[00:00:00] Speaker 07:
Please be seated.

[00:00:02] Speaker 07:
Our case for argument today is 24-1324, Matera vs. Neogenomics Laboratories.

[00:00:09] Speaker 07:
Ms.

[00:00:09] Speaker 07:
Maynard, please proceed.

[00:00:13] Speaker 04:
Thank you, Your Honor, and may it please the Court.

[00:00:14] Speaker 04:
Deanne Maynard for Neogenomics.

[00:00:16] Speaker 04:
I'd like to reserve three minutes for rebuttal.

[00:00:20] Speaker 04:
The preliminary injunction removing Neogenomics's cancer detection test from the market should be set aside for multiple independent reasons.

[00:00:27] Speaker 04:
including because substantial questions exist on obviousness and on whether radar infringes the properly construed claims, and because the public interest in access to this unique and highly sensitive cancer detection test outweighs any harm to Natara.

[00:00:43] Speaker 04:
I'd like to start with obviousness.

[00:00:45] Speaker 04:
So the claims here are just three steps, tagging, amplifying, and sequencing cell-free DNA.

[00:00:52] Speaker 04:
All of these steps were known before the... In particular ways.

[00:00:57] Speaker 04:
In particular, but still, Your Honor, in ways that were known in the art.

[00:01:01] Speaker 04:
So the CAPER reference, our primary reference, teaches basically all of the steps.

[00:01:07] Speaker 04:
And the only... Except for the input.

[00:01:11] Speaker 04:
So the question is whether... Is that right?

[00:01:13] Speaker 04:
Except for the input meeting, except for using the method on cell-free DNA.

[00:01:17] Speaker 04:
That's what you mean.

[00:01:18] Speaker 04:
Yes, Your Honor.

[00:01:18] Speaker 04:
That was the only element the district court found missing.

[00:01:22] Speaker 04:
But that element, too, is known in the art.

[00:01:25] Speaker 04:
And Natera's previous admissions in this court and in other courts and other cases and the prior art make clear that applying basic cell-free DNA processing steps to circulating cell-free DNA was routine and conventional.

[00:01:43] Speaker 07:
Ms.

[00:01:43] Speaker 07:
Maynard, I guess here's my problem.

[00:01:45] Speaker 07:
I completely understand what you're saying.

[00:01:48] Speaker 07:
I have no doubt amplifying cell-free DNA was known.

[00:01:51] Speaker 07:
Tagging cell-free DNA was known.

[00:01:53] Speaker 07:
The problem is there's a bunch of evidence here that this court relied on, and we review it under the clear error standard.

[00:02:01] Speaker 07:
And that evidence suggests that there were lots of problems with CFDNA in terms of the fragmentation, the lower yields, that would make it unsuitable for using it in this CAPER assay.

[00:02:16] Speaker 07:
that would make it such that a skilled artist would not be motivated to substitute it in and use it for this purpose.

[00:02:23] Speaker 07:
So even if cell-free DNA, people knew how to amplify it, people knew how to tag it, people knew how to do these things, these one-off things with it, there's a difference between doing those one-off things and choosing to substitute the cell-free DNA in CAPER in that particular

[00:02:42] Speaker 07:
fluid something assay?

[00:02:44] Speaker 07:
I don't remember what it's called.

[00:02:45] Speaker 07:
Fluid dimerane assay.

[00:02:47] Speaker 07:
Okay, yes.

[00:02:47] Speaker 04:
Yes, Your Honor.

[00:02:48] Speaker 07:
And that's the issue and it's clear error review for us.

[00:02:51] Speaker 07:
So what do we do with that?

[00:02:52] Speaker 04:
So I think two points in response to your question, Your Honor.

[00:02:54] Speaker 04:
First, I think at bottom, even accepting the district court's findings.

[00:02:58] Speaker 07:
Hold on just one second.

[00:03:00] Speaker 07:
John Paul, I might be crazy, but it feels really dark in here to me.

[00:03:04] Speaker 07:
Is there any way to turn the lights up?

[00:03:05] Speaker 07:
I know these things are on dimmers.

[00:03:07] Speaker 07:
Maybe they're not all on.

[00:03:08] Speaker 07:
Am I the only person that thinks it seems a little dark?

[00:03:11] Speaker 07:
I feel the same.

[00:03:13] Speaker 00:
Thank you.

[00:03:17] Speaker 07:
Let there be light.

[00:03:18] Speaker 07:
Go ahead.

[00:03:20] Speaker 04:
So two points in response to your question, Your Honor.

[00:03:23] Speaker 04:
One is, even accepting the district court's findings on obviousness and the obstacles that might exist with respect to applying Kapor to sell free DNA, even accepting those on this legal standard that applies here, which is, did Natera show a lack of a substantial question of obviousness

[00:03:39] Speaker 04:
on this record on the unrebutted facts and their own admissions, the answer to that is, no, they did not.

[00:03:46] Speaker 07:
Because- Well, but you have to prove motivation to combine in order to say there is obviousness, or Matera has to show that there wasn't likely a motivation to combine.

[00:03:57] Speaker 07:
And that's what this seemed to all hinge on for the district court, I think.

[00:04:01] Speaker 04:
So, well, the way that I read the district court's opinion, Your Honor, is that it actually turned to more on reasonable expectation of success.

[00:04:07] Speaker 04:
And that even Natera concedes that there was the classic motivation to use this for cancer detection.

[00:04:13] Speaker 04:
That was the same way in which what CAPER was doing.

[00:04:17] Speaker 04:
That was the motivation in CAPER.

[00:04:19] Speaker 04:
And our expert testified that persons with skill in the art would be motivated to use this on SELFRE and DEA for cancer detection.

[00:04:26] Speaker 07:
Yes, to use SELFRE.

[00:04:28] Speaker 07:
OK.

[00:04:28] Speaker 07:
Yes, to use cell-free DNA in cancer detection.

[00:04:32] Speaker 07:
But that's a really broad thing.

[00:04:34] Speaker 07:
Is there a motivation to use cell-free DNA in this particular Fluidigm access array assay?

[00:04:41] Speaker 07:
I don't know if I'm saying that right.

[00:04:42] Speaker 07:
Yes, you're right.

[00:04:43] Speaker 07:
Because of the lack of precision in using the cell-free DNA, that that made it such that whether you want to frame it as a question of motivation to combine or frame it as a question of likelihood of success,

[00:04:57] Speaker 07:
It almost doesn't matter.

[00:04:58] Speaker 07:
I read the district court's use of the word precision as very much going to this question of whether somebody would have substituted cell-free DNA in this CAPER assay in light of the limitations of using it that were

[00:05:13] Speaker 07:
articulated on pages 9 and 10 of the district court opinion.

[00:05:15] Speaker 04:
And I will address the evidence that shows that we've created substantial question of humility framed that way, Your Honor.

[00:05:20] Speaker 04:
I do think it was error for the district court to rely on with precision, since with precision is an unclaimed feature in these claims.

[00:05:26] Speaker 07:
No, no, no.

[00:05:27] Speaker 07:
Look, with all due respect, you have no chance of winning on that with me.

[00:05:31] Speaker 07:
And you have a chance of winning here, but not with that.

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And the reason you have no chance of winning with that is because I don't read that as going to claim construction at all.

[00:05:37] Speaker 07:
I found their brief quite persuasive on the point

[00:05:41] Speaker 07:
That was the court saying, would a skilled artisan be motivated to take cell-free DNA when it lacks precision and insert it into this test?

[00:05:50] Speaker 07:
And that's the way I read the opinion.

[00:05:51] Speaker 07:
So if you want to spend any of your very short time on that, feel free, but you will not prevail on that.

[00:05:56] Speaker 04:
I've noted my argument, and I will address your honor's questions about the record evidence.

[00:06:00] Speaker 04:
So the record evidence shows, in their own prior admission so, that someone would be motivated and expect to have reasonable success applying a similar

[00:06:10] Speaker 04:
assay to CAPER to cell-free DNA.

[00:06:13] Speaker 04:
And as one of many examples, the 2010 Fluidigm application, which is in the records, prior art, describes similar DNA processing steps using a device like CAPER's for tagging and amplifying cell-free DNA.

[00:06:26] Speaker 04:
That's in volume 3, A13097, paragraph 122.

[00:06:30] Speaker 04:
It shows that Fluidigm, which is the same company behind CAPER, Your Honor, the Fluidigm array, can be used on any fluid, including blood,

[00:06:38] Speaker 04:
and at A13103, paragraph 176, for the purpose of diagnosing cancer.

[00:06:44] Speaker 04:
So again, Fluidigm is the same company behind CAPER.

[00:06:47] Speaker 00:
Was this cited to the district court?

[00:06:49] Speaker 04:
Yes, Your Honor.

[00:06:50] Speaker 00:
Oh, where?

[00:06:53] Speaker 04:
where do we cite fluidine?

[00:06:54] Speaker 00:
I want to know if the district court judge had notice of this particular passage in the fluidine publication such that the judge could evaluate it and understand whether this was possibly enough to raise a substantial question.

[00:07:14] Speaker 04:
Well, so I can give you the pinpoint site when I come back on rebuttal if that's okay, Judge Chen, but this was a key feature of our expert preparation.

[00:07:22] Speaker 02:
I'm sorry, where in the Joint Appendix?

[00:07:26] Speaker 04:
I'm sorry, I'm pointing to 2010 Fluidigm Application, Your Honor, which is Volume 3, A13097.

[00:07:48] Speaker 00:
I guess I just had a broader.

[00:07:50] Speaker 02:
I don't think, I'm sorry.

[00:07:51] Speaker 02:
I don't think that was in the relevant four paragraphs of your 103 argument on 035.

[00:07:57] Speaker 04:
Well, so the, the district court also looked to our expert declaration, your honor, and Van Ness, our expert discussed both the, both the prior art, which is not in any of the pages or paragraphs, as far as I can tell, cited

[00:08:13] Speaker 02:
on this crucial point in your four paragraphs on 035.

[00:08:17] Speaker 04:
So both parties in the district court, Judge Toronto, litigated this largely through the expert reports.

[00:08:24] Speaker 04:
The district court found fault with that with respect to other arguments, but not with respect to the obviousness argument.

[00:08:29] Speaker 04:
And the district court addressed Van Ness and our declaration and Metzger and their declaration.

[00:08:34] Speaker 00:
That's the question, which is

[00:08:37] Speaker 00:
If the judge was on notice, obviously, of this fluid on publication and was on notice of the entire Metzger reply declaration in the Illumina IPR,

[00:08:50] Speaker 00:
is the judge required to look through all of those materials before reaching a conclusion on substantial question of validity, or is it really fair for the district court to just consult the actual paragraphs of various documents that you cited in your opposition to the PI and then go from there.

[00:09:15] Speaker 00:
So, for example, for the Van Ness Declaration you were talking about,

[00:09:20] Speaker 00:
your op cited paragraphs 241 and 248.

[00:09:25] Speaker 00:
And in 241 and 248 I don't see anything about the Pneudon publication, for example.

[00:09:31] Speaker 02:
That was Exhibit 13, which is not cited.

[00:09:36] Speaker 00:
And so this raises a question.

[00:09:38] Speaker 00:
Your briefing raises a lot of interesting quotes from a lot of different documents, including the Metzger Declaration, the Fluidime, on and on and on.

[00:09:48] Speaker 00:
But if those aren't actually contained in the sites in opposition to the PI, I'm not sure what I'm supposed to do about that and think about that.

[00:09:56] Speaker 00:
I mean, maybe for purposes of the final merits, you can raise all of that.

[00:10:01] Speaker 00:
But for the limited purpose of trying to figure out whether

[00:10:04] Speaker 00:
the judge here clearly erred is it would be inappropriate for me to be looking and scouring through the entire record like you have done very well to then conclude that the district court clearly erred.

[00:10:19] Speaker 04:
So two points, your honor.

[00:10:21] Speaker 04:
One, they have an argued waiver of this issue on appeal.

[00:10:24] Speaker 04:
Two, the district court looked through all the materials and addressed the party's expert declarations.

[00:10:29] Speaker 04:
Our expert declaration cites it in her opinion and cited their expert declarations.

[00:10:34] Speaker 04:
We had a long hearing, and our slides are in the day that we presented to the district court at the oral argument on this issue, which calls out a lot of these same pieces of evidence that our slides of the PI hearing begin at Appendix 21068 in Volume 4.

[00:10:53] Speaker 04:
And the slides call out and address many of the same evidence that we are featuring in our appeal brief.

[00:10:59] Speaker 04:
So the judge was definitely on notice, Your Honor.

[00:11:02] Speaker 04:
And I don't think it's just purely a factual question.

[00:11:06] Speaker 04:
The question is, abuse of discretion in granting a preliminary injunction has both a legal aspect and a factual aspect to it.

[00:11:14] Speaker 04:
And the question is whether

[00:11:15] Speaker 04:
there's a substantial question of invalidity on this record.

[00:11:20] Speaker 04:
And there is.

[00:11:20] Speaker 04:
I mean, the judge heard oral argument and we presented all of this evidence and called it out and put up these slides on the screen and talked to her about it.

[00:11:26] Speaker 04:
She was clearly on notice.

[00:11:28] Speaker 04:
She did, as I say, fault neogenomics on other invalidities.

[00:11:33] Speaker 07:
Can you tell me where that slide is that you say that she had in front of her?

[00:11:36] Speaker 07:
What page number you said that was on that contained this information?

[00:11:39] Speaker 04:
I'm sorry, Your Honor.

[00:11:40] Speaker 04:
I was giving you the first page of our slide.

[00:11:42] Speaker 04:
which is A21068.

[00:11:45] Speaker 05:
What volume?

[00:11:46] Speaker 04:
Oh, it's volume four.

[00:12:02] Speaker 04:
And so we do discuss the Fluidigm patent application.

[00:12:06] Speaker 04:
I'm on 21068.

[00:12:07] Speaker 07:
So these are slides that you

[00:12:09] Speaker 07:
Don't worry about time.

[00:12:11] Speaker 07:
This is not going to be a 15-minute case, OK?

[00:12:14] Speaker 07:
So 21068.

[00:12:15] Speaker 07:
I was just giving you the first page, Your Honor.

[00:12:18] Speaker 07:
So where would the thing be that you say should have drawn to the judge's attention your argument about fluidine, and in particular, I think it was a patent on pages 13098?

[00:12:30] Speaker 04:
So we have slides about the fluidine patent and make the point that we make sure.

[00:12:35] Speaker 04:
What page?

[00:12:35] Speaker 04:
I'm sorry.

[00:12:36] Speaker 04:
It's on page A.

[00:12:38] Speaker 04:
21-105.

[00:12:38] Speaker 04:
It shows a picture of their expert, Dr. Metzger.

[00:12:43] Speaker 04:
It says, fluid ime teaches 90 to 16 targets.

[00:12:47] Speaker 04:
This is our point about their claim here in this court that multiplexing in a single volume reaction is their primary invention.

[00:12:55] Speaker 04:
But Dr. Metzger admitted in another case that the Fluid Ime 2010 application teaches.

[00:13:02] Speaker 04:
a single volume reaction with over 9,000.

[00:13:04] Speaker 07:
OK, now you're switching points.

[00:13:06] Speaker 04:
Yes, I am.

[00:13:07] Speaker 07:
Try to just get me to the finish line on the first point, because I'm not there yet.

[00:13:12] Speaker 04:
Understood.

[00:13:13] Speaker 04:
So we pick up 21106, 21105.

[00:13:18] Speaker 07:
Where am I supposed to see that you have directed the district court to pages 13097 and 13098, which is a patent.

[00:13:30] Speaker 07:
I think it's a patent.

[00:13:33] Speaker 04:
So, starting on page A21127, we have portions of Dr. Metzger's Illumina Declaration, Judge Chang.

[00:14:03] Speaker 04:
where we point out that this is a quote from the slide on A21127.

[00:14:09] Speaker 04:
It was further well known by 2008 that one could isolate, amplify, and sequence cell-free genomic DNA.

[00:14:25] Speaker 04:
I'm looking, Your Honor.

[00:14:26] Speaker 04:
I wasn't expecting to be addressing the waiver argument since they haven't argued it.

[00:14:31] Speaker 07:
Paragraph 116.

[00:14:32] Speaker 07:
That first sentence is what you think should have alerted the court to this argument about... I mean, your argument is that the district court erred in having all of these concerns about the use of cell-free DNA because of its fragmentation, because of the lower yields, all of these different documents that the district court cited, which all went, clearly in my mind, to both motivation and consent,

[00:15:02] Speaker 07:
motivation to combine and reasonable quotation success.

[00:15:05] Speaker 07:
And you're saying that was clear error because we pointed the district court to this other thing.

[00:15:10] Speaker 07:
And the district court didn't address the other thing in the opinion.

[00:15:13] Speaker 07:
So I'm wondering, is that a flaw in the district court's part?

[00:15:16] Speaker 07:
Or did you really present this other thing to the district court?

[00:15:18] Speaker 07:
And I'm still struggling to see where you presented the other thing to the district court.

[00:15:22] Speaker 07:
And this doesn't go to waiver, Ms.

[00:15:25] Speaker 07:
Maynard.

[00:15:25] Speaker 07:
It goes to whether or not the district court abused its discretion and therefore clearly aired in its fact-finding

[00:15:33] Speaker 07:
If you didn't raise this argument to it, if you didn't show it this, how can I conclude it clearly aired?

[00:15:41] Speaker 04:
Court's indulgence, Your Honor, while I find the site.

[00:15:55] Speaker 00:
I do find this paragraph 116 interesting.

[00:15:59] Speaker 00:
Was it, in fact,

[00:16:03] Speaker 00:
presented in front of the judge during the hearing, where... I'm sorry, Judge Shin, I've lost the thread.

[00:16:09] Speaker 04:
What paragraph 116?

[00:16:12] Speaker 00:
The 116, the Metzger Declaration in the Illumina IPR, where you said it, you know, you quoted it was well known by 2008, one could

[00:16:25] Speaker 00:
isolate, amplify, and sequence cell-free genomic DNA and that further goes on as such one of skill would have had a reasonable expectation of success in using cell-free DNA from maternal blood in a multi-step PCR method such as fluid dimes.

[00:16:41] Speaker 00:
So, no.

[00:16:43] Speaker 04:
Yes, Your Honor.

[00:16:44] Speaker 04:
Our expert Van Ness explained

[00:16:46] Speaker 04:
in his declaration explaining the prior art, and the declaration was before the district court and was attached to our opposition to the P.I.

[00:16:54] Speaker 00:
motion.

[00:16:54] Speaker 00:
This isn't in paragraphs 241 to 247 of Van Ness's declaration, so that's why I'm curious to know.

[00:17:01] Speaker 00:
I see we have a slide deck here, but was this particular paragraph from the Metzger Declaration of the Illumina IPR actually walked through in front of the judge during the hearing?

[00:17:20] Speaker 00:
paragraph basically says, Dr. Metzger basically opines that skilled artisan would have a reasonable expectation of success in running cell-free DNA through fluidized PCR scale.

[00:17:36] Speaker 04:
Yes, Your Honor.

[00:17:38] Speaker 04:
And that's part of our argument.

[00:17:40] Speaker 04:
It was our argument to the district court as well that Natara had previously taken

[00:18:03] Speaker 04:
So in Dr. Van Ness, our expert's declaration, which appears at A12101 in paragraph 265, he discusses the Fluidine Patent Application 2010.

[00:18:18] Speaker 04:
It's volume 2, A12101.

[00:18:28] Speaker 02:
This is not the paragraph that you were pointing us to, was it?

[00:19:23] Speaker 04:
So at the end of that paragraph, he also refers back to his previous discussion of Dr. Metzger having previously argued this very reference rendered obvious a large-scale multiplex PCR method, which goes to the

[00:19:59] Speaker 04:
In our brief in the district court, we cite to that paragraph on page.

[00:20:03] Speaker 04:
So it's our district court brief on page 11 of our district court brief at the end of our obviousness discussion.

[00:20:11] Speaker 05:
Any idea where I can find that in the appendix?

[00:20:14] Speaker 04:
It's appendix 10-4-9-0, Your Honor.

[00:20:18] Speaker 05:
Do you know what volume?

[00:20:20] Speaker 04:
Volume 22.

[00:20:21] Speaker 02:
That's only for the number of plexings, as you call it, not for anything else.

[00:20:25] Speaker 02:
That's true.

[00:20:26] Speaker 04:
Yeah.

[00:20:26] Speaker 02:
That paragraph is about the number of plexings, Your Honor.

[00:20:29] Speaker 02:
And that's really the way people talk?

[00:20:31] Speaker 02:
Plexing?

[00:20:37] Speaker 02:
The problem is that the citations in this kind of four paragraph argument are thin and the points made about them are not really expressly explained, so you have to do this

[00:20:53] Speaker 02:
First of all, hunting to what is cited, and now apparently supplementation to what was not cited.

[00:20:59] Speaker 02:
And that's a challenge.

[00:21:01] Speaker 02:
This is what the Fourth Circuit sometimes refers to, a passing shot is not enough.

[00:21:09] Speaker 04:
But again, Your Honor, the parties largely did.

[00:21:12] Speaker 04:
Their brief is also thin on this point, and they relied for their burden on their expert declaration as well.

[00:21:19] Speaker 04:
And when the district court decided it, she cited both their expert

[00:21:22] Speaker 04:
and our experts, she was clearly studying the expert opinions.

[00:21:28] Speaker 04:
These things were attached, like the Fluidigm 2010 application was attached.

[00:21:32] Speaker 02:
Were all of these PowerPoint slides walked through in the way that seems to be common before the patent board?

[00:21:40] Speaker 02:
Or is this, here's a stack and we're going to talk about some of them?

[00:21:43] Speaker 04:
No, the hearing oral argument, which is also in the JA, Your Honor, you can read through the hearing, and you can walk through the slides.

[00:21:51] Speaker 04:
And we did show these slides to the district court.

[00:21:56] Speaker 04:
And we did the presentation with the district court by walking through the slides.

[00:22:01] Speaker 02:
I'm sorry, just to continue.

[00:22:05] Speaker 02:
So you did point to a slide with paragraph 116 of Metzger's IPR.

[00:22:11] Speaker 02:
presentation, is there also a slide with the paragraph of the paradigm application that you want to rely on?

[00:22:21] Speaker 04:
Of the Fluidigm application?

[00:22:23] Speaker 04:
Fluidigm, sorry.

[00:22:24] Speaker 04:
Yeah.

[00:22:27] Speaker 04:
Just a moment.

[00:22:59] Speaker 04:
So I mean.

[00:23:26] Speaker 07:
Do you want to look for it and come back up on rebuttal and address it?

[00:23:28] Speaker 04:
Yes, Your Honor.

[00:23:29] Speaker 07:
How about we move to the public interest?

[00:23:31] Speaker 07:
Because I know you wanted to address that, and I have questions about it.

[00:23:34] Speaker 07:
If there's more you want to say on obviousness, please do.

[00:23:37] Speaker 04:
Well, the 2010 Fluidigm application is not the only evidence in the record, nor the only evidence pointing to the district court that shows that Natarra previously has taken the position that it's routine and conventional to apply these types of cell-free

[00:23:55] Speaker 04:
processing steps.

[00:23:55] Speaker 04:
And again, the claims are just basic, selfie-processing steps to sell free DNA.

[00:24:02] Speaker 04:
And the terror has twice convinced this court that it was routine and conventional to do so.

[00:24:09] Speaker 04:
And so the notion, and at this point, too, our burden is only to show that there is a substantial question of obviousness, not to actually finally prove it.

[00:24:18] Speaker 04:
So even if you believe it's not

[00:24:21] Speaker 04:
completely certain whether we will win.

[00:24:23] Speaker 04:
That isn't the standard.

[00:24:24] Speaker 07:
The problem you have is, at this point, your burden is actually to prove the district court clearly erred in the fact findings on motivation can success and reasonable expectation of motivation combined with reasonable expectation of success.

[00:24:35] Speaker 07:
That's your burden.

[00:24:36] Speaker 07:
The burden you're articulating about substantial question or vulnerability, that's the overall burden.

[00:24:41] Speaker 07:
But the district court found specific facts wanting.

[00:24:46] Speaker 07:
And that's how it came to its conclusion.

[00:24:48] Speaker 04:
I do think at some level, Your Honor, it is a legal question, like under Amazon.com.

[00:24:55] Speaker 04:
At some level, even accepting her findings, given the strength of this record, there is a substantial question of obviousness.

[00:25:02] Speaker 04:
But even taking Your Honor's framework, that it is a clear error standard, all the district court found is that there were obstacles.

[00:25:09] Speaker 04:
But the evidence overwhelmingly shows, including admissions from Natara,

[00:25:14] Speaker 04:
that those obstacles, whatever they were, were not deterring other people from doing it.

[00:25:20] Speaker 04:
And in fact, the Foreshoe 2012 publication that they point to as evidence of Radar's infringement of their claims is evidence of contemporaneous independent invention that... I was sort of struck by that.

[00:25:40] Speaker 02:
When I read, to the extent I could

[00:25:43] Speaker 02:
understand which I'm sure is not a hundred percent I took away from that that um Horseshoe and company thought they had done made a really significant advance made me think hmm maybe this is actually helping the other side and then I was wondering when is the last time we gave weight as a secondary consideration

[00:26:11] Speaker 02:
against obviousness to this contemporaneous invention.

[00:26:19] Speaker 04:
I'm not sure when it is.

[00:26:21] Speaker 04:
So, I mean, the case we rely on is a Supreme Court case, which suggests that it's relevant to obviousness that somebody independently, even assuming what they've done is an invention, that somebody independently invented it roughly around the same time.

[00:26:33] Speaker 02:
But there are at least two, I don't know, problems that I've thought about over time.

[00:26:40] Speaker 02:
Um, one is that somebody might not be an ordinarily skilled artisan might be a super artisan or something.

[00:26:47] Speaker 07:
Yeah.

[00:26:48] Speaker 02:
And, and second, it's really hard at least has been for me over the years to square this notion with the patent laws, um, encouragement of patent races with extremely precise priority dates.

[00:27:04] Speaker 02:
Um, so this seems to me like it's a bit of an uphill legal battle to, um, make, uh, for sure.

[00:27:13] Speaker 02:
For sure.

[00:27:13] Speaker 02:
Is it for sure.

[00:27:14] Speaker 02:
So I can assistant for you.

[00:27:18] Speaker 04:
So, well, Dr. For sure.

[00:27:20] Speaker 04:
Uh, is the innovative, one of the innovative co-founders, which is, uh, now a subsidiary of our client.

[00:27:25] Speaker 04:
And it does show that there was independent invention, because the article was accepted for publication before they even filed their patent, which they didn't file until after our product had been published.

[00:27:34] Speaker 07:
That article expressly also acknowledges the fragmentation and the low yield of CFDNA.

[00:27:39] Speaker 07:
The article itself, while it may offer a form of independent invention, does so by articulating the framework of how difficult it was to come to the conclusion that the CFDNA could be used that way.

[00:27:51] Speaker 04:
But the prior art shows that that difficulty, Your Honor, not only that, the other Fluidigm 2010 and the other, the Natara admissions and CARE-DX and Illumina show that those obstacles, whatever they are, were not deterring persons of skill in the art from applying these basic DNA processing methods to cell-free DNA.

[00:28:12] Speaker 04:
Nothing in these claims

[00:28:14] Speaker 04:
claims any kind of overcoming of those obstacles.

[00:28:17] Speaker 04:
So these claims are just basic DNA processing step claims.

[00:28:20] Speaker 04:
They don't claim anything that they did to overcome these obstacles.

[00:28:23] Speaker 07:
Would you like to move on?

[00:28:24] Speaker 07:
You wanted to talk about public interest, and I actually want to hear that argument.

[00:28:29] Speaker 07:
So can you move on to that at this point?

[00:28:31] Speaker 04:
I can, Your Honor.

[00:28:36] Speaker 04:
OK, so I'll just give you one site.

[00:28:38] Speaker 04:
The slide to fluid diamond massacre, where we talked to the district court about the Illumina decoration, that was a 21127.

[00:28:46] Speaker 04:
So yes, Your Honor, I would like to talk about public interest, because here.

[00:28:50] Speaker 04:
21127?

[00:28:51] Speaker 04:
21127.

[00:28:51] Speaker 04:
21127.

[00:28:53] Speaker 00:
In volume four.

[00:28:57] Speaker 00:
Oh, that's the slide itself that we've already been looking at.

[00:29:02] Speaker 00:
Yes, I'm sorry.

[00:29:03] Speaker 04:
The slide has a citation to where it was argued.

[00:29:07] Speaker 00:
Oh, we have a copy of the transcript, right?

[00:29:11] Speaker 04:
The transcript is in the JA, Your Honor.

[00:29:13] Speaker 04:
Yes, the transcript.

[00:29:14] Speaker 00:
So I thought you were citing to me something in the transcript that was discussing this particular slide.

[00:29:20] Speaker 00:
Oh, I'm sorry.

[00:29:20] Speaker 00:
I'll find that on your body.

[00:29:22] Speaker 02:
I'm sorry.

[00:29:23] Speaker 02:
Yes, Your Honor.

[00:29:25] Speaker 02:
So 21127 shows paragraph 116 of Metzger's IPR declaration.

[00:29:32] Speaker 02:
That's not the Fluidigm application, is it?

[00:29:41] Speaker 04:
In Metzger's Illumina Declaration, which is in Volume 3 at A13.

[00:29:51] Speaker 07:
No, no.

[00:29:52] Speaker 07:
This is the slide you presented to the district court.

[00:29:53] Speaker 07:
So tell us what's on this slide.

[00:29:55] Speaker 07:
All right.

[00:29:56] Speaker 07:
Is it on this slide?

[00:29:58] Speaker 07:
Because I'm not going to go hunting and pecking for more stuff that wasn't before the district court.

[00:30:17] Speaker 04:
So the Illumina Declaration is a declaration, Dr. Metzger.

[00:30:21] Speaker 04:
There are experts submitted in support of obviousness.

[00:30:32] Speaker 04:
So the one early approach, like the last sentence, one early approach was to isolate nucleic fetal cells from maternal blood, though because of the rarity of the blood.

[00:30:42] Speaker 06:
I'm sorry.

[00:30:43] Speaker 06:
Are you on the wrong page?

[00:30:44] Speaker 04:
Oh, I'm on the wrong page.

[00:30:46] Speaker 04:
So in the middle of the slide on 127, cell-free genome DNA from maternal blood had also previously been successfully amplified and sequenced.

[00:31:01] Speaker 04:
And the topic sentence of this paragraph is it was further well known by 2008 that one could isolate, amplify, and sequence cell-free genomic DNA.

[00:31:11] Speaker 04:
And the yellow highlighting was the yellow highlighting on this slide.

[00:31:14] Speaker 07:
But just to be clear, and she could be wrong, but my clerk says none of the exhibits cited on this page are to the Fluidine Patent Application.

[00:31:21] Speaker 07:
Can you contradict that?

[00:31:25] Speaker 04:
On this page, you know, that's correct, Your Honor.

[00:31:27] Speaker 04:
This is a site to...

[00:31:29] Speaker 04:
This is more support, different support.

[00:31:31] Speaker 04:
Cite to Dr. Metzger, they're experts.

[00:31:35] Speaker 07:
But he cites exhibit 1006, exhibit 1005.

[00:31:40] Speaker 07:
Even that sentence you just read is exciting to exhibit 1006 abstract and exhibit 1013 abstract.

[00:31:48] Speaker 07:
And so I have no idea what those are, but my law clerk just suggested that her review would show that none of them are the Fluidine patent application.

[00:31:57] Speaker 07:
And is there a reason to think that's inaccurate?

[00:32:01] Speaker 04:
No, but I don't know whether that's accurate or not.

[00:32:04] Speaker 04:
I don't have any reason to believe it isn't.

[00:32:05] Speaker 04:
But that's not our point on these pages.

[00:32:07] Speaker 04:
This is a separate piece of admission by them.

[00:32:10] Speaker 04:
So just to take a step back, our obviousness case is that CAPER discloses all of the steps and that it was known in the art to apply those steps to cell-free DNA.

[00:32:23] Speaker 04:
and as this court has held in lots of context.

[00:32:26] Speaker 07:
I thought, and maybe I'm wrong, maybe I misunderstood.

[00:32:28] Speaker 07:
I thought Judge Chen had asked you where you cited the fluid iron patent application to the district court.

[00:32:35] Speaker 07:
I thought you pointed us to this page.

[00:32:37] Speaker 07:
I thought you were walking through this as part of that same discussion.

[00:32:41] Speaker 07:
I guess I'm wrong and I'm off base.

[00:32:44] Speaker 07:
And so that's what I was trying, when you said C, it says self-radiated.

[00:32:48] Speaker 07:
I thought you were saying, oh, and that is a reference to the Fluidine patent application.

[00:32:52] Speaker 04:
I'm sorry, Your Honor.

[00:32:53] Speaker 04:
This is why I'm confused.

[00:32:54] Speaker 04:
I thought I was answering a question, a different question from Judge Shen, which is, was the Illumina declaration that Dr. Metzger filed in the Illumina IPR presented to the district court?

[00:33:03] Speaker 04:
So we have multiple different places where Natara has conceded that it is routine and conventional

[00:33:09] Speaker 04:
And this Illumina Declaration is one of them where their expert has said it is routine and conventional well before the priority date.

[00:33:16] Speaker 04:
This was an obvious in this case as well, not a 101 case, this PTAB case.

[00:33:22] Speaker 04:
So this is a declaration from their expert in a previous case conceding it was well-known and routine.

[00:33:29] Speaker 04:
And this declaration is talking about fluid on, Your Honor.

[00:33:37] Speaker 07:
Can you please move on to the public interest?

[00:33:40] Speaker 07:
May I add one?

[00:33:42] Speaker 07:
No.

[00:33:43] Speaker 04:
I want to correct something I said to you, Your Honor, which is this declaration is talking about the Fluidigm 2010 Declaration.

[00:33:49] Speaker 04:
So the sites are to a different case.

[00:33:52] Speaker 04:
This is a previous declaration.

[00:33:54] Speaker 07:
This declaration is talking about it.

[00:33:56] Speaker 07:
What you presented to the district court is a single portion of a paragraph from the declaration, and none of the sites

[00:34:03] Speaker 07:
in that to the Fluidine patent application, is that correct?

[00:34:06] Speaker 04:
No, Your Honor, that's not correct.

[00:34:08] Speaker 04:
These are our hearing slides.

[00:34:09] Speaker 04:
These are just PowerPoint slides that were put up.

[00:34:12] Speaker 04:
Dr. Van Ness's declaration includes talking about Dr. Metzger's Illumina Declaration.

[00:34:17] Speaker 04:
It includes the entire Fluidine 42.

[00:34:19] Speaker 07:
But none of those are in the Building 4 paragraphs.

[00:34:21] Speaker 07:
Just move on to public interest, please.

[00:34:23] Speaker 04:
Yes, Your Honor.

[00:34:24] Speaker 04:
So there's significant patient interest here.

[00:34:29] Speaker 04:
They have not disputed that our tests

[00:34:34] Speaker 04:
can be used for cancers that their tests cannot.

[00:34:37] Speaker 07:
The district court expressly held that that was not accurate or had not been established in terms of clinical validity.

[00:34:46] Speaker 07:
Is that correct in the denial of the stay?

[00:34:48] Speaker 07:
I don't know what page it's on.

[00:34:50] Speaker 04:
No, Your Honor.

[00:34:51] Speaker 04:
The district court in denying the stay was talking about our claims of sensitivity, which Natera does dispute.

[00:34:57] Speaker 04:
So the district court said, and I think what you're referencing is the district court

[00:35:01] Speaker 04:
Comments in the state denial that the evidence was not at all clear that our test was more sensitive than their test But it was that the district court was not sorry.

[00:35:12] Speaker 07:
Let's read it.

[00:35:12] Speaker 07:
Let's it's on page 21 3 2 5 and 21 3 2 6 you have it I will Start at the bottom of 21 3 2 5 when you have it.

[00:35:25] Speaker 07:
Let me know alright.

[00:35:26] Speaker 04:
Thank you

[00:35:39] Speaker 04:
I'm with you, Your Honor.

[00:35:41] Speaker 07:
21325, neogenomics contends that radar has a higher sensitivity than the Natera's product and allows it to better detect cancer at early stages.

[00:35:49] Speaker 07:
At that point, it is disputed and not at all clear that this is so.

[00:35:53] Speaker 07:
Here's a more important one.

[00:35:54] Speaker 07:
NOR has neogenomics submitted satisfactory evidence that its radar test is available for cancers for which Natera's product is not available.

[00:36:03] Speaker 07:
So that looks like it is, in fact, a fact-finding that I said he made that you said he did not make, and he only made a fact-finding, or she only made a fact-finding with regard to sensitivity.

[00:36:11] Speaker 04:
I agree.

[00:36:12] Speaker 04:
That question goes to the point I was making.

[00:36:14] Speaker 04:
So I think corrected on that, Your Honor.

[00:36:19] Speaker 04:
But this is not the PI ruling.

[00:36:21] Speaker 04:
This is her state denial.

[00:36:23] Speaker 04:
Yes, this is her state denial.

[00:36:24] Speaker 04:
This is her state denial.

[00:36:25] Speaker 04:
In the PI ruling, she made no such fact.

[00:36:27] Speaker 04:
And to the extent that is a factual assertion, it's clearly

[00:36:31] Speaker 04:
erroneous.

[00:36:31] Speaker 04:
The record does show, and our expert, I mean our, we have an executive affidavit from our company saying that our tests can be used for cancers that their tests cannot, including blood cancers.

[00:36:46] Speaker 07:
Vishal Sakri is the name of the person.

[00:36:49] Speaker 07:
I've read it in detail.

[00:36:50] Speaker 07:
He has 20 years of experience in oncology and he is now the president of one of your company's divisions.

[00:36:57] Speaker 07:
So I certainly read his testimony very closely.

[00:37:00] Speaker 07:
But he asserts that yours is more sensitive and also can be used for different kinds of cancer, potentially.

[00:37:13] Speaker 07:
But I can't find any evidence to support that.

[00:37:18] Speaker 07:
I can't find any evidence at all anywhere that says that your test, for example, has received FDA approval or is otherwise available to be used to treat any kind of cancer

[00:37:30] Speaker 07:
that their product cannot be used for.

[00:37:32] Speaker 07:
So if I'm mistaken I would love for you to walk me through it because I will tell you I made my poor clerk spend her entire weekend trying to figure out if there was evidence about which kinds of cancer yours could be used for or was approved to be used for and which kinds of cancers theirs could be used for or was approved to be used for.

[00:37:51] Speaker 07:
Because this was a very confusing case and there are a lot of

[00:37:55] Speaker 07:
conclusory assertions about things like this, but I'm really interested in finding the evidence.

[00:38:01] Speaker 04:
So it's important to make a framing point, Your Honor, which is there's two ways, as their expert acknowledges, there's two different ways that products like this are used.

[00:38:12] Speaker 04:
And one is by pharmaceutical partnerships for research, and the other is clinicians' use.

[00:38:19] Speaker 04:
And so here the district court did find that the two were clinically validated for

[00:38:23] Speaker 04:
the same cancers, but that's for commercial use in the clinical setting.

[00:38:27] Speaker 07:
For patients.

[00:38:28] Speaker 07:
So for patients, wait, I just want to make sure I understand this.

[00:38:31] Speaker 07:
So from a public interest standpoint, it's not the case that your test is available for use for patients for different forms of cancer that their tests could not be used for also.

[00:38:44] Speaker 04:
The district court said they were clinically validated for the same uses, but we had evidence, including from two doctors, which is the only two

[00:38:53] Speaker 04:
the only evidence in the record of people who have actually used both tests saying that ours was more sensitive and would be better for certain kinds of cancer.

[00:39:01] Speaker 07:
So Dr. Beisch... What do you mean with two doctors who said this?

[00:39:03] Speaker 07:
Where is the evidence?

[00:39:05] Speaker 04:
Dr. Beisch wrote a letter.

[00:39:06] Speaker 04:
It's volume 2A.

[00:39:08] Speaker 07:
Who are you talking about?

[00:39:09] Speaker 04:
His name is Dr. Beisch.

[00:39:11] Speaker 04:
B-E-I-T-S-C-H.

[00:39:13] Speaker 07:
Did you cite this in your brief to us?

[00:39:15] Speaker 04:
Yes, Your Honor.

[00:39:16] Speaker 07:
Okay.

[00:39:16] Speaker 07:
Where in your brief?

[00:39:17] Speaker 07:
Because I want to see where the argument is made.

[00:39:34] Speaker 07:
I think this argument is around pages 49-ish of your blue brief, if that helps.

[00:39:39] Speaker 04:
Yes, thank you.

[00:39:48] Speaker 07:
And are you talking about the blood and bone marrow cancers?

[00:39:51] Speaker 04:
No, so the blood and bone marrow cancers are the kinds of cancers that are

[00:39:58] Speaker 04:
executive explained, the one that you looked at, explained that it can be used for.

[00:40:02] Speaker 04:
And he does discuss, so just to go back to your first question, at volume 2A11283, in paragraphs 35 and 36, he discusses a radar trial

[00:40:12] Speaker 04:
for one of those kinds of cancers.

[00:40:14] Speaker 04:
So wait.

[00:40:15] Speaker 07:
I knew you were going to get this.

[00:40:16] Speaker 07:
Let me just make it.

[00:40:17] Speaker 07:
I want to make sure you know that I understand where you're going.

[00:40:20] Speaker 07:
So wait.

[00:40:21] Speaker 07:
So there's two types of public interest here.

[00:40:23] Speaker 07:
Public interest number one is actually treating real patients who have tumors and want to detect if they're coming back.

[00:40:30] Speaker 07:
And that's what I'm trying to get you to focus on.

[00:40:32] Speaker 07:
I know there's a separate public interest.

[00:40:34] Speaker 07:
And I promise you we will get to it.

[00:40:35] Speaker 07:
And the second public interest is clinical trials that further advance the utilization

[00:40:41] Speaker 07:
of these tools.

[00:40:43] Speaker 07:
And so please understand that I know that those both exist, but I'm trying to understand what evidence there is in bucket number one, which is actual patient use.

[00:40:55] Speaker 07:
Are there patients being deprived of using a test that Natera's test is not a substitute for?

[00:41:02] Speaker 04:
So the blue brief at page 50, like in the paragraph asserts other evidence is similarly compelling,

[00:41:11] Speaker 04:
the likewise sentence.

[00:41:12] Speaker 04:
Likewise, a prominent oncologist familiar with both Radar and Signatera attested by letter that Radar's established high sensitivity is important for studying some cancers, including melanoma and certain breast cancers.

[00:41:24] Speaker 04:
And that's the site to his letter.

[00:41:27] Speaker 06:
And in his letter... Where can I find this letter?

[00:41:30] Speaker 04:
It's in volume two.

[00:41:31] Speaker 04:
It's A11264 and 65.

[00:41:37] Speaker 07:
Well you cite 11265, so should I go there maybe?

[00:41:42] Speaker 04:
It's a two-page letter.

[00:41:44] Speaker 04:
And he also talks about there how he uses it with patients and he finds it more valuable.

[00:41:50] Speaker 04:
And that's the patient harm choice, Your Honor.

[00:41:58] Speaker 07:
Now, with all due respect, choice is not a harm if the two things are equal.

[00:42:02] Speaker 04:
Well this letter says that they are not, and then this

[00:42:10] Speaker 07:
What, this is, with all due respect, what, I don't understand.

[00:42:19] Speaker 07:
How has he established that one is more sensitive than the other?

[00:42:22] Speaker 07:
This is just a letter.

[00:42:24] Speaker 07:
Like, this is like, hey, I found something more sensitive than something else.

[00:42:28] Speaker 07:
What?

[00:42:29] Speaker 04:
He's saying he prefers to use it for certain types of cancers.

[00:42:33] Speaker 04:
Why?

[00:42:33] Speaker 04:
It's the best kind of... Why?

[00:42:35] Speaker 04:
Hang on, I haven't caught up with you.

[00:42:51] Speaker 00:
Yes, he says at the top of 11.265.

[00:42:56] Speaker 04:
Radar is more sensitive than signetera to detect circulating tumor DNA.

[00:43:01] Speaker 04:
levels because of its established analytical sensitivity, especially in low shedding cancer such as melanoma.

[00:43:06] Speaker 07:
This is a guy who just says it.

[00:43:08] Speaker 07:
Where is the proof?

[00:43:10] Speaker 07:
How would he know it's more sensitive?

[00:43:12] Speaker 07:
He's a doctor.

[00:43:14] Speaker 07:
He's not a researcher who has done a study that showed one compared to the other, some head-to-head study.

[00:43:20] Speaker 07:
Look, there's evidence in this record that your client's been out there telling people, yours is more sensitive than theirs.

[00:43:26] Speaker 07:
Maybe that's how he heard it.

[00:43:28] Speaker 04:
He explains how he knows this.

[00:43:32] Speaker 04:
This is the best possible evidence, somebody who actually uses it with patients.

[00:43:36] Speaker 04:
In my current practice treating patients with breast cancer and melanoma, I use MRD assays for cancer monitoring and routinely used tumor MRD.

[00:43:44] Speaker 04:
They have no evidence, Your Honor, no head-to-head studies that it's not more sensitive.

[00:43:49] Speaker 04:
And we have the only evidence in the record of somebody who actually uses both

[00:43:53] Speaker 04:
and says that ours can be used for some things or better for some things than theirs is.

[00:44:01] Speaker 04:
And on a preliminary record, it's in the public interest to call any doubt in favor of patient choice.

[00:44:09] Speaker 04:
The question is whether we should really unlock it.

[00:44:11] Speaker 07:
No, it's not patient choice.

[00:44:13] Speaker 07:
It's only patient choice in light of an existing patent if there's a likelihood of success if there is a benefit to one.

[00:44:20] Speaker 07:
for that patient over the other.

[00:44:22] Speaker 07:
And so that's what I'm trying to get at.

[00:44:24] Speaker 04:
Is there a benefit?

[00:44:24] Speaker 04:
And I'm trying to figure it out.

[00:44:26] Speaker 04:
And this doctor says there is a benefit to using it with certain kinds of low shedding cancers such as melanoma and certain breast cancers.

[00:44:33] Speaker 04:
And this higher sensitivity is important.

[00:44:35] Speaker 07:
But the problem is he hasn't shown that there's a higher sensitivity.

[00:44:40] Speaker 07:
He just says there is one.

[00:44:42] Speaker 07:
How does he know?

[00:44:43] Speaker 07:
A random doctor doesn't know the level of sensitivity of a particular test unless he's hearing about it from someone or performing tests.

[00:44:52] Speaker 04:
He explains the basis for his opinion, Your Honor, in the letter, which is that he uses these tests in his own practice with real patients

[00:45:00] Speaker 04:
and as a surgical oncologist.

[00:45:02] Speaker 07:
If he said, I use their test, and it showed a no result, and then I use the other test, and it showed a yes, and it turns out the answer was yes, so their test is clearly more sensitive than the other guy's test.

[00:45:14] Speaker 07:
He doesn't say anything like this.

[00:45:17] Speaker 07:
Okay, keep going.

[00:45:19] Speaker 04:
So the second thing we cited is a

[00:45:24] Speaker 04:
A presentation from a key opinion leader, and this is also on page 50 of our Bluebeef, reporting positive results from using radar for certain cancer patients while advising against using Signetera for them.

[00:45:34] Speaker 04:
This is at appendix 11-692.

[00:45:36] Speaker 04:
And this is a presentation at a conference, I believe.

[00:45:49] Speaker 02:
By whom?

[00:45:53] Speaker 02:
By the German Breast Group.

[00:45:54] Speaker 04:
By Dr. Turner, who's... I believe.

[00:46:24] Speaker 04:
Yeah, Nicholas Turner on the first page, Your Honor, 11679.

[00:46:27] Speaker 07:
And 11692, I'm sorry, what did you want me to take away from this?

[00:46:39] Speaker 04:
That this is a presentation by doctors who've used both tasks, who are recommending using radar because it's more sensitive than semitera.

[00:46:46] Speaker 07:
Where does it, I'm sorry.

[00:46:47] Speaker 04:
I meant 11692, Your Honor.

[00:46:49] Speaker 07:
11692, where does it say anything about radar?

[00:46:52] Speaker 07:
I'm probably missing something.

[00:46:57] Speaker 04:
The last bullet in the conclusions, Your Honor.

[00:47:01] Speaker 07:
Although Signatera analysis has been approved by Medicare, use is not likely appropriate.

[00:47:06] Speaker 04:
Yes.

[00:47:07] Speaker 07:
I understand.

[00:47:08] Speaker 07:
How does that compare?

[00:47:12] Speaker 04:
The whole thing is about using radar, Your Honor.

[00:47:17] Speaker 04:
The point of it is that

[00:47:20] Speaker 04:
the study reported using positive results from our tests and recommended for certain cancer patients and recommended against using their tests.

[00:47:28] Speaker 04:
And the point to your point about patient choice.

[00:47:31] Speaker 07:
Where does it say?

[00:47:32] Speaker 07:
I'm missing this.

[00:47:33] Speaker 07:
I don't even see the word radar on this slide.

[00:47:35] Speaker 07:
I don't see that it says.

[00:47:38] Speaker 07:
It's not on this slide.

[00:47:39] Speaker 07:
Does it say somewhere that stigmataire is bad at this but radar is good at it?

[00:47:45] Speaker 07:
I'm all about patient choice.

[00:47:47] Speaker 07:
If it's going to make a difference, I mean, even just one person, you got me.

[00:47:51] Speaker 07:
But I just don't, I'm not finding the evidence here of that.

[00:47:56] Speaker 04:
But so, Your Honor, the burden is on them to show that it won't make a difference.

[00:48:00] Speaker 04:
It's in the district court statement.

[00:48:01] Speaker 07:
No, no.

[00:48:02] Speaker 07:
The burden is on them to show public interest.

[00:48:05] Speaker 07:
And public interest weighs heavily in favor of enforcement of intellectual property rights if all things are otherwise equal.

[00:48:10] Speaker 07:
Now, you have responded that things are not equal.

[00:48:13] Speaker 07:
Our test is better than theirs, and we have proof.

[00:48:16] Speaker 07:
And so I'm trying to find that proof.

[00:48:18] Speaker 02:
OK.

[00:48:19] Speaker 02:
I'm looking at, I guess, 11.685, which at least has radar up on the top.

[00:48:28] Speaker 02:
Not quite the heading, but the sun heading.

[00:48:31] Speaker 02:
Can you explain what's going on here?

[00:48:37] Speaker 00:
Sorry, what page are we on?

[00:48:38] Speaker 02:
11685.

[00:48:39] Speaker 04:
So this is this explaining that this study was used during using radar and the descendants that that Judge Shonto has pointed out 11685.

[00:48:53] Speaker 02:
But the conclusion that you pointed to this bottom paragraph on 11692, how does that reflect if it does a comparison between the Signatera that's mentioned and the radar that isn't?

[00:49:08] Speaker 04:
Because this whole report, Your Honor, is the result of a study using radar.

[00:49:12] Speaker 04:
That's the sentence that you pointed out.

[00:49:26] Speaker 07:
OK.

[00:49:26] Speaker 07:
I told you before I knew that there were two buckets for public interest.

[00:49:30] Speaker 07:
Do you want to move to the second bucket now, which is that bucket of clinical use for a study?

[00:49:36] Speaker 04:
Yes, Your Honor.

[00:49:37] Speaker 04:
The research.

[00:49:38] Speaker 04:
And I think it's significant two points.

[00:49:42] Speaker 04:
One is radar has been on the market for clinical use since 2020.

[00:49:47] Speaker 04:
And they waited, and this is a point that goes to both issues, they waited seven months from the time their complaint was filed to sue on their patent.

[00:49:58] Speaker 04:
And this court has held that that length of delay, seven months.

[00:50:02] Speaker 02:
So why isn't it relevant that they filed?

[00:50:06] Speaker 02:
I think literally within a handful of days of the Medicare approval, which was going to make a difference in the effect on them from small and not nothing to worry about to potentially big and something to worry about.

[00:50:20] Speaker 04:
Because most of the harm that they point to and also that the district court relied on your honor was about their supposed irreparable harm from partnerships that they had lost.

[00:50:29] Speaker 04:
yet we'd been on the market since 2020 for clinical partnerships, and yet they didn't sue as soon as the patent issued.

[00:50:37] Speaker 04:
And they didn't even apply for this patent until after we announced our product.

[00:50:41] Speaker 04:
So they waited seven months, which this court has held in Nutrition 21, that it undercuts your claim to irreparable harm a seven-month delay from the time of patent issuance to complaint.

[00:50:55] Speaker 04:
And it's significant, I think, that they filed in Delaware

[00:50:59] Speaker 04:
against Inovato, which is a sub, on the basis of radar, did not assert, in December of 2022, did not assert the 035 patent, even though it had already issued.

[00:51:10] Speaker 04:
And even though they've admitted in this lawsuit that they thought that radar infringed it as of the day that the patent issued.

[00:51:16] Speaker 04:
And they did not seek a preliminary injunction.

[00:51:18] Speaker 04:
Instead, they waited seven months and filed suit in a different court in the District of North Carolina.

[00:51:24] Speaker 04:
and sought this preliminary injunction.

[00:51:26] Speaker 04:
And so that delay is significant.

[00:51:28] Speaker 04:
And the fact that they're really trying to upset the status quo, the Fourth Circuit holds it's a very high burden.

[00:51:34] Speaker 07:
Hold on now.

[00:51:35] Speaker 07:
I think the Fourth Circuit judge did an amazing job of ensuring they would not upset the status quo.

[00:51:41] Speaker 07:
Didn't she multiple times limit the scope of the injunction to ensure

[00:51:48] Speaker 07:
that anyone who was already employing or utilizing your test would be allowed to continue using it in all of the studies that they're doing?

[00:51:56] Speaker 04:
The status quo though that's relevant to this question, Your Honor, is the pre-suit status quo.

[00:52:02] Speaker 04:
And the pre-suit status quo was that

[00:52:04] Speaker 04:
Neogenomics had been on the market for research partnerships since 2020, including for future ones.

[00:52:10] Speaker 07:
You've got to stop saying 2020.

[00:52:11] Speaker 07:
They didn't have a patent in 2020.

[00:52:12] Speaker 07:
Their patent issued long after that.

[00:52:14] Speaker 07:
So you've got to stop saying 2020 as though you're trying to make it sound like they waited four years to sue you.

[00:52:19] Speaker 07:
They couldn't sue you.

[00:52:20] Speaker 07:
They didn't have a patent during a part of that time.

[00:52:21] Speaker 04:
They didn't even apply for the patent until after we announced our... I mean, they didn't apply for the patent until after we publicly announced our product, Your Honor.

[00:52:29] Speaker 04:
So they applied for this patent.

[00:52:30] Speaker 04:
But they still wait seven months to sue, even though they've admitted in their interrogatory answers, which is in the JA, that they believe we infringed on the day.

[00:52:39] Speaker 04:
And that seven-month delay severely undercuts their claim to irreparable harm.

[00:52:44] Speaker 04:
And Judge Strontat, to your question about the Medicare issue, no, both because of what I previously said, but also their own evidence shows that Medicare is not a driver of choice of tests.

[00:52:55] Speaker 04:
So the calendar report says it's like six on the

[00:52:58] Speaker 04:
on the choice and reason people choose things.

[00:53:00] Speaker 04:
So I think that timing is not meaningful.

[00:53:07] Speaker 04:
So to your point, Chief Judge Moore, about protecting patent rights, this court has held that there has to be a causal nexus between the supposed irreparable harm and the claim.

[00:53:17] Speaker 04:
But here, there's nothing in the claims that talks about that there's nothing in the claims that goes to tumor-informed

[00:53:27] Speaker 04:
Yet the demand for our product is driven by its tumor-informed nature.

[00:53:35] Speaker 04:
And the things that we do to make it sensitive and tumor-informed is not related to the patented features.

[00:53:44] Speaker 00:
So we use... The claimed invention is for cell-free DNA, though, right?

[00:53:47] Speaker 00:
So CT DNA is one type of cell-free DNA.

[00:53:55] Speaker 04:
The parties have proceeded on the assumption that CT DNA falls within these claims, but the claims are just a processing cell-free DNA in no specific context, and they're not limited to tumor-informed, yet the district court judge, the only harm it found

[00:54:13] Speaker 04:
was that we would be competing with them in the tumor-informed market, and that we would be the only other competitor.

[00:54:19] Speaker 02:
But why do you think that that matters?

[00:54:22] Speaker 02:
I mean, I take it you don't dispute that.

[00:54:27] Speaker 02:
I think you don't dispute, tell me if you do, that without practice, assuming infringement.

[00:54:34] Speaker 04:
Which we also believe we don't infringe, but we haven't gotten to that.

[00:54:38] Speaker 02:
Assuming infringement.

[00:54:39] Speaker 02:
They couldn't do the tumor-informed one without infringing.

[00:54:45] Speaker 04:
The district court didn't find that, Your Honor.

[00:54:48] Speaker 04:
The district court said, made a finding that it appears we used their technology to come up with our test, but that's, they don't even.

[00:54:57] Speaker 02:
Not to generate the test, but it's just, again, a subset of the inputs into this sequence that is laid out in

[00:55:05] Speaker 02:
in the claim.

[00:55:06] Speaker 04:
So this court has held that just butt four causation in the Apples and B. Samson case, a butt four causation is not enough.

[00:55:13] Speaker 04:
It has to be the

[00:55:14] Speaker 04:
a feature that drives demand for your product.

[00:55:18] Speaker 02:
So you had, I think, one sentence in your opposition to preliminary injunction on this, which cited one paragraph, a secret paragraph, 88.

[00:55:28] Speaker 02:
I did not read that paragraph as saying that whatever this is was a driver of consumer demand, just a description of why secret thought you had certain

[00:55:44] Speaker 02:
qualities to your test.

[00:55:47] Speaker 02:
I don't think there's anything in there about consumer or anything.

[00:55:49] Speaker 04:
Well, what it says is that the reason our product, people purchase our product, is because it's tumor-informed.

[00:56:05] Speaker 04:
I'm not sure it does.

[00:56:07] Speaker 04:
But it's their burden to show that their harm is tied to infringement.

[00:56:14] Speaker 04:
And they didn't separate out their claims to irreparable harm.

[00:56:20] Speaker 04:
Two patents were at issue in the district court, and they didn't separate them out.

[00:56:23] Speaker 04:
And so to the extent that the district court made an error in relying on the tumor informed sort of like should fall on them, not on us.

[00:56:31] Speaker 04:
Because it was their burden to show it.

[00:56:33] Speaker 04:
They didn't make a separate claim for the 035.

[00:56:36] Speaker 04:
a separate irreparable harm showing, like, if you only find on the 035, then here's our irreparable harm.

[00:56:41] Speaker 04:
And the district court picked up on the, well, it's the tumor-informed piece of it that matters.

[00:56:45] Speaker 04:
But this patent doesn't, it's not a feature of this patent, tumor-informed.

[00:56:49] Speaker 04:
And so there's no causal nexus between what they've claimed in this patent, which is just basic DNA processing steps that aren't limited to any context.

[00:56:58] Speaker 07:
But your, unless I'm wrong, your invention can't operate

[00:57:04] Speaker 07:
without performing the claim steps here.

[00:57:08] Speaker 04:
There's no finding to that effect, Your Honor.

[00:57:10] Speaker 00:
Well, let's assume that's the case.

[00:57:12] Speaker 00:
I mean, let's assume that cell tumor or cancer CT DNA is a species of cell-free DNA.

[00:57:25] Speaker 00:
And if that's the case, then why isn't there a causal axis?

[00:57:30] Speaker 04:
Because there's no finding that there's no other way to do it, Your Honor.

[00:57:34] Speaker 04:
The district court focused purely on the harm to having a tumor-informed competitor, but this patent doesn't claim anything about tumor-informed.

[00:57:46] Speaker 00:
But wouldn't it necessarily, if the claim is for a subset of DNA called cell-free DNA, and inside that subset of DNA there's a species of cell-free DNA known as CT DNA, and then it would be claimed, wouldn't it?

[00:58:02] Speaker 04:
So not necessarily, and there's no finding to that effect.

[00:58:05] Speaker 04:
But even if that were true, this court has held, again, in the Apple v. Samsung cases, that but-for causation is not enough.

[00:58:11] Speaker 04:
So just because the battery in your laptop might infringe, the fact that that's not the reason the consumers buy it, and the laptop won't work if it doesn't have a battery, but that doesn't mean you can get an injunction.

[00:58:24] Speaker 00:
I don't know if the facts here are the same as Apple Samsung, where in those cases we were talking about, we were looking at a patented component of some much larger complex device with thousands of components, and here we're talking about

[00:58:42] Speaker 00:
species of cell-free DNA, arguably, that is necessarily encompassed by the recited cell-free DNA in the clay.

[00:58:52] Speaker 00:
It doesn't quite match up.

[00:58:53] Speaker 00:
I mean, your reasoning might ultimately prevail that there's still some kind of

[00:58:58] Speaker 00:
nexus leap you have to make, but you can't just rely on the facts of Apple Samsung.

[00:59:04] Speaker 04:
Well, I think it's the same here.

[00:59:05] Speaker 04:
Natero has never contested that radar doesn't include many features beyond those that they claim infringe, and our evidence shows that we have special biometrics, special proprietary things that we do both before and after these allegedly infringing steps.

[00:59:20] Speaker 04:
that are what make our tests more sensitive and more desirable and is what drives demand for our tests.

[00:59:26] Speaker 07:
As much fun as this is, we are an hour in.

[00:59:28] Speaker 07:
Oh my gosh.

[00:59:30] Speaker 02:
It's a citation question.

[00:59:33] Speaker 02:
So which paragraph of the Fluidigm application were you pointing to as significant?

[00:59:43] Speaker 04:
I would point you to two paragraphs, Judge Toronto, in volume three, paragraph 122.

[00:59:49] Speaker 04:
on A13-097, A13-097-122.

[00:59:55] Speaker 04:
That's the any fluid in blood.

[00:59:57] Speaker 04:
And A13-103, paragraph 176, that shows that it can be used for diagnosing cancer.

[01:00:08] Speaker 07:
Okay.

[01:00:09] Speaker 07:
Let's hear from the opposing counsel.

[01:00:10] Speaker 04:
Thank you, Your Honor.

[01:00:40] Speaker 03:
Thank you, and may it please the court.

[01:00:42] Speaker 03:
The district court committed no error, and certainly no clear error, in finding that NETERA had established a likelihood of success on the merits, and that Neogenomics' obviousness case was not sufficiently substantial to undermine that substantial likelihood.

[01:00:55] Speaker 02:
As far as you know, we haven't given any helpful clarification to what this substantial question standard means.

[01:01:03] Speaker 02:
Is that right?

[01:01:03] Speaker 03:
Well, there's a case called Titan Tire.

[01:01:05] Speaker 03:
I think both eBay and Titan Tire tell you what that substantial question means.

[01:01:10] Speaker 03:
eBay says that our burden is to show a likelihood of success on the merits.

[01:01:13] Speaker 03:
And so something is not a sufficiently substantial question unless it shows that we don't have a likelihood of success on the merits.

[01:01:20] Speaker 03:
And Titan Tire walks through, and it's actually 566 at 1379, talks, walks through the burden of what it means to establish or disprove a substantial question.

[01:01:29] Speaker 03:
And it explains in the end that you've convinced the court that more likely than not, you will be able to prove at trial by clear and convincing evidence that the patent is invalid.

[01:01:36] Speaker 03:
And so substantial question is substantial enough

[01:01:39] Speaker 03:
to defeat the likelihood of success

[01:01:53] Speaker 00:
what we have are different expressions that don't really line up with each other very well.

[01:01:59] Speaker 00:
And so Judge Toronto's question, I think, is fair, is how do we really quantify a substantial question?

[01:02:05] Speaker 00:
I mean, there's, in re-exam practice, substantial new question of patentability.

[01:02:10] Speaker 00:
And substantial new question of patentability is something I think everyone agrees is less than preponderance of evidence of some asserted fact to be true.

[01:02:21] Speaker 03:
Titan Tire walks through that and says, for example, substantial evidence is a very low standard.

[01:02:26] Speaker 03:
And that's what we don't mean by substantial here.

[01:02:29] Speaker 03:
But you couldn't look at substantial question of patentability.

[01:02:32] Speaker 03:
I mean, it's less than something that, in combination with other things or on its own, makes it unlikely that they'll pay that trial.

[01:02:39] Speaker 03:
Because otherwise, you'd have to be overturning eBay.

[01:02:41] Speaker 03:
eBay makes clear that what is the standard?

[01:02:43] Speaker 03:
Likelihood of success on the merits.

[01:02:45] Speaker 03:
What does the other side show?

[01:02:47] Speaker 03:
They show that you're not likely to succeed on the merits.

[01:02:49] Speaker 03:
And so a substantial question has to be substantial enough that we're not likely to prevail.

[01:02:53] Speaker 03:
And I think in the district court, Neogenomics Council agreed, if you turn to page 20269 of the record, they're discussing that substantial question standard.

[01:03:04] Speaker 03:
And the district court asked, so I would not say the patent's invalid.

[01:03:07] Speaker 03:
I would say they have not shown a likelihood of success on validity.

[01:03:09] Speaker 03:
Answer, that's what you would show.

[01:03:11] Speaker 03:
Right.

[01:03:12] Speaker 03:
Not a substantial likelihood of success on the merits.

[01:03:15] Speaker 03:
There's not a substantial question doctrine that departs what eBay standard is.

[01:03:18] Speaker 03:
It's an iteration of eBay that says it's gotta be substantial enough that in combination alone, it means you're not likely to prevail.

[01:03:25] Speaker 03:
But here, turning to merits though, obviousness just requires motivation to combine.

[01:03:30] Speaker 03:
Motivation combined to achieve the claimed invention.

[01:03:34] Speaker 03:
And below, what they relied on was caper.

[01:03:36] Speaker 03:
Caper, which is tumor tissue, whole tumor tissue, essentially pure cancer, not SNPs, not these little tiny single nucleotide variations.

[01:03:46] Speaker 03:
And so what they have to show is that

[01:03:48] Speaker 03:
You multiply, you have a multiple exemplification, so you have 25 to 2,000 SNPs in a single reaction volume, so in this volume.

[01:03:55] Speaker 03:
And then combine that with circulating tumor DNA, CT DNA, which is, you know, this needle in a haystack.

[01:04:02] Speaker 00:
Isn't it true that the entire debate came down to motivation to run CF DNA through this already existing device with a reasonable expectation of success?

[01:04:13] Speaker 03:
No, because I think that the already existing, the Fluidigm access array you're talking about

[01:04:19] Speaker 03:
I didn't understand except for the paragraph in the opening brief, the fluid on access array.

[01:04:26] Speaker 00:
That's the one thing that the district court relied on.

[01:04:30] Speaker 00:
The district court said, I conclude that this would be a very, very difficult thing and very unpredictable thing and it would necessarily need to be done with precision and I'm not convinced that skilled artisan

[01:04:43] Speaker 00:
would believe that it could be done with reasonable precision, and that's why I am not concluding there's a validity issue.

[01:04:51] Speaker 03:
And there's three pieces to that that are really important.

[01:04:54] Speaker 03:
One is the nature of circulating tumor DNA.

[01:04:57] Speaker 03:
It is extraordinarily dilute.

[01:04:58] Speaker 03:
And it's not just extraordinarily dilute.

[01:05:00] Speaker 03:
It's in the sea of CFDNA.

[01:05:03] Speaker 03:
So you can have a tiny cancer tumor, so small that you're not going to detect an image.

[01:05:07] Speaker 00:
The claim is for CFDNA, not CTDNA.

[01:05:10] Speaker 03:
Ah, now it says associated with cancer, the last two words of the claim.

[01:05:15] Speaker 03:
Associated with cancer.

[01:05:16] Speaker 03:
No one really disputed that this was about circulating tumor DNA, because CAPER, their prior art reference, was about tumor DNA, not some cell-free DNA that's not tumor DNA.

[01:05:28] Speaker 03:
So it makes it move over to that.

[01:05:30] Speaker 03:
And it wasn't.

[01:05:31] Speaker 02:
I don't think it's been disputed throughout.

[01:05:33] Speaker 02:
That comes from those last three words.

[01:05:36] Speaker 03:
Yeah, associated with cancer.

[01:05:37] Speaker 03:
And in page 21, 322, the district court is explaining her decision.

[01:05:42] Speaker 03:
And she says, she distinguishes statements about cell-free DNA because, quote, these statements were not discussing circulating tumor DNA.

[01:05:50] Speaker 03:
And circulating tumor DNA is distinct because you might have this little tiny tumor, and it's going to be shutting some DNA.

[01:05:56] Speaker 03:
But the rest of your entire body is shutting cell-free DNA.

[01:06:00] Speaker 03:
So it's the C of CFDNA, and you're looking for that CT DNA.

[01:06:03] Speaker 03:
You're looking for that needle in a haystack.

[01:06:05] Speaker 02:
And on top of that.

[01:06:06] Speaker 02:
So what was missing from either the specifically cited or displayed evidence for, which includes some, you know, concession, argued concession type evidence from Dr. Metzger in the IPR.

[01:06:25] Speaker 02:
Um, and I guess in the care of DX 101, although that wasn't.

[01:06:32] Speaker 03:
So what's always missing, always missing.

[01:06:34] Speaker 03:
Yeah.

[01:06:34] Speaker 03:
What's always missing judge Toronto is to take the things that aren't disclosed in that concession or in that, and that the motivation to combine them with what is disclosed in view of their utter incompatibilities.

[01:06:46] Speaker 03:
And I want to talk about that utter incompatibility because when you have this CTD as a needle in a haystack circulating tumor DNA, you have a huge problem if you try and do what we call multiplex amplification.

[01:06:55] Speaker 03:
more than 25 to 2,000 SNP loci in a single reaction volume.

[01:06:59] Speaker 03:
You're not breaking it up with little pools, like split and pool.

[01:07:02] Speaker 03:
You're going to do it all together.

[01:07:03] Speaker 02:
And that problem you have is... And just to be clear, each of the 48 wells in the Phuodime device is a multi-item reaction chamber.

[01:07:13] Speaker 03:
Right, so... Those are not one SNP per... Yeah, Kaeper discloses that you can use 10 in a single well.

[01:07:21] Speaker 03:
Okay.

[01:07:21] Speaker 03:
But 10 was sort of the outer limit, and we'll explain that sort of

[01:07:25] Speaker 03:
Maybe I should just go to our page.

[01:07:27] Speaker 03:
If you turn to page column 85, line 5, it says, and that's appendix 162 of our panel.

[01:07:35] Speaker 03:
It says, currently performing multiple XPCR reactions of more than 5 to 10 targets presents a major challenge and is often hindered by primer side products such as primer dimers.

[01:07:45] Speaker 07:
Okay, column and line number?

[01:07:47] Speaker 03:
So that's column 85, line 5.

[01:07:50] Speaker 03:
And then in lines, so right now the problem is you create all this junk, and our expert testified about what happens is when you have too many of these different things in a single reaction volume, too many primers, too many targets, you end up getting junk.

[01:08:06] Speaker 03:
You get nonspecific products, various products, Pat once called them mischief products,

[01:08:12] Speaker 03:
junk.

[01:08:12] Speaker 03:
If you look at the transcript, you get all this junk.

[01:08:14] Speaker 00:
So at the bottom of this paragraph in column 85, it says, methods described in the prior art used to multiplex more than 50 or 100 reactions in one reaction volume.

[01:08:27] Speaker 03:
Right, but at that point, he's not talking about the issue of CT DNA, which is the smaller and harder to deal with.

[01:08:34] Speaker 03:
He's talking about things like white caper has.

[01:08:36] Speaker 03:
You've got whole tumor.

[01:08:37] Speaker 03:
You've got these very large pieces which are easy to do.

[01:08:40] Speaker 03:
But when he talks about multiple PCR at the top, I guess it's right before, he's talking about it's particularly useful for small volume, when you have small amounts of DNA.

[01:08:50] Speaker 03:
And then he goes on and he says, okay, you've got the primer dimers and other artifacts.

[01:08:54] Speaker 03:
And then from lines eight to 11, he says, well, that's okay with some things, some types of detection, typically probes is what he's talking about.

[01:09:01] Speaker 03:
And then he continues, lines 11 to 14.

[01:09:04] Speaker 03:
But when using sequencing as a method detection,

[01:09:07] Speaker 03:
The vast majority of sequencing reads would sequence such artifacts and not the desired sequences.

[01:09:12] Speaker 03:
So when you combine up, you have a needle and a haystack, CT and DNA, flooded in a sea of CFGNA.

[01:09:18] Speaker 03:
And then you want to do multiplex amplification.

[01:09:20] Speaker 03:
You get the junk.

[01:09:22] Speaker 07:
Stop.

[01:09:23] Speaker 07:
Page 9 and 10 of the district court's opinion is where it's very cursory, the analysis on this point with regard to obviousness.

[01:09:34] Speaker 07:
And I'm struggling a little bit.

[01:09:36] Speaker 07:
to read into the paragraph starting on nine and spanning 10, this argument you're making about CT DNA.

[01:09:45] Speaker 07:
So try to explain to me how what you're saying now is, in fact, what the district court found in this paragraph.

[01:09:54] Speaker 03:
So I think there's two places you'll look, Your Honor.

[01:09:56] Speaker 03:
First is, in addition to that, she went back at, I think it was Paige,

[01:10:01] Speaker 03:
21322, where she goes back and says, no, no, it's not just CFDNA, CTDNA.

[01:10:05] Speaker 07:
And in those parenthetical... Wait, are you on the page of her opinion?

[01:10:08] Speaker 03:
I've got her opinion.

[01:10:08] Speaker 03:
Yeah.

[01:10:09] Speaker 03:
So on 9 to 10, she's saying... Okay.

[01:10:16] Speaker 03:
She's saying, strictly 200 DNA is just a subset of CFDNA.

[01:10:19] Speaker 03:
It's in lower yields.

[01:10:20] Speaker 03:
So it's this needle in a haystack, right?

[01:10:23] Speaker 03:
And then she talks about

[01:10:24] Speaker 03:
The challenges, the next one is CFDNA and others, presented obstacles to successfully amplifying and sequencing CTDNA with precision... I can't follow you.

[01:10:32] Speaker 07:
You're going too fast.

[01:10:33] Speaker 03:
Oh, I'm sorry.

[01:10:34] Speaker 03:
Page 10.

[01:10:36] Speaker 03:
Top of the page.

[01:10:38] Speaker 03:
These challenges, associated with CFDNA and others,

[01:10:41] Speaker 03:
presented obstacles to successfully amplifying and sequencing CT DNA with precision during the relevant period.

[01:10:48] Speaker 03:
Right.

[01:10:48] Speaker 07:
So what I understand that to mean is the problems that she's observed with cell-free DNA create problems using cell tumor DNA.

[01:10:59] Speaker 07:
Is that what CT stands for, cell tumor?

[01:11:02] Speaker 03:
Circulating tumor.

[01:11:02] Speaker 07:
Circulating tumor DNA.

[01:11:04] Speaker 03:
All right, and the reason for that is, and when she says with precision, she is talking about the testimony from our expert, and he was testified live at the hearing and was subject to cross-examination about what happens when you try and do too much amplification of too many products in one volume at a time.

[01:11:22] Speaker 03:
You get the junk, the primer dimers, the nonspecific products.

[01:11:25] Speaker 03:
these things that interfere with sequencing.

[01:11:27] Speaker 03:
Well, she didn't cite that, did she?

[01:11:28] Speaker 03:
No, she didn't, but she just needs evidence in the record.

[01:11:32] Speaker 07:
So she used the word precision, and now you're telling me I should assume that because she used the word precision that that was her making a finding based on something your expert said that she didn't cite, and it's probably buried in 15 volumes of stuff?

[01:11:45] Speaker 07:
Don't do the needle in the haystack thing to me.

[01:11:48] Speaker 03:
It's not a needle in the haystack, Your Honor, because I would encourage the court just to sit down and read his testimony at the hearing, because his testimony was all about junk.

[01:11:58] Speaker 03:
getting too much junk if you try and amplify too many things in a single reaction volume.

[01:12:03] Speaker 07:
Did she cite his testimony anywhere in this obviously?

[01:12:06] Speaker 03:
No, because she said that she was going to point to the written testimony as opposed to the oral testimony.

[01:12:12] Speaker 00:
But she seems to be relying on Volic.

[01:12:15] Speaker 00:
And Volic is really just talking about cell-free DNA and how there are formidable challenges with cell-free DNA.

[01:12:23] Speaker 03:
And those format when you have even more dilute

[01:12:25] Speaker 03:
circulating in tumor DNA, those challenges become multiplied many-fold.

[01:12:30] Speaker 03:
And so that, I think, is why that's a huge difference, and the patent it's here is about.

[01:12:33] Speaker 00:
Why didn't, you know, the question I have in my mind is, why didn't the district court even address the evidence that the other side did present?

[01:12:45] Speaker 00:
Like, for example, the low reference or the Cantor reference.

[01:12:47] Speaker 00:
I mean, doesn't Cantor even talk specifically about cancer cells?

[01:12:53] Speaker 00:
Yeah, but those actually... You know, here at Cantor, the invention of... This is at JA 13150, paragraph 15.

[01:13:03] Speaker 00:
The invention is also useful in detection of tumor-derived DNA mutations isolated from cells in the plasma of a cancer patient, and detecting donor-derived DNA in the plasma of a transplant recipient.

[01:13:18] Speaker 00:
This seems to be talking about

[01:13:22] Speaker 00:
And then at JA13156 is also talking about circulating tumor-specific nucleic acids in a blood, urine, or stool sample.

[01:13:33] Speaker 03:
Right.

[01:13:33] Speaker 03:
And those would be cited because of the problem and what our expert testified about.

[01:13:37] Speaker 00:
Right now I'm just trying to figure out why didn't the district court address some of these things.

[01:13:43] Speaker 03:
That Van Ness did cite to and even quote things from Cantor, things from Lowe, things from... I think it's because they're not relevant to the combination that you have to have here because you can't combine those because I'm not talking about that multiplex amplification that creates all the junk.

[01:14:03] Speaker 03:
And what I point the court to is

[01:14:04] Speaker 03:
where our expert testifies, and this is Appendix 20183, and he explains, performing multiplex PCR, and he's talking about, you've got your 25 to 2,000 SNPs in a single reaction volume, it's all there, created a lot of, I'll just call it junk, things you would not want to amplify.

[01:14:20] Speaker 03:
And then he describes why that interferes with sequencing.

[01:14:23] Speaker 03:
He says, when I scoop in, so you're taking all this amplified product and scooping it

[01:14:28] Speaker 03:
Chances are I'll get some wild type, but I'll also get some junk.

[01:14:31] Speaker 03:
And if I take a bigger scoop, I may not even get the molecule I'm interested in, the CTDNA, because I'm just sequencing more junk.

[01:14:39] Speaker 03:
And this was known in the art.

[01:14:42] Speaker 03:
This is the testimony that the district court and the district court understood.

[01:14:45] Speaker 03:
And our patent also explains that that's true, because it says, for example, column 47, lines

[01:14:53] Speaker 03:
to 49 is talking about artifacts, primer dimers, things that interfere with detecting the targeted applicants.

[01:15:00] Speaker 00:
We're going to limit the other side to only the pieces of evidence that they presented to the district court for purposes of this P.I.

[01:15:09] Speaker 00:
motion.

[01:15:09] Speaker 00:
I think we would have to do the same thing for your side and limit ourselves to the things that were actually briefed and that the district court ended up relying on.

[01:15:21] Speaker 03:
I think that's entirely fair.

[01:15:23] Speaker 03:
What's good for the goose is good for the gander.

[01:15:24] Speaker 03:
But our goose testified at the hearing, and he specified that you get this junk, and that junk interferes with sequencing.

[01:15:32] Speaker 03:
And that's backed up by the very thing that the court had before, which is the trial.

[01:15:36] Speaker 07:
But she didn't rely on that.

[01:15:38] Speaker 07:
She didn't rely on that.

[01:15:39] Speaker 03:
Yeah, and she also has a footnote that says, the fact that I didn't cite everything or all the evidence doesn't mean I didn't consider it all.

[01:15:44] Speaker 07:
Yes, but there's a difference between considering it and relying on it.

[01:15:49] Speaker 07:
I consider a lot of things.

[01:15:51] Speaker 07:
I rely on very few.

[01:15:52] Speaker 03:
The court pointed out that it's really difficult.

[01:15:54] Speaker 03:
You can't just take caper, which was about whole tumor DNA, and not even about SNPs, a single nucleotide pair that's wrong, and just translate that right over to this multiplex amplification of SNPs in a single reaction volume and have it usable for sequencing.

[01:16:12] Speaker 03:
Instead, she said, look, it was known in the art that there were obstacles to doing this because of the nature of CF, and in particular, CT DNA.

[01:16:19] Speaker 03:
And they haven't shown motivation to combine because they haven't shown how anything in the prior art overcomes that.

[01:16:25] Speaker 00:
Well, your own Metzger's declaration from Illumina, that Illumina IPR was in fact discussed at the hearing, right?

[01:16:34] Speaker 03:
That's right.

[01:16:34] Speaker 00:
And ordinarily...

[01:16:38] Speaker 00:
You know, at A20264 was the other side's attorney walked through paragraph 116 of the Metzger Declaration where this manor was showing us all the content.

[01:16:52] Speaker 00:
That quote, one of ordinary skill in the art, would have expected success in being able to sequence cell-free DNA found in maternal blood.

[01:17:02] Speaker 00:
It was further well known by 2008 that one could isolate, amplify, and sequence cell-free genomic DNA.

[01:17:09] Speaker 00:
These are Dr. Metzger's words that were quoted and presented at the hearing, I believe it was an evidentiary hearing, to the court, and we don't really have a response at A9, A10 from the district court on this.

[01:17:26] Speaker 03:
So I think in each instance when they point and say, this is what Dr. Metzger said, or this is what Fluidigm says, the question we're about to ask is, okay, what's the motivation to combine that with what's left out?

[01:17:37] Speaker 03:
And so what you read there omits one important thing.

[01:17:40] Speaker 03:
First, we're not talking about SNPs, and we're not talking about this multiplex amplification.

[01:17:47] Speaker 00:
in a single reaction volume of something that has that... And everything you're saying right now is sort of like the next level question of drilling down that next layer and then figuring out those sorts of details.

[01:18:00] Speaker 00:
But that's not the level that the district court was playing with.

[01:18:03] Speaker 00:
She was playing at this more broader fundamental question of, do you do cell-free DNA or cell-T DNA through one of these access array things of fluid arms?

[01:18:13] Speaker 00:
No, you just don't.

[01:18:16] Speaker 00:
And I'm going to cite the patent owner's evidence, and I'm not going to cite or discuss or address anything that the defendant brought up on this score, including Dr. Metzger's own words.

[01:18:27] Speaker 03:
Yeah, and under a clear error and abuse of discretion standard, taking what was submitted, the district court did a fine job in pointing out that there's a difference between what CAPER was, and that's their reference, CAPER, and what they're promoting, and what they needed to show was a motivation to combine.

[01:18:42] Speaker 03:
And so what's missing from Metzger as well is the Illumina declaration.

[01:18:48] Speaker 03:
Metzger actually went back and explained why the Illumina fluid access array or anything like it would teach against because it doesn't teach away from doing what the patent says.

[01:18:58] Speaker 03:
Because although it has a preamplification step where you have lots of things in a single reaction volume, it then recognizes that that's a real problem because you get all the junk.

[01:19:09] Speaker 03:
And so then it goes on, and it does what's called a split and pull.

[01:19:13] Speaker 03:
It just does singleton.

[01:19:14] Speaker 03:
When you say it goes on, what do you... I'm not talking about... The fluid-iron axis array that he's relying on at that point.

[01:19:21] Speaker 03:
And that you have to go back and do singleton replication.

[01:19:24] Speaker 03:
And so if it says 9,216, you end up with 9,216 individual aliquots, individual reaction chambers, and you have to do one or maybe potentially 10 if you're doing something else.

[01:19:38] Speaker 03:
in each of those different chambers.

[01:19:40] Speaker 03:
That's the old split and pull method that isn't very accurate.

[01:19:44] Speaker 03:
It's the old split and pull method that's very intensive.

[01:19:46] Speaker 03:
It's the old art.

[01:19:48] Speaker 03:
And that teaches away from what we came up with, which is using that single reaction volume, because they have to do two steps.

[01:19:54] Speaker 00:
They need that as two steps.

[01:19:58] Speaker 00:
Each individual well in a split and pull can't be considered a single reaction volume?

[01:20:04] Speaker 03:
Each individual well might, but you would have to have 25 to 2000 SNP loci being tested for in each individual well in order to meet our claims.

[01:20:14] Speaker 03:
And in those wells, in some instances they say 1, and in other instances it's up to 10, which is consistent with our patent, which said beyond 5 to 10 it really is a problem.

[01:20:23] Speaker 03:
And so that's why they have to go back to split and pool, precisely because the prior art recognized that a single reaction volume

[01:20:30] Speaker 03:
Especially when you're dealing with something rare like ctDNA is really problematic and again This is not anything we can find the district court saying this is well the district court cited more generally the difficulty of transcending caper which was entire tumor tissue not even snips over to this very different method of Multiplex amplification single reaction volume

[01:20:54] Speaker 03:
and for SNPs and for CTDNA, which is like that needle in a haystack.

[01:20:59] Speaker 02:
Can I ask you, the fluid on patent application, which we were discussing in the first half of the argument, does that involve split and pool, or only split and pool?

[01:21:13] Speaker 03:
It has two steps.

[01:21:15] Speaker 03:
It discloses two steps, one of which is that you can put things in a single reaction volume, but then it follows

[01:21:23] Speaker 03:
And it needs, it requires you to go on, follow on and do a split and pull because you end up with all of that junk.

[01:21:30] Speaker 03:
So you have to do that split and pull.

[01:21:31] Speaker 03:
And so in that sense, it teaches away from what we're teaching, which is you can just- Is that different from CAPER?

[01:21:37] Speaker 03:
Pardon?

[01:21:37] Speaker 03:
Is that different from CAPER?

[01:21:38] Speaker 03:
It's not that different from CAPER now because CAPER was using split and pull.

[01:21:42] Speaker 03:
The difference was using the Fluidigm Axis Array.

[01:21:45] Speaker 03:
But the difference is that CAPER was just this whole cell tumor DNA.

[01:21:49] Speaker 03:
these longer strips, like not cell-free DNA, which are little tiny pieces, and not SNPs, not single nucleotide variants, and even fluidine.

[01:21:59] Speaker 02:
So just on that point, in the fluidine patent application, paragraph 175, it says, these methods are applicable to identifying the presence of particular polymorphisms, such as SNPs.

[01:22:15] Speaker 02:
Now, that happens to be the paragraph that, unless I've misunderstood something, is the sole paragraph cited in paragraph 116 of Metzger's IPR declaration, which I think was his exhibit 1003, citing paragraph 175.

[01:22:37] Speaker 02:
Does that?

[01:22:38] Speaker 02:
I don't know.

[01:22:39] Speaker 03:
It does mention that it's applicable to SNPs.

[01:22:41] Speaker 03:
That's correct.

[01:22:42] Speaker 03:
But when it goes through and it's talking about self DNA, this is sort of just a borderline.

[01:22:46] Speaker 03:
It doesn't go and say, this has been proved, this has been, you know, this will work.

[01:22:51] Speaker 03:
You can do this with sequencing.

[01:22:53] Speaker 03:
It doesn't say any of those things.

[01:22:55] Speaker 03:
And as a matter of fact, I think if you were to look at fluid on paragraph 120, when it talks about the split and pull, and it's listing the suitable detection methods, so paragraph 120 is 13097.

[01:23:06] Speaker 03:
And we're a little bit in the weeds here, but it's on the bottom of that page, and it says,

[01:23:12] Speaker 03:
The resulting 9216 reaction chambers, so we're back to split and pull, we've got these 9216, can then be subject to amplification, followed by detection of amplification products which can be carried out by any suitable means.

[01:23:26] Speaker 03:
And then they list these means, but those are not means such as using a massively parallel sequencer.

[01:23:33] Speaker 03:
They're back to the probe methods that the patent explained aren't subject to problems when you have junk product, when you have dimers and other things in there.

[01:23:42] Speaker 03:
They're the things that don't matter.

[01:23:44] Speaker 03:
But if you're gonna add what we have, which is massively parallel sequencing, you're going to need to get around that junk.

[01:23:51] Speaker 03:
And that's what the patent explains in place after place is that you need, if you're gonna do this multiple X amplification, 25 to 2,000 SNP in a single reaction volume, you're gonna have dimers, you're gonna have mischief products, and you're going to have to figure out a way to get around it.

[01:24:07] Speaker 03:
So the last thing I'll just point to in the patent, and I think this is pretty important,

[01:24:12] Speaker 03:
is that it says that the high level of multiplexing with minimal non-target ampli... I'm sorry.

[01:24:18] Speaker 03:
That's page Column 47, what?

[01:24:20] Speaker 03:
Appendix 143, Column 47.

[01:24:23] Speaker 03:
And it's about line 46 to 49.

[01:24:25] Speaker 03:
And it says the high level of multiplexing with minimal non-target amplicons that has now been achieved, that means through the patent, through the specification when it teaches, allows PCR followed by sequencing to be used as an alternative to microarrays.

[01:24:42] Speaker 03:
So where that third piece, massively parallel sequencing, is a critical element of this, and it's because it doesn't work well, it doesn't work at all, if you have all what Dr. Misker called junk.

[01:24:55] Speaker 07:
I see from Judge- This is basically your argument that the FIRA taught a way because it all looked at the split and pull method, whereas you are focused on the single reaction problem.

[01:25:06] Speaker 03:
Is that a fair- That's part of it, that's part of it.

[01:25:09] Speaker 03:
And the last thing I'd point out is that, you know,

[01:25:11] Speaker 03:
Look, CARE-DX, which Metzger was talking about at the time, wasn't about SNPs associated with cancer.

[01:25:17] Speaker 03:
It was about aneuploidy.

[01:25:19] Speaker 03:
I'm not sure I'm saying it correctly, but that's a condition where an entire chromosome is missing.

[01:25:23] Speaker 03:
So you're looking for a big chunk and a big chunk being missing.

[01:25:27] Speaker 03:
And that's a very different issue than when you're looking at something that's very true.

[01:25:31] Speaker 07:
Could you tell me why you waited seven months to sue?

[01:25:35] Speaker 03:
So we were already engaged in litigation against others.

[01:25:41] Speaker 03:
time, it seemed like going after one person at a time was an appropriate way of doing it.

[01:25:45] Speaker 07:
And the district court found, and this was an abuse of discretion stages... There's only two of you in this market with this kind of product, correct?

[01:25:54] Speaker 03:
Now, yes.

[01:25:55] Speaker 03:
At the time, no.

[01:25:56] Speaker 03:
We had a lawsuit against a company called Archer DX at the time.

[01:26:00] Speaker 03:
And Archer DX, we won that case, got an injunction.

[01:26:03] Speaker 03:
And so they are no longer considered a significant player.

[01:26:06] Speaker 03:
So I think at the time we were engaged in litigation and the district court made a specific finding on page 19 of the appendix that it's okay because we are engaged in litigation.

[01:26:16] Speaker 03:
And what made us come forward and actually go in and seek that injunction, sue and almost immediately seek an injunction, is when that irreparable harm became

[01:26:25] Speaker 03:
parent and obvious.

[01:26:26] Speaker 03:
We weren't going to bother the court.

[01:26:28] Speaker 03:
We weren't going to write it.

[01:26:29] Speaker 07:
But when did it become parent and obvious?

[01:26:30] Speaker 07:
Four days after Medicare had announced?

[01:26:33] Speaker 03:
Exactly.

[01:26:33] Speaker 07:
No, but see, that's a problem.

[01:26:35] Speaker 07:
That's not your irreparable harm.

[01:26:37] Speaker 07:
If that was your irreparable harm, that would be different.

[01:26:38] Speaker 07:
The district court found your irreparable harm is all tied to the clinical studies on your product.

[01:26:44] Speaker 07:
It didn't tie it to patient use.

[01:26:47] Speaker 07:
Oh, no.

[01:26:49] Speaker 03:
Not at all, because the district court found, and starting with

[01:26:52] Speaker 03:
There's a huge public interest in ensuring that we protect patents.

[01:26:56] Speaker 03:
But I think our irreparable harm is tied to both.

[01:26:57] Speaker 07:
We're not talking about public interest.

[01:26:59] Speaker 07:
We're talking about irreparable harm.

[01:27:00] Speaker 07:
So stay on topic.

[01:27:01] Speaker 03:
Yes.

[01:27:02] Speaker 03:
So the DIST report starts out with a nascent market.

[01:27:05] Speaker 03:
So this is a relatively new market.

[01:27:08] Speaker 03:
And she talks about there being a first mover advantage, a loss of first mover advantage.

[01:27:12] Speaker 03:
And that's in Appendix 15.

[01:27:14] Speaker 03:
And you lose.

[01:27:15] Speaker 03:
I'm sorry.

[01:27:16] Speaker 07:
But individual patient use isn't what the irreparable harm section is all about.

[01:27:21] Speaker 07:
And she didn't find that.

[01:27:22] Speaker 07:
Your first mover advantage, she ties it all to clinical trials and clinical validation, which will then improve your marketability.

[01:27:31] Speaker 03:
Chief Judge Maher, I disagree with you on that.

[01:27:33] Speaker 07:
Show me where.

[01:27:34] Speaker 07:
Show me where she said something different.

[01:27:39] Speaker 03:
OK, so if we go to volume one, we'll do that.

[01:27:53] Speaker 03:
So if you go to that piece.

[01:28:04] Speaker 03:
She talks about a likelihood of irreparable harm, and that when you have to compete against products that incorporate and infringe your own patent, you have irreparable harm.

[01:28:16] Speaker 03:
That includes competing for doctor use.

[01:28:19] Speaker 03:
And then Vinci talks about evidence of head-to-head competition, lost market share.

[01:28:24] Speaker 03:
When you're talking about clinical trials, that's not market share.

[01:28:27] Speaker 03:
Lost sales, you're not talking about lost sales when you're doing it.

[01:28:31] Speaker 07:
With all due respect, every single doctor market share, that can all be compensated for.

[01:28:36] Speaker 07:
That's not irreparable harm that can't be compensated for with a bond they could easily post.

[01:28:44] Speaker 07:
What's the true irreparable harm?

[01:28:46] Speaker 03:
John, I think the true irreparable harm is, first, when you have a nascent market, right?

[01:28:52] Speaker 03:
You're taking the markets, taking off.

[01:28:53] Speaker 03:
When somebody else takes your invention, takes your innovation, you lose your reputation in terms of being the innovator, your name recognition, your customer relationships.

[01:29:05] Speaker 01:
Where does it say that?

[01:29:07] Speaker 03:
It talks about page 15.

[01:29:09] Speaker 03:
Natera has a first mover advantage.

[01:29:11] Speaker 03:
This advantage includes a period of exclusivity in which you can establish

[01:29:14] Speaker 03:
brand recognition, customer loyalty, and business foundations.

[01:29:18] Speaker 03:
This is where she's talking about that and she cites Douglas Dynamics.

[01:29:21] Speaker 03:
Douglas Dynamics was a case in which someone copied patent snow plow features.

[01:29:27] Speaker 03:
This court upheld an injunction even though they weren't losing sales because the court points out that, look, when someone comes into the market and has your innovation and sells it as their own,

[01:29:39] Speaker 03:
That takes you down and tells them that you're not really an innovator, you're just another one, somebody on the market.

[01:29:45] Speaker 03:
We know bear aspirin because bear came out with it first and the word aspirin got genericized as a result.

[01:29:52] Speaker 03:
Signetera was the first on the market and it was the curve in terms of acceptance.

[01:29:58] Speaker 03:
We pointed out that we invested hundreds of millions of dollars in establishing the market, overcoming doctor resistance, oncologist resistance to this.

[01:30:09] Speaker 03:
And that, you are irreparably harmed when someone else jumps in and says, OK, we have the same exact thing, too.

[01:30:14] Speaker 03:
And on top of that, we point out that that injury is exacerbated when a copyist touts its product as superior.

[01:30:22] Speaker 03:
And not just because they're denigrating you.

[01:30:24] Speaker 03:
If that product does not meet expectations,

[01:30:27] Speaker 03:
That harms the entire market.

[01:30:29] Speaker 03:
That engenders distrust of the entire product market.

[01:30:33] Speaker 03:
And then finally, there's stickiness.

[01:30:34] Speaker 03:
And the court does mention stickiness.

[01:30:36] Speaker 03:
And stickiness isn't just a matter of clinical trials.

[01:30:39] Speaker 03:
Because stickiness is, for example, when a patient starts using one of these, you pretty much have to stay with it for five years because you're working from a baseline.

[01:30:50] Speaker 03:
And you can't go back up and redo it from a baseline, which is why all of the patient uses have been grandfathered.

[01:30:57] Speaker 03:
We have a two-player market, which also shows irreparable harm, because we would be the sole one in the market with irreparable harm.

[01:31:05] Speaker 03:
And look, there's simply no clear error here in showing that there's irreparable harm to us in the market.

[01:31:11] Speaker 03:
When you lose your reputation, when you lose your brand recognition, when you lose your first-mover advantage,

[01:31:16] Speaker 03:
That's not something that's easily happening.

[01:31:18] Speaker 00:
How about causal nexus?

[01:31:19] Speaker 00:
Sure.

[01:31:19] Speaker 00:
After reading our case plan, I'm a little confused how to think about causal nexus in the context of this case.

[01:31:28] Speaker 03:
And I think in this case, it's a little confusing, but the primary reason that it's confusing in this case is a waiver.

[01:31:33] Speaker 03:
Is what?

[01:31:34] Speaker 03:
A waiver.

[01:31:34] Speaker 03:
The opening, the brief below that Neogenomics submitted devoted exactly three sentences to causal nexus.

[01:31:44] Speaker 03:
The first one says there's no causal nexus.

[01:31:46] Speaker 03:
The second is a point they're no longer pursuing.

[01:31:48] Speaker 03:
And here's the third one.

[01:31:49] Speaker 03:
There is insufficient nexus because radar sales are driven by the sensitivity that comes from radars 48 tumor-specific variants in advanced bioinformatics, not Natero's products.

[01:32:00] Speaker 03:
That's the whole of the argument.

[01:32:03] Speaker 03:
Now the argument is, well, you can't look at the tumor-informed market because that's not in the patent.

[01:32:10] Speaker 03:
Now set aside the fact that the patent talks about

[01:32:13] Speaker 03:
snips associated with cancer.

[01:32:16] Speaker 03:
Setting that aside, that's not going to put the judge on notice that we're arguing about which part of the market you should be looking at.

[01:32:22] Speaker 03:
And it's especially true because at the time this was being litigated, there were two patents at issue, the 454 and the 035, the 454 the district court didn't rely on.

[01:32:31] Speaker 03:
The 454 was specific to the tumor-informed market.

[01:32:35] Speaker 03:
So when they say, oh, this argument, which applies to both Natera's patents, plural, district court is going to look at that and say,

[01:32:42] Speaker 03:
This means that I can't look at the tumor-informed market, because they've combined the two patents together.

[01:32:47] Speaker 03:
Obviously, you can look at the tumor-informed market, because at least one of the patents is tumor-informed.

[01:32:51] Speaker 03:
So the distro court just wasn't on notice that somehow she was supposed to say, gee, I should be talking only about the tumor-naive market or the tumor-informed market.

[01:32:59] Speaker 03:
It's just as waived as waived can be.

[01:33:01] Speaker 03:
But it's also just without merit.

[01:33:03] Speaker 03:
Your Honor, it certainly doesn't show an abuse of discretion or some sort of clear error, because new genomics is relying on supposed sensitivity, right?

[01:33:12] Speaker 03:
that sensitivity comes from using our patented technology from infringing our patent.

[01:33:17] Speaker 07:
So that's not what they say.

[01:33:19] Speaker 07:
They say it comes from their algorithm, which is different from yours.

[01:33:22] Speaker 03:
They do, but you wouldn't have any sensitivity unless you could actually do what we're doing.

[01:33:27] Speaker 03:
If you couldn't have that sensitivity, first of all, the algorithms, there's absolutely no record on their bioinformatics.

[01:33:34] Speaker 03:
They just say bioinformatics, nothing else, no record on it.

[01:33:37] Speaker 03:
But even setting that aside, you don't have the requisite sensitivity.

[01:33:42] Speaker 03:
unless you're doing what we claimed, or you went through the claims, where you're doing a single reaction volume with 25 to 2,000 SNP loci.

[01:33:51] Speaker 03:
Because that single reaction volume, and I'm quoting from the patent, appendix 143, column 47, lines 24 to 48, is what reduces variability that can occur between reactions and corrects for amplification bias in the prior art, which is what establishes sensitivity.

[01:34:07] Speaker 03:
If you have to go back to the old split and pool, then you're gonna have

[01:34:11] Speaker 03:
all the problems in the split pool, which undermine the sensitivity.

[01:34:14] Speaker 07:
Are you saying the claims of the 035 patent are directed to tumor-informed testing?

[01:34:20] Speaker 03:
Are they directed to tumor-informed testing?

[01:34:23] Speaker 07:
You said associated with cancer.

[01:34:25] Speaker 07:
So what is it you want me to understand from that?

[01:34:27] Speaker 07:
Am I supposed to understand that the claims of the 035 patent are limited to tumor-informed testing?

[01:34:33] Speaker 03:
I think that's an interesting claim construction issue, but I don't think the patents are necessarily limited to tumor-informed testing.

[01:34:40] Speaker 03:
But they are about SNPs associated with cancer.

[01:34:44] Speaker 03:
And so we're talking about detection of cancer.

[01:34:46] Speaker 03:
And then when they start with CAPER and say CAPER is our starting point, CAPER is about tumor tissue.

[01:34:54] Speaker 03:
And so when you're trying to extend CAPER to something else, to extend CAPER out, you're extending it to CFDNA, which is tumor tissue, or otherwise, circulating tumor DNA.

[01:35:05] Speaker 03:
This is clearly what the case is really about in terms of the fight.

[01:35:08] Speaker 03:
It's circulating tumor DNA.

[01:35:10] Speaker 03:
We're both in the same market.

[01:35:11] Speaker 07:
But on page 17, under the casual nexus analysis, the district court seems to be focusing exclusively on the tumor-informed testing.

[01:35:21] Speaker 03:
That's right.

[01:35:23] Speaker 07:
So if you're telling me the 035 is not limited to tumor-informed testing, how do you meet the causal nexus requirement?

[01:35:30] Speaker 03:
Because even for tumor-informed, you're not going to get anywhere.

[01:35:34] Speaker 03:
you're not going to have a sufficient sensitive product.

[01:35:37] Speaker 03:
You're not going to have a product that really even works at all, unless you are infringing our patent.

[01:35:41] Speaker 02:
And why is that different from the battery in the iPhone, without which none of the rest works?

[01:35:48] Speaker 03:
I do think it's different in the following sense.

[01:35:51] Speaker 03:
That is, what makes it work and what they claim as their differentiator is sensitivity.

[01:35:57] Speaker 03:
And what gets you out from being not sufficiently sensitive, the problems with

[01:36:01] Speaker 03:
split and pool where you might not have any ctDNA in some of the wells and therefore you won't have the right ctDNA that the primers are supposed to be associated with in any of the wells.

[01:36:12] Speaker 03:
You end up with something that's much more reliable and that reliability is a necessary part of what you need for this market.

[01:36:20] Speaker 03:
And that's in true of tumor-informed and not tumor-informed.

[01:36:23] Speaker 03:
And so I think that is on all fours with

[01:36:26] Speaker 03:
what this patent's about.

[01:36:27] Speaker 03:
It's like, before you did it, if you don't use our patent, you get too much junk, and it's not gonna work.

[01:36:33] Speaker 03:
And if you use our patent and techniques, then you get rid of that junk, and you can do massive parallel sequencing, you can be more cost effective as a result, because you don't have to use probe.

[01:36:42] Speaker 03:
It gets around all the problems.

[01:36:43] Speaker 06:
The district court didn't say any of that.

[01:36:47] Speaker 03:
Sorry?

[01:36:47] Speaker 06:
The district court didn't say any of that.

[01:36:49] Speaker 03:
No, the district court was very focused on the tumor-informed market, and the district court didn't say any of that for a specific reason.

[01:36:56] Speaker 03:
because there was no argument below that it was improper to look at the tumor-informed market.

[01:37:01] Speaker 03:
There was those three sentences I spoke about, and there's nothing in those three sentences that say, judge for the 035.

[01:37:05] Speaker 07:
Well, that's because there was originally a motion on both the 454 and the 035, right?

[01:37:11] Speaker 07:
Isn't that the reason why?

[01:37:12] Speaker 03:
Yes, that is it.

[01:37:13] Speaker 07:
She could never address 454 because she addressed 035 instead.

[01:37:17] Speaker 07:
And I think that she got confused and thought 035 was also limited to the tumor-informed market.

[01:37:22] Speaker 03:
I don't think so, because if there's a difference between the two patents and a difference in the sort of remedy that you should have, the burden of the person who's seeking that is to say, you need to limit your remedy or the remedy is not linked.

[01:37:34] Speaker 03:
For the 035, here's one problem.

[01:37:36] Speaker 03:
For the 454, here's another problem.

[01:37:38] Speaker 03:
But the only argument that was made, three sentences, Your Honor, three sentences, was that, oh, we have better sense of- Who sought the injunction?

[01:37:44] Speaker 03:
Pardon?

[01:37:44] Speaker 07:
Who sought the injunction?

[01:37:45] Speaker 03:
We sought the injunction.

[01:37:46] Speaker 07:
So you had the burden.

[01:37:47] Speaker 03:
We had the burden, but not that, if I understand correctly, we said the burden to show causation, and we show that we are suffering all these harms, both in all markets, because... Don't you also have the burden to show causal nexus?

[01:38:01] Speaker 03:
I think that's probably right, we have to show a causal nexus, but I think there is a causal nexus, because they couldn't be in the tumor-informed market in the way they are without using our patent invention.

[01:38:10] Speaker 03:
And it's not that it's a small piece of it, it's

[01:38:13] Speaker 03:
It's everything.

[01:38:14] Speaker 03:
It is basically what drives demand is that sensitivity according to them themselves.

[01:38:18] Speaker 03:
And that sensitivity means they couldn't compete without it.

[01:38:22] Speaker 03:
If the sensitivity is what's important and they cite sensitivity in their affidavit, let's make it different, then they need to get away from split and pull and go to single reaction volume to have that sensitivity.

[01:38:34] Speaker 02:
It's from our pattern.

[01:38:37] Speaker 02:
I'm just thinking about the battery example.

[01:38:43] Speaker 02:
Perhaps your reference to alternatives might translate into the point that I might have a patent on a particular way of doing a battery.

[01:38:56] Speaker 02:
But there are lots of other ways to do a battery.

[01:38:59] Speaker 02:
And if you use one of the, by assumption, dumber ways to have a battery, then you get all the other benefits and everybody will still buy the iPhone.

[01:39:08] Speaker 02:
And that's not true here, right?

[01:39:10] Speaker 02:
I think that's exactly right.

[01:39:11] Speaker 03:
It's not a question between a smarter and a dumber, it's a question between one that works and one that doesn't.

[01:39:17] Speaker 03:
One that gets around the problems of split and pull, and one that incorporates the problems of split and pull.

[01:39:22] Speaker 03:
And I think maybe perhaps I should talk just for a little bit about the public interest.

[01:39:29] Speaker 07:
Or unless the court has... No, talk about public interest, but skip over how important patents are.

[01:39:33] Speaker 07:
We all know that.

[01:39:34] Speaker 07:
Go straight to whether or not... But that's what I have written down at the top, Judge Moore.

[01:39:39] Speaker 07:
That's irrelevant to me.

[01:39:41] Speaker 07:
Start with what are people going to be harmed by not having access to their test?

[01:39:48] Speaker 03:
And the answer is absolutely not.

[01:39:50] Speaker 03:
And I could go to point to just page 20 of the court's opinion, appendix 20.

[01:39:54] Speaker 03:
And it says, Signatera is clinically validated for use with the same cancers as Radar.

[01:40:00] Speaker 03:
No clear error in that.

[01:40:01] Speaker 03:
In fact, it's actually clinically validated for eight more.

[01:40:04] Speaker 03:
And I just went to court to a comparison.

[01:40:06] Speaker 03:
2, 4, 4, 8, 6, paragraph 44, with 1, 1, 2, 7, 1, paragraph 15 and 2, 4, 4, 7, paragraphs 46 to 48.

[01:40:14] Speaker 07:
I don't know what you think I got from that.

[01:40:18] Speaker 03:
That's a comparison of what the validations are.

[01:40:22] Speaker 03:
And if you look at the validations, you realize that our coverage is broad and theirs is narrow.

[01:40:27] Speaker 03:
And I think their Dr. Seakery pointed that out.

[01:40:29] Speaker 02:
Is everything that's in their coverage also covered by you?

[01:40:33] Speaker 03:
That's correct.

[01:40:34] Speaker 03:
That's correct.

[01:40:36] Speaker 03:
And there's no clear error.

[01:40:37] Speaker 02:
What about the blood cancers?

[01:40:38] Speaker 03:
So they don't have clinical validation for the blood cancers.

[01:40:43] Speaker 03:
And there's no reason to believe.

[01:40:45] Speaker 03:
It's just completely unsupported.

[01:40:47] Speaker 03:
And there's no reason to believe that they would get that clinical validation ahead of us.

[01:40:51] Speaker 03:
But if something comes up, if it turns out that there is a validation that they have and we don't, and that there may be harm, that's what a Rule 60 motion is for.

[01:41:01] Speaker 07:
OK, do me a favor.

[01:41:02] Speaker 07:
My clerk said that I may have talked over you.

[01:41:04] Speaker 07:
And when she needs to go back, if she needs to, and find those page numbers, because she spent all weekend basically trying to create this from scratch.

[01:41:11] Speaker 07:
Go ahead and blabber out your page numbers again where you can find a list of different... And I apologize for blabbering.

[01:41:18] Speaker 03:
It's also, the validations, our validations are actually on our website if you want to do it, but I hate to go outside the record.

[01:41:25] Speaker 03:
I'm not going to your website.

[01:41:28] Speaker 03:
Okay.

[01:41:28] Speaker 03:
It's 2446, paragraph 44, 11271, paragraph 15, 2447, paragraphs 46 to 48.

[01:41:32] Speaker 03:
And that's how you would do your comparison.

[01:41:35] Speaker 03:
And it shows that we have eight more.

[01:41:36] Speaker 03:
And the district court just committed no clear error in finding that anybody...

[01:41:40] Speaker 02:
Why is it right to limit the inquiry to what's validated as opposed to, for example, what this doctor in Texas says as a, you know,

[01:41:56] Speaker 02:
I'm not anecdotal.

[01:41:57] Speaker 02:
I don't mean to be disparaging with that word, which is frequently now described as the opposite of evidence-based medicine.

[01:42:08] Speaker 02:
But you can have important stuff going on before there is empirical validation.

[01:42:17] Speaker 03:
Ordinarily, I mean, if you're talking about just sort of off-market, I think in terms of promoting it, in terms of the general use, what you want is, and what Medicare will pay for, and what the insurers will pay for, and what you really should be doing as a physician, you're going to wait for clinical validation.

[01:42:31] Speaker 03:
And both of us are working to get that clinical validation.

[01:42:35] Speaker 07:
OK, I'm sorry, but that's a little bit crazy.

[01:42:36] Speaker 07:
If I had cancer, I'd go off label in 10 seconds.

[01:42:39] Speaker 07:
And so would you.

[01:42:41] Speaker 07:
If you had any reason to think it could be beneficial, you'd pay out of pocket, and you'd go off label.

[01:42:47] Speaker 03:
And then even that, there's simply no basis.

[01:42:49] Speaker 03:
And the district court found that it's disputed and not at all clear that Radar has better sensitivity for any particular indication.

[01:42:57] Speaker 03:
And again, if there's something that's different.

[01:42:59] Speaker 07:
What do you mean?

[01:42:59] Speaker 07:
We've got the testimony.

[01:43:02] Speaker 07:
I don't remember his name, I can find it in a second, of their executive that claims that theirs is an order of magnitude more sensitive than yours.

[01:43:11] Speaker 03:
So first, there's no head-to-head studies.

[01:43:14] Speaker 03:
That's not the big deal.

[01:43:15] Speaker 03:
And there's no expert who opined.

[01:43:17] Speaker 03:
Again, it's not.

[01:43:17] Speaker 03:
It's just a corporate executive.

[01:43:19] Speaker 03:
But that's not the big deal.

[01:43:20] Speaker 07:
What the big deal is is... When you say there's no experts, it's the corporate executive.

[01:43:23] Speaker 07:
This is a doctor and a researcher and a scientist with 20 years of oncology research experience.

[01:43:28] Speaker 07:
Don't refer to him simply as a corporate executive and blow it off as though we haven't read the record and you're going to fool me into thinking he's an accountant.

[01:43:35] Speaker 03:
So let me tell you what the difference is then.

[01:43:37] Speaker 03:
And I apologize if you feel like I'm belittling him.

[01:43:41] Speaker 03:
What matters to patients is how often, how reliably it detects cancer when cancer's present.

[01:43:48] Speaker 03:
And when it comes to that, the record shows that Signetera blows radar away.

[01:43:53] Speaker 03:
If you look at page 7, 9, 3, 2 of the appendix, that's Moskovitz's declaration, it's 93 and 100% for Signetera versus 62 and 64% for the neogenomics product.

[01:44:08] Speaker 03:
And what they're touting when they say greater sensitivity is actually something quite different from it.

[01:44:13] Speaker 02:
I'm sorry, I didn't understand.

[01:44:15] Speaker 02:
I understand the numbers 90 and 60, but what are they percents of?

[01:44:19] Speaker 03:
So that's the clinical test of when there's actually a tumor present, does the assay actually pick it up and say, yes, you have a tumor, as opposed to missing it?

[01:44:30] Speaker 03:
And then what they tell is something actually a little different, which is called limits of detection.

[01:44:34] Speaker 03:
It's not the clinical measure of how accurate are you?

[01:44:37] Speaker 03:
Are you doing a good job with patients?

[01:44:39] Speaker 03:
Which is sort of a measure of how low, how dilute the CTDA theoretically could be and still get picked up in the test.

[01:44:47] Speaker 03:
But even on that, what they're presenting to the court and what they presented below isn't at all persuasive.

[01:44:55] Speaker 03:
For example, Dr. Sikri's declaration says, oh, there's 12 studies.

[01:45:00] Speaker 03:
Well, the first seven studies actually don't mention radar.

[01:45:04] Speaker 03:
I don't know what they're for.

[01:45:06] Speaker 03:
And the difference they're talking about tends to be analytical, which means that you use contrived DNA, and you say, well, contrived DNA, here's what you get in terms of it.

[01:45:16] Speaker 03:
But when you actually try and translate that to actual clinical results with real patients, the advantage goes away.

[01:45:22] Speaker 03:
And that's Appendix 7932, which is the Russell study.

[01:45:25] Speaker 03:
So they had relied on something called FLAC, which was analytical.

[01:45:30] Speaker 03:
contrived DNA.

[01:45:31] Speaker 03:
But when you went to actual patients, that completely disappeared.

[01:45:34] Speaker 03:
And finally, there's a paragraph on the reply in 32, which shows kind of the bad math apples to oranges comparisons that are going on here.

[01:45:42] Speaker 03:
And it looks at it something like a Coakley article, which wasn't the line below, because it's new.

[01:45:47] Speaker 03:
And it does a comparison that wasn't pointed out to the district court, which is to our supposed theoretical limits.

[01:45:53] Speaker 07:
Can you go to page 11287 of the appendix, please?

[01:45:56] Speaker 07:
It's in volume two.

[01:45:57] Speaker 03:
11287.

[01:46:06] Speaker 07:
This is the SICRI testimony, paragraph 44.

[01:46:13] Speaker 07:
So how do you respond to this?

[01:46:24] Speaker 07:
Because this suggests that their test is an order of magnitude more sensitive than your test.

[01:46:34] Speaker 03:
And your honor, that's potentially good marketing, but it is not good science or good patient care.

[01:46:41] Speaker 03:
Because when you're talking about sensitivity, what you really care about is does it detect it when it's there with the patients?

[01:46:46] Speaker 03:
And what I was explaining is if you're looking at something, and I think this all stems from that original FLAC study, if you're looking at just contrived DNA in an analytical study, which isn't actual patient data, that doesn't mean you're going to get better results for active patients.

[01:47:01] Speaker 03:
And there was a later study

[01:47:02] Speaker 03:
afterwards, it's called Russell, 7932, that show that you didn't have an advantage in it.

[01:47:07] Speaker 03:
And if I go to the page 32 of the reply, the Coakley article, which they recite, it kind of points out the nature that the errors were looking at here, because they cite Coakley as saying, our sensitivity, and this is limits of detection, how low can you go?

[01:47:22] Speaker 03:
It's not actually detecting cancer.

[01:47:24] Speaker 03:
It's there, it's the theoretical limit of how little CT DNA can be there before you pick it up.

[01:47:28] Speaker 03:
And they say that they go down to 0.00

[01:47:32] Speaker 03:
11% which is smaller.

[01:47:35] Speaker 03:
But if you look at Coakley, page 901, they don't have a pin site, but you look at page 011, it says .011% which is actually worse than the .01% they attribute to us.

[01:47:47] Speaker 03:
And then when they compare us to Coakley, they're looking at a 2017 source showing our supposed limits of detection, not anything that's current.

[01:47:57] Speaker 03:
And so this is the kind of sort of

[01:47:58] Speaker 03:
bad mathematics, apples to oranges that the district court was presented with.

[01:48:03] Speaker 03:
And the district court didn't have to be persuaded when it came to clinical validation, we were validated for everything that they were.

[01:48:09] Speaker 03:
When it came to what was the actual results for cancer patients, we were better.

[01:48:15] Speaker 07:
So let me just understand.

[01:48:16] Speaker 07:
What is your response to why their claim in this report that, based on this study that was done,

[01:48:26] Speaker 07:
they were an order of magnitude more sensitive in detecting the CT DNA.

[01:48:34] Speaker 03:
Okay, so this actually isn't a head-to-head study.

[01:48:36] Speaker 03:
It's not the same study for the same two products.

[01:48:39] Speaker 03:
It's one study where they say we got 0.001 and another one saying that ours got 0.01 VAF.

[01:48:47] Speaker 03:
And then therefore, based on these two different studies, they do a comparison and say theirs is

[01:48:52] Speaker 03:
more accurate.

[01:48:53] Speaker 07:
I think at some point I remember them saying your .01 VAF came from your own literature.

[01:48:57] Speaker 07:
Is that right?

[01:48:58] Speaker 07:
Does that sound... That's correct.

[01:49:00] Speaker 03:
But remember, you'd have to use the same techniques.

[01:49:02] Speaker 03:
You'd have to use, for example, the same blood samples.

[01:49:04] Speaker 03:
They use a lot more blood sample than we do.

[01:49:07] Speaker 03:
There's lots of differences that make these not comparable.

[01:49:11] Speaker 03:
But what really matters is clinical.

[01:49:13] Speaker 03:
What's happening with the patients?

[01:49:15] Speaker 03:
Not these analytical questions of, gee, how low could you go with this contrived DNA?

[01:49:20] Speaker 03:
And when it came to that,

[01:49:22] Speaker 03:
The district court was presented with evidence and committed no clear error and no abuse of discretion in finding that there isn't a difference.

[01:49:29] Speaker 03:
There isn't.

[01:49:29] Speaker 03:
When you compare it, actually, from 7932, Signatera is far better.

[01:49:38] Speaker 03:
And again, 7932, we explain that when they actually went to clinical data, any advantage disappeared.

[01:49:44] Speaker 03:
Analytical studies say, gee, the limits of detection as opposed to actually detecting in patients simply cannot make that difference.

[01:49:53] Speaker 03:
And certainly the district court didn't commit abuse of discretion or clear error on this topic.

[01:49:57] Speaker 03:
This is why we have hearings.

[01:49:59] Speaker 03:
This is why we have experts.

[01:50:00] Speaker 03:
This is why we have testimony.

[01:50:01] Speaker 07:
And this is why we have district court.

[01:50:03] Speaker 07:
Did the district court say any of what you just said?

[01:50:04] Speaker 03:
So the district court said, I don't quote, that it was disputed and not at all clear that radar achieves higher sensitivity.

[01:50:11] Speaker 03:
Because she was presented with lots of evidence,

[01:50:14] Speaker 03:
Lots of evidence that when it comes to clinical results, patient care, there is no difference in sensitivity.

[01:50:23] Speaker 03:
If the court has no further questions.

[01:50:25] Speaker 03:
Oh, maybe I should mention something about Turner really quickly, because there was this statement.

[01:50:29] Speaker 03:
So they pointed to the Turner presentation.

[01:50:32] Speaker 03:
The German breast group.

[01:50:33] Speaker 03:
Pardon?

[01:50:34] Speaker 03:
The German breast group.

[01:50:35] Speaker 03:
Exactly.

[01:50:36] Speaker 03:
And actually, that points the exact opposite direction, because that Turner study

[01:50:42] Speaker 03:
That Turner study was simply of radar.

[01:50:44] Speaker 03:
It wasn't a signotera.

[01:50:47] Speaker 03:
And so when they pointed out that when it says, oh, don't use signotera, they really meant don't use radar for it.

[01:51:00] Speaker 03:
And we actually argued below and pointed out during the hearing that that type of confusion where somebody has a problem, it's a typo.

[01:51:07] Speaker 03:
It's just a mistake.

[01:51:08] Speaker 03:
Now, they argued otherwise in the district court, orally, but pointed out that this study, if you look at it, it's only studying radar.

[01:51:16] Speaker 03:
It's not studying signetera.

[01:51:17] Speaker 03:
So it's hard to see how this could be this statement saying that signetera doesn't work particularly well could have been.

[01:51:25] Speaker 03:
truly a statement of signature, when all they were studying was radar.

[01:51:29] Speaker 03:
So that type of harm, someone saying bad things about your product or the risk of people saying bad things about your product because they're dissatisfied with a copy cut, even that risk is irreparable.

[01:51:39] Speaker 03:
And it's irreparable harm for the whole market because people lose faith in the products as a whole and in the market as a whole.

[01:51:45] Speaker 03:
If the court has no further questions.

[01:51:47] Speaker 00:
Just a quick question.

[01:51:48] Speaker 00:
CT DNA stands for circulating tumor DNA.

[01:51:51] Speaker 03:
That's correct.

[01:51:52] Speaker 00:
So is this claim directed to CT DNA and not more broadly CF DNA?

[01:52:00] Speaker 03:
So it is CF DNA and then it says associated with cancer.

[01:52:04] Speaker 03:
And I think, for present purposes, the district court understood.

[01:52:08] Speaker 03:
I don't think it's been litigated that it's anything but CTNA at this point.

[01:52:13] Speaker 00:
I'm trying to figure out, from your view, this is a CTNA-directed claim?

[01:52:19] Speaker 03:
So I think it'd be premature to go and do a claim construction, because we're about to do a claim construction.

[01:52:23] Speaker 00:
Just trying to find out what your side view is of what your claim is directed to.

[01:52:28] Speaker 03:
I think it's been assumed to this point in this that that was the case, because the district court said,

[01:52:33] Speaker 03:
distinguished between CFDNA and said these statements were not discussing circling tumor DNA.

[01:52:38] Speaker 03:
I think also, likewise, they started with CAPER, which was tumor DNA.

[01:52:42] Speaker 00:
So you have no objection to it being understood as CT DNA driven?

[01:52:47] Speaker 03:
For this point, yes.

[01:52:48] Speaker 03:
It is directed specifically to CT DNA.

[01:52:51] Speaker 03:
It's cell-free DNA associated with cancer.

[01:52:53] Speaker 03:
It's going to be CT DNA.

[01:52:55] Speaker 03:
It's circulated tumor DNA.

[01:52:57] Speaker 03:
OK.

[01:52:58] Speaker 07:
Thanks.

[01:52:58] Speaker 07:
Just to be clear, I mean, I think that they did argue, and I'm trying to find where,

[01:53:03] Speaker 07:
in their brief that these claims are not directed to the tumor-inhibiting?

[01:53:13] Speaker 07:
Yeah, right.

[01:53:14] Speaker 07:
Am I wrong about that?

[01:53:16] Speaker 03:
I'm sorry.

[01:53:17] Speaker 03:
So it's certainly limited to cell-free DNA associated with cancer, which is going to be circling tumor DNA.

[01:53:24] Speaker 03:
because that word's associated with cancer.

[01:53:26] Speaker 03:
The SNPs have to be associated with cancer.

[01:53:27] Speaker 03:
And the question is?

[01:53:28] Speaker 02:
Tumor-effective.

[01:53:30] Speaker 02:
Tumor-informed?

[01:53:31] Speaker 02:
Tumor-informed.

[01:53:32] Speaker 02:
Oh, whether or not that's a subset yet, because you're designing your

[01:53:37] Speaker 02:
your things you're trying to make up from the patient's own sample, right?

[01:53:42] Speaker 03:
Right.

[01:53:43] Speaker 03:
Whether or not you could, yes.

[01:53:44] Speaker 03:
So I don't think it's this particular patent, unlike the 454, is not limited to tumor informed because you could use the patent, for example, the technique to say, here's a panel of tumors across the universe that we see about people in the United States.

[01:53:57] Speaker 03:
And do we find SNPs that are associated with that?

[01:53:59] Speaker 03:
That's fine.

[01:54:00] Speaker 07:
OK.

[01:54:00] Speaker 07:
So to make sure that we're all on the same page, the 035 could be related to CT DNA.

[01:54:06] Speaker 07:
in terms of the way the claim articulates associated with cancer, but not be limited to tumor-informed testing.

[01:54:16] Speaker 03:
That's correct.

[01:54:16] Speaker 03:
It has to be circling tumor DNA.

[01:54:18] Speaker 07:
They're not one and the same.

[01:54:19] Speaker 07:
And like Judge Toronto said, tumor-informed testing is a subset of... Yes, tumor-informed and tumor naive.

[01:54:26] Speaker 03:
You know, the tumors that everybody in the universe gets versus the tumor that you yourself had.

[01:54:29] Speaker 03:
It covers both.

[01:54:31] Speaker 00:
It's not just can be directed to.

[01:54:33] Speaker 00:
It is directed to CT DNA.

[01:54:35] Speaker 03:
Yes, it is limited to cell-free DNA associated with cancer, which is going to be circulating tumor DNA.

[01:54:43] Speaker 03:
If the court has no further questions, thank you, the court, for its patience this time.

[01:54:49] Speaker 07:
Mr. Mayor, we'll give you two minutes of rebuttal.

[01:54:51] Speaker 07:
I'm just kidding.

[01:54:52] Speaker ?:
I'm just kidding.

[01:54:53] Speaker 04:
You've had enough?

[01:54:54] Speaker 04:
Just really quickly.

[01:54:56] Speaker 04:
So I would like to point you in our preliminary.

[01:54:58] Speaker 07:
I'm just trying to leave.

[01:55:02] Speaker 04:
He's doing his Chief Justice Request invitation

[01:55:04] Speaker 04:
So in our preliminary injunction opposition in the district court, which you can find at A10489-90, we cite Dr. Van Ness's, our expert's, declaration, where he walks through the specific admissions that Nterra has made in the past, including in CARE-DX and in other cases.

[01:55:27] Speaker 04:
And in particular, in response to something Mr. Lampkin said,

[01:55:33] Speaker 04:
at A12591 is a portion of the CARE-DX summary judgment brief that Natera filed, where Natera admits that using circulating tumor DNA to tag, amplify SNPs and sequence was routine.

[01:55:50] Speaker 04:
So I disagree with his assertion that they haven't admitted in this context circulating tumor DNA for SNPs.

[01:55:57] Speaker 04:
I think we already talked about, he's making the argument that the 25 to

[01:56:03] Speaker 04:
to whatever in the claim is the invention here.

[01:56:07] Speaker 04:
But the patent itself acknowledges that it can be done with higher numbers, even in the passages that Mr. Lampkin pointed to.

[01:56:14] Speaker 04:
And the colloquy we had with you earlier, Judge Toronto, where Dr. Metzger, their expert, admitted, and there's a slide to the district court where we show, admitted that the Fluidigm 2010 patent application shows over 9,000 in a single well.

[01:56:29] Speaker 04:
So it's just their split and pool thing.

[01:56:32] Speaker 04:
The taper does not limit it to 10 in a well.

[01:56:35] Speaker 04:
It was just what they were doing.

[01:56:38] Speaker 04:
But it doesn't limit it to 10.

[01:56:41] Speaker 04:
The studies he talked about at the end in the Maschkewitz Declaration at A7932, that's not an apples to apples study that he's pointing to.

[01:56:50] Speaker 04:
It's also apples to oranges.

[01:56:53] Speaker 04:
One was early stage cancer and one was not.

[01:56:55] Speaker 04:
So the district court made no findings in the PI in support of her PI about sensitivity and only made the statement in the stay denial that it was not at all clear.

[01:57:06] Speaker 04:
But again, this was their burden.

[01:57:08] Speaker 04:
And they have no evidence to show that ours isn't more sensitive.

[01:57:12] Speaker 04:
They have no head-to-head study showing that.

[01:57:14] Speaker 04:
And they haven't shown there are no non-infringing alternatives.

[01:57:20] Speaker 04:
If you have no further questions, Your Honor, thank you.

[01:57:22] Speaker 07:
I think both counsels was an excellent argument.