[00:00:02] Speaker 00:
The first case of argument this morning is 18-2133, Merck v. Wyeth.

[00:00:07] Speaker 00:
Mr. Lamkin, good morning.

[00:00:14] Speaker 01:
Good morning, and may it please the court.

[00:00:16] Speaker 01:
Wyeth seems to have invented a formulation that stabilizes polysaccharide protein conjugates to prevent aggregation clumping that's caused by silicon oil.

[00:00:27] Speaker 01:
But the prior art, like Chiron and Allon, taught the same formulation

[00:00:32] Speaker 01:
with the same ingredients to stabilize the same thing, polysaccharide protein conjugates, in the same way.

[00:00:38] Speaker 01:
Claim 1 was thus obvious.

[00:00:40] Speaker 01:
It claimed the same formulation to stabilize any polysaccharide protein conjugate.

[00:00:46] Speaker 01:
Claim 17 was also obvious.

[00:00:48] Speaker 00:
Recited the same formulation yeah, but the big difference is the numbers right claim 17 had seven of these conjugates and Your claim claim 18 that's in dispute has 13 so the board rested on that difference That's right and with the number the one thing that can't make a difference is the number of pallet polysaccharide?

[00:01:06] Speaker 01:
Conjugates because it's the protein the board made this place the protein that causes the aggregation

[00:01:12] Speaker 01:
This formulation acts on the protein.

[00:01:14] Speaker 01:
So adding additional polysaccharides, additional serotypes, isn't going to make that formulation cease to work.

[00:01:20] Speaker 04:
That doesn't seem to me to be an answer to the question, because there is a question of whether there was a motivation to combine the 13.

[00:01:31] Speaker 04:
It may have been that the methodology for combining the 13 was obvious.

[00:01:39] Speaker 04:
was, but where's the motivation to put the 13 together?

[00:01:44] Speaker 04:
The seven had been put together, which are adding an additional six to be sure each of the individual six were known to prior art, but why was it obvious to combine those six with the pre-existing seven?

[00:01:58] Speaker 01:
And Pena provides the answer to that because Pena itself identifies the same exact serotypes, those 13 serotypes that are identified in claim 18 and says that they're in an advanced stage of study of coming up with a conjugate vaccine with those 13 serotypes.

[00:02:15] Speaker 01:
And Pena tells you as well, and so I turn to page 988 of the appendix for Pena.

[00:02:22] Speaker 01:
Pena tells you on page 988 that the seven serotypes

[00:02:27] Speaker 01:
vaccine used CRIM-197 as the protein.

[00:02:31] Speaker 01:
Pena then on page 995 tells you that the nine serotypes, we're adding two more serotypes, two more polysaccharides, is also conjugated to CRIM-197.

[00:02:43] Speaker 01:
Then you go to page 901 of the record, which is Chiron, and Chiron tells you again that CRIM-197 is particularly preferred as the protein.

[00:02:52] Speaker 01:
So now you have the seven valent

[00:02:54] Speaker 01:
the 9-valent using CRM-197.

[00:02:56] Speaker 01:
The polysaccharides are set out.

[00:02:58] Speaker 00:
But the difference is, let me see if I understand.

[00:02:59] Speaker 00:
Pena, the board concluded it might mention these 13 serotypes.

[00:03:09] Speaker 00:
But there's no indication that the formulation was going to be successful or even considered.

[00:03:15] Speaker 00:
And then you're trying to lump that with chiron.

[00:03:18] Speaker 00:
And chiron doesn't disclose these six additional conjugates, right?

[00:03:24] Speaker 01:
So so Pena itself gives you all the seventh all 13 stereotypes and the question is do you conjugate them all to cream 197 I think is maybe what the board is doing if we just turn to the board's decision on page 44 I don't think that You can get the 13 except from that aspect of Kenya that says that this combining the 13 is being studied and

[00:03:49] Speaker 01:
Yes, and it says advanced stages of study.

[00:03:51] Speaker 04:
And the question is whether that's sufficient to provide a motivation to combine it.

[00:03:56] Speaker 01:
And it would.

[00:03:57] Speaker 01:
It should be sufficient because, one, PANIA itself tells you that you have the 13.

[00:04:02] Speaker 01:
You're studying it.

[00:04:04] Speaker 01:
And they're studying it because it's going to become a vaccine.

[00:04:06] Speaker 01:
PANIA tells you that you're using Crohnwein-97 for the protein for 7-valent, 9-valent.

[00:04:12] Speaker 01:
Chiron says it's particularly preferred.

[00:04:13] Speaker 01:
And then Obara and Overturf.

[00:04:16] Speaker 01:
tell you that an overturf is on page 1232 that the 11 valent version and the 9 valent version are using crim 197.

[00:04:23] Speaker 01:
And so if you're trying to figure out what am I going to do, what conjugate am I going to use if I'm going to 13?

[00:04:30] Speaker 01:
We know the conjugate for crim 197 worked for 7, it worked for 9, it worked for 11.

[00:04:36] Speaker 01:
It's particularly preferred according to Chiron.

[00:04:38] Speaker 01:
Why isn't it obvious to use that same conjugate again?

[00:04:40] Speaker 04:
I think that you're right that it might have been obvious to use the conjugate.

[00:04:45] Speaker 04:
But, you know, why put these 13 together?

[00:04:50] Speaker 01:
Oh, why the particular serotypes?

[00:04:52] Speaker 01:
Yeah.

[00:04:53] Speaker 01:
Yes.

[00:04:53] Speaker 01:
So Pena tells you why you would choose those serotypes.

[00:04:56] Speaker 01:
And that is because you're trying to map.

[00:04:57] Speaker 01:
And I'll just turn to Pena on page 992, I believe.

[00:05:02] Speaker 01:
And Pena tells you maybe 993.

[00:05:05] Speaker 01:
Which volume is that?

[00:05:06] Speaker 01:
It says page 993 is the second column.

[00:05:09] Speaker 01:
Volume one.

[00:05:10] Speaker 01:
Pardon?

[00:05:11] Speaker 01:
Volume one.

[00:05:12] Speaker 01:
Volume one.

[00:05:13] Speaker 01:
Second column.

[00:05:16] Speaker 01:
It's the last full, very long paragraph, but right a little in the middle.

[00:05:19] Speaker 01:
It says, they're incorporating new serotypes to the seven-valent conjugate vaccine.

[00:05:24] Speaker 01:
And it tells you the conjugates are being added, 1 and 5, 3 and 7, 6A and 19A.

[00:05:30] Speaker 01:
Those are the ones listed in claim 18.

[00:05:32] Speaker 01:
And it tells you why.

[00:05:34] Speaker 01:
This will broaden the spectrum of ages and countries, although we will continue to have much diversity in coverage.

[00:05:40] Speaker 01:
These are the serotypes you're going to use because you want to conjugate because you want to reach children who don't respond to the unconjugated version.

[00:05:47] Speaker 01:
You want to reach old people who do not respond as well to the unconjugated version.

[00:05:52] Speaker 01:
And you're going to add the most common serotypes.

[00:05:55] Speaker 01:
And Pena tells you the exact serotypes.

[00:05:57] Speaker 01:
They're in claim 18.

[00:05:59] Speaker 01:
And those are the serotypes you want to do to maximize your coverage of ages,

[00:06:04] Speaker 01:
and countries.

[00:06:07] Speaker 01:
Since Pena itself tells you that those are the stereotypes being studied, it seems to me the incentive to study them, the ones to actually do, is apparent.

[00:06:16] Speaker 01:
It actually discloses those 13 stereotypes.

[00:06:20] Speaker 01:
And so in terms of whether or not there's a motivation to do it, another point that's critical.

[00:06:25] Speaker 04:
Just because somebody else is studying them doesn't mean that it would be a motivation to do it, does it?

[00:06:30] Speaker 01:
Well, it certainly is.

[00:06:31] Speaker 01:
If you're trying to maximize your coverage, and you're going to go for the 18 most common serotypes that cause most of the disease, these are the ones you're going to pick in line.

[00:06:39] Speaker 01:
And PANIA tells you to pick those 13.

[00:06:42] Speaker 01:
And if you're looking for all the other places, it goes on.

[00:06:47] Speaker 01:
And one of the key things about this invention, if you look at claim one and claim 17, 18, it doesn't expressly require that it be effective as a vaccine.

[00:06:55] Speaker 01:
So it's enough to want to make it in the lab to study it, as Pena was doing there, making it in the lab to study it.

[00:07:02] Speaker 01:
And once you're making it in the lab to study it, then you're going to have to stabilize it against a silicone-induced aggregation.

[00:07:10] Speaker 01:
Because as the board explained on pages 23 to 25 of its opinion, silicone is ubiquitous in labs.

[00:07:15] Speaker 01:
It's in beakers.

[00:07:16] Speaker 01:
It's in stoppers.

[00:07:17] Speaker 01:
If you're doing animal studies, it's going to be in the syringes.

[00:07:21] Speaker 01:
And the patent itself, if you look at page 307, column 14, about five lines down, actually touts the patent's utility.

[00:07:28] Speaker 01:
In the lab, the patent itself says, again this is page 307, column 14, and it says,

[00:07:49] Speaker 01:
The novel formulations are particularly advantageous in that they stabilize and inhibit precipitation in immunogenic formulations comprised in the containerized means throughout the various stages of research, processing, development.

[00:08:01] Speaker 01:
So this is something you would do even if you're testing.

[00:08:02] Speaker 04:
Did you have an expert who said there would be a motivation to produce the 13-valent version?

[00:08:07] Speaker 04:
Did you have experts or an expert who said it would have been obvious

[00:08:14] Speaker 04:
to use the 13-valent combination.

[00:08:17] Speaker 01:
Yes.

[00:08:17] Speaker 01:
I think our experts did say that you were going to do the same 13 serotypes because they are the most common serotypes.

[00:08:24] Speaker 01:
And those are the serotypes that are listed.

[00:08:25] Speaker 01:
Where do we find that?

[00:08:26] Speaker 01:
I'm going to have to come back to you on that because I don't know the exact citation where our experts would talk about it.

[00:08:30] Speaker 01:
Those 13 serotypes are the most common.

[00:08:33] Speaker 01:
And it's hard for anyone to say that you're not going to do these very common serotypes.

[00:08:37] Speaker 01:
Because pain itself tells you Wyeth.

[00:08:39] Speaker 01:
He's a Wyeth.

[00:08:40] Speaker 01:
Let me ask you.

[00:08:41] Speaker 00:
Look at the board's analysis.

[00:08:43] Speaker 00:
I know we cut you off when you were trying to point us to page 44 or something.

[00:08:47] Speaker 00:
But look at appendix 83, which is where the board uses your evidence.

[00:08:53] Speaker 00:
And it says, you had a declarant which provide evidence that the 13 stereotypes recited were known in the art.

[00:09:00] Speaker 00:
And that goes on to say, but you have not established persuasively or even explained in any specific way that the prior art or the knowledge, blah, blah, blah,

[00:09:10] Speaker 00:
motivated the artisan to further modify prevenom.

[00:09:15] Speaker 00:
What's wrong with that?

[00:09:16] Speaker 01:
So it says, modify prevenom to include the 13 conjugates with reasonable expectation of sexually doing so.

[00:09:23] Speaker 01:
So why do you go from 7 to 13 conjugates?

[00:09:25] Speaker 01:
The same exact reason Pena tells you to do it, because it expands you to reach children and the elderly people who are not going to respond to the unconjugated version.

[00:09:35] Speaker 01:
And what's wrong with the expectation of successfully doing so?

[00:09:38] Speaker 01:
The board doesn't tell you why it wouldn't be expected to be successful.

[00:09:42] Speaker 00:
Well, where is your expert testimony in the appendix that said that it would?

[00:09:46] Speaker 00:
It says, pardon?

[00:09:47] Speaker 00:
Did you have expert testimony?

[00:09:49] Speaker 00:
Yes.

[00:09:49] Speaker 01:
Our expert says specifically that there was no reason to think that this would not work.

[00:09:54] Speaker 01:
That just as it worked for seven and nine and 11, it's going to work for 13.

[00:09:58] Speaker 01:
And for example, paragraph 45 on page 697,

[00:10:01] Speaker 01:
the expert goes through and says, everybody skilled in the art knows that the 7-valent version combined with 690, CRM 197 is working.

[00:10:09] Speaker 01:
So this testifies it's 697?

[00:10:10] Speaker 01:
697, correct.

[00:10:12] Speaker 01:
Paragraph 45.

[00:10:15] Speaker 01:
And in fact, I don't think it's possible for the board to be saying, gee, no one could have thought that CRM 197 was going to be used for this, because the board refused to consider an Irish EPA document

[00:10:30] Speaker 01:
And that, it said, that's merely cumulative.

[00:10:32] Speaker 01:
But the Irish EPA document.

[00:10:34] Speaker 00:
But even though you try to avoid talking about this national progression argument on appeal,

[00:10:39] Speaker 00:
That was the argument you presented to the board.

[00:10:41] Speaker 00:
So the board looks at this natural, OK, you're assuming there's a natural progression.

[00:10:46] Speaker 00:
And they said, no, no, no, that's not good enough under our analysis of prior art, KSR.

[00:10:52] Speaker 01:
So I think that the phrase natural progression is just another way of saying it's obvious.

[00:10:57] Speaker 01:
Because if you have a set of solutions, like conjugating chroma 197 that works for your 7-valent version,

[00:11:04] Speaker 01:
and it works for your 9-valent version, and it works for your 11-valent version, and CRM-197 is, to find it's particularly preferred, then it's obvious that it's going to be a candidate for your 13-valent version as well.

[00:11:18] Speaker 01:
I think that's just a standard application of KSR.

[00:11:21] Speaker 01:
It's not, whether you call it natural progression or the same solution, CRM-197 worked for all the other versions, it's an obvious candidate for the 13-valent version as well.

[00:11:29] Speaker 00:
The board rejected that at 83, and they cited kinetic, and they said that the way to avoid hindsight reasoning is to really have an explanation of how or why the recited references do what they do.

[00:11:44] Speaker 00:
And so they rejected that theory as not being enough.

[00:11:47] Speaker 01:
I'm not sure.

[00:11:49] Speaker 01:
When I read that, I think what the board might be asking for is to have any single reference

[00:11:54] Speaker 04:
197 together with the 13 serotypes which I believe Pena actually provides properly read because it talks about Adding additional serotypes to the existing seven, but I think it would be helpful for you to identify for us where your expert said Specifically that it would have been obvious to choose these 13 and put them together.

[00:12:19] Speaker 04:
I don't see that on 697

[00:12:22] Speaker 01:
Okay, I will have that for you on rebuttal, but I think the short answer is that we didn't understand the board to be saying, hey, those 13 known serotypes weren't obvious candidates because Pena itself tells you that they are obvious candidates because it says these are the 13 serotypes.

[00:12:37] Speaker 01:
It sets out the 13 serotypes in Pena itself, gives you the progression from 7 to 9 to 11, tells you the exact serotypes of the 13.

[00:12:45] Speaker 01:
And the board says, hey, we know Pena tells you.

[00:12:48] Speaker 04:
But what you need, I think, under those circumstances, I mean, Pena helps you.

[00:12:53] Speaker 04:
But what you need is some expert testimony from someone who says, I read Pena.

[00:12:57] Speaker 04:
I'm familiar with his art.

[00:12:59] Speaker 04:
This would have been giving me a motivation to put the 13 together and to select those 13.

[00:13:04] Speaker 04:
But so far, I don't see that.

[00:13:09] Speaker 01:
OK.

[00:13:09] Speaker 01:
So turning to page 698, it says, claim 18.

[00:13:14] Speaker 01:
It has the 13 conjugates of Prevnar-13.

[00:13:17] Speaker 01:
As of April 2006, Eposca would have found it obvious to select the 13 conjugates recited in Pena 2004, each conjugated CRM-197 for a polysaccharide protein conjugate vaccine.

[00:13:28] Speaker 01:
And it says, I understand they may not be the patent only claim they're not obvious because they're conjugated to the same carrier protein.

[00:13:34] Speaker 01:
But the specific serotypes chosen in Pena

[00:13:39] Speaker 01:
are there.

[00:13:40] Speaker 01:
Pena says, here is the serotypes we're testing.

[00:13:42] Speaker 01:
And you're going to pick those serotypes for the reasons Pena gives.

[00:13:45] Speaker 01:
And you're going to choose those because that's how you expand coverage.

[00:13:49] Speaker 01:
If you look, there's a list of serotypes.

[00:13:51] Speaker 01:
You know how common they are.

[00:13:52] Speaker 01:
And you keep going to the next most common for the geographic regions at issue.

[00:13:58] Speaker 01:
I did not understand the board to be saying, oh, gee, who would have known to follow Pena for the choice of serotypes when Pena gives you the serotypes.

[00:14:05] Speaker 01:
The only thing I thought the board might

[00:14:07] Speaker 00:
You're well into your rebuttal.

[00:14:08] Speaker 00:
I apologize.

[00:14:09] Speaker 00:
Thank you.

[00:14:10] Speaker 00:
All right.

[00:14:10] Speaker 00:
Thank you.

[00:14:41] Speaker 03:
May it please the court.

[00:14:43] Speaker 03:
The board's decision upholding claim 18 should be affirmed.

[00:14:48] Speaker 02:
At page 42 of the blue brief, Merck says that you, quote, never suggested that merely combining the claim conjugates with the stabilizing formulation as siliconized containers beyond the artisan's skill.

[00:15:04] Speaker 02:
Is it beyond the artisan's skill?

[00:15:07] Speaker 02:
If so, why?

[00:15:14] Speaker 03:
Yes, Your Honor, it is beyond the artisan's skill.

[00:15:19] Speaker 02:
What tells me that in the record?

[00:15:33] Speaker 03:
What tells us that in the record, Your Honor, is that the 13-valent conjugate that's described in claim 18 is nowhere described in the prior art.

[00:15:43] Speaker 03:
While the seven serotypes recited in claim 18 are set forth in the Pena reference, those seven serotypes are not shown or suggested anywhere in the prior art to be conjugated to the crim carrier protein.

[00:16:00] Speaker 03:
this is this is the this is what about well you heard mr lampkin this morning and he's talking about the disclosure in henya why isn't that sufficient at least as an obviousness to try theory it's not sufficient your honor because the well first penya describes those vaccines as an advanced phases of study and not yet marketed and as the board found that information alone

[00:16:26] Speaker 03:
is not sufficient to see whether those vaccines were even tried, considered, or successful.

[00:16:31] Speaker 03:
And given the fact that the prior art was showing that there was a trend towards using multiple carrier proteins rather than a single carrier protein like

[00:16:41] Speaker 03:
claim 18 specifies, there would be no reason to try this because the prior art was trending towards multiple carrier proteins.

[00:16:49] Speaker 00:
Did you have an expert testified about that?

[00:16:52] Speaker 03:
We certainly did, Your Honor.

[00:16:53] Speaker 03:
Our expert, Dr. Fatone, testified about this in the record, and this is at

[00:17:07] Speaker 03:
Appendix 689, beginning at Appendix 689, paragraphs 19, 21, and 22 of Dr. Fratone's testimony.

[00:17:17] Speaker 04:
And in the- I don't understand that to be the basis for the board's decision.

[00:17:23] Speaker 04:
Are you agreeing that it would have been obvious to select the 13 then, but that what's non-obvious about this is the way, is the method of producing it?

[00:17:34] Speaker 03:
My understanding of the board's decision, Your Honor, is that the board found that Merck failed to show a motivation to combine the 13 valent conjugates or to modify the prior art to yield the 13 valent conjugate formulation of Claim 18.

[00:17:54] Speaker 03:
Because Merck failed to show that... Let me interrupt your presentation.

[00:17:59] Speaker 03:
689?

[00:18:00] Speaker 03:
6089.

[00:18:01] Speaker 03:
Oh, okay.

[00:18:02] Speaker 03:
Sorry.

[00:18:04] Speaker 03:
In the second volume.

[00:18:05] Speaker 03:
Apologies.

[00:18:10] Speaker 03:
Thank you.

[00:18:11] Speaker 03:
To respond to your honor, the board found that Merck failed to show any teaching or suggestion of a formulation comprising the 13 polysaccharide protein conjugates in claim 18.

[00:18:24] Speaker 03:
And based on Merck's failure to make that showing, the board found that there was no motivation to get to the claimed subject matter.

[00:18:35] Speaker 04:
I'm trying to be clear about this.

[00:18:37] Speaker 04:
Are you agreeing with Mr. Lamkin that it would have been obvious to choose the 13 to produce the vaccine?

[00:18:44] Speaker 03:
Absolutely not, Your Honor.

[00:18:46] Speaker 03:
So there was, as early as 1983, there was Pneumovax, which is a free polysaccharide vaccine that had 23 serotypes.

[00:18:55] Speaker 03:
This was a free polysaccharide.

[00:18:58] Speaker 03:
So it had all but one of the serotypes that are recited in Claim 18.

[00:19:03] Speaker 03:
People, there were a wide variety of serotypes to choose from.

[00:19:06] Speaker 03:
The fact is that from 1983, it took 17 years to get the first conjugate vaccine.

[00:19:13] Speaker 04:
Did you have an expert who said it wouldn't have been obvious to choose the 13?

[00:19:23] Speaker 03:
I believe we did, Your Honor.

[00:19:25] Speaker 03:
We have our expert

[00:19:28] Speaker 03:
our expert again, Dr. Fatoum, what he said wouldn't be obvious would be to choose the 13 and conjugate them to the crim carrier protein.

[00:19:37] Speaker 03:
That's different.

[00:19:38] Speaker 04:
That's different.

[00:19:39] Speaker 04:
Did he say it wouldn't have been obvious to choose the 13?

[00:19:45] Speaker 03:
I would... Sorry.

[00:20:20] Speaker 03:
Your honor, our expert doctor for Tome testified at page 6087 of the appendix.

[00:20:26] Speaker 03:
6087.

[00:20:27] Speaker 03:
In paragraph 16 of his testimony.

[00:20:31] Speaker 03:
That the 23-valent vaccine was existing in the prior art and

[00:20:52] Speaker 03:
and that it would not have been obvious to conjugate these serotypes, additional serotypes in vaccines of higher valency to crimp for the reasons that I stated that these vaccines with conjugated to... I'm not seeing where he's focusing on the would not be obvious to combine 13.

[00:21:32] Speaker 03:
I apologize, Your Honor.

[00:21:34] Speaker 03:
But I believe our expert testified that the problem here was the selection of serotypes and the conjugation to the carrier protein, CRIM.

[00:21:45] Speaker 03:
The pain you referenced does identify a 7-valent vaccine conjugated to the CRIM carrier protein.

[00:21:51] Speaker 02:
What about your paragraph 14, page 6?

[00:21:58] Speaker 02:
I mean, that's as close as I think

[00:22:13] Speaker 04:
It, again, looks as though he's saying it wouldn't have been obvious to the conjugated using this particular protein.

[00:22:21] Speaker 03:
I believe that's correct, Your Honor.

[00:22:23] Speaker 03:
But that was the problem that the board identified, that Merck, in its petition, never showed, while it showed, for example, with respect to claim 17, Merck found, the board found that in appendix page 39 of the decision,

[00:22:41] Speaker 03:
that unlike the seven-valent conjugate of claim 17, Petitioner has not demonstrated that Chiron teaches or suggests incorporating a 13-valent conjugate into its formulation.

[00:22:54] Speaker 03:
And the board looked at claim 17 and saw in Chiron an express reference to Streptococcus de Monnier and then an express citation of a reference which is called the Rubin reference, which identified with specificity

[00:23:09] Speaker 03:
the seven-valent vaccine, but the Rubin reference did not identify the 13-valent vaccine.

[00:23:17] Speaker 03:
In fact, no reference in this record shows the 13-valent vaccine conjugate where all 13 serotypes are conjugated to CRM.

[00:23:28] Speaker 03:
Merck relies on, in the natural progression argument, they rely on a 9-valent vaccine, which was conjugated to CRIM.

[00:23:37] Speaker 03:
That vaccine was in a lyophilized formulation.

[00:23:39] Speaker 03:
It was not an aqueous buffer formulation, as required by the claim.

[00:23:44] Speaker 03:
Merck also relies on an 11-valent vaccine.

[00:23:48] Speaker 03:
There's no showing in the prior art of studies regarding the 11-valent vaccine, no showing of efficacy regarding that 11-valent vaccine.

[00:23:58] Speaker 03:
And moreover, they're showing that Sanofi, for example, its 11-valent vaccine used a multiple carrier approach.

[00:24:10] Speaker 03:
The fact is that the prior art was trending towards a multiple carrier approach.

[00:24:15] Speaker 03:
Sanofi studied single carrier protein vaccines in 2002 and came to the conclusion that a mixed carrier would be required.

[00:24:26] Speaker 03:
That's in Appendix 5214.

[00:24:28] Speaker 03:
GSK tried to make an 11-valent vaccine and with a single carrier called protein D. They found that vaccine to be lacking efficacy for certain otitis media episodes for serotype 3.

[00:24:44] Speaker 03:
GSK ultimately switched that single carrier protein to a multiple carrier protein.

[00:24:50] Speaker 03:
The fact is that there's no art in the record here showing that a 13-valent vaccine where all 13 serotypes are conjugated to CRIM was tried, considered successful, obvious, or anywhere in the art.

[00:25:06] Speaker 03:
And that was the basis for the board's decision that there was no motivation to combine and that there was a lack of reasonable expectation of success.

[00:25:20] Speaker 03:
What happened in the invention, the development of the invention, Wyeth, the patent owner, was the maker of Prevnor 7, which comes up in the record.

[00:25:31] Speaker 03:
Prevnor 7, when Wyeth was developing the 13-valent vaccine, which is the subject matter, Claim 18, they tested Prevnor 7, and they saw that Prevnor 7 did not aggravate.

[00:25:47] Speaker 03:
They were surprised when they put lots of the 13-valent vaccine into siliconized containers.

[00:25:55] Speaker 03:
They saw aggregation.

[00:25:58] Speaker 03:
And that's what the invention is meant to do.

[00:26:01] Speaker 03:
meant to solve.

[00:26:05] Speaker 03:
The inventors found that when they formulated the vaccine with aluminum in a buffer, as described in the claim, as described in claim 18, that they did not get aggregation.

[00:26:17] Speaker 04:
If it was obvious to do claim 17 and to conjugate it with this particular protein, why is it not obvious?

[00:26:32] Speaker 04:
in claim 18 to add the additional six.

[00:26:38] Speaker 03:
Because adding the additional, adding six additional serotypes to a vaccine in this field is not a simple matter, Your Honor.

[00:26:46] Speaker 03:
This is an unpredictable field here.

[00:26:49] Speaker 03:
The seven-valent vaccine was approved in 2000.

[00:26:52] Speaker 03:
The 13-valent vaccine did not get approved until 2010.

[00:26:57] Speaker 03:
When one adds serotype conjugates to these vaccines, a lot can happen in terms of the phenomena called immune interference and carrier induced epidemic suppression.

[00:27:09] Speaker 03:
When you add additional conjugates to a vaccine, you're adding additional antigens.

[00:27:15] Speaker 03:
You're adding additional carrier protein.

[00:27:18] Speaker 03:
When you add additional carrier protein and you give those vaccines to subjects, that additional carrier protein will elicit an immune response in those subjects, often overpowering the immune response of the serotypes.

[00:27:35] Speaker 04:
Did your expert say that?

[00:27:36] Speaker 03:
Yes, Your Honor.

[00:27:37] Speaker 03:
Our expert said that.

[00:27:42] Speaker 03:
Again, this is Dr. Fatom who testified about this, Your Honor.

[00:28:08] Speaker 03:
Dr. Fatom testified this at

[00:28:17] Speaker 03:
In his declaration at 6090, for example, in paragraph 22, the recommendation to use a mixed carrier approach

[00:28:29] Speaker 03:
for the eight-valent vaccine was a common approach.

[00:28:31] Speaker 03:
As discussed below, there was a concern that increasing amount of carrier protein in multivalent vaccines could induce carrier-induced epitopic suppression for some of the serotypes.

[00:28:42] Speaker 03:
He goes on to discuss this at length in paragraphs 24 through the end of his declaration.

[00:28:49] Speaker 04:
He was saying that 17 was also not obvious, right?

[00:28:59] Speaker 03:
Uh...

[00:29:04] Speaker 03:
I don't think Dr. Fatone was specifically opining on claim 17, Your Honor.

[00:29:10] Speaker 03:
I believe Dr. Fatone was discussing the theory, not the theory, the fact that adding additional serotypes to a vaccine, adding additional conjugates to vaccines cause immune interference and cause induced bicarbonate induced epitopes.

[00:29:28] Speaker 00:
In paragraph 22, he's talking about the eight.

[00:29:32] Speaker 02:
I think you want paragraph 26, but I'm just guessing.

[00:29:37] Speaker 00:
Paragraph... That's talking about the 13 as Judge Walla points out, which is what the discussion here is about.

[00:29:44] Speaker 03:
Paragraph 26 is talking about immune interference when developing the 13-valent conjugate.

[00:29:49] Speaker 03:
Thank you, Your Honor.

[00:29:52] Speaker 03:
Paragraph 22, just to help, just to clear that problem I raised.

[00:30:00] Speaker 03:
Paragraph 22 is the instance that I discussed earlier.

[00:30:04] Speaker 03:
Dr. Fatom was discussing Sanofi's efforts to develop

[00:30:09] Speaker 03:
eight valent vaccines and they found because of immune interference that a multiple carrier approach would be the optimal approach for developing these vaccines once you were increasing valency above the Prevnar 7 valent vaccine.

[00:30:27] Speaker 00:
Can I just point out, in appendix 86 is where the board, I think, you can point me to something else if you think, but

[00:30:35] Speaker 00:
They seem to reject reliance of Pena by saying, all Pena says is these 13 conjugates, this is an advanced phase of study.

[00:30:45] Speaker 00:
But it seemed like all the board relied on was, we can't assess whether the study was ever considered, if such an attempt was even considered, tried, and successful.

[00:31:01] Speaker 00:
Can you just talk to me a little about that?

[00:31:03] Speaker 00:
I mean, if Peña does talk about this being an advanced phase of study, why isn't that sufficient to establish motivation?

[00:31:12] Speaker 00:
They didn't have to show that it was successful, right?

[00:31:17] Speaker 00:
Is that what's required by the law?

[00:31:20] Speaker 03:
The board pointed out that Pena failed to show the additional serotypes conjugated to

[00:31:32] Speaker 03:
And it saw in PANIA no discussion of any data at all related to those advanced, related to even the 9 and 11 vaccines that are described in PANIA.

[00:31:47] Speaker 03:
So one skilled in the art would not know whether those vaccines would be efficacious or work.

[00:31:54] Speaker 03:
And it simply would not be, given what was going on in the prior art with the trend toward mixed carrier approaches, one skilled in the art would not be motivated to apply crim to the additional serotoxin.

[00:32:08] Speaker 00:
Well, the board says was even considered, tried, and successful.

[00:32:12] Speaker 00:
Is that what's necessary to establish a motivation to combine?

[00:32:16] Speaker 00:
that the study in Pena would have been successful using the 13 conjugate vaccine?

[00:32:22] Speaker 03:
This is a very unpredictable field, and I think the board recognized that, Your Honor, and that's why they, in finding claim 17 obvious, they were able to find that motivation because they saw an explicit reference in the prior art to the 7-valent vaccine of claim 18 that was linked to Chiron, the primary reference,

[00:32:43] Speaker 00:
But we need a reasonable expectation of success, not a demonstration in the prior art that it was successful, right?

[00:32:50] Speaker 03:
That's fair, Your Honor.

[00:32:52] Speaker 03:
But I believe that there is no reasonable expectation of success in April of 2006.

[00:32:57] Speaker 00:
Well, I mean, you believe it.

[00:32:59] Speaker 00:
I mean, that doesn't help us.

[00:33:01] Speaker 03:
I'm misspoke.

[00:33:02] Speaker 03:
The evidence and the witnesses, our witnesses, testify that there was no reasonable expectation of success in April of 2006.

[00:33:12] Speaker 03:
to generate a 13-valent vaccine, recited in Claim 18, where all of the carrier protein was the cream carrier protein.

[00:33:22] Speaker 00:
Okay.

[00:33:22] Speaker 00:
We're way beyond your time.

[00:33:24] Speaker 03:
Yes.

[00:33:24] Speaker 03:
Thank you very much.

[00:33:27] Speaker 00:
Three minutes.

[00:33:45] Speaker 01:
Thank you, Your Honor.

[00:33:46] Speaker 01:
I think a lot of the discussion shows that, frankly, it's not at all clear what the board's rationale was here.

[00:33:52] Speaker 01:
Some of us have been talking about whether or not the choice of the particular 13 serotypes that are expressly disclosed in Peña was obvious.

[00:34:00] Speaker 01:
But Peña discloses them.

[00:34:01] Speaker 01:
And if the court wants to know why they were done, I would direct the court to Hausdorff on page 1219, which talks about the frequency of running into those particular pneumonia serotypes.

[00:34:11] Speaker 02:
I think your problem is that the board

[00:34:15] Speaker 02:
didn't cite to some materials that were raised by Wyeth's expert.

[00:34:23] Speaker 02:
But there's plenty there to support what they did.

[00:34:26] Speaker 01:
So if the board met C's, and I think there's a lot of discussion about that, the fact that, or the assertion that in theory, if you put too many serotypes on a particular protein, it will have immune interference.

[00:34:39] Speaker 01:
But that cannot be what the board met.

[00:34:41] Speaker 01:
And it can't be what the board met for three reasons.

[00:34:44] Speaker 01:
The first is the board didn't address the Irish EPA document.

[00:34:48] Speaker 01:
It said we're not going to look at the Irish EPA document because it's cumulative or we've set another ground.

[00:34:52] Speaker 01:
But the Irish EPA document, and our expert talks about it on page 697 and 698 of the record, the Irish EPA document showed that Merck itself was using a single carrier protein crim for its 7, 9, 11, and 13 valent versions.

[00:35:07] Speaker 01:
So it can't be that there's no evidence that you can use it without C's, and yet we won't consider the document that actually shows it's being used.

[00:35:14] Speaker 01:
The second reason is this.

[00:35:15] Speaker 01:
Wyeth itself admits on page 57 of the brief that the board, and I'm quoting, did not reach Wyeth's arguments regarding immune interference.

[00:35:24] Speaker 01:
If there's one thing clear from administrative law generally, it is that the court can't affirm on the basis of an argument or a theory or fact findings the board never made.

[00:35:33] Speaker 01:
And if the board were going to go off on a C's theory that somehow there

[00:35:36] Speaker 01:
You know, people are deterred from doing 13 because of immune interference.

[00:35:40] Speaker 01:
You would have had to address the admission from Wyatt's own expert who said, let me say this, C's is not something that will prevent you from developing any vaccine with any valency.

[00:35:51] Speaker 01:
It's a risk management and risk evaluation.

[00:35:53] Speaker 01:
The patent nowhere suggests the innovation is somehow overcoming seas.

[00:35:57] Speaker 01:
Nowhere in the patent does it say that.

[00:35:59] Speaker 01:
And finally, Rubin, which is one of the references that the board considered on page 1889, talks about increasing valencies.

[00:36:08] Speaker 01:
On page 1889, it says, look, going from 7 to 9 to 11, you haven't seen immune interference.

[00:36:15] Speaker 01:
Why does it suddenly become not even obvious as a candidate of something obvious to do in the lab when you're just going from 11 to 13?

[00:36:24] Speaker 01:
There's another reason why Cs can't be the answer, and that's because the board repeatedly found

[00:36:29] Speaker 01:
And the patent itself, the claims themselves make clear that you don't have to have any particular level of immunogenicity in these claims.

[00:36:37] Speaker 01:
So if you're having some decree, or it doesn't even have to be effective as a vaccine, the notion that you're going to be deterred from even trying it out

[00:36:45] Speaker 01:
when there's no particular level of immunogenicity required from the claims, it's pretty hard to square when the board repeatedly says no required degree of immunogenicity.

[00:36:54] Speaker 01:
You're at least going to test it.

[00:36:56] Speaker 01:
At least you're going to want to try it.

[00:36:58] Speaker 01:
And it's the obvious one, because the serotypes are set out in Senya, and CRM-197 is the one that keeps working in the past.

[00:37:06] Speaker 01:
It's yours for 7, 9, 11, and it's particularly preferred under Kairat.

[00:37:10] Speaker 01:
Look, Wyeth has other patents that cover the composition

[00:37:15] Speaker 01:
an immunological version of it that says, we have a vaccine, it has these 13 serotypes, and it works.

[00:37:23] Speaker 01:
They can't strip out the requirement of it having an immune effect.

[00:37:27] Speaker 01:
Add an obvious stabilizing formula, and then try and extend the duration of those patents by another year.

[00:37:32] Speaker 01:
The stabilization formula that's the focus of the patents was held obvious, and it's not challenged before this court.

[00:37:39] Speaker 01:
13 valence, the particular 13 valence are sitting there in the prior and Pena,

[00:37:44] Speaker 01:
conjugating the cream 197 is obvious as well because that's the one that everyone works and goes to and if the court looks to 1232 in particular it says Wyeth itself is using cream 197 for its 9-valent version and it's 11-valent version if there's some magic reason why that combination Pena's 13 serotypes

[00:38:03] Speaker 01:
And CRM-197 isn't going to work, even though it worked for the first seven, the next two, the next two up to 11 serotypes.

[00:38:09] Speaker 01:
Some magic reason it's not going to work or it's not obvious to try it out.

[00:38:12] Speaker 01:
The board's going to have to tell us why, but it doesn't.

[00:38:15] Speaker 01:
And I think it doesn't because it made a mistake of obviousness law.

[00:38:19] Speaker 01:
It asked whether or not it found the actual combination in the prior art, CRM-197, together with those 13 serotypes, when the question is, is it obvious to put them together?

[00:38:30] Speaker 01:
And when you look at seven, nine, 11,

[00:38:32] Speaker 01:
particularly preferred, Prume 197 or Chiron, it is at least obvious to try that out in the lab.

[00:38:37] Speaker 01:
If there are no further questions, we ask the quick reverse.

[00:38:40] Speaker 00:
Thank you.

[00:38:41] Speaker 00:
We thank both sides, and the case is submitted.

[00:38:59] Speaker 00:
The next case for argument is 18-2261, La Moisana versus United States.