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`Trials@uspto.gov
`571-272-7822
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`Paper No. 53
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`UNITED STATES PATENT AND TRADEMARK OFFICE
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`NALOX-1 PHARMACEUTICALS, LLC
`Petitioner,
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`v.
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`ADAPT PHARMA OPERATIONS LIMITED, and
`OPIANT PHARMACEUTICAS, INC.,
`Patent Owner.
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`Case IPR2019-00685 (Patent 9,211,253 B2)
`Case IPR2019-00688 (Patent 9,468,747 B2)
`Case IPR2019-00694 (Patent 9,629,965 B2)
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`Record of Oral Hearing
`Held: May 19, 2020
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`Before ERICA A. FRANKLIN, ZHENYU YANG and
`MICHAEL A. VALEK, Administrative Patent Judges.
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`Case IPR2019-00685 (Patent 9,211,253 B2)
`Case IPR2019-00688 (Patent 9,468,747 B2)
`Case IPR2019-00694 (Patent 9,629,965 B2)
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`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER:
`
`RICHARD J. BERMAN, ESQUIRE
`ARENT FOX, LLP
`1717 K Street, N.W.
`Washington, D.C. 20006
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`ON BEHALF OF THE PATENT OWNER:
`
`JESSAMYN S. BERNIKER, ESQUIRE
`Williams & Connolly, LLP
`725 12th Street, N.W.
`Washington, D.C. 20005
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`The above-entitled matter came on for hearing Tuesday, May 19, 2020,
`commencing at 10:31 a.m. EDT, by video.
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`Case IPR2019-00685 (Patent 9,211,253 B2)
`Case IPR2019-00688 (Patent 9,468,747 B2)
`Case IPR2019-00694 (Patent 9,629,965 B2)
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`P R O C E E D I N G S
`1
`JUDGE YANG: Good morning and welcome everyone. This is the
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`consolidated hearing for IPR 2019-00685, 688 and 694. The challenged
`3
`patents are 9,211,253, 9,468,747 and 9,629,965. I am Judge Yang and as
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`you can see, we also have Judges Franklin and Valek on the line.
`5
`Counsel, please introduce yourself. Let’s start with Petitioner.
`6
`MR. BERMAN: Yes. Good morning, Your Honors. Richard
`7
`8 Berman of Arent Fox, LLP on behalf of Petitioner, Nalox-1
`9 Pharmaceuticals, LLC.
`JUDGE YANG: Thank you. Welcome.
`10
`Patent Owner?
`11
`MS. BERNIKER: Good morning, Your Honors. Jessamyn Berniker
`12
`of Williams & Connolly on behalf of the Patent Owners.
`13
`JUDGE YANG: Thank you and welcome.
`14
`Before we start the oral argument, we have a few housekeeping items
`15
`I’d like to address first. This is a public hearing, so please proceed
`16
`accordingly. And on that topic, there is a pending motion to seal from
`17
`18 Patent Owner, I believe, at paper 32 in ‘688. Patent Owner asked us to seal -
`- to enter the default protective order and to seal several 2000 series of
`19
`exhibits. We will issue a decision on that motion shortly, but I noticed there
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`is Exhibit 1248 that was also filed as protective order material, but there was
`21
`no motion to seal that exhibit.
`22
`Petitioner, this is your exhibit. Did you intend to file it under seal?
`23
`MR. BERMAN: I’m not currently aware of that. I can have -- I can
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`get back to you on that.
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`Case IPR2019-00685 (Patent 9,211,253 B2)
`Case IPR2019-00688 (Patent 9,468,747 B2)
`Case IPR2019-00694 (Patent 9,629,965 B2)
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`JUDGE YANG: Okay. Yes, please check. If you meant to file it as
`1
`protective order material, we need a motion on that.
`2
`MR. BERMAN: Yeah, that’s apparently -- I’m sorry. Excuse me,
`3
`4 Your Honor. That’s apparently the deposition transcript of Dr. Jones, the
`5 Patent Owner’s expert. That must have been mistaken. We did not intend to
`file that under seal.
`6
`JUDGE YANG: All right.
`7
`MR. BERMAN: (Indiscernible) that.
`8
`JUDGE YANG: Okay. So we’ll probably figure it out later. Patent
`9
`10 Owner, is there any protective material in that deposition? Do you by any
`chance know? Do you intend to keep it sealed or should we unseal it?
`11
`MS. BERNIKER: I should be able to answer that question
`12
`(indiscernible) today. The only thing that I could imagine would be related
`13
`to the same subject matter as the exhibits that we had sealed and so we can
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`take it upon ourselves to see whether there is reference to anything in the
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`transcript.
`16
`JUDGE YANG: Very good. I don’t want you to rush and make any
`17
`18 mistake, so if you both can confer afterwards and send us an email and let us
`know, that’ll be great.
`19
`MS. BERNIKER: Certainly. Thank you, Your Honor.
`20
`JUDGE YANG: All right. Thank you.
`21
`MR. BERMAN: Not a problem, Your Honor.
`22
`JUDGE YANG: All right. Moving on to another item I want to
`23
`check for today’s hearing, we received Patent Owner’s demonstratives.
`24
`25 Thank you. Petitioner, we did not receive any demonstratives from you. I
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`Case IPR2019-00685 (Patent 9,211,253 B2)
`Case IPR2019-00688 (Patent 9,468,747 B2)
`Case IPR2019-00694 (Patent 9,629,965 B2)
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`1 want to make sure there is no oversight there. Did you have any --
`MR. BERMAN: That is correct, Your Honor.
`2
`JUDGE YANG: Okay. Very good.
`3
`Then for today’s hearing, each party has 45 minutes to present its
`4
`argument. We’ll start with Petitioner followed by Patent Owner and each
`5
`side can reserve time for rebuttal and we will deal with that when we get to
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`it.
`7
`During the argument, please clearly identify the record so the
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`transcript is clear and it is especially important for us today since we cannot
`9
`see what you are pointing to. Last week, I did have a hearing and counsel
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`11 was pointing to slides and I was like, “I cannot see you.” But, we have all of
`the records here and you can identify through your slide number, your paper
`12
`number, your exhibit number, you have the idea. Just be specific and we
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`14 will be able to follow you.
`Also today we will be discussing all three cases. I understand from
`15
`the parties that we’ll use the record from ‘688 for most of the argument, but
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`if there is any case-specific argument or paper, please bring those to our
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`attention. Lastly, the most important part, please mute yourself and only
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`unmute when you are talking. That includes myself, and other judges too
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`because the -- otherwise, the feedback can be unbearable.
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`Any questions?
`21
`MR. BERMAN: No, Your Honor.
`22
`JUDGE YANG: All right.
`23
`MS. BERNIKER: No, Your Honor. No questions.
`24
`JUDGE YANG: So Petitioner, would you like to reserve any time for
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`Case IPR2019-00685 (Patent 9,211,253 B2)
`Case IPR2019-00688 (Patent 9,468,747 B2)
`Case IPR2019-00694 (Patent 9,629,965 B2)
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`your rebuttal?
`1
`MR. BERMAN: Yes. I would like to reserve 10 minutes of my time
`2
`for rebuttal, please.
`3
`JUDGE YANG: Okay. Ten minutes. I will, with my hi-tech -- set
`4
`5 my timer. I’ll try to get you a -- oh, 5-minute warning, but please, if you
`can, try to keep track of your own time that way we don’t have any issues
`6
`there. If --
`7
`MR. BERMAN: I will try to be succinct, yes.
`8
`JUDGE YANG: -- there is nothing else, you may start whenever
`9
`you’re ready.
`10
`MR. BERMAN: Great. Wyse in combination with certain secondary
`11
`references renders all of the claims in the challenged patents obvious. Wyse
`12
`discloses all of the essential ingredients of the claims. The same use of the
`13
`same drug, the same excipients, even the same container with the same
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`amount of solution.
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`The main question at the heart of these IPRs is does Wyse, or any
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`other prior art, teach away from using benzalkonium chloride, BAC, in an
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`intranasal naloxone formulation. The answer to that question is no. I’ll also
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`be discussing how a POSA would have been highly motivated to choose a
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`four gram dose of naloxone, but first the teaching away question.
`20
`As we know, a POSA is not an automaton. He or she is assumed not
`21
`only to have the full knowledge of the prior art, but also to make inferences
`22
`and take creative steps based on the prior art, but Patent Owners would have
`23
`the POSA put on its blinders and just read the words on the pages of the
`24
`25 Wyse patent without any critical thinking at all and that is improper under
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`Case IPR2019-00685 (Patent 9,211,253 B2)
`Case IPR2019-00688 (Patent 9,468,747 B2)
`Case IPR2019-00694 (Patent 9,629,965 B2)
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`1 KSR and its progeny.
`Here, while Wyse states the preliminary conclusion that BAC was not
`2
`an acceptable preservative due to increased degradation of the formulation, a
`3
`4 POSA with the full knowledge of the prior art would have been highly
`skeptical of this preliminary conclusion. Why, because a POSA would have
`5
`known that any naloxone degradants in Wyse’s formulation could not have
`6
`been cause by BAC. How would a POSA have known that BAC was not the
`7
`culprit? The answer is within the Wyse patent itself.
`8
`Wyse, in Example 5, conducted an accelerated stability study where
`9
`he subjected test solutions to increased heat and higher pH to purposefully
`10
`accelerate degradation and he found that increasing the pH of the solutions
`11
`lead to an increase in oxidative degradation.
`12
`Now, the POSA knows from the prior art that naloxone is subject to
`13
`oxidative degradation, but whatever is happening --
`14
`JUDGE YANG: Counsel, I’m sorry.
`15
`MR. BERMAN: -- in these solutions -- yes? When something is
`16
`acting as an oxidizing agent --
`17
`JUDGE YANG: So did Wyse actually say that it’s oxidation
`18
`degradation?
`19
`MR. BERMAN: Yes. Wyse taught that -- Wyse said in its -- Wyse
`20
`is Exhibit 1007, of course. At 27 -- column 27, lines 20 through 24 he
`21
`discusses that increasing the pH lead to an increase in degradation, but a
`22
`decrease in the pH lead to a decrease in the oxidative degradants. So a
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`24 POSA knows --
`JUDGE YANG: (Indiscernible). Okay. Carry on. I’ll ask you a
`25
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`Case IPR2019-00685 (Patent 9,211,253 B2)
`Case IPR2019-00688 (Patent 9,468,747 B2)
`Case IPR2019-00694 (Patent 9,629,965 B2)
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`question later.
`1
`MR. BERMAN: Okay. A POSA knows that BAC is not an
`2
`oxidizing agent therefore a POSA easily understands that BAC could not
`3
`have directly caused naloxone degradation and Patent Owners do not even
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`try to rebut this fact.
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`Instead, Patent Owners presented two theories, one about the effect of
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`surfactant micelle’s and one about Wyse’s test vials, two theories for how
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`the BAC could have indirectly caused naloxone degradation.
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`And I’m going to discuss the problems with each of these theories in a
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`10 minute, but as an initial matter and very importantly, Patent Owners do not
`cite a single reference showing that BAC indirectly causes the degradation
`11
`of any compound much less naloxone.
`12
`So now I’ll turn to the first of Patent Owner’s two theories. First,
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`14 Patent Owners argued that surfactant micelles are to blame for the
`degradation. So first a bit of background on what is known about surfactant
`15
`16 micelles. BAC, in addition to being a preservative is also a surfactant. And
`like other surfactants, once a certain amount is added to a solution, and this
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`amount is known as the critical micelle concentration, once this amount of
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`surfactant is reached, the surfactant spontaneously form structures called
`19
`20 micelles and micelles are small circular agglomerations of molecules that
`can entrap compounds within the circle.
`21
`Imagine kids sitting in a little circular baby pool. The kids are the
`22
`compounds and the baby pool is the micelle. So in some pharmaceutical
`23
`formulations, and this is shown in Patent Owner’s own references that they
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`cite, entrapping a compound inside that micelle can have a protecting affect.
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`Case IPR2019-00688 (Patent 9,468,747 B2)
`Case IPR2019-00694 (Patent 9,629,965 B2)
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`1 Having the compound inside the micelle keeps it safe from the degradants
`outside the micelle in effect locking the compound out of harm’s way.
`2
`So in these cases, the micelles help stabilize the pharmaceutical
`3
`formulation which is a good thing, but Patent Owners ignore these known
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`advantages of micelles. Instead, Patent Owners rely on non-analogous art,
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`references dealing with environmental remediation or specialized chemical
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`synthesis to show that certain surfactant micelles not BAC, other surfactant
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`8 micelles, can facilitate the oxidation of compounds.
`So these are highly controlled conditions where the chemists are
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`trying to oxidize the target compounds. To clean up the environment, for
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`example. It’s not something you’re trying to do in a pharmaceutical
`11
`formulation, but how does this work? First, the conditions are specially
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`adjusted so the target compound is forced into the micelle. Then an oxygen
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`source, mainly air, is bubbled through the solution. The oxygen also enters
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`the micelles and, in time, forms a large reservoir of oxygen in the micelles.
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`So there’s lots of oxygen in a small space, more little kids in the baby
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`pool. The oxygen can more easily react with the target compound thus the
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`oxidation rate is increased inside the micelles. But as the prior art says, in
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`order for this reaction to work, you need a large oxygen source to create this
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`large reservoir of oxygen within the micelles. If you don’t have that large
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`oxygen source, the reaction doesn’t work.
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`So now going back to Wyse. A POSA plainly understands that Patent
`22
`23 Owner’s micelle theory wouldn’t work here. In the Wyse patent, far from
`bubbling oxygen through the naloxone solution, Wyse did the opposite.
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`25 Wyse removed the oxygen by bubbling inner nitrogen gas through the
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`Case IPR2019-00688 (Patent 9,468,747 B2)
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`solution and even put nitrogen into the headspace, the empty space above the
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`liquid in the vial, to ensure that very little oxygen was present.
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`So as Patent Owners acknowledge, there’s a reduced amount of
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`oxygen in Wyse’s formulations not increased oxygen and a POSA would
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`know that with no oxygen source BAC micelles are not oxidizing the
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`naloxone.
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`Now, the Patent Owner’s second theory that BAC is reacting with
`7
`8 Wyse’s test vials. Patent Owner’s argue that the BAC could be reacting
`9 with the glass vial itself or the rubber stopper, that BAC may be pulling
`oxidizing compounds out of these things which then react with the naloxone
`10
`and this theory could be compelling if there was any evidence that it was
`11
`true, but it’s not.
`12
`Instead, with regard to the rubber stopper, the prior art shows that, if
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`anything, BAC may be pulled into the rubber like a sponge. It doesn’t pull
`14
`anything out of the rubber. So a POSA would know there wasn’t a problem
`15
`16 with the rubber stoppers. And as for the glass vial, Patent Owner’s theory is
`completely unsupported. They have not submitted any evidence that BAC
`17
`has any effect on glass. So a POSA would know that there wasn’t a problem
`18
`19 with the glass vials either.
`In sum, a POSA would have recognized that BAC was not the direct
`20
`cause of naloxone degradation, evidence that is unrebutted and a POSA
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`22 would know that none of the indirect causes that Patent Owners speculate
`about would have been responsible either. So a POSA would have plainly
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`recognized that Wyse’s preliminary conclusion that BAC caused the
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`degradation was simply wrong and would not have been lead away from
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`using BAC in a naloxone nasal spray.
`1
`Moving on from Wyse, Patent Owners argue that other prior art
`2
`teaches away, but none of these would have dissuaded a POSA from using
`3
`4 BAC. The Handbook of Pharmaceutical Excipients does disclose that using
`5 BAC and EDTA together produces a short-term inflammatory reaction, but
`this effect was completely reversible. In fact, the prior art states that using
`6
`7 BAC and EDTA together was fine for emergency or short-term use. It
`8 might only be an issue with a product used on a long-term basis. That is not
`the situation we have here.
`9
`And there’s also the fact that the FDA has approved many nasal
`10
`sprays having BAC and EDTA together in a formulation, thus a POSA
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`12 would not have been led away from using BAC and EDTA together in a
`naloxone nasal spray.
`13
`Patent Owners also argue that a POSA might not have used any
`14
`preservatives at all, but even Wise disclosed that a preservative could or
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`could not be used in a naloxone nasal spray and Wyse chose to include one
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`and there’s good reason a POSA would have included a preservative in this
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`spray.
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`This is not a spray that’s sitting quietly in a dark medicine cabinet.
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`20 Rather, it likely will be subjected to extreme conditions and physical stress.
`It’s in an addict’s back pocket or in a homeless camp in the summer time.
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`It’s out of its foil packaging. It’s cracked or it’s broken.
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`In these situations, a POSA would know it just makes sense to add a
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`preservative. So there’s no teaching away and, in fact, a POSA would have
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`been highly motivated to use BAC in a naloxone nasal spray. It is the most
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`1 widely used preservative. The first choice and the best choice and it’s easier
`to get FDA approval if you use BAC. So there’s all sorts of reasons for a
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`3 POSA to go out of their way to use BAC.
`I’d like to shift the discussion the naloxone dose, 4 milligrams. First,
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`as the Board stated in the institution decision, Wyse teaches an overlapping
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`range of 0.5 to 5 milligrams so there is a presumption that 4 milligrams is
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`obvious. Patent Owners argue that 4 milligrams was not obvious because
`7
`emergency medical professionals using the prior art MAD device initially
`8
`administered 2 milligrams intranasally not 4 milligrams, but a POSA would
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`have recognized that’s an incomplete analysis.
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`First, as all parties acknowledge, the POSA here was seeking to
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`develop a community-use product, a product for lay persons not a product
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`that is specifically designed for emergency medical professionals. Lay
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`persons don’t have access to ventilators or other safety equipment that
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`emergency medical professionals have on-hand. All that they have is this
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`one shot and since a number of prior art studies show that re-dosing, giving
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`another dose of naloxone, was needed for the patient to breathe normally
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`again, having only 2 milligrams doesn’t do the trick.
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`So for a community-use product where you have untrained bystanders
`19
`or addicts who may be high themselves and you may have just one shot at
`20
`saving this person’s life, it just makes sense to build in a second dose, 4
`21
`22 milligrams. Then you also have the strong motivation from FDA. I’m
`doubtful anyone at FDA has read the KSR case, but FDA certainly provided
`23
`a POSA with a finite number of identified solutions.
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`FDA said that if you want to be approved quickly, your nasal spray
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`should mimic the blood levels of the approval parenteral product. The
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`product that’s given by injection or infusion and the starting dose range of
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`that product was 0.4 to 2 milligrams. In other words, FDA said that if your
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`nasal spray is bioequivalent to a dose between 0.4 to 2 milligrams given
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`parenterally, FDA will approve your nasal spray quickly.
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`So for a POSA connecting the dots is pretty straight forward. FDA is
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`giving you a small range of doses to mimic, 0.4 to 2 milligrams and you’re
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`8 making a community used prosed, folks who may have one shot at saving
`this person’s life. It’s easy to see why a POSA would chose the highest of
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`the approved parenteral starting doses, 2 milligrams, as the target dose for a
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`nasal product and the prior art shows that a little more than double the dose
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`of the nasal product would have the same bioavailability as the parenteral
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`product. So it would have been obvious to a POSA to choose 4 milligrams
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`nasal to mimic the blood levels of 2 milligrams parenteral.
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`JUDGE YANG: So counsel, I have --
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`MR. BERMAN: Now, Patent Owners tried -- yes?
`16
`JUDGE YANG: Sorry to interrupt --
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`MR. BERMAN: Go ahead.
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`JUDGE YANG: -- but I have a question.
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`MR. BERMAN: Yeah.
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`JUDGE YANG: So I hear you emphasizing on the community-use,
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`but I believe Patent Owner did bring up another product, I think it’s called
`22
`23 Evzio which is an auto-injector that is also approved for community-use and
`I believe that dosage was .4, right? And if --
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`MR. BERMAN: Correct.
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`JUDGE YANG: If like what you’re saying, a lay person doesn’t have
`1
`access to a ventilator, I mean, for Evzio it’s the same. Why would they start
`2
`3 with a -- at the lower end of the range there while you have to go to the
`higher end?
`4
`MR. BERMAN: Well, so a couple of issues. One, Evzio, as you
`5
`6 mentioned, is an injection product and for an injection product, it was
`standard practice going back a long time to use 0.4 milligrams as the
`7
`standard dose by emergency medical professionals so you can see why it
`8
`9 would have been an easy route for FDA approval to get an injection for 0.4
`10 milligrams approved for general use.
`However, in a --
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`JUDGE YANG: But I mean --
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`MR. BERMAN: -- nasal spray --
`13
`JUDGE YANG: All right. Sorry. Let me just make sure I understand
`14
`15 what you said. Is that for injection it has been routine or traditionally it has
`been .4 milligrams initial dosage; is that correct?
`16
`MR. BERMAN: That’s for under the emergency medical
`17
`professional care, titrating the dose starting at 0.4 milligrams. I won’t say
`18
`it’s the standard of care because I don’t believe there was a standard of care
`19
`as we showed in our papers, but it certainly was widely accepted as a
`20
`starting dose and it was in the labeling as the lowest of the starting doses.
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`JUDGE YANG: Okay.
`22
`MR. BERMAN: So Patent Owners try to make a very big deal out of
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`the issue of “withdraw” but it’s a big red herring in this case. It’s true the
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`prior art does state that a potential trade-off with administering higher doses
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`Case IPR2019-00685 (Patent 9,211,253 B2)
`Case IPR2019-00688 (Patent 9,468,747 B2)
`Case IPR2019-00694 (Patent 9,629,965 B2)
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`of naloxone to save the patient is the increased risk of triggering acute
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`2 withdraw symptoms. Acute withdraw symptoms may be very upsetting to
`see. That is absolutely true and it is something a caregiver may have to deal
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`4 with, but the prior art is very, very clear on this point. Acute withdraw
`symptoms are not serious and certainly not remotely life-threatening. It also
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`has been stated that withdraw symptoms are subjectively severe, but
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`objectively mild.
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`A 2007 New England Journal of Medicine article summed it up well.
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`“Concerns that naloxone will harm the patient with opioid dependence are
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`unfounded.” That’s Exhibit 1023 at page 5. Patent Owner showcased a long
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`list of prior art they say cautions about withdraw, but don’t take that at face
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`value. Many of those references don’t mention withdraw concerns and those
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`that do, many of those same references are simply reciting the trade-off I just
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`discussed and others go on to state that if withdraw happens, it’s not a big
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`deal.
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`For example, the (indiscernible) Goldfrank’s Toxicologic
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`17 Emergencies which Patent Owners included in their demonstratives slides
`states that if withdraw occurs, quote, “all that is generally required is
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`protecting them from harm and reassuring the patient that the effects will be
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`short-lived.” Does that outweigh administering a less than effective dose
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`and having the patient die? A POSA would not have thought so. A 4
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`22 milligram dose would have been the obvious choice.
`And if there are no further questions, I’ll reserve the remainder of my
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`time for rebuttal.
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`JUDGE YANG: I actually do have a question. So we talked earlier
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`Case IPR2019-00685 (Patent 9,211,253 B2)
`Case IPR2019-00688 (Patent 9,468,747 B2)
`Case IPR2019-00694 (Patent 9,629,965 B2)
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`about .4 milligrams as the initial dose for, paraphrasing what you said, under
`the medical supervision as the initial dose for injection. For intranasal
`administration, I believe Patent Owner insisted that there is no evidence on
`the record to show anything higher than 2 milligrams and 2 milligrams
`reportedly was effective.
`So the simple question for me is, yeah, you can increase it. If it is
`safe, then you can increase it to, I don’t know, I think you guys argued up to
`10 milligrams. Why? Why would you -- if two is working, why would you
`increase it is my question.
`MR. BERMAN: So two is working to a point. I guess that’s the
`easiest way I can say it. Two is working to a point, but re-dosing, giving
`another dose of naloxone, was reportedly necessary in the vast majority of
`these instances. You’re having --
`JUDGE YANG: Okay. Let me stop --
`MR. BERMAN: -- 30, 40, 50 percent of the patients having to be
`administered a second dose --
`JUDGE YANG: Okay. Let me --
`MR. BERMAN: -- which would be well understood --
`JUDGE YANG: Counsel --
`MR. BERMAN: -- as an --
`JUDGE YANG: -- can I --
`MR. BERMAN: -- emergency medical professional who had that on-
`hand. I’m sorry. Go ahead.
`JUDGE YANG: No, that’s okay. I should have mentioned there is
`an audio delay, so we might have to be patient there. You just said the vast
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`Case IPR2019-00685 (Patent 9,211,253 B2)
`Case IPR2019-00688 (Patent 9,468,747 B2)
`Case IPR2019-00694 (Patent 9,629,965 B2)
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`1 majority of the patients receiving intranasal, naloxone would have to be re-
`dosed. Can you point me to some records, some evidence, anywhere to say
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`the vast majority?
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`MR. BERMAN: No, I’m -- what -- if I said “vast majority,” I
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`5 misspoke. It is not the vast majority, but it is 30, 40, 50 percent in some
`cases of --
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`JUDGE YANG: That’s fine.
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`MR. BERMAN: -- patients having --
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`JUDGE YANG: Can you --
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`MR. BERMAN: -- to be --
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`JUDGE YANG: Can you --
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`MR. BERMAN: -- re-dosed.
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`JUDGE YANG: -- point me to anything that says 50 percent or 30
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`percent? You don’t have to do it --
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`MR. BERMAN: Sure.
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`JUDGE YANG: -- now. If you want to do it during your rebuttal
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`time, that’s fine.
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`MR. BERMAN: Yes.
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`JUDGE YANG: And I have another question. In the petition and as
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`you just mentioned, you said that there is a presumption of obviousness
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`because the claimed 4 milligram dosage falls within the dosage disclosed in
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`22 Wyse. I’m sure you noticed that Patent Owner points out that in your reply
`you no longer mention presumption. So my question is, are you still saying
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`there is a presumption or are you dropping that argument?
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`MR. BERMAN: Oh, we are absolutely still saying that. I wasn’t
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`Case IPR2019-00685 (Patent 9,211,253 B2)
`Case IPR2019-00688 (Patent 9,468,747 B2)
`Case IPR2019-00694 (Patent 9,629,965 B2)
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`aware that we had to repeat ourselves --
`JUDGE YANG: Okay.
`MR. BERMAN: -- at each item.
`JUDGE YANG: Okay. Yeah, I just wanted to make sure that -- I
`don’t have any other questions.
`Judge Franklin and Judge Valek, do you have any questions at this
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`time?
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`JUDGE FRANKLIN: None from me. Thank you.
`JUDGE VALEK: I have a question. This is Judge Valek. Counsel,
`does the only obviousness theory advanced in the petition hinge upon us
`finding that it would be obvious to use BAC in an intranasal formulation?
`MR. BERMAN: Yeah, that -- well, I guess when it comes down to
`brass tacks, that is really what this case is about and so yes, I would say that
`all of our argument has been tailored to the obviousness of using BAC. It’s
`(indiscernible).
`JUDGE VALEK: That’s true even for those claims that are not
`expressly limited to BAC?
`MR. BERMAN: Well, we have not presented additional arguments
`outside of the petition as to why those would not have been obvious. So to
`the extent the Board finds our petition evidence persuasive on those points,
`then certainly we are not dropping that. But all of the additional evidence
`that we have put forward is directed specifically to the BAC issue.
`JUDGE VALEK: Thank you.
`JUDGE YANG: All right. You have 10 minutes left here and you
`have 10 minutes reserved, so you have 20 minutes if you need for your reply
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`Case IPR2019-00685 (Patent 9,211,253 B2)
`Case IPR2019-00688 (Patent 9,468,747 B2)
`Case IPR2019-00694 (Patent 9,629,965 B2)
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`and I’ll jot that down. That’s very high tech right here. Thank you, very --
`MR. BERMAN: Thank you, Your Honor.
`JUDGE YANG: Thank you, very much.
`And Patent Owner, would you like to reserve any time for surrebuttal?
`MS. BERNIKER: Yes, Your Honor. I’d like to reserve five minutes.
`JUDGE YANG: Okay. Five minutes for you. Five minutes here.
`Just one sec. And -- 40 minutes. All right. You can start whenever you are
`ready.
`MS. BERNIKER: Thank you, Your Honors. Good morning.
`Jessamyn Berniker for the Patent Owner. The patent here cannot be invalid
`because Nalox-1’s argument requires the person of skill in the art to do
`exactly what the references teach not to do, use benzalkonium chloride in a
`naloxone formulation, combine it with EDTA and seek a high and fast
`pharmacokinetic profile by (indiscernible).
`At every term, Nalox-1’s argument is to undermine and discredit the
`very references it claims a person of skill in the art is supposed to be
`following. Beyond the primary case, the non-obviousness of the invention
`here is supported by every possible kind of secondary objective evidence
`and I’d just like to emphasize one piece before turning to the merits of the
`case.
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`By 2015, the opioid crisis in this country was raging and there had
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`long been a need for an easy to use needle-free community product
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`(indiscernible), a product for lay people. The FDA recognized that need as
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`did many others and Patent Owners who were two public health companies
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`25 were the only ones who succeeded in developing a product that solved this
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`Case IPR2019-00685 (Patent 9,211,253 B2)
`Case IPR2019-00688 (Patent 9,468,747 B2)
`Case IPR2019-00694 (Patent 9,629,965 B2)
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`problem and saved thousands of lives around the country. No one else
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`arrived at the invention and no one else even developed an FDA approved
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`product. Others tried, but they failed. This (indiscernible) --
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`JUDGE YANG: Counsel, I have --
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`MS. BERNIKER: -- (indiscernible) --
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`JUDGE YANG: Counsel, I have a question there. So I understand
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`that this is the first FDA approved intranasal product, but as Petitioner points
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`out and I’m sure you agree, that the MAD device used, I guess off-label of
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`the injectable form, it has been used for a long time, right? So people are
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`using that, correct? So even though there is no, say, FDA approved product,
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`intranasal injection has been widely used.
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`MS. BERNIKER: Certainly the mass product has been used for a
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`long time and I think as you recognized earlier, Your Honor, that those 2
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`14 milligrams (indiscernible), but what’s obvious from the FDA 2012 meeting
`and the literature and I’ll direct your attention to the slide that we included at
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`the end of our presentation regarding objective evidence of the success of
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`this product that we see is the MAD, Slide 47. What we see is that there was
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`a tremendous need for something that was materially (indiscernible) and
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`used (indiscernible).
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`What was recognized in the evidence from both Dr. Jones and
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`21 Dr. Williams which is undisputed in how challenging by comparison it was
`to use the MAD because it had required several people to put together. And
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`so what you see as you look at Slide 37 is a reflection of the need that’s
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`identified by the FDA and this is why the FDA in 2012 asked companies to
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`look in this area because despite the MAD,
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