[00:00:00] Speaker 04:
Hey, good morning.

[00:00:05] Speaker 04:
We have a number of oral arguments this morning, but first order of business are some motions to the court, and first I'd like to turn it over to our colleague Judge Lynn.

[00:00:20] Speaker 02:
Thank you very much.

[00:00:22] Speaker 02:
It is my pleasure this morning to move the admission of Daniel Kazdan.

[00:00:29] Speaker 02:
I know Mr. Kazdan quite well, having worked closely with him for the past year as my law clerk.

[00:00:36] Speaker 02:
I am, based on my first-hand experience with him, I am thoroughly convinced he has all the necessary qualifications and character

[00:00:48] Speaker 02:
to be an outstanding member of this bar.

[00:00:51] Speaker 02:
He's contributed to the work of my chambers and to the work of this court.

[00:00:57] Speaker 02:
And for that reason, I am pleased to formally move the admission of Daniel Kazan, who's a member of the bar and is in good standing with the highest courts of California and the District of Columbia.

[00:01:10] Speaker 02:
I have knowledge of his credentials and am satisfied that he possesses the necessary qualifications.

[00:01:18] Speaker 05:
Yes.

[00:01:20] Speaker 04:
Then it's unanimous.

[00:01:23] Speaker 04:
The motion is granted.

[00:01:24] Speaker 04:
Mr. Kazan, congratulations.

[00:01:27] Speaker 04:
We have one more motion.

[00:01:30] Speaker 04:
Judge Hughes.

[00:01:32] Speaker 03:
I also have an admission for my clerk, Jose Restio, who has been with me for almost two years and started shortly after I did.

[00:01:41] Speaker 03:
So we have almost identical experience at the clerk.

[00:01:47] Speaker 03:
He's been a tremendous clerk for many reasons and has really helped me transition from my former career to the bench.

[00:01:56] Speaker 03:
And so I appreciate everything he's done.

[00:01:59] Speaker 03:
And so I move the admission of Jose M. Marcia, who is a member of the bar and is in good standing with the highest courts of Virginia and the District of Columbia.

[00:02:08] Speaker 03:
I have knowledge of his credentials and am satisfied that he possesses the necessary qualifications.

[00:02:14] Speaker 05:
okay uh... thank you judge you the motion is granted and i congratulate both mister rep you know and it's a top-down uh... people both uh... and and they put the court

[00:02:42] Speaker 02:
Welcome to the bar, welcome.

[00:02:46] Speaker 04:
All right.

[00:02:48] Speaker 04:
We have three patent cases that are going to be argued today.

[00:02:52] Speaker 04:
The first one is appeal number 2014-1838, Avenir Pharmaceuticals Incorporated versus PAR Pharmaceutical Incorporated.

[00:03:03] Speaker 04:
Ms.

[00:03:03] Speaker 04:
Carlin?

[00:03:06] Speaker 04:
You've got to reserve three minutes for rebuttal.

[00:03:08] Speaker 00:
Yes, I'm reserving three minutes, please.

[00:03:10] Speaker 04:
Whenever you're ready.

[00:03:11] Speaker 00:
Good morning.

[00:03:12] Speaker 00:
My name is Jeanine Carlin, and I represent the appellate.

[00:03:16] Speaker 00:
May it please the court.

[00:03:18] Speaker 00:
The central question here today is, is 10 to 30 range less than 150?

[00:03:27] Speaker 00:
The district court found that it is not, and that is clear error.

[00:03:32] Speaker 00:
The district court found that the prior art does not disclose 10 to 30 milligrams of quinidine when the prior art reference of the 053 application discloses an encompassing range of 150 milligrams or less.

[00:03:47] Speaker 04:
Are you referring to claim seven?

[00:03:49] Speaker 00:
We're referring to the disclosure in two places in the 053 application.

[00:03:53] Speaker 00:
It is in claim seven.

[00:03:55] Speaker 00:
and it's also in another location in the reference at appendix 19168-69 where it specifically discloses that the applicant believed that 150 milligrams or less of quinidine would work.

[00:04:12] Speaker 04:
Did it ever suggest that zero quinidine would work?

[00:04:17] Speaker 00:
It suggested a range of less than 150, but of course when the invention or the application is to a combination of

[00:04:25] Speaker 00:
quinidine with dextromethorphan.

[00:04:27] Speaker 00:
So there would be no opportunity to have zero quinidine.

[00:04:31] Speaker 04:
Right.

[00:04:32] Speaker 04:
I'm just trying to remember.

[00:04:33] Speaker 04:
I don't remember anything in the prior art references that specifically said anything below the number of 50 milligrams of quinidine that would be helpful and useful or therapeutically effective for PBA.

[00:04:49] Speaker 04:
So what in the 053 application specifically says something below 50?

[00:04:56] Speaker 00:
In the 053 application, there's a suggestion, a belief, the applicant says that you could go less than 150 milligrams.

[00:05:04] Speaker 00:
And he points to 50 as a such as.

[00:05:06] Speaker 00:
An example, 50.

[00:05:08] Speaker 00:
He doesn't say anywhere, and no prior art says, that 50 is a floor.

[00:05:14] Speaker 00:
No prior art says that you should not go less.

[00:05:17] Speaker 03:
So no prior art specifically says you can go below 50 either, does it?

[00:05:22] Speaker 00:
There are.

[00:05:22] Speaker 00:
Not just the 053 application that has the encompassing range of 150 milligrams or less, but also the Yakatan poster.

[00:05:31] Speaker 00:
Now the Yakatan poster is Avenir's own prior art study that they published before they filed the application.

[00:05:37] Speaker 00:
And within that study there is a chart that shows

[00:05:43] Speaker 00:
A lot of lower doses of quinidine, including doses within the claimed range.

[00:05:49] Speaker 00:
20 milligrams, for example, was able to provide enough section with Thorphan in six out of seven individuals, more than 80%.

[00:05:59] Speaker 04:
And that reference... What part of the Yaktan reference said that?

[00:06:05] Speaker 00:
The reference at A19100 has a chart that explains how you can go lower doses of quinidine.

[00:06:15] Speaker 00:
And within that same reference, there is discussion that the purpose of quinidine, or the goal of the study that they were doing, was to find the minimal amount of quinidine that could sustain therapeutic

[00:06:33] Speaker 00:
level in the blood.

[00:06:34] Speaker 00:
That's again at A19100.

[00:06:37] Speaker 04:
Right, and the judge below determined that, as made a fact finding, that one of ordinary skill in the art at the time this invention was made believed that you needed 100 nanograms per milliliter, or whatever the units were, of the DM in the person's bloodstream, right?

[00:07:00] Speaker 00:
The court made that finding, and it is one of the errors of the court, but when you look at the prior art as a whole, you'll see that that's incorrect.

[00:07:08] Speaker 00:
For example, in the Akatan poster, you see that at that level of 20 milligrams of quinidine, the volunteers, the people who took the drug, had a blood level of something in the 60 percent, 60 nanograms per milliliter range.

[00:07:26] Speaker 00:
And that showed that more than 80% of the folks were able to have enough dexamethorfin in their blood to be therapeutic.

[00:07:33] Speaker 04:
That's assuming that 60 is high enough.

[00:07:37] Speaker 04:
That people of ordinary skill in the art back in 2002 believed that 63 was a high enough amount in the blood.

[00:07:46] Speaker 00:
That's what the prior art shows.

[00:07:47] Speaker 04:
But the district court found otherwise, and now we have to ask ourselves why was that finding clearly erroneous when there seemed to be testimony from all the doctors that testified that people understood at that time that you needed 100 nanograms in the bloodstream.

[00:08:07] Speaker 00:
Well, we do have some of the references.

[00:08:10] Speaker 00:
Some of the sites that the court looked to were Avenue's own subjective belief.

[00:08:15] Speaker 00:
which should not be considered here.

[00:08:18] Speaker 00:
But also, it was based on testimony, first of all, experts did say, far as experts did say, that they would look to the prior art such as the 248 example and also the Yakitan poster, which shows that these blood levels do have an effect.

[00:08:37] Speaker 00:
But the testimony of Avenir's expert

[00:08:42] Speaker 00:
which said, you know, we'd look at 100 nanograms per milliliter is not something that's supported anywhere in the references.

[00:08:50] Speaker 00:
You have one reference, the Smith's abstract, that has a range, an average range, which means it could be less than 100 nanograms per milliliter.

[00:09:00] Speaker 00:
And then you have other prior art, such as the 248 patent and the Yakitan poster showing lower blood levels.

[00:09:05] Speaker 00:
But really, the point here of quinidine is to work

[00:09:12] Speaker 00:
It's not the active ingredient here.

[00:09:14] Speaker 00:
Dextromethorphan is the active ingredient.

[00:09:16] Speaker 00:
And quinidine is what makes the dextromethorphan available.

[00:09:20] Speaker 00:
And you have the teachings of the Akatan poster, which shows even down to five milligrams of quinidine per day.

[00:09:31] Speaker 00:
people were able to get an effect in their blood.

[00:09:35] Speaker 00:
And that, the act hand poster teaches, that's what you're looking for, to be therapeutic.

[00:09:41] Speaker 04:
What if we were to conclude that it was not clearly erroneous for the district court to find that one ordinary skill in the art back in 2002 expected that you needed, the therapeutic amount was 100 nanograms per milliliter in the blood.

[00:09:55] Speaker 04:
Would you lose?

[00:09:56] Speaker 00:
No.

[00:09:58] Speaker 00:
There are two reasons.

[00:09:59] Speaker 00:
One is that under Galderma, looking at the 053 application, you look at whether the range that's claimed is within the encompassing range.

[00:10:11] Speaker 00:
And we have an encompassing range of 150 milligrams or less.

[00:10:16] Speaker 03:
So can you point to me in that pattern where it says that it can be anywhere from 0 to 150?

[00:10:24] Speaker 00:
It's in the 053 application.

[00:10:27] Speaker 00:
It says less than 150 milligrams is believed to work.

[00:10:31] Speaker 03:
But that's not a range.

[00:10:33] Speaker 03:
A range is 10 to 150 or 5 to 150.

[00:10:38] Speaker 03:
Less than 150 isn't the kind of range that Gelder talked about.

[00:10:44] Speaker 00:
It is an encompassing range situation where you have a range of 150 down to an amount that will work, which is not zero.

[00:10:53] Speaker 00:
And claim seven is the same situation.

[00:10:56] Speaker 00:
not to be one hundred fifty what did the district i'm sorry no good what did the district court say about claim seven the district court said nothing about things like that uh... because it wasn't ready it was not the stuff the typical trial the reason is we have the pain disclosure of the one hundred fifty milligram range in another place neoplasia application and we had testimony on it we had a claim chart on it is it the same kind of disclosure though

[00:11:26] Speaker 03:
You know, up to 150 or 150 or less.

[00:11:30] Speaker 00:
It's slightly different language, but it's basically the same concept.

[00:11:34] Speaker 00:
150 milligrams or less liquidity.

[00:11:36] Speaker 03:
It just doesn't seem to me that that's clear enough to actually disclose the range.

[00:11:40] Speaker 03:
I mean, it doesn't say anything about what the lower end is, and it leaves, you know, the public to guess at what might be an effective range.

[00:11:50] Speaker 00:
In this case, you have a range from 150 down to it can't be zero.

[00:11:57] Speaker 00:
And here, we have one of ordinary skill and the art, of course, would know that can't be zero, until your range is something a little closer to zero.

[00:12:05] Speaker 03:
Well, how do you know it can't be?

[00:12:06] Speaker 03:
I mean, we know for this,

[00:12:08] Speaker 03:
particular drug combination it can't be zero because you need the cue to come around.

[00:12:13] Speaker 03:
Exactly.

[00:12:14] Speaker 03:
But I can see if we establish a rule that 150 or less or a number or less is a sufficient range that if somebody you know decides that you don't need the second drug at all that they're going to say 150 or less includes zero and that seems like

[00:12:34] Speaker 03:
You know, it kind of doesn't cabin the way we look at disclosures.

[00:12:39] Speaker 00:
Now in this case, it's taught throughout the O5-3 application and through the other prior art that quinitine, the whole purpose of it, is to make the dextranethorphan available in the blood.

[00:12:51] Speaker 00:
if you didn't have quinidine, and it's taught throughout the department of art, then the dextrinothoracan goes away very quickly.

[00:12:59] Speaker 03:
But to me it sounds like you're saying that then we have to understand the range 150 or less as one would have understood at the time to be what would have been an effective dose.

[00:13:09] Speaker 03:
And at the time, everybody thought that 150 or more was the effective dose.

[00:13:15] Speaker 00:
First, that's not the standard of GALDERMA where you have an encompassing range.

[00:13:20] Speaker 00:
The range is there, and then the claimed range is within it, and then after that, the avenue must come forward with some secondary considerations.

[00:13:29] Speaker 00:
To show that range of 10 to 30,

[00:13:31] Speaker 00:
is critical or special.

[00:13:33] Speaker 04:
Why wouldn't the range in the O5-3 be arguably 50 to 150 when it says in the reference dosages of only 150 milligrams per day are effective in increasing BM concentrations?

[00:13:48] Speaker 04:
And it is believed by the applicant that even lower dosages, parentheticals such as 50 milligrams per day, close parenthetical, will be effective in at least some patients.

[00:14:01] Speaker 04:
You know, it's a little equivocal about the 50 number, but it suggests that maybe 50 is going to work for some people.

[00:14:09] Speaker 00:
The absent believed, that strong language, that 150 milligrams less than that would work in patients.

[00:14:18] Speaker 00:
Such as 50 is an example, but it is not a floor.

[00:14:22] Speaker 00:
And nowhere in the reference is there any suggestion that there is a floor, that there is a 50 is it, or that you can't go lower.

[00:14:30] Speaker 02:
And so under GALDERMA, I mean, it's certainly... But there's no suggestion in the reference either that things less than 50 might be expected to work.

[00:14:40] Speaker 00:
The suggestion is within the language of applicant believed this would work in its arrange.

[00:14:46] Speaker 02:
But again, under the GALDERMA framework... But applicant believed that 50 would work.

[00:14:50] Speaker 00:
I'm sorry?

[00:14:51] Speaker 02:
Applicant believed that 50 would work.

[00:14:53] Speaker 00:
Applicant believed that 150 or less would work, and 50 was an example, such as 50.

[00:15:00] Speaker 00:
There's nowhere else in the reference.

[00:15:01] Speaker 02:
But there's nothing to suggest anything below 50.

[00:15:04] Speaker 00:
There is.

[00:15:04] Speaker 00:
Other than less than.

[00:15:06] Speaker 00:
The ranges themselves, yes.

[00:15:08] Speaker 02:
So you think the reference teaches, obviously it teaches more than zero.

[00:15:13] Speaker 00:
It teaches more than zero, yes.

[00:15:15] Speaker 02:
One?

[00:15:16] Speaker 00:
It could be one, and I'm in my rebuttal time.

[00:15:19] Speaker 02:
Could be one, really.

[00:15:21] Speaker 01:
uh... okay uh... here from the other side mister serrano didn't get my pronouncement yes you're going to think about that may please the court on the street or women who are going to hold on behalf of them your honor's went right to the point or fifty three

[00:15:41] Speaker 01:
discloses at best 50 mgs per day of quantity.

[00:15:46] Speaker 01:
How do we know that?

[00:15:48] Speaker 01:
Every expert in this case stated that.

[00:15:50] Speaker 01:
Not just Avenue's experts, Hart's experts.

[00:15:52] Speaker 01:
They certainly could have looked at Claim 7 and said other words.

[00:15:55] Speaker 01:
They chose not to.

[00:15:56] Speaker 01:
They could have looked at the disclosure of 053 application and said other words.

[00:16:01] Speaker 01:
They chose not to.

[00:16:02] Speaker 01:
The court's finding on this is therefore not clearly erroneous.

[00:16:05] Speaker 01:
It hasn't been challenged.

[00:16:06] Speaker 01:
Their own experts, time and time again, Dr. Paulson said, and I quote, Joe 53 Applicate teaches that dose is lower than 150, and it's speculated that even maybe, even maybe, down to 50 milligrams a day will likely be effective.

[00:16:22] Speaker 01:
Never said anything less than that.

[00:16:25] Speaker 01:
And they had the opportunity, and they failed to do so.

[00:16:27] Speaker 01:
Notwithstanding the fact that Claim 7, of course, was not discussed at all below.

[00:16:31] Speaker 01:
not a single word of testimony from any party on that claim.

[00:16:35] Speaker 01:
Again, I assume when their experts reviewed that reference, they reviewed the entire reference, and for what it disclosed, they said 50 milligrams a day.

[00:16:43] Speaker 01:
With regard to the Yakutown poster that was pointed out by me,

[00:16:47] Speaker 01:
adversary uh... yet to have posted a pk study has no efficacy data we heard the word applications effective quite a few times had nothing to do with treating pb simply to determine how much of the drug would get into the blood at various levels but people knew at the time that converting people to an effective metabolizer to a poor metabolizer was a key element to

[00:17:13] Speaker 04:
having therapeutic efficacy with DM, right?

[00:17:17] Speaker 01:
I don't mean to bicker with the word, Your Honor.

[00:17:20] Speaker 01:
Key element, it was an element, but it showed nothing as to efficacy.

[00:17:25] Speaker 04:
If you were an effective metabolizer, then you were very unlikely to be getting an effective treatment of DM, right?

[00:17:33] Speaker 01:
I would agree with the word unlikely, yes.

[00:17:35] Speaker 04:
Okay, so, and then the Yakatan reference does talk about one place, one data point about

[00:17:42] Speaker 04:
how 20 milligrams of Q, quinidine, was sufficient to convert several people from an effective metabolizer to a poor metabolizer.

[00:17:52] Speaker 04:
That's correct.

[00:17:53] Speaker 04:
Thereby creating a pathway for the DM dosage to go straight to the bloodstream.

[00:17:59] Speaker 01:
Yes, sir.

[00:18:00] Speaker 04:
That would be the logical conclusion once you become a poor metabolizer, right?

[00:18:05] Speaker 01:
But it says nothing about efficacy, whether that will work to treat it.

[00:18:09] Speaker 01:
Certainly at the levels discovered at that 20 McDo's, there's no evidence.

[00:18:14] Speaker 01:
And again, PARS experts never said at the time, persons who are looking at that evidence would have concluded that this would have been an efficacious treatment.

[00:18:23] Speaker 01:
In fact, they went further.

[00:18:25] Speaker 01:
They said that there's no correlation, no PK, how much drug is in your blood, PD correlation.

[00:18:32] Speaker 01:
PD is whether it's efficacious or not.

[00:18:34] Speaker 01:
They're experts-testified.

[00:18:35] Speaker 01:
There's no correlation whatsoever.

[00:18:37] Speaker 01:
So a PK study is nice, and you can learn some data from it, but it says nothing about efficacy.

[00:18:42] Speaker 01:
And let's look what happened in the real world.

[00:18:43] Speaker 03:
Even if we could extrapolate from that study to disclose a range, given that this is a factual finding and there's other evidence going the other way, would that make it clearly erroneous?

[00:19:00] Speaker 03:
I didn't phrase that very clearly.

[00:19:02] Speaker 03:
Let's assume the Yakatan art shows the range sought, or at least elucidating the range shot.

[00:19:14] Speaker 01:
Does that make the district court's factual finding clearly erroneous?

[00:19:17] Speaker 01:
Absolutely not, Your Honor.

[00:19:19] Speaker 01:
The findings that have not been challenged ultimately was that you needed 100 nanograms per milliliter to get efficacious treatment.

[00:19:27] Speaker 01:
And what we look at with regard to the XM posters, I believe the number is 63, I think was the actual number.

[00:19:33] Speaker 01:
If you look at each and every other piece of data that you have from the Smith abstract when they actually dosed patients to see efficacious treatment, all 12 of those patients had more than 100 nanograms per milliliter.

[00:19:46] Speaker 01:
So that's what the art talked about, and that's what the judge found.

[00:19:51] Speaker 04:
Then there's the example 2 of the O248 patent, right?

[00:19:54] Speaker 04:
Where there was a patient that had something less than 60, something like 50 nanograms, and it appeared to work for that particular patient.

[00:20:06] Speaker 01:
Yes, that was the person's allegation.

[00:20:09] Speaker 04:
So isn't that an indicator that you don't need 100 nanograms in the blood?

[00:20:14] Speaker 04:
No, Your Honor.

[00:20:15] Speaker 04:
50 would work, because it actually did work?

[00:20:19] Speaker 01:
Well, what actually did work was a dose of 60-150.

[00:20:22] Speaker 01:
So a maximum inhibiting dose of 50.

[00:20:25] Speaker 04:
Yeah, I'm not talking about the dosage.

[00:20:26] Speaker 04:
I'm talking about the amount that's in the blood.

[00:20:29] Speaker 01:
So, Your Honor, there were findings back on that as well, which remain unchallenged and not shown to be clearly erroneous.

[00:20:34] Speaker 01:
Those findings were that that particular example was discredited.

[00:20:38] Speaker 01:
That one skill in the art would not rely on it because of the faults in the example.

[00:20:42] Speaker 01:
Also, the district court found that you wouldn't just look at that one example and ignore all the rest of the evidence, including other evidence that was supplied in the 248 reference, for example, example three.

[00:20:54] Speaker 01:
Example three, the next example shows much higher blood levels.

[00:20:58] Speaker 01:
that was also found, by finding a fact by the judge, an expert testimony that was much more reliable, because it took out placebo effect, all the other issues that we had with example two were not present in example three.

[00:21:11] Speaker 04:
What were those other problems?

[00:21:13] Speaker 04:
I mean, we're talking about two examples in the same patent.

[00:21:17] Speaker 04:
One something that we should just kick to the curb, and the other one is terrific, and we should embrace it.

[00:21:22] Speaker 01:
Your Honor, there was expert testimony concerning example three where they started and stopped the patient's treatment.

[00:21:30] Speaker 01:
Not my testimony, the expert's testimony, that that takes out the placebo effect of the potential of the drug.

[00:21:35] Speaker 01:
That was credited by the district court over the objections of PARS experts.

[00:21:40] Speaker 01:
That's a finding that hasn't been disputed and is not clearly erroneous.

[00:21:43] Speaker 01:
When it comes to the actual example itself, example two, remember these are case studies, so they're not run exactly the same way.

[00:21:50] Speaker 01:
It's two different patients treated two different ways.

[00:21:52] Speaker 01:
They court found, example two does not disclose, when the blood samples were drawn, or how or where they were stored, where the patient had reached a steady state level of DM, and even if he had, whether his blood levels were measured at C max or trough levels.

[00:22:07] Speaker 01:
And the patient's medical history of pre-dosing.

[00:22:10] Speaker 01:
So there were findings that were undisturbed by Paul.

[00:22:12] Speaker 04:
Did we have all that information for the patient in example three?

[00:22:14] Speaker 01:
We have more of that information for example three.

[00:22:17] Speaker 01:
Again.

[00:22:17] Speaker 01:
Some of it.

[00:22:18] Speaker 01:
Not all of it.

[00:22:18] Speaker 01:
Yes, sir.

[00:22:19] Speaker 01:
Well, let's not just talk about example three.

[00:22:21] Speaker 01:
Let's talk about all the other ones, because once in the art we're presumed to have looked at all the others.

[00:22:24] Speaker 01:
And you have to look at the Smith abstract also.

[00:22:26] Speaker 01:
That is,

[00:22:27] Speaker 01:
12 patients who showed efficacious treatment.

[00:22:30] Speaker 01:
All 12 patients had over 100 nanograms per milliliter.

[00:22:34] Speaker 01:
So if you want to talk about just efficacy, you have a total population of efficacy of 14 patients, 13 of which had over 100 nanograms per milliliter.

[00:22:43] Speaker 01:
The court found, as the experts specified, one skill in the art would look to the weight of the evidence.

[00:22:48] Speaker 01:
They wouldn't take the one over the 13.

[00:22:50] Speaker 01:
It would make no sense.

[00:22:52] Speaker 01:
In common sense, I know it creeps into these once in a while, but that makes sense even to me.

[00:22:57] Speaker 01:
So, at the end of the day, the Akatan poster was nothing more than a P.K.

[00:23:01] Speaker 01:
study.

[00:23:01] Speaker 01:
And if we want to talk about the real world experience, Your Honor, what was done with that Akatan evidence in the 20 minutes?

[00:23:09] Speaker 01:
It wasn't carried forward into the clinic.

[00:23:11] Speaker 01:
It was rejected.

[00:23:12] Speaker 01:
What they carried forward in the clinic was a 60-60 dose, the 60 being also a maximum inhibiting dose.

[00:23:19] Speaker 01:
Why?

[00:23:20] Speaker 01:
Because again, to get the higher blood levels.

[00:23:22] Speaker 01:
So the real world showed that the 60-20 didn't play a part of going forward.

[00:23:27] Speaker 01:
It was a data point that didn't factor going forward with regard to clinical work.

[00:23:35] Speaker 04:
Just so I understand your invention, which is using 40-20 or 20-10

[00:23:42] Speaker 04:
You're not suggesting you get a better therapeutic effect with those lower doses than 6150, right?

[00:23:51] Speaker 04:
The invention is the discovery that a lower dosage

[00:23:58] Speaker 04:
gets you the equivalent therapeutic?

[00:24:01] Speaker 01:
The word that was used by the answer was comparable.

[00:24:03] Speaker 01:
Comparable.

[00:24:04] Speaker 01:
Comparable efficacy.

[00:24:05] Speaker 01:
But it's not just our invention.

[00:24:07] Speaker 01:
It's comparable efficacy with better safety results.

[00:24:10] Speaker 01:
And also it's treating the entire claim elements, we're treating PVA at those particular dosages at a particular weight to weight ratio, which we've heard nothing from the comments about weight to weight ratios because that appears nowhere in the art.

[00:24:24] Speaker 01:
Those particular ratios don't appear.

[00:24:26] Speaker 01:
And so the comparable efficacy was achieved at submaximally inhibiting doses, which was surprising, and better safety.

[00:24:36] Speaker 01:
The better safety came in that if you metabolize the DM2 quickly, it produces a metabolic byproduct called dextor fat.

[00:24:44] Speaker 01:
We used DX for short.

[00:24:46] Speaker 01:
And that was a problem.

[00:24:47] Speaker 01:
The more dexorphine you had accumulating, the bigger problem side effects you had.

[00:24:51] Speaker 01:
By doing it this way, we were surprised to find that you didn't have that accumulation, that you weren't getting those side effects.

[00:24:56] Speaker 01:
So it's a multi-phase approach as to not just comparable efficacy, but also improved safety.

[00:25:04] Speaker 01:
With regard to Galderma, I think it's quite clear that there is no range case here because there is no range that encompasses our invention.

[00:25:13] Speaker 01:
There's just simply no number in any pattern, any prior disclosure, encompassing the claimed dosage range.

[00:25:20] Speaker 01:
When you look at the reference, DOE 53 reference in particular, the word less than was used a number of times.

[00:25:26] Speaker 01:
The words less than never appear in the claim or in the disclosure.

[00:25:30] Speaker 01:
The claim talks about not exceeding and some of the other quotations that were referred to talk about that perhaps a lower DOE such as 50 will be used, but it never says less than.

[00:25:43] Speaker 01:
And again, Your Honor, the despicable evidence here, unchallenged evidence here, by all experts, is that at best, that disclosure goes down to 50.

[00:25:51] Speaker 01:
It doesn't go below that.

[00:25:52] Speaker 01:
Therefore, we do not have an accomplishing range.

[00:25:54] Speaker 01:
Therefore, gel derma does not apply.

[00:26:03] Speaker 01:
Your Honor, at the end of the day, this is a six-day bench trial.

[00:26:07] Speaker 01:
The district court issued a 63-page opinion analyzing all the evidence presented at the trial, including both the credibility experts presented by both sides.

[00:26:15] Speaker 01:
The district court held that Carr failed to show by clear convincing evidence that either the 053 application or the priority as a whole renders the 282 and 484 patents obvious.

[00:26:26] Speaker 01:
Par failed to show that there was a problem to be solved below.

[00:26:30] Speaker 01:
As Your Honor pointed out, there was a 6150 formulation already existed.

[00:26:33] Speaker 01:
Worked fine.

[00:26:34] Speaker 01:
There was no problem that had to be solved.

[00:26:36] Speaker 01:
also failed to show there was any motivation to combine or modify the prior in the way that it suggests.

[00:26:42] Speaker 01:
The reality is, Parr's entire case below was about the use of hindsight.

[00:26:46] Speaker 01:
That's the only way you can look at example two and say, that's something I should be worried about.

[00:26:51] Speaker 01:
That's the only way, because you have to try to retrofit that example into the invention you know that already exists.

[00:26:57] Speaker 01:
That's called hindsight.

[00:27:00] Speaker 01:
Parr seeks to do over here, if you will, Your Honor, and seeks this court to essentially ask this court for a review anew of the factual record below.

[00:27:08] Speaker 01:
While that's clearly improper, Parr compounds the problem by asking this court to accept lawyer argument over the testimony of a skilled artist and a person of ordinary skill at the time of the invention.

[00:27:21] Speaker 01:
This is, of course, required by Parr since it raises arguments that were never even raised below, including claims 7.

[00:27:28] Speaker 01:
As Your Honor is aware, the standard review here is pretty clear.

[00:27:31] Speaker 01:
They have to show clear error in the district court's findings.

[00:27:36] Speaker 01:
We find little more than lip service to that effect.

[00:27:40] Speaker 01:
The initial consideration of evidence is not the appellate role.

[00:27:46] Speaker 01:
This court has rejected finding clear error based on a reference that was, quote, placed in the record by the district court, but was not the subject of testimony or any other form of evaluation by the court.

[00:27:57] Speaker 01:
And that is A.D.

[00:27:58] Speaker 01:
Robertson v. United States Steel Deck, 820 Fred 2nd, 348-389.

[00:28:06] Speaker 01:
Again, unsubstantiated attorney argument regarding the meaning of technical evidence.

[00:28:10] Speaker 01:
Again, we heard that.

[00:28:11] Speaker 01:
We saw that in the briefs with regard to what Claim 7 and what the O53 patent means.

[00:28:16] Speaker 01:
It is no substitute for competent, substantiated expert testimony.

[00:28:20] Speaker 01:
It should give in no way to appeal.

[00:28:23] Speaker 01:
I will just address quickly, Your Honor.

[00:28:27] Speaker 01:
the secondary considerations here.

[00:28:29] Speaker 01:
I think they both, both threw unexpected results and teaching away.

[00:28:35] Speaker 01:
There's no challenge to the facts on the teaching away issue here, Your Honor.

[00:28:39] Speaker 01:
I think it was clear, as testified and found by the court, that all the art was directing this towards maximal inhibition.

[00:28:45] Speaker 01:
There was no discussion, no evidence, no reference that showed less than maximal inhibition to treat this disease.

[00:28:51] Speaker 01:
I think the prior taught away.

[00:28:54] Speaker 01:
There, with regard to unexpected results, again, Your Honor, we started a moment ago.

[00:28:58] Speaker 01:
It was unexpected that you could treat this disease with comparable efficacy at a dose lower than maximal inhibition and still receive a safety profile that was not as comparable but was better.

[00:29:09] Speaker 01:
That was a surprise.

[00:29:10] Speaker 01:
We've not seen this before.

[00:29:12] Speaker 01:
Your Honor, there's also secondary considerations that are in effect here.

[00:29:16] Speaker 01:
Obviously, with regard to commercial success, there was not a challenge to either the numbers or the nexus.

[00:29:23] Speaker 01:
Not a single word dedicated to challenging those.

[00:29:26] Speaker 01:
Those stand unrebudded.

[00:29:30] Speaker 01:
The only argument there was a blocking patent argument, which quite frankly, Your Honor,

[00:29:36] Speaker 01:
It doesn't make a lot of sense in this context because the patent at issue, the 248 patent expired one year into the... Before you run out of time, I did have one more question.

[00:29:47] Speaker 04:
Yes, Your Honor.

[00:29:50] Speaker 04:
This claim covers ratios of 2010, 40, 20.

[00:29:56] Speaker 04:
But as I understand it,

[00:29:59] Speaker 04:
your client didn't actually run tests on whether those worked until several years after the patent application was filed.

[00:30:07] Speaker 01:
That's correct, John.

[00:30:08] Speaker 01:
When they took the 60-60 formulation that we mentioned earlier into the clinic, the results were so robust beyond anything they could have thought of that they then came up with the invention of lowering it even further.

[00:30:22] Speaker 01:
It was eventually proved out later in subsequent testing.

[00:30:27] Speaker 04:
Okay, there's no written description case in front of us now, right?

[00:30:31] Speaker 04:
No.

[00:30:31] Speaker 04:
Okay.

[00:30:33] Speaker 04:
Okay.

[00:30:34] Speaker 04:
Thank you.

[00:30:34] Speaker 04:
Thank you, Your Honor.

[00:30:37] Speaker 04:
All right.

[00:30:38] Speaker 04:
Ms.

[00:30:38] Speaker 04:
Carlin?

[00:30:39] Speaker 00:
Thank you, Your Honor.

[00:30:41] Speaker 00:
First, I'd like to start with the notion that every expert said that there's 50 milligrams on the floor, and that is not true.

[00:30:49] Speaker 00:
We have our expert, Dr. Paulson, who did not say it was speculated.

[00:30:52] Speaker 00:
He actually said, stipulated, that it could be less than 150 milligrams.

[00:30:57] Speaker 00:
He said in many pages of testimony that he explained the 053 application and that can be shown at the appendix of A15785 through Q86 that this range is disclosed within the less than 150.

[00:31:16] Speaker 00:
So it is not true that all experts said that.

[00:31:20] Speaker 00:
The only thing Dr. Paulsen did say is that 150 milligrams is not a floor.

[00:31:27] Speaker 00:
The other thing I need to point out is that TAR does challenge factual findings as you can see from our briefing.

[00:31:34] Speaker 00:
And second, with respect to example two.

[00:31:38] Speaker 00:
Example two, I wanted to address the issue of it being disregarded by the court by some sort of theory that maybe is not enabled.

[00:31:49] Speaker 00:
But this is a 103 case.

[00:31:51] Speaker 00:
And example two is

[00:31:54] Speaker 00:
can be seen by one of ordinary skill in the art and can be read for what it discloses.

[00:31:59] Speaker 00:
And in fact, our experts stated that that example should work and so should the others.

[00:32:05] Speaker 00:
But in this case, that reference, the 248 patent, is looked at as a whole and for all that it teaches.

[00:32:14] Speaker 00:
Also, I wanted to address the fact that the court had a 63 page opinion, but

[00:32:20] Speaker 00:
It's interesting that there were only six lines of findings of fact on the 05-3 application, and the expert for Avenir only had about four sentences in his direct testimony on this 05-3 application.

[00:32:33] Speaker 00:
Turning to teaching away, we of course do challenge that on a number of grounds, but one of the issues with teaching away is that even absolutely no piece of prior art shows that you should not go below a certain amount.

[00:32:49] Speaker 00:
There's no teaching away.

[00:32:50] Speaker 00:
There's no criticism.

[00:32:52] Speaker 00:
There's nothing in the references that say, do not do this.

[00:32:56] Speaker 00:
That cannot be, therefore, a teaching away.

[00:33:00] Speaker 00:
With respect to unexpected results, again, taking a look at the Yakatan reference, the poster, it does tell that in a dose of 20 milligrams of quinidine per day, that one would expect to have enough DM in the blood to be therapeutic.

[00:33:19] Speaker 00:
So this is not unexpected.

[00:33:22] Speaker 00:
It was shown that it should work.

[00:33:28] Speaker 00:
And we believe that the patents in suit are obvious over both Galderma framework and with respect to the prior art as a whole, and no secondary considerations overcome.

[00:33:40] Speaker 00:
Thank you, Your Honor.

[00:33:41] Speaker 04:
Thank you, Ms.

[00:33:42] Speaker 04:
Carlin.

[00:33:42] Speaker 04:
The case is submitted.