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`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________
`
`KVK-TECH, INC.,
`Petitioner,
`
`v.
`
`SHIRE PLC,
`Patent Owner.
`
`__________
`
`Case IPR2018-00290 (Patent 8,846,100 B2)
`Case IPR2018-00293 (Patent 9,173,857 B2)
`__________
`
`Record of Oral Hearing
`Held: April 4, 2019
`__________
`
`
`
`
`Before RAMA G. ELLURU, SHERIDAN K. SNEDDEN, and
`DEVON ZASTROW NEWMAN, Administrative Patent Judges.
`
`
`
`
`
`
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`Case IPR2018-00290 (Patent 8,846,100 B2)
`Case IPR2018-00293 (Patent 9,173,857 B2)
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`
`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER:
`
`
`STEVEN ROTH, ESQ.
`THOMAS VETTER, ESQ.
`DAVID J. GALLUZO, ESQ.
`Lucas & Mercanti LLP
`30 Broad Street
`New York, New York 10004
`212-661-8000
`sroth@lmiplaw.com
`tvetter@lmiplaw
`djg@lmiplaw
`
`
`
`ON BEHALF OF THE PATENT OWNER:
`
`
`JOSEPH R. ROBINSON, ESQ.
`ROBERT SCHAFFER, ESQ.
`Troutman Sanders LLP
`875 Third Avenue
`New York, New York 10022
`212-704-6000
`joseph.robinson@torutman.com
`robert.schaffer@troutman.com
`
`and
`
`DUSTIN B. WEEKS, ESQ.
`Troutman Sanders LLP
`600 Peachtree Street, NE, Suite 3000
`Atlanta, Georgia 30308
`404-885-3446
`dustin.weeks@troutman.com
`
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`Case IPR2018-00293 (Patent 9,173,857 B2)
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`The above-entitled matter came on for hearing on Thursday, April 4,
`
`2019, commencing at 10:08 a.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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`10:08 a.m.
`JUDGE NEWMAN: Good morning. This is Judge Newman from
`Portland, Oregon. Judges Snedden and Elluru are in the courtroom there
`with you. I will be running the Portland -- the hearing from Portland here,
`so a couple of things to consider there.
`First of all, I can't see what is on the screen; however, I do have a
`copy of the demonstratives. So if you would please speak clearly into the
`microphone and let me know what slide it is that you're looking at and what
`it is that you're pointing at, that will help me to keep track of what's going on
`with the hearing.
`Has everyone there given a card to the court reporter so that the court
`reporter can identify who you are?
`MR. ROTH: Yes, Your Honor.
`MR. ROBINSON: Yes, Your Honor.
`JUDGE NEWMAN: Okay. Great. Let's start by putting everyone
`on the record starting with Petitioner.
`MR. ROTH: Yes, this is Steven Roth from Lucas & Mercanti for
`Petitioner. With me is David Galluzo and Tom Vetter from Lucas &
`Mercanti. Anthony Tabasso who is president of KVK-Tech is also here.
`JUDGE ELLURU: Thank you.
`For Patent Owner?
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`MR. ROBINSON: Yes, I'm Joseph Robinson for Patent Owner
`from Troutman Sanders. I'm here with my partners Dustin Weeks and
`Robert Schaffer, as well as Tanya Leavy. Also present is David Banchik,
`who is chief of litigation for Takeda, who is now Shire.
`JUDGE NEWMAN: Thank you. Both parties have requested and
`been given 60 minutes for oral argument this morning. As you know, you
`can reserve some time for rebuttal. How would you like to split the
`argument, starting with Petitioner?
`MR. ROBINSON: It's not clear. Probably 45 to 50 minutes
`initially and 10 to 15 for rebuttal.
`JUDGE ELLURU: Okay. So you would like -- would you like me
`to tell you in about 45 minutes?
`MR. ROBINSON: Yes.
`JUDGE NEWMAN: Okay. So you'd like to reserve about 10 to 15
`minutes to respond?
`MR. ROBINSON: Yes, although it may be less depending on
`quickly it takes me to get through it. So, but --
`JUDGE NEWMAN: Understood. Okay.
`And then Petitioner?
`MR. ROTH: We would request the same, Your Honor.
`JUDGE NEWMAN: Okay. And then, Patent Owner, under the
`new Trial Practice Guide you are allowed to have a small response at the
`end. Would you like to do that as well?
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`MR. ROBINSON: Yes, Your Honor, we would take approximately
`one-third of whatever time we have for rebuttal and leave it for the
`surrebuttal.
`JUDGE NEWMAN: Okay. Before we get started there was one
`objection issue for the demonstratives. We have considered that issue and
`we -- our ruling is to allow slide 5 to be shown for the purposes of showing
`the graph only, not to allow discussions of the transit times as we agree that
`that is new information to the record. Any questions on that issue?
`Okay. Great. Any other final issues before we get started?
`MR. ROTH: Just a technical issue. I'd like to enlarge that screen
`for the Court here.
`JUDGE NEWMAN: You may begin when ready.
`MR. ROTH: Okay. So I'm going to go through a few slides as a
`general background, so let's go to slide 2. It shows that Patent Owner's
`three amphetamine patents, bead patents that are at issue in this matter,
`Burnside and Couch, the first two, are prior art to Sojai, and Sojai are the
`two patents at issue in this matter. They all disclose immediate release,
`delayed release and sustained release beads and in various combinations.
`So let's look -- quickly look at what these three beads are.
`So the immediate release bead is a core with amphetamine or a --
`layered with amphetamine. It dissolves quickly. Burnside says
`immediately upon administration. Two of Patent Owner's experts, Dr.
`Trout and Dr. Polli, say that happens in the stomach.
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`The DR bead is the immediate release bead and coated with a
`delayed release coating, a pH-sensitive coating, an enteric coating like
`Eudragit. Burnside says the entire coat, entire dose is released in 30 to 60
`minutes. And where does that happen? It depends on the Eudragit. Both
`Burnside and Sojai have the same two Eudragits that are exemplified. One
`dissolves at a pH of 6.0 and the other at a pH of 6.8, but both will dissolve in
`the intestines and release in the intestines quickly. That is a -- that's what
`they describe as the pulse speed, in 30 to 60 minutes.
`I'm going to skip the next slide; we'll come back to it, and talk
`about -- let's talk about the SR bead. We're on slide 6. The sustained
`release bead is the delayed release bead but coated with a semi-permeable
`membrane that slows release. Example 4 exemplifies that and it is the same
`example, or nearly the same example in both Burnside and Sojai. The only
`difference is the talc in the Opadry, which are insubstantial -- have an
`insubstantial effect on release. And that's -- my source for that is Dr.
`Burgess' declaration, Exhibit 1004 at paragraph 87. And that is -- she's not
`disputed on that point.
`Patent Owner calls this bead atypical. They call it an inside-out
`bead. I haven't seen any evidence that it's atypical, but that as it may,
`Burnside discloses it.
`JUDGE ELLURU: I have a question about the SR bead. I
`understand it is just really the DR bead with the suspended release coating
`around it. Why do you still need the enteric coating underneath it?
`MR. ROTH: So that it will release in the intestines as opposed --
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`JUDGE ELLURU: But that's the outer -- that's the suspended
`release, correct, that --
`MR. ROTH: So the idea is that it will release -- the sustained
`release will release slowly --
`JUDGE ELLURU: I understand that.
`MR. ROTH: -- but start that release in the intestines.
`JUDGE ELLURU: Right, and that's due to the Surelease, correct?
`MR. ROTH: That's right, the Surelease.
`JUDGE ELLURU: So why do you need the enteric coating
`underneath it?
`MR. ROTH: Because it could start releasing -- well, Patent Owner
`can speak to that better than I can, but it's my understanding otherwise you
`could have a release in the stomach.
`JUDGE ELLURU: Thank you.
`MR. ROTH: This is Burnside's in vitro data on this example 4, and
`I want to direct your attention to the quote on the left which is how they
`describe this example figure. Figure 6 illustrates the drug release of
`example 4 which exemplifies the present invention. So the point is that
`Patent Owner is describing example 4 as part of the invention. They're not
`teaching away from it example 4; they're teaching towards example 4.
`JUDGE ELLURU: Is there any evidence in the record that in vitro
`data correlates or translates to in vivo data?
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`MR. ROTH: Yes, Dr. Jusko described that in paragraph 37 that the
`in vitro data -- that sustained release in vitro would -- one would expect from
`that sustained release in vivo and --
`JUDGE ELLURU: So he just testifies that it would be expected?
`MR. ROTH: Yes. And Dr. Burgess testified that -- in her
`deposition, which is Exhibit 2071 at pages 72 to 73, that one could predict
`performance in the body generally based on in vitro data.
`So let's go to the next slide, Number 8. Where is the Burnside
`sustained release bead released? We have -- I'm providing three areas of
`testimony here: Dr. Trout said in the intestines; Dr. Burgess said 70 percent
`in the small intestines, 20 to 30 percent in the colon; and Dr. Polli, who is
`Patent Owner's expert, as is Dr. Trout, by the way, said it would be in the
`lower small intestines and the colon.
`So with that background, let's go to the heart of this.
`JUDGE SNEDDEN: Excuse me. Let me -- I have one question.
`If you can go back to the previous slide? With respect to the slow or
`sustained release bead and -- are these the -- is that the idea, this is what it's
`thought to do or is there -- or has this actually been used to treat patients, or
`is there any data showing that this sustained release has actually been used?
`MR. ROTH: Sustained release has been on the market for 50 years.
`JUDGE SNEDDEN: In this context? Like this Burnside.
`JUDGE ELLURU: But with amphetamines?
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`MR. ROTH: Yes, but not exactly in this structure. But the idea of
`sustained release amphetamine has been around -- and I'm going to get to
`this in a few minutes.
`JUDGE SNEDDEN: Okay. I just -- you have -- you're just
`referencing the experts. I just wonder -- they're commenting just the
`concept of sustained release and not so much the use of a sustained release
`with the amphetamines, right?
`MR. ROTH: So Dr. Burgess is relying on the data in the patent; for
`example, the in vitro data --
`JUDGE SNEDDEN: Yes.
`MR. ROTH: -- and her understanding of how these correlate. Dr.
`Trout and Dr. Polli, I'm not sure what they're relying on. They're not our
`experts.
`JUDGE SNEDDEN: Right. Understood. Thank you.
`MR. ROTH: So if I may, let's go to -- I want to spend a bit of time
`on this slide. This is the heart of it. And I'm going to do more talking than
`showing.
`So Sojai Claim 1 is obvious. Two combinations from the
`institution: Adderall XR plus Burnside example 4, or Burnside example 5
`plus Burnside example 4. As you know Adderall XR and Burnside
`example 5 have the two immediate release and delayed release beads.
`So two questions: One, what's the suggestion to combine? And for
`that I'm going to point to two things: First, as you've already noted, the
`desire to extend treatment of ADHD beyond what the Adderall XR could do,
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`and we cite to that Kratochvil reference; I'm always having trouble
`pronouncing that, that at Exhibit 1010 that taught the common practice back
`then in the prior art of administering Adderall XR in the morning and
`Adderall Immediate Release 8 to 10 hours later.
`JUDGE ELLURU: So I understand that the prior art recognized a
`need for an extended treatment, but was there any teaching in the prior art
`about combining these three types of beads?
`MR. ROTH: Right. And the only thing I could point to on that is
`the second point, which is Burnside itself. And Burnside taught that --
`taught the extended release, the SR bead and taught that it would extend
`release of amphetamine. And the patent is directed to the treatment of
`ADHD.
`So as our experts have pointed out, one would be led to using that
`bead that's taught in Burnside to combine it with the two other beads that are
`taught in Burnside to extend the release beyond the Adderall XR. And I
`asked Dr. Polli in his deposition this question, what was the purpose of
`adding the sustained release bead to Adderall XR and he said the intent in
`adding the SR bead was to prolong duration of therapy. I mean obviously
`he doesn't know Shire's intent, but he was testifying as what would their
`intent be? Because that would be the natural intent of adding that bead, to
`extend release, to extend therapy. And I cite to that in -- that's Exhibit 1046
`at page 20 in his deposition.
`The second question is what is the reasonable expectation of
`success? And for that I want to point to four things: first, going back to
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`what we've been discussing, the SR bead has been disclosed in Burnside as
`being directed to extend a sustained release as directed for treatment of
`ADHD. It was also disclosed in his Couch reference, which is that second
`reference of the trio. And that's also in the prior art. And it also taught
`sustained --
`JUDGE ELLURU: Does Couch disclose in vivo data for the SR
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`bead?
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`MR. ROTH: No, it doesn't. And that's -- I'm glad you asked that
`question. I'm about to make that point right now.
`Patent Owners argue that these -- that both Couch and Burnside are
`prophetic. They've also called it untried recently. So what does that mean?
`It means -- well, certainly it's not prophetic in the classic sense because they
`actually made these beads and tested them at least in vitro.
`So what does -- what do they mean? They mean it hasn't been
`tested in a pharmacodynamic trial, PD data. And in their slides they're
`going to show you a very nice picture of amphetamine going to the brain, a
`nice colorful picture of a brain. And they're pointing out that there's no PD
`data. There's no clinical efficacy data in Burnside and Couch on the
`sustained release beads, but what they're not going to tell you is that the
`Sojai patents at issue here doesn't have that data either. They have no
`clinical efficacy data in the Sojai patents, nothing to support that it works for
`ADHD. And I want to add that --
`JUDGE NEWMAN: Counsel, would that -- is that required for
`patentability?
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`MR. ROTH: No, it's not. In fact, we think that the dissolution data
`and the data in the patents is enough to suggest that it would work because
`you're -- and the reason I say this; and this gets me to point 2, is that
`amphetamine to treat ADHD has been around for a very long time; in fact
`100 years, or coming up on 100 years, 90-something. And for that I cite to
`the Burgess declaration at paragraph 30. And amphetamine in sustained
`release form, although not exactly the structure claimed here, but it's --
`JUDGE ELLURU: Counsel, what do you mean by not exactly the
`structure claimed here?
`MR. ROTH: Yes, I -- the -- I'm referring to the Dexedrine product,
`Dexedrine product -- sustained release called Dexedrine Spansules. And
`they only have dextroamphetamine. They don't have the other three
`amphetamine salts. They just have the dextroamphetamine. This has been
`in use since the 1970s, probably earlier. And Dr. McCracken discussed this
`product in his declaration at -- his exhibit is --
`JUDGE ELLURU: How does it differ from the SR bead in
`Burnside?
`MR. ROTH: I'm not clear on that. It does have the various
`polymers that sustain release like the ethyl cellulose, et cetera, I believe, but
`it doesn't have -- we're not talking about the exact same structure of the
`Burnside bead, but we are talking about the idea of sustaining release in
`order to sustain efficacy. Sustaining blood levels in order to sustain
`efficacy. And that is 50 years old.
`JUDGE SNEDDEN: Is that the same therapeutic agent?
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`MR. ROTH: Yes.
`JUDGE SNEDDEN: Yes?
`MR. ROTH: Or I think it's three-quarters of the -- I think three-
`quarters of it is dextroamphetamine. The other quarter is the other salts. I
`believe that's how it works, but I'm not 100 percent sure. It's in the labels.
`Dr. McCracken cites to various exhibits in support of his citations to
`Dexedrine SR including the Pelham reference, the James reference, Exhibits
`1052 and 1053. And we'll discuss that later.
`JUDGE SNEDDEN: So one more -- so this -- what's the name of
`the product again one more time?
`MR. ROTH: Dexedrine --
`JUDGE SNEDDEN: Dexedrine SR?
`MR. ROTH: -- Spansules or Dexedrine SR.
`JUDGE SNEDDEN: Okay. And so this product has been used to
`treat patients?
`MR. ROTH: Yes.
`JUDGE SNEDDEN: Yes. Okay.
`MR. ROTH: Decades. Since the '70s, maybe earlier.
`JUDGE SNEDDEN: So it's a sustained release amphetamine used
`to treat patients?
`MR. ROTH: Yes.
`JUDGE SNEDDEN: All right.
`JUDGE ELLURU: But you don't know if it's the same structure of
`Surelease?
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`MR. ROTH: I don't know. I'm only speaking of extending the
`blood levels, and by extending the blood levels you're extending therapy.
`Because there was a Dexedrine Immediate Release, too, which did not have
`the same profile, blood profile. The extended release extended the blood
`profiles a lot longer than the immediate release and also extended efficacy
`by doing that.
`So I want to go to point 3, which is that the sustained release was
`expected to release later and over a longer period of time. And this really
`ties with what I was saying before. Dr. Jusko testified that a person of
`ordinary skill would have expected the sustained release to continuing
`releasing for many hours after the immediate release and delayed release
`were depleted providing many hours of efficacy. And that's in her
`declaration at Exhibit 1006, paragraph 37.
`And Dr. Polli, Patent Owner's expert, also said in several places in
`his declaration that Burnside example 4 would be releasing later than the
`beads in Adderall XR. And his declaration is Exhibit 2060. And take a
`look at paragraph 140 and 204 for that -- those admissions.
`Four, and this actually relates to that exhibit, Demonstrative 5 that I
`was -- that's been a subject of this motion here to strike. And this is an
`analysis that comes from Dr. Burgess and also Dr. McCracken, but in
`particular Dr. Burgess. Her exhibit is 1004. And it shows up in paragraphs
`167 and 168.
`And this analysis actually directly relates to Patent Owner's
`argument of GI obstacles. And it's interesting that the GI obstacles that
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`they're going to talk about is the very reason one would use the sustained
`release bead. And why? GI obstacles are -- the difficulty in releasing drug
`in the -- it's not as easy as -- you're in there for a lot longer, but it's not as
`easy to -- because it's more solid and less fluid, et cetera. It just doesn't
`release as fast as in the small intestines.
`So what do you do if you want to have a third bead to extend your
`release? How do you structure that? You could put a pulse release, a
`second pulse or a third pulse release, actually. But where would you put it?
`If you had it releasing in the pH 6 or 6.8, it would release at the same time as
`the second -- first delayed release bead, and that wouldn't help because you'd
`just get a big spike. It would be toxic potentially and it wouldn't give you
`the extension you need.
`If you set it to release pH 7.2, 7.5, even 8, well, then you run into the
`opposite problem. The body might never get to that pH. The GI tract
`might not get there given the variability. In fact, if it gets there at all, it
`might be very late and you won't get enough out.
`So what makes sense? Well, the only thing that makes sense
`actually is exactly the Burnside example 4 bead.
`JUDGE ELLURU: But what about the absorption issues in the
`colon? Were there any barriers to absorption or was it going to be the
`same? And where is the data showing that there was conventional teaching
`about absorption?
`MR. ROTH: Well, what Burnside says is that the easiest absorption
`is the small intestines and then it sharply declines in the colon, which is right
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`out of Burnside. As far as data I don't have data per se that's in the prior art
`because as we mentioned, there's no data in the body on the sustained release
`bead per se on this example 4 bead. It's only in vitro data. So I don't have
`that data in the prior art. Post-prior art obviously, but not in the prior art per
`se.
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`JUDGE SNEDDEN: So this takes us to the differences between the
`dextro -- or Dexedrine SR. What am I -- Dexedrine --
`JUDGE ELLURU: Dexedrine.
`JUDGE SNEDDEN: -- Dexedrine SR --
`JUDGE NEWMAN: Dexedrine SR.
`JUDGE SNEDDEN: -- yes, versus the Adderall. And those are
`two different drugs. And I guess we're assuming they behave the same if
`we're going to rely on some disclosure testimony or evidence related to the
`Dexedrine SR.
`MR. ROTH: Yes, well, as far as the active is concerned it's
`amphetamine. It's both amphetamine. But both -- three-quarters -- is that
`right, three-quarters of the Adderall product -- I mean, the Claim 1 says salts
`of amphetamine anyway. We're talking about salts of amphetamine, and
`that's --
`JUDGE SNEDDEN: But you -- when we're combining the art,
`we're combining evidence related to Dexedrine SR and Adderall SR.
`MR. ROTH: But if we're trying to invalidate Claim 1, we don't
`need to show more than one salt because -- or -- I mean, Dexedrine is an
`amphetamine obviously. It's --
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`JUDGE SNEDDEN: Right.
`MR. ROTH: -- dextroamphetamine, which is three-quarters of the
`Adderall XR amphetamine.
`JUDGE SNEDDEN: But how similar is it to the active agent in
`Adderall?
`MR. ROTH: It's -- well, it's the same drug. It's a different salt. I
`mean, the salt disassociates very quickly in the body. Salts in general come
`off right away.
`JUDGE SNEDDEN: Okay.
`MR. ROTH: So I just want to show you quickly why we're even
`fighting for this. I mean, this shows the pH in the GI and where it would
`land in the GI tract. We've got pH 6 is in the duodenum which is at the very
`upper part of the small intestine; 6.8 which is that second Eudragit mid-SI,
`following the blue line which I drew in. And that's the middle part of the
`small intestines.
`So this is a study on 33 subjects, 33 patients. And the three lines,
`the middle line is the median and the low is the low end and the top one is
`the highest, but you could see how much -- how it varies. And if you were
`to coat it with even a pH 7.5, that third bead, you wouldn't know where it
`was going to land or if it would release at all, because if you had a patient
`with low pH, it might not even get to 7. It might not even get to 7, so you
`might get nothing out or it might be very, very late.
`So the only thing that works is to force it to begin release at pH 6
`because you know it's going to start releasing in the intestines. In fact 6.0
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`will release earlier; 6.8 still in the middle of the intestines. But you need
`that 6.0 for your SR bead to -- 6-something to get -- to start the release in the
`intestines. And then you slow it down because you don't want that spike.
`You don't want three spikes in a row, so you've got to slow it down.
`So the only thing that makes sense is to have that started early, but
`slow it down with the Eudragit. That's what makes sense here. And that's
`the fourth reason why one would do this, one would pick that bead to extend
`the release and expect it to work.
`I want to go to slide 10. So Sojai made several arguments in the
`prosecution over Burnside. The first argument in the first Office Action --
`the first Office Action was that Burnside doesn't disclose the sustained
`release bead. Well, in fact that was wrong. They should have known it,
`because it's their own patent. They should have known that it discloses the
`same bead as Sojai.
`And the second action, I'm not sure what they were doing there. I
`think they conceded that example 4 does have the Surelease coating, but the
`Patent Office rejected it again. And in response they went to the third
`argument that they have -- that the sustained release bead in Sojai and
`Burnside are different, that Sojai discloses this unique inside-out
`construction whereas Burnside doesn't. It has the typical construction. But
`that turned out to be wrong, too. I mean, that was wrong, too. I mean, they
`both disclosed the same construction.
`JUDGE ELLURU: I'm not sure I understand the impact on the
`prosecution history.
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`MR. ROTH: Right. Well, actually what --
`(Simultaneous speaking.)
`JUDGE ELLURU: -- your case.
`MR. ROTH: I'm actually going for a different point here, which is
`during the entire prosecution they never argue their main teaching away
`point now, which is acute tolerance. Acute tolerance is what they're
`arguing for teaching away now. They never argued it in the prosecution.
`What is acute tolerance? Tolerance means that you get used to the
`drug. It loses its impact over time. There's chronic tolerance. It could
`take weeks or months to -- before it loses efficacy. And acute. It could
`happen very rapidly, within hours. So they're arguing acute tolerance.
`And basically -- I'm going to slide 11. This is their acute tolerance
`defense. They're relying on Dr. Polli. Dr. Polli says that what acute
`tolerance means is that the drug goes up, then it begins to plateau and go
`down. Right? So that's -- once it goes down, once it plateaus and begins to
`decline, there's a rapid dissipation of efficacy. That's acute tolerance.
`JUDGE ELLURU: And where is the evidence that the SR bead
`would account for acute tolerance?
`MR. ROTH: Well, it's our position that there is no acute tolerance
`for amphetamine.
`JUDGE ELLURU: And your best evidence for that?
`MR. ROTH: Best evidence for that is Dr. McCracken's opinion
`
`and --
`
`JUDGE ELLURU: But that --
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`MR. ROTH: This one right here.
`JUDGE ELLURU: -- but he did not come to any conclusive
`decisions about acute tolerance, did he?
`MR. ROTH: Yes, in his opinion in this case he said there is no
`acute tolerance for -- there's little evidence of acute tolerance based on his
`own work, based on his own studies.
`JUDGE ELLURU: Thank you.
`JUDGE NEWMAN: That's a current opinion that was not
`necessarily explained in the original publication, correct?
`MR. ROTH: As the Patent Owner points out, he didn't address
`acute tolerance in his 2003 publication because it wasn't -- he said in his
`testimony actually Shire didn't even study it. They weren't concerned with
`the issue. As you could see, they didn't argue it during the patent -- during
`the prosecution. It wasn't an issue that Shire ever focused on because it was
`something -- it was never something of concern to them. And as I go
`through this you'll see what I mean.
`JUDGE NEWMAN: Okay. I understand your position.
`MR. ROTH: Okay. This is the second patent, Couch. The second
`patent in that trio. It's prior art to Sojai. And Couch says the SR
`formulations of his invention will be effective to treat ADHD. And look at
`the bottom: Low incidence of tolerance and tachyphylaxis. Tachyphylaxis
`is acute tolerance. That's the medical term. And tolerance, to differentiate,
`I assume means the chronic tolerance.
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`What is Dr. McCracken's opinion based on? This is part of it. And
`I'm going to get to his analysis in a little more -- in a minute.
`JUDGE ELLURU: But this is not -- this isn't talking about the SR
`formulation after two pulses, correct? It's just talking about SR
`formulations on its own?
`MR. ROTH: This is talking about amphetamine. It's just for
`amphetamine formulation.
`JUDGE ELLURU: But not after a formulation that contains two
`prior pulses, correct?
`MR. ROTH: Adderall XR has two prior pulses. Adderall IR is one
`pulse. Adderall XR has two pulses.
`JUDGE NEWMAN: What is the SR formulation in Couch, though?
`MR. ROTH: Couch just describes sustained -- various sustained
`release formulations of amphetamine including the -- it does describe the
`bead in examples 1 or 2.
`JUDGE ELLURU: But it was not an SR formulation with any other
`type of bead or any other type of --
`MR. ROTH: It does in paragraph 9. It doesn't have an example of
`it, but in paragraph 9 he teaches that the --
`JUDGE ELLURU: Is immediate release.
`MR. ROTH: -- SR and the IR can be combined. Yes, in is patent
`application there's a --
`(Simultaneous speaking.)
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`JUDGE SNEDDEN: Why wouldn't a person of ordinary skill in the
`art be directed to a third pulse release?
`MR. ROTH: Well, actually I'm glad you asked that. That was the
`same point I was making a few minutes ago.
`JUDGE SNEDDEN: Oh, the --
`(Simultaneous speaking.)
`MR. ROTH: Where would you put that third pulse?
`JUDGE SNEDDEN: About the pH might not ever get to 7.8?
`MR. ROTH: Might never get to 7. And if you had it in the 6s, it
`would -- it could be very well be too close to the first DR bead and you just
`get a big spike which could be dangerous and wouldn't give you the
`sustained release you need.
`So this -- the point of this is that blood levels are going out and
`they're beginning to decline at three hours for Adderall IR, seven hours for
`Adderall XR, but efficacy is continuing five to seven hours. What acute
`tolerance,
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