[00:00:01] Speaker 02:
Final case for argument is 17-2121, United Therapeutics versus Steadymet.

[00:00:37] Speaker 01:
whenever you're ready.

[00:00:53] Speaker 00:
Good morning.

[00:00:53] Speaker 00:
May I please record?

[00:00:55] Speaker 00:
The board erred in anticipation with respect to claim two because it never addressed differences in the impurity profile of the product.

[00:01:04] Speaker 00:
The FAROs reference never showed whether steps A and B were actually performed with respect to that product.

[00:01:13] Speaker 02:
So there's no way to know, even if you... You're not appealing the PTAB's invalidation of 1, 3 to 5, 7 to 9, 11 to 14, or 16 to 20, right?

[00:01:24] Speaker 00:
That's correct, John.

[00:01:25] Speaker 00:
Okay.

[00:01:26] Speaker 02:
So are you talking about Claim 2 now?

[00:01:28] Speaker 00:
I'm talking about Claim 2, and even if the board

[00:01:33] Speaker 00:
was correct in finding that it had at least 99.5% purity, there's no way to know if the remaining impurities necessarily would have been the same as the product produced by Steps A, B, and C as our claim recite.

[00:01:50] Speaker 00:
The Ferris Ruffins in that working example does not disclose what the origin is of the tropostanil on which it performed Step C. The Board never really addressed this point

[00:02:04] Speaker 00:
in their holding.

[00:02:06] Speaker 02:
In addition to that... Let me ask you about the testimony of Dr. Williams, which the PTAB found was unpersuasive.

[00:02:18] Speaker 02:
And in fact, Dr. Williams conceded that he knew of no literature supporting one of his contentions, which is at 1744 and 45.

[00:02:28] Speaker 02:
Yet you rely extensively on his testimony in an attempt to undermine the evidence relied on by the PTAB.

[00:02:34] Speaker 02:
Now look, you know perfectly well our standard of review on factual determinations.

[00:02:39] Speaker 02:
Why should we consider his testimony when the PTAB found it to be unpersuasive?

[00:02:45] Speaker 02:
And there's record evidence that shows he's contradictory.

[00:02:51] Speaker 00:
Well, I think that Dr. Williams' evidence was based on certificates of analysis.

[00:02:57] Speaker 00:
So we're all submitted to the FDA as part of the FDA's review that ultimately determined

[00:03:04] Speaker 00:
that this product had a higher average purity.

[00:03:07] Speaker 00:
And Dr. Ruffalo, whose unrebutted testimony established the procedures by which the FDA reviewed all that, shows the validity of the determination.

[00:03:20] Speaker 00:
Now, the board quibbled with particular aspects of Dr. Williams' testimony and the fact that there were certain facts.

[00:03:27] Speaker 02:
Well, that's an interesting word.

[00:03:29] Speaker 02:
I mean, there was clear contradiction in his testimony.

[00:03:34] Speaker 02:
I mean, I'll take you to where, in the record, where he concedes that he doesn't know of any support for what he's saying.

[00:03:41] Speaker 02:
I don't know that that's quibbling.

[00:03:44] Speaker 00:
Dr. Williams' testimony was that the average purity of the products of the 393 claims was higher as a result of these many, many certificates of analysis, all of which were required to be submitted to FDA.

[00:04:01] Speaker 00:
The board never disagreed

[00:04:05] Speaker 00:
with the FDA's ultimate determination that the mean purity was higher for the products of the 393 claim.

[00:04:15] Speaker 00:
Now, putting aside this evidentiary question with respect to claim construction, the 393 specification clearly states that the impurities from steps A and B are reduced as a result of step C. It makes that statement

[00:04:32] Speaker 00:
unequivocally with respect to the claimed products as a whole.

[00:04:36] Speaker 00:
It's not some preferred embodiment.

[00:04:40] Speaker 00:
And despite this unequivocal statement and the fact that it was further argued during the prosecution history with the Walsh Declaration, the board would not agree that the claims could be construed to require the unique impurity profile.

[00:04:58] Speaker 00:
So on claim construction, there's a separate reason

[00:05:01] Speaker 00:
to overturn the board's decision as to claim two.

[00:05:05] Speaker 00:
And the board erred here the same way that it did in N. Ray Smith International by taking a broadest possible interpretation.

[00:05:15] Speaker 00:
It wasn't consistent with what is stated in the specification.

[00:05:20] Speaker 02:
Where in the record did you request PTAB to construe the term product ellipsis prepared by a process comprising

[00:05:31] Speaker 00:
Steps A to C and optionally D. So in the patent owner response at 380, Appendix 380, there's discussion of claim construction.

[00:05:55] Speaker 00:
It's also in our reply brief at pages 14 to 16.

[00:06:00] Speaker 00:
But that's a discussion of the fact that the impurity profile is connected to steps A through C of the product by process claim.

[00:06:13] Speaker 00:
So there was a separate discussion of the word product, but there was also a discussion of claim construction in the patented response as the steps A through C requiring this impurity profile.

[00:06:31] Speaker 00:
So I think you have to look at that as a whole, product made by a process comprising Steps 83C.

[00:06:40] Speaker 00:
The board relied on the plain meaning of the word product and turned incorrectly to extrinsic evidence to make that determination without regard to what was in the specification or the file history.

[00:06:59] Speaker 02:
I take that as a no.

[00:07:05] Speaker 00:
Your Honor, the claim construction was addressed in a way that tried to link the claims of the process steps A through C to the impurity profile.

[00:07:19] Speaker 00:
I think that when you read product, you can't divorce the word product from steps A through C because it is a product by process claim.

[00:07:31] Speaker 00:
Now another aspect of the board decision that I want to point out is with respect to motivation for combining Barrow's and Moriarty together with claim two.

[00:07:43] Speaker 00:
In one part of its decision, the board says that if you combine these references, you necessarily get a product of at least 99.5% purity.

[00:07:55] Speaker 00:
But in an earlier part of its final written decision, the board concluded that

[00:08:00] Speaker 00:
If you perform salt purification step C, that would be a reason to eliminate an intermediate purification step of Moriarty.

[00:08:10] Speaker 00:
But if you do that, then you wouldn't know what the end result would be, what impact it would have on purity.

[00:08:18] Speaker 00:
So the board never resolves this contradiction in its stated motivation for combining the two references together.

[00:08:27] Speaker 00:
Also, with respect to claims 6, 10, 15, 21, and 22, which all require step B, the board introduced two other references here, Kawakami and Ege.

[00:08:39] Speaker 02:
With respect to those references- I have some real specific questions I'd like answered.

[00:08:45] Speaker 02:
In the blue brief at 18, you discuss two batches of troposinol in their respective purity levels and melting points.

[00:08:55] Speaker 02:
citing JA5438.

[00:08:57] Speaker 02:
In the red brief at 16, SteadyMed states that on this page, data concerning a batch labeled UTC15-010203 can be found, but there's no data concerning a batch labeled UTC15-01101.

[00:09:24] Speaker 02:
When I go to the gray brief to look for a reply to that, at four, you discuss the relationship between purity and levels and melting points.

[00:09:36] Speaker 02:
And you cite me to 100 pages in the record, JA 5420 to 5532.

[00:09:45] Speaker 02:
Is that 100 and plus page?

[00:09:52] Speaker 02:
range your response to the inaccurate citation alleged in the red brief?

[00:09:58] Speaker 00:
What do you expect out of us?

[00:10:02] Speaker 00:
The specific batch number is not the 100 pages.

[00:10:06] Speaker 00:
But the point we are trying to make is that the board relied selectively on certain batches.

[00:10:14] Speaker 00:
And if you look at these certificates of analysis, these individual batch records,

[00:10:21] Speaker 00:
you see that there are batch-to-batch variations.

[00:10:24] Speaker 00:
And in fact, the same is true when you compare purity and melting points in all of these certificates of analysis.

[00:10:32] Speaker 00:
And there are some that have a bigger disparity than others.

[00:10:36] Speaker 00:
But the error is that the board relied on individual batches as opposed to looking at the evidence as a whole the way that it was presented in the Williams Declaration.

[00:10:47] Speaker 02:
Okay, so take me back to the beginning of your answer.

[00:10:50] Speaker 02:
when you said the specific batch number is not what?

[00:10:55] Speaker 00:
I didn't hear that word, is not.

[00:10:58] Speaker 00:
The specific batch number is not represented by those 100 pages.

[00:11:03] Speaker 00:
It's one specific batch.

[00:11:09] Speaker 02:
In the blue brief at 28, you say that a posita

[00:11:14] Speaker 02:
would have understood, quote, would have understood that a natural product dash, a product that is found in nature dash, should not be conflated with a pharmaceutical manufacturing product that is synthetic in origin.

[00:11:27] Speaker 02:
You don't provide any support for that statement.

[00:11:31] Speaker 02:
What's your support in the record?

[00:11:40] Speaker 02:
I mean, you know, we read these briefs and we were scribbling notes.

[00:11:44] Speaker 00:
I think that this was discussing the claim construction with respect to the word product and the fact that the board, in its final written decision, had relied on products that were natural products, whereas the context of this invention is that it's a pharmaceutical manufacturing product.

[00:12:06] Speaker 00:
And that is described in the claim construction section of the Patent and Response.

[00:12:13] Speaker 00:
that was presented in the IPR.

[00:12:16] Speaker 02:
When counsel in a patent case says that a person having ordinary skill in the art would understand something, they have to base that on some kind of evidence, don't they?

[00:12:31] Speaker 02:
So where is that evidence?

[00:12:33] Speaker 02:
I understand what you're driving at, but that's beside the point.

[00:12:40] Speaker 00:
I think that this was such a basic issue, the question of a naturally occurring product as opposed to a synthetic product, that we treated it as being self-evident when we made this statement in the brief, Your Honor.

[00:12:58] Speaker 00:
So it's pure attorney argument in other words.

[00:13:02] Speaker 00:
Well, when you go back and you look at the various dictionaries that are cited for support of the word product, I think there are dictionaries that separate products and articles that use the word product in connection with pharmaceutical.

[00:13:18] Speaker 00:
There's others that use the word product in connection with naturally occurring product.

[00:13:23] Speaker 00:
Here the 393 pattern is dealing with pharmaceutical products of synthetic origin that have nothing to do with

[00:13:31] Speaker 00:
naturally occurring or naturally isolated products.

[00:13:37] Speaker 02:
You're into your rebuttal, why don't we turn to the other side and we'll retain your rebuttal time.

[00:13:42] Speaker 00:
Yes, three minutes.

[00:14:06] Speaker 01:
Good morning, Your Honors.

[00:14:08] Speaker 01:
May it please the court?

[00:14:11] Speaker 01:
I have two main arguments.

[00:14:13] Speaker 01:
First, there's substantial evidence here for the numerous factual findings made by the board regarding the eight questions raised by United Therapeutics in their opening brief.

[00:14:29] Speaker 01:
Second is that the claim construction here of the very fundamental patent

[00:14:36] Speaker 01:
acclaim words seen in many claims, the words product and the word comprising, those constructions finding that their ordinary meanings, the meaning of comprising being including but not limited to, and product being defined by the process steps, that was a correct construction finding the ordinary meaning and there's no reason to reverse here.

[00:15:01] Speaker 01:
Let me first turn to the substantial evidence

[00:15:06] Speaker 01:
challenge here.

[00:15:08] Speaker 01:
There's really, I think, three main challenges.

[00:15:11] Speaker 01:
One is about the chemical in the Farris reference.

[00:15:15] Speaker 01:
That chemical is identical to the chemical in claim two.

[00:15:19] Speaker 01:
And based on the evidence of two professors that were credited by the court, that chemical has at least the same purity as the chemical claimed in claim two.

[00:15:33] Speaker 01:
Similarly, once you combine Farris and Moriarty is no question, all three process steps are in the prior art.

[00:15:44] Speaker 01:
It appears in the briefs that they didn't challenge the combination of Moriarty and Farris on this appeal.

[00:15:51] Speaker 01:
And there was no dispute below that all three steps are there.

[00:15:56] Speaker 01:
Therefore, since it's the same process, it must be the same product.

[00:16:00] Speaker 01:
And finally,

[00:16:01] Speaker 01:
on the combination to invalidate claim 6, 10, 15, 21, and 22, there was substantial evidence supporting a reason to combine the Farreys and Moriarty pair with the Kawakami and Egea pair.

[00:16:22] Speaker 01:
And the board explained, actually gave two reasons for making that combination, not just one.

[00:16:29] Speaker 01:
So there were two independent

[00:16:30] Speaker 01:
grounds for that.

[00:16:34] Speaker 01:
Are there any questions about the substantial evidence or I'll go on to claim construction?

[00:16:39] Speaker 02:
Nope.

[00:16:41] Speaker 02:
Other than I think your opposing counsel conceded on those claims.

[00:16:47] Speaker 02:
I don't know why you need to discuss them.

[00:16:51] Speaker 01:
Okay.

[00:16:52] Speaker 01:
Let me address then the claim construction result, which is not only correct, but

[00:16:59] Speaker 01:
I don't think anyway it would change the result in this case if the claim construction were changed to my learned friend's proposal of a substance produced from a chemical reaction.

[00:17:14] Speaker 01:
All of the prior art references are substances produced from chemical reactions.

[00:17:19] Speaker 01:
They're all chemical references.

[00:17:22] Speaker 01:
In addition, here we have the word product.

[00:17:27] Speaker 01:
The next word after that is

[00:17:29] Speaker 01:
comprising, even if we were to somehow interpret product to mean a product having an impurity profile for a representative batch conferred by its process steps, if we would put all that language in, even if product meant that and somehow incorporated some impurity profile, even though the record showed there were no impurity profiles associated with these products,

[00:17:59] Speaker 01:
Even if all that were true, the word comprising right after, which adds including but not limited to, would allow for other impurities to be included in the claim.

[00:18:08] Speaker 01:
So the claim would both include the profile plus other impurities.

[00:18:13] Speaker 01:
So it really wouldn't matter even if we went as far as this other pseudo-construction if they haven't really advocated.

[00:18:25] Speaker 01:
Are there any questions on claim construction?

[00:18:30] Speaker 01:
Okay, are there any further questions and any other issues?

[00:18:34] Speaker 01:
Then I'll cede my time and let counsel robot.

[00:18:48] Speaker 00:
Thank you, Your Honor.

[00:18:50] Speaker 00:
In the last remaining minutes, I just want to point out that one of the cases cited in study meds brief, the Aventos v. Amino Chemicals case,

[00:18:59] Speaker 00:
shows that a purity-related limitation can be construed without a numerical limit.

[00:19:05] Speaker 00:
In that case, the court found that it was appropriate to construe a purity-related limitation to mean, quote, largely but not wholly made up of a certain compound.

[00:19:19] Speaker 00:
I think that's analogous to what we're asking for with respect to our claim construction.

[00:19:24] Speaker 00:
But even if you completely put aside claim construction,

[00:19:28] Speaker 00:
I want to come back to claims 6, 10, 15, 21, and 22, where the board combined the Kawakami and Ege references.

[00:19:37] Speaker 00:
And there's really no motivation to put those on top of Moriarty and Ferris.

[00:19:44] Speaker 00:
Kawakami relates to forming a salt of a different compound that has easy isomers.

[00:19:51] Speaker 00:
Tropostinol is not capable of forming easy isomers.

[00:19:57] Speaker 00:
In addition to that, Kawakami's composition was already very impure.

[00:20:02] Speaker 00:
It was 77.8% pure.

[00:20:06] Speaker 00:
And it's very different from Moriarty, which was already a highly pure material.

[00:20:13] Speaker 00:
So it's unclear.

[00:20:14] Speaker 02:
Do you disagree with the statement in the red brief that, quote, even Dr. Williams agreed that the impurity profile will be different in each batch of Moriarty?

[00:20:29] Speaker 00:
The individual batches do have variations.

[00:20:33] Speaker 00:
And Dr. Williams agreed with that.

[00:20:36] Speaker 00:
The tiny impurities, yes.

[00:20:41] Speaker 00:
The EGAE is just a textbook that simply shows that you can convert a salt to an acid.

[00:20:49] Speaker 00:
So it clearly doesn't give you a reason to add a step D on top of ferrous and Moriarty.

[00:20:59] Speaker 02:
Well, trypostinol is a carboxylic acid, yes.

[00:21:07] Speaker 00:
Trypostinol-free acid, yes.

[00:21:09] Speaker 00:
It does have a carboxylic acid.

[00:21:14] Speaker 00:
But there's really no reason to... Then why doesn't Edgate teach step D?

[00:21:20] Speaker 00:
It teaches the chemical reaction.

[00:21:23] Speaker 00:
That's all.

[00:21:24] Speaker 00:
But there's no reason to apply that extra step

[00:21:29] Speaker 00:
Given that you already have a highly pure product, that's the contradiction in the reasoning of the board.

[00:21:37] Speaker 00:
If Moriarty is already 99.7% pure, there's no reason to apply Kawakami and Ege.

[00:21:45] Speaker 00:
And there's also no reasonable expectation that forming a salt would make Moriarty even more pure and allow you to eliminate the column chromatography step.

[00:21:59] Speaker 00:
the Moriarty-Ruffins, which is what Dr. Williams found to be very surprising.

[00:22:04] Speaker 00:
So the motivation just doesn't add up for combining those four Ruffins.

[00:22:10] Speaker 00:
Thank you, Your Honor.

[00:22:12] Speaker 02:
We thank both sides.

[00:22:13] Speaker 02:
The case is submitted.

[00:22:14] Speaker 02:
That concludes our proceedings for this morning.

[00:22:17] Speaker 00:
All rise.

[00:22:20] Speaker 00:
The honorable court is adjourned until tomorrow morning.

[00:22:22] Speaker 00:
It's an o'clock a.m.