[00:00:00] Speaker 03:
The next case for argument is 23-1334, Gavardis versus Regeneron.

[00:01:18] Speaker 01:
Please proceed.

[00:01:19] Speaker 01:
Good morning, Your Honors.

[00:01:20] Speaker 01:
May it please the Court, William J. for the appellants.

[00:01:23] Speaker 01:
This invention solved a long-standing and very difficult problem in the industry that leading companies had tried and failed to solve.

[00:01:30] Speaker 01:
The Board justified finding it all obvious anyway because, based on reliance on non-prior art and failing to recognize the teaching away in the key reference, which is boulange.

[00:01:43] Speaker 01:
So the Boulanger reference, of course, disparages stopper C, which is the stopper that the board relied upon in the combination that invalidated all the claims.

[00:01:55] Speaker 01:
And the board justified not treating that as a teachaway by primarily by looking to the notion that there's a plus or minus 4 Newton range within which the prior art taught that variation was okay.

[00:02:13] Speaker 01:
That's not based on anything in the prior art.

[00:02:15] Speaker 01:
That's based on the ILEA data that is not in the prior art, that is secret this very day.

[00:02:21] Speaker 04:
The claim doesn't demand that the breakthrough force remain static, right?

[00:02:30] Speaker 04:
That's right.

[00:02:31] Speaker 04:
So the claim tolerates some increase in force, as long as it's below 11 newtons.

[00:02:37] Speaker 01:
But where the question is, would a skilled artisan have combined boulange, which is not an ophthalmic reference, but which is this reference teaching low silicon oil syringe, with the ophthalmic invention of sig, you absolutely would focus on the things that make such a combination undesirable.

[00:02:59] Speaker 01:
One of the things that would make a combination that involved stop or see undesirable is the variability.

[00:03:04] Speaker 03:
But you're talking about teaching away.

[00:03:06] Speaker 03:
Yes.

[00:03:06] Speaker 03:
Which is more than a kind of undesirability type thing, right?

[00:03:11] Speaker 01:
That's right.

[00:03:12] Speaker 01:
I think the two work together and I see these as the two layers.

[00:03:16] Speaker 01:
One is that Boulange itself disparages

[00:03:20] Speaker 01:
the stopper C, that's without even getting to the reasons why you wouldn't use a highly variable stopper in an ophthalmic injection.

[00:03:29] Speaker 01:
But so Boulange itself disparages stopper C as not suitable for a medical device.

[00:03:34] Speaker 03:
And the second layer is... There's an answer to that.

[00:03:37] Speaker 03:
I mean, there's a response to that, which is I think this is the one because there are a lot of issues that you raise in your case, but this is the one where

[00:03:43] Speaker 03:
It doesn't really do that with respect to this particular, I don't know what the terminology is, but it's not the siliconized stuff or seed that they're talking about.

[00:03:54] Speaker 03:
So there's an argument, the board adopted it, the board bought it, and you're asking us to reject their analysis on that point?

[00:04:02] Speaker 01:
Well, the board, the basis on which the board projected it was not just where, where the different disparagements are placed within table five versus table seven of the reference, but the board

[00:04:16] Speaker 01:
concluded that when a skilled artisan would look at the data in Boulange, that the variability in table five was within this supposed four Newton range.

[00:04:29] Speaker 01:
You don't get that four Newton range out of anything in Boulange.

[00:04:32] Speaker 01:
The board purported to get it from two places.

[00:04:36] Speaker 01:
One is the Aelia data, not prior art.

[00:04:39] Speaker 01:
And the second is the colloquies at deposition with two of Novartis's medical experts.

[00:04:46] Speaker 01:
And those medical experts did not testify about what the force profile of an Ileus syringe was.

[00:04:54] Speaker 04:
Is there any evidence in the record that a change of four Newtons is just intolerable?

[00:05:00] Speaker 01:
The neither sides experts testified about what a what a

[00:05:11] Speaker 04:
prior what a skilled artisan in 2012 would have thought of sufficient right so that's why I'm trying to understand why we sit here and second guess the board when there really isn't any evidence in the record that suggests that a skilled artisan in 2012 would find an increase of four newtons to be totally unacceptable and very very scary.

[00:05:33] Speaker 01:
Recall that the board is relying on this for Newton point to justify looking past the disparagement in the boulange reference itself and to say, even though this is like this is not the stopper that boulange recommends using.

[00:05:50] Speaker 01:
Nonetheless, a skilled artisan in 2012 would look at this data and, based on this four Newton range, think that that's OK.

[00:05:57] Speaker 01:
But the board didn't ground that on anything in the prior art in 2012.

[00:06:02] Speaker 01:
And there's no substantial evidence supporting the funding.

[00:06:03] Speaker 04:
I don't recall the board making that connection between the increase in Newton for the breakthrough force from after a few months to being the basis for why it's OK to look at stopper C.

[00:06:19] Speaker 01:
Page 61, I think, is the place where it does that.

[00:06:23] Speaker 01:
The variance of 4.7 Newtons to 8.4 Newtons, and here it's discussing the variation in Table 5 of Boulange for Stopper C.

[00:06:35] Speaker 01:
is within accepted industry standards and would have been a viable option for the Posita.

[00:06:40] Speaker 01:
C, non prior art data, and the Wolf and Kalman depositions.

[00:06:47] Speaker 04:
And if you look at the- My understanding is this entire section of the opinion is really trying to evaluate your teaching away argument.

[00:06:55] Speaker 01:
Exactly.

[00:06:55] Speaker 04:
And then they're saying, well, we're just not convinced that there's a teaching away problem based on this increase in Newtons.

[00:07:03] Speaker 01:
So I think it's the opposite, Judge Chen.

[00:07:05] Speaker 01:
I think they're saying that because the increase isn't so big, based on the board's perception that variation of four is not a problem, that we don't have to worry about the disparagement in Boulange itself.

[00:07:22] Speaker 01:
But when you pull out the four Newton range,

[00:07:25] Speaker 01:
and see that that's not based on any substantial evidence from the prior art from 2012, then the board's reasoning falls apart.

[00:07:31] Speaker 01:
In other words, the board doesn't have a reason.

[00:07:33] Speaker 01:
The board doesn't say that Boulange itself recommends or even doesn't disparage the stopper.

[00:07:40] Speaker 04:
What if we read the board decision differently, where all these different arguments are actually separate from each other?

[00:07:47] Speaker 04:
It seems like you're integrating them all.

[00:07:49] Speaker 04:
The supposed disparagement because stopper

[00:07:52] Speaker 04:
because stopper C is markedly inferior to stopper B1, and the board said, well, ultimately, they're both acceptable, but just one is much superior to the other.

[00:08:03] Speaker 04:
So that's not a teaching way.

[00:08:05] Speaker 04:
And then second, when the statement in Boulogne about the idea that, well, this particular stopper wouldn't be acceptable to use as a medical device,

[00:08:14] Speaker 04:
the board said, we read that particular statement in the context of non-siliconized stopper C, not the siliconized version of stopper C, which is the actual stop version that's being relied on for the combination.

[00:08:27] Speaker 04:
And then finally, for this increase in force, this is a separate teaching away argument, which ultimately wasn't proven to be a true disparagement of using stopper C, because there's nothing in the record that says,

[00:08:41] Speaker 04:
please don't do this when there's an increase of four, when Mr. Kohler says, you know, you would expect there'd be some increase of the mutants.

[00:08:54] Speaker 01:
So a couple of points in response to that, because I see those not as three different things.

[00:08:59] Speaker 01:
I agree that there are two different things at work here.

[00:09:02] Speaker 01:
One is, is the force level too high to begin with?

[00:09:05] Speaker 01:
And the second, which is extremely important in the ophthalmic context, is,

[00:09:09] Speaker 01:
are the forces too variable, even if they are all within some kind of low range?

[00:09:16] Speaker 01:
Is there too much variation?

[00:09:17] Speaker 01:
And both sides experts agreed that variability in the ophthalmic setting is highly dangerous because of the muscle memory that ophthalmologists develop in giving these injections.

[00:09:29] Speaker 01:
So the initial force is much of what your question to me

[00:09:34] Speaker 01:
talking about, you know, table five versus table seven and the coding versus the, you know, the siliconization versus unsiliconized.

[00:09:42] Speaker 01:
That's about the initial force, right?

[00:09:45] Speaker 01:
But the point about variability, the board's only, the only way in which the board addressed the concern about variability in table five with the siliconized stopper that they say is the invent, the device they would use in the combination.

[00:10:00] Speaker 01:
The only way they respond to that concern about variability

[00:10:02] Speaker 01:
is A, the prior art data, and B, the more general statement that this is a level of variability that would be accepted in the industry at the time.

[00:10:12] Speaker 01:
And that does not rest on any substantial evidence.

[00:10:14] Speaker 01:
It rests on non-prior art data and on the, I think it would help if I just sort of explain for a minute what the doctors testified about.

[00:10:25] Speaker 01:
The non-prior art data is sort of a bell curve, right?

[00:10:29] Speaker 01:
It is data about

[00:10:33] Speaker 01:
the ILEA break loose forces.

[00:10:35] Speaker 01:
And if you take the extreme end of the bell curve, like the one with the lowest force in the sample of 70, and the one with the largest in the sample of 70, it's a little bit less than four Newtons.

[00:10:47] Speaker 01:
But the doctors did not testify at all that they had experienced that kind of variation in their use of ILEA.

[00:10:54] Speaker 01:
They just said, generally, when I use ILEA, it seems to have consistent break loose forces.

[00:10:59] Speaker 01:
It doesn't tell you that they've experienced

[00:11:01] Speaker 01:
of the low end and the high end, and the odds are that they did not.

[00:11:06] Speaker 01:
And this is, of course, all non-priority data.

[00:11:09] Speaker 01:
Compounding that problem is the fact that the Kalman exchange that the board also relies on expressly is based on a 2022 publication.

[00:11:20] Speaker 01:
called Lee about break loose forces, not prior art, not permissible for the board to rely on.

[00:11:27] Speaker 00:
I'll clarify something for me.

[00:11:29] Speaker 00:
Are you arguing that the board can never rely on non prior art data?

[00:11:33] Speaker 00:
We're not.

[00:11:33] Speaker 01:
This court's decision in YETA, among others, makes clear that there are proper roles for non-prior art considerations.

[00:11:44] Speaker 01:
It could shed light on the level of skill in the art, for example.

[00:11:47] Speaker 01:
But what it can't be used for is what the board used it for here, which is to say, at the priority date,

[00:11:55] Speaker 01:
people in the art would have expected industry standard to have this level of variation.

[00:12:00] Speaker 01:
And therefore, when you look at this data, you look at it in light of that industry standard.

[00:12:04] Speaker 01:
You can't prove an industry standard by post-priority secret data.

[00:12:10] Speaker 01:
And I would like to spend just a minute on the objective indicia.

[00:12:12] Speaker 01:
But if anyone's going to ask a question about this, I certainly don't want to preempt you.

[00:12:17] Speaker 01:
The point we'd like to leave the court with on objective indicia is just that the board's reasoning

[00:12:25] Speaker 01:
is that there are significant unclaimed features, and that therefore the significant commercial success of Lucentis isn't attributable to the claimed invention.

[00:12:34] Speaker 01:
I would just point the court to the fact that the claimed invention, it includes the veg of antagonists, it includes terminal sterilization, and it includes the low-break loose forces.

[00:12:44] Speaker 01:
In other words, if you look at all of the things that the board says at page 94,

[00:12:51] Speaker 01:
All of those things go to the efficacy of the invention.

[00:12:56] Speaker 01:
In other words, they say, well, the tip cap, for example, aids in terminal sterilization.

[00:13:02] Speaker 01:
That's the point.

[00:13:03] Speaker 01:
Terminal sterilization is part of this invention.

[00:13:06] Speaker 04:
So the board's... But there's no claim construction of terminal sterilization that requires a tip cap or that requires a particular rib configuration or any of the other things that the board, I think, reasonably found to be unacclaimed features.

[00:13:21] Speaker 01:
They are unclean but what the board suggested is that the tip cap drove, for example, drove the commercial success, but the only way in which the tip cap could drive the commercial success is in achieving the terminal sterilization and the terminal sterilization is a claimed feature.

[00:13:39] Speaker 01:
That really is the key point that like the innovation is the combination of low silicone oil and terminal sterilization and the very, very finicky veg of antagonist all in a pre-filled syringe presentation.

[00:13:52] Speaker 01:
No one had been able to do that before.

[00:13:53] Speaker 01:
Genentech had tried extensively and failed.

[00:13:56] Speaker 01:
And these are the, but this combination, as the court said in

[00:14:01] Speaker 01:
in Fox Factory, you look at whether the combination is what drove the commercial success.

[00:14:09] Speaker 01:
And here I think we've shown more than enough to get the presumption of nexus.

[00:14:13] Speaker 01:
I see that I'm in a rebuttal time unless the court has questions.

[00:14:16] Speaker 03:
Thank you.

[00:14:21] Speaker 02:
Your Honors, may it please the Court Anishinaabe for Regeneron.

[00:14:26] Speaker 02:
This is a substantial evidence appeal of a 127-page final written decision finding the 631 claims obvious.

[00:14:32] Speaker 02:
The Board's decision should be affirmed because there is substantial evidence supporting the factual determinations regarding motivation to combine reasonable expectation of success and secondary considerations.

[00:14:43] Speaker 02:
And I'll go straight to the points on motivation to combine and the teaching away.

[00:14:48] Speaker 02:
Importantly, Novartis does not dispute the board's finding that a person of skill and the art would have been motivated to combine Syng and Belange in order to minimize silicon oil and reduce or avoid negative interactions after the board's decision at appendix 54 to 55.

[00:15:01] Speaker 02:
The focus of Novartis' position is about the stopper.

[00:15:05] Speaker 02:
Now, Sig discloses a pre-filled syringe with a stopper.

[00:15:09] Speaker 02:
All these syringes have stoppers.

[00:15:11] Speaker 02:
And the petition explained that a skilled artisan would have been motivated to combine either Stopper B1 or Stopper C, and there was reasons to do both.

[00:15:20] Speaker 02:
And Stopper C is a typical configuration that was in commercial use already.

[00:15:25] Speaker 02:
That's in the board's decision.

[00:15:27] Speaker 02:
Stopper B1 was the invention in Boulange with a newer type of coding.

[00:15:31] Speaker 02:
The board found that the arguments and evidence regarding stopper C were sufficient, and decided not to address the stopper B. Novartis's rebuttal was that there is a teaching away with respect to stopper C. Now stopper C is not some experimental stopper.

[00:15:49] Speaker 02:
It was the commercially available benchmark by which Boulange was comparing its newer stopper, B1.

[00:15:56] Speaker 02:
And at appendix 56, the board found that stopper C was a typical stopper configuration and was already in use in a prior art terminally sterilized pre-filled syringe that included a VEGF antagonist.

[00:16:11] Speaker 02:
So the point being here is that Novartis' arguments regarding... Where did the board say that stopper C was already being commercially used in the terminally sterilized pre-filled syringe?

[00:16:22] Speaker 02:
That's at appendix 56.

[00:16:24] Speaker 02:
And that goes, that's prior to them addressing this argument regarding the Delta, the 8.4 Nunes, and Novartis' arguments that that would be unacceptable.

[00:16:34] Speaker 02:
And the key point is that Novartis was trying to make the point that 8.4 Nunes... Well, you're talking about Mukugan.

[00:16:41] Speaker 02:
Correct.

[00:16:42] Speaker 02:
And there's also other evidence that the board cited about rubber stopper with silicon oil being a typical configuration.

[00:16:48] Speaker 04:
Was it known in the art at the time that McCougan was using stopper C?

[00:16:51] Speaker 02:
It was a syringe in public use.

[00:16:54] Speaker 04:
But we don't know if people at Skill in the Art knew that McCougan's product had stopper C in it.

[00:17:01] Speaker 02:
There's other evidence from the experts that, for example, Appendix 6618, 6619, that's the Kohler Declaration, he testified and the board adapted that a rubber stopper with a silicon coating was a typical pre-filtered syringe stopper.

[00:17:20] Speaker 02:
There's Appendix 10793, that's the deposition

[00:17:23] Speaker 02:
of Novartis' expert also acknowledging that a Brimmel-Butyl rubber stopper was a typical stopper for a pre-filled syringe.

[00:17:30] Speaker 02:
And of course, Boulange itself, Appendix 3937, shows that Stopper C was a commercially available stopper from West.

[00:17:37] Speaker 02:
So this was not an experimental stopper.

[00:17:39] Speaker 02:
This was the benchmark stopper that was in use.

[00:17:42] Speaker 02:
Now, it was Novartis that came forward and said, well, 8.4 Newtons is unacceptable, or a delta of 4 Newtons would be unacceptable.

[00:17:50] Speaker 02:
And there's a teaching away because of that.

[00:17:52] Speaker 02:
But as Your Honor picked up, there is no evidence in the record that 8.4 Newtons would be unacceptable.

[00:17:58] Speaker 02:
There is no evidence in the record that 4 Newtons, a delta of 4 Newtons would be unacceptable.

[00:18:04] Speaker 02:
And in fact, the board rejected this argument.

[00:18:06] Speaker 02:
and there was substantial evidence to support that.

[00:18:09] Speaker 04:
For example, the patents... I'm a little concerned about the reliance on the non-prior art.

[00:18:14] Speaker 04:
Could this case be affirmed if we strip out all of the non-prior art?

[00:18:19] Speaker 02:
Absolutely, Your Honor.

[00:18:20] Speaker 02:
The Board relied on other evidence, substantial evidence, that 8.4 Newtons would not be unacceptable.

[00:18:26] Speaker 02:
For example, the admission in the patent spec, that's at Appendix 269, that typical pre-filled syringes for intravitreal injection had less than 20 Newtons.

[00:18:36] Speaker 04:
And of course, it doesn't quite say it like that, right?

[00:18:39] Speaker 02:
The entire paragraph starts with having too great a force required to move the stopper can cause a problem.

[00:18:45] Speaker 02:
Smooth administration of the eye is particularly important in sensitive tissues such as the eye.

[00:18:50] Speaker 02:
Break-loosen slide forces for pre-filter inges known in the art are typically less than 20 Newtons.

[00:18:54] Speaker 02:
Now, of course, 8.4 Newtons is well below 20 Newtons.

[00:18:58] Speaker 02:
So that's the patent spec right there.

[00:19:01] Speaker 02:
But the point being Novartis,

[00:19:02] Speaker 02:
had no evidence to say that 8.4 Newtons was unacceptable.

[00:19:06] Speaker 02:
They were the ones coming forward with the argument you wouldn't use this because of the 8.4 Newtons.

[00:19:11] Speaker 02:
They had the burden of production there on that point.

[00:19:14] Speaker 02:
And the non-prior information can be used, of course, to rebut this argument.

[00:19:19] Speaker 02:
In other words, an expert comes forward and says 8.4 Newtons would be unacceptable, but it has no evidence to support that.

[00:19:25] Speaker 02:
No data to support that.

[00:19:27] Speaker 02:
And the non-prior art here, the testimony from the ophthalmologist, demonstrates that there's no basis for that argument.

[00:19:33] Speaker 02:
The Kalman depot.

[00:19:35] Speaker 04:
But Kalman wasn't saying, here's what I understood in the art back at the priority date, 2012.

[00:19:41] Speaker 04:
And back at 2012, yeah, it's OK to have

[00:19:45] Speaker 04:
to tolerate some increase in the breakthrough force.

[00:19:49] Speaker 02:
That's not his testimony.

[00:19:52] Speaker 04:
I don't think we could say that the ILIA data, even though it's post-priority data, somehow reveals what skilled artists knew at the time of the invention of 2012.

[00:20:05] Speaker 02:
That's correct, but that's not the purpose of that testimony or that evidence.

[00:20:08] Speaker 02:
The purpose of that testimony and that evidence is to demonstrate that Novartis's position that 8.4 Newtons would be unacceptable has no basis.

[00:20:16] Speaker 02:
There is other sufficient motivations to use stopper C, the fact that it was a commercially available and the benchmark stopper that was already in use in a terminally sterilized pre-filter range.

[00:20:28] Speaker 02:
The purpose of the Kalman deposition, the Wolf deposition, is to demonstrate that no vartysis position, the unsupported position that 8.4 Newtons would be unacceptable, has no basis.

[00:20:38] Speaker 02:
Because even today, these ophthalmologists are injecting and say, for example, Kalman testified that he uses Avastin and Ilia the most,

[00:20:47] Speaker 02:
And the ILEA syringe can require up to 10 Newtons, and it varies between three and 10 Newtons.

[00:20:51] Speaker 02:
So that is concrete evidence demonstrating that Novartis is positioned at 8.4 Newtons would somehow be unacceptable, has no basis.

[00:21:00] Speaker 02:
And of course, there is the patent spec.

[00:21:02] Speaker 02:
And then, Your Honor, I think you also brought up the claim language.

[00:21:07] Speaker 02:
And I think the board was right to consider the claim language in assessing whether an 8.4 Newtons would be unacceptable.

[00:21:13] Speaker 02:
And here's the reason.

[00:21:14] Speaker 02:
It demonstrates how Novartis' position is somewhat nonsensical.

[00:21:18] Speaker 02:
Novartis says that 8.4 Newtons would be unacceptable for his position.

[00:21:22] Speaker 02:
And if we look at the claim scope, that really makes no sense because the claims cover a PFS with a break loose force of up to 11 Newtons.

[00:21:30] Speaker 02:
There's no limitation on the break-who's-force when it's measured.

[00:21:34] Speaker 02:
Is Novartis really arguing that they wrote a claim and they covered a range that they now say would be unacceptable to a physician?

[00:21:43] Speaker 02:
That absolutely makes no sense.

[00:21:45] Speaker 02:
And that's why the board was correct to consider the claim like.

[00:21:48] Speaker 02:
It wasn't a matter of hindsight.

[00:21:49] Speaker 02:
It was a point that you are actually claiming a range that you are now arguing would be unacceptable.

[00:21:54] Speaker 02:
And that doesn't make any sense.

[00:21:57] Speaker 02:
As far as the confidential information, I think, Your Honor, I've covered that point with respect to other data.

[00:22:04] Speaker 04:
I guess getting back to the confidential markings in these briefings, I'm at the moment at a loss on how we would write an opinion, given the way so much details here have been marked confidential.

[00:22:22] Speaker 02:
Your Honor, with respect to the

[00:22:26] Speaker 02:
I think the vast majority of the redactions are in the Objective Editia section, and I believe that's primarily Novartis' redactions.

[00:22:36] Speaker 02:
I believe the only redaction that we have is with respect to the data from the ILEA PFS.

[00:22:43] Speaker 00:
From the what?

[00:22:45] Speaker 00:
The data from what?

[00:22:46] Speaker 02:
The ILEA PFS.

[00:22:47] Speaker 02:
The ILEA pre-filter range, the force data.

[00:22:49] Speaker 02:
I believe that's the only redaction that we have.

[00:22:52] Speaker 03:
Why don't you turn to the secondary consideration?

[00:22:54] Speaker 02:
Yes.

[00:22:55] Speaker 02:
Now, with respect to secondary considerations, the law is clear that commercial success, if it's due to an unclaimed feature of the device or if the feature that creates commercial success was known in the prior art, the success is not pertinent.

[00:23:09] Speaker 02:
Now, the board rejected Novartis's position that the Lucentis PFS is coextensive with the claim.

[00:23:15] Speaker 02:
That was in Appendix 75 to 80.

[00:23:16] Speaker 02:
They cited substantial evidence of significant unclaimed features of the Lucentis PFS

[00:23:22] Speaker 02:
And I think importantly, the board also pointed out the claims are far broader than the Lucentis PFS and encompass embodiments that would not be commercially successful.

[00:23:32] Speaker 02:
For example, I think my friend mentioned that the claims cover the VEGF antagonists, but they cover VEGF antagonists that have not been successful.

[00:23:41] Speaker 02:
This is covered in the board's opinion in Appendix 80-81.

[00:23:45] Speaker 02:
The board also addressed the number of features.

[00:23:50] Speaker 04:
How many antagonists are covered by this claim?

[00:23:54] Speaker 02:
Let's say there were 40 different antagonists covered by this claim.

[00:24:16] Speaker 04:
Novartis wouldn't have to prove commercial success for all 40 in order to get the presumption of nexus, would it?

[00:24:26] Speaker 02:
Well, I think to show coextensiveness, if their claim specifically covers a product that has been shown to be absolutely unsuccessful, I think that's a very big problem.

[00:24:37] Speaker 02:
And that is the case here.

[00:24:38] Speaker 04:
I'm asking a different question.

[00:24:40] Speaker 04:
Theoretically, they have one really good commercial

[00:24:46] Speaker 04:
commercially successful environment, one particular active ingredient, one particular antagonist.

[00:24:53] Speaker 04:
But the claim is broad enough that it covers 39 others.

[00:24:56] Speaker 04:
To what extent, in order to be granted the presumption of nexus, would Novartis have to somehow convince a fact finder that the other 39, even though they're not in commerce, would also enjoy the same level of commercial success?

[00:25:14] Speaker 02:
I think that's a problem if you have a claim that is far broader than your commercial product and includes things that you would have to demonstrate some level of connection between all those other items and the success.

[00:25:29] Speaker 02:
But that's not the only point with this claim.

[00:25:32] Speaker 02:
The board also found that Novartis argued that it would be safer and more convenient and they found that the safety

[00:25:38] Speaker 02:
was about the very low silicon oil content in the Lucentis PFS, which is redacted in the briefs.

[00:25:44] Speaker 02:
So I cannot say that amount, but it is far lower.

[00:25:47] Speaker 02:
The actual amount in the claim, in the product is far lower than what's the range that's claimed.

[00:25:53] Speaker 02:
And the board actually found and pointed out

[00:25:55] Speaker 02:
that the range that's claimed includes amounts that would have been unsuccessful, that were admittedly would have been unsuccessful in the Lucentis PFS.

[00:26:05] Speaker 02:
So again, that's another problem with the claim not being coextensive and not lining up with the actual product.

[00:26:12] Speaker 02:
And then there was the host of other items that Novartis acknowledged were unique and necessary to achieve the terminal sterilization.

[00:26:22] Speaker 02:
Again, those are all redacted in the briefs, but those are not claimed.

[00:26:28] Speaker 02:
And then the last point with respect to the low silicon oil and terminal sterilization.

[00:26:34] Speaker 02:
Again, terminal sterilization and low silicon oil amounts.

[00:26:39] Speaker 02:
are features of the prior art.

[00:26:41] Speaker 02:
And again, go back to the case law that says, if the features that create commercial success were known in the prior art, the success is not permanent.

[00:26:48] Speaker 02:
The board made factual findings that low-silicon oil and terminal sterilization are features of the prior art.

[00:26:55] Speaker 04:
Genentech couldn't figure this out, and then it had to take a license on this patent.

[00:27:00] Speaker 04:
And then the product was not gangbusters.

[00:27:06] Speaker 02:
So your honor, with respect to Genentech and the license, the board made a number of findings with respect to that license, all of which are redacted in the brief.

[00:27:12] Speaker 02:
But the bottom line with that license is that it covered a far substantial amount than the patent itself.

[00:27:18] Speaker 02:
And those are set forth in the board's decision in appendix 98 to 99.

[00:27:21] Speaker 02:
So there's really no way for Novartis to establish a nexus with respect to the license.

[00:27:26] Speaker 02:
And with respect to Genentech's failure and the long felt need issue, Novartis itself framed the issue as

[00:27:32] Speaker 02:
The need that was not met was a syringe with low levels of silicon oil to prevent silicon oil injection in the eye.

[00:27:39] Speaker 02:
That's at Appendix 96.

[00:27:41] Speaker 02:
But the board found that the claims do not actually meet that need, as they only pertain to the amount of silicon oil applied to the barrel and do not prevent silicon oil from being introduced by the stopper or the filling process.

[00:27:53] Speaker 02:
That's at Appendix 96.

[00:27:56] Speaker 02:
The board also found that whether silicone oil migrates into the eye is a question of the process that's used to apply the silicone, which is also not claimed.

[00:28:05] Speaker 02:
For example, the claims do not require baked on siliconization, which is the process that prior art process that reduces the amount of free silicone oil on the barrel.

[00:28:15] Speaker 02:
That's also the appendix 96 and 97.

[00:28:18] Speaker 02:
And with respect to Genentech, the board did find that the project was abandoned due to degradation of the VEGF antagonists, but also found that that did not necessarily translate to a failure to reduce silicon oil levels.

[00:28:30] Speaker 02:
So there was not a connection between what Novartis was arguing was the long felt need and their claims, as well as Genentech's failure.

[00:28:36] Speaker 02:
And that was at Appendix 96.

[00:28:38] Speaker 00:
So your argument is that if there's any of the elements that existed in the priority, that that's an impediment towards commercial success.

[00:28:48] Speaker 02:
Well, the precise language of the law is that if the feature that creates commercial success was known in the prior art, the success is not pertinent.

[00:28:56] Speaker 02:
That's a quote from the Ethicon case, A12, F3, 1034.

[00:29:00] Speaker 02:
And there are factual findings that were made.

[00:29:03] Speaker 00:
Low silicon oil?

[00:29:04] Speaker 00:
What about rearranging some of these features that are known in the prior art?

[00:29:10] Speaker 00:
And now, before it was A, B, C, D, and now you rearrange them as F, G, Z, F,

[00:29:18] Speaker 00:
And that leads to commercial success.

[00:29:22] Speaker 00:
In your view, you couldn't have commercial success in that situation.

[00:29:26] Speaker 02:
Well, I don't agree with that, Your Honor.

[00:29:27] Speaker 02:
I respectfully disagree.

[00:29:28] Speaker 02:
I think that there could be situations where you are rearranging the part and changing the puzzle pieces in a way that could do that for you.

[00:29:35] Speaker 00:
Isn't that what your friend on the other side's arguing?

[00:29:37] Speaker 02:
That's what he's arguing, but I would submit that that's not the situation here.

[00:29:41] Speaker 02:
There is no rearranging of terminal sterilization and low-silicon.

[00:29:45] Speaker 00:
But the fact that there's elements that existed in the prior

[00:29:50] Speaker 00:
That does not necessarily mean that you cannot have commercial success, right?

[00:29:56] Speaker 02:
That's correct.

[00:29:57] Speaker 02:
But in this situation, a terminally sterilized pre-filled syringe containing a VEGF antagonist was already on the market.

[00:30:07] Speaker 02:
The inventors here did not contribute terminal sterilization to the art.

[00:30:12] Speaker 02:
The inventors also did not contribute a low-silicon oil syringe.

[00:30:18] Speaker 02:
That's the board made that finding because the inventors did not bring forward baked on siliconization.

[00:30:23] Speaker 02:
They did not actually claim a syringe that had a low silken amount because they only claimed the amount on the barrel and did not place any limitation on the amount of silken oil applied to the stopper.

[00:30:35] Speaker 00:
You're arguing that their claimed advance existed in the priority.

[00:30:41] Speaker 00:
Absolutely, Your Honor.

[00:30:42] Speaker 00:
So that in a way there's nothing new there.

[00:30:44] Speaker 00:
So you can't have commercial success.

[00:30:46] Speaker 02:
that's attributable to the claimed invention.

[00:30:48] Speaker 00:
What explains the sharp rise in sales and things of that nature?

[00:30:53] Speaker 02:
Well, first of all, the drug product is paramount and it is clear and it was found that the convenience of a pre-filled syringe is an advantage, but Novartis and this invention did not

[00:31:09] Speaker 02:
bring forward the convenience of a pre-filled syringe because pre-filled syringes already existed, including one with a VEGF antagonist.

[00:31:16] Speaker 02:
So certainly the convenience increases the sales, but that is not something that Novartis contributed.

[00:31:26] Speaker 02:
Thank you, Your Honor.

[00:31:27] Speaker 03:
Thank you.

[00:31:30] Speaker 03:
We'll give you an extra two minutes to even it out.

[00:31:34] Speaker 01:
Oh, thank you, your honor.

[00:31:35] Speaker 01:
I just have four points, and the first one actually ties together where my friend left off about the combination, and actually also the point about stopper C being in the prior art.

[00:31:47] Speaker 01:
He relied heavily on the idea that Becton Dickinson was using stopper C in macugin.

[00:31:53] Speaker 01:
That's refuted at page 92 of the board's decision.

[00:31:56] Speaker 01:
I urge the court to just look at that one page, which is in the objective indicia discussion, but it discusses exactly why macugin did not achieve the success of the invention.

[00:32:06] Speaker 01:
Macugin didn't achieve the low silicon oil part of the combination.

[00:32:09] Speaker 01:
So the idea that stopper C is in the prior art and already known to be usable for these purposes.

[00:32:16] Speaker 01:
Remember that boulange is about low siliconization.

[00:32:20] Speaker 01:
The problem is stopper C boulange itself says is markedly inferior.

[00:32:25] Speaker 01:
Part of the reason for that is variability.

[00:32:27] Speaker 01:
That's my second point.

[00:32:28] Speaker 01:
On variability, you had a number of questions for my friend about the disparagement and whether the board's reliance on prior art affected its decision or whether it could be sustained on other grounds.

[00:32:43] Speaker 01:
The main thing that he pointed to was the statement in column five of the specification about 20 Newtons.

[00:32:50] Speaker 01:
That doesn't say anything about variability.

[00:32:52] Speaker 01:
So even if you take it as they take it, which we disagree with, we don't think it's talking about in the ophthalmic context at all, because there are many pre-filled syringes for many other uses.

[00:33:03] Speaker 01:
But that says nothing about variability.

[00:33:06] Speaker 01:
And then just to compound the problem with reliance on the non-prior art data, in answering your questions, my friend relied on the testimony of Dr. Kalman.

[00:33:17] Speaker 01:
What was Dr. Kalman testifying about?

[00:33:19] Speaker 01:
Non-prior art, Lee article from 2022.

[00:33:21] Speaker 01:
This is at page 10938 to 39 of the appendix.

[00:33:25] Speaker 01:
That's the 10 Newton figure that he cited to you from the non-prior art article.

[00:33:31] Speaker 01:
The last point is just about the objective indicia.

[00:33:35] Speaker 01:
So Lucentis indisputably practices the claims.

[00:33:39] Speaker 01:
That's not disputed.

[00:33:41] Speaker 01:
The answer to your question, Judge Chen, about whether you have to show that every single species within the genus would be commercially successful, squarely rejected by Teva versus Eli Lilly, 8F4 at page 1362.

[00:33:57] Speaker 01:
We didn't cite that in our papers because the other side did not defend this particular finding.

[00:34:01] Speaker 04:
Is that a presumption of nexus case?

[00:34:04] Speaker 01:
It is.

[00:34:05] Speaker 01:
And it says, we can't imagine that.

[00:34:08] Speaker 01:
If you have a commercially successful species and a claim to the entire genus, you can't imagine that you wouldn't get a presumption of nexus in that case.

[00:34:17] Speaker 01:
That went up being a functional claim in case, and the court didn't apply the presumption in that case.

[00:34:22] Speaker 01:
But in this case, we're talking about the species of vegevantagonist, which is a recognized set of products being used for this purpose.

[00:34:34] Speaker 04:
What about the one species that the other side brought up that

[00:34:37] Speaker 04:
wasn't particularly good.

[00:34:39] Speaker 01:
So that's Bay of you.

[00:34:40] Speaker 01:
And my response to that is we're looking at the combination.

[00:34:45] Speaker 01:
So the fact that one veg of antagonists may be more successful than another, that doesn't disparage the.

[00:34:54] Speaker 01:
Maybe I shouldn't use that word.

[00:34:56] Speaker 01:
That doesn't undermine the point that the pre-filled syringe presentation of a VEGIF antagonist leads to more commercial success.

[00:35:03] Speaker 01:
In other words, when you take a VEGIF antagonist and put it in a pre-filled syringe presentation, that can improve the results, just like the results that we depicted in our brief for Lucentis, where the sales had been going down, the pre-filled syringe presentation becomes available, and the total sales go up.

[00:35:23] Speaker 04:
But I guess the idea is if you take an old drug that's in a vial and then you put it in a pre-filled syringe and then people buy a lot of that old product that's now in the pre-filled syringe because people really like the convenience of having just a pre-filled syringe.

[00:35:41] Speaker 04:
We're going to give a patent out every single time for something like that, because all of a sudden people are buying a lot more of the pre-filled syringe than they were of the vial itself.

[00:35:50] Speaker 01:
When achieving that pre-filled syringe presentation means tackling and solving the most vexing problem in the industry, how do you achieve terminal sterilization and low silicone oil for this ophthalmic product, which is itself extremely finicky?

[00:36:06] Speaker 01:
Genentech tried to solve that problem.

[00:36:09] Speaker 01:
So and failed.

[00:36:10] Speaker 01:
So we're not saying that anything that leads to convenience is itself, you know, like that's going to be enough for the Nexus.

[00:36:16] Speaker 01:
The point is, and this goes to Judge Raina's questions as well, where what achieves the convenience is the PFS presentation and where what makes the PFS presentation possible is the combination of elements that only the patent owners have achieved.

[00:36:31] Speaker 01:
That is commercial success.

[00:36:32] Speaker 01:
That is Nexus.

[00:36:33] Speaker 01:
And that's not obvious.