[00:00:00] Speaker 04:
All right, the next argued case is number 20, 2106, ADAPT Pharma Operations Against Teva Pharmaceuticals USA.

[00:00:09] Speaker 04:
Ms.

[00:00:10] Speaker 04:
Getson.

[00:00:12] Speaker 02:
Thank you, Your Honors, and may it please the court.

[00:00:14] Speaker 02:
My name is Kate Getson.

[00:00:15] Speaker 02:
I represent the appellants, opiant, and ADAPT.

[00:00:18] Speaker 02:
The district court committed three errors in this case.

[00:00:23] Speaker 02:
was that it failed to identify the motivation to select and combine the specific elements of ADAPT's invention out of what were millions of options.

[00:00:34] Speaker 02:
Error number two, it did not apply this court's teachaway test.

[00:00:39] Speaker 02:
Instead, it offered reasons why a person of skill in the art might have chosen to ignore a clear teachaway.

[00:00:46] Speaker 02:
And error number three, the court impermissibly put the burden on ADAPT

[00:00:51] Speaker 02:
to overcome its premature obviousness conclusion with objective considerations.

[00:00:58] Speaker 02:
Any one of these errors warrants reversal, but I'd like to start today by discussing the teachaway.

[00:01:05] Speaker 02:
The closest prior art in this case and the only reference reporting any stability testing of a formulation relevant to this case is the wise patent.

[00:01:16] Speaker 02:
Everyone agrees with both of those principles.

[00:01:19] Speaker 02:
What's the prior art?

[00:01:20] Speaker 02:
Only stability testing.

[00:01:22] Speaker 02:
That patent, WISE, expressly criticized the benzalkonium chloride, BZK, that was used in this formulation, finding it not acceptable because it degraded the active ingredient, naloxone.

[00:01:38] Speaker 02:
Ms.

[00:01:38] Speaker 02:
Destin, this is Judge Pro.

[00:01:40] Speaker 03:
What was the concentration of BZK in WISE?

[00:01:45] Speaker 02:
The concentration of BZK and WISE, because it was part of a stability test, was intentionally higher than it would be used in a regular formulation.

[00:01:55] Speaker 03:
But I would point out... It's half to 25 times higher than what is called for in the past, correct?

[00:02:02] Speaker 02:
Yes, I believe that's correct.

[00:02:04] Speaker 03:
But why is that sufficient?

[00:02:07] Speaker 03:
And this wasn't in contrast to Chemours.

[00:02:10] Speaker 03:
This was not the only prior art reference.

[00:02:12] Speaker 03:
You say this was the closest.

[00:02:14] Speaker 03:
But there were other prior art references relied on by the district court that did nothing close to TeachAway.

[00:02:22] Speaker 03:
They encouraged.

[00:02:24] Speaker 03:
So you've got this one case and they're using dosages that astronomically exceed

[00:02:31] Speaker 03:
the dosage in the patent, why isn't that enough to kind of question why this would be the kind of teach-away case that our previous precedent has endorsed?

[00:02:44] Speaker 02:
So Judge Prost, let me give a two-part answer to that two-part question, if I can.

[00:02:49] Speaker 02:
First, with respect to the concentration, Wise didn't say

[00:02:53] Speaker 02:
that BZK is not acceptable at this concentration.

[00:02:57] Speaker 02:
He said why, he said BZK is unacceptable full stop.

[00:03:01] Speaker 02:
So reasoning, as the district court did, that maybe a POSA would be motivated to use a lower concentration of BZK in the face of an express warning that says this is not acceptable because it degrades naloxone.

[00:03:16] Speaker 02:
Again, that's...

[00:03:19] Speaker 05:
Oh, I was just going to ask, I mean, when we look at teaching away, it's supposed to be whether it teaches away from that claimed invention, right?

[00:03:28] Speaker 02:
Yes.

[00:03:29] Speaker 05:
And so, I mean, and that's my first question.

[00:03:32] Speaker 05:
That's my first reason for why your answer doesn't really resonate with me, which is that, you know, the claimed invention, again, is at a much lower concentration.

[00:03:42] Speaker 05:
And then second, you know, even where WISE says, you know, don't use BDK or something, don't you think a POSA has to read that in the context of what is actually tested in WISE?

[00:03:57] Speaker 02:
I think that not only does APOSA have to read that in the context of what was tested, but so did the PTAB.

[00:04:03] Speaker 02:
And as we pointed out in our brief, the PTAB, using the right legal teachaway standard, had no dispute that the WISE patent taught away.

[00:04:14] Speaker 02:
In fact, what it said was, APOSA would have given significant weight, and I'm quoting now, to the only naloxone formulation stability data disclosed in WISE.

[00:04:24] Speaker 02:
That PTAB, of course, had exactly the same thing in front of it.

[00:04:28] Speaker 02:
It had the wise patent.

[00:04:30] Speaker 02:
It had the concentration.

[00:04:31] Speaker 02:
Well, Ms.

[00:04:31] Speaker 03:
Benson, this is Judge Proust.

[00:04:33] Speaker 03:
I appreciate what you're saying, but what we've got in front of us is a district court opinion.

[00:04:37] Speaker 03:
And you would agree, would you not, that the standard of review is clear error?

[00:04:43] Speaker 03:
So why does that standard of review where the district court says they concluded that the most you learn from WISE is not to use such an extremely high concentration of BZK, why is there sufficient basis to say clear error?

[00:05:03] Speaker 02:
Judge Prost, I don't agree.

[00:05:04] Speaker 02:
I think the general standard of review of district court findings of fact is clear error, and that's actually in contrast, of course, to the PTAB.

[00:05:12] Speaker 02:
where the challenger actually has a more accommodating standard of review.

[00:05:17] Speaker 02:
But with respect to this particular conclusion, the problem that we have is not a clear error problem.

[00:05:23] Speaker 02:
It's that this district court in its first patent trial didn't even cite, much less apply, the teachaway standard.

[00:05:32] Speaker 02:
Instead, it went kind of searching for reasons why that teachaway maybe wouldn't teach away.

[00:05:38] Speaker 02:
to the earlier question.

[00:05:40] Speaker 02:
It said, well, maybe there's a higher concentration.

[00:05:42] Speaker 02:
Maybe someone could infer from other prior art that you could reach a different result.

[00:05:47] Speaker 02:
But that brings me back to the second part of Judge Stoll's earlier question, I believe.

[00:05:52] Speaker 02:
And that has to do with the prior art.

[00:05:54] Speaker 02:
No one disputes, I will say it again, that WISE is the closest prior art.

[00:05:59] Speaker 02:
No one disputes that WISE is the only prior art containing stability data.

[00:06:04] Speaker 02:
And very important for this argument

[00:06:07] Speaker 02:
No one disputes that WISE is also the most recent prior art.

[00:06:12] Speaker 05:
Can I ask you a question?

[00:06:14] Speaker 05:
This is Judge Stoll.

[00:06:15] Speaker 05:
First of all, when we look at teaching away, again, we're looking at how a person of ordinary skill in the art would read their reference.

[00:06:24] Speaker 05:
I mean, here, I understood the district court not to just be looking for reasons to distinguish WISE, but instead heard some very thorough and

[00:06:35] Speaker 05:
somewhat compelling expert testimony explaining how a poser would read wise and say that a poser would have to read wise to just be saying that it would not be good to use BZK at these levels of concentration, right?

[00:06:51] Speaker 05:
So why couldn't the district court rely on that expert testimony putting the wise statements in the context of the testing that was actually done in wise?

[00:07:02] Speaker 02:
Because I think the expert, Judge Stoll, was drawn into the same mistake that the district court made.

[00:07:08] Speaker 02:
The expert testimony on this, about the concentration maybe not dissuading APOSA from trying BZK, about an earlier reference containing no data, maybe giving APOSA the reason to infer that something was stable, all of those things, again, are resisting the teachaway.

[00:07:28] Speaker 02:
The teachaway in WISE, the most recent,

[00:07:31] Speaker 02:
closest prior art and the prior art that the PTAB said with no dispute, teaches away from this patent, why says, and this is not one of those cases I should add where- It's a PTAB statement of a teaching way, which is factual determination.

[00:07:48] Speaker 05:
Is that somehow binding on the district court or on us?

[00:07:53] Speaker 02:
No, it's not.

[00:07:54] Speaker 02:
The reason I keep pressing on it though is because I think it is the most

[00:07:58] Speaker 02:
the sharpest example of why the departure from the legal standard actually matters.

[00:08:03] Speaker 05:
Okay, let me ask you another question, which is my understanding is that WISE was first published after the invention date, you know, of the Naloxone patents.

[00:08:13] Speaker 05:
Am I wrong about that?

[00:08:16] Speaker 02:
WISE was filed prior to the publication date, and there's actually no dispute here, including Teva,

[00:08:23] Speaker 02:
that wise is prior art.

[00:08:25] Speaker 02:
Wise talks in its brief about, Teva talks in its brief about wise.

[00:08:29] Speaker 05:
Well, I'm just thinking about how a person would have read wise or known of wise.

[00:08:33] Speaker 05:
Would a person have known of wise at the time of the invention?

[00:08:37] Speaker 02:
That argument, first of all, doesn't square with the statute.

[00:08:41] Speaker 02:
The statute says that prior art is whatever is filed.

[00:08:44] Speaker 02:
And, you know, what you look at is the date of filing, not whether a particular person, of course, because that's not what you're looking at when you talk about a posa,

[00:08:52] Speaker 02:
whether a particular person would have grasped this particular filing.

[00:08:56] Speaker 02:
Wise teaches away, full stop.

[00:08:59] Speaker 02:
That's what the PTAB said.

[00:09:00] Speaker 02:
And the district court went out looking for reasons why it didn't.

[00:09:04] Speaker 02:
The other impact of... Can I ask you about that?

[00:09:08] Speaker 03:
This is Judge Prout.

[00:09:09] Speaker 03:
Because the suggestion is...

[00:09:11] Speaker 03:
sort of like, you know, that they went for reasons not to follow the law?

[00:09:16] Speaker 03:
I mean, I don't, is there an argument, you rejected, you understand clear error applies, but you say it doesn't apply here.

[00:09:23] Speaker 03:
And I guess that suggests that you say there was some clear, there was some error of law.

[00:09:30] Speaker 03:
Where are you finding that in the district court opinion?

[00:09:32] Speaker 03:
Did they misstate what our cases say about the standards for teaching the way?

[00:09:38] Speaker 03:
This is, I know it's a long opinion, it's like 90 pages, chock full of enormous number of fact findings.

[00:09:44] Speaker 03:
Can you point to us what the district court said that you think is sort of the legal, by making, you know, a legal statement that's not correct?

[00:09:56] Speaker 02:
I can, Judge Prost, and it's the fact that within those 90 pages, the district court never once cites

[00:10:03] Speaker 02:
the teach-away standard.

[00:10:04] Speaker 02:
Never once cite... Well, can you show us... You can't show us anything affirmative.

[00:10:09] Speaker 03:
You're saying because they don't cite a teach-away standard.

[00:10:14] Speaker 03:
Where's the discussion of teaching away?

[00:10:16] Speaker 03:
When they're applying the standard, presumably they're at least inherently saying what the standard is.

[00:10:22] Speaker 03:
What is... You're saying it didn't say anything wrong, but because it didn't say what you think is right, that's clear error?

[00:10:31] Speaker 03:
I'm not...

[00:10:32] Speaker 02:
Judge Prost, I apologize for stepping on your question there.

[00:10:36] Speaker 02:
The answer is it's an error of law because the district court didn't even cite or apply the right legal standard.

[00:10:42] Speaker 02:
The standard, of course, that asks does a reference criticize or discourage or discredit something that's claimed in the patent?

[00:10:49] Speaker 02:
If you look at appendix 65 to 66, this is the part where the district court talks about the teachaway.

[00:10:55] Speaker 02:
You won't find the standard there.

[00:10:57] Speaker 02:
You won't find a site there.

[00:10:59] Speaker 02:
What you find is the district court again bringing on this evidence from the expert that talks about reasons why APOSA would have ignored the teachaway.

[00:11:09] Speaker 02:
That is the legal error we are claiming here.

[00:11:12] Speaker 02:
It is not an error in fact finding.

[00:11:14] Speaker 02:
It is a significant omission and it doesn't matter what the volume of the decision is in terms of pages and facts.

[00:11:21] Speaker 02:
It's what's missing that matters.

[00:11:23] Speaker 05:
And that's actually a good time to wait.

[00:11:25] Speaker 05:
Judge Stoll, you told us to look at pages 65 to 66 for the district court's statement on teaching away.

[00:11:38] Speaker 05:
But what about page 87 to 88 to 89?

[00:11:42] Speaker 05:
I think, actually, 87 to 88 is where the teaching away analysis is, where the legal standard is discussed.

[00:11:52] Speaker 05:
I see, I was just wondering if you had looked at that.

[00:11:57] Speaker 02:
I have indeed, yes.

[00:11:59] Speaker 02:
And the question is, the issue is that the court, you know, at that point cites one teachaway case, but he doesn't square the facts that he's already found with what that teachaway case says he has to do.

[00:12:13] Speaker 02:
That's, that's the problem.

[00:12:15] Speaker 02:
And again, he was, this was new to him.

[00:12:17] Speaker 02:
So it's not a surprise and this does happen.

[00:12:20] Speaker 02:
But that is the problem.

[00:12:21] Speaker 02:
It's what's not in the district court's opinion, rather than what is.

[00:12:28] Speaker 02:
Let me speak briefly, if I could, to the other two issues, since we've taken up some time on TeacherWay.

[00:12:32] Speaker 02:
Motivation to combine.

[00:12:34] Speaker 02:
I want to take 30 seconds and walk through for this court the reasons why Keva's main cases are in a posit here, because I think they shine a helpful light on the motivation to combine issue.

[00:12:47] Speaker 02:
In reapplied materials involved a polishing pad.

[00:12:51] Speaker 02:
The issue was depth and width and pitch of the polishing pad.

[00:12:56] Speaker 02:
All anybody had to do was simply fiddle with those dials.

[00:13:00] Speaker 02:
DuPont was an oxidation reaction, temperature plus pressure.

[00:13:04] Speaker 02:
Galderma, inactive ingredients were all conceivably obvious.

[00:13:08] Speaker 02:
The only question was range.

[00:13:10] Speaker 02:
Merck, this is the case on which Teva most relies.

[00:13:14] Speaker 02:
The prior arc disclosed 1,200 combinations, Teva says.

[00:13:17] Speaker 02:
every single one of those combinations was proclaimed in the prior art to be effective.

[00:13:24] Speaker 02:
So all of those combinations were effective.

[00:13:27] Speaker 02:
Here, in contrast, what you have is a vast multiplicity of combinations and options.

[00:13:33] Speaker 02:
And the problem, again, with the district court's decision, and you can find this at 56 to 58, is that the district court homes in on exactly the elements that are used in this patent.

[00:13:44] Speaker 02:
Not all of the other ones that were available in the prior arc.

[00:13:47] Speaker 02:
And finally, briefly, on objective indicia, there's really no question that the district court applied the wrong legal standard.

[00:13:53] Speaker 02:
It did that because Teva asked it to.

[00:13:55] Speaker 02:
And once it did, it made a number of clearly erroneous factual findings.

[00:13:59] Speaker 03:
What is that wrong standard?

[00:14:00] Speaker 03:
What is the wrong standard that you think that they applied and that was wrong?

[00:14:08] Speaker 02:
Certainly, Judge Prosen.

[00:14:09] Speaker 02:
I think that was Judge Prosen.

[00:14:10] Speaker 02:
Forgive me.

[00:14:10] Speaker 02:
I know I'm really running out of time.

[00:14:12] Speaker 03:
I guess the main thing is the district court considered the secondary considerations and analyzed them in an enormous amount of detail before it reached its ultimate conclusion of law that the patent was obvious, right?

[00:14:27] Speaker 03:
I don't see where the error is.

[00:14:30] Speaker 02:
That is not correct.

[00:14:32] Speaker 02:
If you look at Appendix 59, the court concluded before even getting into the objective indicia that the patents are rendered obvious by the prior art, full stop.

[00:14:42] Speaker 02:
That is exactly the error that this court called out in Recyclo-Ben-Supreme.

[00:14:48] Speaker 02:
So with respect to when the court made its obviousness finding, this is what the court talked about at length in that case.

[00:14:55] Speaker 02:
The district court found something obvious, put the burden on ADAPT, Appendix 67, to show any secondary considerations of non-obviousness, sufficient to overcome.

[00:15:06] Speaker 02:
the prima facie case.

[00:15:07] Speaker 02:
So whatever happened after that, it was through the lens of the district court already having made that finding.

[00:15:13] Speaker 02:
That's the problem.

[00:15:14] Speaker 02:
But with respect to... Well, I know you're familiar with KSR.

[00:15:19] Speaker 03:
There's two references to KSR on secondary considerations.

[00:15:23] Speaker 03:
One of them is neither here nor there.

[00:15:25] Speaker 03:
But at the end, when they talk about, they say, finally, we conclude that the patent owner in this case has shown no secondary factors to dislodge the determination that the claims are obvious.

[00:15:42] Speaker 03:
Doesn't that sound exactly like what you're saying the district court said?

[00:15:46] Speaker 03:
about the prima facie case of obviousness and then said the secondary considerations do not dislodge that prima facie determination.

[00:15:56] Speaker 03:
Is that an error?

[00:15:57] Speaker 03:
Is that a legal error?

[00:15:59] Speaker 02:
What this court did, though, was to make a determination of obviousness.

[00:16:04] Speaker 03:
So this court pointed out in... What you pointed us to... I'm sorry to keep interrupting, but time is short.

[00:16:10] Speaker 03:
What you pointed us to occurs in the district court's analysis of the facts.

[00:16:17] Speaker 03:
It's under the fact heading, fact finding, not in the conclusion of law, which certainly comes after, in the fact finding, their detailed analysis of secondary consideration.

[00:16:30] Speaker 03:
Right?

[00:16:32] Speaker 02:
Judge Prost, the issue that we have is that Teva invited and the judge accepted the invitation to find obviousness before discussing those objective considerations.

[00:16:44] Speaker 02:
And with respect to KSR, I'd again refer you to cyclobenzaprine.

[00:16:48] Speaker 02:
There is a discussion in that case about how some courts talk about a rebuttal of a prima facie case and that that is a dangerous way to talk about this because the burden never moves.

[00:17:00] Speaker 03:
But are there not cases before and after N-ray cyclobizetrine are cases that use the terminology prima facie case and then goes to secondary considerations to see whether they've been dislodged or rebutted, et cetera?

[00:17:19] Speaker 03:
Aren't there cases, are cases, preceding and following N-ray cyclobizetrine that use that terminology?

[00:17:26] Speaker 02:
I think there are cases that both proceed and follow it.

[00:17:29] Speaker 02:
And I, so I think in, in recycled Ben Supreme did not, you know, at adequately maybe sweep up some of the language that gets used.

[00:17:36] Speaker 02:
The important thing is the shifting of the burden, not so much the language that's used.

[00:17:41] Speaker 02:
And the other thing that I would mention here very briefly is that even if we're in clear error land, I would urge the court to look, for example, at the finding of no long felt need.

[00:17:53] Speaker 02:
which is clearly error given the FDA's announcement.

[00:17:55] Speaker 02:
Unexpected results, clearly error in light of OREXO, this case, court's case from 2018 involving improvement in bioavailability.

[00:18:06] Speaker 02:
Skepticism, clear error in light of all of the testimony that no one was using doses above 2 milligrams.

[00:18:13] Speaker 02:
And copying, clear error in light of all of the other companies that copied this formulation right after ADAPT filed for it.

[00:18:22] Speaker 02:
I apologize for going long.

[00:18:23] Speaker 02:
I thank you for your attention.

[00:18:26] Speaker 04:
Okay.

[00:18:26] Speaker 04:
Thank you.

[00:18:27] Speaker 04:
It's time for your rebuttal time.

[00:18:29] Speaker 04:
And let's hear from Mr. Rosendahl.

[00:18:32] Speaker 00:
Thank you, Judge Newman.

[00:18:34] Speaker 00:
May it please the court?

[00:18:37] Speaker 00:
At trial, this case was a classic battle of the experts, and ADAPT lost it fair and square.

[00:18:46] Speaker 00:
In an uncommonly thorough 97-page opinion, the district court resolved in Teva's favor

[00:18:52] Speaker 00:
the key factual disputes underlying the three issues on appeal, namely the motivation to combine prior art references with a reasonable expectation of success, the use of benzalkonium chloride with naloxone, and the secondary considerations of non-obviousness.

[00:19:07] Speaker 00:
Naturally, on appeal, ADAPT claims that it is raising legal issues rather than factual ones.

[00:19:12] Speaker 00:
But how a post-it would have understood the prior art, whether a post-it would have been discouraged from using benzalkonium chloride with naloxone,

[00:19:20] Speaker 00:
and whether secondary considerations are present are all factual issues and not legal ones.

[00:19:25] Speaker 00:
The two sides' experts presented very different views of the relevant facts, and in each case, the district court found Teva's expert to be credible and a DAPT expert to be unpersuasive.

[00:19:37] Speaker 00:
The district court's factual findings on these issues were correct and well supported in the record.

[00:19:42] Speaker 00:
Certainly, they are not clearly erroneous.

[00:19:45] Speaker 00:
Therefore, this court should affirm the district court's ultimate conclusion

[00:19:49] Speaker 00:
that the patents in suit are invalid due to obviousness.

[00:19:55] Speaker 00:
We spent a fair amount of time on the teacher way issue and I am happy to go there directly.

[00:20:03] Speaker 00:
So we had a situation where the wise reference has a preliminary conclusion

[00:20:12] Speaker 00:
uh... that uh... bentokonium chloride which was used as the court observed in an extremely high concentration many times more uh... then would be used in the patent institute and more indeed than had ever been used in any f d a approved uh... nasal spray formulation there was a preliminary conclusion that uh... it was not uh... suitable but if we eat you know the the what adapt wanted to do is look at a single sentence in wise which says

[00:20:42] Speaker 00:
that it's not a suitable preservative, and stop.

[00:20:49] Speaker 00:
And just say, okay, well if there's a sentence in here that says it's not a suitable preservative, then APOSA would take that at face value and forever forswear using bentylponium chloride as a preservative.

[00:21:03] Speaker 00:
But that's not a reasonable reading of the reference, at least it's not the reading of the reference that the court credited.

[00:21:09] Speaker 00:
And if we look at what, what wise actually says, it is not at all as stark a teach away as, um, as adapt would have it.

[00:21:18] Speaker 00:
So we know that it's, it's a preliminary conclusion that bento alcohol, uh, and paraben preservatives were acceptable.

[00:21:25] Speaker 00:
The bento cone implore, it was not, but then later studies, uh, we find out, and I'm reading now from, uh, appendix page 68, 94, if the court cares to follow along in column 27,

[00:21:36] Speaker 00:
um... at line fifty later studies indicated that methylparaben and propylene glycol and glycerin had a negative impact after all we don't know what the um... the further studies would have shown about ventoconium chloride because there weren't any further studies to follow up on that if we go to column twenty eight and we look at the actual conclusion that life comes to this is starting in about line twenty three it says net

[00:22:04] Speaker 00:
Applicant found that, surprisingly, commonly used excipients, including one or more of ascorbic acid, hypromellose, propylene glycol 400, sorbitol, glycerin, polypropylene glycol, methylparaben, propylparaben, benzalkonium chloride, were found to increase degradation of naloxone.

[00:22:25] Speaker 00:
And then comes the key sentence.

[00:22:27] Speaker 00:
While some of the excipients might work individually,

[00:22:31] Speaker 00:
The combination of many of these was found to be unacceptable for various reasons as outlined above.

[00:22:39] Speaker 00:
And so there's just not the strong, categorical, clear teach-away as a matter of fact in here that ADAPT would like there to be.

[00:22:50] Speaker 00:
And certainly there's not a statement, there's no legal error of the district court crediting Teva's expert testimony that APOSA

[00:23:00] Speaker 00:
reading wise as a whole would not be dissuaded from using phenylchloride at the far lower concentrations found in the patents, found in other prior parts.

[00:23:17] Speaker 05:
that is actually relied on for the teaching away.

[00:23:20] Speaker 05:
Maybe I'm wrong, but I thought it was more in column 27 around lines 29 to 31 would have been the sentence that they probably would have cited.

[00:23:30] Speaker 05:
So what's your response to that, which is a sentence that says the results further surprisingly showed that the use of, I think this is BZK, a common nasal product preservative resulted in additional degradant

[00:23:43] Speaker 05:
And my misunderstanding, I thought this was the part of the reference that they primarily relied on.

[00:23:49] Speaker 00:
Sure, but I guess my point, Your Honor, is that that sentence has to be read in the context of the article as a, the patent as a whole.

[00:23:57] Speaker 00:
And what that says is that in Formulations 7, 9, 14, and 14A,

[00:24:05] Speaker 00:
there was degradation and because benzalkonin chloride was in there, the preliminary conclusion was that benzalkonin chloride might be contributing to the degradation.

[00:24:14] Speaker 00:
But if we go to the page before that, table 13 at the bottom of column 26, we can see the different formulations that were used.

[00:24:23] Speaker 00:
And if, first of all, if we look at, for example, formulation number 12, that has benzalkonin chloride doesn't show any degradation.

[00:24:31] Speaker 00:
14 and 14A are the same formulation.

[00:24:34] Speaker 00:
It's just that 14A is a more acidic version of it.

[00:24:37] Speaker 00:
But those contain glycerin and propylene glycol, which are in the list of disfavored excipients.

[00:24:44] Speaker 00:
If we go to number nine, we see polyethylene glycol and sorbitol, which are in the list of disfavored excipients.

[00:24:52] Speaker 00:
If we go to number seven, we've got hypermellos and sorbitol, which are also in the list of disfavored excipients.

[00:24:57] Speaker 00:
And tellingly,

[00:24:58] Speaker 00:
And if we look at number 7 and we compare it to 7M in table 14, we'll see that it's the same formulation except that the BZK has been replaced with benzo alcohol as the preservative.

[00:25:14] Speaker 00:
And Wise tells us in column 29 at line 54, formulation 7M had markedly increased degradation

[00:25:22] Speaker 00:
And so what that tells us is that the substitution of benzylconium chloride for their preferred preservative, benzyl alcohol, didn't actually improve the degradation problem, which suggests that other elements in the formulation are responsible for it.

[00:25:37] Speaker 00:
So I think the testimony was that a person reading that sentence from Wise, in the context of the data

[00:25:45] Speaker 00:
behind it and in in the context of the other statement in wine and bearing in mind the extremely high concentration uh... might have been dissuaded from from using them but couldn't chloride at high concentrations but not at the ones that were here and it is worth noting that uh... the curve formulation and the uh... davis uh... formulation both relied which are uh... were part of the obvious of combinations both had been dark and chloride in them car with used

[00:26:13] Speaker 00:
in a clinical trial in Australia over an 18-month period with no noticeable problems due to the presence of bentarconium chloride.

[00:26:25] Speaker 03:
I'm sorry, of the district court's opinion, the district court relied on those two factors, right?

[00:26:33] Speaker 03:
One, the higher concentration, much higher than the patents in suit, and also that it was commonly used preservative that has been used in over 200 internasal products.

[00:26:45] Speaker 03:
And it referred specifically to the J.B.'

[00:26:47] Speaker 03:
's reference in the Kerr formulation, correct?

[00:26:50] Speaker 03:
Correct, Your Honor.

[00:26:52] Speaker 00:
yeah so we haven't an extremely popular widely used preservative uh... and you know the question is that this one straight sentence in in why is that enough to cause a post that it give up on that uh... preservative completely and and the answer uh... that the district court found with no so uh... if there are no further questions on the teach away i'm happy to touch on uh... the other uh...

[00:27:19] Speaker 00:
issues briefly that were... Pardon me.

[00:27:22] Speaker 01:
Excuse me.

[00:27:23] Speaker 01:
I'm going to pause the proceedings.

[00:27:24] Speaker 01:
It looks like Judge Newman has disconnected.

[00:27:40] Speaker 04:
Is everyone on the line?

[00:27:44] Speaker 03:
I'm here.

[00:27:44] Speaker 03:
This is Jennifer.

[00:27:46] Speaker 01:
Everyone appears to be on the line, Judge Newman.

[00:27:49] Speaker 01:
I'm sorry.

[00:27:50] Speaker 04:
OK.

[00:27:50] Speaker 04:
Can we pick up where, if you all heard the click, where I was disconnected?

[00:27:59] Speaker 00:
Your Honor, this is J.C.

[00:28:00] Speaker 00:
Rosendahl.

[00:28:01] Speaker 00:
I'm afraid I didn't hear the click exactly.

[00:28:06] Speaker 04:
Go back a paragraph or so in what you were saying.

[00:28:11] Speaker 00:
Well, I believe we had come to the point

[00:28:16] Speaker 00:
uh... i think we've sort of come to come to closure on the uh... uh... teaching away issue the point being that uh... uh... for for i don't know if you heard judge posts uh... question to me about the district courts uh... discussion of it but my question preceded it and then i think the part i think i heard the time uh... but there go off in terms of your time uh... i'm sorry i didn't hear the buzzer either uh... well then i'll try to be very fast on the other uh...

[00:28:44] Speaker 00:
point forward to finish the point you were making so for uh... secondary addition i think i don't think it is uh... fair or accurate characterize the the district court opinion as improperly shifting the burden to uh... to adapt and we certainly uh... didn't invite the uh... district court uh... to do that i think that what we see in the in the district courts decision uh... regarding

[00:29:14] Speaker 00:
description of the of the legal issue at page eighty eighty eight and eighty nine the heading uh... on page eighty eight is planned to show any secondary considerations of non-obviousness to support patentability sufficient to overcome tevis prima facie showing of obvious mess and so i think it's quite clear that what the district court was doing uh... was uh... dealing with a prima facie case of obvious missing with had not improperly shifted the burden

[00:29:42] Speaker 00:
to the other side to disprove obviousness.

[00:29:46] Speaker 00:
On the substance of the secondary indicia, these are weak indicia.

[00:29:53] Speaker 00:
I think if we take, for example, industry skepticism, the skepticism that it was expressed was not that anyone thought the invention would not work for its intended purpose.

[00:30:04] Speaker 00:
The skepticism was that if you use a high dose of naloxone, you might get an increased incidence of withdrawal symptoms.

[00:30:12] Speaker 00:
Um, but of course that is exactly what happens.

[00:30:16] Speaker 00:
There is a higher dose in the Narcan product and it does have a higher incidence of what's are all symptoms.

[00:30:21] Speaker 00:
And so this is not a situation where the, uh, inventors identified a problem and then found a way to solve it.

[00:30:28] Speaker 00:
Uh, the, the inventors identified a problem and then decided to go ahead and bring up the product anyway.

[00:30:34] Speaker 00:
So that's not the sort of skepticism and indeed the skepticism was from people like police chiefs and not from posters or

[00:30:40] Speaker 00:
formulators, so it's just a very weak basis.

[00:30:43] Speaker 00:
The same thing is true of the copying.

[00:30:45] Speaker 00:
Mundipharma doesn't contain the excipients that are claimed here.

[00:30:50] Speaker 00:
Ezio isn't even an intranasal product.

[00:30:53] Speaker 00:
If they were attempting to copy these companies failed miserably.

[00:30:58] Speaker 00:
The fact that they ended up using a higher dose of naloxone doesn't rise to the level of copying because the patent doesn't cover all four milligram doses of naloxone.

[00:31:07] Speaker 00:
With regard to the long felt but unmet need, it was clear from the testimony at trial that it was a failure to get FDA approval that was the basis for that argument.

[00:31:19] Speaker 00:
We know, however, that the reason why there wasn't an earlier FDA approved product was economic and not technical.

[00:31:28] Speaker 00:
There was evidence put in by ADAPT itself that the economic case for a new naloxone product was dismal

[00:31:35] Speaker 00:
in part because of the difficulty of getting patent protection.

[00:31:38] Speaker 00:
And only after the FDA determined that clinical trials for efficacy and safety would not be needed and that a simpler approval process would be possible, was there interest in the product.

[00:31:49] Speaker 00:
And then as soon as that decision was made, very quickly, products came to the market.

[00:31:54] Speaker 00:
So I think if we look at the totality of the district court's opinion, which was carefully reasoned and contains an awful lot of detailed fact-finding, there's plenty of evidence to support

[00:32:05] Speaker 00:
the finding of non-obviousness, and although ADAPT has tried to dress up its arguments in legal garb, the factual findings carry the day here.

[00:32:15] Speaker 00:
If the court has no further questions, I will conclude.

[00:32:20] Speaker 04:
Okay.

[00:32:20] Speaker 04:
Any more questions for Mr. Rosendahl?

[00:32:24] Speaker 04:
Okay, then Ms.

[00:32:24] Speaker 04:
Stetson, you have your rebuttal time.

[00:32:27] Speaker 02:
Thank you, Judge Newman.

[00:32:28] Speaker 02:
I want to make a few quick points on what Mr. Rosendahl said and didn't say.

[00:32:33] Speaker 02:
The first is when Mr. Rosendahl was offering his complex explanation about why a POSA might not have read WISE at face value, what he said was a POSA wouldn't give up on using BZK.

[00:32:47] Speaker 02:
That, of course, is our point.

[00:32:48] Speaker 02:
That's not the legal standard.

[00:32:50] Speaker 02:
The standard is, did WISE teach away?

[00:32:52] Speaker 02:
And as the PTAB specifically held, it did.

[00:32:56] Speaker 02:
The fact that this district court found older non-data-supported references to trump that was a legal error, not a factual error.

[00:33:06] Speaker 02:
Second, on motivation to combine, I again would urge the court to review the cases that Teva cite because none of them involve the kind of multiplicity of compounds here.

[00:33:20] Speaker 02:
A couple points on that, Appendix 57.

[00:33:23] Speaker 02:
The court talks about the pH adjusting agent.

[00:33:26] Speaker 02:
And the court says, APOSA would have used hydrochloric acid.

[00:33:30] Speaker 02:
But there are at least three pH adjusting agents.

[00:33:33] Speaker 02:
So why hydrochloric acid?

[00:33:35] Speaker 02:
Appendix 58, APOSA would have used sodium chloride because it was a known tonicity agent.

[00:33:41] Speaker 02:
There were several tonicity agents to choose from.

[00:33:44] Speaker 02:
Why sodium chloride?

[00:33:45] Speaker 02:
Appendix 59, BCK is commonly used as a preservative.

[00:33:50] Speaker 02:
There are five different preservatives

[00:33:52] Speaker 02:
disclosed in the prior arc.

[00:33:54] Speaker 02:
YBZK, particularly in light of Ys.

[00:33:58] Speaker 02:
Third and final point is... Counsel, this is Judge Stoll.

[00:34:01] Speaker 05:
I just want to point out that you didn't make these points in your opening argument, and therefore Mr. Rosenthal did not get to address them.

[00:34:08] Speaker 05:
Now, I would have liked to have heard his response if you were going to make these points.

[00:34:14] Speaker 02:
Judge Dole, I apologize.

[00:34:15] Speaker 02:
I did make the point in the opening argument right at the beginning.

[00:34:19] Speaker 05:
You didn't talk about motivation.

[00:34:20] Speaker 05:
You really talked about teaching away.

[00:34:22] Speaker 05:
You didn't talk about these specific points.

[00:34:24] Speaker 05:
Anyway, next time I suggest if you want to make an argument that you make it in your opening and don't wait until the end when opposing counsel has no opportunity to respond.

[00:34:35] Speaker 02:
Understood, Judge Dole.

[00:34:36] Speaker 02:
As I said in my opening,

[00:34:38] Speaker 02:
I would encourage with respect to motivation to combine the court to look at the key cases in TEVA's brief because I think in the end you will conclude, as I mentioned earlier, that those key cases help us and not TEVA.

[00:34:52] Speaker 02:
With respect finally to the burden shifting, TEVA is wrong, Mr. Rosendahl is wrong that he did not invite the error.

[00:35:01] Speaker 02:
What Appendix 5292 says is that ADAPT bears the burden of proof

[00:35:07] Speaker 02:
on its assertions of secondary indicia.

[00:35:09] Speaker 02:
And this was not just a one-off error.

[00:35:12] Speaker 02:
The court at appendix 90, 91, 92, 95, every time said ADAPT failed to establish, ADAPT failed to carry its burden.

[00:35:24] Speaker 02:
That is the failure with respect to objective considerations.

[00:35:27] Speaker 02:
But again, in the end, what we will come back to is that shortest path to reversal here is that plain teachaway.

[00:35:35] Speaker 02:
Mr. Rosendahl took the first few minutes of his argument today, attempting to explain his way out of the teachaway.

[00:35:42] Speaker 02:
That's what the expert tried to do again below.

[00:35:44] Speaker 02:
It's what the court did below.

[00:35:46] Speaker 02:
But you can't explain your way out of the teachaway, why someone wouldn't nevertheless be deterred.

[00:35:53] Speaker 02:
This teachaway, as the PTAB found says, wise says, this is unacceptable.

[00:35:59] Speaker 02:
Full stop.

[00:35:59] Speaker 02:
That should be the most straightforward path to reversal for this court, if there are no further questions.

[00:36:05] Speaker 04:
Any more questions?

[00:36:08] Speaker 04:
All right.

[00:36:09] Speaker 04:
Thank you.

[00:36:10] Speaker 04:
Thanks to counsel for both sides.

[00:36:13] Speaker 04:
The case is taken under submission.

[00:36:15] Speaker 04:
And that concludes this panel's argument schedule for this morning.