[00:00:07] Speaker 04:
The next case for argument is 16-2610, UCB versus Accord Health Care.

[00:00:41] Speaker 04:
Now, appellants are splitting time.

[00:01:00] Speaker 04:
Nine and four, is that correct?

[00:01:02] Speaker 04:
Okay.

[00:01:03] Speaker 04:
And Ms.

[00:01:04] Speaker 04:
Wirka, you're first?

[00:01:07] Speaker 04:
We'll run the clock at nine just so you'll be able to keep up.

[00:01:11] Speaker 03:
I'd like to focus my limited time here on three legal errors by the district court, two of which were related to the double patenting case and one of which was related to the obvious to purify part of the case regarding the event of standard

[00:01:28] Speaker 03:
Mr. Greco will be addressing, on behalf of the court defendants, the structural obviousness.

[00:01:33] Speaker 04:
Can I just jump to the double patenting and ask you?

[00:01:36] Speaker 04:
We've got a detail fact-finding record by the district court here.

[00:01:42] Speaker 04:
And on the double patenting issue, what are the top three reasons, for example, why you think he was wrong in concluding that there was no reasonable expectation of success?

[00:01:55] Speaker 03:
The first reason, Your Honor, is that we've

[00:01:58] Speaker 03:
Effectively, his finding made the 301 patent, the claims 44 and 45, the 301 patent invalid for lack of enablement.

[00:02:08] Speaker 03:
Correct.

[00:02:09] Speaker 03:
Patent is presumed valid.

[00:02:11] Speaker 03:
The patent is represented to the Patent Office that the patent claims were valid and enabled in response to enablement rejections.

[00:02:20] Speaker 03:
And by finding that there was no reasonable expectation

[00:02:23] Speaker 03:
that a compound with methoxymethyl at the R3 position would be successful as an anticonvulsant, the court essentially found that those claims would not be enabled.

[00:02:39] Speaker 02:
For enablement, just for me to clarify, the full range of the embodiments covered by the claim, every single one of those would have to be

[00:02:49] Speaker 02:
have an expectation of success?

[00:02:52] Speaker 03:
No, but under the court's reading, there would be no compound whatsoever that would fall within that claim.

[00:03:00] Speaker 03:
Not one that would fall within that claim that would be enabled.

[00:03:03] Speaker 02:
You're telling me that if I were to look at the enablement of that claim, I only have to find one embodiment that would be enabled in order to enable the claim?

[00:03:11] Speaker 02:
So it could be something other than what the claim convention is in this case?

[00:03:16] Speaker 03:
No, what you would have to find is at a minimum a representative species that would fall within the claim that would be enabled, and there would be none under the court's reading of that claim.

[00:03:29] Speaker 03:
There would be none because there would be no data on any compound that had methoxymethyl at R3.

[00:03:38] Speaker 03:
None.

[00:03:39] Speaker 03:
And the most obvious one would be the one with the unsubstituted methoxymethyl.

[00:03:44] Speaker 02:
reasonable expectation of success findings just based on the lack of data?

[00:03:50] Speaker 03:
It was found based on the lack of data and the lack of data specifically with a non-aromatic substituent at R3, a non-aromatic carbon-based substituent at R3.

[00:04:06] Speaker 03:
So if the claim had, if claim 44 or 45 had an aromatic compound at

[00:04:13] Speaker 03:
At R3, that might've been enabled, but that isn't what was at the R3 in the claim 44.

[00:04:21] Speaker 02:
In the claim if you're going to look at the claimed intention and recreate.

[00:04:26] Speaker 03:
Correct.

[00:04:27] Speaker 03:
There is literally no compound that would have been enabled under the court's reading of what claim 45 is.

[00:04:33] Speaker 04:
What were your other two points?

[00:04:35] Speaker 04:
Because your clock is running.

[00:04:36] Speaker 04:
So you had three reasons?

[00:04:38] Speaker 03:
Yes.

[00:04:38] Speaker 03:
The second reason would be that the court made a clear error of law in discarding the available information regarding the 3L compound, which was the most potent compound at the time, and also in discarding the information in 729 patent and the data that was in there regarding the closest

[00:05:06] Speaker 03:
compound that Legault found to the methoxymethyl, which is compound 86B.

[00:05:11] Speaker 05:
When you say disregarding, the court talked about those.

[00:05:14] Speaker 05:
You just didn't like the way the court resolved the question of the applicability of those to this case.

[00:05:22] Speaker 03:
I think what he did was he concluded that nothing other than an aromatic, non-carbon-based compound would work or would be believed to have worked.

[00:05:33] Speaker 03:
at the R3, and by doing that, he did not take into account the most potent analog, or the most potent methaxyamino.

[00:05:42] Speaker 05:
He didn't say he didn't take into account.

[00:05:43] Speaker 05:
You really mean he discounted it because he didn't believe that they were particularly pertinent to the factual inquiry, right?

[00:05:54] Speaker 05:
Correct.

[00:05:54] Speaker 05:
And I think that... It was not really a factual question, to get back to Judge Stoll's question.

[00:06:00] Speaker 03:
Yes, that is a factual question.

[00:06:02] Speaker 03:
We would be challenging that under the clearer rules.

[00:06:05] Speaker 04:
What about all of the work that Dr. Cohn had done beforehand?

[00:06:10] Speaker 04:
What about the district court's treatment of that information?

[00:06:14] Speaker 04:
Because it seems that you did have quite a bit of information, quite a factual record, with regard to the experimentation done by Dr. Cohn.

[00:06:21] Speaker 03:
Correct.

[00:06:22] Speaker 03:
And the experimentation that was done by Dr. Cohn suggested that not just an aromatic compound

[00:06:28] Speaker 03:
would work, but that also non-aromatic compounds would work and compounds with a carbon base would also work at the methoxy amino, I'm sorry, at the R3 position.

[00:06:41] Speaker 05:
But hadn't the evidence up to the time of the patented suit really indicated through Dr. Cohn's work that the polar analogs did not have strong potency and it was really the

[00:06:58] Speaker 05:
aromatic and the heteroaromatic these constituents that actually carried the greatest promise.

[00:07:08] Speaker 03:
That's correct, but to say that... You don't quarrel with that.

[00:07:11] Speaker 03:
Right.

[00:07:12] Speaker 03:
I don't have a quarrel with that, but I do have a quarrel, except for the methoxyamino compound was the most potent, and that was... As it turns out, right.

[00:07:19] Speaker 03:
Right.

[00:07:19] Speaker 03:
Well, and that was published.

[00:07:21] Speaker 03:
That was published and available as prior art, but the methoxyamino was the most potent, and in fact, that's what the

[00:07:27] Speaker 03:
like Poston mentioned, the guys were doing, were using as kind of the comparator.

[00:07:33] Speaker 03:
But I think the art did not exclude at all the use of the methoxymethyl, which is again, for double patented purposes, we assume that's constant.

[00:07:46] Speaker 03:
And the polar analogs, for example, Compound 86B, were actually published as having

[00:07:56] Speaker 03:
comparable potency to marketed drugs, to drugs that were on the market and being sold in 1996.

[00:08:04] Speaker 03:
Compound 86B I think had an ED of 50 of 61 and a marketed drug that it was compared to in the table was 62.

[00:08:14] Speaker 03:
So it had, it may not have been the best, but it certainly was in the realm of a viable

[00:08:22] Speaker 03:
compound to use as an anti-convulsant as it was comparable to what was already on the market in 1996 and being sold.

[00:08:32] Speaker 03:
So for that reason, I think it was clearly erroneous to disregard or not count the evidence related to non-aromatic groups at the R3.

[00:08:48] Speaker 05:
I don't recall this specifically.

[00:08:51] Speaker 05:
was Compound 86B one of the compounds as to which there was a concern of liver toxicity?

[00:08:59] Speaker 03:
I don't believe there was any data on Compound 86B with regard to liver toxicity.

[00:09:05] Speaker 03:
And that's the compound that Ligol, when he published Compound 107E, predicted that the

[00:09:14] Speaker 03:
predicted the activity of 107E as well.

[00:09:17] Speaker 03:
So this is not a circumstance.

[00:09:19] Speaker 02:
There is no data.

[00:09:20] Speaker 02:
He had no data on 107E.

[00:09:21] Speaker 02:
Correct.

[00:09:22] Speaker 02:
He had no data on 107E.

[00:09:23] Speaker 02:
He just said it might have a positive result.

[00:09:26] Speaker 03:
Right.

[00:09:27] Speaker 03:
But what he was doing was looking at the compounds he was testing, including 86B.

[00:09:32] Speaker 03:
And from that examination, had decided that and declared that he thought that 107E would also be structurally similar to 86B would be

[00:09:43] Speaker 03:
one with anti-convulsant activity.

[00:09:46] Speaker 05:
When was the first time that methoxymethyl at the R3 came up in the prior R?

[00:09:53] Speaker 03:
The only time it did is in the 301 patent, your honor.

[00:09:56] Speaker 03:
Well, I'm sorry.

[00:09:57] Speaker 03:
No, I'm sorry.

[00:09:58] Speaker 03:
In 1987, Ligol published it in his thesis, compound 107E.

[00:10:04] Speaker 05:
Oh, but other than 107E.

[00:10:06] Speaker 05:
Right.

[00:10:07] Speaker 05:
Did it ever show up before the 301?

[00:10:10] Speaker 03:
It did not show up before the 301.

[00:10:11] Speaker 05:
Technically, it's not prior art, I guess.

[00:10:14] Speaker 03:
Correct.

[00:10:15] Speaker 03:
Was it in the prior art?

[00:10:16] Speaker 03:
It was in the thesis, it was in the Ligol thesis, and then it was in the 301 patent.

[00:10:20] Speaker 03:
But nowhere else?

[00:10:21] Speaker 03:
Nowhere else.

[00:10:22] Speaker 02:
So just to clarify, 301 is not prior art.

[00:10:24] Speaker 02:
The 301 patent is a double patenting reference.

[00:10:27] Speaker 02:
So I understand in this case, it's a double patenting reference, but technically, is it prior art?

[00:10:33] Speaker 03:
It is not prior art.

[00:10:34] Speaker 03:
The specification is shared with the 729 patent, which predated it, and that is prior.

[00:10:42] Speaker 03:
So the claim in the 301 with the 729 specification is the double patenting case.

[00:10:51] Speaker 03:
Thank you.

[00:10:57] Speaker 04:
Thank you.

[00:10:58] Speaker 04:
Mr. Greco, you've got four minutes.

[00:11:04] Speaker 00:
Good morning, Your Honors.

[00:11:05] Speaker 00:
May it please the Court.

[00:11:06] Speaker 00:
My name is Richard Greco.

[00:11:08] Speaker 00:
I represent the Court of Health Care and Intense Pharmaceuticals.

[00:11:11] Speaker 00:
And I'd like to first address the issue of obviousness.

[00:11:14] Speaker 00:
The claims of the patent in this case are obvious because there is no difference between the objective scope of the claims and the literal teachings of the prior art.

[00:11:25] Speaker 00:
The claims in issue are to the R-stereoisomer of a prior art structure known as 107E and its use as an anti-convulsant.

[00:11:34] Speaker 00:
The Priorart-Lidol thesis taught 107E as a member of a class of anticonvulsants, stated that it may have good activity, taught that the R-stereoisomer of the parent compound 107E and another close relative was 13 times more potent than the S, and expressly stated that you had the choice of making separate stereoisomers.

[00:11:56] Speaker 00:
The Priorart-729-PAP, known by the plaintiffs, confirms that 107E

[00:12:01] Speaker 00:
and its R-stereoisomer is an effective anticonvulsant because it is included in the formula claimed as such.

[00:12:10] Speaker 00:
That patent also teaches the R-stereoisomer is preferred.

[00:12:14] Speaker 00:
Anyone who read Lugal and the 1729 patent would already know exactly what is claimed in this case, that the preferred R-stereoisomer of 107E was an anticonvulsant.

[00:12:29] Speaker 00:
Rather than showing an objective difference between the prior art and the claims as required by the Supreme Court test, the plaintiffs in the court below applied a subjective standard of trying to determine what a person of ordinary skill in the art would prefer to select to develop or would find most promising.

[00:12:49] Speaker 00:
The problem with that standard is it doesn't address the basic issue of obviousness.

[00:12:53] Speaker 00:
Is the claim new, or is it something that was already taught in the prior art?

[00:12:58] Speaker 02:
I understand it's a lead compound analysis, that's what's being said.

[00:13:02] Speaker 02:
That's right, it's... Do you agree that there should have been a lead compound analysis?

[00:13:06] Speaker 02:
No, I think the lead compound analysis, and this is... Just inapplicable in this case, or is it just never should be applied?

[00:13:14] Speaker 00:
The lead compound, as defined in the Yotsuka case, I believe is incorrect, and I've been straight up on that in my brief, that it's inconsistent with the KSR, it's inconsistent with Ray Dillon.

[00:13:25] Speaker 00:
And here's the reason why.

[00:13:26] Speaker 00:
That kind of analysis doesn't compare the claim to the entire prior art, but only to a narrow subset of the prior art that's carved out on the basis of a retroactive judgment of what a person of ordinary skill would have preferred to develop.

[00:13:42] Speaker 00:
In fact, it allows an old idea that's fully known and fully developed in the art to be claimed as an invention, as long as that wasn't one of the preferred pieces of prior art.

[00:13:54] Speaker 00:
And that can't be right.

[00:13:57] Speaker 00:
And it's made clear here, I think, in the opinion below by the court's ruling that no functionalized amino acid compound could be an elite compound.

[00:14:08] Speaker 00:
In effect, saying that in spite of the patent and the numerous articles about functionalized amino acids and all the teachings of how to make them and how to change them to make new ones, nothing could be obvious in that field because it hadn't been approved by the FDA.

[00:14:26] Speaker 00:
makes sense in terms of what an invention is.

[00:14:29] Speaker 00:
The plaintiffs also deal with the 729 patent by suggesting this is simply a classic case of a separate genus and species patent.

[00:14:40] Speaker 00:
But that doesn't really fit here, because 107e was known in the prior art.

[00:14:45] Speaker 00:
The plaintiffs did not

[00:14:48] Speaker 00:
claim a new species that they derived from the genus of the 729 patent.

[00:14:53] Speaker 00:
That was already known.

[00:14:54] Speaker 00:
It did not have to be derived from the genus.

[00:14:57] Speaker 00:
What they claimed was the preferred and obvious version of a known chemical species.

[00:15:04] Speaker 00:
I wanted to do anticipation, but I'm out of time.

[00:15:07] Speaker 00:
I'd like to hear briefly on that.

[00:15:09] Speaker 00:
I think we're good.

[00:15:10] Speaker 00:
Thank you.

[00:15:11] Speaker 00:
OK, thank you.

[00:15:19] Speaker 04:
Good morning.

[00:15:20] Speaker 01:
Good morning, Your Honor.

[00:15:20] Speaker 01:
I'm Dimitris Dribas for UCB Research Cooperation in Paris.

[00:15:25] Speaker 01:
There is one critical difference between the 551 patent and the 301 patent in all the prior art.

[00:15:31] Speaker 01:
And that is that the claimed compound in the 551 patent is for chronic administration.

[00:15:39] Speaker 01:
And that was proved with liver toxicity data, which does not appear anywhere in the prior art.

[00:15:46] Speaker 01:
Liver toxicity was a side effect

[00:15:49] Speaker 01:
that plagued all epilepsy drugs.

[00:15:53] Speaker 01:
Epilepsy is a heterogeneous disease.

[00:15:56] Speaker 01:
The causes are unknown.

[00:15:57] Speaker 01:
It differs from patient to patient.

[00:16:00] Speaker 01:
And it is so difficult to develop drugs in this area that the NIH set up its anti-convulsant screening program.

[00:16:09] Speaker 01:
From 1975 to 1996, 16,000 compounds were tested, and only one was FDA approved.

[00:16:18] Speaker 01:
One year after approval, they had to issue a black box warning because of its side effects on liver toxicity and aplastic anemia.

[00:16:26] Speaker 01:
So this is a terribly unpredictable area.

[00:16:31] Speaker 01:
If I could address the double patent issue.

[00:16:34] Speaker 05:
I'm a little confused about the way you began, because I thought that the issue of liver toxicity and the therapeutic effect of the drug was confined to

[00:16:48] Speaker 05:
not to claim 9, but to claim 10.

[00:16:51] Speaker 05:
Claim 10?

[00:16:52] Speaker 05:
Are you now making an argument that that same liver toxicity factor applies to claim 9, or are you just focusing on claim 10 now?

[00:17:00] Speaker 01:
Focusing on claim 10, there is a specific term in claim 10 that says therapeutic composition.

[00:17:05] Speaker 05:
Yes, and I understand that argument.

[00:17:07] Speaker 05:
When you let off with that, it seemed to me you were leading off with an argument which doesn't show up until about page 58 of your brief.

[00:17:15] Speaker 01:
If you read the specification of the 551 packet, it distinguishes all other functional amino acids that came before it as not being suitable for chronic administration.

[00:17:28] Speaker 05:
That may be, but 9 doesn't require a composition that's suitable for chronic administration, right?

[00:17:36] Speaker 01:
It doesn't require, but that is one of the properties of that drug that prior compounds don't have and weren't shown to have.

[00:17:45] Speaker 01:
Certainly in claim 10, it is there.

[00:17:47] Speaker 01:
And that claim construction is uncontested.

[00:17:51] Speaker 01:
So going through the double patenting issue and the 301 patent and the 551 patent.

[00:17:57] Speaker 04:
Can you address the first thing we addressed with your friend on the other side, which was the enablement question on 301?

[00:18:04] Speaker 01:
It's not a question of enablement.

[00:18:06] Speaker 01:
As I see double patenting, the 301 patent claim 45 covers millions of compounds.

[00:18:12] Speaker 01:
And the question really is, is claim 9 of the 551, does it cover a patently distinct species within that huge genus?

[00:18:23] Speaker 01:
And the answer is yes.

[00:18:25] Speaker 04:
But why don't you answer my question?

[00:18:26] Speaker 04:
I know you find you can come up with other questions and answer your own questions, but what about my question about it, whether or not 301 is enabled?

[00:18:34] Speaker 01:
It is enabled.

[00:18:35] Speaker 01:
It is enabled for anticonvulsants generally.

[00:18:38] Speaker 01:
It doesn't have to enable every single compound within that huge genus.

[00:18:44] Speaker 01:
And a person of ordinary skill in the art looking at that genus would have to select, assuming that R3 is kept constant in 301, claim 45, with an methoxymethyl group, the person of skill in the art would have to select R and R1 to put on that compound to get to claim 9 of the 551.

[00:19:08] Speaker 01:
The argument is, well, benzyl and methyl were new in the prior art, and that should direct the person of ordinary skill in the art.

[00:19:16] Speaker 01:
But in the Gauss thesis, the polar group compounds all had terrible activity, and they had benzyl and methyl on the two ends.

[00:19:27] Speaker 01:
Not with methoxymethyl, but with other polar groups.

[00:19:30] Speaker 01:
So a person of ordinary skill in the art looking at that

[00:19:33] Speaker 01:
would not be able to say, well, then benzyl and methyl are the obvious choice for methyl methoxy, because those compounds exhibited terrible activity.

[00:19:44] Speaker 01:
Then the question is 86B.

[00:19:47] Speaker 01:
86B was not a polar group compound.

[00:19:50] Speaker 01:
It had a nitrogen in there.

[00:19:52] Speaker 02:
Can I go back to the enablement question for a minute?

[00:19:54] Speaker 02:
Could you maybe explain why does the whole scope

[00:20:00] Speaker 02:
the claim have to be enabled in order for the claim to be enabled?

[00:20:05] Speaker 02:
How do you respond to your adversary's specific statement that as a result of Judge Stark's ruling in this case, that claim is not enabled?

[00:20:14] Speaker 02:
What had to be enabled and what didn't?

[00:20:18] Speaker 02:
What was the requirement there?

[00:20:20] Speaker 01:
What had to be enabled is a genus of compounds that exhibited anti-combulsant activity with this general chemical structure, and that is enabled.

[00:20:30] Speaker 02:
How do you know that?

[00:20:32] Speaker 02:
How do we know that?

[00:20:34] Speaker 01:
Well, there is no example that they've come forward where it doesn't work, specifically, for anti-convulsive activity.

[00:20:42] Speaker 01:
Some anti-convulsive activity.

[00:20:45] Speaker 01:
Some are not good.

[00:20:46] Speaker 01:
Some are better than others.

[00:20:47] Speaker 01:
You don't have to enable the entire scope of the client.

[00:20:52] Speaker 01:
If there's one compound that doesn't work as well as another, that doesn't defeat enabled

[00:20:59] Speaker 05:
To go to the argument that's, I guess, the simplest form of the argument that's made by your adversary in the brief, you've got the R3 is fixed per claim 45, I guess, of the 301.

[00:21:14] Speaker 05:
So we're starting out with that as the baseline.

[00:21:18] Speaker 05:
Then what you're left with is benzoyl at R and methyl at R1.

[00:21:24] Speaker 05:
enantiomers, but the enantiomers wash out.

[00:21:27] Speaker 05:
I think we can all agree that that doesn't give you a patentably distinct basis for arguing that the lacosamine is different from what's in the prior art, right?

[00:21:40] Speaker 05:
That you're not hanging your hat on the enantiomers, right?

[00:21:45] Speaker 05:
All right.

[00:21:46] Speaker 05:
So why isn't it enough to

[00:21:50] Speaker 05:
To bring into question Judge Stark's conclusion, that the 729, which is prior art, says that the most preferred component at the R is benzoyl and the most preferred component at the R1 is methyl.

[00:22:11] Speaker 01:
Well, 729 says unsubstituted or substituted benzoyl.

[00:22:17] Speaker 01:
And there are the fluorobenzoyl compounds

[00:22:20] Speaker 01:
would show a greater protective index than those with benzene.

[00:22:26] Speaker 01:
So one skilled in the art would assume that perhaps fluorobenzene or some other unsubstituted benzene, which is subsumed in a 301 claim, would be a better selection for making a compound.

[00:22:44] Speaker 05:
So that's the basic distinction on which

[00:22:48] Speaker 05:
you're predicating your cases is the possibility that the 729 includes both substituted and unsubstituted forms of benzoylmethyl.

[00:23:02] Speaker 05:
That's one of them.

[00:23:03] Speaker 05:
What's the other, though?

[00:23:05] Speaker 05:
I think we eliminated everything else, didn't we?

[00:23:07] Speaker 01:
Then again, the question is, is claim 9, which is one compound, the RN-Anshimer lacosamide, patentably distinct from that genus?

[00:23:18] Speaker 05:
But the genus has been narrowed by the R3 being fixed.

[00:23:25] Speaker 05:
And if you agree with your opposing counsel, the R1 and the R being fixed as methyl and benzyl respectively, what's another argument besides the one you just made about substantiated and untouched?

[00:23:42] Speaker 01:
R1 and R are not fixed.

[00:23:47] Speaker 01:
has a choice of millions.

[00:23:48] Speaker 05:
No, but fixed by the references to the most preferred substituents at R and R1.

[00:23:58] Speaker 05:
You said you had other arguments besides the unsubstituted.

[00:24:01] Speaker 05:
What do you have?

[00:24:03] Speaker 01:
The teaching is a general teaching with many different R3 groups.

[00:24:08] Speaker 01:
The selection of which of those two substitutions will be best with

[00:24:14] Speaker 01:
a select R3 group is not enough.

[00:24:16] Speaker 01:
But we're starting with a fixed R3.

[00:24:19] Speaker 05:
I thought we agreed on that.

[00:24:20] Speaker 05:
Yes.

[00:24:21] Speaker 05:
OK.

[00:24:21] Speaker 05:
So what we're left with is R and R1, correct?

[00:24:25] Speaker 05:
Correct.

[00:24:26] Speaker 05:
OK.

[00:24:26] Speaker 05:
And we have told by the 729 that the most preferred at R is benzyl and the most preferred at R1 is methyl.

[00:24:33] Speaker 05:
Now, you tell me, ah, but there is substituted and unsubstituted forms of methyl and benzyl.

[00:24:42] Speaker 05:
And then I said, well, is that it?

[00:24:43] Speaker 05:
And you said, no, no, there are other things.

[00:24:45] Speaker 05:
What?

[00:24:46] Speaker 05:
I come back to my question.

[00:24:48] Speaker 01:
What else?

[00:24:49] Speaker 01:
Looking at the ARCH would look at the different publications, understand that those two groups were fixed in order to study the effect of R3 and changing R3 in that compound.

[00:25:04] Speaker 02:
Does the 729 patent say that?

[00:25:08] Speaker 02:
One thing I thought in looking at the 729 patent is there's other

[00:25:13] Speaker 02:
I don't know if they've been described as preferred embodiments.

[00:25:30] Speaker 01:
They are different embodiments.

[00:25:38] Speaker 01:
where you fix R3 and vary the other groups, and don't vary the other groups, you're really looking just at R3 and its effect.

[00:25:45] Speaker 01:
So you don't know what the effect of changing the different other R groups would be.

[00:25:51] Speaker 01:
So a person of skill in the art would not have any teaching as to what would be best with methoxymethyl.

[00:25:58] Speaker 01:
Because there is totally no teaching

[00:26:01] Speaker 01:
as to what the best R groups on methoxymethyl are.

[00:26:04] Speaker 02:
So as I understand your argument, you're saying maybe it's obvious to try, but there's no reasonable expectation of success?

[00:26:10] Speaker 01:
There is no reasonable expectation of success at all in this field.

[00:26:14] Speaker 01:
And I would say there's a reasonable expectation.

[00:26:16] Speaker 04:
But you said, you used the word, oddly, you used the word that it was the best.

[00:26:19] Speaker 04:
I mean, reasonable expectation of success doesn't mean require that he establish that it was the best.

[00:26:26] Speaker 04:
That's right.

[00:26:27] Speaker 01:
But in this field, where everything is unpredictable,

[00:26:31] Speaker 01:
And it's these phenotypic tests.

[00:26:33] Speaker 01:
There is no structure analysis because the mechanism of epilepsy and how these drugs work is unknown.

[00:26:40] Speaker 01:
So you have to test each compound in these phenotypic tests to see what's going on.

[00:26:45] Speaker 01:
And you can't possibly draw a conclusion from that.

[00:26:48] Speaker 01:
And that's why the furanil compound, which was the best, turned out to be highly toxic to the liver.

[00:26:54] Speaker 01:
And that's what the prior art teaches.

[00:26:56] Speaker 01:
Surprisingly and unexpectedly, this methoxymethyl compound

[00:27:00] Speaker 01:
didn't have those liver toxicity problems.

[00:27:03] Speaker 05:
I know that your own had toxicity problems.

[00:27:07] Speaker 05:
Am I wrong in my vague recollection from the record was that AB6V had toxicity problems.

[00:27:13] Speaker 05:
Is that wrong?

[00:27:14] Speaker 05:
I didn't ask your opposing counsel.

[00:27:15] Speaker 01:
I just wanted to see if I'm... I don't think it was tested for toxicity.

[00:27:20] Speaker 05:
OK.

[00:27:20] Speaker 05:
That's funny.

[00:27:21] Speaker 05:
I am wrong, I think.

[00:27:25] Speaker 01:
Thank you.

[00:27:26] Speaker 01:
So turning to the obviousness issue,

[00:27:30] Speaker 01:
One ordinary skill in the art, the court, in an extensive decision, 96 pages, 50 pages of findings of fact, concluded that a person of ordinary skill would not select 107E as a lead compound or 3M.

[00:27:47] Speaker 01:
They would look to FDA approved drugs to try to change those drugs or some compound that had gone into clinical trials and had some data surrounding it.

[00:28:01] Speaker 01:
There was absolutely no data on 107e.

[00:28:04] Speaker 01:
Whatever Lagalle said in his thesis comparing 107e to the 86b compound was pure speculation.

[00:28:12] Speaker 01:
And in the intervening years, nobody did anything with 107e.

[00:28:17] Speaker 01:
In fact, when they came up with lacosamide finally and went to these same leading drug companies to develop lacosamide and offer it for a license, they turned it down because they thought it would be toxic.

[00:28:30] Speaker 01:
They didn't know its mechanism of action and for other reasons that they just thought it would not be the compound to take forward.

[00:28:39] Speaker 01:
And that is indicative of what a person of ordinary skill in the art would select as a lead compound.

[00:28:44] Speaker 01:
If the drug industry that was developing these compounds was turning this compound down even after they had data, that to me is probative of what a person of ordinary skill in the art would select as a lead compound going forward in the drug development program.

[00:28:59] Speaker 01:
And they just don't meet that grade in their obvious determination.

[00:29:04] Speaker 01:
As far as anticipation, this claims of the 551 patent are not anticipated by the legal thesis.

[00:29:13] Speaker 01:
There was absolutely no data.

[00:29:15] Speaker 01:
It was no indication that the RN Anshumer at that time in functional amino acids would be the one to select.

[00:29:23] Speaker 01:
That didn't come.

[00:29:24] Speaker 01:
That publication.

[00:29:26] Speaker 01:
by Dr. Cohn came after the overall thesis.

[00:29:29] Speaker 01:
So there was no motivation there.

[00:29:32] Speaker 01:
Thank you.

[00:29:43] Speaker 04:
With respect to the enablement... Just to be clear, I think we've got four minutes left on rebuttal, right?

[00:29:51] Speaker 03:
With respect to the enablement position by UCB, the statement that the entire scope of the claim is enabled means, as a matter of law, that anything that falls within the scope of Claim 44, we would reasonably expect success with.

[00:30:06] Speaker 03:
So if the entire scope of the claim is enabled, as counsel admitted, then anything that falls within there, you would reasonably expect to work as a anti-convulsant

[00:30:17] Speaker 03:
drug, which is what is described as the utility in the 301 patent, and is also described in the 729 patent as the goal of these functionalized amino acids.

[00:30:28] Speaker 05:
But there is a huge range and levels of success, it would seem to me, in this field.

[00:30:34] Speaker 05:
And one of the things that emerges from the record quite clearly is that there are a lot of drugs that have some potency, but very few drugs that have really strong potency and no toxicity.

[00:30:46] Speaker 05:
The ED50, I guess, is the measure of that.

[00:30:50] Speaker 05:
Correct.

[00:30:50] Speaker 05:
To finish the question in a sense, why isn't it sufficient to say there's no reasonable expectation of success, to say that there's no reasonable expectation of exceptional success within a large number of species as to which there is some modest degree of success?

[00:31:11] Speaker 03:
I don't think it's necessary to say that the whole scope of the claim is enabled, or you would reasonably expect success with the entire scope of the claim, when you can expect success with the most obvious of the species that falls within that claim.

[00:31:30] Speaker 03:
The most obvious species that falls within that claim is unsubstituted methyl, which the court found was the only thing that worked, and unsubstituted benzyl,

[00:31:40] Speaker 03:
or two types of substituted fluorobenzyls.

[00:31:45] Speaker 03:
So basically, on the benzyl, on the arc substituent, the only choices that were shown to work in other compounds well were the unsubstituted benzyl and the fluorinated benzyl, the two types of fluorinated benzyls.

[00:32:00] Speaker 03:
You have three choices there.

[00:32:02] Speaker 03:
There's no requirement that each of these be, that you show that the unsubstituted benzyl is the best.

[00:32:08] Speaker 03:
No requirement in the law for that.

[00:32:10] Speaker 03:
So the most obvious compound would be either with the methoxymethyl at the R3, with either the unsubstituted benzyl or one of the two fluorinated benzyls, and definitely the unsubstituted methyl, which the court found as a fact was the only thing that worked on the R1 substitute.

[00:32:32] Speaker 05:
To bring you back to the point that I was talking with Mr. Greaves about,

[00:32:40] Speaker 05:
On column 5 of the 729, the reference to the preferred use of benzoyl at the R and methyl at the R1, Mr. Avis said that included both substituted and unsubstituted benzoyl and methyl.

[00:32:56] Speaker 05:
Do you agree with that?

[00:32:57] Speaker 03:
I agree with that.

[00:32:59] Speaker 03:
There's a spot in column three where it says preferred is unsubstituted, or you can also have substituted.

[00:33:07] Speaker 03:
But if you look at the data in the patent, the data in table one of the 729 patent, 54 compounds were tested.

[00:33:14] Speaker 03:
49 of those 54 had unsubstituted benzyl.

[00:33:19] Speaker 03:
Only five had substituted benzyl, the floral substitutions, and only two of those floral substitutions

[00:33:26] Speaker 03:
showed as good an activity as the unsubstituted benefit.

[00:33:31] Speaker 03:
And if there's nothing further?

[00:33:33] Speaker 03:
No.

[00:33:33] Speaker 03:
Thank you.

[00:33:34] Speaker 03:
Thank you.

[00:33:34] Speaker 03:
We thank both sides and the case system.