[00:00:07] Speaker 04:
We have four cases on the calendar this morning, one patent case from the PTAB, two claims cases, a veteran's case, and one of the claims cases will be heard on the briefs and not be argued.

[00:00:27] Speaker 04:
The first case is Mylan Pharmaceuticals et al.

[00:00:31] Speaker 04:
v. Research Corporation Technologies, 2017.

[00:00:37] Speaker 04:
88, 89, and 91.

[00:00:40] Speaker 04:
Mr. Parmoley.

[00:00:44] Speaker 03:
Thank you, Your Honor.

[00:00:45] Speaker 03:
Steve Parmoley for Appellants.

[00:00:46] Speaker 03:
May it please the court?

[00:00:48] Speaker 03:
We believe the board's decision can be reversed due to at least three errors which we set forth on page 33 of our opening brief.

[00:00:56] Speaker 03:
But basically, the board substituted a reason offered by RCT to modify the lead compound in place of our reason, as petitioners to modify it.

[00:01:06] Speaker 04:
How did 3L get to be a league compound?

[00:01:09] Speaker 03:
3L was the most potent drug of any of those enumerated in the Cohen 1991 reference.

[00:01:19] Speaker 04:
Then where was the motivation to modify it if it was such a good drug?

[00:01:25] Speaker 03:
The motivation was that a person of ordinary skill would have looked at that compound and seen that it had an NO bond.

[00:01:34] Speaker 03:
NO bond, this bond between two heteroatoms, was considered to be unstable at a physiological pH, and it was a bond that would have been easily fixed.

[00:01:47] Speaker 00:
But didn't Cone itself indicate that the compounds, those compounds, were all stable?

[00:01:55] Speaker 03:
I think there were some melting point studies, but I don't know that they considered them stable.

[00:02:00] Speaker 03:
I think, though, that any person with an ordinary skill in the art looking at that

[00:02:04] Speaker 03:
compound would see that the NO bond is very rare in pharmaceuticals.

[00:02:08] Speaker 03:
I think there's only one compound on the market that has an NO bond.

[00:02:12] Speaker 03:
So a post-it would see that that's a potentially unstable bond, and it's so easily remedied.

[00:02:18] Speaker 03:
And that's why we said it should be selected as a lead compound in the first place, along with the reason that it was the most highly potent compound in that list of compounds.

[00:02:29] Speaker 03:
In fact, it was more potent than two of the most

[00:02:33] Speaker 03:
highly marketed, or most commonly used, AEDs on the market, that being phenytoin and valethyl.

[00:02:41] Speaker 04:
Well, where was the motivation to change the NO to a methylene?

[00:02:48] Speaker 03:
Well, the motivation was, it's what was opposed to would know to do, because that's a standard substitution under bioisosteric conditions.

[00:03:00] Speaker 04:
Well, that seems very strange to me.

[00:03:03] Speaker 04:
Methylene is an isostere of the amino oxide.

[00:03:09] Speaker 04:
And if, in fact, the oxyamene was so unusual, then there really isn't an isostere for that.

[00:03:17] Speaker 04:
And I see the Silverman paper that lists it horizontally.

[00:03:23] Speaker 04:
But there's also oxygen sulfasolinium

[00:03:29] Speaker 03:
Well, I think the part of the problem in substituting those other bioisosteers would be if you put an oxygen next to an oxygen, then you've got a peroxide.

[00:03:38] Speaker 03:
If you put a sulfur in there, you've still got a bond between two heteroatoms.

[00:03:43] Speaker 03:
Only carbon would solve that problem, only the methylene substitution, and it was an easy fix to do.

[00:03:50] Speaker 00:
As I understand, at least part of your argument is predicated on the

[00:03:54] Speaker 00:
theory, which is supported by Cone, I guess, 91 and 93, that having an oxygen two atoms removed from the alpha carbon is associated with high potency.

[00:04:08] Speaker 03:
You're absolutely right.

[00:04:10] Speaker 00:
But the other point that's made by Cone, and I think this is principally, if not exclusively, in Cone 94, is that having an amino group at the alpha carbon

[00:04:24] Speaker 00:
site is also highly associated with potency.

[00:04:29] Speaker 00:
Now, why then would you throw one of those two indicators of potency out the window in favor of simply having the one?

[00:04:41] Speaker 00:
I understand your argument about the labile state of the NO bond, but

[00:04:48] Speaker 00:
But is there any other reason, any other inducement to get rid of the nitrogen?

[00:04:54] Speaker 03:
Well, I think the cone 94 paper you're referring to was sort of a structure activity relationship study on that nitrogen and what they could attach to it.

[00:05:04] Speaker 03:
So there's examples in that paper of compounds with the nitrogen that are duds as far as activity.

[00:05:12] Speaker 00:
Oh, sure.

[00:05:13] Speaker 00:
There are lots of duds in all of the

[00:05:17] Speaker 00:
Dr. Cohen's work, but the ones that are good, with a couple of exceptions that you point out, 2C and 2D, I guess, are two of the exceptions, but most of the ones that are good do have the nitrogen.

[00:05:29] Speaker 00:
And he does say that the results, this is 94, documented that excellent protection can be achieved by incorporation of a basic alpha carbon amino substituent.

[00:05:44] Speaker 00:
So that's a pretty strong

[00:05:47] Speaker 00:
pointer in the direction of holding on to that alpha carbon amino substituent, isn't it?

[00:05:54] Speaker 03:
But if you look at cone 91, apart from the cone 94 SAR studies and the effect of electrophiles, electron groups, and all that that they were doing in 94, if you go back to cone 91, where the key to potency was really that carbon, or the oxygen atom, two atoms removed from the alpha carbon.

[00:06:16] Speaker 03:
That's the key to potency.

[00:06:17] Speaker 03:
So you can have a nitrogen at the alpha carbon.

[00:06:21] Speaker 03:
You can have a carbon at the alpha carbon.

[00:06:24] Speaker 03:
There's examples in cone 91 of highly potent compounds.

[00:06:27] Speaker 03:
And just switching the nitrogen to a carbon was responsible for perhaps a minor decrease in potency.

[00:06:34] Speaker 03:
And that's what the board recognized in the institution decision.

[00:06:37] Speaker 03:
It would be a small decrease in potency.

[00:06:40] Speaker 03:
3L was so highly potent, more potent than any of the others, that

[00:06:45] Speaker 03:
A post-it would have known you had room to work with that.

[00:06:49] Speaker 03:
And part of pharmaceutical development is optimizing.

[00:06:52] Speaker 03:
It's a give and take.

[00:06:53] Speaker 03:
If I have high potency, maybe I have a little bit of room.

[00:06:57] Speaker 03:
Just because you have high potency doesn't mean you can give a drug to a person if it's unstable in vivo.

[00:07:04] Speaker 03:
Or unstable in vivo.

[00:07:07] Speaker 03:
So if you can remedy the instability that would occur in vivo by putting in

[00:07:12] Speaker 03:
of making a simple substitution at the carbon for the nitrogen, then you've taken care of that problem.

[00:07:19] Speaker 02:
Let me ask you about your battling experts.

[00:07:21] Speaker 02:
In the red brief at 45, 46, the appellees discussed Dr. Rausch and your argument that he failed to account for physiological influences such as solvent molecules in water or binding site interactions.

[00:07:42] Speaker 02:
And then they say, Dr. Rausch explained, usually the solvent of interest is water to see what the conformation in water is.

[00:07:51] Speaker 02:
But that becomes, frankly, much less relevant when you're looking at the conformation of a molecule when bound in a protein, because when bound in a protein, there's not water associated with it.

[00:08:03] Speaker 02:
And then they discuss, Rausch explained, physiological influences.

[00:08:12] Speaker 02:
And they say Dr. Wang did not identify any alternate method that would have accounted for those physiological influences.

[00:08:23] Speaker 02:
Where in the record does he, if he does?

[00:08:26] Speaker 03:
Well, I'm not sure.

[00:08:26] Speaker 03:
The physiological differences is that the carbon at that position would have been the standard.

[00:08:37] Speaker 03:
I'm not sure.

[00:08:38] Speaker 03:
If that's the question you're asking for about Dr. Wayne.

[00:08:40] Speaker 02:
Yeah, what I'm asking is to respond to their argument that he doesn't identify any alternate method that would have accounted for those physiological influences.

[00:08:50] Speaker 03:
We have the testing in the animals from compounds that do have the carbon and oxygen.

[00:08:59] Speaker 03:
So that's in tone 91.

[00:09:01] Speaker 03:
I don't know that they tested stability.

[00:09:04] Speaker 02:
So Dr. Wang didn't address it then?

[00:09:09] Speaker 03:
I don't recall that he did or not.

[00:09:12] Speaker 04:
The board made fact findings that a change of the nature that occurred here would have led to a reduction in activity, significantly different confirmation in biological activity.

[00:09:28] Speaker 04:
Those are fact findings, right?

[00:09:30] Speaker 04:
We have to give them deference.

[00:09:32] Speaker 03:
There's substantial evidence for it.

[00:09:35] Speaker 03:
We pointed out that there's not.

[00:09:37] Speaker 03:
The board went through several fact findings that weren't supported.

[00:09:41] Speaker 03:
They have some, and that makes some analogous comparisons between compounds, and we point out in our opening brief and then in the reply why those were inapt.

[00:09:53] Speaker 03:
For example, one of them was putting, the board said, well you can simply put two oxygens together, you can substitute an oxygen there.

[00:10:00] Speaker 03:
Well, the fact of the matter is,

[00:10:03] Speaker 03:
If you put an oxygen next to an oxygen, you're going to generate a peroxide.

[00:10:06] Speaker 03:
So that's an example of how the board really got a little off track in doing that sort of fact finding that you're referring to, Your Honor.

[00:10:16] Speaker 02:
You called Dr. Rausch's modeling crude because he manually rotated bonds.

[00:10:22] Speaker 03:
Right.

[00:10:23] Speaker 02:
Where in the record is there evidence by Mylan or by Dr. Wang of a less crude method?

[00:10:33] Speaker 03:
Dr. Wang and Mylan did not do computer modeling.

[00:10:37] Speaker 03:
This was a post-hoc computer modeling that Dr. Rausch engaged in.

[00:10:42] Speaker 03:
And it was incomplete.

[00:10:45] Speaker 03:
We believe and we point out why it was incomplete.

[00:10:48] Speaker 03:
He didn't rotate the cartons and things like that.

[00:10:52] Speaker 03:
So we felt that the computer modeling was just another in-app comparison.

[00:10:59] Speaker 03:
Again, post-hoc.

[00:11:05] Speaker 04:
We can save the rest of your time if you would.

[00:11:08] Speaker 03:
All right, yes.

[00:11:08] Speaker 04:
All reserved time.

[00:11:09] Speaker 03:
Thank you.

[00:11:12] Speaker 04:
Mr. Blumenthal.

[00:11:19] Speaker 01:
Thank you.

[00:11:20] Speaker 01:
I would like to start with a question that, Dr. Flory, that you asked.

[00:11:25] Speaker 01:
And that is, how did 3L get to be a lead compound?

[00:11:28] Speaker 00:
And when you read- If you could.

[00:11:31] Speaker 00:
I hate to jump on you right at the beginning, but since this is a discrete issue here with respect to the appealability, I want to make sure that we get a chance to talk about that.

[00:11:42] Speaker 00:
So if you don't mind, if you could postpone the 3L discussion for just a minute.

[00:11:46] Speaker 00:
I take it that your position really is one of statutory construction.

[00:11:50] Speaker 00:
There isn't, I mean, we talk about the

[00:11:54] Speaker 00:
the question of whether there's a sufficient interest here for an appeal and so forth.

[00:11:59] Speaker 00:
But it really is just federal construction, is it not?

[00:12:01] Speaker 00:
The question of whether a party for purposes of Section 319 is the same as a party for purposes of Section 315C.

[00:12:10] Speaker 00:
That's really all it is, right?

[00:12:12] Speaker 01:
That's right.

[00:12:13] Speaker 01:
We're not arguing an Article III standing issue.

[00:12:16] Speaker 01:
We're arguing that under these circumstances, a joint party

[00:12:23] Speaker 01:
And that's the word the statute uses.

[00:12:26] Speaker 01:
We use that, join party, who was time barred from bringing its own idea.

[00:12:31] Speaker 00:
I understand the argument, but just to cut to the chase here, your argument would require us to conclude, I take it, that the word party in section 319 means something other than the word party in section 315C.

[00:12:45] Speaker 00:
Is that correct?

[00:12:46] Speaker 01:
That is correct.

[00:12:47] Speaker 00:
Well, go ahead.

[00:12:49] Speaker 00:
You can give an explanation.

[00:12:51] Speaker 01:
I'll put a little gloss on that, and then I'll turn back to where I was starting.

[00:12:54] Speaker 01:
And the gloss I would put on that is that the party of 315C is in the discretion of the director or the board in this case, and not a statutory right.

[00:13:10] Speaker 01:
And in this case, the way they describe themselves was an understudy.

[00:13:16] Speaker 01:
Yes, they were a party under 315, but their role in the IPR was as an understudy.

[00:13:21] Speaker 01:
They did not have and did not take full rights of participation.

[00:13:25] Speaker 01:
And it seems very odd that when the party that actually filed the petition can't appeal, that the understudies do get to appeal.

[00:13:33] Speaker 01:
And unless, Your Honor, there's more questions about that, I'm going to flip back to the other issue.

[00:13:39] Speaker 01:
And where I was starting, George Lowery, was your question about how 3L got to be a lead compound.

[00:13:45] Speaker 01:
And when you read the board decision, they did not decide that 3L was the lead compound.

[00:13:52] Speaker 01:
They assumed arguendo, and that's the term they used at page A17.

[00:13:58] Speaker 01:
that 3L was the lead compound, that's what the appellants were promoting.

[00:14:03] Speaker 00:
But we couldn't conclude here without remanding the case, I take it, that 3L really can't be the lead compound because we can't affirm the board on reasons other than those given.

[00:14:16] Speaker 01:
I think that is absolutely right, Your Honor.

[00:14:19] Speaker 00:
So we really kind of stuck with 3L as the lead compound, even if we really don't think it should be.

[00:14:23] Speaker 01:
And I'm not arguing that point other than to say it was an assumption, not a finding.

[00:14:29] Speaker 01:
And if that became important, I think you're right that it has to be remanded, that you can't decide it.

[00:14:34] Speaker 01:
But the question I was going to raise is, once 3L is regarded as a lead compound, why would someone of skill in the art have changed it?

[00:14:46] Speaker 01:
I'll go back to where, Judge Bryson, where you went, and that is Cohn 1991 teaches that the best compounds had a nitrogen at the alpha carbon.

[00:15:00] Speaker 01:
Cohn 1994 then says it's important to have an amine, a nitrogen at the alpha carbon in order to get good activity.

[00:15:15] Speaker 01:
Why would someone change that?

[00:15:17] Speaker 01:
And there is no reason someone would change it.

[00:15:20] Speaker 01:
And Mr. Carmely referred to a small reduction in potency.

[00:15:27] Speaker 01:
There's no evidence as to what the reduction in potency would have been.

[00:15:30] Speaker 01:
That number that they put in their brief, it didn't exist in the prior art.

[00:15:35] Speaker 01:
That was just something that more or less was made up.

[00:15:40] Speaker 01:
So that was unknown.

[00:15:42] Speaker 00:
But on the bio-isosterism point, because that is the basis for their conclusion as to why you would do this, the evidence... Well, maybe I misunderstand the record here, but I thought that the argument about the small difference in potency was with respect to the comparison between compounds 3A and 2A.

[00:16:05] Speaker 00:
That's correct.

[00:16:07] Speaker 00:
that when you go from the nitrogen to a CH2 group at the alpha carbon site, you have a reduction in activity.

[00:16:16] Speaker 00:
But it's a very small one relative from 65 up to 76, modest increase.

[00:16:22] Speaker 01:
15%, 16%.

[00:16:26] Speaker 00:
That's their argument.

[00:16:26] Speaker 00:
Their argument is therefore there wouldn't be this potency

[00:16:30] Speaker 00:
potential isn't such a big deal that you wouldn't have other reasons that would overcome it to get rid of the nitrogen, such as the stability and synthetic factors.

[00:16:43] Speaker 01:
Right.

[00:16:43] Speaker 01:
And I think that is their argument.

[00:16:44] Speaker 01:
My point was that when it comes to switching from a methoxyamino to methoxymethyl, which is what they're saying here, there was no evidence as to what effect that particular substitution would have.

[00:16:58] Speaker 01:
On the stability point, Your Honor,

[00:17:00] Speaker 00:
Other than the inferences one might draw from bioisosterism.

[00:17:06] Speaker 01:
Right.

[00:17:06] Speaker 01:
And I'd like to get back in a minute to the bioisosterism point.

[00:17:10] Speaker 01:
But before I do, on the stability, there is no evidence anywhere in this record that there was a stability issue with 3L.

[00:17:19] Speaker 01:
There is none.

[00:17:20] Speaker 01:
The only evidence of stability is in the Cone 91 paper.

[00:17:24] Speaker 01:
This is at A2406 to 2407.

[00:17:29] Speaker 01:
which says it's right at the top of 2407 that these compounds are stable.

[00:17:36] Speaker 01:
That is the only evidence.

[00:17:39] Speaker 01:
We do know a little more than that.

[00:17:41] Speaker 01:
We know that that compound, which is called stable in the cone paper, was injected into a mouse, that they were able to measure the effects that that had.

[00:17:54] Speaker 01:
And you would think that that would be some evidence that it was stable.

[00:17:57] Speaker 01:
But my point is,

[00:17:58] Speaker 01:
They put in no evidence that there was instability problem with this particular compound.

[00:18:03] Speaker 04:
Tell us what you wanted to tell us about bioisosteres.

[00:18:06] Speaker 01:
I do want to talk about bioisosterism.

[00:18:09] Speaker 01:
And it is a general principle.

[00:18:11] Speaker 01:
The Silverman chapter is out there.

[00:18:15] Speaker 01:
And as Your Honor pointed out, it says that the methylene is a bioisosteres for the amino group.

[00:18:23] Speaker 01:
But it also says oxygen, sulfur, selenium.

[00:18:27] Speaker 01:
And what Dr. Cohen did in his experiments in 1991, his experiments in 1993, and his two articles is he compared the efficacy and also the toxicity, to some degree, of the same compounds.

[00:18:45] Speaker 01:
But some of them had nitrogen at the alpha carbon.

[00:18:50] Speaker 01:
Some had carbon.

[00:18:51] Speaker 01:
Some had oxygen.

[00:18:52] Speaker 01:
Some had sulfur.

[00:18:53] Speaker 01:
None had selenium.

[00:18:55] Speaker 01:
But he compared those four.

[00:18:57] Speaker 01:
And every single time that he did a comparison, the activity was reduced when you went from a nitrogen to any of those other isostears.

[00:19:11] Speaker 01:
And the board specifically found that this is an A28.

[00:19:17] Speaker 04:
Does that include going to the methylene compound, which is claimed?

[00:19:22] Speaker 01:
Yes, it does.

[00:19:22] Speaker 01:
Every time there was a substitution from an amine to a methylene,

[00:19:27] Speaker 01:
There was a reduction, the most graphic example of that is the isoxazolidine to the two tetrahydroferans, which were in the 1993 article where there was a dramatic reduction two to three times in activity.

[00:19:51] Speaker 01:
But what the ward found, because they looked at all this evidence, was

[00:19:55] Speaker 01:
that, and this is at A28, petitioner does not identify any specific example in the prior art of record in which substitution of a non-nitrogen-containing moiety for a nitrogen at the alpha carbon substituent failed to reduce potency.

[00:20:11] Speaker 04:
I wonder why lacosamide then is the product that was developed, not the 3L compound.

[00:20:19] Speaker 01:
And that's an interesting question, but I will say that

[00:20:25] Speaker 01:
is we've litigated this case before in the district court, in this court, and other places, that it was surprising to the people who ultimately tried it.

[00:20:38] Speaker 01:
And they tried hundreds of different compounds.

[00:20:41] Speaker 01:
They tried to find the best.

[00:20:43] Speaker 01:
And it wasn't, and this isn't in the record anywhere, I don't think, but it wasn't like they went from 3L in 1991 to lacosamide.

[00:20:52] Speaker 01:
It was years and years of research later.

[00:20:55] Speaker 04:
Tell us about the Legale thesis.

[00:20:58] Speaker 04:
Doesn't that disclose the same claimed compound for the specified use?

[00:21:06] Speaker 01:
No, not at all.

[00:21:07] Speaker 01:
One, it's not part of the record in this case, but was not one of the grounds for institution.

[00:21:15] Speaker 01:
But the Legale thesis discloses a racemate, 107E.

[00:21:21] Speaker 01:
It does not disclose what became leukosamide

[00:21:25] Speaker 01:
And it also discloses no pharmacological data, nothing that would lead someone to use that compound.

[00:21:32] Speaker 01:
In fact, it's in a group that's in the Legalt thesis of compounds that had terrible activity.

[00:21:40] Speaker 04:
But you're saying it wasn't instituted upon, and that wasn't appealed, and so that's not for us.

[00:21:48] Speaker 01:
It's not part of this appeal.

[00:21:52] Speaker 00:
Mr. Blumenfeld.

[00:21:56] Speaker 00:
The question that troubled me about the two atoms removed from the alpha carbon theory of efficacy is that you responded to that very briefly in your brief, I think, at page 43.

[00:22:13] Speaker 00:
You gave it a paragraph.

[00:22:14] Speaker 00:
And the response essentially was, well, there was also a reference to the

[00:22:21] Speaker 00:
alpha carbon amino substituent.

[00:22:23] Speaker 00:
And also, this was presented to the board.

[00:22:26] Speaker 00:
And therefore, since the board had this evidence, we shouldn't really pay much attention to it.

[00:22:32] Speaker 00:
Of course, if it hadn't been presented to the board, you'd be arguing waiver.

[00:22:35] Speaker 00:
So I think we need a more substantive answer than that.

[00:22:39] Speaker 00:
Do you have a better answer than the one you gave on brief?

[00:22:42] Speaker 01:
Well, Your Honor, there were several things that were disclosed by the art.

[00:22:46] Speaker 01:
And by the way, all of the art here was Cohen's art.

[00:22:50] Speaker 01:
But he disclosed

[00:22:52] Speaker 01:
that nitrogen was essential or was critical to getting good efficacy.

[00:23:01] Speaker 01:
He also had a theory, which he put in his papers about.

[00:23:04] Speaker 00:
Well, that's a little strongly put, isn't it?

[00:23:06] Speaker 00:
I mean, he indicated that it was associated frequently with good efficacy.

[00:23:12] Speaker 00:
But there are certainly compounds that are in the list that have good efficacy that don't have the amide, right?

[00:23:20] Speaker 01:
The compounds, your honor, that had good efficacy, that did not have nitrogen at the alpha carbon, were by and large heteroaromatic compounds.

[00:23:32] Speaker 01:
They were things that had rings.

[00:23:34] Speaker 01:
Totally different compounds.

[00:23:34] Speaker 00:
Were they aromatic or were they just cyclic?

[00:23:36] Speaker 01:
They were aromatic.

[00:23:39] Speaker 01:
They were both.

[00:23:39] Speaker 01:
They were cyclic.

[00:23:40] Speaker 01:
And there were some compounds like the tetrahydroferan that I talked about that was not aromatic.

[00:23:46] Speaker 01:
It had bad efficacy.

[00:23:47] Speaker 01:
But if you look at the data,

[00:23:51] Speaker 01:
The 10 most efficacious compounds, two were 3L and 3N, the nitrogen containing compounds, and the other eight, I believe, were all heteroaromatic compounds.

[00:24:06] Speaker 01:
And it is correct that Dr. Cohen also mentioned that it looked as though having a heteroatom, two atoms from the alpha carbon,

[00:24:18] Speaker 01:
was important, but that didn't make the other things unimportant.

[00:24:22] Speaker 01:
The heteroaromatic ring was important, and the nitrogen was important.

[00:24:28] Speaker 01:
One thing he never said was important was having a methylene group there.

[00:24:32] Speaker 01:
And in fact, if you look at the data and the only data we had, there was not a single compound with a carbon at the alpha carbon

[00:24:47] Speaker 01:
that was something that anyone was interested in.

[00:24:50] Speaker 01:
Certainly, you're not hearing it from the other table, but there's nothing in the literature where anyone was interested in doing that, not until lacosamide became a product.

[00:25:01] Speaker 00:
Well, but the methyl oxymethyl group added to compound 3A, for example, made a whopping difference.

[00:25:12] Speaker 00:
In efficacy, it was much better with the methoxymethyl group, was it not?

[00:25:18] Speaker 00:
When you went from compound 3A to compound 3L.

[00:25:22] Speaker 00:
And that was a pretty strong indication that.

[00:25:25] Speaker 01:
That was going from an amine to a methoxymethyl.

[00:25:29] Speaker 00:
That's right.

[00:25:30] Speaker 00:
But the point is that that is showing potentially the efficacy of the oxygen 2 atoms removed from the alpha carbon, right?

[00:25:39] Speaker 01:
That may have had some contribution.

[00:25:41] Speaker 01:
That certainly was not the conclusion that Dr. Cohen drew when he wrote his 1994 article saying having a basic alpha carbon amine was critical.

[00:25:59] Speaker 01:
He didn't mention the other thing, but it was both things.

[00:26:02] Speaker 01:
Nobody ever said having a carbon at the alpha carbon and having

[00:26:08] Speaker 01:
a heteroatom removed by two atoms made a good compound.

[00:26:13] Speaker 01:
And you're looking at two things.

[00:26:15] Speaker 01:
One, what would a person of skill in the art have come away from looking at what was in the prior art?

[00:26:20] Speaker 01:
And second, more importantly, what did the board found?

[00:26:23] Speaker 01:
And the board considered both of those things, and it found that there was no reason and no reasonable likelihood of success from the prior art to go from methoxyamino to methoxymethyl.

[00:26:38] Speaker 04:
Thank you, counsel.

[00:26:40] Speaker 01:
Thank you, Your Honor.

[00:26:43] Speaker 04:
Mr. Connolly.

[00:26:49] Speaker 04:
You have four minutes if you need it.

[00:26:52] Speaker 03:
Thank you.

[00:26:53] Speaker 03:
There was a question about remand for determination whether 3L was a lead compound, although we don't think that's necessary.

[00:27:02] Speaker 03:
The case could be reversed as is.

[00:27:04] Speaker 03:
But if there is a remand, then we think that the other grounds of institution

[00:27:08] Speaker 03:
The other grounds in the petition that weren't instituted, the board should be instructed to institute pursuant to SAS.

[00:27:18] Speaker 03:
There was also some questions about whether you can modify a lead compound for particular reasons, such as potency.

[00:27:27] Speaker 03:
Well, you can modify a lead compound for a variety of reasons.

[00:27:31] Speaker 03:
It doesn't have to be just one reason.

[00:27:33] Speaker 03:
I think the law on that is pretty well established, even under KSR.

[00:27:37] Speaker 03:
It doesn't have to be one particular reason to modify.

[00:27:41] Speaker 02:
Well, House came in question.

[00:27:42] Speaker 02:
Did you raise Valpro 8 before the PTAB?

[00:27:45] Speaker 02:
Yes, Your Honor.

[00:27:46] Speaker 02:
Where is that?

[00:27:47] Speaker 03:
We'll have the site for you.

[00:27:52] Speaker 03:
OK, thank you.

[00:27:54] Speaker 03:
My colleague, there was also the standing issue.

[00:28:01] Speaker 03:
My colleague may find.

[00:28:03] Speaker 03:
Congress's statutory framework odd, but the remedy is with Congress as far as standing, not with this court.

[00:28:12] Speaker 03:
There's no evidence of record that Argentum, the original petitioner, couldn't have appealed.

[00:28:17] Speaker 03:
There's no evidence on that point at all.

[00:28:20] Speaker 03:
As a matter of efficiency before the board, we did agree to take a backseat role, and the parties to speak as one voice.

[00:28:27] Speaker 03:
That's done as a matter of efficiency in many jurisdictions.

[00:28:33] Speaker 00:
I'm not sure that that's just an accommodation on your part.

[00:28:38] Speaker 00:
I think, at least in light of some of our case law, that you may have been required to take a back seat, weren't you?

[00:28:47] Speaker 00:
If you look at the NYDEC concurring opinion, doesn't that suggest as much?

[00:28:52] Speaker 03:
I don't know that the concurring opinion does.

[00:28:55] Speaker 03:
I know it's a matter of board practice.

[00:28:57] Speaker 03:
That's what they want to see is the party speaking with one voice for a matter of efficiency

[00:29:03] Speaker 03:
in front of the agency.

[00:29:09] Speaker 03:
My colleague also says there was no evidence of instability.

[00:29:13] Speaker 03:
The NO bond is the very reason that RCT said you would ignore 3L in the first place because of that potential instability.

[00:29:21] Speaker 03:
So it's a seesaw analysis that they're trying to conduct.

[00:29:27] Speaker 03:
And that's exactly what KSR prohibits.

[00:29:30] Speaker 03:
Another issue.

[00:29:32] Speaker 03:
was the Lagall thesis that came up.

[00:29:35] Speaker 03:
That Lagall thesis is in the record.

[00:29:38] Speaker 03:
We offered it in an effort to address the secondary considerations.

[00:29:44] Speaker 04:
But it wasn't instituted upon, right?

[00:29:46] Speaker 03:
It wasn't instituted upon because there wasn't evidence of its status as a printed prior publication at the time, because much of that evidence was under seal at the district court.

[00:29:56] Speaker 03:
And it didn't become unsealed until after the board had already instituted.

[00:30:01] Speaker 04:
It's not part of the board decision, is it?

[00:30:05] Speaker 04:
Because it wasn't instituted upon, and therefore it's not before us.

[00:30:10] Speaker 03:
It's part of the record, because we then offered it as prior art to be considered as the closest prior art in the consideration of the secondary, or addressing the secondary considerations.

[00:30:22] Speaker 03:
So it is in the record.

[00:30:25] Speaker 03:
It just wasn't available earlier.

[00:30:26] Speaker 04:
It's in the record, but not in the decision of the board that we're reviewing.

[00:30:31] Speaker 03:
I will have to check and see if they mentioned the Lagall thesis.

[00:30:35] Speaker 03:
I believe they ignore it completely, which we think is error in itself.

[00:30:41] Speaker 02:
Why was it unavailable as under seal?

[00:30:45] Speaker 03:
I'm not privy to the thinking or what was going on between the parties at the time.

[00:30:52] Speaker 03:
It wasn't otherwise available in the community?

[00:30:59] Speaker 03:
Where the Lagall thesis was,

[00:31:01] Speaker 03:
kept the University of Houston library.

[00:31:04] Speaker 03:
The University of Houston refused to cooperate as far as making their librarians available, is my understanding, for providing the testimonies to their procedures.

[00:31:20] Speaker 03:
I just have a few seconds left.

[00:31:23] Speaker 03:
If there's any further questions, Your Honor, we think this case really should merit reversal.

[00:31:30] Speaker 04:
Thank you, counsel.

[00:31:31] Speaker 04:
We'll take the case on revising.