[00:00:00] Speaker 00:
The next case for argument is 23.2186, Agilent Technologies versus Franco Corporation.

[00:00:41] Speaker 00:
It's been a while.

[00:00:43] Speaker 02:
Thank you, Your Honor.

[00:00:44] Speaker 02:
Please proceed.

[00:00:45] Speaker 02:
And may it please the Court.

[00:00:47] Speaker 02:
Your Honor, so the decision below has a lot of moving pieces, but this Court need resolve only one issue in order to remand.

[00:00:53] Speaker 02:
Did the abandoned Pioneer hybrid patent application teach and enable the functionality of the claimed guide RNA?

[00:00:59] Speaker 02:
Because no facts or law support a finding that it showed possession of, much less enabled that functionality,

[00:01:05] Speaker 00:
Can I ask you for some help here, because I got a little confused.

[00:01:10] Speaker 00:
The only way I understand this, and I hope you'll agree that's what your argument is, is you're making two really separate arguments.

[00:01:16] Speaker 00:
You're making an argument of anticipation based on functionality.

[00:01:20] Speaker 00:
And then the enablement comes in sort of at the second piece, which is a second argument, which is what had to be enabled, and does this satisfy the enablement?

[00:01:30] Speaker 00:
are they kind of two separate arguments?

[00:01:33] Speaker 02:
They are, Your Honor, although they kind of parallel each other a little bit.

[00:01:36] Speaker 00:
I guess so, but I really had a hard time just teasing out the one versus two, and I meant two different arguments.

[00:01:44] Speaker 02:
Yes, so I think that's correct, Your Honor, and I guess the way I would draw the distinction is

[00:01:49] Speaker 02:
The first question is, do we think that the Pioneer hybrid discloses the functionality of guide RNAs at all sufficient to put the FASTA in possession of that knowledge?

[00:02:01] Speaker 02:
And then if they do disclose it, have they given enough information that you can enable someone to make it?

[00:02:07] Speaker 00:
But even on the first question of functionality, that also includes not enablement per se, but it includes the sufficiency.

[00:02:14] Speaker 00:
You bring in testing.

[00:02:16] Speaker 00:
You bring in the actual performance.

[00:02:18] Speaker 00:
kind of a quasi-enablement thing, but you intend it to be separate on functionality.

[00:02:23] Speaker 00:
And then we get to the enablement part.

[00:02:25] Speaker 02:
I think that is correct, Your Honor.

[00:02:26] Speaker 02:
That's right.

[00:02:26] Speaker 02:
If we think that the Pioneer Hybrid Reference didn't actually teach functionality sufficient to put people in possession of it, you do not need to resolve anything further.

[00:02:39] Speaker 02:
Even if you thought, well, it's written down, the board articulated this new theory that because they called them guide polynucleotides, they must be guiding.

[00:02:48] Speaker 02:
Then I think you would get to the second question of, is there enablement?

[00:02:52] Speaker 02:
Did that actually give enough information for people of ordinary skill in the art to make and use functional guides?

[00:02:58] Speaker 00:
Okay, so on the functionality point, the functionality deals with the associating and the targeting stuff, right?

[00:03:07] Speaker 02:
Correct.

[00:03:07] Speaker 00:
And you're saying that to establish functionality is the question.

[00:03:13] Speaker 00:
Is it what you're saying?

[00:03:14] Speaker 00:
To establish functionality

[00:03:16] Speaker 00:
the prior art disclosure has to show that it was actually performed.

[00:03:21] Speaker 00:
Is that your argument?

[00:03:22] Speaker 00:
What's the problem?

[00:03:23] Speaker 00:
Why isn't this sufficient to satisfy the functionality?

[00:03:26] Speaker 02:
So I think there are two answers to that.

[00:03:29] Speaker 02:
First, as to the reasoning the board actually used, which was new reasoning not presented below, their argument

[00:03:35] Speaker 02:
it is because we called it a guide policy.

[00:03:38] Speaker 02:
That has to be wrong.

[00:03:40] Speaker 02:
And I think that fact that that is wrong and the board relied on it is independently a ground for remand.

[00:03:45] Speaker 02:
On the substantive merits of the evidence, what we suggest is that Pioneer Hybrid threw everything at the wall because it had no idea what might work and what might not work.

[00:03:55] Speaker 02:
And so there are a quadrillion, quadrillion possibilities.

[00:04:00] Speaker 02:
And they said, hey,

[00:04:02] Speaker 02:
Maybe you could do unmodified guides.

[00:04:04] Speaker 02:
Maybe you could do modified guides in six different ways.

[00:04:06] Speaker 02:
Maybe you could modify any particular place at two different domains.

[00:04:11] Speaker 02:
Their teaching was actually directed primarily at DNA guides that everyone agrees now don't work.

[00:04:17] Speaker 00:
I mean, we're talking about, and I think the board felt this way, too.

[00:04:21] Speaker 00:
You make arguments about what they've done or not done sufficiently for the DNA.

[00:04:25] Speaker 00:
But that's not what's necessary for this case, because we're looking at prior art to this claim limitation that is

[00:04:32] Speaker 00:
Not DNA.

[00:04:35] Speaker 02:
I think the reason it's relevant on the function, it is certainly relevant on the enablement point.

[00:04:39] Speaker 02:
But even on the functionality point, I think the reason it is relevant is the question is would a person of skill in the art reading this document feel that they were in possession of functional guide RNAs?

[00:04:50] Speaker 02:
And this document doesn't, I think, direct you towards a functional guide RNA.

[00:04:56] Speaker 02:
It never actually shows you a functional guide RNA.

[00:04:59] Speaker 02:
And the fact that it is suggesting

[00:05:02] Speaker 02:
systems that don't work, that we discovered don't work, I think is going to cause the person of ordinary skill in the art reading it to say, this is just guesswork.

[00:05:11] Speaker 00:
So is this a factual or a legal question?

[00:05:13] Speaker 00:
I mean, whether it shows sufficient whatever, factual performance, whatever.

[00:05:18] Speaker 00:
The board did quite a thorough analysis of each of those points, including the functionality.

[00:05:24] Speaker 00:
Do you agree it's a question of substantial evidence, and you're just arguing that there's not substantial evidence?

[00:05:29] Speaker 02:
On this point, I believe that's correct, Your Honor.

[00:05:31] Speaker 02:
I think on the original point, the fact that the board chose a new and sort of legally improper theory is reason to remand independent of this.

[00:05:42] Speaker 04:
Could you address whether the Pioneer H brand does or does not differentiate functional from the non-functional guides?

[00:05:52] Speaker 02:
Certainly you're right.

[00:05:53] Speaker 02:
So the PHB does nothing to actually teach functionality.

[00:05:58] Speaker 02:
They identify an enormous number of things as guide polynucleotides.

[00:06:03] Speaker 02:
That includes DNA sequences.

[00:06:05] Speaker 02:
That includes unmodified RNA guides.

[00:06:09] Speaker 02:
And the evidence suggests, I think without contradiction, none of those would work.

[00:06:13] Speaker 02:
But they call them all guide polynucleotides.

[00:06:16] Speaker 02:
And I think the reason for that is they were trying at a very early stage in the process of CRISPR to just see anything that might work to get CRISPR in.

[00:06:26] Speaker 02:
So why not suggest everything?

[00:06:28] Speaker 02:
There's a point at which they suggest falsely that they had actually performed one of these.

[00:06:34] Speaker 02:
The board agrees that that was a misstatement in the application.

[00:06:39] Speaker 04:
All these examples are prophetic.

[00:06:43] Speaker 04:
disclosed the modifications that would be made?

[00:06:47] Speaker 02:
It discloses a number of possible modifications in a number of possible places.

[00:06:52] Speaker 04:
And that disclosure is aimed at towards functionalities?

[00:06:57] Speaker 02:
Well, we don't know that, Your Honor.

[00:06:59] Speaker 02:
So they disclose, as we indicated, a quadrillion quadrillion possible combinations.

[00:07:04] Speaker 02:
We know many of them don't work.

[00:07:06] Speaker 02:
We know the only ones they tested don't work.

[00:07:09] Speaker 02:
It turns out that among that quadrillion quadrillion are ones that the

[00:07:13] Speaker 02:
patentee figured out how to make work, but that's because the patentee figured out something that is not taught in pioneer hybrid, which is you need to use RNA, not DNA, you need to use the two primal methyl group, and you need to put the modifications at the ends and not in the middle.

[00:07:28] Speaker 02:
And the pioneer hybrid affirmatively teaches away from that.

[00:07:31] Speaker 02:
And I guess what I would suggest, even if... Please, there you are.

[00:07:37] Speaker 01:
Getting back to the functionality question, there are a number of prophetic examples

[00:07:42] Speaker 01:
that note functionality with respect to the modified guide polynucleotides.

[00:07:49] Speaker 01:
What's wrong with that in terms of providing support for the board?

[00:07:56] Speaker 02:
Well, I think there actually turns out to be very few that might fit within the scope of the patent claims and that might work.

[00:08:01] Speaker 02:
There are a number of references to unmodified guides as possibly functional.

[00:08:06] Speaker 02:
We know that doesn't work.

[00:08:08] Speaker 02:
There are a number of references to DNA guides, and the vast majority of Table 8 is DNA, not RNA guides.

[00:08:13] Speaker 02:
We know those don't work.

[00:08:15] Speaker 02:
There is one specific reference that says maybe, and it's the one pointed to by the board, maybe you could

[00:08:21] Speaker 02:
co-deliver multiple things and do two crispers at once.

[00:08:26] Speaker 02:
There's no reason to think that works as far as I know no one has ever tried it.

[00:08:29] Speaker 02:
That's the one thing where they say you could do this.

[00:08:33] Speaker 02:
But I think reading all of that in the context of the uncertain state of the art, a person of ordinary skill in the art is not gonna be able to say these people were in possession of functionality.

[00:08:44] Speaker 02:
But even if they were your and this is I think this becomes the enablement piece of things right even if you thought OK they wrote down somewhere this kind of bear thing writing that down is not sufficient to enable somebody to make and use it particularly given that they said hey try anything I try all these things and all of these things didn't work.

[00:09:04] Speaker 02:
A person of skill in the art, which was new and very uncertain at the time, would have had to do some sort of testing and experimentation to try to figure out which of the quadrillion possibilities might work.

[00:09:16] Speaker 01:
But weren't there certain guidelines in terms of the kinds of things you would have to try or test or look at?

[00:09:23] Speaker 01:
as opposed to the quadrillion quadrillion?

[00:09:26] Speaker 02:
Well, there you are.

[00:09:27] Speaker 02:
In fact, I think what Payner-Helbert does is point you in the wrong direction.

[00:09:31] Speaker 02:
They strongly prefer DNA.

[00:09:32] Speaker 02:
They suggest DNA.

[00:09:34] Speaker 02:
The one thing they actually test is DNA.

[00:09:36] Speaker 02:
We know DNA doesn't work.

[00:09:37] Speaker 02:
They say you may put the modifications anywhere throughout the sequence.

[00:09:41] Speaker 02:
We know that doesn't work, that only modifications to the end work.

[00:09:44] Speaker 00:
But that brings me to, before your time runs out, to the pure kind of enablement issues, which is like part two of your argument.

[00:09:51] Speaker 00:
And am I correct that the legal issue you're presenting, sort of a la Amgen, is whether or not when you're using prior art for anticipation purposes, you have to deal with enablement of the entire prior art or just show enabling of the

[00:10:10] Speaker 00:
limitations that are used for establishing anticipation?

[00:10:13] Speaker 00:
It's a lie, Your Honor.

[00:10:14] Speaker 00:
We are not arguing.

[00:10:15] Speaker 00:
Oh, OK.

[00:10:15] Speaker 00:
So we're good, and our cases say that.

[00:10:18] Speaker 00:
So doesn't that limit the number we're talking about?

[00:10:21] Speaker 00:
We're not talking about DNA.

[00:10:24] Speaker 00:
We're talking about the example.

[00:10:27] Speaker 00:
So if you agree with that legal principle, doesn't it then become a question of substantial evidence question as to whether or not that is satisfied here?

[00:10:38] Speaker 00:
Enablement is a question of law based on underlying facts.

[00:10:41] Speaker 00:
I was going to say exactly.

[00:10:43] Speaker 00:
Quite a detailed analysis separate from the functionality just on this enablement, concluding that there was sufficient.

[00:10:51] Speaker 02:
Well, I'm not sure they did, Your Honor, right?

[00:10:54] Speaker 02:
Because what they told us was – so it is an ultimately illegal question.

[00:10:58] Speaker 02:
It is based on factual findings.

[00:11:00] Speaker 02:
That's absolutely correct.

[00:11:01] Speaker 02:
But to me, the legal question here is, if the prior art reference says, try anything, throw things at the wall and see what sticks,

[00:11:09] Speaker 02:
Would a person of ordinary skill in the art know, let me pick out the one thing that the patentee later found out worked?

[00:11:17] Speaker 02:
Or would they have to test to know which of the things might work and which might not work?

[00:11:21] Speaker 02:
And here, I think, where Amgen is useful is Amgen says, if all you've got is a trial and error method and there are lots of possibilities, that's not sufficient.

[00:11:31] Speaker 00:
The part of Amgen, Amgen is different as a legal matter.

[00:11:34] Speaker 00:
And that's where the slice and dice comes in, in terms of what you have to enable.

[00:11:39] Speaker 00:
Because in Amgen, maybe I'm wrong, but I recall, you had to look at the entire specification.

[00:11:43] Speaker 00:
It was a basic enablement case of a particular patent.

[00:11:49] Speaker 00:
This is different, and you've already agreed with me, that you only have to enable in the prior art that specific portion that is relied on to establish anticipation.

[00:11:59] Speaker 02:
I absolutely agree with that, Your Honor.

[00:12:02] Speaker 02:
And so to do that, what they had to do was teach a person a skill in the art that they could identify a functioning part of this invention without undue experimentation.

[00:12:13] Speaker 02:
And what we suggest is no evidence supports that whatsoever.

[00:12:17] Speaker 02:
Because of all the possibilities, because they point in the wrong direction, the only way to figure out

[00:12:24] Speaker 02:
which of these things might turn out to work is the trial and error method.

[00:12:28] Speaker 02:
They are not pointing you or directing you towards the subset of things that work.

[00:12:33] Speaker 02:
To the contrary, they are pointing you away.

[00:12:35] Speaker 02:
And finally, I would like to note, even if you disagree on both of these grounds, right, I think there's still, remit is still appropriate on the dependent claims, on the single guide RNA claims and the thiopase claims.

[00:12:48] Speaker 02:
And here the notable difference is the board made no specific findings

[00:12:53] Speaker 02:
about functionality of those things.

[00:12:55] Speaker 02:
So the single-guide RNA claims are not in Table 8.

[00:13:01] Speaker 02:
The only single-guides disclosed in Pioneer Hybrid are unmodified ones.

[00:13:04] Speaker 02:
There's no indication that says the single-guide claims would have been functional even in a prophetic example.

[00:13:11] Speaker 02:
And the board makes no specific findings.

[00:13:12] Speaker 02:
They merely point back to their earlier findings about general.

[00:13:20] Speaker 04:
What about the use of neural techniques?

[00:13:27] Speaker 02:
Not in this case, Your Honor, I think because this entire technology was less than a year old, there weren't known techniques for this purpose.

[00:13:34] Speaker 02:
There were known techniques in how to manufacture guides, and we are not arguing the manufacturer is something that a person of ordinary skill in the art couldn't do.

[00:13:43] Speaker 02:
The challenge was figuring out which one of them would work, and the only way to do that was to test.

[00:13:47] Speaker 02:
And as to the single guide RNA claims, because there is no specific board ruling and as to the fire pace claims, which are not even mentioned in pioneer hybrid, there's no specific board finding of functionality.

[00:14:00] Speaker 02:
They merely point back to their general findings that pioneer hybrid discloses functionality.

[00:14:05] Speaker 02:
We think that is both procedurally improper and really they don't make separate arguments.

[00:14:09] Speaker 02:
We absolutely did, Your Honor.

[00:14:11] Speaker 02:
And I confess that I am a little mystified by the suggestion that we've somehow waived this.

[00:14:16] Speaker 02:
You will find specifically in the opening brief page 60 to 61 that we brought it on appeal.

[00:14:24] Speaker 02:
And you will find the arguments below in quite a bit of detail at appendix 794, appendix 8488 to 91 for the single-guide claims, and appendix 815 to 816

[00:14:39] Speaker 02:
806 and 807 and 998 for the for the fire pace claims and I'm happy to walk through those right now if you'd like.

[00:14:47] Speaker 00:
We're way beyond our time.

[00:14:49] Speaker 00:
Thank you Your Honor.

[00:15:03] Speaker 03:
Good morning and may it please the court.

[00:15:09] Speaker 03:
As the court established in that questioning, this is essentially a substantial evidence appeal.

[00:15:15] Speaker 03:
What's noteworthy is that the phrase substantial evidence doesn't appear at all in the reply brief.

[00:15:22] Speaker 03:
There's no effort to show that there's no substantial evidence or to grapple with the standard review.

[00:15:28] Speaker 03:
And in the opening brief, it recites it in mechanical form in the standard review section.

[00:15:33] Speaker 03:
but never uses the phrase to try to apply and meet that standard.

[00:15:37] Speaker 03:
And there's good reason for that.

[00:15:39] Speaker 03:
And the good reason is that this is a very straightforward case.

[00:15:43] Speaker 03:
If you look, this idea that all that pioneer hybrid did was throw things against the wall, right, which is essentially the premise of the appellate argument we just heard, is disposed of by table A. If you look at table A, and a good place to look at is in our response period for 14.

[00:16:02] Speaker 03:
It has kind of a handy way to look at it.

[00:16:07] Speaker 03:
But table 8 lists the exact sequence that's an embodiment of the claims at issue and thus an anticipation.

[00:16:18] Speaker 03:
The literal sequence down to the base number with the modifications

[00:16:26] Speaker 03:
it's sequence number sixty four and sixty five sequence number sixty six and sixty seven so there's not a mystery

[00:16:35] Speaker 03:
where you have to go about and try to figure out a big puzzle, it's a preferred embodiment.

[00:16:40] Speaker 03:
In Table 8, it says, here are the guide RNAs that you can use.

[00:16:45] Speaker 03:
It also includes DNA.

[00:16:47] Speaker 03:
It does.

[00:16:48] Speaker 03:
But it lists the guide RNAs.

[00:16:50] Speaker 03:
And it says, photophosphothiate bonds near ends.

[00:16:55] Speaker 03:
And then it shows it with the bonds near the ends.

[00:16:58] Speaker 03:
So it's just a head fake.

[00:17:02] Speaker 03:
Now, with respect to the DNA,

[00:17:05] Speaker 03:
what's to understand is when you approach the Pioneer Hybrid reference, is what they're essentially saying is guide RNA modifications were known.

[00:17:17] Speaker 03:
And they're known actually even in the, there were other references that had them in the context of CRISPR.

[00:17:23] Speaker 03:
What we're doing is we provide evidence that a new class of molecules, DNA, can also be used.

[00:17:31] Speaker 03:
So they're saying, okay, we're gonna get out there,

[00:17:35] Speaker 03:
plow new ground with the DNA guides, but the RNA guides are already known.

[00:17:42] Speaker 03:
So it would be very natural for someone that wanted to use something and not be on the cutting edge to just use the guide RNA and then you turn to table 8 and you have guide RNA that are the ones they claim.

[00:17:54] Speaker 03:
So you have an anticipation.

[00:17:56] Speaker 03:
it's that simple.

[00:17:57] Speaker 03:
And the rest is fancy lawyer stuff.

[00:18:01] Speaker 03:
Now let me address more specifically.

[00:18:04] Speaker 03:
There are two arguments.

[00:18:05] Speaker 03:
Judge Post correctly parts that.

[00:18:07] Speaker 03:
In terms of the functionality, whether it's disclosing that the guide RNA have the functionality of association and targeting, it's absolutely clear.

[00:18:16] Speaker 03:
That's the whole point.

[00:18:17] Speaker 03:
It says it all over the place.

[00:18:19] Speaker 03:
But more to the point, and easier, is that

[00:18:24] Speaker 03:
Agilent itself acknowledges that.

[00:18:28] Speaker 03:
In their patent owner's response at A7-88, they referred to a declaration of functionality.

[00:18:34] Speaker 03:
So they said there's a declaration of functionality, as though that somehow makes it non-functional.

[00:18:39] Speaker 03:
But they acknowledge that it declares functionality.

[00:18:43] Speaker 03:
And then in their applied appeal brief before this court,

[00:18:46] Speaker 03:
They're for a prophetic assertion of functionality.

[00:18:50] Speaker 03:
It's not really debatable that there's, in fact, a statement of functionality.

[00:18:54] Speaker 03:
The whole point of the guide RNA is that.

[00:18:58] Speaker 00:
Forgetting what was said this morning, but going back to the briefs, my understanding of the argument was more of a legal argument, which is that the requirement of the law is that they show actual performance.

[00:19:08] Speaker 03:
That can't be, NOVO, NORDISC refutes that.

[00:19:16] Speaker 03:
That's not the argument.

[00:19:18] Speaker 03:
The argument I think is a really factual one that on these facts, because you have the DNA that didn't show good cleaving,

[00:19:27] Speaker 03:
that that quite cast doubt on all of it.

[00:19:29] Speaker 00:
Well, yeah, they make the testing data as connection with the cleaving, right?

[00:19:33] Speaker 00:
That's the argument.

[00:19:34] Speaker 03:
The argument is that for the new ground that Pioneer heartbeat was trying to break in DNA, that because the DNA guides didn't do well in terms of cleaving,

[00:19:46] Speaker 03:
you would doubt that the RNA guides work, which doesn't make any sense, because Pioneer Hybrid itself, and we'll see if Mr. Lemley acknowledges this in reply, states that guide RNA is already known.

[00:20:00] Speaker 03:
We're going with a new class of DNA.

[00:20:02] Speaker 03:
So their argument is that this DNA, really, the gist is that you- That's the testing data, and that deal with cleavage.

[00:20:08] Speaker 00:
But what about, I thought there was kind of a separate argument about how, for getting the testing data, you need to show actual performance.

[00:20:16] Speaker 03:
I just think it's based on this argument that the DNA casts doubt on things.

[00:20:21] Speaker 03:
But no, because I think the prior case is Novo.

[00:20:25] Speaker 03:
And then, of course, Antor and Alcon's another one established that in Alcon, it was chemically stabilizing amount.

[00:20:33] Speaker 03:
There was no need for data there.

[00:20:35] Speaker 03:
I mean, the patent itself makes clear that it associates with the Cas9 and that it targets the DNA.

[00:20:46] Speaker 03:
And another point I want to raise on this is the problem with the DNA is the cleaving, is that it doesn't actually, efficiently it seems, that's the argument from the other side, cleave.

[00:20:59] Speaker 03:
But that doesn't mean that it doesn't associate and target.

[00:21:05] Speaker 03:
And in fact,

[00:21:07] Speaker 03:
With respect to that, their own briefing acknowledges that you might want to do situations where you don't cleave, where you just associate and target.

[00:21:15] Speaker 03:
They have that in their brief.

[00:21:16] Speaker 03:
I think it's a page eight of their opening brief.

[00:21:19] Speaker 03:
And if that's true, and the presumption of enablement applies, which it does, that's uncontested.

[00:21:26] Speaker 03:
The board found that.

[00:21:27] Speaker 03:
That's not appealed.

[00:21:29] Speaker 03:
and the cases hold that, then you would presume that it does those elements of functionality that are claimed, which is association.

[00:21:38] Speaker 00:
OK, can I move you to the more of the main question?

[00:21:41] Speaker 00:
Anything you'd like.

[00:21:41] Speaker 00:
Although they're getting a little muddled here.

[00:21:43] Speaker 00:
But we're all familiar with Amgen.

[00:21:47] Speaker 00:
Professor, one of your teachers in that oral argument, the Supreme Court.

[00:21:51] Speaker 00:
Why is it like this case?

[00:21:54] Speaker 00:
Why aren't we faced with a gazillion things that were unknown?

[00:22:00] Speaker 03:
OK, so factually, I think I dispensed with this gazillion things.

[00:22:03] Speaker 03:
Table 8 has four RNAs.

[00:22:08] Speaker 00:
OK, what about, I thought we were going to talk about examples 4 and 5, is that right?

[00:22:12] Speaker 03:
Examples 4 and 5 house table 7 and 8, so it would be a little confusing.

[00:22:17] Speaker 03:
It can be confusing.

[00:22:18] Speaker 03:
But table 8 is within that, and that just lays it out.

[00:22:21] Speaker 03:
It just has it, the exact sequence.

[00:22:23] Speaker 03:
That's anticipatory.

[00:22:25] Speaker 03:
That's it.

[00:22:26] Speaker 03:
But in any event, getting to your point, why is Amgen not legally relevant?

[00:22:31] Speaker 03:
Very simple.

[00:22:32] Speaker 03:
Amgen, the problem was they were claiming the whole genus, right?

[00:22:36] Speaker 03:
It was everything.

[00:22:37] Speaker 03:
There could have been millions of them, and they only showed 28 working.

[00:22:41] Speaker 03:
And what the Supreme Court was rightly concerned about, and Professor Lamley for that matter, is how can you claim all of this if so much of it's just

[00:22:51] Speaker 03:
unknown and there's not similarity between the 28 you've proven and all the others that you're claiming.

[00:22:56] Speaker 03:
This is anticipation.

[00:22:59] Speaker 03:
And as such veteran jurists as you know, anticipation, all you need is one embodiment.

[00:23:05] Speaker 03:
Prying a hybrid doesn't have to enable the entire scope of the claims.

[00:23:12] Speaker 03:
of the Agilent patents.

[00:23:13] Speaker 03:
That would be silly.

[00:23:15] Speaker 03:
That's not the law.

[00:23:16] Speaker 03:
So it's completely different in terms of the legal structure.

[00:23:19] Speaker 03:
That's why Amgen's irrelevant.

[00:23:21] Speaker 03:
The Amgen considered that the breadth of the claim versus the disclosure is not at issue here.

[00:23:27] Speaker 04:
You may need one embodiment, but you still have to find one.

[00:23:30] Speaker 03:
Yes.

[00:23:32] Speaker 03:
And at table 8 right here, it has them.

[00:23:35] Speaker 03:
It recommends them.

[00:23:36] Speaker 03:
And it's undisputed that this one and this one, which is 84, 85, and secrets 86, 87, actually fall within the scope.

[00:23:45] Speaker 03:
Now, it's just a subsidiary argument we didn't hear today.

[00:23:49] Speaker 03:
But it's worth pointing out.

[00:23:50] Speaker 03:
The third one, which is 58, 59, they say, well, that might not work because it's got too many methyls.

[00:23:57] Speaker 03:
In other words, they're putting methyl on.

[00:23:59] Speaker 03:
Quite a number of different and if you look at you see those M's you know it's almost like every other fact is that In claims 18 and 32 of the 034 patent it claims The patent suit claims more than 20 metals so their argument that these have to that this has too many metals to work it falls within the scope of their claims and

[00:24:24] Speaker 03:
because it's got more than 20 methyls is completely inconsistent with their open-ended claim to more than 20, which the board pointed out and said, well, this seems odd that you're saying that this one's inoperative.

[00:24:37] Speaker 03:
But it doesn't matter.

[00:24:38] Speaker 03:
And it wasn't even argued here.

[00:24:40] Speaker 03:
It discloses specific embodiments.

[00:24:42] Speaker 03:
And I showed it to your honor, table eight right here.

[00:24:45] Speaker 03:
And then table seven.

[00:24:47] Speaker 03:
doesn't give you the full sequence, so in that sense it's a little bit of a broader disclosure, but it says you can use two-methyl RNA bases, resistance to ribonuclease, which is what you want to avoid, because that can create instability.

[00:25:07] Speaker 03:
And phospho-fluoride-thyroid bonds are very resistant to nucleus cleavage, so it's saying these techniques with RNA work well,

[00:25:15] Speaker 03:
And it makes it clear that it's for the functionality, nucleotide base and photodiester bond modifications, to decrease unwanted nucleus degradation.

[00:25:25] Speaker 03:
That's the functionality.

[00:25:26] Speaker 00:
If time runs out, can you deal with the final argument?

[00:25:29] Speaker 03:
The phosphatite?

[00:25:30] Speaker 03:
The PACE?

[00:25:31] Speaker 00:
Yes.

[00:25:31] Speaker 03:
They call PACE.

[00:25:32] Speaker 03:
Well, there's the single nucleotide, single strand, and phosphatite.

[00:25:37] Speaker 03:
They didn't develop them at all.

[00:25:39] Speaker 03:
There were stray references amidst the other argument.

[00:25:41] Speaker 03:
But let me address the SGNA, the single guide.

[00:25:45] Speaker 03:
Pioneer says they can be single or double right after table 7 and 8.

[00:25:53] Speaker 03:
And that's at A2613.

[00:25:55] Speaker 03:
So it is expressly disclosed.

[00:25:57] Speaker 03:
It says, oh, we're doing those.

[00:25:58] Speaker 03:
And they can be single or double.

[00:26:02] Speaker 03:
Now the argument that I understand is made is, well, if you do a single sequence rather than a double sequence,

[00:26:11] Speaker 03:
You might need special synthesis.

[00:26:13] Speaker 03:
The board featuring, I might add, a PhD geneticist from Yale is on the board panel here, the three judges, all technically trained in this area, said,

[00:26:25] Speaker 03:
Oh, well, the synthesis argument, it's not credible that you're saying there's problems with synthesis.

[00:26:32] Speaker 03:
No one could identify what the reason was.

[00:26:34] Speaker 03:
You don't have any special synthesis methods in your patent.

[00:26:37] Speaker 03:
So if you're saying you need special voodoo, special sauce synthesis in order to do single guide, you don't even tell people how to do it.

[00:26:46] Speaker 03:
So the board, in a very meticulously written point, absolutely said it's not credible that synthesis of single guide is... But he also, I think he also was making the point of the insufficiency and the lack of specificity and detail in the board's conclusion, that they just relied to earlier things and they didn't

[00:27:06] Speaker 00:
They spent more time on it.

[00:27:08] Speaker 00:
Make findings about a reasonable expectation of success and motivation combined and all of that stuff so that the board's analysis was deficient or insufficient.

[00:27:17] Speaker 03:
Yeah, that's more for the pace I think than the single but I do want to get to the single because it was stated that it wasn't expressly disclosed and if you look at 2613 you'll see it's very explicitly disclosed.

[00:27:29] Speaker 03:
As to the pace and your reasonable expectation of success

[00:27:33] Speaker 03:
The board spent more time on it than Agilent did.

[00:27:39] Speaker 03:
But the point being made is these modifications to RNA were well established through many, many systems.

[00:27:47] Speaker 03:
Not just CRISPR, but many systems before.

[00:27:50] Speaker 03:
And they were well known.

[00:27:52] Speaker 03:
And there was a variety of them, the methyls that we talked about, but also PACE.

[00:27:57] Speaker 03:
And so since it was a well-known modification

[00:28:02] Speaker 03:
Pioneer hybrid suggests using RNA and establishes that RNA was well known.

[00:28:08] Speaker 03:
Therefore, with respect to PACE, you could substitute the PACE, because PACE was another one of the known modifications, which is well established for the backbone, for the phosphodiester backbone.

[00:28:23] Speaker 03:
So that's the point.

[00:28:25] Speaker 03:
And here, I don't know if it was in the papers, but Agilent seeks a preliminary injunction

[00:28:32] Speaker 03:
against SYNTEGO to prevent, to essentially own CRISPR based on modifications that were used by RNA modifications that were used forever for RNA guides.

[00:28:44] Speaker 03:
And they're saying, well, doing it in this new context is different, but many, and this was addressed in the secondary considerations, many others proposed

[00:28:55] Speaker 03:
and disclosed using RNA guides that had historically been used in CRISPR.

[00:29:00] Speaker 03:
And there's no showing that it didn't work, the RNA ones, just the DNA, which was something that Pioneer Hybrid was trying to do as a new thing.

[00:29:12] Speaker 01:
With respect to the functionality of the modified guide, polynucleotides, I mentioned to Professor Lemme that there were a number of prophetic examples, and he seemed to

[00:29:25] Speaker 01:
sort of poopoo those things.

[00:29:27] Speaker 01:
The board only addressed, as I understand it, two prophetic examples, but I found a number of prophetic examples in the pioneer.

[00:29:38] Speaker 01:
And what's your comment about whether those prophetic examples have consequence here?

[00:29:49] Speaker 03:
a very valid point, and here's the response.

[00:29:53] Speaker 03:
First of all, the law is very, very settled from long ago in this court that saying something should be used without saying that it actually was used, and that's just what prophetic said.

[00:30:06] Speaker 03:
fancy as law professor term for should be used versus would be used.

[00:30:13] Speaker 03:
So it discloses that it should be used, that's sufficient.

[00:30:18] Speaker 03:
And with respect to RNA, there's no showing that any of the RNAs that are disclosed, table 7, table 8, don't work or have any problems.

[00:30:26] Speaker 03:
In fact, they basically admit they do work.

[00:30:28] Speaker 03:
They fall within the scope of their claims.

[00:30:32] Speaker 03:
It's disclosing it as legally met, and they work, and it's specifying them in table eight.

[00:30:38] Speaker 03:
So it's not a bunch of spaghetti against a wall.

[00:30:41] Speaker 03:
All right.

[00:30:42] Speaker 03:
Are there any other questions?

[00:30:44] Speaker 04:
Yes.

[00:30:45] Speaker 03:
Sure.

[00:30:46] Speaker 04:
There's something that's been in the background of my mind.

[00:30:48] Speaker 04:
There seems to be a law made out of it that the Pioneer H brand

[00:30:55] Speaker 04:
What can you address that?

[00:30:58] Speaker 04:
What's the impact of that?

[00:30:59] Speaker 03:
Yeah, it has no impact.

[00:31:03] Speaker 03:
There's no challenge from Agilent that's presumed to be enabling, which gets us 90% of where we need to go.

[00:31:11] Speaker 03:
They're not challenging that legal principle.

[00:31:12] Speaker 03:
They're not saying, because it was a ban, that that principle doesn't apply.

[00:31:18] Speaker 03:
criticizing it that way.

[00:31:20] Speaker 03:
In fact, foreign patents have issued off of it, and they're still pending applications we checked this week that are still pending through the system.

[00:31:29] Speaker 03:
I think abandon means in the sense of the way in the US there's continuation practice that the court knows about, so it was just abandoned for another continuation.

[00:31:38] Speaker 03:
Thank you.

[00:31:39] Speaker 03:
Thank you.

[00:31:46] Speaker 00:
We'll restore three minutes.

[00:31:52] Speaker 02:
Thank you, Your Honor.

[00:31:53] Speaker 02:
Let me just address a couple of things, one on a sort of factual statement that I think is incorrect in Mr. Ryan's argument and then on the legal issue.

[00:32:03] Speaker 02:
He says table eight lists the exact sequence that is the invention and calls it the preferred embodiment.

[00:32:10] Speaker 02:
It does not.

[00:32:11] Speaker 02:
It never uses the term preferred embodiment.

[00:32:14] Speaker 02:
But it does not even show that that sequence will work.

[00:32:17] Speaker 02:
And there is no evidence that suggests that the sequence will work.

[00:32:21] Speaker 02:
Those are not sequences that fit within the scope.

[00:32:26] Speaker 02:
They are truncated sequences.

[00:32:28] Speaker 02:
And what the evidence shows, and the board actually does talk about this in some detail, is you can cut down from 20 down maybe to 17.

[00:32:37] Speaker 02:
If you cut down to 16, it won't work.

[00:32:38] Speaker 02:
What those sequences are are 17, and then they suggest, and now start modifying and cutting them.

[00:32:44] Speaker 02:
We don't know to this day whether any of the sequences that Pioneer Hybrid proposes will work.

[00:32:49] Speaker 02:
it is certainly not the case that they have shown enablement of those sequences, much less that they were their preferred embodiment and they worked.

[00:32:58] Speaker 02:
And that, I think, brings us to the legal point.

[00:33:00] Speaker 02:
So the argument here that we are making is not you must always test in order to enable.

[00:33:07] Speaker 02:
The argument is that you have to test or give us evidence if the person of a skill in the art could not otherwise tell which sequences would work and which wouldn't.

[00:33:16] Speaker 02:
Impacts makes that clear.

[00:33:18] Speaker 02:
The OSI case makes that clear.

[00:33:20] Speaker 02:
Even their own case, Alcon, makes that clear.

[00:33:22] Speaker 02:
It says, you don't have to test if there's no risk or no worry of inoperable species.

[00:33:28] Speaker 02:
Here, the PHB is entirely full of inoperable species.

[00:33:31] Speaker 02:
The reason it was abandoned, the reason they're still trying 12 years later with a very different set of patent claims to get something, is their proposal, their approach, didn't work.

[00:33:40] Speaker 02:
What they are saying as a prior art reference is, well, you know what?

[00:33:45] Speaker 02:
It turns out that when you go back and look at it, the idea that we made work is something that maybe somebody could have found among this enormous number of possibilities.

[00:33:54] Speaker 02:
And Judge Lynn asked about the prophetic examples piece, which I did not intend to poo-poo, Your Honor.

[00:34:00] Speaker 02:
What I intended to suggest, I think, is

[00:34:04] Speaker 02:
If you prophesy things and they keep turning out to be wrong, people are unlikely to believe you.

[00:34:09] Speaker 02:
So there are, in fact, prophetic examples throughout PHB that say this would work, this would work, this would work.

[00:34:16] Speaker 02:
They turn out one after the other to be wrong, or at the very least unproven.

[00:34:20] Speaker 02:
There's no reason a person of skill in the art reading that would think that, oh, this particular one, unlike all the others, is gonna turn out to be correct.

[00:34:29] Speaker 02:
The only thing they would do

[00:34:31] Speaker 02:
is try to figure out, well, I need to test them.

[00:34:34] Speaker 02:
I'm going to have to figure out what to work.

[00:34:35] Speaker 02:
And that would require undue experimentation.

[00:34:38] Speaker 02:
And then the final point I'd like to make, your honor, is on the single-guide RNA, all they disclose at A2613, which he points, are unmodified single-guide RNAs, not within the scope of the claim, not the subject of the invention.

[00:34:52] Speaker 02:
And as to FirePaste, there is not even that.

[00:34:54] Speaker 02:
So on those claims, we suggest remand is appropriate, even if you agree with Phil on the other issues.

[00:35:00] Speaker 00:
Thank you.

[00:35:00] Speaker 00:
Thank you, Ron.