[00:00:00] Speaker 04:
Our next case is Seijin versus Daichi, AstraZeneca, 2023, 2024, and 1176.

[00:00:08] Speaker 04:
Mr. Sipes.

[00:00:09] Speaker 04:
Thank you, Your Honor.

[00:00:12] Speaker 02:
May it please the Court, my name is Christopher Sipes, and I'm here on behalf of the appellants, Daichi, Senkyo, and AstraZeneca.

[00:00:25] Speaker 02:
The appeal here from the district court involves patent claims that were first filed in 2019, 15 years after the 2004 application to which they claim priority.

[00:00:38] Speaker 02:
It is undisputed that they were filed after CJUN learned of appellant's antibody drug conjugate, Enhirtu, and were drafted specifically to capture that product.

[00:00:49] Speaker 04:
This court has made clear, for example, in Quake v. Lowe that- There's nothing inherently wrong with that if they had proper support in the application.

[00:00:59] Speaker 02:
That is correct.

[00:01:00] Speaker 02:
What this court said in Quake v. Lowe, however, is that it's particularly important in such cases that the requirements of Section 112 are met.

[00:01:08] Speaker 02:
That is, that the application clearly show that it is what the inventors invented and enabled at the time of filing, because there is a contrary concern in such circumstances.

[00:01:19] Speaker 02:
which is that an old expansive filing is being used to capture the innovation of others that came later.

[00:01:26] Speaker 02:
And that's exactly what is going on here.

[00:01:29] Speaker 02:
We have an incredibly broad 2004 application that does not describe the invention later claimed and claims that were then drafted 15 years later to capture not the invention described in 2004,

[00:01:47] Speaker 02:
but the invention made later by appellants of Enfirito.

[00:01:51] Speaker 02:
So, for example.

[00:01:54] Speaker 02:
We've got a jury verdict here, right?

[00:01:56] Speaker 02:
We did get a jury verdict, Your Honor.

[00:01:57] Speaker 02:
And this court has not hesitated in prior cases, for example, Novizheim and Idenics, to enter JMOL after a jury verdict because of a lack of written description in fact circumstances like this, where later claims are added to capture later arising innovations.

[00:02:17] Speaker 02:
And in fact, in Center Court, this court said, I think, correctly, that the court can look at the specification.

[00:02:23] Speaker 02:
And on the specification alone, it can be sufficient to show that the jury area in JML should be considered.

[00:02:29] Speaker 05:
Was there substantial evidence supporting the jury's verdict on damages?

[00:02:32] Speaker 02:
On damage, Your Honor, we believe there is not, because the two licenses that were the starting point and the reliance for the damage presentation are not in any way comparable.

[00:02:46] Speaker 02:
They were not exclusive.

[00:02:48] Speaker 02:
They were worldwide.

[00:02:51] Speaker 02:
They uncovered a trade secret and other patents so that they were the wrong starting point.

[00:02:57] Speaker 02:
And this court has recognized a number of times that the wrong starting point could lead to no substantial evidence.

[00:03:06] Speaker 02:
But let me come back to the breadth of the specification here, because this court has emphasized in its headquarters that that's really the foundation for evaluating written description.

[00:03:15] Speaker 02:
The issue for purpose of written description is the linker.

[00:03:19] Speaker 02:
The linker is part of the chemical aspect of the antibiotic drug conjugate that links.

[00:03:26] Speaker 04:
The tetrapeptide.

[00:03:28] Speaker 02:
That is correct.

[00:03:29] Speaker 02:
But not just any tetrapeptide.

[00:03:31] Speaker 02:
What is claimed is a narrow subset of 81 tetrapeptides in which peptides, of course, are made of amino acids.

[00:03:40] Speaker 02:
The specification here discloses the possible use, without differentiation, of 83 possible amino acids, as the inventor himself admitted, every natural amino acid that I can imagine, as well as a plethora of non-coded amino acids.

[00:03:57] Speaker 02:
So what is claimed is a linker that is a tetrapeptide made in which each of the four amino acids in the tetrapeptide is either glycine

[00:04:10] Speaker 02:
or phenylalanine.

[00:04:13] Speaker 02:
So only technically three of the 83 possibilities, because phenylalanine has two isomers in it.

[00:04:21] Speaker 02:
So that comes to 81.

[00:04:22] Speaker 02:
The total number of claimed peptide linkers in the patent is 108 sextillion.

[00:04:32] Speaker 04:
Well, your point is that they haven't been described.

[00:04:35] Speaker 02:
They haven't described the subset.

[00:04:36] Speaker 02:
They're possible.

[00:04:38] Speaker 02:
Correct.

[00:04:39] Speaker 02:
Even within tetrapeptides, what is encompassed by this enormous specification is

[00:04:45] Speaker 02:
47 million tetrapeptides and 108 sextillion peptide linkers.

[00:04:51] Speaker 02:
There are 17 illustrative examples of peptide linkers in the patent, 11 dipeptides, 3 tripeptides, and 3 tetrapeptides.

[00:05:02] Speaker 02:
None of those peptide linkers are glycine phenylalanine only, which for simplest they are referred to as GF only.

[00:05:11] Speaker 02:
None of them are GF only.

[00:05:13] Speaker 02:
None of the tetrapeptides are GF only.

[00:05:16] Speaker 02:
One of the three tetrapeptides comes close, if you will.

[00:05:21] Speaker 02:
Going backwards, it's a P2 position.

[00:05:26] Speaker 02:
It's leucine rather than phenaline, which is to say it comes close to one of the possible members of the genus.

[00:05:36] Speaker 02:
It doesn't come close, of course, to the genus as a whole, but it comes close to one of them.

[00:05:41] Speaker 02:
The problem with that is twofold.

[00:05:43] Speaker 02:
One, of course, is this isn't horseshoes.

[00:05:45] Speaker 02:
Close doesn't count.

[00:05:46] Speaker 02:
This court has been adamant on that, that what matters here is disclosure.

[00:05:51] Speaker 04:
You cannot submit.

[00:05:52] Speaker 04:
It's not obvious.

[00:05:54] Speaker 02:
Correct.

[00:05:55] Speaker 02:
The court has made this very clear in a number of cases.

[00:05:58] Speaker 03:
It's very expert.

[00:05:59] Speaker 03:
Dr. Batrosi said something about, I read this back.

[00:06:09] Speaker 03:
I see GFLG.

[00:06:10] Speaker 03:
And when I see GFLG, I also see GFGG or GFFG.

[00:06:18] Speaker 02:
Yes, GFFG, correct.

[00:06:21] Speaker 02:
So there's several problems with her testimony that make it not disclosure, not a blaze mark, if you will, to the genus.

[00:06:29] Speaker 02:
As in her words, it would be a straightforward leap, a leap nonetheless.

[00:06:34] Speaker 02:
This court said in Lockwood, it is not sufficient that the disclosure, when combined with the knowledge of the art, would lead one to speculate as to modifications that the inventor might have envisioned but failed to disclose.

[00:06:46] Speaker 02:
So let's think about what she's saying.

[00:06:48] Speaker 02:
She's saying, I can see that and then modify it to get to GFFG.

[00:06:54] Speaker 02:
She's not saying that a post would look at,

[00:06:57] Speaker 02:
GFLG and recognize the L doesn't mean L. It means F. She's saying you can modify the disclosure.

[00:07:05] Speaker 05:
She's saying that a person of ordinary skill would understand what the next step is.

[00:07:11] Speaker 02:
That is correct.

[00:07:11] Speaker 02:
And the key aspect is it is the next step.

[00:07:14] Speaker 02:
And as this court has made clear in many cases, including most colorfully in its language, Lockwood,

[00:07:20] Speaker 02:
Next step is not disclosure.

[00:07:23] Speaker 02:
It is, in fact, modification of what is disclosed.

[00:07:27] Speaker 02:
Of course, having disclosed 107 septillion possibilities and a number of examples, the three tetrapeptides, the other two are very far away, which I'll come to in a minute.

[00:07:38] Speaker 02:
One can, after the fact, come up with all sorts of modifications

[00:07:42] Speaker 02:
the inventors might have made, but did not disclose.

[00:07:47] Speaker 03:
What if we were to read the expert testimony?

[00:07:50] Speaker 03:
Maybe she didn't use the best words, but what if we read her testimony as saying, I understand this says GFLG.

[00:08:00] Speaker 03:
But I also understand this disclosure ultimately to be contemplating GFFG.

[00:08:10] Speaker 03:
Because when I look at other examples disclosed of peptides at the P2 position, I see the use of F at the P2 position.

[00:08:22] Speaker 03:
And everybody knows, because when you read all the relevant

[00:08:27] Speaker 03:
journal articles, the value and importance of having phenylalanine at that position?

[00:08:37] Speaker 02:
There would be several problems with that.

[00:08:39] Speaker 02:
One, of course, is it's still modification.

[00:08:41] Speaker 02:
It's still the language of obvious.

[00:08:43] Speaker 02:
But even let's move past that.

[00:08:45] Speaker 02:
There's two other problems with that.

[00:08:47] Speaker 02:
One, of course, is what is claimed here is not the species GFFG.

[00:08:52] Speaker 02:
But the genus, GRF at position one, GRF at position two, GRF at position three, GRF at position four, it's four choices in a maze-like path.

[00:09:04] Speaker 02:
It's not teaching GRF at the first, GRF at the second, GRF at the third, GRF at the fourth.

[00:09:10] Speaker 02:
It's identifying a compound.

[00:09:12] Speaker 02:
This court has made clear that even if you could have clenched to a compound, that might not be enough for

[00:09:18] Speaker 02:
a subgenus, for example, the BASF case they cited.

[00:09:21] Speaker 02:
Founded species supported, but not the subgenus.

[00:09:26] Speaker 02:
But also, it's worth thinking about that, this idea that somehow the POSA modifies GFLG to be GFFG.

[00:09:33] Speaker 04:
You're talking about a person of ordinary skill.

[00:09:35] Speaker 02:
Person of ordinary skill.

[00:09:37] Speaker 04:
Speaking English.

[00:09:38] Speaker 02:
I apologize.

[00:09:38] Speaker 02:
A skilled artisan.

[00:09:42] Speaker 02:
So what this court said, for example, in the Regents v. Gilead case quite recently is

[00:09:48] Speaker 02:
When you point to the disclosure of the patent, that the common structural features, which was using a way similar to blaze marks, must exist between a claim and a punitive priority disclosure, those features must constitute the near entirety of the structures being compared.

[00:10:06] Speaker 02:
And in that case, where the priority encompassed a significantly larger genus than what was claimed, it was not sufficient.

[00:10:12] Speaker 02:
That's also a flaw with what Dr. Bertozzi is suggesting.

[00:10:16] Speaker 02:
So if a person looks at what's disclosed, first you have to get to tetrapeptides.

[00:10:21] Speaker 02:
Because remember, the disclosure goes from 2 to 12 amino acids, and I think from dipeptides to dodecapeptides, which itself is enormous.

[00:10:32] Speaker 02:
But even having made the choice of tetrapeptides,

[00:10:35] Speaker 02:
What does the patent teach about limiting choice one to G or F?

[00:10:41] Speaker 02:
It teaches a way.

[00:10:42] Speaker 02:
It teaches G or A, for example, in the three examples.

[00:10:46] Speaker 03:
So in your view, what

[00:10:49] Speaker 03:
was needed in this disclosure to be said that wasn't said.

[00:10:54] Speaker 03:
Do you demand that the spec literally say, by the way, preferred environments are GF-only tetrapeptides for my linker?

[00:11:05] Speaker 02:
There needed to be either some sort of disclosure identifying as preferred tetrapeptides over other lengths.

[00:11:13] Speaker 02:
glycine and phenaline other choices, which would be one way to beat blaze marks to there.

[00:11:20] Speaker 05:
What if it's well-known in the art?

[00:11:23] Speaker 02:
Again, that's coming back to exactly what this court has repeatedly condemned, for example, in Lockwood.

[00:11:29] Speaker 02:
It's not enough for somebody to come in and say, well, because of what's well-known, one would modify the disclosure.

[00:11:35] Speaker 02:
We're not talking about a case where what we're saying is there's a term used in the application.

[00:11:41] Speaker 02:
And that term would be understood by a skilled artisan based on what was known to have the meaning of this.

[00:11:51] Speaker 02:
All the time we're coming back to, we have to modify what was in the application to come up with the sentence.

[00:11:57] Speaker 02:
And this court is repeatedly condemned.

[00:11:58] Speaker 04:
I want to save the rest of your time.

[00:11:59] Speaker 04:
I'll continue.

[00:12:00] Speaker 02:
I'm happy to reserve the rest of my time for a robot.

[00:12:02] Speaker 04:
I'll save it for you.

[00:12:05] Speaker 04:
Thank you.

[00:12:11] Speaker 00:
Good morning, Your Honors.

[00:12:12] Speaker 00:
Sarah Horton for Appellee with me here today are Dane Sowers and Devin Edwards.

[00:12:19] Speaker 01:
After a five-day jury trial with testimony from 19 different witnesses, the jury found that the 039 patent was willfully infringed and not invalid and awarded C-GEN a reasonable royalty.

[00:12:30] Speaker 04:
Appellants?

[00:12:30] Speaker 04:
Counsel, I realize, we all realize, this is a jury verdict.

[00:12:35] Speaker 04:
And written description is a fact question, although enablement isn't.

[00:12:42] Speaker 04:
We can look at the specification.

[00:12:44] Speaker 04:
We can look at the claim.

[00:12:47] Speaker 04:
The claim encompasses a lot of compounds.

[00:12:52] Speaker 04:
But it requires the tetrapeptide to be only glycine and phenylalanine.

[00:13:01] Speaker 04:
Are there any such descriptions in the patent?

[00:13:07] Speaker 01:
Your question, Your Honor, is there literally a description of a GF-only tetrapeptide as one of the examples in the specification?

[00:13:15] Speaker 01:
No, that is not listed specifically.

[00:13:17] Speaker 04:
So there's no written description of what's claimed?

[00:13:20] Speaker 01:
No, Your Honor.

[00:13:21] Speaker 01:
I think the written description question looks at how one of ordinary skill in the art would reasonably review the four corners of the specification

[00:13:29] Speaker 01:
to understand whether or not the inventors possessed what had claimed.

[00:13:33] Speaker 01:
And here, I think the evidence that Dr. Bertozzi provided and the jury heard was from the specification itself, actually, that tetrapeptides were claimed specifically, that G and F

[00:13:46] Speaker 01:
were two of the amino acids that could be used preferably in those tetrapeptides.

[00:13:51] Speaker 01:
And that also there were blaze marks to the specifically claimed tetrapeptide with GF only.

[00:13:58] Speaker 01:
Those blaze marks included that of the tetrapeptides that were described specifically in the specification, one of them used

[00:14:10] Speaker 01:
G and F for two of the three amino acids.

[00:14:14] Speaker 01:
She also explained that they tried peptides that were explained in the specification.

[00:14:19] Speaker 01:
All use F at the two positions.

[00:14:22] Speaker 04:
But that's not what's claimed.

[00:14:24] Speaker 04:
She said it would be a straightforward leap.

[00:14:27] Speaker 01:
Yes, she did.

[00:14:28] Speaker 04:
Well, straightforward sort of calls forth the concept of obviousness.

[00:14:34] Speaker 04:
But a leap, a leap

[00:14:37] Speaker 04:
means it's not there.

[00:14:39] Speaker 04:
You have to jump.

[00:14:40] Speaker 04:
You have to go there.

[00:14:42] Speaker 04:
And there's nothing to tell you.

[00:14:45] Speaker 04:
There are all sorts of possibilities of tetrapeptides, but there aren't any with just phenylalanine and lysine.

[00:14:56] Speaker 01:
Your Honor, I don't think that the court's jurisprudence has required that there be exact

[00:15:00] Speaker 01:
identity of the specific claimed species in the written description as it stands.

[00:15:06] Speaker 01:
There are other ways to find written description within the four corners.

[00:15:10] Speaker 01:
The straightforward leap quote that appellants cite to in their blue brief is, I think, a little bit misread.

[00:15:21] Speaker 01:
She explained that the shared specification in 2004 and 2019 disclosed exemplary tetrapeptides with three

[00:15:29] Speaker 01:
g n f amino acids this g f l g sequence that we've heard about and that it would have been a straightforward leap from that example as to what is claimed in view of the other teachings that are in the patent and what was known in the art her choice of language could have been some somewhat better it was a little imprecise but reading her testimony as a whole tell us what the straightforward

[00:15:50] Speaker 04:
direction to go to a tetrapeptide with only phenylalanine and lysine.

[00:16:01] Speaker 04:
Where is that direction to suggest going there?

[00:16:08] Speaker 01:
Well, the suggestion is as we've

[00:16:13] Speaker 01:
we've talked about is in the specification itself.

[00:16:15] Speaker 01:
The specification provides the general chemical formula for the claimed ADC.

[00:16:20] Speaker 01:
The specification provides that the peptide linker may be a tetrapeptide.

[00:16:25] Speaker 01:
The specification provides that glycine and phenylalanine are two of the 39 potential amino acids that could be used.

[00:16:32] Speaker 01:
That's it.

[00:16:34] Speaker 01:
They're the 39.

[00:16:35] Speaker 01:
Yes.

[00:16:35] Speaker 01:
Right.

[00:16:35] Speaker 01:
So, Your Honor, one of the cases that Appellant brought up was the BASF case.

[00:16:40] Speaker 01:
And if I could analogize to that case for a moment,

[00:16:43] Speaker 01:
There, appellants argue that the specification expressly identified canola as preferred embodiment of the invention by listing it as one of other 14 species.

[00:16:58] Speaker 01:
So one of 14 here.

[00:17:00] Speaker 01:
The O39 patent likewise discloses GNF as two of the among 39 amino acids suitable for the WW- But we're talking about 47 million possible candidates.

[00:17:11] Speaker 03:
Is that right?

[00:17:12] Speaker 01:
Well, that's not what's claimed, Your Honor.

[00:17:13] Speaker 03:
That's the number- I know, I know.

[00:17:15] Speaker 03:
We're trying to whittle down 47 million to the precious 81 or 83 magic beans here.

[00:17:22] Speaker 03:
And I'm trying to figure out how to get there.

[00:17:25] Speaker 03:
Your brief at page 62 says that the patent says that GNF are preferred amino acids.

[00:17:36] Speaker 03:
And I didn't find that in the patent.

[00:17:38] Speaker 03:
And it's a very long patent.

[00:17:40] Speaker 03:
So do you have column in line somewhere in this patent that makes it clear that GNF are preferred amino acids when it comes to this peptide linker?

[00:17:54] Speaker 01:
So G and F are used in tetrapeptides at column 67.

[00:18:02] Speaker 01:
That is where we see the GFLD.

[00:18:05] Speaker 03:
Right, but it's fair to say that I'm not going to find anywhere in this patent where the patent says, hey, G and F are preferred amino acids for my claimed BDC.

[00:18:19] Speaker 01:
Sure, what I think is meant by that, Your Honor, is that G and F are among the two amino acids that are disclosed, right?

[00:18:26] Speaker 01:
From there, we have the patent disclosure showing 13 different amino acids of those 39 are used in the 17 exemplary, excuse me, WW units that my friend just discussed.

[00:18:44] Speaker 01:
So those 17 exemplary units are

[00:18:48] Speaker 01:
made up of 13 different amino acids, not the 39, and there's only 17 in the disclosure itself.

[00:18:56] Speaker 01:
In those 17 exemplary WW units, nine of those are GNF.

[00:19:01] Speaker 01:
So really, nine of the WW units.

[00:19:04] Speaker 04:
The question is not whether GNF

[00:19:07] Speaker 04:
I don't use the F. The P for phenylalanine.

[00:19:14] Speaker 04:
Only phenylalanine in lysine.

[00:19:17] Speaker 04:
That's what's in the claim.

[00:19:18] Speaker 04:
Let me move you to enablement, which is a question of law.

[00:19:26] Speaker 04:
Part of the claim talks about the drug moiety being

[00:19:36] Speaker 04:
cleaved in a patient.

[00:19:41] Speaker 04:
Given the breadth of the claim and talks about a drug mortgage, which is rather broad, and the specification really only talks about dolastatins and orastatins, why isn't

[00:20:00] Speaker 04:
Why isn't this an enablement problem to show that that function of being cleaved in a patient has been met?

[00:20:11] Speaker 01:
Sure.

[00:20:12] Speaker 01:
Well, Your Honor, of course, enablement is a question of law, but the underlying facts are reviewed for substantial evidence.

[00:20:17] Speaker 01:
And here, the jury heard evidence about why the O39 patent enables one of ordinary skill in the art to practice the intercellular cleavage limitation, which is what I think Your Honor is striving at.

[00:20:28] Speaker 01:
The patent actually discloses that the peptide linkers will cleave intercellularly when exposed to protases present in the tumor cells.

[00:20:36] Speaker 01:
That's at columns 66 through 46.

[00:20:40] Speaker 04:
With any drug?

[00:20:42] Speaker 01:
So the patent discloses how that works in certain drugs at columns 66.

[00:20:50] Speaker 04:
Well, two types of drugs that aren't an issue here.

[00:20:56] Speaker 01:
Well, Your Honor, the specification does talk about chemotherapeutic agents in parts of its disclosure, and the prior art also taught numerous methods for testing in our cellular cleavage and whether or not that had occurred.

[00:21:08] Speaker 01:
I think that the point of the invention is that

[00:21:12] Speaker 01:
You could use these amino acid sequences and see that the drug was released inside the cancer cells, because the protases themselves that are inside the cells would break down the linker.

[00:21:22] Speaker 03:
That is the point, and that's the testimony that the... Just to confirm, any time someone created one of these claimed compounds that fits within this claim,

[00:21:33] Speaker 03:
You would have to test that manufactured compound to see if it in fact would intracellularly cleave in a patient.

[00:21:43] Speaker 03:
Is that right?

[00:21:43] Speaker 03:
You wouldn't know ex-ante once you've manufactured that antibody-drug conjugate whether in fact it does intracellularly cleave in a patient.

[00:21:54] Speaker 01:
So I think the issue there is, Your Honor, is that what is cleaving is the linker.

[00:22:00] Speaker 01:
So you could test the ADC, sure.

[00:22:02] Speaker 03:
But what you're really driving at is whether or not the... Whether you would need to test it.

[00:22:07] Speaker 03:
Could any scientist making a compound that fits within this claim

[00:22:11] Speaker 03:
after making it say, yes, it's going to definitely meet the intracellular cleaving in a patient limitation?

[00:22:19] Speaker 03:
Or would the scientists need to go further and say, okay, now we got to go test it to see if it works or not?

[00:22:25] Speaker 01:
So the disclosure and the invention is that

[00:22:28] Speaker 01:
when the claimed linker is used in the claimed intercellular cleavage would follow.

[00:22:32] Speaker 01:
There is testimony from the inventors and from the experts on both points.

[00:22:36] Speaker 01:
Our evidence shows it's the linker that cleaves when the protase comes into contact with the peptide chain.

[00:22:43] Speaker 03:
This is new to me.

[00:22:45] Speaker 03:
I did not realize that your position was you didn't need to test.

[00:22:53] Speaker 03:
You would know ahead of time.

[00:22:55] Speaker 01:
Well, I think the nature of the invention is that one ordinary skill in the art would know that it was cleaved, and if you wanted to prove their test... After you tested it.

[00:23:03] Speaker 03:
Well, if you tested it, you would find that it did, and there are tests that are... Right, but my question is, do you need to test at all to know that it, in fact, works?

[00:23:13] Speaker 03:
Well, if you... This is where the undue experimentation comes in.

[00:23:16] Speaker 03:
Do you need to do this sort of trial and error testing

[00:23:21] Speaker 03:
to determine whether the created compound meets the functional limitation of intracellular cleaving.

[00:23:29] Speaker 01:
One of ordinary skill in the art, I think based on reading the specification and understanding the invention, would understand that the cleavage would occur based on how the compound is

[00:23:39] Speaker 01:
is structured.

[00:23:39] Speaker 01:
But if testing were necessary to determine the cleavage, then the methods for doing so were known.

[00:23:44] Speaker 03:
So where is that testimony in the record where your expert said, no testing required.

[00:23:49] Speaker 03:
The spec tells me all I need.

[00:23:51] Speaker 03:
Any time I make one of these conscious gifts that falls within the claim, it's definitely going to intracellularly cleave without me needing to do any testing on it.

[00:24:03] Speaker 01:
Your Honor, I don't know that that exact testimony is there, but I'll point you to two places.

[00:24:07] Speaker 01:
One is in the patent itself at column 66, 43 to 45, where the patent speaks generally about how protases will break apart the linkers in the cell.

[00:24:15] Speaker 01:
It says the amino acid unit can be enzymatically cleaved by one or more enzymes, including tumor-associated protase to liberate the drug unit.

[00:24:24] Speaker 01:
Dr. Brotozzi similarly testified at Apex 3141 that protases are enzymes that cut peptides.

[00:24:31] Speaker 01:
I often like to think of them as acting.

[00:24:33] Speaker 03:
OK, so then your view is of column 30

[00:24:36] Speaker 03:
of column 66, every single one of the contemplated amino acid units in these two columns here will do the intracellular cleaving?

[00:24:48] Speaker 03:
I don't know, where were we, like sexta trillion or something like that?

[00:24:52] Speaker 01:
Well, of the claims, so look, we're in enablement.

[00:24:57] Speaker 03:
We're looking at what is actually claimed, and I think that what is claimed is... I know, but you're relying on this statement from the spec, which follows

[00:25:03] Speaker 03:
the whole laundry list of possible variations on an amino acid sequence is telling us that, yes, they all will do the cleaving.

[00:25:15] Speaker 03:
So that gets us out of 47 million and all the way up to that

[00:25:19] Speaker 03:
very large, unpronounceable number.

[00:25:21] Speaker 01:
Well, what the jury heard testimony was, was enablement of the claim itself, which was the GF-only tetrapeptide winger.

[00:25:31] Speaker 04:
Why isn't this case governed by Amgen, where the Supreme Court unanimously affirmed us on enablement of a claim that had a functional aspect to it and said, you can't

[00:25:48] Speaker 04:
be sure, without undue experimentation, that this function would be enabled?

[00:25:56] Speaker 01:
Your Honor, I think Amgen is, this case does not squarely fit into the facts of Amgen.

[00:26:03] Speaker 01:
In Amgen, the Supreme Court found that the claims were defined by their function.

[00:26:07] Speaker 01:
It sought to monopolize every antibody with a certain property, and the only way to know if an antibody would bind to the enzyme was to create candidates and then to screen them.

[00:26:16] Speaker 01:
Amgen had no structural limitations to narrow the claims at all.

[00:26:19] Speaker 01:
But here is a 039.

[00:26:20] Speaker 04:
But there's an important function here, the claimage in a patient.

[00:26:24] Speaker 01:
There is a function here, the intercellular cleavage.

[00:26:27] Speaker 04:
The concocted in vitro in a patient.

[00:26:30] Speaker 01:
I think there is testimony on that as well in the record that the jury heard, but the 039 patent does not claim every ADC that binds to a tumor cell and cleaves intercellularly.

[00:26:41] Speaker 01:
If it did, that is more like Amgen.

[00:26:43] Speaker 01:
Here we have claims to ADCs with a particular chemical structure.

[00:26:48] Speaker 01:
The particular chemical structure has, according to the math of appellants, one of 81 possible tetrapeptide lingers.

[00:26:55] Speaker 01:
That is not an unknowable, unlimited universe of compounds.

[00:26:59] Speaker 03:
How many drug moieties are covered by this claim?

[00:27:02] Speaker 01:
I think the testimony below is that it could cover any drug moiety.

[00:27:08] Speaker 03:
OK.

[00:27:08] Speaker 03:
So I'm just trying to get a grip in my mind as to what's the number of possible candidates overall that are covered by this claim?

[00:27:17] Speaker 03:
Is it just a couple hundred?

[00:27:21] Speaker 03:
Or is it a couple hundred thousand?

[00:27:23] Speaker 01:
I don't really know.

[00:27:23] Speaker 03:
Or is it in the millions?

[00:27:25] Speaker 01:
I don't know that the number was part of the testimony or is below.

[00:27:31] Speaker 01:
But the specification discusses many drug moieties.

[00:27:35] Speaker 01:
There are drug moieties discussed at trial.

[00:27:36] Speaker 01:
And the specification does not so limit the drug moieties to any specific number.

[00:27:41] Speaker 03:
OK, so it covers any drug moiety.

[00:27:43] Speaker 03:
Correct.

[00:27:44] Speaker 04:
Thank you, counsel.

[00:27:45] Speaker 01:
Thank you.

[00:27:49] Speaker 04:
Mr. Seitz has some letters on.

[00:27:55] Speaker 02:
Let me pick up first enablement, and then I have a few comments on written description.

[00:28:01] Speaker 02:
On enablement, the idea that no testing is required is rather a new argument to me.

[00:28:05] Speaker 02:
We've not heard it before.

[00:28:06] Speaker 02:
If you look, for example, on page 56 of the red brief, of their brief, it discusses that one is skill in the art.

[00:28:15] Speaker 02:
that there existed numerous in vivo and in vitro assays that could be used to test for intracellular cleavage.

[00:28:21] Speaker 02:
The notion that a skilled organism would simply know that all would work, I think, is both contrary to the record, which suggests that not all will work, and contrary to how one would determine whether it cleaves from system testing.

[00:28:33] Speaker 02:
And let me point you to that record evidence.

[00:28:38] Speaker 02:
First, with regard to the question of whether they all work,

[00:28:43] Speaker 02:
The inventor, Dr. Klein, was asking that question.

[00:28:48] Speaker 02:
And there's no one linker that will work for every drug?

[00:28:51] Speaker 02:
Answer, there is no one linker that will work for every drug.

[00:28:56] Speaker 02:
How would one know?

[00:28:57] Speaker 02:
Again, Dr. Klein, when the inventor says.

[00:29:00] Speaker 02:
And I apologize.

[00:29:01] Speaker 02:
That was at appendix 3297, 7913 to 15, and then appendix 3296, 7821 to 791.

[00:29:13] Speaker 02:
Uh, he testifies that you would need to do an assay to determine.

[00:29:17] Speaker 02:
You don't know until you do the assay.

[00:29:19] Speaker 03:
I agree.

[00:29:19] Speaker 03:
He necessarily must have found that there was no undue experimentation here.

[00:29:24] Speaker 03:
So why can we take that away from them?

[00:29:26] Speaker 02:
Because Amgen and Bexalta makes clear that where the patent has a functional requirement that requires iterative trial and error over the course of

[00:29:37] Speaker 02:
In Wythe and Cortis, it was tens of thousands.

[00:29:41] Speaker 02:
In Amgen, it was millions.

[00:29:42] Speaker 02:
In Pixalta, it's millions.

[00:29:44] Speaker 02:
Here, it's actually millions of millions, because you have millions of possible drug moieties and millions of possible antibodies.

[00:29:52] Speaker 03:
I didn't see any testimony on that.

[00:29:54] Speaker 02:
Where is it?

[00:29:55] Speaker 02:
Your Honor, I believe there is testimony, although I apologize that I do not have it to hand, both from Dr. Lambert, both that

[00:30:05] Speaker 02:
There are millions of possible antibodies and drugs.

[00:30:09] Speaker 02:
But what is clear, and it was actually CJENT who sought this construction, neither drug moiety nor antibody is limited to any particular antibody or any particular drug.

[00:30:21] Speaker 02:
So it covers any antibody targeting any particular cell and any drug.

[00:30:27] Speaker 02:
And with regard to how the idea that anyone uses it, that's not what the patent teaches.

[00:30:32] Speaker 02:
If you look, for example, at column 67, 57 to 59, the patent just teaches useful linker units can be designed and optimized in their selectivity for enzymatic cleavage by a particular enzyme, for example, a tumor-associated protease.

[00:30:53] Speaker 02:
So the patent is not teaching just to use anyone.

[00:30:56] Speaker 02:
It's saying you have to design your linker specific to the particular

[00:31:01] Speaker 02:
target cell.

[00:31:03] Speaker 02:
And again, because you have multiple, any possible antibody could be any possible cell.

[00:31:10] Speaker 02:
So it does not teach that anyone could be used.

[00:31:15] Speaker 02:
Turning to, and so that's exactly Amgen and Bexalta were, again, in the face of a jury verdict, the fact that the patent claim was so broad and required iterative trial and error to determine the functional limitation.

[00:31:29] Speaker 04:
Do you have a final thought?

[00:31:31] Speaker 02:
Yes, very quickly, for written description, Your Honor, that point that they're now making that you could use any peptide linker, anyone at all, and they say that the patent suggests you could use any linker, that defeats place marks.

[00:31:47] Speaker 02:
As the court said in Ruschig, it is no help in finding a trail or in finding one's way through the woods where the trails have disappeared.

[00:31:53] Speaker 02:
to be confronted simply by a large number of unmarked trees.

[00:31:56] Speaker 02:
If they're right that the patent teaches you could use any linker, then there is no blazing.

[00:32:02] Speaker 04:
Thank you, counsel.