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

[00:00:04] Speaker 04:
We have four oral arguments this morning.

[00:00:07] Speaker 04:
Two of them are in the same case.

[00:00:10] Speaker 04:
We've separated the argument on the appeal and the cross-appeal in number 18-1590.

[00:00:19] Speaker 04:
Ajinomoto versus ITC will begin with the argument on the appeal.

[00:00:26] Speaker 04:
and counsel could just stay in their places for a second.

[00:00:29] Speaker 05:
Thank you, Your Honor.

[00:00:48] Speaker 05:
Good morning, Your Honors, and may it please the Court.

[00:00:51] Speaker 05:
On the issue of replacing the native promoter, the ITC's decision should be reversed.

[00:00:57] Speaker 05:
The only support for the ITC's construction is a narrowing in the prosecution history.

[00:01:02] Speaker 05:
It is incorrect for at least three reasons.

[00:01:05] Speaker 03:
Isn't there some support in the spec that is the use of the word substitution?

[00:01:13] Speaker 05:
That is in the only embodiment.

[00:01:14] Speaker 05:
That's correct, Your Honor.

[00:01:15] Speaker 05:
The use of the word substitution is used an example for, which is the sole embodiment in the specification.

[00:01:20] Speaker 05:
But the other parts of the specification make clear that there are broad methods

[00:01:26] Speaker 05:
useful for making these changes to a DNA expression.

[00:01:29] Speaker 03:
And what's the state of the record, either the party submissions or the commission's reliance, and here I'll include either the ALJ or the commission itself, on what you might call extrinsic evidence?

[00:01:42] Speaker 03:
That is, usage of a phrase like substitute a promoter or replace a promoter, where the word is replace or substitute and the object of the word is the whole promoter, as either being

[00:01:56] Speaker 03:
generally used to refer to the entire nucleotide sequence making up the promoter or just you start with one promoter and you end up with another even if all you've done is replace a component.

[00:02:11] Speaker 05:
So I believe neither one of those terms was expressly defined in the extrinsic evidence of record.

[00:02:16] Speaker 05:
What was disclosed in the extrinsic evidence of record is that those of skill in the art knew of numerous methods of replacing or changing promoter sequences, such as mutagenesis or we've called kind of wholesale cut and replace.

[00:02:32] Speaker 04:
Well, that's not really an issue, right?

[00:02:34] Speaker 04:
Everybody agrees that there are ways of doing it.

[00:02:37] Speaker 04:
The question is what was meant by the language here.

[00:02:40] Speaker 05:
That's correct, John.

[00:02:43] Speaker 04:
In other words, you're telling us

[00:02:44] Speaker 04:
We don't get anything from the extrinsic evidence about the linguistic usage.

[00:02:51] Speaker 05:
From the linguistic usage, that's correct.

[00:02:52] Speaker 05:
But we do get from the extrinsic evidence that those of skill in the art, those genetic engineers with the toolbox ahead of them to change promoters knew that mutagenesis was a very well-known way to do that for decades.

[00:03:03] Speaker 05:
And substitution was a different way to do it.

[00:03:05] Speaker 05:
And there were other methods of increasing expression that were well-known in the art.

[00:03:11] Speaker ?:
OK.

[00:03:11] Speaker 05:
So the dialogue between the examiner and the applicant here makes very clear that the issue was not with how to change these promoters.

[00:03:21] Speaker 05:
It was with what are the changes to enhance expression occurred.

[00:03:24] Speaker 05:
And that's clear both from examiner statements and applicant statements.

[00:03:29] Speaker 05:
On the examiner's side, every single time the examiner identified an issue with the claim, he always tethered that issue to the expression regulation sequence, which is-

[00:03:41] Speaker 02:
the language from altering to replacing.

[00:03:44] Speaker 02:
Now, it may not.

[00:03:45] Speaker 02:
appear to me that it was necessary based on the exchange with the examiner, but you still did it.

[00:03:50] Speaker 02:
And you put the public on notice of that change.

[00:03:52] Speaker 02:
So why shouldn't that change be interpreted exactly the way it was interpreted below by the ITC?

[00:03:59] Speaker 02:
You want me to say that change was irrelevant.

[00:04:02] Speaker 02:
I don't think any change during prosecution should be treated as irrelevant.

[00:04:05] Speaker 02:
People have a right to believe, because they're put on notice, that you made this change for a reason.

[00:04:12] Speaker 05:
So our position is not that it's irrelevant.

[00:04:14] Speaker 05:
It's that it can't be so narrowed to just the preferred embodiment in example four.

[00:04:19] Speaker 05:
And that's clear because the examiner noted that there was mutagenesis, well-known methods of mutagenesis in the record.

[00:04:27] Speaker 02:
But there are lots of cases we have where it wasn't necessary

[00:04:32] Speaker 02:
for an applicant to limit their claims the way they did, but they nonetheless limited them.

[00:04:37] Speaker 02:
And the question isn't what could you have been allowed to claim.

[00:04:41] Speaker 02:
The question is, what would the world, those of skill in the art reading this prosecution, understand you to have limited yourself to?

[00:04:48] Speaker 05:
So those of skill in the art reading our prosecution history would have seen that the examiner said, your substitution is enabled.

[00:04:56] Speaker 05:
And in response, we made an amendment from altering to replacing.

[00:05:00] Speaker 05:
And we said, that's consistent with your recognition.

[00:05:04] Speaker 05:
We didn't say it equates to your recognition.

[00:05:06] Speaker 05:
And indeed, consistent with does not equal equates.

[00:05:08] Speaker 05:
It does not mean equates.

[00:05:10] Speaker 05:
And if we had wanted to equate the term replacement with the term substitution, we would have just used the term substitution.

[00:05:17] Speaker 05:
There was no need to try a different term unless we were trying to get something else and not limit ourselves.

[00:05:26] Speaker 02:
You're suggesting that basically by choosing a different word, you intentionally created ambiguity in what you were doing.

[00:05:34] Speaker 05:
I don't know that we intentionally created ambiguity, but it certainly did create ambiguity.

[00:05:38] Speaker 05:
And that's also supported.

[00:05:39] Speaker 02:
And you think that ambiguity should iner to the patentee in a claim construction issue as opposed to a prosecution history estoppel issue.

[00:05:47] Speaker 02:
But when I'm construing the claims, if I think it's ambiguous, it should err in favor of the patentee.

[00:05:52] Speaker 02:
My natural instinct is quite the opposite, since you're the one with the ability and the obligation to put the world on notice as to what you're claiming.

[00:06:00] Speaker 05:
We think that in yours in terms of a disclaimer rule, where it has to be clear and unambiguous.

[00:06:04] Speaker 05:
And here, there's statements in the prosecution history.

[00:06:06] Speaker 02:
This isn't about disclaimer.

[00:06:07] Speaker 02:
This is more about how we should interpret the scope of the claims.

[00:06:12] Speaker 02:
That's a different question than from disclaimer.

[00:06:14] Speaker 02:
Disclaimer is when there's a plain meaning that absolutely entitles you to something.

[00:06:18] Speaker 02:
You don't have that here.

[00:06:19] Speaker 02:
You don't have a plain meaning that absolutely entitles you to what you're asking for.

[00:06:23] Speaker 02:
You have some ambiguous language where we're not sure what you're entitled to.

[00:06:27] Speaker 02:
So disclaimer only comes into play when you're taking something out of what is an otherwise plain meaning.

[00:06:34] Speaker 05:
So the examiner noted, and the commission also noted below, that the applicant considered broad methods of changing expression within the scope of its claim.

[00:06:45] Speaker 05:
And that is the broad methods that we're talking about.

[00:06:48] Speaker 05:
And there must be something in the prosecution history that makes it very clear that you're giving up those broad methods.

[00:06:54] Speaker 02:
No, no.

[00:06:55] Speaker 02:
It's your claim language, which dictates what you consider.

[00:06:57] Speaker 02:
There are lots of specs that disclose a million different things, and they claim narrowly only one aspect of a particular invention.

[00:07:04] Speaker 02:
Often there are continuations, hiding in the wings, waiting with other aspects.

[00:07:07] Speaker 02:
But it's not the breadth of what you contemplated that you get coverage for.

[00:07:11] Speaker 02:
It's what you claim.

[00:07:13] Speaker 05:
And our position is that the term replacement is not so narrow as substitution, and it has been used in other art of record that's not prior art, but discusses age-old mutagenesis techniques as a replacement, a single nucleotide as a replacement.

[00:07:27] Speaker 04:
But don't we have to assume that it means something different than alteration?

[00:07:31] Speaker 05:
You don't have to, but you can.

[00:07:33] Speaker 05:
And if it does mean something different, I just don't think it means

[00:07:35] Speaker 05:
what the ITC has said it means and what CJ says it means because in the context of expression regulation sequences, alteration made sense because it would include things like deletions.

[00:07:49] Speaker 05:
In the context of a promoter, if you deleted a promoter, you would decrease expression.

[00:07:53] Speaker 05:
That would not make sense at all.

[00:07:55] Speaker 05:
So to the extent there are some differences in the context there could be, we just don't think it goes to the level of defining the invention only by substitution.

[00:08:08] Speaker 05:
We also think that other extrinsic evidence of record supports that.

[00:08:13] Speaker 05:
Because CJ's expert has admitted that whether you change a nucleotide sequence, a single nucleotide sequence by mutagenesis, or whether you cut and paste according to the method of example four, what you get is a new promoter.

[00:08:28] Speaker 05:
There is a more potent promoter there.

[00:08:30] Speaker 05:
And it doesn't matter whether you've done the replacement or the substitution.

[00:08:39] Speaker 05:
And I see I'm coming up on my time now.

[00:08:42] Speaker 04:
Want to save the rest of your time for a moment?

[00:08:44] Speaker 04:
Yes, I would.

[00:08:44] Speaker 04:
OK.

[00:08:44] Speaker 04:
Thank you.

[00:08:47] Speaker 04:
This is more Ed.

[00:08:55] Speaker 01:
May it please the court.

[00:08:58] Speaker 01:
We're not litigating here whether DNA mutagenesis was known or not.

[00:09:04] Speaker 01:
When the commission looked at the intrinsic evidence,

[00:09:08] Speaker 01:
The examiner made clear that the specification did not enable specific alterations to the expression regulation sequence to increase the activity of the protein.

[00:09:30] Speaker 01:
And what the patentees did is they did not challenge that characterization of the examiner.

[00:09:38] Speaker 01:
And they said, we're amending the claim consistent with what the examiner recognized that was enabled, which is the changing by substitution, the native promoter.

[00:09:51] Speaker 01:
So the commission followed the law here.

[00:09:53] Speaker 01:
And the patentee cannot now come and say, no, we want this broader scope.

[00:10:02] Speaker 03:
So as I understand the prosecution history, the examiner said two things.

[00:10:07] Speaker 03:
You've enabled substitution of promoters.

[00:10:11] Speaker 03:
You haven't enabled alteration of expression regulatory sequence.

[00:10:16] Speaker 03:
So there are two things on opposite sides.

[00:10:21] Speaker 03:
The examiner did not say you haven't enabled alteration of promoters.

[00:10:27] Speaker 01:
Well, the native promoter is a region of the expression regulation sequence.

[00:10:34] Speaker 03:
But there's a lot more in the expression regulatory sequence.

[00:10:37] Speaker 01:
There can be other, yes.

[00:10:39] Speaker 03:
Or at least there's more.

[00:10:40] Speaker 03:
I don't know about a lot more.

[00:10:41] Speaker 01:
But the examiner didn't say that any specific alteration within this broader sequence, which includes any specific alteration to the native promoter, that there are no examples in the specification that provide how you can increase DNA expression

[00:10:57] Speaker 01:
by following this method of altering specific nucleotide sequences within the entire expression regulation sequence, including within the native promoter sequence.

[00:11:09] Speaker 01:
And so they never challenged any of the characterizations of the examiner.

[00:11:15] Speaker 01:
And they amended the claim consistent with what the examiner said was enabled, which is the change in bisubstitution to native promoter.

[00:11:28] Speaker 03:
Why would there have even been an enablement concern with taking a promoter, say a six nucleotide promoter, using any technique you felt like to change the first letter, resulting in a new promoter when the

[00:11:52] Speaker 03:
chemical mutagenesis to change a first letter was, I think, by everybody's agreement, well known in the art.

[00:12:01] Speaker 01:
Well, what the examiner said is not that it was not well known.

[00:12:04] Speaker 01:
What he said is that there are no examples that show that when you follow this method, you're going to increase DNA expression of the gene.

[00:12:12] Speaker 01:
So what specific alterations need to be made in order to achieve the intended benefit of the invention, which is to increase the expression of the gene itself?

[00:12:25] Speaker 01:
They said what the specification enables is when you change by substitution the native promoter and you use a more potent promoter,

[00:12:35] Speaker 01:
Thereby you increase, it is known that you will increase the expression of that gene.

[00:12:40] Speaker 01:
But what specific alterations need to be made to the native promoter or to the expression regulation sequence?

[00:12:48] Speaker 01:
The specification did not include any of those examples of that happening.

[00:12:53] Speaker 01:
And so the examiner rejected the claims for lack of enablement based not only on the lack of guidance as to

[00:13:03] Speaker 01:
what the structure of the expression regulation sequence is, but also lack of guidance on how to increase the DNA expression or the expression of the gene by making those specific alterations.

[00:13:16] Speaker 01:
And the patentee did not challenge, even if the examiner was wrong in making that statement,

[00:13:24] Speaker 03:
They didn't challenge that.

[00:13:27] Speaker 03:
Right.

[00:13:28] Speaker 03:
It seems to me there are two different arguments here.

[00:13:31] Speaker 03:
One is that what the examiner said more or less drove them into the choice they made.

[00:13:38] Speaker 03:
But the softer argument is that what the examiner said actually left room for them to do several different things.

[00:13:47] Speaker 03:
But the thing that they did, the choice they made was, in fact, was to

[00:13:53] Speaker 03:
do the extremely safe thing of simply adopting a small variant of the language the examiner had himself articulated as sufficing.

[00:14:05] Speaker 01:
That's exactly right, Your Honor.

[00:14:11] Speaker 01:
Okay.

[00:14:11] Speaker 04:
Thank you.

[00:14:11] Speaker 04:
Thank you, Ms.

[00:14:13] Speaker 04:
Martin.

[00:14:30] Speaker 00:
I think what's happening here is that Enjinomoto was attempting to divide the term replacing the native promoter with a more potent promoter into the first part of that term which is replacing.

[00:14:44] Speaker 00:
What the Commission did in their claim construction and what Enjinomoto told the examiner during prosecution was to look at the whole term.

[00:14:52] Speaker 00:
The Commission has said removing the native promoter, inserting a new promoter.

[00:14:56] Speaker 00:
engine motor during the prosecution said, we're changing the native promoter by substituting with a more potent promoter.

[00:15:05] Speaker 00:
Now when they talk about alterations, they're saying, let's look at just the replacing term.

[00:15:11] Speaker 00:
They're forgetting that you also have to do something with a new promoter coming in.

[00:15:17] Speaker 00:
They're just saying replace or alter a nucleotide.

[00:15:21] Speaker 00:
And that's specifically, as Ms.

[00:15:23] Speaker 00:
Murad just said, what the examiner said was not

[00:15:26] Speaker 00:
You can't make specific changes and expect them to have a function of increasing the YDGG production.

[00:15:34] Speaker 00:
And in fact, in the brief, the blue brief, 43 to 44, when Enshinomoto... Can I ask you this question?

[00:15:40] Speaker 03:
Is there reason in the record or otherwise to think that if you, say you started with a six nucleotide promoter and you ended with the same six nucleotides, except the first one, first nucleotide was different.

[00:15:56] Speaker 03:
Is there anything, any reason to think that the potential effect on increasing the

[00:16:03] Speaker 03:
tryptophan production or whatever would be affected at all by how you made that first letter change?

[00:16:13] Speaker 00:
You wouldn't know whether it would go up, down, or have no effect.

[00:16:17] Speaker 00:
And that's the point.

[00:16:18] Speaker 03:
So that the effect on the cellular production of the identical six nucleotides

[00:16:26] Speaker 03:
might be different according to how you've got to them?

[00:16:30] Speaker 00:
No, Your Honor.

[00:16:31] Speaker 00:
Actually, promoter is more like 40 or 90.

[00:16:35] Speaker 00:
Whatever.

[00:16:36] Speaker 00:
You make one change, you don't know what the effect of that change is.

[00:16:39] Speaker 00:
There's no argument that you can make a change.

[00:16:42] Speaker 00:
but you have no idea what the effect of that change will be.

[00:16:45] Speaker 00:
Will it decrease the promoter?

[00:16:47] Speaker 00:
Will it increase the promoter?

[00:16:48] Speaker 00:
Or will it do nothing?

[00:16:50] Speaker 00:
You just don't know.

[00:16:51] Speaker 00:
And that's why the examiner said you haven't enabled making specific alterations to improve production of YDDG, which is the whole point of using a more potent promoter.

[00:17:01] Speaker 00:
You want to make

[00:17:02] Speaker 00:
greater production of YDDG.

[00:17:05] Speaker 00:
And since you don't know which changes you can make, you therefore can't make those changes.

[00:17:10] Speaker 04:
In other words, people knew how to distinguish among motors in terms of potency, but they didn't know what the effect of changing a particular nucleotide sequence might be.

[00:17:23] Speaker 00:
Correct.

[00:17:23] Speaker 00:
You could take one out and put a new one in, but you couldn't just change one and expect it to be better or worse.

[00:17:29] Speaker 00:
You just wouldn't know.

[00:17:32] Speaker 00:
And as I say, when Enjinomoto quoted the rejection, they left out the portion that said you can't enable specific changes.

[00:17:41] Speaker 00:
The other thing, one of the questions that you asked was if there was anything else in the specification that talked about substitution.

[00:17:48] Speaker 00:
And if you look in the specification at volume one, appendix 190 to 191, it starts out on 190 saying the present inventions are as follows.

[00:18:00] Speaker 00:
And then it lists 11 subparagraphs.

[00:18:04] Speaker 00:
And one of those subparagraphs, subparagraph number four on page 191,

[00:18:08] Speaker 00:
says the bacterium according to the above bacterium, wherein the native promoter of said DNA is substituted with a more potent promoter.

[00:18:17] Speaker 00:
In none of those 11 topics do they say altering an individual nucleotide or changing an individual nucleotide.

[00:18:26] Speaker 00:
And so the specification, I think, is consistent with the way Enjinomoto interpreted this, with the way the examiner interpreted it, and where the commissioner interpreted it in terms of replacing

[00:18:37] Speaker 00:
Promoter with something else not changing something which had maybe no effect at all Okay, anything more I think not thank you very much about Mr.. Livingstone Thank you honor I Would like to address the point that you were just discussing about specific alterations in the promoter sequence because I think that's incorrect and

[00:19:02] Speaker 05:
The examiner could not have been talking about specific alterations in the promoter sequence because the specification cited conventional methods as mutagenesis, clearly known, and the specification discloses sequence ID number 9, which is the promoter for the YDDG, the native YDDG promoter.

[00:19:18] Speaker 05:
Now the commission found below that there is a clear link between what's called the consensus sequence and promoter strength.

[00:19:26] Speaker 05:
And here there is testimony that those of skill in the art looking at sequence ID number nine and looking at that promoter would know as they moved individual nucleotides towards consensus that would make the promoter stronger.

[00:19:38] Speaker 05:
So you could affect promoter strength based on the sequence.

[00:19:48] Speaker 05:
The next question is to your question, Judge Moore.

[00:19:56] Speaker 05:
Under Phillips, you can use the prosecution history, of course, to determine claim scope.

[00:20:00] Speaker 05:
But you have to look at the entirety of the intrinsic and extrinsic record.

[00:20:03] Speaker 05:
And we think the entirety of the record indicates that there was no

[00:20:07] Speaker 05:
Narrowing of the claims such that was to the preferred embodiment of example for to this very specific substitution method and to the exclusion of Decades old methods of mutagenesis to increase promoter strength Anything further Okay, thank you.

[00:20:25] Speaker 04:
Thank all counsel The appeal is submitted and we'll turn to the cross appeal and here we start with mr. Haley I

[00:20:49] Speaker 00:
May it please the Court.

[00:20:51] Speaker 00:
Today I'm going to address two issues that are in our appeal and both are dispositive with respect to Strain 4151.

[00:20:59] Speaker 00:
The first is the Commission eared at law in disregarding the FESTO instructions that in order to find rebuttal on the tangential prong, the reason for the amendment must be apparent from the specification, from the prosecution, excuse me, and

[00:21:17] Speaker 00:
that the prong is rarely invoked and is very narrow.

[00:21:21] Speaker 00:
Secondly, I want to address written description.

[00:21:23] Speaker 00:
Here, the Commission ignored Arias' sure principle that you need to have a representative number of species.

[00:21:30] Speaker 00:
And the Commission pointed to four that are not representative of the virtually infinite number of more potent promoters that are described.

[00:21:37] Speaker 00:
So let's talk about Festo.

[00:21:42] Speaker 00:
As a first step in Festo for tangential

[00:21:45] Speaker 00:
Rebuttal you need to look to the prosecution history and find an objectively apparent reason for the amendment here the Commission found nothing they cited nothing from the prosecution and if you look at That's the Commission's decision volume 1 43 to 44 Nothing in the prosecution gave a reason for the amendment and if you look for that, it's a volume 1 appendix 5 6 1 7

[00:22:14] Speaker 00:
What the prosecution said, and this is at volume 156, also 5617, they said, in view of this amendment, Lipschitz, which is the prior act, no longer anticipates.

[00:22:26] Speaker 00:
All that says is I've distinguished the prior act.

[00:22:28] Speaker 00:
It doesn't say I'm taking back some of my amendment.

[00:22:31] Speaker 00:
It says I've distinguished the prior act.

[00:22:33] Speaker 00:
That's not enough to allow tangential rebuttal.

[00:22:37] Speaker 00:
Second, Amgen's narrowing amendment took a claim that was this big covering any protein that had one or more changes compared to sequence ID2.

[00:22:47] Speaker 00:
Was it one or more?

[00:22:49] Speaker 03:
Wasn't there some sort of several limit?

[00:22:51] Speaker 00:
Yes, one or several changes.

[00:22:52] Speaker 00:
That's correct.

[00:22:53] Speaker 03:
Well, one or more could change everybody, one of them, right?

[00:22:56] Speaker 00:
That's true.

[00:22:57] Speaker 00:
And so the claim was this big.

[00:23:00] Speaker 00:
Now they said the claim is this big.

[00:23:01] Speaker 00:
It's sequence ID 2 and those things that hybridize to it.

[00:23:05] Speaker 00:
And under Festo, you've given up, surrendered the thing between the old claim and the new claim.

[00:23:11] Speaker 00:
Ange and Amono never said in the prosecution, well, we're not actually giving up all of that.

[00:23:15] Speaker 00:
We're only giving up a part of it.

[00:23:17] Speaker 00:
Under public notice, the public is allowed to rely on what Enjinomoto chose to make the amendment.

[00:23:23] Speaker 00:
Maybe they could have made a different amendment.

[00:23:25] Speaker 00:
But I think, as Judge Moore said on the replacing side, they didn't.

[00:23:28] Speaker 00:
This is what they chose to do.

[00:23:29] Speaker 00:
And CJ is allowed to do that.

[00:23:31] Speaker 00:
And it's not disputed that 4151 does not hybridize to sequence ID number one.

[00:23:39] Speaker 00:
I'll now turn to lack of written description.

[00:23:41] Speaker 03:
Can I just ask, would your argument be any different if it were apparent, just by assumption, if it were apparent that the reason for the amendment was to bring the claim down to YDDG proteins to avoid, was it Lipschitz was a YFIK or something?

[00:24:04] Speaker 00:
If in the amendment, which obviously didn't happen,

[00:24:08] Speaker 00:
the patentee, the applicant at the time, had said, my amendment is designed to only cover YDDG proteins, then we might have had a different case.

[00:24:18] Speaker 00:
But that's not what they said.

[00:24:19] Speaker 00:
They said, my amendment gets rid of the priorat, and nothing else am I saying about it as being less than that.

[00:24:27] Speaker 03:
OK, so now take the opposite as an assumption.

[00:24:32] Speaker 03:
Let's assume that they said, we are trying to get down to YDDG proteins.

[00:24:37] Speaker 03:
Then how do we think about the tangential nature question?

[00:24:42] Speaker 00:
Then they would have to show, I think that if the function way result with the tangential question, I think would be a more difficult case for us because they could legitimately say your YDDG protein falls within the claim by the doctrine of equivalence because we didn't mean to exclude that.

[00:25:02] Speaker 00:
But that's not the case here.

[00:25:04] Speaker 00:
On written description, as Dr. Ropey said at Volume 1A 1135, Question 305, the genus of multiple promoters is virtually infinite.

[00:25:16] Speaker 00:
It can come from any organism.

[00:25:18] Speaker 00:
And the Commission's decision cannot stand on the Ariad for three reasons.

[00:25:23] Speaker 00:
the four promoters to which it points are not representative of this genus.

[00:25:28] Speaker 00:
In fact, they are representative of three E. coli and one viral promoter.

[00:25:34] Speaker 00:
Secondly, testing known promoters to see which one of them may be more potent than the YDG promoter when the YDG promoter was not known and its strength was not known is not written description.

[00:25:46] Speaker 00:
It doesn't show a recognition of the genus of more potent promoters.

[00:25:52] Speaker 00:
And finally, there's no common structure that links more potent promoters.

[00:25:57] Speaker 00:
Turning to the first, representative species.

[00:26:00] Speaker 00:
As Dr. Ropey said, it's a virtually infinite number of promoters fit within the more potent promoters.

[00:26:08] Speaker 00:
All of them have different structures.

[00:26:09] Speaker 00:
Dr. Stephanopoulos, Engina Motors expert, said that in his 1998 textbook, volume 3A 6285.

[00:26:22] Speaker 00:
Ab V Deutschland is a very similar case.

[00:26:25] Speaker 00:
Yes, it's about antibodies, but there were 300 antibodies, not just for promoters, and those 300 antibodies weren't representative of the entire class of antibodies because they differed in structure, just like the promoters in this case in more potent promoters differ in structure.

[00:26:42] Speaker 00:
Second, finding that the person skilled in the art could actually go off and test

[00:26:49] Speaker 00:
the promoters that were known in the art to see which ones were more potent, that's enablement.

[00:26:55] Speaker 00:
That's not written description.

[00:26:57] Speaker 00:
And Ariad specifically says at 1356, an invitation for further research does not constitute written description of a class of compounds used in a method.

[00:27:09] Speaker 00:
And when you look at the various written description cases, when there's known promoters in the art,

[00:27:16] Speaker 00:
compounds in the art that are known to have the specific activity that's required in the claim, that's a different story.

[00:27:22] Speaker 00:
This is not that.

[00:27:24] Speaker 00:
Here, promoters were known in the art, but not which ones were more potent.

[00:27:28] Speaker 00:
So that doesn't allow the skilled worker to visualize what the genus of more potent promoters was.

[00:27:34] Speaker 00:
And M. Gen.

[00:27:35] Speaker 00:
Sanofi is another

[00:27:36] Speaker 00:
Good example, there they said, at page 1377 to 78, they said, finding of adequate written description merely from a finding of ability to make and use runs afoul of what is perhaps the core ruling of Ariad.

[00:27:52] Speaker 00:
So you can't go off and just test.

[00:27:54] Speaker 00:
That's a research plan.

[00:27:55] Speaker 00:
That's not written description.

[00:27:57] Speaker 00:
And finally, the decision at 46, subparagraph 4, that there's a consensus sequence leaking the more potent promoters.

[00:28:06] Speaker 00:
is wrong.

[00:28:07] Speaker 00:
It mischaracterizes the odd at the priority date.

[00:28:10] Speaker 00:
Ariad says that's where you look for written description, the priority date.

[00:28:14] Speaker 00:
And at the priority date, it was textbook knowledge that the consensus sequence did not apply to E. coli.

[00:28:20] Speaker 00:
And one example of that is the Jensen textbook from 1998, volume 4A9149.

[00:28:27] Speaker 00:
Statements made about what was going on 15 years earlier.

[00:28:31] Speaker 00:
That's not substantial evidence You have to look at what the skilled worker knew at the priority date and here at the priority date The skilled worker knew that the consensus rule did not link E. Coli promoters, which is the specific bacterium of the claim So we ask that you reverse the commission and find the 655 patent invalid the lack of written description

[00:28:56] Speaker 00:
Thank you, love, reserve the rest of my time.

[00:29:11] Speaker 01:
May it please the court?

[00:29:14] Speaker 01:
CJ admits that the promoters were known in the art.

[00:29:18] Speaker 01:
They argued that the YDDG promoter was not known.

[00:29:22] Speaker 01:
The commission disagreed with that specific point.

[00:29:26] Speaker 01:
The commission found, for example, at Appendix 145-146 that the native promoter was known by virtue of the disclosure of sequence ID number 9 in the 655 patent specification.

[00:29:40] Speaker 01:
And the Commission also stated that there is a specific method here that is defined in the specification to assess the potency of the native promoter and to compare the other promoters that are well known in the art relative to the native promoter.

[00:30:00] Speaker 04:
In terms of the tangential issue, would it be fair to say that the claim amendment that we have here went from a

[00:30:09] Speaker 04:
structural definition of the protein to essentially a way of describing the way the protein was made?

[00:30:20] Speaker 01:
Your Honor, that is correct.

[00:30:24] Speaker 01:
I mean, what the hybridization does is that you don't have to have the exact gene that encodes for that protein that would be within the scope of the claim.

[00:30:37] Speaker 01:
When you allow for hybridization, you expand the breadth of the claim, and you allow something that is homologous to sequence ID number one, which is the sequence

[00:30:49] Speaker 01:
of the YDDG.

[00:30:51] Speaker 04:
It seems to me what the ITC said here is that because we end up with the same protein, that somehow the amendment is tangential, whereas it seems to me that the amendment was designed to define the end result in terms of the process by which it was made, as though it's sort of a product by, like a product by process claim.

[00:31:19] Speaker 04:
and that the fact that you end up with the same thing by a different process, I'm not sure that I understand why that makes it tangential.

[00:31:28] Speaker 01:
That was not the only reason.

[00:31:31] Speaker 04:
The fact that we end up... So you think that reason isn't a good one?

[00:31:34] Speaker 01:
No, I actually believe that that reason is a good one because that reason yields an absurd result because we have a protein that is within the range of equivalence.

[00:31:46] Speaker 04:
What's absurd about the result?

[00:31:48] Speaker 04:
I mean, what they're saying is we're covering certain proteins, but we're defining what's covered in terms of the way it's made, essentially.

[00:31:57] Speaker 01:
Right, but when you look at the reason, and it's incorrect to say that the Commission did not look at the prosecution history, because at Appendix 44, the Commission stated that what the amendment was meant to do was to exclude these other types of genes, like the YFIK gene, which are not homologous to the YDDG gene,

[00:32:20] Speaker 01:
and which are not going to hybridize, they're not expected to code for a protein that is equivalent to the YDDG protein.

[00:32:30] Speaker 01:
And there is no evidence in the prosecution history that any of the genes was anything other than the native form of the gene.

[00:32:39] Speaker 01:
So here what we have is a gene that hybridizes in its native form.

[00:32:45] Speaker 01:
But when they apply codon randomization, which has no scientific use whatsoever, but only takes advantage of the redundancy of the genetic code, so you end up with the same protein.

[00:32:57] Speaker 04:
I don't think that's really responsive to the suggestion.

[00:33:01] Speaker 04:
I mean, they chose to make an amendment which defined

[00:33:06] Speaker 04:
the thing in terms of the process by which it was made.

[00:33:10] Speaker 04:
And it seems to me that what the commission did is to say that doesn't matter as long as we end up with the same protein.

[00:33:19] Speaker 01:
The fact that you end up with the same protein is part of the analysis, but it's not the entire analysis.

[00:33:29] Speaker 01:
The analysis that the commission did was that you have a gene

[00:33:33] Speaker 01:
that hybridizes in the native form and codes for the exact same protein as the codon randomized version of the gene.

[00:33:42] Speaker 01:
And when you look at the reason, because that's what the law says, is what is the rationale behind the amendment?

[00:33:48] Speaker 01:
If that reason

[00:33:49] Speaker 01:
is related to the accused equivalent, then yes.

[00:33:54] Speaker 01:
But here what happened is that they narrowed the claim term to exclude genes that in their native form, there is no evidence that those genes were not anything other than their native form, that are so different from the YDDG gene that they would not hybridize and they would not code for a protein that is equivalent to the YDDG protein.

[00:34:19] Speaker 04:
Okay.

[00:34:20] Speaker 04:
All right.

[00:34:20] Speaker 04:
Thank you, Ms.

[00:34:21] Speaker 04:
Morath.

[00:34:25] Speaker 04:
Mr. Livingston.

[00:34:29] Speaker 05:
Thank you, Your Honor, and may it please the Court.

[00:34:32] Speaker 05:
Going to the tangential exception.

[00:34:35] Speaker 05:
First, the limitation at issue was never amended.

[00:34:38] Speaker 05:
Sequence ID number two was never amended.

[00:34:41] Speaker 05:
Under Honeywell, estoppel is on a limitation by limitation basis.

[00:34:44] Speaker 05:
We believe that estoppel should not apply at all.

[00:34:47] Speaker 05:
To the extent the court finds the estoppel does apply, we do think the tangential exception applies because Festo says you only surrender if the rationale is not discernible from the prosecution history of record.

[00:35:02] Speaker 05:
And we think the rationale for the amendment is manifest throughout the prosecution history.

[00:35:07] Speaker 05:
The examiner said, you've got this term that properly interpreted could virtually read on any protein.

[00:35:15] Speaker 05:
And we identified this one that happened to be from one of our inventors called YFIK.

[00:35:19] Speaker 05:
And so your term broadly interpreted.

[00:35:21] Speaker 04:
The problem is if you make an amendment, even if the amendment is broader or different than what would have been required by the examiner's rejection, you're still stuck with it.

[00:35:33] Speaker 04:
It seems to me that the tangential argument that you're making basically says, well, it's tangential if it covers more than was necessary to avoid the rejection.

[00:35:50] Speaker 05:
Our tangential argument is that the amendment was made to define the claim scope to YDDG proteins and variants thereof by species or by how they're encoded by DNA.

[00:36:02] Speaker 05:
What we gave up was totally unrelated YFIK proteins and proteins in between other proteins that might be in there.

[00:36:13] Speaker 03:
Is the following a version of

[00:36:16] Speaker 03:
what you're saying, and I just may misunderstand, but that the amendment was about confining the resulting proteins.

[00:36:27] Speaker 03:
The equivalence analysis for purposes of whether the codon randomized sequence is tangential to that is tangential to changing the protein because it doesn't change the protein.

[00:36:42] Speaker 03:
That's the whole point of codon randomization, that you can have different triplets producing the same sequence of amino acids and therefore the same protein.

[00:36:51] Speaker 05:
Respectfully, I don't think that quite works, because I think that by not changing the protein, they are a YDDG variant.

[00:36:57] Speaker 05:
And what we were trying to give up were non-YDDG variants.

[00:37:01] Speaker 05:
And so under the equivalence analysis, under sequence ID number two, you have a codon randomized version of a non-E.

[00:37:09] Speaker 05:
coli species that does the exact same thing as other things

[00:37:13] Speaker 05:
that literally in French, which is the definition of the use of doctrinal equivalence.

[00:37:17] Speaker 04:
But you chose to define what was claimed by the amendment in terms of how the protein was made, right, essentially?

[00:37:29] Speaker 05:
I don't know that it's how the protein was made.

[00:37:31] Speaker 04:
It's a DNA sequence that when read by- I'm simplifying it, but is that not an accurate sort

[00:37:39] Speaker 04:
Summary the DNA sequence does ultimately end up translated into that's right, but you chose to define it that way and Why aren't you stuck with that and why why is Why is that tangential because we chose to define it that way in view a prior that had nothing to do with yddg?

[00:38:01] Speaker 05:
And cases from this court have said, if the prior art doesn't have anything to do with the amendment at hand, here, the prior art wasn't non-E.

[00:38:08] Speaker 05:
coli YDDG species.

[00:38:10] Speaker 05:
It wasn't codon-randomized versions of those sequences.

[00:38:15] Speaker 05:
It was a totally unrelated YFIK protein that had nothing to do with this protein at all.

[00:38:23] Speaker 05:
On the 112 issue, the commission made specific findings

[00:38:28] Speaker 05:
on the representative species, including identifying the four examples that are in the patent.

[00:38:35] Speaker 05:
The patent describes those four examples and also describes and the like.

[00:38:39] Speaker 05:
It specifically discloses other examples that were well known in the art, like the Deutschlandartikel.

[00:38:45] Speaker 05:
There are numerous prior articles on the front of the patent that also disclose other promoters.

[00:38:51] Speaker 05:
And there are hundreds of examples of more potent promoters that are in the art and have record described in our blue brief, for instance, at page 15.

[00:38:58] Speaker 05:
More importantly, there was a finding that the consensus link did exist at the time of patenting.

[00:39:05] Speaker 05:
And in fact, the quote that's in CJ is very brief at 11.

[00:39:11] Speaker 05:
that at the time of the patenting, the promoter efficiency cannot be predicted entirely from conformity to consensus sequence.

[00:39:18] Speaker 05:
The beginning of that quote says, occasional exceptions to this rule show.

[00:39:23] Speaker 05:
And that's not in the brief.

[00:39:25] Speaker 05:
But that's what Lewin says.

[00:39:26] Speaker 05:
The paragraph before says, consensus sequence is the rule.

[00:39:30] Speaker 05:
What about Jensen?

[00:39:31] Speaker 05:
Jensen?

[00:39:32] Speaker 03:
I think that Mr. Haley referred to Jensen, which is a 1998 article as indicating at that time in the census.

[00:39:40] Speaker 03:
I'm going to summarize.

[00:39:42] Speaker 03:
The consensus sequence didn't apply to ECOE.

[00:39:44] Speaker 05:
They state that Jensen shows promoters which differ from consensus at the minus 35 and minus 10 and the spacer, none of which is in Jensen Table 2, under any reasonable reading of Jensen Table 2.

[00:39:57] Speaker 05:
That's incorrect.

[00:39:59] Speaker 04:
OK.

[00:39:59] Speaker 04:
Thank you, Mr. Louis.

[00:40:09] Speaker 00:
Just a couple of points, Your Honor.

[00:40:11] Speaker 00:
First of all, there's been a lot of discussion about what the amendment said in terms of tangential.

[00:40:17] Speaker 00:
And what is clear from appendix page 44 in the decision, the Commission never pointed to anything in the prosecution.

[00:40:27] Speaker 00:
Now there's an argument that it was meant to exclude only YFIK, not YDG, that was amended to exclude only the native forms of genes, not codon-randomized genes.

[00:40:37] Speaker 00:
It was to exclude non-YDD genes.

[00:40:41] Speaker 00:
None of that's in the prosecution.

[00:40:42] Speaker 00:
The prosecution simply says, Lifshitz no longer anticipates in view of the amendment.

[00:40:48] Speaker 00:
The public notice allows CJ and the public to rely on the amendment that Anjanomoto chose.

[00:40:54] Speaker 00:
Second, on the discussion of examples of more potent promoters in the art.

[00:41:01] Speaker 00:
There's no examples of more potent promoters in the art.

[00:41:03] Speaker 00:
There's examples of promoters in the art.

[00:41:06] Speaker 00:
To determine if it's more potent, which is a comparison, you need to compare it to the strength of the YDD gene promoter.

[00:41:14] Speaker 00:
And that was not known at the priority date.

[00:41:19] Speaker 00:
Sequence ID 9 in the specification is 160 base pair sequence.

[00:41:23] Speaker 00:
It doesn't identify what the promoter is.

[00:41:25] Speaker 00:
The promoter is somewhere in there.

[00:41:27] Speaker 00:
But it certainly doesn't identify the strength of the promoter.

[00:41:30] Speaker 00:
Thank you very much.

[00:41:32] Speaker 00:
OK.

[00:41:32] Speaker 00:
Thank you.

[00:41:32] Speaker 00:
Thank all counsel.

[00:41:33] Speaker 00:
The case is submitted.