[00:00:00] Speaker 04:
Our last case this morning is Strick v. Ravgen, 23-1989.

[00:00:10] Speaker 04:
Similar claim, but a different file.

[00:00:14] Speaker 04:
Mr. Dustin, when you're ready.

[00:00:16] Speaker 04:
Good morning, Your Honor.

[00:00:18] Speaker 02:
Good morning, Your Honors.

[00:00:19] Speaker 02:
May it please the Court, Thomas Dustin, on behalf of the appellant, Strick.

[00:00:23] Speaker 02:
I would like to take up the formaldehyde issue first, then briefly address the misapplication

[00:00:28] Speaker 02:
of the motivation to combine with respect to Pertle, Chu, and Granger, and then take the questions on the standing issue.

[00:00:35] Speaker 02:
Now, the undisputed evidence, Your Honors, was that formaldehyde use to prevent cell lysis in combination with PCR remained common at the time of the invention and for decades before.

[00:00:47] Speaker 02:
Notwithstanding, published concerns with respect to its toxicity and reports of random damage to nucleic acids.

[00:00:55] Speaker 02:
In fact, Your Honors, there were no studies

[00:00:58] Speaker 02:
that specifically informed a person of skill in the art that formaldehyde was any less suitable for PCR analysis of cell-free nucleic acids.

[00:01:08] Speaker 02:
The board acknowledged that there was no evidence, no data, specific to formaldehyde's use prior to the patent with either cell-free DNA or cell-free fetal DNA.

[00:01:19] Speaker 02:
Now, Rabgen contends that a person of skill in the art would have expected formaldehyde to react differently

[00:01:27] Speaker 02:
with cell-free DNA as opposed to cellular DNA.

[00:01:31] Speaker 02:
And on appeal, they assert that the board agreed with that proposition.

[00:01:36] Speaker 02:
And they assert that the board relied on evidence that cell-free fetal DNA was small, more limited in quantity, and easily damaged.

[00:01:49] Speaker 02:
Now, I submit to your honors that the board did not make those findings, but had the board

[00:01:54] Speaker 02:
made those findings.

[00:01:56] Speaker 02:
Those findings would have been legal error, Your Honors, because the statements relied upon for the proposition that cell-free fetal DNA is small and easily damaged were statements made in 2017 in a declaration that was 15 years after the fine with patent application.

[00:02:15] Speaker 02:
And for support for the statements in that declaration, that declaration cited articles and studies that occurred after

[00:02:23] Speaker 02:
the filing of the patent application.

[00:02:26] Speaker 02:
These were not studies, these were not characteristics or properties of cell-free fetal DNA in this record that were known to persons of skill in the art before the filing of the patent application.

[00:02:39] Speaker 04:
Why don't you address the prior art, Pertil and Granger.

[00:02:43] Speaker 02:
Yes, sir.

[00:02:49] Speaker 02:
So, Your Honor, the Board erred in requiring

[00:02:53] Speaker 02:
that Streck established, that Pirtle motivated a person of skill in the art, that it made the suggestion not only of the problem that needed to be solved, but the solution to that problem.

[00:03:06] Speaker 02:
And that is not the law of this circuit, Your Honor.

[00:03:09] Speaker 02:
The primary reference need not provide the motivation.

[00:03:12] Speaker 02:
The motivation come from virtually anywhere, from teachings, knowledge of skill in the art, et cetera.

[00:03:17] Speaker 02:
And as we pointed out in our petition,

[00:03:19] Speaker 02:
A person of skill in the art viewing Pertle would have realized that Pertle was complaining, was citing as a problem, background DNA.

[00:03:28] Speaker 02:
Background DNA can out-compete fetal DNA for amplification, and so background DNA should be minimized or eliminated.

[00:03:37] Speaker 02:
Chu taught us what was the source of the background DNA.

[00:03:42] Speaker 02:
Chu taught us that through its experimentation, it localized

[00:03:47] Speaker 02:
the source of this maternal background DNA to the lysis of maternal cells that were in the sample.

[00:03:53] Speaker 02:
And it did that by removing the cells, the maternal cells from the sample, and then showing that by doing that, by preventing the lysis of those cells, the total background DNA in the sample was reduced considerably.

[00:04:08] Speaker 02:
All of these facts were undisputed, Your Honor.

[00:04:13] Speaker 02:
The problem that the board had with CHU was not only did they ignore the teachings of CHU that by preventing maternal cell lysis you would reduce background DNA and therefore enhance the technique that protocol is describing,

[00:04:33] Speaker 02:
But it required us to show that by means of preventing maternal DNA lysis, maternal lysis rather, that we would achieve some substantial and considerable improvement in the reduction of background DNA.

[00:04:49] Speaker 02:
They pointed to evidence that we showed from Rabjan's own expert during deposition who read Pertle as a person of skill in the art would read Pertle, looked at the data that Pertle reported,

[00:05:02] Speaker 02:
and testified that kernel, I'm sorry, I misspoke, Chu's data, looked at Chu's data and spoke to the issue of what a person of skill in the art would understand Chu was telling you when you read his data or her data.

[00:05:18] Speaker 04:
But Granger discloses formaldehyde.

[00:05:20] Speaker 02:
It does, your honor.

[00:05:21] Speaker 04:
And that's the question, whether it should have been combined.

[00:05:25] Speaker 04:
And we know from listening all morning,

[00:05:29] Speaker 04:
that formaldehyde can damage DNA.

[00:05:34] Speaker 02:
We do, Your Honor, but here's the point.

[00:05:36] Speaker 04:
And so you're relying on the combination of fertile and grain.

[00:05:39] Speaker 02:
We are, Your Honor.

[00:05:41] Speaker 02:
And the point I'm making is that before the patent was filed, no one knew that you could expect any more disqualifying damage from formaldehyde

[00:05:53] Speaker 02:
to cell-free DNA than was expected with respect to cellular DNA.

[00:05:57] Speaker 02:
Formaldehyde interacted with both types of DNA.

[00:06:00] Speaker 02:
And after all, cell-free DNA is merely cellular DNA that is outside the cell.

[00:06:06] Speaker 02:
So what the ARC taught was that up until the time of the invention, it was common to use formaldehyde in combination with DNA that was going to undergo PCR analysis.

[00:06:17] Speaker 02:
And there was nothing in the record other than the relative quantities

[00:06:21] Speaker 02:
of cell-free DNA versus cellular DNA that would teach a person of skill in the art that the properties of cell-free DNA would cause it to react any differently to formaldehyde than known, most common, most sought after, most acceptable fixative in use at that time for these types of PCR analyses.

[00:06:42] Speaker 02:
That's the point, Your Honor.

[00:06:43] Speaker 02:
There is nothing in the record.

[00:06:45] Speaker 04:
PCR simply amplifies this.

[00:06:47] Speaker 02:
It is, Your Honor.

[00:06:48] Speaker 04:
Absolutely right.

[00:06:48] Speaker 04:
It's not operative otherwise.

[00:06:50] Speaker 02:
It amplifies DNA.

[00:06:52] Speaker 02:
And that's exactly the point.

[00:06:55] Speaker 02:
That's what the board did not provide.

[00:06:57] Speaker 02:
It did not consider any of the evidence concerning how PCR actually operates.

[00:07:02] Speaker 02:
The testimony of Dr. Patterson in the record about the fact that... The question is formaldehyde.

[00:07:08] Speaker 04:
I mean, PCR amplifies, but that doesn't prevent lysis of cells.

[00:07:17] Speaker 02:
The formaldehyde prevents slices of cells, Your Honor.

[00:07:20] Speaker 02:
Yes.

[00:07:21] Speaker 04:
Yes, but it's subject to leakage.

[00:07:25] Speaker 02:
Well, no, there is no evidence in this record, Your Honor, of leakage from cells caused by formaldehyde.

[00:07:32] Speaker 02:
I heard that, frankly, for the first time here today as to the LabCorp record.

[00:07:36] Speaker 02:
This record has no evidence in this record that formaldehyde causes leakage from cells.

[00:07:42] Speaker 02:
In fact, if anything, the record in this proceeding, Your Honor,

[00:07:47] Speaker 02:
establishes just the opposite.

[00:07:51] Speaker 02:
Because as Dr. Patterson testified, and as his article at appendix 3105 and 3107 and 1308, and again at 15980, these references teach that the most common use

[00:08:15] Speaker 02:
The most common fixative for what was called in situ PCR, which is where you keep the DNA inside the cell and you amplify it inside the cell.

[00:08:25] Speaker 02:
You have to maintain the integrity of the cell to conduct in situ PCR.

[00:08:30] Speaker 02:
The DNA has to remain in it.

[00:08:33] Speaker 02:
formaldehyde was used to fix those cells in order to conduct that type of PCR.

[00:08:38] Speaker 02:
So the DNA remains in the cell.

[00:08:41] Speaker 02:
It has to for that particular type of PCR.

[00:08:44] Speaker 02:
And formaldehyde was commonly used for that particular type of PCR.

[00:08:48] Speaker 02:
And that's the evidence in this record.

[00:08:50] Speaker 02:
There is no evidence that formaldehyde will cause any DNA to escape the cell, Your Honors.

[00:08:57] Speaker 04:
Now, the other... The board credited Dr. Van Ness's testimony that

[00:09:03] Speaker 04:
would have been dissuaded from modifying Pearl's method with Granger's from alcohol.

[00:09:13] Speaker 04:
That's his conclusion, right?

[00:09:16] Speaker 02:
That is, that was the conclusory statement contained in one of two paragraphs, only one of two paragraphs cited by the board in connection with its final written decision.

[00:09:25] Speaker 04:
The board said we are unpersuaded that Granger's

[00:09:29] Speaker 04:
RNA amplification would have suggested success with amplification and detection of your cell-free fetal DNA isolated from maternal plasma in Pearl.

[00:09:43] Speaker 02:
Well, Your Honor, I think that was a statement with respect to whether or not Granger taught or was the motivation to use cell-free, use formaldehyde in a cell-free context.

[00:09:55] Speaker 02:
We don't rely on Granger for that.

[00:09:57] Speaker 02:
Granger teaches that formaldehyde will fix cells and that its presence in samples is not incompatible with DNA or nucleic acids.

[00:10:06] Speaker 04:
Boatswain is not apparent that Granger was amplifying and detecting a scarce analyte, rare nucleic acid sequences against a background of excess sequences amplified like Pertil.

[00:10:21] Speaker 02:
That is correct, Your Honor.

[00:10:22] Speaker 02:
In the study reported in Granger,

[00:10:25] Speaker 02:
He was testing his concept against cellular RNA to determine whether or not the cellular RNA was adversely affected by the presence of formaldehyde.

[00:10:34] Speaker 02:
But remember, Granger's ultimate goal was to provide a preservative solution for the analysis of blood samples looking for the detection of AIDS virus.

[00:10:46] Speaker 02:
So Granger was interested in using a preservative solution, your honor, that was intended for a very rare analyte.

[00:10:54] Speaker 02:
the AIDS virus, and he saw no incompatibility with his use of formaldehyde in that particular context, Your Honor.

[00:11:06] Speaker 02:
I'm into my verbal time, but let me just make a couple more points.

[00:11:15] Speaker 02:
I apologize, Your Honor, I didn't know that alarm was on.

[00:11:17] Speaker 02:
Let me make a couple more points about formaldehyde.

[00:11:21] Speaker 02:
So as I said,

[00:11:23] Speaker 02:
The only evidence in this record of the differences between cell-free and cellular DNA in terms of its reaction to formaldehyde, in terms of PCR, is that cell-free DNA, cell-free fetal DNA, is less in quantity than cellular DNA.

[00:11:43] Speaker 02:
Now, the reality is that what the board did not grapple with

[00:11:49] Speaker 02:
was the fact that there was no evidence of the degree to which formaldehyde would damage cell-free fetal DNA, whether that damage would be sufficient in the view of a person of skill in the art to disqualify formaldehyde for PCR amplification, when all that is required for PCR amplification is a very small amount of DNA that is then replicated or amplified into billions of copies.

[00:12:15] Speaker 02:
So the other point that it also wasn't grappled with was the board did not consider that

[00:12:20] Speaker 02:
By adding formaldehyde, you in addition reduce the maternal component in the sample, the component that Pertil said could out-compete the relatively lesser amount of fetal DNA.

[00:12:35] Speaker 02:
So what you're getting with formaldehyde is you're reducing the component that out-compete the fetal DNA, and you're not damaging the fetal DNA in such a way that you're going to prevent its amplification.

[00:12:49] Speaker 04:
Counsel, as you pointed out here, into your rebuttal time, assume you want to save some.

[00:12:54] Speaker 02:
I do, Your Honor.

[00:12:55] Speaker 02:
I want to make just one more point, though, and that is the board specifically found in this record that PCR would not be adversely affected by formaldehyde.

[00:13:07] Speaker 02:
It rejected the evidence that Rabgen presented on that and noted that Dr. Patterson persuasively explained that the steps involved in PCR amplification, particularly

[00:13:18] Speaker 02:
this protease digestion step would reverse any cross-linking that might impede PCR analysis.

[00:13:26] Speaker 02:
So that's in this record.

[00:13:27] Speaker 02:
I didn't hear that in the lab report.

[00:13:30] Speaker 02:
I'll reserve the remainder of my time here.

[00:13:38] Speaker 04:
We'll save it.

[00:13:39] Speaker 04:
Mr. Maddie's doing heavy duty today.

[00:13:41] Speaker 01:
Last one.

[00:13:41] Speaker 01:
Thank you, Your Honor.

[00:13:42] Speaker 01:
May it please the Court.

[00:13:44] Speaker 01:
So here the appellant is taking a scattershot approach, disputing virtually every facet of the board's decisions below, and ultimately asking this court to reweigh the evidence, which this board does not do.

[00:13:57] Speaker 01:
The PTAP took a careful approach here under the proper obviousness framework to reach its decisions, and in this one they took three important steps to get to their ultimate conclusions.

[00:14:07] Speaker 01:
First, the board considered Streck's prior art collectively and explained how Streck and its expert repeatedly overstated the disclosures in its prior art.

[00:14:17] Speaker 01:
Second, the board examined whether the Granger formaldehyde combination would have been a suitable option, again, without requiring that it be perfect or that it be the most desirable.

[00:14:27] Speaker 01:
And third, the board performed a detailed analysis of all the evidence presented and explained why on balance the evidence failed to establish obviousness under KSR.

[00:14:38] Speaker 01:
So on the first point regarding Pertil and Chu,

[00:14:42] Speaker 01:
For Pertle, the board went through step by step and responded to Streck's arguments regarding motivations that Pertle itself was providing according to Streck.

[00:14:52] Speaker 01:
And it responded on each of those and found that Streck was overstating the Pertle reference.

[00:14:58] Speaker 01:
And importantly, I think the board didn't just stop there.

[00:15:01] Speaker 01:
In some of its briefings, Streck faults the board for supposedly requiring motivation to come only from Pertle or for focusing only on Pertle.

[00:15:10] Speaker 01:
The board didn't do that.

[00:15:11] Speaker 01:
What they did was they responded to Streck's arguments regarding Pirtle, but then they said after they had addressed Pirtle at Appendix 67, quote, this is not the end of the inquiry because Petitioner also had cited Chu.

[00:15:25] Speaker 01:
So they weren't putting some heightened burden on motivation to just come out of Pirtle.

[00:15:29] Speaker 01:
They responded to Streck's arguments on Pirtle and then they acknowledged that's not the end of the inquiry.

[00:15:34] Speaker 01:
They had to take into account the other motivations, purported motivations that had been put forth.

[00:15:40] Speaker 01:
So then the board addressed Chu and this argument that Chu supposedly disclosed a 25% fetal DNA recovery level.

[00:15:52] Speaker 01:
And Streck there accuses the boards of applying an arbitrary threshold to what they were required to show in the prior art.

[00:16:00] Speaker 01:
But again, this isn't the board putting in an arbitrary threshold or any threshold at all.

[00:16:05] Speaker 01:
They were just responding to Streck's argument.

[00:16:08] Speaker 01:
Streck said there's 25% in Chu, and the board responded squarely to that.

[00:16:13] Speaker 01:
And it found that argument to be unsupported and actually contradicted by some of the shifting that Streck and its expert did between the petition and the reply in this case.

[00:16:23] Speaker 01:
And the board looked at it.

[00:16:24] Speaker 03:
If you do the arithmetic, as Streck does in his brief, from Chu's figures, I guess it's three and four, you can reach a conclusion, struck me,

[00:16:37] Speaker 03:
that 25% is an accurate figure.

[00:16:40] Speaker 03:
Now, Chu didn't reach that conclusion.

[00:16:43] Speaker 03:
And I gather that no one reached that conclusion for a few years after Chu.

[00:16:48] Speaker 03:
But nonetheless, it does appear

[00:16:51] Speaker 03:
that the math adds up to 25%.

[00:16:54] Speaker 01:
Is that right?

[00:16:55] Speaker 01:
The arithmetic that is in the briefing, we don't take issue with if you divide one number by the other and multiply it by the third, you get 25.

[00:17:03] Speaker 01:
But we do take issue with that being a proper calculation or a calculation that you or anyone of skill in the art appreciated back at the time of this invention.

[00:17:12] Speaker 03:
I can understand the failure to appreciate it, but why is it not a proper calculation?

[00:17:18] Speaker 03:
I mean, if Chu had sat down and said, and by the way,

[00:17:21] Speaker 03:
If you compare these two figures, you end up with 25%.

[00:17:26] Speaker 03:
That wouldn't have been improper, right?

[00:17:29] Speaker 03:
For Chu to draw that conclusion from the figures.

[00:17:31] Speaker 01:
If Chu said that, then that would have been what Chu describes.

[00:17:35] Speaker 01:
The problem is the figures is the starting point.

[00:17:39] Speaker 01:
As Strax expert admitted, it's hard to read the figures.

[00:17:42] Speaker 01:
It's hard to tell.

[00:17:43] Speaker 01:
These numbers that go into the equation aren't written in the figures.

[00:17:47] Speaker 01:
You have to sort of guesstimate.

[00:17:48] Speaker 01:
And that's where, as the board noted at Appendix 47, Patterson actually called it a bad graph.

[00:17:54] Speaker 01:
And he said if you were reviewing this, he would have asked for a new one.

[00:17:57] Speaker 01:
But maybe more to your Honor's question, if Chu had really gotten 25% and appreciated that, they would have been singing that from the rooftops.

[00:18:06] Speaker 01:
What Chu, as the board acknowledged at page 70, Chu did not disclose the calculations or report 25%.

[00:18:12] Speaker 01:
Instead, what Chu and others actually and repeatedly reported, both in Chu, before Chu, and in years after Chu, was the 3% to 6% recovery.

[00:18:22] Speaker 01:
And on this shifting between petition and reply, Dr. Patterson actually agreed with us on this.

[00:18:28] Speaker 01:
In the petition itself, in his opinion that he put in to support the petition at the first step of this case, at appendix 2977, paragraph 97 of his opinion, Dr. Patterson said at the start of the case, Chu reported 3% to 6%.

[00:18:43] Speaker 01:
Again, at his deposition after institution, we asked him, we wanted to make sure.

[00:18:49] Speaker 01:
Chu and Lo, those references were on the table in front of him.

[00:18:52] Speaker 01:
And at appendix 15180 to 81, he agreed what Chu and Lo in the early 2000s were reporting was three to six percent.

[00:19:01] Speaker 01:
So the board noted that not only is there failure of support here, but also there's some shifting even in the expert's own testimony as far as what a person of ordinary skill in the art would have appreciated from Chu.

[00:19:13] Speaker 01:
Then the second step the board took.

[00:19:16] Speaker 01:
The board went and examined the Granger combination, and it did that here explicitly in the context of whether Granger would have been a, quote-unquote, suitable combination.

[00:19:27] Speaker 01:
Just as it did with Pertle and Chu, the board proceeded to step through and address Streck's proposed motivations to combine the Granger reference.

[00:19:35] Speaker 01:
The main one struck forward here was what they call the shipping motivation, that one of ordinary skill would have been motivated to use Grainger to allow shipping samples between laboratories, and the board noted that those assertions were simply unsupported in the record.

[00:19:52] Speaker 01:
They had cited Dr. Patterson's opinion that merely repeated what the attorney argument was in the briefing, and they dismissed that additional argument for Grainger.

[00:20:03] Speaker 01:
In discussing Grainger here,

[00:20:05] Speaker 01:
Again, it's critical.

[00:20:07] Speaker 01:
The board never required that remote shipping or Granger's formaldehyde or anything in this combination be superior or perfect to any other approach.

[00:20:17] Speaker 01:
At Appendix 75, the board took that head on.

[00:20:20] Speaker 01:
They said, we know the law.

[00:20:22] Speaker 01:
We know what we're supposed to do.

[00:20:23] Speaker 01:
We're performing the proper analysis.

[00:20:26] Speaker 01:
The board says it was not suggesting that a person of ordinary skill must choose only the best solution, but merely it must be a suitable combination based on the record evidence.

[00:20:38] Speaker 01:
So the board put the standard right there in their decision.

[00:20:40] Speaker 01:
They applied the proper inquiry here, and they performed the proper analysis.

[00:20:45] Speaker 00:
Does counsel first strike right that in this record, as opposed to the other ones we've been looking at this morning, there's no evidence that formaldehyde causes leakage?

[00:20:54] Speaker 00:
in cells or adversely affects PCR, or that its toxicity might discourage its use?

[00:21:01] Speaker 00:
Is the record different here in that regard?

[00:21:04] Speaker 01:
In some respects.

[00:21:05] Speaker 01:
There is evidence in this record of leakage and toxicity.

[00:21:10] Speaker 01:
I will agree with counsel that, unlike in the previous decision, here the board did not have a second separate DNA leakage rationale for its decision.

[00:21:19] Speaker 01:
It didn't rely on that.

[00:21:21] Speaker 01:
Here, what the board did is it went back to what we've been talking about, the DNA damage points, and rested its decision here on a person of ordinary skill being dissuaded from the combination because of formaldehyde's potential to damage DNA.

[00:21:35] Speaker 03:
Was the Bianchi reference not in this record in this case?

[00:21:39] Speaker 03:
Because that's the reference that seemed to most clearly refer to the leakage issue.

[00:21:46] Speaker 03:
The permeability issue, call it.

[00:21:49] Speaker 01:
Right.

[00:21:49] Speaker 01:
I'll be honest, Your Honor.

[00:21:50] Speaker 01:
I don't remember if it was in the record.

[00:21:52] Speaker 01:
It was not in the same way.

[00:21:55] Speaker 01:
That's for sure.

[00:21:57] Speaker 01:
So what the board did is they carefully, again, weighed both sides' evidence on this DNA damage question, and ultimately found at appendix 87, here, a person of ordinary skill would have been dissuaded

[00:22:13] Speaker 01:
from adding Granger's paraformaldehyde to Pertle because formaldehyde was known to damage nucleic acids.

[00:22:23] Speaker 01:
And similar to the cases that we've heard before, the board relied on expert testimony in addition with the underlying evidence that was in the record regarding formaldehyde's potential to damage DNA.

[00:22:36] Speaker 01:
They credited Dr. Van Ness' opinion regarding a person with ordinary skill being dissuaded.

[00:22:41] Speaker 01:
They referenced the Srini Vasan reference.

[00:22:43] Speaker 01:
They referenced the Swinburne reference that disclosed the formaldehyde's potential to damage DNA.

[00:22:50] Speaker 01:
And again, the board did all of this, as they did in the other decisions, in the important context of cellular cell-free DNA analysis, which was in the claims.

[00:23:01] Speaker 01:
They noted again the testimony from Strex Mr. Hunsley, which I know counsel talked about.

[00:23:05] Speaker 01:
I want to respond to a couple points that he made.

[00:23:09] Speaker 01:
I think STREC is trying to distance themselves from Mr. Hunsley's statements regarding cell-free DNA being small and the quantities being limited, easily damaged.

[00:23:18] Speaker 01:
And what we heard was those statements were made later in 2017.

[00:23:21] Speaker 01:
I actually think that context is very important here because when STREC filed their own patent to cover using a formaldehyde releaser in cell-free DNA analysis, they argued in 2010 that wouldn't have been obvious.

[00:23:36] Speaker 01:
That's totally at odds with what they're arguing here, that that combination somehow would have been obvious back in 2003.

[00:23:42] Speaker 01:
And Mr. Hunsley, in his testimony, he put what he was saying squarely in the context of the invention we're talking about here.

[00:23:50] Speaker 01:
In the background of his declaration, he cites to the discovery of free fetal DNA in the late 1990s and puts everything in the context of this sort of burgeoning field of cell-free fetal DNA analysis.

[00:24:02] Speaker 01:
So I don't think Streck can just dismiss the testimony from their own VP of R&D based on the fact that he signed a paper in 2017.

[00:24:10] Speaker 01:
Then turning last to Granger.

[00:24:19] Speaker 01:
The board here noted, again, in the important context of cell-free fetal DNA analysis, Grainger uses formaldehyde, but it didn't use it in the context of what is claimed here.

[00:24:30] Speaker 01:
As the board found at appendix 83 to 84, Grainger was describing intracellular nucleic acids, and ultimately, even with all of Grainger's disclosures, as the board found at appendix 85,

[00:24:42] Speaker 01:
It was unpersuaded that Granger would have suggested success with amplification and detection of rare cell-free fetal DNA isolated from maternal plasma and Pertil.

[00:24:54] Speaker 01:
Again, rooting its decision not just in Pertil and what it was about, but in the specific context of this claim that requires determining the sequence of cell-free fetal DNA that is isolated from a maternal sample.

[00:25:11] Speaker 01:
So ultimately, here the board walked through every motivation that STREC had offered.

[00:25:17] Speaker 01:
It considered countervailing evidence from RAVGEN, rebutting each point.

[00:25:22] Speaker 01:
It made no legal error in its analysis.

[00:25:24] Speaker 01:
Its findings were supported by substantial evidence, and thus we request that the board's decision be affirmed.

[00:25:30] Speaker 01:
And unless your honors have further questions for me, I'll stop there.

[00:25:35] Speaker 04:
Thank you, counsel.

[00:25:35] Speaker 04:
Mr. Dustin has a lot of time.

[00:25:46] Speaker 02:
Thank you, Your Honors.

[00:25:47] Speaker 02:
Quickly, there was mention of 3% to 6% and repeated recognitions that that was the reported amount of cell-free fetal DNA.

[00:25:57] Speaker 02:
That simply was statements that Lowe had reported in 1998 that 3% to 6% cell-free fetal DNA was found.

[00:26:06] Speaker 02:
That's not consistent with the testimony with respect to Chu.

[00:26:09] Speaker 02:
Chu clearly showed that it was able to achieve a greater cell-free fetal DNA fraction

[00:26:16] Speaker 02:
within the sample by the processing techniques it used.

[00:26:20] Speaker 03:
Are you talking about the 25%?

[00:26:21] Speaker 02:
The 25%, yes, Your Honor.

[00:26:24] Speaker 03:
But Chu did not... Chu didn't do the calculations.

[00:26:28] Speaker 03:
And nobody seemed to have done it for several years.

[00:26:31] Speaker 03:
to come up with 25%.

[00:26:34] Speaker 02:
Well, I would point out that Dr. Van Ness presented with a copy of the SHU article.

[00:26:38] Speaker 02:
He had read it.

[00:26:40] Speaker 02:
He had studied it.

[00:26:40] Speaker 02:
He had opined on it.

[00:26:43] Speaker 02:
When he was presented with the graphs, that was exactly the interpretation he gave.

[00:26:46] Speaker 02:
It would be the interpretation that any person would make.

[00:26:50] Speaker 03:
I mean, the question is, would a person of skill in the art, reading two, have said, aha, 25 percent?

[00:26:55] Speaker 02:
Well, the question is not so much whether they would have said 25 percent, but would they have said that if I reduced maternal cell lysis... Well, I understand that, with respect to the particular question of 25 percent versus 3 to 6 percent.

[00:27:09] Speaker 03:
A person of ordinary skill reading CHU would say CHU accepts three to six percent as the max that we're going to get.

[00:27:15] Speaker 02:
No, I disagree with that, Your Honor, because of the... Because of the arithmetic, you think?

[00:27:19] Speaker 02:
No, CHU, his jumping off point is, if I don't process these samples, if I don't do anything to them, three to six percent is what you get.

[00:27:28] Speaker 02:
Let's take a look at what happens when I process them to eliminate lysis.

[00:27:32] Speaker 02:
Now I've got graphs showing that I improved the fraction of cell-free DNA in the sample considerably.

[00:27:38] Speaker 02:
And that's what he says, or that's what Chu says in the article, Your Honor.

[00:27:43] Speaker 02:
With respect to leakage, Your Honor, if you search these briefs, if you search the appendix, you're not going to find the word leakage anywhere.

[00:27:52] Speaker 03:
Bianchi was not a reference, was it, in this record?

[00:27:55] Speaker 03:
No.

[00:27:57] Speaker 03:
But Bianchi, it's hard to keep the references straight among all these cases.

[00:28:03] Speaker 03:
But Bianchi does seem to.

[00:28:05] Speaker 03:
talk about permeation of the cell walls, right?

[00:28:09] Speaker 02:
I'm not familiar with the reference, because it's not a reference in this particular record.

[00:28:13] Speaker 02:
All I would say, Your Honor, is coming back to appendix at 16991 through 16992 is the testimony of Dr. Patterson with respect to in-suit to PCR, where the integrity of the cell has to be maintained.

[00:28:28] Speaker 02:
And it is maintained by formaldehyde.

[00:28:30] Speaker 02:
No DNA is released.

[00:28:32] Speaker 02:
OK, thank you.

[00:28:36] Speaker 04:
Do you have a final statement?

[00:28:38] Speaker 02:
Yes, Your Honor, I do.

[00:28:39] Speaker 02:
The unfortunate thing is we are the tenth in line on these IPRs.

[00:28:45] Speaker 02:
I think what may have happened in this process was that by the time we arrived before the Board, we had to combat fatigue and inertia and momentum towards a decision that had been replicated over and over again before our particular evidence was presented to the Board.

[00:29:01] Speaker 02:
And I think what happened here was we made arguments here with respect to the untimeliness

[00:29:06] Speaker 02:
the lack of prior art disclosures, and the fact that PCR was practiced with respect to formaldehyde, that the digestive steps would have corrected the problems that were reported in these earlier IPRs.

[00:29:20] Speaker 02:
But by the time we arrived, we were sort of at the whim of the motion, the momentum, the inertia that had happened.

[00:29:30] Speaker 02:
And all I would say, Your Honor, is in this record, in terms of how

[00:29:34] Speaker 02:
The board has failed to grapple with all of this evidence with respect to how formaldehyde would not have caused someone to avoid its use, even in cell-free fetal DNA applications.

[00:29:47] Speaker 02:
The fact that they didn't grapple with all of the evidence that is counter to their conclusions, I think, doesn't give this court much of a record to really determine whether or not there's substantial evidence supporting that.

[00:29:59] Speaker 02:
And I would at least urge this court

[00:30:02] Speaker 02:
to suggest or suggest to this court that it remand this matter back to the board to do more comprehensive and more complete finding that your honors could then evaluate as to whether or not that evidence is there.

[00:30:14] Speaker 02:
Thank you.

[00:30:14] Speaker 04:
Thank you, counsel.

[00:30:15] Speaker 04:
We will grapple with whatever is before us.

[00:30:18] Speaker 04:
The case is submitted.