[00:00:00] Speaker 02:
Okay, we'll hear next number 20-1552, Takeda Pharmaceutical Company versus Torrent Pharmaceuticals Limited, Mr. Sabrewall.

[00:00:12] Speaker 02:
Here, because the two of you are discussing different issues, we'll let you have

[00:00:19] Speaker 02:
two replies, but that's not a good practice.

[00:00:22] Speaker 02:
But go ahead, Mr. Staplewell.

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

[00:00:24] Speaker 00:
Thank you, Your Honor.

[00:00:25] Speaker 00:
Yes, I do recognize that.

[00:00:26] Speaker 00:
We are only addressing the obvious type double patenting argument.

[00:00:33] Speaker 00:
Your Honor, again, thank you.

[00:00:34] Speaker 00:
Thank you to the Court for your time.

[00:00:37] Speaker 00:
We've served over 40,000 pages for this appeal.

[00:00:40] Speaker 00:
But for today, Your Honors, my argument relies upon only one sentence.

[00:00:45] Speaker 00:
that I'd like to read into the record, and this is from APGX 31.

[00:00:50] Speaker 00:
The main point of dispute between the parties concerns the motivation of the Feng patent of Opposa to modify only the scaffolds of claim 162 of the Feng patent to replace it with the uracil scaffold based on the disclosures regarding uracil and quim.

[00:01:09] Speaker 00:
Your honor, that statement is not from Takeda.

[00:01:12] Speaker 00:
That statement is not from Torrent.

[00:01:14] Speaker 00:
That is from the courts.

[00:01:15] Speaker 00:
The court focused the issue, the main point of the dispute, as the motivation of the POSA.

[00:01:24] Speaker 00:
However, what the court did not do is ever tell either any of the parties what the POSA is.

[00:01:31] Speaker 00:
One would think that if the fact finder is going to identify motivation of a POSA as the main dispute, then it was incumbent upon the fact finder to define the POSA.

[00:01:41] Speaker 00:
The court did anything but that.

[00:01:42] Speaker 00:
The court absolutely refused to do so and made a series of four reversible errors.

[00:01:48] Speaker 00:
Number one is set forth above.

[00:01:49] Speaker 02:
The court said it comes out the same way, whatever verbal skill in the art you attribute to the posa.

[00:01:57] Speaker 02:
So how is that error?

[00:02:01] Speaker 02:
It may not be a desirable way to approach it, but certainly if the court says

[00:02:06] Speaker 02:
I'm not going to decide the issue because it comes out the same way under either definition.

[00:02:12] Speaker 02:
Where's the mistake?

[00:02:14] Speaker 00:
Your Honor, the mistake is simple.

[00:02:18] Speaker 00:
If the court assumes the defendant's definition, the person of ordinary skill in the art, is correct, then Takeda's expert by his own admissions during deposition testimony admitted that he cannot and does not meet that definition.

[00:02:35] Speaker 00:
So if you're going to, on the one hand, say, all right, I am going to assume that we will use Torrance definition, which requires at least some years of experience in DPP-4 inhibitors and or diabetes, well, then what the court should have done is given far more credibility to the only expert who met that definition, and that was Torrance expert.

[00:02:58] Speaker 00:
Tocadis expert is in a completely different field.

[00:03:02] Speaker 00:
He spent 47 years studying hallucinogens, LSD, antipsychotics.

[00:03:09] Speaker 00:
He has no experience in this area, Your Honor.

[00:03:12] Speaker 00:
And this is not, we're not talking about fish oil here.

[00:03:15] Speaker 00:
We're not talking about a headache treatment.

[00:03:18] Speaker 00:
We are talking about a specific type of inhibitor called the DPP4 inhibitor.

[00:03:23] Speaker 03:
Did you do a Daubert motion to exclude Dr. Nichols?

[00:03:27] Speaker 00:
We did not, Your Honor, and that's an interesting question.

[00:03:29] Speaker 03:
Did you ever object to his testimony?

[00:03:32] Speaker ?:
Yes.

[00:03:32] Speaker 00:
Yes, we did.

[00:03:33] Speaker 00:
Yes, we did.

[00:03:34] Speaker 00:
We did extensive cross-examination to the objection of counsel during his trial.

[00:03:41] Speaker 00:
We didn't file a doubter motion for two reasons.

[00:03:43] Speaker 00:
Number one, first of all, it's a bench trial.

[00:03:45] Speaker 00:
And that would have only succeeded in upsetting the judge.

[00:03:49] Speaker 00:
It probably wouldn't have worked because the judge in a bench trial wants to weigh their evidence.

[00:03:54] Speaker 00:
And more importantly, and perhaps more disconcertingly, the parties

[00:03:57] Speaker 00:
Your honor, and this is in footnote one of our briefs, the party especially agreed that it wouldn't, that we wouldn't do this.

[00:04:05] Speaker 00:
And I was very surprised and disappointed to see the council has now come back despite a written agreement between the parties at accusing us of some sort of omission because we didn't file it down.

[00:04:17] Speaker 02:
The theory that you have is that Mr. Nichols or Dr. Nichols

[00:04:24] Speaker 02:
wasn't a posa, and therefore that the district court couldn't rely on his testimony, if I understand it.

[00:04:32] Speaker 02:
But if I read the district court's decision, that it would have come out the same way without relying on Dr. Nichols' testimony.

[00:04:40] Speaker 02:
Am I incorrect about that?

[00:04:42] Speaker 00:
Yes, Sean, respectfully you are.

[00:04:44] Speaker 00:
And the reason is because the court exalted Dr. Nichols' opinion

[00:04:51] Speaker 00:
over Dr. Rotella on every single major issue.

[00:04:55] Speaker 00:
And I have the site pages for that.

[00:04:57] Speaker 00:
For example, let's start with the most important issue.

[00:05:00] Speaker 00:
The main point of dispute, motivation.

[00:05:03] Speaker 00:
The court said motivation is the most important issue here.

[00:05:05] Speaker 00:
By the way, I'm going to rely on Dr. Nichols, APPX32.

[00:05:09] Speaker 00:
Dr. Nichols said the chem reference does not mention DPP4 inhibitors and therefore there's no motivation to come up.

[00:05:16] Speaker 00:
Aside from the fact that that is factually incorrect.

[00:05:20] Speaker 00:
That is exactly the opposite of what the court was supposed to do.

[00:05:23] Speaker 00:
If the court said, I am going to utilize Torrance's definition, what the court should have done is not rely on Dr. Nichols for Kim, not rely on Dr. Nichols for scaffold replacement, not rely on Dr. Nichols for the priority, and not rely on Dr. Nichols for- I'm sorry, sir.

[00:05:40] Speaker 03:
Where on A32 did, can you show me where, the district court lack of motivation

[00:05:50] Speaker 03:
to make the adjustments to F-162 in view of Kim?

[00:05:55] Speaker 00:
Sure.

[00:05:57] Speaker 03:
Relying on Dr. Nichols?

[00:05:59] Speaker 00:
Yes.

[00:06:01] Speaker 00:
It's in footnote three.

[00:06:02] Speaker 00:
Dr. Nichols stated that dayanel is a known drug for treating diabetes.

[00:06:09] Speaker 00:
The Kim reference does not mention DPP4 inhibition.

[00:06:13] Speaker 00:
Transcript site 61, 25 to 62, 2.

[00:06:20] Speaker 00:
The court relied on Dr. Nichols, Your Honors, even though he said he was going to utilize defendant's definition.

[00:06:30] Speaker 00:
This is a clear error that cannot be reconciled.

[00:06:34] Speaker 00:
This was an irreconcilable conflict.

[00:06:36] Speaker 03:
Well, where does Kim mention DPP IV inhibition?

[00:06:41] Speaker 03:
Where does Kim say this thing called uracil inhibits

[00:06:49] Speaker 00:
the DPP IV enzyme.

[00:06:52] Speaker 00:
It's a DPP-4, Your Honor, and it does not mention DPP-4 inhibitors, but that was the problem.

[00:06:58] Speaker 00:
As Dr. Rotella... Okay, so it doesn't mention it.

[00:07:01] Speaker 00:
It does not mention it.

[00:07:03] Speaker 00:
That is correct.

[00:07:04] Speaker 03:
It does not mention it.

[00:07:04] Speaker 03:
Okay, so then what is wrong with that statement?

[00:07:07] Speaker 03:
Because... In quote three that, quote, the Kim reference does not mention DPP-4 inhibition.

[00:07:13] Speaker 00:
Because the court relied upon the fact that the Kim reference does not mention that.

[00:07:18] Speaker 00:
as a lack of motivation, your honor.

[00:07:21] Speaker 00:
And that's the point here.

[00:07:24] Speaker 02:
Where's the motivation?

[00:07:25] Speaker 02:
The motivation that you're arguing for comes only from the fact that these compounds mentioned in Kim have beneficial effects on the treatment of diabetes.

[00:07:38] Speaker 02:
Is there anything more to it than that?

[00:07:39] Speaker 02:
I mean, there's no mention of uracil in Kim, right?

[00:07:44] Speaker 00:
But there doesn't need to be, because in the record, there's extensive prior art.

[00:07:51] Speaker 00:
The Canstrup reference, 2004, the Marks reference, 2004, talking about the use of DPP4 inhibitors in this area.

[00:08:01] Speaker 00:
Talking about DPP4 inhibitors.

[00:08:05] Speaker 00:
The fact that the Kim reference specifically doesn't have all of the elements required

[00:08:11] Speaker 00:
does not mean that there was no motivation.

[00:08:14] Speaker 00:
A person of ordinary skill in the art is presumed to know the common knowledge.

[00:08:18] Speaker 00:
And as Dr. Rotel extensively defined, there was a huge amount of information that came to the surface between 2000 and 2004, including but not limited to the use of DPP4 inhibitors in this area.

[00:08:34] Speaker 00:
The fact that the decino-benzoyl and amino-piprodenyl.

[00:08:38] Speaker 00:
Okay, I'm sorry.

[00:08:40] Speaker 03:
I just want to make sure I understand.

[00:08:41] Speaker 03:
Sure.

[00:08:42] Speaker 03:
The Kim reference doesn't say anywhere that uracil lowers blood glucose by inhibiting the DPP4 enzyme, right?

[00:08:55] Speaker 03:
It doesn't say that.

[00:08:57] Speaker 03:
It does not say that.

[00:08:57] Speaker 03:
Okay.

[00:08:58] Speaker 03:
Is there some other reference, even if it's not Kim, but maybe somewhere else?

[00:09:03] Speaker 03:
whether the teaching in the prior art that uracil inhibits this particular enzyme.

[00:09:12] Speaker 00:
Yes, Your Honor.

[00:09:13] Speaker 00:
And that comes from at least two references that we have.

[00:09:17] Speaker 00:
The Canstrup reference, that is APX333246,

[00:09:25] Speaker 00:
to 33347 JTX5, which discloses xanthine structures in which uracil is part of the two-ring structure that are listed as potent DPP4 inhibitors.

[00:09:37] Speaker 00:
Example 16 of CanStrupp discloses... I got lost there.

[00:09:44] Speaker 03:
Sorry.

[00:09:44] Speaker 03:
What's the name of this reference at 33246-47?

[00:09:48] Speaker 00:
I apologize, Your Honor.

[00:09:49] Speaker 00:
I've had too much coffee this morning.

[00:09:50] Speaker 00:
I'm talking too fast.

[00:09:52] Speaker 00:
The CanStrupp reference, 2004.

[00:09:55] Speaker 00:
The APPX numbers are 333-246-33347.

[00:10:02] Speaker 02:
Can you point us to some expert testimony that says that someone skilled in the art would have taken the uracel structure from these prior art references and that that would give a motivation to use it to replace the scaffolding in the 162?

[00:10:26] Speaker 00:
Yes, Your Honor, that came from the testimony of Dr. Rotella.

[00:10:30] Speaker 02:
Where is that?

[00:10:32] Speaker 00:
Your Honor, I don't have the exact pages of the trial transcript, but there was an extensive discussion of the prior art.

[00:10:39] Speaker 00:
And Dr. Rotella specifically talked about the cancer references we showed demonstrators for this.

[00:10:45] Speaker 02:
OK, but you're supposed to come to oral argument prepared to show us.

[00:10:49] Speaker 02:
You can't just say, oh, it's in there somewhere.

[00:10:52] Speaker 00:
Your Honor, I apologize, it's a huge record.

[00:10:55] Speaker 00:
I will ask one of my colleagues to find the specific pages in the transcript and hopefully I'll get that to you before the end of this.

[00:11:07] Speaker 00:
But I will represent you.

[00:11:09] Speaker 02:
I think we're out of time unless my colleagues have further questions for you.

[00:11:14] Speaker 02:
Okay, so we'll hear from Mr. Poulos.

[00:11:20] Speaker 02:
who's presumably going to discuss the obviousness question, right?

[00:11:25] Speaker 04:
That's right, Your Honor.

[00:11:26] Speaker 04:
Yes, Ivan Pulas on behalf of Appellant Indico Remedies.

[00:11:30] Speaker 04:
May it please the court.

[00:11:33] Speaker 04:
We're asking the court to reverse the district court's judgment on obviousness on the basis of three independent legal errors.

[00:11:40] Speaker 04:
First, as you just heard, the court failed to define the level of skill of art despite that level being in dispute.

[00:11:46] Speaker 04:
But second, and independently,

[00:11:49] Speaker 04:
The court did not conduct its analysis through the lens of a person having ordinary skill in the art, because both sides agreed that such a person would quote absolutely, and that's a quote from Takeda's expert Dr. Nichols, have used structure activity relationships to guide the path forward.

[00:12:09] Speaker 04:
But there was no actual analysis by the court on that question.

[00:12:13] Speaker 02:
Okay, but I think you have a, let's assume that we get past the lead compound issue and we assume that you're correct about the lead compound issue.

[00:12:25] Speaker 02:
And let's assume that you're right about the skill in the R and that we're going to not pay any attention to Dr. Nichols' testimony because of that.

[00:12:35] Speaker 02:
Now, even when you get past the lead compound analysis, you still

[00:12:42] Speaker 02:
have to be able to find that there would have been a motivation to replace the structure of DCAX, which is your lead compound, with your cell structure, correct?

[00:12:59] Speaker 02:
That's right, Your Honor.

[00:13:00] Speaker 02:
OK, so what's the motivation to do that?

[00:13:03] Speaker 02:
I mean, it seems to me that all you talk about is, well, chemists like to find new compounds, and they're trying to avoid the prior arc.

[00:13:12] Speaker 02:
I'm not sure that's sufficient.

[00:13:13] Speaker 02:
What other motivation is there?

[00:13:16] Speaker 04:
Well, Your Honor, when you have a lead compound that is potent like this one is, the key is that you actually know why it's potent, and it's because of those two main substituents for which there's a lot of evidence that we've resided to, and that's the cyano and the amino groups.

[00:13:33] Speaker 04:
Now, the motivation to then produce additional potent compounds based on that is the fact that

[00:13:41] Speaker 04:
is that the post, though, would want to make additional compounds that are free of patent protection, that may, in fact, have more potency.

[00:13:57] Speaker 04:
There's a motivation to improve upon the potency and properties of the compound that existed.

[00:14:03] Speaker 04:
And really, all that requires is it's based on the assumption.

[00:14:07] Speaker 02:
But why would the using uracel

[00:14:10] Speaker 02:
as the scaffolding for GCAX resulted in a more potent compound.

[00:14:16] Speaker 02:
What's the evidence that that would be the case?

[00:14:19] Speaker 04:
Well, Your Honor, the evidence and the requirement is that the new compound have properties that are, quote, similar to the old.

[00:14:28] Speaker 04:
So there would definitely be an expectation that it would be a potent compound.

[00:14:32] Speaker 04:
And that's the motivation that we need to show.

[00:14:37] Speaker 02:
That's because of the- Exactly.

[00:14:39] Speaker 02:
Why is there a motivation to replace the Zantac scaffolding with the Uracel scaffolding?

[00:14:52] Speaker 04:
Two parts to that answer.

[00:14:53] Speaker 04:
The first is that you would want to keep those substituents because that is what's responsible for the potency.

[00:15:03] Speaker 04:
Now, replacing the scaffold

[00:15:05] Speaker 04:
is not expected to affect the potency if you can hang those scaffolds, hang those substituents in the same relative locations to do the same job.

[00:15:15] Speaker 04:
And that's where the similarity between xanthine and uracil comes in.

[00:15:19] Speaker 04:
They're both obviously nitrod.

[00:15:21] Speaker 02:
What's the motivation to change the scaffolding?

[00:15:26] Speaker 04:
To make additionally potent compounds.

[00:15:29] Speaker 02:
To do what?

[00:15:31] Speaker 04:
First of all, the motivation to change the scaffold is to make additional potent compounds, which is how this field developed.

[00:15:40] Speaker 04:
You make analogs and further develop potent compounds that you know why they're potent.

[00:15:47] Speaker 04:
You say, let's make some more and see if we can improve it.

[00:15:51] Speaker 04:
The motivation to do it in particular

[00:15:53] Speaker 04:
is because xanthine and uracil are very similar and they have corresponding positions where you can put these two substituents such that they would be in the same place.

[00:16:04] Speaker 04:
And if you see in our brief, we actually have a picture of that.

[00:16:09] Speaker 04:
So, you're able to take these same cyano and amino groups and hang them in the same places on a very similar scaffold.

[00:16:19] Speaker 04:
And, you know, there are other advantages.

[00:16:21] Speaker 04:
You're going from two rings to one ring.

[00:16:25] Speaker 03:
If I may just cut in there, we have testimony from your expert that said we want to keep as much of that xanthine scaffold as possible.

[00:16:40] Speaker 03:
And you'd only want to make small changes to a molecule, small conservative changes, not big ones.

[00:16:48] Speaker 03:
And here, you're looking to pull out the entire scaffold and replace it with a new one.

[00:16:54] Speaker 03:
And the record is quite clear that in this particular art, even small changes to a molecular structure can have dramatic effects on the properties of the molecule.

[00:17:04] Speaker 03:
And so it's like a seesaw.

[00:17:05] Speaker 03:
The more substantial you do a modification, the less predictable

[00:17:09] Speaker 03:
what the result is going to be and therefore the more evidentiary support you're going to need to conclude that a POSA, even your preferred POSA person of skill in the art would have some reasonable expectation of success that you can do this full swap out of these two scaffolds.

[00:17:32] Speaker 03:
And I think ultimately that's the concern and that was the

[00:17:39] Speaker 03:
finding against you here by the district court after going through a full trial.

[00:17:45] Speaker 03:
And I'm just wondering how is it that that was an unreasonable fact finding here, given that your references that you're relying on don't talk about inhibiting this particular enzyme or scaffold swaps

[00:18:08] Speaker 03:
So if you could just speak to that.

[00:18:11] Speaker 04:
Sure.

[00:18:12] Speaker 04:
First of all, Your Honor, the similarity between the two scaffolds, that's what he's talking about, and that is why you would use, if I can finish my answer, I see my time.

[00:18:24] Speaker 04:
The two scaffolds are very similar.

[00:18:28] Speaker 04:
If you look at the left-hand side of that,

[00:18:31] Speaker 04:
uracil on the left-hand side of the xanthine, they're identical.

[00:18:35] Speaker 04:
They're the same on that left-hand side.

[00:18:37] Speaker 04:
So the rest, so the scaffolds actually are very similar to each other, and that's the point that our expert was making, is that that's why you choose uracil, because it's very close to xanthine.

[00:18:47] Speaker 04:
And in fact, the evidence does show that there are DPP4 inhibitors where the scaffold has been changed, and that's the

[00:18:56] Speaker 04:
reference that's at Appendix 33489 and specifically in Figure 2.

[00:19:01] Speaker 04:
And there was testimony from our expert at Appendix 1017 that said take a look at those compounds.

[00:19:09] Speaker 04:
They all have different scaffolds.

[00:19:11] Speaker 04:
They all have the cyano and the amino groups in the same relative locations.

[00:19:18] Speaker 04:
And those differences are a lot, differences between those scaffolds are much more different than xanthine to uracil.

[00:19:26] Speaker 04:
I think a person of ordinary skill, and if the court had looked at the evidence through that lens, would have understood that the change from xanthine to uracil is not a major change.

[00:19:37] Speaker 04:
It's in fact a conservative change because scaffolds are not what are responsible for the activity.

[00:19:42] Speaker 03:
Did Weidman show a xanthine to uracil swap?

[00:19:47] Speaker 04:
It did not show a xanthine to your full swap.

[00:19:49] Speaker 04:
No, Your Honor.

[00:19:50] Speaker 04:
Yeah.

[00:19:50] Speaker 04:
That's right.

[00:19:51] Speaker 04:
But it showed this idea of scaffold hopping was prevalent in the DPP-4 context.

[00:19:56] Speaker 04:
That's right.

[00:19:59] Speaker 04:
I'm happy to keep answering questions, though, or to continue.

[00:20:04] Speaker 04:
I heard the timer.

[00:20:04] Speaker 04:
I think that means my time is up, and I'm happy to answer more questions.

[00:20:08] Speaker 02:
Are there more questions from the panel?

[00:20:10] Speaker 02:
No.

[00:20:11] Speaker 02:
OK.

[00:20:12] Speaker 02:
All right.

[00:20:12] Speaker 02:
So we'll give each of you two minutes for a rebuttal, and we'll hear from Mr. Castañas.

[00:20:17] Speaker 01:
Thank you, Your Honor.

[00:20:19] Speaker 01:
Thank you, Your Honor, and may it please the Court.

[00:20:24] Speaker 01:
This Court and the Supreme Court have said time and again that a trial is the main event, not a tryout on the road.

[00:20:31] Speaker 01:
In this case, Judge Chesler heard the party's evidence and their experts, made explicit findings under Rule 52.

[00:20:38] Speaker 02:
She seems to have made some mistakes.

[00:20:40] Speaker 02:
I mean, you would seem concerned about this.

[00:20:44] Speaker 02:
argument about what's a posa here.

[00:20:47] Speaker 02:
In fact, your first argument in your brief is that there was invited error here, which seems to me an odd argument to make.

[00:20:57] Speaker 02:
The parties, the experts may have stumbled a bit on each side, but the position of the parties as to what's a posa have been consistent throughout, haven't they?

[00:21:10] Speaker 01:
Well, I think that it's true that the position of each party has been clear, but the defendants offered two different definitions of a POSA.

[00:21:22] Speaker 01:
Their expert, Dr. Rotella, the expert who they offered on obviousness type double patenting, offered a higher standard than Dr. Ferraris did.

[00:21:38] Speaker 01:
In fact, Dr. Ferraris, who was the

[00:21:40] Speaker 01:
expert who presented their statutory obviousness defense under section 103.

[00:21:47] Speaker 01:
Not once did he suggest in his testimony that his understanding of a person of ordinary skill included specific experience with type 2 diabetes or DPP-4.

[00:22:04] Speaker 01:
In fact, he claimed to have been an expert.

[00:22:08] Speaker 02:
Let's just get to the heart of this.

[00:22:09] Speaker 02:
Suppose they're right.

[00:22:10] Speaker 02:
about the level of skill in the art and it has to be somebody who's had experience with DPP4 inhibitors or with diabetes treatment.

[00:22:21] Speaker 02:
And let's assume they're correct about that and that Dr. Nichols doesn't qualify under that standard and we have to take Dr. Nichols' testimony out of the picture for that reason.

[00:22:33] Speaker 02:
Is there still a basis for sustaining what the district court did here?

[00:22:39] Speaker 01:
Not only is there a basis for sustaining what the district court did, that is exactly what the district court did do here.

[00:22:46] Speaker 01:
The district court properly recognized that the burdens belong to the defendants to show invalidity, and those burdens required them to show invalidity on each of their grounds by clear and convincing evidence.

[00:22:58] Speaker 01:
And this judge, and I think the exchange, Judge Dyke, I think it was you who had the back and forth with my friend Mr. Stobberwall earlier in the argument,

[00:23:09] Speaker 01:
Actually, I think Judge Chen then followed up with regard to his citation to Appendix page 32, note 3.

[00:23:18] Speaker 01:
Judge Chessler here considered the defendant's expert's testimony as it was given.

[00:23:26] Speaker 01:
He did not, particularly at that footnote at page Appendix 32, he didn't rely on Dr. Nichols.

[00:23:35] Speaker 01:
He simply observed what Dr. Nichols had said in this context.

[00:23:38] Speaker 01:
What the defendant's experts were found lacking on was not just the substance of their testimony, which was found lacking, but also basic credibility.

[00:23:48] Speaker 01:
This judge made affirmative credibility findings against each of these experts.

[00:23:55] Speaker 02:
Some of those findings seem to be pretty questionable, such as the suggestion that one of the experts had spent his early work on a

[00:24:06] Speaker 02:
particular kind of inhibitor.

[00:24:10] Speaker 02:
I have trouble following why that was incredible.

[00:24:13] Speaker 02:
But let's assume again that the credibility findings with respect to the defendant's experts were mistaken and that so we take Dr. Nichols out of the picture, we say the defendant's

[00:24:31] Speaker 02:
are not incredible because of these things that they testified to.

[00:24:39] Speaker 02:
But is there still a problem here if we were to do that?

[00:24:45] Speaker 01:
There are ample problems with that, Judge Dyke.

[00:24:49] Speaker 01:
And the biggest problem, and this was identified by Judge Chesler with regard to both expert witnesses of the defendant and each of their theories.

[00:25:01] Speaker 01:
was that they engaged in hindsight analysis.

[00:25:04] Speaker 01:
They knew the conclusion that they had to get to and they worked from that direction.

[00:25:09] Speaker 02:
With regard to Dr. Ferraris, his section 103... I'm trying to put that aside and focus on exactly what the argument here is with respect to double patenting and obviousness.

[00:25:24] Speaker 02:
On obviousness, I mean assuming that the judge is wrong about the lead compound,

[00:25:29] Speaker 02:
there's still this necessity to replace the syntax scaffolding with the uracil scaffolding.

[00:25:40] Speaker 02:
And what's the evidence that they presented that someone skilled in the art would have done that?

[00:25:52] Speaker 02:
All I'm hearing is that there would be a desire to,

[00:25:59] Speaker 02:
create new compounds that would avoid the prior art.

[00:26:03] Speaker 02:
This seems to be a critical feature of the obviousness analysis.

[00:26:09] Speaker 01:
And that's not enough.

[00:26:11] Speaker 01:
In fact, if you look, for example, at the testimony of Dr. Rotella at pages appendix 911 to 912, he goes through and is asked about Wiedemann.

[00:26:24] Speaker 01:
He's asked about the W0496 patent.

[00:26:28] Speaker 01:
He's asked about the CA730 patent, and he says that Uracel has never mentioned or disclosed in any of those references.

[00:26:36] Speaker 01:
And in fact, he goes so far as to mention the Mark 2004 patent, which is the Kenstrip reference that my friend Mr. Soberwald referred to in his opening argument.

[00:26:47] Speaker 01:
And the testimony is as follows, and this is at 912 line 3, and the Mark 2004 patent discloses a large number of DPP4 inhibitors yet,

[00:26:58] Speaker 01:
doesn't say one word about using uracil as a scaffold.

[00:27:01] Speaker 01:
Doesn't.

[00:27:02] Speaker 01:
Answer, no.

[00:27:04] Speaker 01:
So where they're looking for motivations, they are recreating their case after the fact based on having to assume, as Judge Dyck, you've had to make a number of assumptions, just in their cases, just to get to this point, assume that the judge didn't do what he explicitly said that he did, which is to properly consider

[00:27:27] Speaker 01:
the person of ordinary skill level through the higher lens that we have heard a lot about in the opening arguments.

[00:27:36] Speaker 01:
And that's particularly, that's particularly evident when it comes to his discussion of the, Judge Chesler's discussion of the obviousness type double patented arguments at pages 39 to 42.

[00:27:49] Speaker 01:
He explicitly states that he is using

[00:27:55] Speaker 01:
Dr. Rotella's higher standard in that regard.

[00:27:59] Speaker 01:
So again, with regard to the attack on Dr. Nichols, I'm not sure where that gets them because they bore the burden.

[00:28:08] Speaker 01:
This was a classic case of competing experts.

[00:28:13] Speaker 01:
Their experts were found wanting.

[00:28:15] Speaker 01:
Their experts were found to have engaged in hindsight analysis.

[00:28:19] Speaker 01:
Their experts were, in fact, in both cases, were found to have

[00:28:23] Speaker 01:
been given their starting reference, not by searching the prior art, but by the lawyers in the case.

[00:28:30] Speaker 01:
So the, I, I, I end with where I started, which is that the trial is the main event.

[00:28:39] Speaker 01:
The judge made findings.

[00:28:40] Speaker 01:
They're not clearly erroneous.

[00:28:42] Speaker 01:
He applied the proper legal standards and he said both, uh, at page eight 30, and then again at pages eight 39 to 42,

[00:28:52] Speaker 01:
that he was applying the higher standard that they're arguing.

[00:28:55] Speaker 01:
That's why we've said that even if there was an error, even if they could possibly show on this record that the lower standard of a person of ordinary skill was applied, they would have invited that error because in fact, their Dr. Ferraris used exactly that standard in his testimony.

[00:29:15] Speaker 01:
So unless the court has further questions for me, I think we can rest on the briefs of the argument already given.

[00:29:20] Speaker 03:
When it comes to the obviousness type double patenting challenge, I heard the opposing counsel talk about how this Kim reference is very important, very relevant in what it teaches about uracil.

[00:29:36] Speaker 03:
And then I believe he made a reference to a prior art reference in the record that establishes that it was known in the art that uracil

[00:29:50] Speaker 03:
inhibits this BPP4 enzyme.

[00:29:56] Speaker 03:
Do you have a response to that?

[00:29:59] Speaker 01:
Dr. Chen, I think I must not have spoken clearly because that's the Canstrip reference, which we refer to in our briefs as the Mark 2004 patent from the Berendur-Ingelheim company.

[00:30:13] Speaker 01:
That's the one that does not at all mention uracil.

[00:30:18] Speaker 01:
And that's also relevant to the testimony that I just read to you from Dr. Rotella who at page appendix 912 lines 3 to 6 said it doesn't say one word about using uracil as a scaffold, does it?

[00:30:35] Speaker 01:
And he agreed with that and said no, it does not.

[00:30:38] Speaker 03:
Okay.

[00:30:40] Speaker 03:
And then I know it's, there's been a lot of talk here about how to properly define the

[00:30:49] Speaker 03:
relevant person of skill in the art for purposes of this case.

[00:30:54] Speaker 03:
I think the other side is citing a Federal Circuit decision called Daiichi, 2007, and relying on that.

[00:31:08] Speaker 03:
And I was just wondering if you could speak to why you believe your proposed articulation of the skilled artist

[00:31:18] Speaker 03:
is appropriate.

[00:31:22] Speaker 03:
It doesn't maybe have to be the very best, but at least it's appropriate for purposes of this case.

[00:31:30] Speaker 01:
So, Judge Chen, I think the answer is that, as the record reflected here, medicinal chemistry, people work in multiple areas, and they take from these various areas.

[00:31:43] Speaker 01:
And that's why both Dr. Nichols and Dr. Ferraris

[00:31:49] Speaker 01:
did not have the specific to the particular technology that is actually claimed in the patent DPP-4 and type 2 diabetes as part of the definition.

[00:32:04] Speaker 01:
I think that the testimony of Dr. Nichols on this point, and again, as agreed to by Dr. Ferraris, should make that clear.

[00:32:15] Speaker 01:
What we believe is going on here is that

[00:32:19] Speaker 01:
The higher standard that was proposed only by Dr. Rotella is being used to cover up a number of sins in their case by suggesting that a person of ordinary skill would be able to make all of these counterintuitive leaps that Judge Chesler at length described in his opinion with regard to both of their theories.

[00:32:46] Speaker 02:
Well, that sort of hurts you because that seems to suggest that if we were to agree with the appellant that their killing the art was appropriate, that that would get them home.

[00:32:59] Speaker 01:
No, I certainly didn't mean to suggest that for a second.

[00:33:03] Speaker 01:
I was simply trying to point out what the to unpack what the strategy is that's being used by one of the two defendants in this case.

[00:33:13] Speaker 02:
Well, I mean, the Daiachi case

[00:33:15] Speaker 02:
lays forth a number of factors that you would consider.

[00:33:20] Speaker 02:
And neither one of you really seems to analyze the question based on the Diachi factor.

[00:33:27] Speaker 02:
I mean, this is a pretty specialized area.

[00:33:31] Speaker 02:
And Dr. Nichols' experience didn't include working on diabetes or DPP4 inhibitors.

[00:33:44] Speaker 01:
Well, I think I also need to bring the court back to one other citation in the record with regard to that.

[00:33:52] Speaker 01:
And one of the reasons why this isn't really established in the record is that the other side didn't make an objection to this.

[00:34:00] Speaker 01:
Mr. Sabharwal talked about this being a bench trial and not wanting to irritate the trial judge, but quite frankly, you still have to make your objections.

[00:34:08] Speaker 01:
And if I could point you to page 1136 of the appendix,

[00:34:12] Speaker 01:
After Dr. Nichols was qualified as an expert, our lawyer said, Your Honor, we proffer Dr. Nichols as an expert in medicinal chemistry, pharmacology, and drug development.

[00:34:25] Speaker 01:
Mr. Stoverwall, no objection, Your Honor.

[00:34:28] Speaker 01:
The court so deemed.

[00:34:30] Speaker 01:
So again, with regard to the late coming objection to Dr. Nichols, his testimony was viewed as relevant and

[00:34:40] Speaker 00:
Arguing this at rule 52 strikes me as a bit too late in the game I'm running out of time unless the court has further questions Okay hearing then we'll hear from mr. Sabre wall for two minutes Thank You honors the honors asked the question several times if we take dr. Nichols out of the picture and

[00:35:05] Speaker 00:
Is it essentially game over?

[00:35:07] Speaker 00:
And the answer is yes, for the simple reason that there were only two witnesses at this trial.

[00:35:12] Speaker 00:
There was Dr. Rotella and there was Dr. Nichols.

[00:35:15] Speaker 00:
There were no other witnesses.

[00:35:17] Speaker 00:
The judge gave us very little time to present our case.

[00:35:20] Speaker 00:
There were no opening statements and no closing arguments.

[00:35:23] Speaker 00:
Dr. Nichols does not have any scintilla of experience in this field.

[00:35:29] Speaker 00:
I don't know why Takeda chose this expert, but they did.

[00:35:32] Speaker 00:
Dr. Rotella, on the other hand, has extensive experience.

[00:35:36] Speaker 00:
Nevertheless, the judge said, even though I'm going to agree with you that the higher standard applies, he then relied on the testimony, who by his own definition, his own witness, his own statement said, I don't meet this definition.

[00:35:50] Speaker 00:
So that's number one.

[00:35:52] Speaker 00:
Let me go back to a question that was asked about the cancer references and the MARCS references.

[00:35:57] Speaker 00:
And by the way, my colleague, Mr. Kansenitis, had misspoke on those.

[00:36:02] Speaker 00:
So I'm going to start with APPX 1473 to 1474 that discusses both the Canstrup reference and the Marx reference.

[00:36:13] Speaker 00:
And in both of those, Your Honor, in both of those, there is a two-member ring, one of which is a uracil ring.

[00:36:21] Speaker 00:
And based upon that, the authors discussed the use of this as a DPP for inhibitor.

[00:36:27] Speaker 00:
This was in the prior art.

[00:36:28] Speaker 00:
We also did demonstratives.

[00:36:30] Speaker 00:
Those are at pages 43090 to 43091.

[00:36:35] Speaker 00:
With respect to Rotella's testimony, that is at APPX 898 to 899.

[00:36:40] Speaker 00:
So we sufficiently and extensively discussed these references.

[00:36:45] Speaker 00:
Your Honors, I'm going to do something unusual today.

[00:36:47] Speaker 00:
And I'm doing this only because I would have never thought that my counsel on the other side would have accused us

[00:36:57] Speaker 00:
of waiving our rights to file a Daubert motion.

[00:37:01] Speaker 00:
I have an email.

[00:37:04] Speaker 00:
John, can I finish just one last sentence?

[00:37:07] Speaker 02:
Yeah, but you can't refer to something that's outside the record.

[00:37:12] Speaker 00:
OK.

[00:37:12] Speaker 00:
Just so the record is clear, I would have never expected that the other side would accuse us of waiving this when we had already agreed, which is why we didn't include it in the record.

[00:37:21] Speaker 00:
But may I have one more minute?

[00:37:25] Speaker 02:
I think we're out of time unless there are questions from my colleagues.

[00:37:30] Speaker 02:
I know.

[00:37:31] Speaker 02:
Okay.

[00:37:31] Speaker 04:
Thank you.

[00:37:32] Speaker 02:
We'll hear from Mr. Poulos for two minutes.

[00:37:35] Speaker 04:
Thank you, Your Honors.

[00:37:39] Speaker 04:
The first point I wanted to make is on the motivation.

[00:37:44] Speaker 04:
The law in this court has made clear that it's sufficient to show that the claimed and prior art compounds possess a sufficiently close relationship

[00:37:54] Speaker 04:
to create an expectation in light of the totality of prior art that the new compound will have similar properties to the old.

[00:38:02] Speaker 04:
And that's the Otsuka case.

[00:38:04] Speaker 04:
So the point there being, Your Honor, is that the motivation can come from anywhere and does not need to be the absolute best, that there was only one way forward.

[00:38:15] Speaker 04:
Rather, it's the fact that you have a lead compound, and the whole purpose of the lead compound is to make modifications to it.

[00:38:23] Speaker 04:
As is in the record, both

[00:38:25] Speaker 04:
two independent companies, Behringer Ingelheim and Novo Nordisk, came up with DCACS.

[00:38:31] Speaker 04:
And it was called a lead, or it was, there's evidence in the record that that was their lead.

[00:38:37] Speaker 04:
And that's our expert's testimony, Appendix 1000 to 1001.

[00:38:44] Speaker 04:
That this was their lead, they were gonna make modifications to it, and that's how this art proceeds.

[00:38:52] Speaker 04:
And the prior art actually says something about that too.

[00:38:55] Speaker 04:
the bone reference at appendix 33375 that the aim of scaffold hopping is to discover structurally novel compounds starting from known active compounds by modifying the central core of the structure of the molecule and that this is a central task of modern medicinal chemistry.

[00:39:12] Speaker 04:
And in the introduction to that reference, it basically says what the Otsuka case, what this court has recognized is that science proceeds by making these small modifications to see if you can improve the properties.

[00:39:27] Speaker 04:
And that's all that's needed to be shown for the lead and for the motivation.

[00:39:32] Speaker 04:
It doesn't have to be that it was the single best solution that is predictable.

[00:39:38] Speaker 04:
It just has to have a reasonable expectation of success, and that's what's shown here, given the similarity in the scaffolds.

[00:39:44] Speaker 02:
Thank you, Your Honor.

[00:39:45] Speaker 02:
Okay.

[00:39:46] Speaker 02:
Thank all counsel.

[00:39:47] Speaker 02:
The case is submitted.

[00:39:48] Speaker 02:
That concludes our session for this morning.

[00:39:52] Speaker 03:
The Honorable Court is adjourned from day to day.