could you remind me what evidence this
`decision relies on for the 360 mg per day that was -- what are they
`referencing there when they say that?
`MR. KELLEY: So, Your Honor, when you say this decision, you
`mean the previous final decision?
`JUDGE SNEDDEN: Yes, what you have presented up here on the
`screen.
`MR. KELLEY: So the 360 milligram a day dose was a dose in
`Kappos 2006 that --
`JUDGE SNEDDEN: Oh, I see. I, forgive me.
`JUDGE HARLOW: Mr. Kelley, I apologize for the interruption.
`MR. KELLEY: That's okay.
`JUDGE HARLOW: Could you please let me know what slide you are
`displaying?
`MR. KELLEY: I'm sorry. Yes, we're on Slide 8, I apologize, Your
`Honor.
`JUDGE HARLOW: Thank you, sir.
`JUDGE SNEDDEN: All right. They're not, and they're not
`establishing a fact here. They're just making a conclusion and I understand
`now. You can go ahead.
`MR. KELLEY: Right. And of course the final written decision in
`that case was that obviousness had not been shown, that the burden hadn’t
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`been carried by the coalition and the reason was as stated in the decision that
`there was no rebuttal to the secondary consideration evidence.
`And of course we have that rebuttal here. And the secondary
`considerations evidence has been argued against all four grounds so I'll
`cover that when I get to it later but I just didn’t want to start with grounds
`four because that’s the grounds the Board has already gone through, they've
`already established what needs to be established for a prima facie case.
`JUDGE SNEDDEN: Understood, thank you.
`MR. KELLEY: So I'm going to turn now to Slide 7, again, these are
`the four grounds that are in dispute here in this IPR and I'm going to start
`with Ground 1.
`So Ground 1 requires or relies on two prior art references and they're
`both 102(b) references. The first reference is the January 2006 press release
`by Biogen. And the press release by Biogen in January 2006 told those
`skilled in the art that DMF mono therapy was successful at treating MS.
`That is that phase II study reached its end point.
`So those skilled in the art at the priority date, more than one year
`before the priority date were aware that it was a successful treatment of MS.
`The question is the dosing.
`So Schimrigk 2004 which is the other reference that we rely on for
`Ground 1 was a phase II study by Schimrigk that also tested the
`effectiveness of DMF over an extensive period of time and I want to stop
`and explain what the phase II study looked at and how it operated.
`So DMF was administered at 360 and 720 milligram doses and it was
`administered as Fumaderm. Now as the Board is aware at this point,
`Fumaderm has other components in it as well and I'm going to get to that in
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`a minute but the dosages that the study designers referred to were the
`dosages of DMF in Fumaderm and not the dose of Fumaderm in full.
`So the doses in the study were 360 milligrams and 720 milligrams.
`The 720 was the initial dosage. It was titrated up over an 18 week period
`and then there was a washout period of four weeks where nothing was given
`to the subjects. And then there was a 40 week period where the lower dose
`was given at 360 milligrams.
`And what Schimrigk concluded was that the oral fumarate therapy
`significantly reduced the number and volume of GD plus lesions over the
`full 70 week period. So they saw the initial drop in lesions and also what
`they saw is that more lesions did not occur and so they concluded that that
`treatment at 720 followed by an extensive period at 360 milligrams was a
`successful treatment of MS.
`So at this point, someone skilled in the art knows two things. They
`know that monotherapy, I'm sorry, that yes, that monotherapy of dimethyl
`fumarate is successful in treating MS and they also know from the
`Schimrigk study that when it comes to doses, doses of 360 up to 720
`milligrams have been used to treat MS dosed as Fumaderm.
`So there is other information that someone skilled in the art would
`bring to bear on the question of whether or not someone would have
`combined those two teachings to arrive at the claimed invention.
`And so I'm going to turn now to Slide 12 which is the Nieboer
`reference.
`JUDGE SNEDDEN: Can I just pause you there? I think patent
`owner is making an argument that this Schimrigk reference really just shows
`that the 720, I understand (inaudible) correctly.
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`MR. KELLEY: Well, that argument is in this case, Your Honor, but
`let me clarify something. There is, there are two different references. There
`is the press release which is the reference that we are relying on in Ground 1
`and the press release is just what it shows on Slide 9 which I turn back to
`now.
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`So Slide 9 is the press release and the press release just identifies the
`success of the MS treatment with DMF. What Your Honor is referring to is
`the underlying study itself, the underlying study itself is referred to in the
`grounds as Kappos 2006 and that study had dosages of in addition to a
`placebo 240 milligrams, 360 milligrams and 720 milligrams.
`And the dispute Your Honor is referring to is the success of the 360
`milligram dose whether or not the error in counting the, accounting for the
`baseline lesions for the group taking the 360 milligrams whether that error
`would have been seen at the time by skilled artisans.
`That is not we would submit relevant to the Ground 1 inquiry because
`the Ground 1 inquiry is related simply to the press release which talks about
`the success of MS treatment with DMF as well as the dosages taught by
`Schimrigk.
`JUDGE SNEDDEN: How does Schimrigk then support the position
`that the 360 milligram doses are effective or are you trying to establish that
`in this ground?
`MR. KELLEY: So we are trying to establish that in this ground and
`Schimrigk states in the abstract and I’ll return now to Slide 11, this is from
`Schimrigk 2004 the conclusion and I’ll read right from the slide. Oral
`fumarate therapy significantly reduced the number and volume of GD plus
`lesions over 70 weeks of treatment.
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`And then the next highlighted phrase at the end of that slide. These
`findings indicate that oral fumarates may be a promising new treatment for
`RRMS.
`The treatment they are referring to and I'll back up now to Slide 10 is
`the treatment in their study which was again and starting with the first
`highlighted phrase that you see, a six week baseline, an 18 week treatment.
`Now that 18 week treatment is at 720 milligrams followed by a four
`week washout and then a 360 milligram extended treatment for 40 weeks.
`And remember that this is relapsing remitting MS.
`So yes, initially during the 720 milligram treatment phase and after,
`the number of lesions dropped but also significantly they stayed at a low
`level throughout the entire part of the test, you know, throughout all of the
`phase II study which is why the conclusion by Schimrigk is not just that
`oops, that 720 milligrams was effective.
`Schimrigk says it proved effective over the entire 70 week treatment
`period. And so that’s where we are getting a statement of success from
`Schimrigk from the use of 360 milligrams, dosed as Fumaderm, for the
`treatment of MS. That’s what we’re getting at from that reference.
`JUDGE HARLOW: Counsel, does Schimrigk establish, let me
`rephrase that. Is your position that Schimrigk establishes the 360 is an
`effective doss for treatment based on the fact that it stabilized the results of
`the 720 or is it something else? I just want to make sure I understand what
`your assertion is with regard to that 360 milligram dose from Schimrigk.
`MR. KELLEY: Your Honor, I guess I would point to what Schimrigk
`itself says is that the therapy significantly reduced the number and volume of
`GD lesions over the 70 weeks of treatment. So I think what Schimrigk is
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`saying there is that they reduced the volume and number and that number
`reduction continued over the 70 weeks.
`JUDGE HARLOW: Does Schimrigk indicate that during the weeks
`of treatment with the 360 milligram dose the number of lesions continued to
`go down or did it stabilize? And does that matter?
`MR. KELLEY: So let me, let’s see which slide is that? Well, what it
`says in the top part of the slide is exactly what they're reporting, significant
`reductions from baseline legions were observed starting after week 12.
`So week 12 would have been and remember, the initial period is 18
`weeks of the 720 milligrams of week 12 is about I don’t know, two thirds of
`the way through that.
`So they're observing at that point and afterwards a reduction in the
`number of lesions and in addition, Schimrigk says there were significant
`reductions from baseline and GP plus lesion volumes starting after week 12.
`So I think what is observed is the drop in number and then that is
`followed by a low baseline. I'm not sure if I answered Your Honors
`question.
`JUDGE HARLOW: I think so and I think also our colloquy hits on
`the fact that it's a bit difficult to tease out exactly what Schimrigk is saying
`but at a minimum Schimrigk is indicating that there was a drop with the
`higher dose and that baseline, that new baseline was maintained throughout
`treatment with the lower dose, is that fair?
`MR. KELLEY: Yes, that is fair and that one skilled in the art reading
`Schimrigk would have seen Schimrigk's conclusion that its dosing protocol
`which includes an extended period at a 360 milligram dose was successful in
`the treatment of MS at least within the confines of that phase II trial which is
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`what we are relying on the DG for.
`JUDGE HARLOW: Thank you.
`MR. KELLEY: So the other art that would have been brought to bear
`by someone skilled in the art at the time of the critical date of the 514 patent,
`it begins with the Nieboer reference, Nieboer 1990 and now I'm referring to
`Slide 12.
`So in 1990, Fumaderm had been used to treat psoriasis and Fumaderm
`has DMF in it but it also has salt of monomethyl fumarate acids, I hope I
`said it right. And it has these additional components in it.
`And so what Nieboer set to determine was whether or not it’s the
`DMF component of Fumaderm which is doing the work or whether it’s
`some sort of combination of the DMF and these other ingredients within
`Fumaderm.
`And what Nieboer concluded was that the Fumaderm itself has no
`significantly better effect than monotherapy with DMF alone. So Nieboer's
`conclusion is that a 480 milligram dose in a monotherapy approach where
`only DMF is given, had the same or was no worse than a 480 milligram dose
`of DMF dosed as Fumaderm.
`So Nieboer recognized that it was the DMF in Fumaderm that was
`doing the heavy lifting with respect to the psoriasis treatment. And
`particularly at the 480 milligram dose level. And that observation was
`confirmed by Kolbach 1992 and this is Slide 13 I'm referring to now.
`And Kolbach said that apparently a dosage of 480 milligrams of
`DMFAE, that’s DMF delivered in a mono therapy and not as Fumaderm is
`necessarily to achieve satisfactory improvement. So the prior art understood
`that there was such a thing as mono therapy DMF and that also there was
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`DMF dosed as Fumaderm. And the prior art at this point understood also
`that it was the Fumaderm that was doing the work.
`And so you’ll see that the prior art continued to refer to the dose level
`of Fumaderm, I'm sorry, of DMF within Fumaderm as sort of the effective
`dose of what it was delivering. In other words, prior art artisans started to
`sort of ignore the other part of the Fumaderm.
`So Drugs 2005 and I'm turning now to Slide 14. This was a test
`where DMF was dosed at 120, 360 and 720 milligrams. And what was
`determined was the success of that dosing in a psoriasis treatment had a dose
`dependent effect. That is the 720 milligram and you’ll see that in the second
`highlighted phrase, portion on Slide 14 was effective at 71 percent. The 360
`was effective at 52 percent. The 120 was effective at 31 percent and the six
`percent was for a placebo.
`And so Drugs 2005 tells those skilled in the art that not only is DMF
`an effective treatment of psoriasis, an autoimmune disease, but that the
`treatment is dose dependent.
`So those last three prior art references I discussed Nieboer, Kolbach,
`and the Drugs 2005, those were all about the treatment of psoriasis with
`DMF. And so a question in this case is why is it that those skilled in the art
`would connect the dots between DMF and psoriasis and DMF against
`multiple sclerosis.
`And so now I've turned to Slide 15. Slide 15 is from the, well there
`are two things on Slide 15, Exhibit 1006 is from a Schimrigk study and what
`it says is that oral fumarate is an effective and safe therapy for the treatment
`of psoriasis. Similar to psoriasis, the inflammatory process in multiple
`sclerosis is taught to be mediated by a team one helper type cytokine
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`reaction due to global immune suppression of TH2 mediated by standard
`suppression.
`Which is all to say that the effective pathway that’s going on behind
`the scenes with psoriasis is similar to the effective pathway that’s going on
`behind the scenes with MS.
`And our expert, Dr. Greenberg gets at this and the -- what’s going on
`is that DMF is an immunomodulating drug. DMF is sort of turning off the
`TH-1 pro inflammatory response and turning on a TH-2 anti-inflammatory
`response.
`And the benefit of that shift is that in the background it takes an
`immuno reaction like we see in psoriasis or like we see in MS and begins to
`benefit that in a way that its, it slows it down.
`And so those skilled in the art recognize that. Schimrigk recognized
`that, and you will see example Exhibit 10,000 or 1012. That psoriasis and
`chronic -- is a chronic T cell mediated disease in which immune suppression
`have also been found to be effective.
`Similar to MS, a pro inflammatory T helper 1 cytosine profile
`predominates in lymphocytes isolated from psoriatic plaques. So it’s the
`same basic underlying disease function that is being looked to for cures for
`both MS or at least treatments for both MS and psoriasis.
`So stepping back and I’ll just stay on Slide 15 for a second. Stepping
`back what the prior art would have taught at this point the skilled artisan is
`that DMF is a known treatment for MS. That’s what we get from the Biogen
`2005 press release. I'm sorry, January 2006 press release.
`As for dosages, we get from the Schimrigk 2004 study that 360
`milligrams was an effective dose and 720 milligrams was an effective dose.
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`Those skilled in the art were also aware at the time that DMF had GI side
`effects. They were also aware that there was a similar disease function
`behind the scenes.
`And so one skilled in the art would have understood to find a dose
`rate, a dosage level that was below 720 milligrams, it was lower than the
`dose level that was the maximum permitted dose level for Fumaderm for
`example, but was at the level that was effective and that was also at a level
`to minimize side effects.
`And that level that’s claimed in the 514 patent in Claim 1 is squarely
`between the 360 milligrams and 720 milligrams. And that's why we think
`there is a prima facie case of obviousness for Ground 1 as well. Just as the
`Board concluded as there was for Ground 4 in the previous IPR.
`So what I want to do then is turn to the secondary considerations
`evidence. Because in the secondary considerations argument in this case
`carry the day in the previous IPR and the reason they carried the day is that
`there was no rebuttal. There was no evidence put up against those secondary
`considerations.
`So now I'm turning to Slide 36. So they have two major secondary
`consideration arguments they make in this case. Two what I’ll call serious
`secondary consideration arguments. One is unexpected results. And the
`other is commercial success.
`The unexpected results argument relies entirely on their position that
`the 360 milligram teaching from the Kappos 2006 study which is what Your
`Honor referred to earlier, that that taught those skilled in the art not to use
`360 milligrams. And they build on that.
`They say okay. If someone skilled in the art would not have used 360
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`milligrams and someone skilled in the art would have used 720, then our
`claims to 480 must be unexpected because they're closer to 360 than they are
`to 720. And there are two problems with that argument.
`The first problem is that they’re wrong that 360 milligrams would
`have been understood by those skilled in the art to not be successful. And
`the reason they're wrong about that is that as our experts explained and as
`those skilled in the art recognized afterwards, the Kappos 2006 study was
`incorrect.
`The phase II initial conclusion that the 360 milligram dose level
`wasn’t effective was based on a failure to account for the baseline lesion
`numbers for the groups of patients that took 360 milligrams in that study.
`So let me slow down and explain what I mean by that. The way that
`the Kappos phase II study worked is that they gave monotherapy DMF at
`240 milligrams, 360 milligrams and 720 milligrams.
`And the way they judged effectiveness was by counting the number of
`lesions at various points in the trial. By subjecting the subjects to MRI's and
`looking at the lesions that had been highlighted by gadolinium.
`And what they failed to account for is that in their pool of patients, the
`patients that were given the 360 milligram dose had a higher baseline
`number of lesions. That is everybody went in with a baseline number of
`lesions that was a little under one, approximately around point eight.
`But the patients that were given the 360 milligram dose all happened
`to have a higher number of lesions as a baseline and the number was a little
`over two. When they got to the end of the study, they looked at the number
`of lesions that the patients had at the end of the study and at various points in
`the study.
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`And what they concluded was well, 360 must not be working because
`we haven’t seen a reduction in the number of lesions as we have seen in 720.
`But what they didn’t do is they didn’t account for the baseline discrepancy.
`And so what our experts have said is that someone skilled in the art
`just looking at, it’s just looking at this data would have said wait a second,
`there’s a problem here. And the problem isn’t a post hoc rationalization.
`The problem is, is that the end point of that study was counting the
`number of lesions and the number of lesions was significant because it told
`them whether or not to treatment was working. But they simply failed to
`account for walking in the door, the people at 360 milligrams had a higher
`number of lesions to begin with. Now their --
`JUDGE HARLOW: Counsel --
`MR. KELLEY: Yes.
`JUDGE HARLOW: -- before you move on.
`MR. KELLEY: Sure.
`JUDGE HARLOW: Does Kappos 2006 allow us to see this
`discrepancy in the results or do we need to turn to later disclosures in order
`to be able to see the baseline number of lesions for each treatment?
`MR. KELLEY: Well, Kappos 2006 does -- I guess I'm not sure what
`Your Honor is asking. Kappos 2006 does give all for the data to the skilled
`artisans, particularly the slide presentation that Dr. Kappos gave where he
`shows the actual information about the baseline numbers. That was
`provided to somebody skilled in the art.
`If Your Honor is asking does Kappos 2006 actually identify the
`problem and account for it in the results, it doesn’t. It doesn’t do that and
`that’s the problem with relying on the conclusion about 360 milligrams. But
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`Kappos --
`JUDGE HARLOW: No, I appreciate that. What I'm trying to discern
`is at what time point the skilled artisan would have had the information
`necessary to make this determination.
`So would it have been upon public disclosure of the Kappos 2006
`reference that you’re relying on? Would it have been when the slide
`presentation was given? Would it have been at some point in between those
`two end points? That’s all I'm trying to understand.
`MR. KELLEY: That's fair, Your Honor, I understand that. And my
`response is that it’s not that someone skilled in the art would have to be
`notified of there being a problem and what the solution was and then at that
`point it becomes subject matter for someone skilled in the art.
`Instead -- I'm sorry, Your Honor.
`JUDGE HARLOW: The skilled artisan needs to know what the
`baseline lesion rate is in order to reach the conclusion you’re saying it would
`have reached. And I'm simply trying to understand -- I'm not quibbling with
`the idea right now of whether a skilled artisan would have been able to
`appreciate the problem.
`I'm simply asking when would the skilled artisan have had the
`information they need to recognize the problem? So in my rudimentary
`understanding, that would simply be they would need to know the baseline
`number of lesions for the 360 treatment group and then the ultimate number
`of lesions observed in that treatment group, right. Is that fair?
`MR. KELLEY: That is fair and one skilled in the art would have
`known that before the critical date because Dr. Kappos when he reported the
`results of his study, he actually had slides that had those baseline numbers
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`on it.
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`JUDGE HARLOW: Okay. So it would have been when those slides
`were presented or disclosed and not when the Kappos 2006 abstract itself
`was made public, is that fair?
`MR. KELLEY: Not when the abstract was made public, right.
`Because what needs to happen is that someone skilled in the art needs not
`have been exposed to the data from which they could say ah-ha, there is a
`problem.
`JUDGE HARLOW: Right.
`MR. KELLEY: And I'm turning now to Slide 20 and Slide 20 is a
`part of this presentation that Dr. Kappos gave about his study and this is
`where someone skilled in the art would have appreciated that there was a
`problem with the mean baseline numbers for the 360 milligram group.
`And this is part of the prior art. Right. This is not, it is not that we are
`pointing to things after the critical date where people recognized the problem
`and we said ah-ha, someone would have known then.
`What we are saying is that our experts looked at the materials
`available to someone skilled in the art before the critical date. They saw this
`discrepancy and our expert said well, you know, I would have accounted for
`that because this whole study is aimed at counting the number of lesions so
`of course you’re going to count from the baseline.
`JUDGE HARLOW: Understood. And that -- so that data was
`available prior to the critical date and then your expert’s conclusion I believe
`you argue are corroborated by and by studies that were published after the
`critical date that confirmed that an ordinarily skilled artisan would have seen
`this problem. Is that correct or am I misremembering?
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`MR. KELLEY: No, you’re not misremembering at all. That is our
`position that --
`JUDGE HARLOW: Okay.
`MR. KELLEY: -- that our expert saw a problem and that in fact it’s
`not a problem created for this case. It’s a problem that other people skilled
`in the art recognized as well.
`And I just want to add one more thing because I think its important to
`this inquiry is that their, Biogen’s position is that here is what happened.
`There was a phase II study. The phase II study indicated a 360 milligrams
`was not successful.
`Then there was a phase III study. The phase III study indicated that
`480 milligrams was successful. And so then what happened, the skilled
`artisan said wait a second. If 480 milligrams is working at the end of the
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