[00:00:38] Speaker 02:
Next case is amniopharmaceuticals versus endopharmaceuticals, 2016-2017.

[00:00:45] Speaker 02:
Ms.

[00:00:47] Speaker 02:
Jolie.

[00:00:58] Speaker 00:
Good morning.

[00:00:58] Speaker 00:
May it please the court, I'm Brenda Jolie on behalf of Appellant Amniopharmaceuticals.

[00:01:03] Speaker 00:
As this court stated in the Kao case, claimed subject matter is not presumed to change as a function of how one elects to measure it.

[00:01:13] Speaker 00:
The patent trial and appeal board overlooked this crucial point and failed to recognize the prima facie case of obviousness presented by the prior art Oschlack patent.

[00:01:24] Speaker 03:
Well, your citation to Enrique Kao was incomplete, wasn't it?

[00:01:28] Speaker 03:
I mean, the sentences that follow the sentence that you quote has

[00:01:32] Speaker 03:
completely explains the context of that, right?

[00:01:38] Speaker 00:
I think this was a crucial point.

[00:01:39] Speaker 00:
And I think the follow-up doesn't change the crucial point in this context, especially as applied to the Ocelot patent, which was not being considered in that opinion.

[00:01:50] Speaker 03:
Well, what about the board's finding that, in fact, there was submitted abundant medical evidence that, in fact, there is a difference

[00:02:02] Speaker 03:
based on the measurement mechanism.

[00:02:07] Speaker 00:
I don't think that is a dispositive fact finding of the actual relevant legal question.

[00:02:12] Speaker 00:
The only thing that the board found was that the two methods don't have a specific mathematical correlation or are not exactly equivalent.

[00:02:22] Speaker 00:
But that does not answer the question of whether the formulation was obvious.

[00:02:28] Speaker 00:
And a key point to keep in mind in that regard is that there isn't a specific dissolution profile claim.

[00:02:34] Speaker 00:
There are broad ranges recited.

[00:02:36] Speaker 00:
And at most, all that Amniel would have to show is that those ranges overlap at least slightly.

[00:02:44] Speaker 00:
And a finding that they are not exactly equivalent is not a finding that they would not at least overlap slightly by a preponderance of the evidence.

[00:02:57] Speaker 00:
The PTAB aired as a matter of law because it failed to apply the appropriate standard for obviousness and placed an undue burden on Amniel.

[00:03:06] Speaker 00:
It wasn't Amniel's burden to prove a specific mathematical correlation between the dissolution measurements made by the alternate USP-approved dissolution methods.

[00:03:15] Speaker 00:
Amniel met its burden to prove that the claims were obvious by showing the prior art would motivate or teach a person of ordinary skill in the art

[00:03:23] Speaker 00:
how to arrive at the claimed subject matter with a reasonable expectation of success.

[00:03:28] Speaker 03:
But I mean, as the portion of in-reg how that you don't cite makes clear, that what is important is whether the skilled artist would have been prompted by the prior art.

[00:03:41] Speaker 03:
What they would be prompted to do is, in fact, within the scope of the pending claim.

[00:03:45] Speaker 03:
And you didn't show an overlap.

[00:03:47] Speaker 00:
First of all, I'd like to point out that

[00:03:50] Speaker 00:
These are functional claim limitations, not structural limitations.

[00:03:55] Speaker 00:
And while functional claiming is not per se wrong, as long-standing precedent from this court, like the Swinehart and Schreiber cases cited in the briefing show, when a functional limitation lies at the alleged point of novelty, a patent applicant was always supposed to bear the burden to produce evidence establishing that the structurally similar prior art subject matter

[00:04:17] Speaker 00:
would not contain the same functional characteristic in order to refute a prima facie case of unpatentability.

[00:04:25] Speaker 00:
Otherwise, patents could be obtained simply by reciting a property not explicitly disclosed in the prior art or not explicitly disclosed by the exact measurement method that the PTO lacks the ability to test to disprove.

[00:04:44] Speaker 00:
The claim's same subject matter is presumed to not change.

[00:04:49] Speaker 00:
And indeed, Oschlack is presumed enabled as a matter of law.

[00:04:53] Speaker 00:
So presumptively, the difference in the recited measurement method, which is the only difference between the Oschlack claims and the 216 claims.

[00:05:00] Speaker 03:
Was there any debate below whether Oschlack was enabled?

[00:05:04] Speaker 03:
I didn't really understand that argument that you were making.

[00:05:07] Speaker 00:
There wasn't really debate about that.

[00:05:08] Speaker 03:
But the point of that being- Why did you go to such length in your brief to argue about

[00:05:13] Speaker 03:
that the board was unfair in putting a burden on you to show that OSLEC was enabled?

[00:05:21] Speaker 00:
Because OSLEC is presumed enabled as a matter of law, and it claims controlled release oxymorphone formulations effective over at least 12 hours, which is the same thing that Enda was claiming here.

[00:05:34] Speaker 00:
So what that means is presumptively the difference in the recited measurement methods, which is, again, the only difference,

[00:05:41] Speaker 00:
does not change a person of ordinary skill in the arts ability to achieve controlled release oxymorphone formulations effective for at least 12 hours.

[00:05:51] Speaker 00:
By issuing the OSHLAC claims, that's what the PTO found, is that one of skill in the art would be able to achieve controlled release oxymorphone formulations effective for 12 hours by following the dissolution profile recited in OSHLAC.

[00:06:12] Speaker 00:
Reciting in patent claims physiological properties that result from administering an obvious formulation also does not make the formulation patentable.

[00:06:23] Speaker 00:
That's not invention.

[00:06:25] Speaker 00:
It's just observation.

[00:06:26] Speaker 00:
And the patent trial and appeal board also placed an incorrect burden here on AMNIL in requiring it to prove that one of those pharmacokinetic limitations regarding the multiple peaks

[00:06:38] Speaker 00:
are found in every immediate release formulation of oxymorphone.

[00:06:43] Speaker 03:
Well, that's not really what they said.

[00:06:45] Speaker 03:
You make that argument that they said you have to show that it shows up everywhere.

[00:06:53] Speaker 03:
But that's not really what they said, did they?

[00:06:56] Speaker 00:
Well, their fact finding was that Amul had not presented sufficient evidence to show

[00:07:02] Speaker 00:
multiple peaks in every formulation of oxymorphone.

[00:07:05] Speaker 00:
And what they were referring to is that they hadn't shown it in every single immediate release formulation shown in the patent.

[00:07:13] Speaker 00:
But that wasn't Endo's burden.

[00:07:15] Speaker 00:
And in fact, it was undisputed that at least some of the immediate release formulations showed it.

[00:07:21] Speaker 03:
If you're trying to show that something's inherent, and I'm not even sure why this inherency even applies in these circumstances, but doesn't inherency mean that it necessarily follows?

[00:07:33] Speaker 00:
But here, the only thing that would have to necessarily follow is that it isn't necessary in the controlled release formulations of oxymorphone, even if it's not inherent to all immediate release formulations.

[00:07:45] Speaker 03:
Did you put this evidence forward?

[00:07:49] Speaker 00:
We did put the evidence forward that it was shown in at least some immediate release formulations.

[00:07:53] Speaker 00:
And the evidence was there to show that.

[00:07:55] Speaker 00:
And the fact that it is undisputably shown, even in the patent data that's presented for some of the immediate release formulations,

[00:08:02] Speaker 00:
shows that it's not related to just certain controlled release formulations.

[00:08:06] Speaker 00:
It's not related to certain controlled release excipients.

[00:08:09] Speaker 00:
It is related to the active pharmaceutical oxymorphone itself.

[00:08:13] Speaker 03:
But you argued below that it would be inherent in all release formulations, did you not?

[00:08:23] Speaker 00:
We made an argument that it is inherent to the drug itself, but we also said at the least it is inherent to all controlled release formulations.

[00:08:34] Speaker 00:
And that is the only burden that we actually had to meet.

[00:08:37] Speaker 00:
And in fact, ENDO itself in the prosecution history stated that it is inherent to all controlled release formulations.

[00:08:45] Speaker 00:
And therefore, based on the doctrines of prosecution history and judicial estoppel,

[00:08:50] Speaker 00:
They shouldn't even be able to dispute that it is inherent to the controlled release formulations of the prior art.

[00:08:55] Speaker 03:
Where did you argue the prosecution history argument below?

[00:08:58] Speaker 00:
It was cited in the original petition.

[00:09:11] Speaker 03:
But that only related to the nexus prong as it relates to the objective condition, right?

[00:09:16] Speaker 00:
No, it was not cited just in relation to the secondary considerations.

[00:09:20] Speaker 00:
It was also cited in discussing the prima facie case based on Oshlak itself.

[00:09:25] Speaker 03:
Where?

[00:09:26] Speaker 03:
What's the site?

[00:09:36] Speaker 00:
In appendix 97.

[00:09:37] Speaker 00:
I'm sorry.

[00:09:38] Speaker 00:
Wait, that's the wrong site.

[00:09:43] Speaker 02:
Maybe you could cite it on rebuttal.

[00:09:46] Speaker 00:
I can find that on rebuttal.

[00:09:56] Speaker 02:
Anything further?

[00:09:58] Speaker 00:
Yes.

[00:09:59] Speaker 00:
I just want to point out that all of the evidence presented in the IPR was consistent with multiple peaks being inherent to at least the controlled release formulations taught by the prior art.

[00:10:10] Speaker 00:
The only fact found by the Patent Trial and Appeal Board

[00:10:13] Speaker 00:
that AMNIL didn't present evidence sufficient to show it in every immediate release formulation doesn't answer the relevant legal question.

[00:10:28] Speaker 00:
As I pointed out before, the fact that you see it in at least some of the data in the patent itself on some of the immediate release formulation shows that it's not related to certain excipients.

[00:10:38] Speaker 00:
And as was explained in the evidence presented in the IPR,

[00:10:43] Speaker 00:
Just because you couldn't see it in the certain data that was shown in the patent from certain studies doesn't mean that it wouldn't be present in all other immediate release formulations if the correct data were collected.

[00:10:56] Speaker 00:
The problem is those studies were never designed to be looking for or presenting evidence of multiple peaks.

[00:11:03] Speaker 03:
But of course, it's your burden.

[00:11:05] Speaker 00:
It's our burden to show that it is inherent to controlled release formulations.

[00:11:09] Speaker 00:
We didn't have to show it.

[00:11:11] Speaker 00:
that we had the data to show it in every immediate release formulation.

[00:11:16] Speaker 00:
That wasn't our burden.

[00:11:25] Speaker 00:
And even Endo's expert admitted that there was no reason to think multiple peaks wouldn't be found in all controlled release oxymorphone formulations.

[00:11:33] Speaker 00:
The only thing she

[00:11:34] Speaker 00:
said is that you haven't shown the data to show it in every immediate release formulation.

[00:11:38] Speaker 00:
She never said that it would not be present in all controlled release formulations.

[00:11:42] Speaker 00:
So we met our burden regarding the controlled release formulations.

[00:11:47] Speaker 00:
And ENDO should be a stop from asserting otherwise anyway based on their prosecution history statements.

[00:11:56] Speaker 00:
With that, I'll reserve the rest of my time.

[00:11:57] Speaker 02:
We will save it for you, Mr. Mahoney.

[00:12:04] Speaker 03:
Good morning, and may it please the court.

[00:12:06] Speaker 03:
Can you start where she left off?

[00:12:08] Speaker 03:
Let's do multiple peaks first.

[00:12:10] Speaker 03:
The multiple peaks.

[00:12:11] Speaker 03:
Sure, Your Honor.

[00:12:13] Speaker 03:
Sorry to throw you off your schedule.

[00:12:15] Speaker 03:
But what is your response to this notion that as long as they proved that it would be inherent and controlled release, assuming they did, that that would be enough?

[00:12:26] Speaker 01:
It is not enough.

[00:12:28] Speaker 01:
And indeed, they did not establish that there are multiple peaks present in a controlled release oxymorphone formulation.

[00:12:39] Speaker 01:
And as I think you pointed out, in their petition, the evidence that they put forward was directed to the inherency questions around

[00:12:55] Speaker 01:
immediate release formulations.

[00:12:59] Speaker 01:
So that's what we responded to in our patent owner response.

[00:13:07] Speaker 01:
And that was what was part of the trial.

[00:13:10] Speaker 01:
And there was no evidence put forward with respect to inherency related to control release oxymorphone formulation.

[00:13:22] Speaker 03:
Is there anything that your expert said that you think would

[00:13:25] Speaker 03:
would lend support to the argument that they're making?

[00:13:29] Speaker 01:
All she said, Your Honor, was that she wasn't sure and that that was possible.

[00:13:36] Speaker 01:
She had no data in front of her.

[00:13:39] Speaker 01:
I believe that she focused on the question of whether there were data in the record, whether there was data put forward in front of her to say one way or the other.

[00:13:49] Speaker 01:
And I think that she could not exclude the possibility

[00:13:55] Speaker 01:
that multiple peaks would be present in a controlled release formulation.

[00:14:01] Speaker 01:
In fact, there are multiple peaks with the OPANA-ER formulation, which is the commercial embodiment covered by the claims.

[00:14:08] Speaker 03:
Right.

[00:14:08] Speaker 03:
So she said you'd have to look at it on a case-by-case basis.

[00:14:11] Speaker 01:
You would.

[00:14:12] Speaker 01:
You would have to look at it on a case-by-case basis, Your Honor.

[00:14:15] Speaker 03:
What about the prosecution history argument, putting aside the waiver issue?

[00:14:21] Speaker 01:
First of all, that was not considered below.

[00:14:24] Speaker 01:
It was not put forward as an argument.

[00:14:28] Speaker 01:
It is a new argument.

[00:14:29] Speaker 01:
Our position is that they waived it.

[00:14:32] Speaker 01:
But the prosecution history does not change the outcome of this case.

[00:14:38] Speaker 01:
Their focus on the prosecution history, they claim that Endo admitted during prosecution that all

[00:14:49] Speaker 01:
controlled release, oxymorphone formulations, regardless of excipients, would exhibit multiple peaks.

[00:14:58] Speaker 01:
And that's not what we said.

[00:15:00] Speaker 01:
And what they rely on is a declaration by Stanford professor David Yeomans, which is at A604 to 612.

[00:15:16] Speaker 01:
In his declaration, he is analyzing whether there are peaks present with respect to OPANA-ER.

[00:15:24] Speaker 01:
Again, a very specific formulation that, yes, it's covered by the claims, but in no way did Dr. Yeomans state in his declaration that any and all oxymorphone controlled release would provide those peaks.

[00:15:46] Speaker 01:
So again, we think it's a new argument that should not be considered.

[00:15:50] Speaker 01:
But even if it were, it would not change the outcome of the case, because it's not an admission.

[00:16:01] Speaker 01:
With respect to the enablement question, I would like to respond to that as well.

[00:16:07] Speaker 01:
I think, as you certainly know, enablement is not

[00:16:13] Speaker 01:
Inherency.

[00:16:14] Speaker 01:
There's not an equation of the OSHLAC patent and the fact that it may be presumed enable for what it states because it was issued by the PTO.

[00:16:30] Speaker 01:
That does not equate to whether it inherently teaches the equivalence between the basket dissolution method at 100 RPMs

[00:16:44] Speaker 01:
and paddled at 50.

[00:16:48] Speaker 03:
Was there even a debate below over whether OSLEC was enabled?

[00:16:54] Speaker 03:
No.

[00:16:55] Speaker 03:
What the board found was even if it's enabled for its own purposes, it doesn't teach this correlation, right?

[00:17:04] Speaker 01:
That's exactly right, Your Honor.

[00:17:06] Speaker 01:
That's exactly right.

[00:17:08] Speaker 01:
And on these questions, there are two issues in this case.

[00:17:13] Speaker 01:
One is whether

[00:17:14] Speaker 01:
The claim dissolution profiles are disclosed in the Oshlak reference.

[00:17:19] Speaker 01:
And then secondly, on the multiple peaks, and that is whether the claim multiple peaks are inherent to oxymorphone compositions.

[00:17:27] Speaker 01:
And both of these are fact questions that were subject to an extensive record during the IPR trial.

[00:17:35] Speaker 01:
And the board's factual determinations on these issues are supported by, in the board's own words, abundant scientific evidence.

[00:17:44] Speaker 01:
That's at A26.

[00:17:47] Speaker 01:
And simply put, in this case, Amniel failed to carry its burden.

[00:17:52] Speaker 01:
And with respect to the dissolution elements of the claims, the board's finding that Oshlak does not disclose the claim dissolution limitations was supported by expert testimony from Professor Diane Burgess.

[00:18:14] Speaker 01:
who's a renowned dissolution expert at the University of Connecticut School of Pharmacy.

[00:18:21] Speaker 01:
She's conducted dissolution research for upwards of 30 years.

[00:18:26] Speaker 01:
Her declaration is at A3803 to 3830.

[00:18:35] Speaker 01:
It's supported by pharmaceutical textbooks, scientific papers.

[00:18:39] Speaker 01:
Those are at A2658 to 2813.

[00:18:45] Speaker 01:
And all of these show that the paddle method at 50 RPM and the basket method at 100 are not roughly equivalent.

[00:18:54] Speaker 01:
The only evidence that Amniel put forward was this handbook on dissolution.

[00:19:00] Speaker 01:
The handbook on dissolution said that the basket and the paddle methods are roughly equivalent.

[00:19:10] Speaker 01:
But there was no citation.

[00:19:12] Speaker 01:
There was no support for that.

[00:19:15] Speaker 01:
And the board found actually the opposite, again, based on abundant scientific evidence, the evidence that we endo put into the case.

[00:19:27] Speaker 01:
And so there's not an overlap or a correlation between the two different methods.

[00:19:35] Speaker 01:
With respect to Ian Neal's arguments on appeal about the burden, the burden on persuasion and the burden shifting,

[00:19:45] Speaker 01:
I refer to the July 2016 case, Magnum Oil Tools, that essentially holds that this burden shifting notion onto the patent owner has no place in an IPR.

[00:20:02] Speaker 01:
The citation there is 829, F3rd, 1364.

[00:20:10] Speaker 01:
You've seen also, Your Honors, in E.M.

[00:20:13] Speaker 01:
Neal's briefing,

[00:20:15] Speaker 01:
that the paddle and the basket are the same, same test, simply because they are expressed in different units.

[00:20:29] Speaker 01:
And this is, as the board found, this is scientifically wrong.

[00:20:36] Speaker 01:
And this is not a case where Ando claimed, let's say, one inch.

[00:20:43] Speaker 01:
When the prior art taught 2.54 centimeters between English and metric units, there is an established correlation.

[00:20:55] Speaker 01:
That is completely inapplicable to this situation between basket and paddle, because the evidence here shows that there's no correlation between the dissolution profiles.

[00:21:09] Speaker 03:
Do you concede, as does the director,

[00:21:14] Speaker 03:
Because in light of synopsis, the gelling agent claims are still fair game for attack in some other form.

[00:21:22] Speaker 01:
Is there no estoppel as to those gelling agent claims?

[00:21:25] Speaker 01:
On the estoppel question, we think that E.M.

[00:21:30] Speaker 01:
Neal improperly raised those on appeal.

[00:21:33] Speaker 01:
But also, the estoppel question, we feel, belongs in the district court.

[00:21:39] Speaker 01:
There is a district court case, and it's up on appeal.

[00:21:45] Speaker 01:
And in fact, Ando filed a motion.

[00:21:47] Speaker 03:
So you're disagreeing with what the PTO director says with respect to what 315E means as it relates to claims that have not been instituted?

[00:21:59] Speaker 01:
On that topic, our primary position is that it's an issue for the district court.

[00:22:07] Speaker 01:
But if it is considered in this proceeding, we think, as we briefed, that you could take into consideration the overlapping of the prior art related to 72 to 82 and some of the claim language.

[00:22:28] Speaker 01:
But again, our primary position is that it's better left for the district court, and it's not part

[00:22:36] Speaker 01:
of these proceedings.

[00:22:42] Speaker 02:
Anything further?

[00:22:43] Speaker 01:
No.

[00:22:44] Speaker 01:
If there are no further questions, I'm prepared to submit on the briefs.

[00:22:48] Speaker 02:
Thank you, counsel.

[00:22:50] Speaker 01:
Thank you, your honor.

[00:22:50] Speaker 01:
Ms.

[00:22:50] Speaker 02:
Jolie has some rebuttal time.

[00:23:02] Speaker 00:
First of all, in response to the earlier question, in the appendix at 95, and again, in the appendix at 126, were the petition cites to the Cal cases recitation of the file history declaration, where they, and it was submitted that it appeared that extended release formulations of oxymorphone, not limited to formulations with any specific excipient, cause multiple peaks in oxymorphone blood concentration.

[00:23:28] Speaker 00:
And the court in Cal relied on that file history statement.

[00:23:31] Speaker 00:
under both the doctrines of judicial estoppel and prosecution history estoppel, and no shouldn't even be allowed to dispute that multiple peaks would be inherent to the controlled release formulations of the prior art, such as taught by Oschlack.

[00:23:50] Speaker 00:
To address opposing counsel's statement earlier about the burden-shifting argument

[00:23:56] Speaker 00:
We don't dispute that under statute, amnil bears the burden of persuasion and the burden to prove a proposition of impatient ability by a preponderance of the evidence.

[00:24:06] Speaker 00:
However, even in the litigation context as well as in the examination context, it has always been the law that the burden of production shifts after a prima facie case of obviousness has been established.

[00:24:19] Speaker 00:
And the Novo Nordis case cited in the briefing discusses that.

[00:24:25] Speaker 00:
And the magnum case that counsel referred to did not say differently.

[00:24:29] Speaker 00:
It did not deal with the shifting burden of production.

[00:24:31] Speaker 00:
And it also did not have in that case at issue a functional limitation at the alleged point of novelty, which is exactly what is at issue here and which longstanding precedent like the Schreiber and the Swinehart cases indicate once that prima facie case of obviousness has been established based on structural similarity in the prior art, the burden should shift to the patent applicant or patentee

[00:24:54] Speaker 00:
to establish that the functional immunization that they are claiming would not actually be in that prior art.

[00:25:01] Speaker 00:
And ENDO has never done that.

[00:25:04] Speaker 00:
In fact, what they argued on remand.

[00:25:06] Speaker 03:
Do you have anything else?

[00:25:07] Speaker 03:
I think that's a misstatement of the law.

[00:25:08] Speaker 03:
But go ahead and make your next argument.

[00:25:12] Speaker 00:
And ENDO has never done that.

[00:25:13] Speaker 00:
And even if it were our burden,

[00:25:16] Speaker 00:
Again, here the only thing at most we would have to show is that those ranges would potentially overlap at least slightly.

[00:25:23] Speaker 00:
And that is not a fact finding that the PTAB made.

[00:25:27] Speaker 00:
The only fact finding that they made was that these two measurement methods are not necessarily always exactly equivalent.

[00:25:34] Speaker 00:
But that does not answer the question of whether there would be an overlap or does not answer the question of whether one of skill and the art would reasonably expect

[00:25:43] Speaker 00:
them to be similar and therefore have a reasonable expectation of success of getting subject matter simply by varying, or by aiming for dissolution still within the range claimed, the percentage range claimed by OSLEC but simply measured by one of the alternate USP approved measurement methods.

[00:26:08] Speaker 00:
With that, I will submit my question.

[00:26:09] Speaker 02:
Thank you.

[00:26:10] Speaker 02:
Ms.

[00:26:10] Speaker 02:
Drulli will take the case under her advisement.