[00:00:32] Speaker 00:
Next case is Purdue Pharmaceutical versus Octavis Elizabeth, 2015, 1659.

[00:00:41] Speaker 00:
When you're ready, Mr. Sipes.

[00:00:46] Speaker 01:
Thank you, Your Honors, and Happy New Year.

[00:00:48] Speaker 01:
Christopher Sipes here on behalf of the appellants.

[00:00:52] Speaker 01:
The inventors here did exactly what the patent law is designed to encourage.

[00:00:58] Speaker 01:
They developed a new and better way of treating a disorder, middle of the night insomnia.

[00:01:03] Speaker 01:
by giving patients suffering from the disorder both less drug and giving it less frequently.

[00:01:09] Speaker 01:
This was a clear departure from the teachings of the prior art.

[00:01:12] Speaker 03:
The court itself found... But you're acting as though we're the trial or a fact here.

[00:01:18] Speaker 03:
We had a bench trial before the district court and the district court found against you.

[00:01:24] Speaker 03:
So what error did the district court make?

[00:01:28] Speaker 01:
The district court made both

[00:01:30] Speaker 01:
errors of law and its handling of the prior art and of the objective conditions, considerations of non-obviousness, and it made clear errors of fact.

[00:01:38] Speaker 01:
And let me start with its handling of the prior art and the legal errors there.

[00:01:42] Speaker 01:
There are two of them that make it clear.

[00:01:44] Speaker 01:
One of the key departures here was the abandonment of non-prophylactic dosing.

[00:01:50] Speaker 01:
That is treating people who wake up in the middle of the night from insomnia, not by giving them drug every night at bedtime,

[00:01:56] Speaker 01:
by treating them with drug only in the middle of the night and in a way that avoided problems in the morning.

[00:02:01] Speaker 00:
But if someone has no trouble falling asleep, it doesn't make perfectly good sense that he doesn't need the drug when he's going to bed.

[00:02:13] Speaker 00:
But if he wakes up in the middle of the night, that's when he needs the drug and so it's for a shorter period of time.

[00:02:19] Speaker 00:
So it's a lower dose.

[00:02:20] Speaker 00:
Why isn't that

[00:02:21] Speaker 00:
Very clearly.

[00:02:22] Speaker 01:
That's the exact opposite of the teachings of the prior art, and it's exactly that after the fact common sense.

[00:02:28] Speaker 03:
Opposite of the teachings of the prior art?

[00:02:29] Speaker 01:
But the prior art taught, and the court recognized this at page A81, page 71 of his opinion, that the prevailing approach for treating middle of the night insomnia

[00:02:39] Speaker 01:
was dosing people at nighttime and trying to keep them asleep.

[00:02:44] Speaker 01:
And if they woke up, give an extra dose.

[00:02:46] Speaker 01:
They treated it with more drug in the middle of the night.

[00:02:49] Speaker 01:
There's reasons for that.

[00:02:50] Speaker 01:
As the court recognized, the drive to sleep is much greater at bedtime than it is in the middle of the night.

[00:02:55] Speaker 03:
There were prior art studies which showed that even if you gave it to somebody in the morning, it caused them to go to sleep.

[00:03:00] Speaker 01:
Actually, the Kim study, actually, Your Honor, was a sedation study.

[00:03:04] Speaker 01:
It found that the patients were not allowed to go to sleep.

[00:03:07] Speaker 01:
In those studies, they were found to be

[00:03:09] Speaker 03:
Sedate but More to the point there was extensive art that Discussed how much was needed and that are taught away, but there's a more important point there was your own art taught that you were all you're talking about Ross and Vogel and correct that the show Ross didn't do a statistical analysis on the five milligram treatment and and

[00:03:39] Speaker 03:
Vogel seems to say that the five milligram treatment was effective in getting people to go to sleep.

[00:03:46] Speaker 01:
Vogel says specifically that statistical differences was only seen at seven and a half and above.

[00:03:51] Speaker 01:
And Roth, if you look at the error bars, shows that the placebo in five milligram overlapped.

[00:03:58] Speaker 01:
And those were big studies.

[00:04:00] Speaker 01:
Those were studies of over 200, over 400 patients.

[00:04:02] Speaker 01:
Roth was 400.

[00:04:04] Speaker 01:
the mulati and the kin that they rely on are small.

[00:04:06] Speaker 03:
I don't think your statement about Vogel is accurate.

[00:04:09] Speaker 03:
If you look at 3073, Vogel says over all doses, that is including the five milligram, zodepim significantly improves sleep efficiency on each of the first four consecutive hours of bedtime, but not thereafter.

[00:04:25] Speaker 03:
So, I mean, it does seem to

[00:04:28] Speaker 03:
to work to some extent on all the doses, right?

[00:04:31] Speaker 01:
Well, it did a statistical analysis, Your Honor.

[00:04:33] Speaker 01:
You'll see that there's an indication, this is on A3073, for those that were significantly different from placebo.

[00:04:39] Speaker 01:
The 7.5 has that tilde above an entry, and the 5 milligram does not.

[00:04:45] Speaker 01:
But there's a more fundamental point here, which is there was art that specifically discussed how to use zolpidem to treat middle of the night insomnia.

[00:04:55] Speaker 01:
And that art, for example, was the title bound paper.

[00:04:58] Speaker 01:
that said specifically that you needed to use 10 milligrams at bedtime and at least 5 milligrams at night if they woke up, which is much heavier dosing.

[00:05:07] Speaker 01:
And it even said, and this was recognized, that if that caused problems in the morning, if there were residual side effects, switch to a different drug.

[00:05:15] Speaker 01:
It taught away from using Zolpidem A non-provolactically and B in lower doses.

[00:05:22] Speaker 01:
And similarly, the art the court relied on, Delgramji, Danju, and Hindmarch,

[00:05:28] Speaker 01:
They, too, said that Zolpidem was not suitable.

[00:05:31] Speaker 01:
Doug Ramsey looked at both Zolpidem and Zalopon, a different drug, and said only Zalopon appears to be suited for middle of the night administration.

[00:05:40] Speaker 01:
This isn't 2000.

[00:05:40] Speaker 01:
This isn't past.

[00:05:41] Speaker 03:
But the district court relied on studies which supported what it said.

[00:05:46] Speaker 03:
And why is that clearly wrong?

[00:05:50] Speaker 03:
It may be that you put in contrary evidence, but the district court

[00:05:55] Speaker 03:
said it considered all of this evidence and had reached out, made a finding, an underlying finding of fact with respect to the obviousness question.

[00:06:04] Speaker 03:
How should we set that aside when there's evidence to support it?

[00:06:08] Speaker 01:
You know, the court at A99 said specifically it's reliant for non-prophylactic dosing.

[00:06:13] Speaker 01:
It said non-prophylactic dosing, it claims 1 in 12 of the 131 patent are obvious based on Delgramji, Danju, and Hindmarch, as well as the nature of middle of the night insomnia.

[00:06:24] Speaker 01:
That's what it was reasoning for non-prophylactic dosing.

[00:06:28] Speaker 01:
Well, Dogramji, Danju, and Hindmarch specifically say zolpidem is not suitable for middle-of-the-night dosing.

[00:06:36] Speaker 01:
So it was relying on the prior art that taught a way.

[00:06:39] Speaker 01:
You said it's not suitable.

[00:06:41] Speaker 01:
Where did that say it's not suitable?

[00:06:42] Speaker 01:
Dogramji, at A3002, looked at both zolpidem and xaloplan and said only xaloplan appears to be suited for middle-of-the-night administration.

[00:06:54] Speaker 01:
So this is just like the Eli Liddick case and the St.

[00:06:57] Speaker 01:
Paris case, where the prior looked at the option and another option and said only the other option, the unclaimed option, a different drug was suitable.

[00:07:05] Speaker 01:
Their own expert, Winkleman, admitted.

[00:07:07] Speaker 03:
What page is that?

[00:07:08] Speaker 01:
That's A 3002.

[00:07:10] Speaker 01:
That's the Gramsci.

[00:07:12] Speaker 01:
It reads, only Zalpon appears to be suited for middle of the night administration.

[00:07:17] Speaker 01:
This is the art the district court relied on.

[00:07:20] Speaker 01:
Their own expert.

[00:07:21] Speaker 01:
Dr. Winkelman testified, this is at A-1601, test one at 7.188 through 8.9, the conclusions, talking about this art, Del Rangy and Danju, the conclusions were that if you wanted to choose a drug to use in the middle of the night for insomnia, that you would use Xalaplan and that you would not use Zolpidem.

[00:07:43] Speaker 01:
So the very art at A-99 that the district court relied on to find it obvious to use Zolpidem non-prophylactically,

[00:07:51] Speaker 01:
said specifically, only zalaclan is suitable for that use, not zolpidem.

[00:07:57] Speaker 01:
So it relied on what they taught away without properly considering the teaching away.

[00:08:01] Speaker 01:
And it relied on what they called the nature of middle of the night.

[00:08:04] Speaker 01:
That's the classic hindsight error of looking at something after the fact and saying, well, it's common sense.

[00:08:11] Speaker 01:
It must be obvious.

[00:08:12] Speaker 01:
We know it's not common sense.

[00:08:14] Speaker 01:
Because Tidelbaum specifically says, use more.

[00:08:17] Speaker 01:
This is the only art that specifically discusses how to use zolpidem.

[00:08:21] Speaker 01:
in the middle of the night.

[00:08:23] Speaker 01:
And that art, the Teitelbaum article says specifically, use 10 at bedtime and then add five more in the middle of the night.

[00:08:32] Speaker 01:
Again, they're all an expert in mid.

[00:08:33] Speaker 01:
That's what Teitelbaum teaches.

[00:08:35] Speaker 01:
And it also says, which is very striking, that if you're having problems with the residual side effects, switch to xalapalm.

[00:08:43] Speaker 01:
So this, too, directly teaches away from what the court thought was common sense.

[00:08:49] Speaker 01:
And there's a reason for that because, of course, it's not common sense.

[00:08:52] Speaker 01:
It's only common sense now that the inventors have made their invention.

[00:08:56] Speaker 01:
Now it's common sense to go to lower doses.

[00:08:59] Speaker 01:
The FDA didn't find it common sense because they, after the invention here, after the inventors had done the clinical studies and submitted the data showing that the low doses worked, they changed the dosing not just for permitting this drug, Intermezzo,

[00:09:19] Speaker 01:
but for all the other zolpidem containing drug products, including Ambien, which had been around for more than a decade before this invention.

[00:09:28] Speaker 01:
And that's at A4031 to 32.

[00:09:31] Speaker 01:
And again, their expert at A1705, at page 8174, lines 18 to 21, admitted, after reviewing the intermeso studies, which in that article at A431 to 32, FDA said were particularly informative.

[00:09:45] Speaker 01:
They reduced the dosing for a drug that had been around

[00:09:48] Speaker 01:
for more than a decade before this invention.

[00:09:50] Speaker 01:
And in fact, further demonstrating the mishandling of the art here and the temptation of hindsight, Ambien CR was developed and approved.

[00:10:00] Speaker 03:
What's the significance here of the fact that physicians were prescribing half a dose for middle of the night insomnia?

[00:10:13] Speaker 03:
Is that itself evidence?

[00:10:17] Speaker 03:
That relates to the question of obviousness?

[00:10:21] Speaker 01:
So the district court made no finding of prior use of non-prophylactic fractional ambient.

[00:10:27] Speaker 03:
Well, they made a finding that doctors had done it before 2004.

[00:10:33] Speaker 01:
The finding actually is, while it is unclear how common the practice was, if it's A20 to 21, at least some doctors were prescribing fractional half of one ambient to treat mildenite insomnia prior to the other one.

[00:10:45] Speaker 01:
The problem with that is that's not necessarily

[00:10:48] Speaker 01:
non-prophylactic.

[00:10:49] Speaker 01:
In fact, TITOBIOL, the art we're talking about, teaches fractional dose on top of the original dose.

[00:10:58] Speaker 03:
What's the significance of that finding that doctors were doing this before 2004?

[00:11:04] Speaker 01:
I think it shows that the prior art was teaching away, because that's extras openin, not less openin.

[00:11:10] Speaker 01:
In fact, their expert said the analogy to that... I thought that the

[00:11:16] Speaker 03:
testimony the district court relied on talked about middle of the night dosing.

[00:11:20] Speaker 01:
So there's two sensitive, all of this is post art.

[00:11:24] Speaker 01:
So there's two things there is that December 2008 study of prescribing habits and of course title on professional that's A2509.

[00:11:33] Speaker 01:
Some doctors instruct patients to cut the amputee in half and take a second only before 3 a.m.

[00:11:39] Speaker 01:
And at A, 1795, that's Dr. Williams' testimony, at 966 to 67.

[00:11:44] Speaker 03:
But his doctor, the class who was one of your witnesses, testified that this was done.

[00:11:52] Speaker 03:
And then Winkleman also testified that it was done by physicians, right?

[00:11:57] Speaker 01:
In fact, the only description of non-prophylactic dosing before the invention here is the testimony in court of Dr. Winkleman that he said he did it.

[00:12:08] Speaker 01:
Now, he also admitted, and this is an ace.

[00:12:10] Speaker 03:
Where does Dr. O'Classon say that he's talking about middle of the night dosing after a previous prophylactic dosing?

[00:12:18] Speaker 01:
So Dr. O'Classon was actually an executive at the company.

[00:12:22] Speaker 01:
He was not a doctor prescribing it.

[00:12:24] Speaker 03:
He said he'd heard about this.

[00:12:26] Speaker 03:
He heard about people doing this.

[00:12:28] Speaker 01:
He was referring to 2004, right?

[00:12:31] Speaker 01:
What he said, and this is referring to, was, for example, in 2008,

[00:12:36] Speaker 01:
The company did a survey of what doctors are doing.

[00:12:39] Speaker 01:
That's what I referred to at A25.

[00:12:40] Speaker 03:
Well, I'm talking about his testimony.

[00:12:42] Speaker 03:
I think it's 1140.

[00:12:43] Speaker 03:
He says, when you began working on Intermezzo, you were aware that physicians were filling ambient pills to treat middle-of-the-night insomnia correct.

[00:12:52] Speaker 03:
And then he says, only in the most anecdotal fashion.

[00:12:56] Speaker 03:
So he appears to be admitting that this had happened, right?

[00:12:59] Speaker 03:
He had received reports that it had happened.

[00:13:01] Speaker 01:
So what he's talking about is the marketing survey, I think in December 2008,

[00:13:06] Speaker 01:
that they were given fractional doses.

[00:13:08] Speaker 01:
But that study showing that they were given fractional doses, this is at A2509, as a second dose on top of bedtime.

[00:13:15] Speaker 01:
And at A1795, that's confirmed.

[00:13:19] Speaker 01:
The only testimony of a non-prophylactic before was the in-court testimony of their expert, Dr. Winkleman.

[00:13:28] Speaker 01:
And he admitted there's no corroboration, no lecture notes.

[00:13:32] Speaker 01:
No CLE notes, no patient notes, nothing to corroborate that.

[00:13:37] Speaker 01:
And in fact, he admitted that his own publications throughout this period taught the reverse.

[00:13:43] Speaker 01:
For example.

[00:13:44] Speaker 00:
Mr. Sipes, you're well into your rebuttal time.

[00:13:46] Speaker 00:
I assume you'd like to reserve it.

[00:13:48] Speaker 01:
I would like to reserve it.

[00:13:50] Speaker 01:
I just want to note that there was no finding by the court about fractional use non-prophylaxis.

[00:13:54] Speaker 01:
Thank you, Your Honor.

[00:13:56] Speaker 00:
Mr. Holdree?

[00:13:57] Speaker 01:
Yes, sir.

[00:14:03] Speaker 02:
Thank you, and may it please the court, I will be presenting the appellee's argument for all of the appellees today.

[00:14:10] Speaker 02:
As the court observed, there was an extensive trial in this case, and the trial judge was very diligent in considering all of the disputes raised in appellant's brief.

[00:14:21] Speaker 02:
There was substantial evidence presented by over a dozen witnesses on invalidity, and the trial judge had a basis for each of the findings that he made in this case.

[00:14:34] Speaker 02:
The appellants essentially seek to retry the issues that were tried at the trial court in detail.

[00:14:44] Speaker 02:
To address a couple of questions of the court just now, Mr. O'Classen made clear that he was aware of as-needed or non-prophylactic dosing prior to the critical date.

[00:14:56] Speaker 02:
It's at A1147.

[00:15:01] Speaker 02:
volume 2 of the trial transcript at page 82.

[00:15:04] Speaker 02:
And he was asked at line 10, this is a study that attempts to quantify the practice of specifically splitting ambient doses with an instruction to take the split ambient on an as-needed basis at the time of awakening.

[00:15:24] Speaker 02:
And he says yes.

[00:15:24] Speaker 02:
And then the question was,

[00:15:26] Speaker 02:
Although you quantified this in 2008, you knew what was going on in 2004 when you started the project, anecdotally.

[00:15:34] Speaker 02:
And he says only anecdotally, only as a possibility.

[00:15:37] Speaker 02:
Dr. Winkleman further testified at Appendix 1666, which is Volume 8 of the trial transcript.

[00:15:49] Speaker 02:
And on page 19,

[00:15:51] Speaker 02:
He was asked, you yourself used fractional Ambien to treat patients for middle of the night insomnia without prophylactic dosing.

[00:16:00] Speaker 02:
And he says, absolutely, for years.

[00:16:03] Speaker 02:
And he was asked, and you used less than five milligrams.

[00:16:06] Speaker 02:
And he said, I did.

[00:16:06] Speaker 02:
And those people were five, where I suspected that five milligrams was too much.

[00:16:11] Speaker 02:
And he continues.

[00:16:12] Speaker 02:
We've cited in our briefs further testimony of Dr. Winkelmann on that subject.

[00:16:16] Speaker 02:
I think the significance of that testimony is both that there was prior use,

[00:16:21] Speaker 02:
low-dose fractional ambient as needed in the middle of the night, admittedly is an oral swallow.

[00:16:28] Speaker 02:
So it could be prior art.

[00:16:30] Speaker 02:
The trial court considered it only for what it was worth.

[00:16:34] Speaker 02:
I think it also is a secondary consideration showing simultaneous invention at the very least.

[00:16:42] Speaker 02:
The prior art was also very clear that low-dose insulinum was effective to put people to sleep.

[00:16:47] Speaker 02:
That's the Kim study.

[00:16:49] Speaker 02:
that the court just noted.

[00:16:51] Speaker 02:
Kim is found in the record at A2733.

[00:16:57] Speaker 02:
And Kim's explicit conclusion was that when zolpinum 5 milligram and zolpinum 10 milligram treatments, these were oral swallow, were compared to placebo and to each other, a significant reduction in sleep latency on the first four tests was found.

[00:17:19] Speaker 02:
So there was certainly explicit prior art which explicitly taught that low doses were effective to put people to sleep.

[00:17:27] Speaker 02:
And one of the critical issues of the trial court was that the 10 milligrams ultimatum, the larger dose, was prescribed to keep people asleep all night.

[00:17:37] Speaker 02:
It wasn't that there was a belief that that higher amount was necessary to get people to sleep.

[00:17:43] Speaker 02:
So the trial court had to resolve the evidence which showed that higher dose ultimatum was necessary for all night sleep.

[00:17:50] Speaker 02:
There was no belief that lower dose would not work to get people to sleep.

[00:17:54] Speaker 02:
In fact, the prior explicitly taught that it would.

[00:17:56] Speaker 02:
There was also the Merlotti study for that proposition.

[00:18:00] Speaker 02:
On the subject of teaching away, the Dog-Ramji reference in particular is very clear that that investigator was investigating the side effects of the commercially recommended 10-milligram dose of Zolpidum and Zaloplan.

[00:18:19] Speaker 02:
The only thing that he taught was that 10 milligrams was too much because there were residual sedative effects.

[00:18:26] Speaker 02:
There was extensive testimony we've cited in our briefs that the teaching of Dogramji, Hindmarch, and Danju would teach one of skill in the art that 10 milligrams of zolpidum in the middle of the night is too much, and that one of skill would therefore reduce the dose.

[00:18:41] Speaker 02:
And that is a fact finding the trial court made.

[00:18:44] Speaker 02:
how one of skill and the art understood the references and whether they were teaching away are factual conclusions that were supported by evidence in the record.

[00:18:51] Speaker 02:
And so whether or not a different fact finder might reach a different conclusion, that is the conclusion the trial court reached, and it was well supported.

[00:18:59] Speaker 02:
Unless the court has other questions, we will rest on our briefs for the remainder.

[00:19:06] Speaker 00:
What about the freedom from residual effects?

[00:19:09] Speaker 02:
So that was well understood, and the Merlotti study is one of the references that is most clear.

[00:19:15] Speaker 02:
That was acknowledged as one of the most significant pieces of prior art.

[00:19:20] Speaker 02:
It's found in the record at A2275.

[00:19:23] Speaker 02:
And one of the first things that Merlotti says is that artisans working in the field understood it's important to find the lowest effective dose, and that is because it should be less likely to produce

[00:19:38] Speaker 02:
adverse effects.

[00:19:40] Speaker 02:
And so the skilled artisan was highly motivated to look for the lowest effective dose.

[00:19:45] Speaker 02:
That's exactly what the Merlotti study did in order to reduce side effects or residual sedative effects.

[00:19:53] Speaker 02:
There was extensive testimony in the record that a skilled artisan would understand how to do a study like Merlotti did in order to find the lowest effective dose.

[00:20:03] Speaker 02:
And that was in fact admitted by

[00:20:07] Speaker 02:
some of the plaintiffs' experts.

[00:20:11] Speaker 02:
In particular, the defense expert, Dr. Michniak Cohen, talks about dose finding at A1480 in Volume 6.

[00:20:24] Speaker 02:
Dr. Winkelman talks about dose finding in, or as you may,

[00:20:37] Speaker 02:
His testimony, the site is in our briefs.

[00:20:38] Speaker 02:
I apologize I'm not finding it right away.

[00:20:40] Speaker 02:
Dr. Drover and Dr. Seisler, who are plaintiff's experts, talked about the understanding and the art of the importance of finding the lowest effective dose in order to avoid residual sedative effects.

[00:20:53] Speaker 02:
And Dr. Seisler is particularly clear on that point at the appendix at 1924 in volume 10 of the trial transcript.

[00:21:02] Speaker 02:
where he says the Food and Drug Administration generally requires anyone coming out with a new drug application to identify the lowest effective dose because that minimizes side effects.

[00:21:13] Speaker 02:
He was asked, do you agree with that?

[00:21:15] Speaker 02:
He said, I agree fully.

[00:21:16] Speaker 02:
And then he discussed the Melati study as an example of how an artisan could do a routine clinical study with every expectation of success to find the lowest effective dose that would avoid residual sedative effects.

[00:21:29] Speaker 00:
Thank you, Mr. Holdree.

[00:21:32] Speaker 00:
Mr. Sipes has two minutes.

[00:21:38] Speaker 01:
Your Honor, very quickly first as to the fractional dose, at 1147, what Mr. O'Classon says, 9-2, is as needed at the time of awakening.

[00:21:48] Speaker 01:
That's not necessarily non-prophylactic.

[00:21:51] Speaker 01:
There's no question that Tadeban teaches, and the pilot were using, 10 milligrams of bedtime, and then as needed, five more if you woke up.

[00:21:59] Speaker 01:
And that's what the 2008 study that's being discussed there found.

[00:22:03] Speaker 01:
What is at issue here is a decision to give a low dose in the middle of the night without bedtime dosing.

[00:22:10] Speaker 01:
And there's nothing in the prior art except Dr. Winkleman's uncorroborated in-court testimony that shows that everything was moving in the opposite direction.

[00:22:20] Speaker 01:
Even title bound teaches that if you're having problems with the residual set of effects, go to a different drug.

[00:22:27] Speaker 01:
It was not believed that zolpidin was suitable

[00:22:30] Speaker 01:
for as needed dosing only, without prophylactic dosing, in the middle of the night.

[00:22:35] Speaker 01:
And the references, and the district court did not rely on prior use.

[00:22:40] Speaker 01:
A99 relied on the art that specifically changes the way, art that post-states this Marlotti paper by a decade.

[00:22:48] Speaker 01:
This is the opposite of the recent Merck case.

[00:22:51] Speaker 01:
This is a case in which

[00:22:52] Speaker 01:
The teaching way is current and present, the present teaching.

[00:22:56] Speaker 01:
A few months after his invention, Sanofi came out with Ambien CR, higher doses to treat middle of the night insomnia.

[00:23:03] Speaker 01:
That's at A1672, page 843, and A1671, page 867.

[00:23:10] Speaker 01:
That's where the art was going.

[00:23:12] Speaker 01:
As to the dose finding, the dose here isn't even five.

[00:23:16] Speaker 01:
The claimed dose is 3.5.

[00:23:19] Speaker 01:
The court at A78 found that obvious, a reasonable expectation of success of 3.5 administered in the middle of the night without any other dosing, dramatically below the 10 milligram approved FDA dose, which we just heard was the lowest effective dose, is what FDA approves, found that by assuming perfection.

[00:23:41] Speaker 01:
One, they had to get down to five milligrams, which we think was clear error, assuming perfection.

[00:23:46] Speaker 01:
in the yard.

[00:23:48] Speaker 01:
The court found that a person with ornate skill in the yard would expect 100% bioavailability through transmucosal.

[00:23:57] Speaker 01:
That's at A89.

[00:23:59] Speaker 00:
Thank you, Mr. Sykes.

[00:24:00] Speaker 00:
As you can see, the red light is on.

[00:24:03] Speaker 00:
So please take the argument and take the case under review.

[00:24:06] Speaker 01:
Thank you.