[00:00:00] Speaker 02:
We will hear argument next in several cases combined, both of them called 10x genomics against parsed biosciences, 25-1199 and 25-1618. Thank you. May it please the court. Just some quick road mapping now that the cases are consolidated.

[00:00:19] Speaker 04:
Thank you.

[00:00:24] Speaker 04:
For the second set of cases, the real separate issue there was the 013 patent, where there just wasn't the analysis in the board's final written decision. For everything else across the two cases, the errors are all part of this common pattern in which the board repeatedly allowed PARs to change its theories and then failed to address 10x's counterarguments to those new theories. And so we saw the morphing of theories over time from the petition where you're looking at substantially all the mRNA in tissue samples being dual tagged with seven nucleotide barcodes.

[00:01:08] Speaker 04:
to a new theory that's about sort of some of the mRNA in bacteria or yeast and longer barcodes. But even if those changes were accepted, we then have the problem, which is we came back and pointed out that their own experts had contradictory testimony on substantially all that the board doesn't address in its final written decision.

[00:01:33] Speaker 02:
So can I just try to separate out...

[00:01:38] Speaker 02:
the following. Suppose I thought that the petition did adequately refer to the possibility to tags without limitation to seven base pairs. And so suppose that was a reasonable reading of the petition and so the arguments about there just aren't enough 16,000 plus possibilities of seven base pairs couldn't possibly make this thing effective because there are too many.

[00:02:16] Speaker 02:
You need much more than that. But if you had four to the 20th, then you'd have a trillion or something.

[00:02:24] Speaker 02:
How much does that strip away from your case? I know you don't want to concede.

[00:02:29] Speaker 04:
Exactly. Without conceding any of that, that puts a dent in it. The board didn't separate out the different strands of this here. It talked about sort of the number of blue-blue tides, it talked about the switch to bacteria or yeast, and it talked about, you know, the other shifts that are making all together. So we don't have a finding from the board that, you know, just that alone would have the decision stand. So it certainly would go up.

[00:03:00] Speaker 04:
I think another unaddressed point in that is their theory in the petition was that, quote, the method would be identical to the approach already set forth in Linterson, except that the tags in Linterson would be conceptually divided. So When we talk about going up, I don't think even if the number's going up there, there's sort of full resolution from the board about... We're not talking about going up to infinity.

[00:03:30] Speaker 04:
Linterson has 20 nucleotide tags. They talk about conceptually dividing that. The only higher number that was offered was they said, well, you go up to 20 or 30, but then you have a 20 to 30 barcode fitting in the 20 tag.

[00:03:44] Speaker 02:
Would 20 be...

[00:03:49] Speaker 02:
I mean, four to the 20th is about a trillion. Is that too small a number?

[00:03:54] Speaker 04:
It's not that that's necessarily too small a number. It's that it leads to another question, which was the board never made a finding that you would increase Linnerson.

[00:04:07] Speaker 04:
Even when it was saying, we're not going to hold you to seven nucleotides. And so we had a theory about what was going to fit within Linnerson, And the board never addresses this, well, wait a minute, you have this alternative argument about fitting a 20 to 30 nucleotide barcode in the 20 nucleotides. But if we take one step even before that, I mean, I don't think that the board itself recognized that, quote, the petition clearly proposes using seven nucleotides.

[00:04:40] Speaker 03:
I'm sorry, clearly proposed what?

[00:04:42] Speaker 04:
Using seven nucleotides. Yeah.

[00:04:45] Speaker 00:
Counsel, do you agree that the amplification bias and obvious design choice are independent motivations to combine?

[00:04:52] Speaker 04:
No, not at all. So the design choice argument, as it was, was a single sentence in the petition under a section that began by discussing analogous arguments. So the breakdown of the petition is you have first, the poser would have found McCloskey and Linnerson to be analogous art. Do you have a page you want to see? Yes, this is 1093 of the appendix.

[00:05:25] Speaker 00:
Of which appendix?

[00:05:28] Speaker 04:
Sorry, volume one of the appendix. Of which appeal? Of the first appeal, the 1199.

[00:05:38] Speaker 02:
You said page 1093?

[00:05:40] UNKNOWN:
1093.

[00:05:41] Speaker 02:
I thought the petition starts at around 8,000.

[00:05:48] Speaker 03:
My petition starts at 8,001.

[00:05:49] Speaker 02:
Or is this the one of the two cases?

[00:05:56] Speaker 02:
I think you're right.

[00:05:58] Speaker 03:
Apologies, Your Honor. It's 8064...

[00:06:07] Speaker 04:
This is the first APL, the 1199, Volume 3.

[00:06:15] Speaker 04:
So the breakdown we have in the petition is the structure you can see starting at 8064. First, the poser would have had reason to consider McCloskey because Linerson and McCloskey are analogous art.

[00:06:29] Speaker 04:
We have under that this statement about the...

[00:06:36] Speaker 04:
design choice.

[00:06:38] Speaker 04:
Where they talk about motivation, it's on 8065. You can see second, if POSA would have been motivated to combine Lindstrom and McCloskey. And then it continues, if you jump over to 8067, you can see POSA has a reasonable expectation of success. So what we have is this alleged design choice argument that that isn't offered as here's a separate motivation to combine, right? It's under the analogous argument.

[00:07:08] Speaker 00:
And then... I mean, but doesn't it say first and second? Why wouldn't those imply that they're two different things?

[00:07:14] Speaker 04:
Oh, because the first, right, what is the first? First, a poser would have had reason to consider McCloskey because Linnerson and McCloskey are analogous arguments.

[00:07:27] Speaker 04:
So it's just setting up, you know, these references would be considered together. And then it moves on. And so it doesn't set up the design choices. Here's a separate motivation based on the design choice, the motivation stuff.

[00:07:42] Speaker 04:
Even if you saw it as a separate argument, though, the entirety of the design choice argument is a single sentence that cites their expert...

[00:07:55] Speaker 04:
What their expert says here, their expert, this is the bottom of 8064, so this is the single, would have been obvious design choice, they cite their expert testimony. The paragraph 187 you see there at the bottom of 8064, that's their expert just saying these are in the same field, they're analogous art. And the paragraph 192 is his conceptual division of Linnerson's tag argument, to which we responded to at length. So in addition to the sort of placement of the design choice argument, substantively there isn't any independence in the design choice.

[00:08:34] Speaker 04:
Where the entirety of the argument is a single sentence that relies solely on this cross-reference to the expert declaration, where that portion of the expert declaration is something that we rebutted at length, There isn't an independent design choice argument here that could sustain the board's opinion. It all collapses into the other arguments and the strength of the argument is painful. And that's a good reason, because we do have to be disciplined around the concept of design choice, lest it swallow obviousness law.

[00:09:09] Speaker 04:
And so when we are there rebutting at length the motivation to combine, to treat that as, oh, that alone is a separate path, would be incorrect. Now, on the amplification bias, I draw particular attention to the substantially all issue, So there, the board, the setup was, the petition is saying you would have to tag each sample polynucleotide, which is absolutely correct, because to avoid the amplification bias, if you're leaving things untagged, then after amplification, you're going to have a confusing count.

[00:09:51] Speaker 04:
The board approached that as, well, that's the sample. It's not all the polynucleotides in the cell.

[00:10:00] Speaker 03:
What it wasn't addressing was that... But isn't it the case that you could at least make some progress against amplification bias by testing fewer than substantially all of the nucleotides?

[00:10:16] Speaker 04:
In... I mean, maybe in a different... I'm not sure because... It's a matter of degree, isn't it?

[00:10:24] Speaker 03:
Well, because if you're doing fewer... If you sample everything, not just substantially, but everything, then you have a way of determining with 100% accuracy whether there's amplification bias, correct?

[00:10:38] Speaker 04:
Right. If you successfully tag everything, yes.

[00:10:40] Speaker 03:
So if you do a sampling of less than everything, depending on what percentage of the body of molecules you're testing, you're going to get some lesser degree of confidence that you're finding amplification bias, but still some.

[00:11:02] Speaker 04:
I'm not sure I'm following, but by sampling you mean tag fewer than... I'm sorry, you mean tag fewer. Right, if you tag fewer, and then... So imagine you don't have enough tags, for example, which is what we have here, but tag fewer, and then you amplify everything using the universal amplification technique they're doing, then what you end up with is a mess on your

[00:11:29] Speaker 03:
It may be a mess, but it's less of a mess than if you don't tag any.

[00:11:38] Speaker 03:
Right? Because you're going to find some duplication. At least that's my understanding. I didn't say anything in the group to suggest why that is not true.

[00:11:50] Speaker 04:
I'll put it that way. We don't have any findings from the board on that.

[00:11:53] Speaker 03:
I understand that. I'm trying to get my bearings here. You're making an argument that if they didn't tag pretty much everything, then it's useless. And I don't see that you've... You certainly haven't satisfied me that that's the case. Maybe you can now, but you didn't in your brief.

[00:12:11] Speaker 04:
Yeah, maybe we're talking about... We're saying you really have to be tagging everything in the sample for it to be useful, because if you're not... But I want to know why.

[00:12:19] Speaker 03:
Why is it not the case that if you tag fewer than all of the molecules, that you will nonetheless... depending on how many you do, be able to get some assurance that there hasn't been amplification bias or some indication of the degree of it?

[00:12:39] Speaker 04:
So I think the issue is, imagine there's sort of gene overexpression, which would be one of the things we're looking at for cancer. If you've started with multiple copies of that polynucleotide and you're not successfully tagging them all, then you come out of the amplification, and you'll have some that'll be tagged, but you'll have copies of that that won't be tagged, and you won't be able to untangle at that point.

[00:13:13] Speaker 04:
Hold on a second. Were there...

[00:13:17] Speaker 04:
Were there 10 mRNAs to begin with? Were there three mRNAs to begin with? You won't know, you won't be able to understand the overexpression that's happening.

[00:13:30] Speaker 04:
Or, I mean, let me just say, there is, they bear the burden of proof on this. There's no evidence in the record about this partial theory. Their partial theory was simply that you would reduce the sample size. Even their petition says the motivation is to tag each sample polynucleotide. Where the board's going astray is that it's applying McCloskey to Linnersen's sample. And as we point out in our surreply, their own expert says, quote, Linnersen describes a method which is designed to be applied to substantially all mRNA molecules of a given cell.

[00:14:13] Speaker 04:
So the distinction the board made is that the board says, I sort of search for substantially all. It says in the sample rather than in the cell. But the point was this was being applied to Linnerson's sample, and their own expert in describing Linnerson's sample is saying what Linnerson's doing is it's releasing everything. And so this is also 7821 of the appendix.

[00:14:42] Speaker 04:
Their expert says, a POSA would understand that because mRNA is indiscriminately released from each single cell, and because Linnersen does not describe any additional elimination or filtration, the released mRNA sample comprises substantially all mRNA molecules of said cell.

[00:15:03] Speaker 00:
So what in the patent itself, though, and the claims themselves require... all of the MRA present to be taxed.

[00:15:11] Speaker 04:
The patent itself doesn't have that as an express claim limitation. But this is similar to this court's intelligent biosystems case, right? It's the theory of the petition. The motivation here, if the motivation here is to address amplification bias, and their petition says each sample polynucleotide, and they apply this to Linnersen, and their own expert says, about the passage that's cited in their petition is saying that would be understood as all the mRNA, then that's an issue that the board needs to grapple with, and you'll find absolutely nothing about that in the board's final written decision.

[00:15:52] Speaker 04:
This is our failure to address argumentary issues. We go back and forth on substantially all, but at the end of the day, in our surreply, 8407 of the appendix, we make this argument. We say this is what their expert is saying. It was in the other proceeding, and the board doesn't address that. The other failure to address argument we have is on this, the testimony from their expert is, Judge Bryson really going against this idea of, oh, we'd be happy with partial, is he says we really want at least a 100 to 1 ratio of tags to make sure that we're tagging everything.

[00:16:34] Speaker 04:
We, again, point this out in our surreply and say their expert is pointing to a number that would have to be much higher. The board doesn't address that in its final written decisions. So we have two core failures to address arguments.

[00:16:51] Speaker 00:
So what exactly, then, are you saying is wrong in terms of what's addressed on Appendix Pages 37 to 38 of the first appeal with respect to this point you've been talking about in terms of quality?

[00:17:07] Speaker 00:
I sense that you're indicating that this is insufficient, but I want to know specifically what you find.

[00:17:15] Speaker 04:
Correct. So on 37 to 38, the board says two things. First, it says the claims don't require that. That doesn't answer it for purposes of motivation because of their theory. And then the board, it says, we've searched through. It basically says we see their petition as arguing you have to tag each sample polynucleotide.

[00:17:41] Speaker 04:
And it says, so each sample polynucleotide, that may be the sample. That might not be everything in the cell.

[00:17:51] Speaker 04:
But what we had said in response to that argument was their own expert has said, looking at the passage from Linnersen that they were relying on in their petition, that the relevant sample in that portion of Linnersen is substantially all of the mRNA. So the board just stopped short. It said there's a distinction between the sample and everything in the cell, but it didn't ask, in their combination, applying this to Linnersen, what is the sample that is being applied to there, and the sample there is substantially all.

[00:18:27] Speaker 04:
So those two failures to address that I've noted would be themselves... the sufficient grounds should be a remand. They are set up. One of the reasons that you hear me talking about the SIR reply so much is because we had these shifting theories, right? No mention whatsoever of bacteria or yeast in the petition. So some of our arguments are responding to things in the reply for the first time, and then the board doesn't address them. No separate design choice, rationale, And then we have on the 013 just no discussion whatsoever of the underlying... They jump right to ligation and don't address the underlying... On that, just looking through the papers, it wasn't clear to me that with respect to the 013 there was anything...

[00:19:21] Speaker 03:
any discussion or motivation to combine other than with respect to Ligand? Can you point me to where you made an argument, as you did with respect to some of the other issues, two other patents, where in the 013 discussion your...

[00:19:39] Speaker 03:
Patent owner response raises an objection to something other than the ligand.

[00:19:47] Speaker 04:
So on, this would be 13382, so volume three of that appendix.

[00:19:58] Speaker 03:
If you give me the page number again.

[00:19:59] UNKNOWN:
13382.

[00:19:59] Speaker 04:
What does three mean?

[00:20:22] Speaker 03:
I still don't have the number. Could you give me the number again?

[00:20:25] UNKNOWN:
13382.

[00:20:25] Speaker 04:
So the setup in this set of IPRs is there's an initial argument about legation.

[00:20:36] Speaker 04:
And then there's an argument about lack of particularity.

[00:20:43] Speaker 04:
there, where we're saying we don't know what you're talking about because this petition didn't have the level of detail of some of the other petitions.

[00:20:56] Speaker 04:
And so on this issue of McCloskey's length of the barcode, the thrust of these pages is us saying we don't understand exactly what you're saying in the petition here that you're trying to combine. They then come back in their reply and make a series of arguments sort of similar to what we see in the other proceedings, the non-identical.

[00:21:22] Speaker 04:
And so the board, and then we come back in our sur-reply and address that. And then the board doesn't have this. I would say, even if we hadn't said the word here, the board, in motivation combined, one of the basic stepping stones here of the analysis. And so if the board didn't have this analysis of why would we be combining these two references in the first place, that would be problematic in its own right.

[00:21:53] Speaker 04:
I mean, it's just a basic failure to address. I am conscious of my time.

[00:22:00] Speaker 02:
Thank you, Mr. Reines.

[00:22:05] Speaker 01:
Thank you, Your Honor. Edward Reines for...

[00:22:10] Speaker 01:
Parse Biosciences.

[00:22:13] Speaker 01:
Good afternoon.

[00:22:13] Speaker 03:
If you don't mind, could you start with the 013 since we've got the books open to those pages? This is one of those free-floating issues that we can pin it down and move things along. Thank you.

[00:22:28] Speaker 01:
Yeah, I think the issue is, as Your Honor identified it, that everyone considered this to be the ligation patent in the psychology And the challenge to the motivation to combine here wasn't to the underlying motivation to combine based on amplification bias for Linderson and McMurtry itself.

[00:22:58] Speaker 03:
McCloskey.

[00:22:58] Speaker 01:
McCloskey, excuse me. And so that's why when the court restated what our position was, which we'd laid out, and that was the same position you've seen in all the two other IPRs, it didn't treat that as a heavily contested item because by the failure of my friend to identify for you where they actually contested that motivation to combine, it wasn't joined up. But in any event, what the board did was it laid out all our arguments, on Motivation to Combine, based on amplification bias, and then said that was sufficient, and then took on the contested issue, which was ligation, the 013 being treated as the ligation patent because it was in the independent claims.

[00:23:49] Speaker 01:
So that's how we got there. And I think your questioning of it surfaced that.

[00:23:55] Speaker 01:
I think I'd like to start on the main argument of – Judge Serrano, you asked the incisive question of if one doesn't accept the seven nucleotide barcode limitation or cabining for the petition, what's really left of these arguments about numerosity, these arguments about organism, a million or not a million? And the answer is nothing is left of those.

[00:24:26] Speaker 01:
Because first, they have to create the number problem before they can get into these other issues. If there's no number problem, if the teaching is that you can use any amount of nucleotides, you just have to use this flexible formula that's disclosed by the prior art, then you just don't have to worry about the confines.

[00:24:55] Speaker 03:
So let me start at the... You think the formula, you're referring to the four to the nth?

[00:24:58] Speaker 01:
The barcode, yeah. Yes, under the heading barcode, exactly, four to the nth.

[00:25:02] Speaker 03:
McCluskey's characterization of the implication being that you could blow this up to as big as you want.

[00:25:08] Speaker 01:
Right, and that's exactly where I want to start, because just to give context to this overall prior art theory...

[00:25:19] Speaker 01:
The original patent is a patent about this reflex method. It's actually one of the rare ones where it's pretty clear. The summary of the invention only refers to the reflex method. It's not one of these where there's a kitchen sink or vagueness. This is a typical thing we see actually in this particular industry of late claiming, where they buy someone's patent applications and then remine it, create new claims. That itself isn't the sin, but it explains how we got here. When challenged, this is in their reply brief, as to where the invention is described, it's actually described in the invention of MID under tag, which is in column six under the definition.

[00:25:55] Speaker 01:
So it's in the glossary section. And in that section, it always captures me, is on six at like 53, 54, 55, it says, well, these tags can range in length from two to 100 nucleotides.

[00:26:15] Speaker 01:
This is at A75, column 6, at line 53 to 56 of the 981 patent. It's in each of the patents in the same text, basically. But in any event, the point is, it acknowledges, and then it cites the prior art that tells you that these tags can be 2 to 100.

[00:26:38] Speaker 01:
So this sort of artificial idea that there's this boundary that...

[00:26:45] Speaker 01:
prior artisans would feel about how long they could make things. This is just conjured. It acknowledges prior art here. They tried to come up with a very broad thing, this dual tagging, and make it an invention, even though the patent doesn't defend that in any way, because it's not about it at all. So that's how we got, that's why this is so weird.

[00:27:07] Speaker 01:
In terms of the references, the references are perfectly good references. One of them is just a routine use of tagging for the uniqueness of the cell.

[00:27:22] Speaker 01:
And the other one has the uniqueness of the cell or other features, and then the uniqueness of the molecules from the cell. And because tagging is so ubiquitous in the field, The basic theory is here's one set of tags. Here's another set of tags that solves the problem that the first prior art reference included. And so what this is an example of is this Inray Keller case, which is a classic CCPA case about bodily incorporation, is what you're seeing is the tug of war.

[00:28:02] Speaker 01:
We're saying they say you can use tags. They say it's a matter of the basic prior arts within the competency of a skilled artisan.

[00:28:10] Speaker 01:
They say you can use them for these different uses. No one's ever identified any challenge in scaling the number or any challenge at all. In fact, reasonable expectation of success isn't even in their appeal brief.

[00:28:24] Speaker 01:
The issue to decide is just motivation to combine.

[00:28:29] Speaker 01:
And so there's no challenge. These are tags everyone uses all the time. None of that's denied. And they're trying to make this a Mr. Potato Head case where, okay, you're taking the very specific experiment of each and putting them together. And it gets to, I think, a cartoonish point with respect to their seven-nucleotide argument, which is really the heart of the appeal, because the other arguments fall away.

[00:28:54] Speaker 01:
The IPR petition does not mention...

[00:28:58] Speaker 01:
the seven nucleotide barcode. It would be such an incredibly stingy reading of the petition to say that this was bound to the example in that reference, McCloskey, when it isn't even mentioned in the petition. If you then go to the expert report, which is where they can find it, it's under the reasonable expectation of success.

[00:29:27] Speaker 01:
portion of the analysis.

[00:29:29] Speaker 01:
Intelligent Biosystems, which was referenced earlier, said... This is the Cooper Declaration? Yes, Professor Cooper.

[00:29:37] Speaker 01:
He talks about it for... So it's not even in the right branch of the analysis. Intelligent Biosystems, the big issue there was, wait a minute, don't conflate motivation to combine and reasonable expectation of success. Two different things. It's exactly what the whole theory of their appeal is here. Because...

[00:29:55] Speaker 00:
also ask you some of the questions I have for opposing counsel. One thing in particular is whether or not they're independent motivations to combine, or I think opposing counsel said that at least two of the ones I was discussing with him actually collapse into each other. So why don't you start there and then I'll ask the follow-up.

[00:30:14] Speaker 01:
That's a great question. So there's amplification bias, which is extremely potent They don't even really have an argument to it other than the seven nucleotide barcode. Because if you can flexibly use it, which was in the basic competence in the art, you're satisfied. On the basic design choice, that goes to understanding this case and the record by understanding how basic ligation is. I mean, ligation is like saying to someone that works with paper, use a paper clip or a staple for these artisans.

[00:30:47] Speaker 01:
And it's not denied.

[00:30:50] Speaker 01:
it's how you put DNA. If you have two pieces of DNA, you put them together, you ligate. That's how you do it. So it's so basic, and this is very responsive to your question in the sense that what the board said is these are basic skills in the art. How to use these things, tagging is simple.

[00:31:13] Speaker 00:
I'm missing something here. I'm trying to figure out First, maybe it's more fundamental what I'm asking is whether or not these are independent.

[00:31:19] Speaker 01:
They are independent because it's like saying, if you're working with paper and someone says, staple it or paper clip it, and you say, okay, I'll paper clip it, do you need a heavy motivation to choose between staple or clip? So the basic point is it's so elementary to what these artisans are doing that you don't need to have some driving need. And the classic case is? KSR, where that's what the whole point...

[00:32:04] Speaker 00:
but there should have been more that should have been done in the balance.

[00:32:07] Speaker 01:
Okay. I mean, I think if that's referring to amplification bias, it's because which organisms you measure or whether you use just the sample ones you choose if you might want to do a subset, let's say you're only interested in particular genes, those all fall away if you don't accept this...

[00:32:32] Speaker 01:
I think, indefensible seven-nucleotide barcode limitation.

[00:32:36] Speaker 02:
So Mr. Saunders said, no, they don't fall away.

[00:32:43] Speaker 01:
The only one he said that didn't – I was listening extremely closely. They do fall away.

[00:32:47] Speaker 02:
Sample versus all. That's the one I thought he was focusing mostly on that I may have missed.

[00:32:54] Speaker 01:
I think what I heard, because there's really – they fall away, is that there's this limit to linersin because it happens to have 20 nucleotides. And so you're always bounded by that 20 nucleotide. So even if you could flexibly use more – With McCloskey, Linnerson would now be the limitation on the number. They have to come up with a limitation on the number somewhere. And so they do it by this bodily incorporation. They're saying, well, Linnerson, you'd just be working with the specific...

[00:33:26] Speaker 01:
design they have there, which has 20 nucleotides. And that's where Cooper says, for example, you could take the 20 nucleotide tag and conceptually break it up into two. And just it was an illustration for thought. And so the argument that I think they say still remains is, well, if you're limited to 20 here, even if you could scale – because everyone knows you could just make more tags by increasing the length of the unique molecule from a cell tag, then you'd run into the problem over on Linnerson because you're compliant to 20.

[00:34:07] Speaker 01:
But all these... Oh, go ahead. No, no, you probably had a good question, so I want to hear it.

[00:34:10] Speaker 03:
Well, I just... I don't recall whether Cooper said anything about the point you're now making as to whether Linnerson is infinitely expensive.

[00:34:19] Speaker 01:
Uh...

[00:34:20] Speaker 01:
So there's two things. One is there was a reference of testimony where he says it could go to 2030, I believe, in the reply brief.

[00:34:27] Speaker 03:
But was there any suggestion that there's no linen? It's just that the winner said it's a concept, but that concept could be expanded willfully.

[00:34:40] Speaker 01:
This is where I think a patent challenger can just have frustration because the patent document, the quality of the disclosure in the patent document, the patent document says it's prior art. You could go 2 to 100.

[00:34:51] Speaker 01:
So why are we creating this false concept that there's a challenge of going over 20 when even the patent owner has never come forward?

[00:35:02] Speaker 03:
Okay, but did Cooper say anything about that?

[00:35:05] Speaker 01:
I think Cooper said that it could go to 20, 30, 20 or 30.

[00:35:10] Speaker 00:
Do you have a page? Can you give us a page?

[00:35:12] Speaker 01:
I don't have the, not offhand, I don't have the 20 to 30.

[00:35:15] Speaker 01:
But it's all by, so there's two sources of limitation.

[00:35:19] Speaker 03:
I guess another way of asking the same question is, is there any conceptual limit, a practical limit, on how much letters could be expanded?

[00:35:28] Speaker 01:
Because of the exponential nature of As Judge Toronto said, like a password, you get the 12 and all of a sudden, right?

[00:35:40] Speaker 03:
Because you don't need, you know. But is there a practical constraint that comes into effect at some point? That's why I've been confused really from the start about why there's so much focus on the individual numbers when what we seem to be talking about is something that's more conceptual.

[00:36:03] Speaker 01:
The issue is that this is all basic technique, tagging, labeling, ligating, that there isn't a technological limit. Let's just hold off on conceptual. You've heard of no technological limit. The other side, zero. Expensive pages and pages of briefing. Never. Not one. No challenge to reasonable expectation of success at all.

[00:36:34] Speaker 01:
So technologically, there's no limit.

[00:36:38] Speaker 01:
Record. In their own patent, where they say it describes the invention, it says you can do this 2 to 100 as prior art.

[00:36:47] Speaker 01:
I mean, what this is is it's a Keller problem, is that they're trying to limit things to bodily incorporation and saying, well, you have to take the experiment of Linnerson and take the experiment of McCloskey, and you've got to merge them, and the numbers have to work. And that's nonsense.

[00:37:10] Speaker 01:
That wasn't the theory in the petition. That's not what the art requires. Tags are known. Different ways to attach them are there.

[00:37:19] Speaker 01:
We put all that in. It helps with amplification bias. Here's a reference that tells you. This one says you might have an issue with amplification bias. You put them together and you've got the claims. And they run from that. They run from arguing the technology to arguing our theory in the petition that's an abusive discretion standard.

[00:37:40] Speaker 01:
And if they lose the abusive discretion on this really indefensible limit of seven nucleotides. It's not in the IPR petition. It's not contained in the IPR petition, any reference to seven nucleotides.

[00:37:54] Speaker 01:
It's a little embarrassing that that's the argument, is that the petition's limited to an example from a prior reference, and the example's not in the petition?

[00:38:02] Speaker 01:
That's what we've come to here on this.

[00:38:04] Speaker 00:
So what's your best support in the petition for the explanation of flexibility?

[00:38:09] Speaker 01:
Flexibility? Yeah, the best portion of that is the point that there's two basic ways you can do this. Let me see if I can do it right in front of you. I think it's A, 8369, 8369 through 70. I believe that's where that is. But In plain English, with respect to flexibility, it's just another way to do something that's basic in the art.

[00:38:47] Speaker 01:
You either incorporate it through PCR, where you incorporate the bases in, or you ligate it and just attach it. Those are your two basic points. And to answer, Your Honor, Judge Cunningham, The flexibility is when you just attach it on and you don't have to do it during the initial incorporation, you can do it later in the process. So it gives you the flexibility to do the attachment of the tags and figure out how many tags you want later in the process so you're not doing it at the outset.

[00:39:18] Speaker 02:
The pages you gave were from the reply? Wait, from their reply? I think so.

[00:39:26] Speaker 01:
Let me just check that. I could certainly be wrong.

[00:39:31] Speaker 01:
Let me get this.

[00:39:33] Speaker 02:
Do you have pages in the petition?

[00:39:39] Speaker 00:
Yeah, I think it's... Well, I have it in the...

[00:39:50] Speaker 01:
Okay. I have it at A1116 is the opening expert report, which I thought what the original question was like, where's our expert evidence on the point?

[00:40:01] Speaker 00:
No, I asked the petition. Petition. Okay.

[00:40:04] Speaker 01:
Where does the petition have?

[00:40:05] Speaker 00:
I want to stage citations from the petition.

[00:40:07] Speaker 01:
It's in, just to be clear, it's at paragraph 243 of A1116. Okay.

[00:40:34] Speaker 01:
Yeah, I don't know. I don't think I have.

[00:40:41] Speaker 01:
In front of me. Actually, give me a second.

[00:40:56] Speaker 01:
Wait, okay, so I'm confused. This was the original site I gave. Okay.

[00:41:01] Speaker 00:
I thought you gave us reply citations.

[00:41:04] Speaker 01:
No, the original thing I gave was to the IPR petition at 8369.

[00:41:10] Speaker 02:
So when I look at 8369, it's page 20 of a document, and I go back to page 1, and the title page in front of page 1 is petitioner's reply to patent owner's response.

[00:41:24] Speaker 01:
Oh, okay. I see what you're saying. Okay.

[00:41:28] Speaker 01:
Yeah, I think that is where we get into the flexibility particularity.

[00:41:35] Speaker 02:
And why, if that's where it gets introduced in your submission documents, not evidence, why is that not a kind of shifting target or whatever the expression was that Mr. Saunders focused on?

[00:41:55] Speaker 02:
adding something that was not really part of the petition unless maybe the petition somewhere cites the petition, I'm sure it does cites paragraph 243 of the Cooper Declaration

[00:42:26] Speaker 01:
This is the issue. So among other points, they had said that ligation is equivalent, the argument was ligation is equivalent to incorporation, so there's no additional benefit to doing it that way, and that was the argument against the motivation to combine, as I recall.

[00:42:48] Speaker 01:
And that doesn't seem like very strong position at all.

[00:43:01] Speaker 01:
What the board stated was that the proposed modification was not beyond the skill level, right? And the prior art would have taught that you could use ligation for this.

[00:43:16] Speaker 01:
So they've admitted that it's conventional. It says that in their own patent.

[00:43:25] Speaker 01:
So I just think we're at the situation, you know, with respect to the ligation edition and the edition of the second tag, with respect to both of those, these are just basic tools in the art, and I think the record's more than abundant that they were known to skilled artisans at the time.

[00:43:53] Speaker 01:
Thank you.

[00:43:53] Speaker 02:
Thank you.

[00:44:05] Speaker 04:
On the argument that everything falls away with the size of the nucleotide tag, what you won't find is a finding from the board on that point. We'd have a different situation if the board had said, we end our analysis here. They didn't. They addressed all of them together. If that argument's going to be addressed, it should be addressed in the first instance on remand. In connection with addressing that, the board could address the fact that, to Jay's question, there isn't any testimony from Dr. Cooper or that Linnerson is infinitely expandable.

[00:44:37] Speaker 04:
It also wasn't their theory, right? In their petition, they said, quote, the method would be identical to the approach already set forth in Linnerson, except that the tags in Linnerson would be conceptually divided into two portions. That's 8067 through 8068 of the appendix. So, Sorry, that is volume three of the appendix in the first appeal. It would be identical except for... Except for they'd be conceptually divided, which would fit in the McCloskey tag.

[00:45:12] Speaker 04:
So their petition doesn't say flex Linterson. It says identical to Linterson. They don't have expert testimony saying Linterson would go up. So if we are talking about this number of tags... going up, that would be something for the board to address on remand.

[00:45:32] Speaker 04:
In terms of the seven nucleotide, I don't think that the board was off base when it said the petition clearly proposes using seven nucleotides. What they rely on in the petition is figure one, which shows seven nucleotides, and then they cross-reference their expert's testimony to where in paragraph 192 of the Cooper Declaration in the First Appeal is where he talks about fitting the seven nucleotide tag of McCloskey into Renison's barcode.

[00:46:05] Speaker 04:
Now, we heard today for the first time, well, we can't rely on that paragraph. as part of motivation, because it actually goes to something else, reasonable expectation of success. I just want to point out, coming full circle here, when we were talking about design choice in the beginning, that is the very paragraph that is their sole support for the one-sentence design choice argument they gave here. It's really the heart of Dr. Cooper's opinion, and their theory of the case was take Linnerson as it is, divide it, and fit McCloskey in there.

[00:46:40] Speaker 04:
When they wanted to go up In the other IPRs, in separate rounds, they brought in the McCloskey 2 reference. It's a very stark contrast, which is they're pointing to McCloskey, pointing to the figure with seven nucleotides. They're experts saying seven nucleotides. When they wanted to have a different theory, They brought in a different reference, which is not part of any of the combinations in the first appeal. It's only in the last rounds of the other appeals.

[00:47:10] Speaker 04:
And so I think that's a telling sign that what the petition was saying was a different theory, and we have a change of theory here.

[00:47:19] Speaker 04:
And then just very briefly, coming back to this substantially, all... We went through the pages in the opening of the argument, but their expert's own description of Linnersen as releasing all this mRNA so you'd be dealing with substantial at all is the key missing piece in that part of the board's analysis because it's saying apply McCloskey, to Linnersen, it stops with this distinction between everything in the sample, but it doesn't address our argument, well, hold on a minute, the Linnersen sample they're pointing to is substantially all.

[00:47:57] Speaker 04:
So for all these reasons, it's substantially all the mRNA in the cell. And then just very briefly on the 013 patent, Judge Bryson, it's following the way it played out.

[00:48:13] Speaker 03:
You can see what I was pointing to there. For example, the patent owner's response, round six, has several subsections, all of which deal with ligation.

[00:48:30] Speaker 04:
Right, and then the final section of the patent owner response is this point where we are saying we don't understand what they're proposing to combine here. It's going to this sort of McCloskey versus Winterson. They come back in their reply. I didn't understand that point. I'm sorry. So the point was, apart from ligation, going back to the basic combination of McCloskey with Linerson, in the other IPRs they had presented a theory as to why they would be combined and how they would be combined.

[00:49:16] Speaker 04:
This points out, it says, you haven't done that here. We don't know what your theory is. They then come back in their reply and present sort of their amplification bias argument And then we come back in our surreply and say, oh, we'll hold on a second and make our full set of arguments around this.

[00:49:35] Speaker 03:
Where in your patent owner's response do you make the argument you've just now identified? That's what I wasn't able to find.

[00:49:43] Speaker 04:
Right. The patent owner response, the way it plays out, is the patent owner responds at 11382.

[00:49:50] Speaker 03:
Well, unfortunately, I pulled this out of the appendix, so I don't have an appendix page. But if you can give me a reference to the patent owner's response by page 49 of the patent owner's response.

[00:50:04] Speaker 04:
In the 013? In the 013, yes, which is volume 2. It's really 48 through 49.

[00:50:19] Speaker 00:
Can you also give us the appendix page?

[00:50:21] Speaker 04:
The appendix page is 13381 through 13382. So there's been a discussion of ligation.

[00:50:36] Speaker 04:
And then there's this separate subsection at the end of the patent owner's response that says there's a lack of particularity in the petition. We don't know what you're saying. What exactly is this combination? It hasn't been explained in the same way it was before.

[00:50:51] Speaker 04:
They then come back in their reply and respond to that argument with their sort of full set of arguments similar to what we see in the other appeal. And we come back in our sur-reply at 1, 3, 5, 7, 6 of that appendix with a section that says petitioner's motivation to combine still fails. And you'll see page after page of us stressing the basic motivation to combine McCloskey and Linnerson.

[00:51:19] Speaker 02:
If we to that basic Winters and McCloskey thing.

[00:51:31] Speaker 02:
Why would any deficiency as in the OM3 on this point that you're just making, be prejudicial?

[00:51:42] Speaker 04:
It's prejudicial because there was, even in the way they articulated it in the 013, there was a slight difference in that they didn't have the conceptual division testimony. And so it plays out slightly differently in the argument.

[00:52:02] Speaker 04:
It may be that the board will reach the same result in the end. I think it's one where we can't say, oh, it's harmless error, we can't prejudge it there, because there was that difference.

[00:52:13] Speaker 02:
And so the board would have to look at it and say, well, looking at these arguments... In your briefing to us, do you make a harmfulness argument?

[00:52:23] Speaker 04:
Yes, we do, Your Honors.

[00:52:27] Speaker 04:
When we, in the 013, in that section, we...

[00:52:32] Speaker 04:
finish by saying, no, there are differences.

[00:52:38] Speaker 04:
Here's page 32 of the blue brief.

[00:52:40] Speaker 03:
This is right at the beginning of the argument section, right? The first two pages, right.

[00:52:49] Speaker 04:
Yeah.

[00:52:51] Speaker 04:
So this final paragraph, page 32 of the briefs, The board's conclusion to the other proceedings can't excuse the lack of finding on the 013. You make this point I just made that they didn't make the same argument on the 013 as they did there.

[00:53:10] Speaker 04:
And they didn't dispute that in their opposition brief.

[00:53:16] Speaker 02:
I'm not completely sure that that's the same thing as a harmfulness argument.

[00:53:25] Speaker 02:
observation under 706?

[00:53:26] Speaker 04:
Oh, Your Honor, I think it is because the board is charged with the fact-finding here.

[00:53:35] Speaker 02:
If you have an unaddressed argument, if they don't line up one on top of one another... But isn't the 706, the rule of prejudice standard require you to say...

[00:53:54] Speaker 02:
I've not only shown you that there are differences, but why those differences could reasonably lead to a different result.

[00:54:07] Speaker 04:
Right. And so I think that here where the heart of their argument in the other proceedings is this conceptual division.

[00:54:21] Speaker 04:
and you take it over to another proceedings, ways it could lead to a different result are twofold. One is, substantively, the board could say, well, we relied on that explanation in these other proceedings, and it's not here, and it fails. But it also could be procedural. And it's not here in this proceeding, and it fails. But it also could be a procedural change in which it would say, oh, we do see this then as a deficiency.

[00:54:52] Speaker 04:
Because without that theory, which was the heart of what you were offering in the other cases, we're not sure what you're saying, we're not sure how these pieces fit together. So that would be, it's that it was so central, it's in their other final written decisions, and so they did not have that in this procedure.