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

[00:00:00] Speaker 00:
Next case is 2020-22-20.

[00:00:05] Speaker 00:
Genowine, or maybe it's Genowine Biotechnology versus the ITC.

[00:00:16] Speaker 00:
Ms.

[00:00:16] Speaker 00:
Sikorski, please proceed.

[00:00:19] Speaker 02:
Thank you.

[00:00:19] Speaker 02:
Good morning, Your Honors.

[00:00:20] Speaker 02:
My name is Nicole Sikorski.

[00:00:22] Speaker 02:
I represent Genowine.

[00:00:23] Speaker 01:
Ms.

[00:00:24] Speaker 01:
Sikorski, I'm sorry to butt in right at the beginning, but I think since

[00:00:30] Speaker 01:
You have asked that the various control strains not be identified by number.

[00:00:38] Speaker 01:
I wonder if we can start off with a convention that we will identify the first control strain, the one that shows up on page 17 of the commission's brief first on line four as strain A.

[00:00:56] Speaker 01:
Next one on page 17 of the commission's brief, two lines down as strain C and the strain that shows up on page 36 in the footnote on line three of the footnote as strain B and avoid disclosing the names of each of those strains.

[00:01:18] Speaker 01:
Does that work for you and the others presumably?

[00:01:22] Speaker 02:
Yes, I've got it.

[00:01:23] Speaker 02:
Thank you.

[00:01:24] Speaker 01:
All right.

[00:01:24] Speaker 01:
Go ahead.

[00:01:25] Speaker 01:
Sorry.

[00:01:26] Speaker 02:
So starting with the negative control issue, I think there are three key points.

[00:01:29] Speaker 02:
The first is that we start with the claim language, that to establish infringement, the claim needs to measure, or the task needs to measure activity of the inserted gene.

[00:01:41] Speaker 02:
That is, the claim refers to the activity of the exogenous functional gene that is in a certain level.

[00:01:47] Speaker 02:
So that's the requirement of the claim.

[00:01:49] Speaker 02:
The second point is that there's an issue here, which is that background noise exists, that these tests can show the activity of the gene and they can also show other factors.

[00:01:58] Speaker 02:
And we have put in undisputed evidence that shows that the Miller protocol, which is the method for doing the test, does not account for that background noise.

[00:02:06] Speaker 02:
And so that takes me to the third point, which is in order to prove infringement here, glycosin had to use a negative control strain, meaning a strain that lacks the gene and can't show beta-galactosidase activity.

[00:02:18] Speaker 02:
Otherwise, it's not proving that the activity that it's measuring is actually the activity of the inserted gene.

[00:02:23] Speaker 02:
And I'd like to go right to the second step.

[00:02:26] Speaker 02:
I think the first step is undisputed at this point.

[00:02:28] Speaker 02:
That is a matter of what the claim requires.

[00:02:31] Speaker 02:
The language says that it has to measure the activity of the inserted gene.

[00:02:35] Speaker 02:
This is not what the ALJ said, but I understand the parties to not be disputing it at this point.

[00:02:40] Speaker 02:
And so the second point is really... Ms.

[00:02:42] Speaker 01:
Sarski, I'm sorry.

[00:02:43] Speaker 01:
This is Judge Bryson again.

[00:02:45] Speaker 01:
I wanted to clarify one thing at the outset that I found confusing.

[00:02:52] Speaker 01:
And that is at the beginning of your summary of the argument, you say that the strains, 1540 and 2410, the accused strains, do not infringe and they do not produce any beta-gal activity at all.

[00:03:11] Speaker 01:
But as I understand Dr. Parshet's testimony, she, as I understand it, testified that they do have a low level of beta-gal activity.

[00:03:25] Speaker 01:
Is your position that they lack any beta-gal activity at all?

[00:03:31] Speaker 02:
Yes.

[00:03:31] Speaker 02:
And that's based on the way that they're designed, that there are these two fragments that are inserted into the gene.

[00:03:36] Speaker 02:
And there's a temperature regulator so that one of the fragments is essentially bound up

[00:03:40] Speaker 02:
and can't express the gene until it reaches a certain temperature.

[00:03:44] Speaker 01:
And there is not a functional gene.

[00:03:46] Speaker 01:
And your position is that there is no leakage from the temperature regulator, correct?

[00:03:53] Speaker 01:
Correct.

[00:03:54] Speaker 02:
Dr. Patters suggested.

[00:03:56] Speaker 01:
Well, what do you do with Dr. Parsha's testimony that this 1540 does, in fact, have activity at a low level?

[00:04:07] Speaker 02:
Yes, respectfully, I think it's Dr. Prather's testimony that's glycosin expert who suggested that there could be leakage.

[00:04:14] Speaker 02:
She did not do tests or anything that that showed that there was leakage with respect to our strains in particular was, I think, more of a hypothetical and we don't think that the Al J made a factual finding along those lines.

[00:04:25] Speaker 02:
And that just goes, I think, to the question of the measurement, the Miller unit activity measured of our strains, but it doesn't answer the question of whether there needs to be a negative control strain.

[00:04:35] Speaker 02:
And I think the really, the key, absolutely key point here is that there is undisputed evidence in the record.

[00:04:41] Speaker 02:
And I'm not talking about tests that we did.

[00:04:43] Speaker 02:
I'm talking about peer-reviewed studies and evidence from one of the co-inventors of this patent.

[00:04:48] Speaker 02:
that if you test a cell that lacks the beta-galactoside A gene using the Miller protocol, that you can get Miller unit readings that are within the range claimed in the patent.

[00:04:58] Speaker 02:
And that's the co-inventors testimony that we cited in the record that said the readings can be up to 0.2.

[00:05:04] Speaker 02:
And that's the literature that we cited from tests in Italy, in England, in the U.S.

[00:05:09] Speaker 02:
that had Miller units of, say, 1.1, 3.6, et cetera.

[00:05:14] Speaker 02:
And I just think this is really key because it's something that the ALJ never grappled with, this evidence.

[00:05:19] Speaker 02:
It's something that the other side, that the ITC's lawyer and that Glykason don't grapple with in the brief now.

[00:05:26] Speaker 02:
And I understand that their argument is one that pokes holes or tries to call into question tests that Yennawine conducted and says that there are issues with those tests.

[00:05:37] Speaker 02:
But this is not an argument that depends on any of our tests at all.

[00:05:40] Speaker 02:
It depends on the fact that it's undisputed in the literature and from the co-inventor.

[00:05:45] Speaker 02:
that if you test a cell that lacks the gene and it just can't make beta-glycosidase activity, then it still gives you Miller unit readings within the range.

[00:05:54] Speaker 02:
And so that means that you have to have a negative control.

[00:05:57] Speaker 02:
And once you need to have a negative control, then there can't be a finding of infringement here because it's undisputed that glycosin did not test with a negative control.

[00:06:09] Speaker 03:
The Miller protocol doesn't call for this sort of negative control, is that right?

[00:06:14] Speaker 02:
That's right, but this isn't a question about what the Miller protocol requires, it's what the claim requires.

[00:06:19] Speaker 02:
The Miller protocol is just a way to run a task, right?

[00:06:22] Speaker 03:
I understand that, I understand that, but I guess my question then becomes why, my understanding is that the claim was understood to be referencing Miller units and you measure Miller units according to the Miller protocol.

[00:06:38] Speaker 03:
And so then the whole point of the Miller protocol is to determine the

[00:06:44] Speaker 03:
beta-gal activity in a particular sample.

[00:06:49] Speaker 03:
So I guess the question is, why shouldn't we just follow the Miller protocol?

[00:06:58] Speaker 02:
Because the Miller protocol is just a way of doing the test, but it doesn't get at the question.

[00:07:02] Speaker 03:
It's just a way to measure, but it doesn't get at what is... Well, isn't it the way to do the test?

[00:07:06] Speaker 03:
Because we're talking about Miller's unit.

[00:07:11] Speaker 02:
Right.

[00:07:12] Speaker 02:
It is a test that is designed to measure beta-galactosidase activity.

[00:07:15] Speaker 02:
But the problem is at the very low levels that are claimed in the patent, this 0.05, that there is background noise.

[00:07:22] Speaker 02:
And that's why I was talking about the undisputed evidence that we put forth that background noise exists under the Miller protocol and that it's not accounted for in the Miller protocol.

[00:07:31] Speaker 02:
So I understand your honor's point that the Miller test is specified in the patent.

[00:07:37] Speaker 02:
But what the patent also specifies

[00:07:39] Speaker 02:
is that the level that's measured has to be the level of the exogenous functional gene.

[00:07:44] Speaker 02:
And if it is undisputed that background noise exists, the Miller protocol, and our evidence shows that the Miller protocol doesn't account for it, then that is a problem with meeting the language.

[00:07:54] Speaker 03:
Let me ask you, I guess, a hypothetical.

[00:07:58] Speaker 03:
Imagine there's a patent on all shoes with a length of 9 to 11 inches according to the king's ruler.

[00:08:07] Speaker 03:
Now, people in the King's Court believe that the King's ruler is not really that precise.

[00:08:14] Speaker 03:
And maybe the markings for each inch on the King's ruler is a bit smaller than they should be, but no one's really sure about that.

[00:08:23] Speaker 03:
And the best, most accurate ruler is housed somewhere else, say in the Department of Measurements.

[00:08:28] Speaker 03:
But because the patent is actually relying on the King's ruler as the measuring stick, then the scope of the patent right

[00:08:37] Speaker 03:
has to be defined by that reference point and not a different one.

[00:08:44] Speaker 03:
So I guess the question is why shouldn't we be thinking of this particular patent in a similar way that it's defined the measuring stick, the Miller's protocol.

[00:08:56] Speaker 03:
Miller's protocol gives us an algorithm of how to do the measurement.

[00:09:03] Speaker 03:
I understand you're saying it's not as precise as it could be or should be, but nevertheless, if that's the measuring stick, then, you know, the rules are the rules and the ruler is the ruler.

[00:09:19] Speaker 02:
What's that thinking?

[00:09:22] Speaker 02:
We don't dispute that Miller provides the measuring stick.

[00:09:25] Speaker 02:
The problem, I think, in your analogy is that Miller is not just measuring the shoes, but there's, say, a giant piece of gum on the back of the shoes.

[00:09:32] Speaker 02:
And the question is, are you going to account for the giant piece of gum?

[00:09:36] Speaker 02:
And so you shouldn't have a measurement that includes that, because that's not the shoes.

[00:09:39] Speaker 02:
And the same thing is true in our case.

[00:09:41] Speaker 02:
that you've got, you're supposed to be measuring the beta-galactosidase activity, but there's something else there.

[00:09:46] Speaker 02:
And that's what that evidence from the literature and from the co-inventor says.

[00:09:50] Speaker 02:
And so basically, for your analogy, I'd say you have to take off the piece of gum that I could come up with right now.

[00:09:56] Speaker 01:
Ms.

[00:09:56] Speaker 01:
Saharsky, I looked at the numbers and here's what is bothering me about your control and the numbers that are associated with it.

[00:10:05] Speaker 01:
Normally, a control, it's pretty simple.

[00:10:08] Speaker 01:
You have something that has X and Y in it.

[00:10:11] Speaker 01:
You get a certain number based on the components, the entire package.

[00:10:17] Speaker 01:
and then you do a control that lacks X but has Y and you get a smaller number and therefore you know what presumably the X has contributed.

[00:10:27] Speaker 01:
But the problem here that I see is the 1540 has miller unit levels that are much smaller than the levels that are associated with strains A and B, which suggests that the

[00:10:43] Speaker 01:
The controls are not perfect controls.

[00:10:48] Speaker 01:
In fact, the only control that looks like it may have been suitable is Control C, which is the one that's mentioned in the email that says that Control C did not show that there was a, that the beta-gal level was below the claimed range.

[00:11:12] Speaker 01:
Could you respond to that?

[00:11:13] Speaker 01:
And the numbers that I found were, for example, the 1540, setting out, throwing out the one high value, which you also threw out, is between 0.06 to 0.62 Miller units.

[00:11:27] Speaker 01:
And the strain A is 1.2 to 2.2.

[00:11:33] Speaker 01:
And strain B is 0.66 to 0.91, both larger than the tested levels for 1540.

[00:11:43] Speaker 01:
How do you square that?

[00:11:45] Speaker 02:
Sure, two responses, Your Honor.

[00:11:46] Speaker 02:
First of all, I think these questions go to whether, don't go to whether a negative control strain is used, but what would be an appropriate negative control strain.

[00:11:55] Speaker 01:
How about strain C as a negative control?

[00:12:00] Speaker 02:
Well, I think that goes to the second point, Your Honor, which is the

[00:12:06] Speaker 02:
Numbers here that are being measured are at the absolute low limit of what the Miller protocol can detect.

[00:12:11] Speaker 02:
That's what the co-inventor of the patent said.

[00:12:13] Speaker 02:
And so to the extent that these numbers are so close to each other or have some of the anomalies that you identified, I think it's because of measurement uncertainty as opposed to something else.

[00:12:23] Speaker 01:
But shouldn't we then conclude that negative controls of the sort that you've offered into evidence simply have to be disregarded because they don't give reliable measurements?

[00:12:35] Speaker 02:
I don't think that's right.

[00:12:36] Speaker 02:
Negative controls are well known.

[00:12:38] Speaker 02:
They were noted in the literature.

[00:12:40] Speaker 01:
Of course, but there are some negative controls that just don't work because, as you suggested, they may be in an area in which the measurements are just not precise enough to give...

[00:12:54] Speaker 02:
Glycosine has never proposed a different negative control.

[00:12:56] Speaker 02:
In fact, they got our negative controls and then just decided inexplicably not to use them.

[00:13:01] Speaker 02:
But I think this goes to a second question as to what negative controls to use on which glycosine would have the burden of infringement and not the initial question of, do you need a negative control in the first place?

[00:13:12] Speaker 02:
And I can see that I'm in my rebuttal time.

[00:13:13] Speaker 02:
So unless the court has further questions, I'd like to reserve the remainder of my time.

[00:13:17] Speaker 03:
Yeah, just one quick question.

[00:13:19] Speaker 03:
Your preferred negative control strain

[00:13:24] Speaker 03:
Is it true that it lacks elements three and four of the claimed bacterium?

[00:13:36] Speaker 03:
The inactivating mutation and then also the... So, okay, thanks.

[00:13:47] Speaker 02:
I think the point of the negative control strain is to get it to be as close as possible, and then just have the one difference be to have it lack the gene.

[00:13:56] Speaker 02:
And so, again, Glycosine didn't propose an alternative negative control strain here, if I could reserve the rest of my time.

[00:14:02] Speaker 00:
We will give you three minutes of rebuttal time, Ms.

[00:14:07] Speaker 00:
Dostoevsky.

[00:14:07] Speaker 00:
Vince Morad.

[00:14:08] Speaker 05:
Thank you.

[00:14:10] Speaker 05:
Good morning, Your Honor.

[00:14:11] Speaker 05:
May it please the Court?

[00:14:14] Speaker 05:
I'd like to first address the

[00:14:16] Speaker 05:
the acute strain because I'd like to correct something that Appalachian Council said that the ALJ or the commission did not make a finding as to the leakage of the temperature regulator.

[00:14:33] Speaker 05:
Actually, at Appendix 102, the commission did make specific findings and relied on Dr. Prather's testimony that these temperature regulators leak.

[00:14:45] Speaker 05:
and that was not disputed by Conowhine.

[00:14:49] Speaker 05:
With respect to the negative control strain, I agree with you that with one strain, they were not able to defeat infringement.

[00:15:02] Speaker 05:
With one strain, they were able to, but the result was getting negative Miller Units.

[00:15:10] Speaker 05:
I would argue that this would make the claims less definite.

[00:15:14] Speaker 05:
because it is not clear what negative control strain would the parties use.

[00:15:21] Speaker 05:
And the claim language here not only requires the presence of the beta-galaxosidase gene, but requires following the Miller assay.

[00:15:30] Speaker 05:
The Miller assay does not call for subtracting a negative control strain.

[00:15:36] Speaker 05:
The commission credited expert testimony that you don't do that, you don't subtract

[00:15:42] Speaker 05:
negative strains from the tested strains when you run the Miller assay.

[00:15:46] Speaker 05:
The Commission did that as Appendix 111.

[00:15:48] Speaker 05:
In fact, even the literature that General Wine points to, they do side-by-side comparisons of negative strains with tested strains, but there's never a subtraction of the Miller results of one strain from another.

[00:16:06] Speaker 05:
And the glycogen expert confirmed that

[00:16:09] Speaker 05:
at Appendix 29627 and 29628.

[00:16:14] Speaker 03:
Ms.

[00:16:15] Speaker 03:
Murad?

[00:16:16] Speaker 03:
Yes.

[00:16:16] Speaker 03:
This is Judge Fenn.

[00:16:18] Speaker 03:
What do you have to say about the evidence that Jenowyn introduced in the record that shows there are example strains in the literature that don't have the beta-galgene but nevertheless produce positive Miller unit readings?

[00:16:39] Speaker 03:
And so, therefore, that we should take away from that, that whatever genoines, acute strains are registering as Miller unit readings, there's some component of that is due to things that have nothing to do with a beta-gal gene.

[00:17:04] Speaker 05:
Well, to respond to your question, I have to...

[00:17:08] Speaker 05:
direct you to the Miller assay itself, which points to potential sources of noise, like fermentation media cellular debris, which has been taken care of by the parties by centrifugation, but also the reactant, ONPG.

[00:17:27] Speaker 05:
There is a potential for that reaction to hydrolyze spontaneously.

[00:17:32] Speaker 05:
And the way you take that into account, as explained in Miller, is by doing an ONPG control.

[00:17:41] Speaker 05:
So your blank has to include ONPG to account for that spontaneous hydrolysis.

[00:17:47] Speaker 03:
That's according to the... I'm sorry.

[00:17:50] Speaker 03:
Oh, that's... You do all those things, though.

[00:17:54] Speaker 03:
You take care of all those things under Miller's protocol.

[00:17:57] Speaker 03:
Is that correct?

[00:17:59] Speaker 05:
Glycogen did that in its testing, but Genowine did not.

[00:18:02] Speaker 05:
And that could explain why their negative strains have positive values.

[00:18:07] Speaker 03:
Yeah, I'm referring to the evidence at the gray brief, page 10.

[00:18:13] Speaker 03:
I don't know if you have Genowine's reply brief.

[00:18:16] Speaker 03:
And there, they identified three categories of different kinds of evidence that shows that when you undertake the Miller protocol for a

[00:18:29] Speaker 03:
for a sample, for a strain that doesn't contain the beta-gal gene, there are examples of when you still nevertheless get Miller unit readings.

[00:18:39] Speaker 03:
And I guess are you trying to say that, well, you would prefer to dismiss all of these because all of these examples certainly must have failed to properly follow the Miller protocol?

[00:18:55] Speaker 05:
What we explained in the page 36 and 37 of our brief is that there is no evidence that the scientific literature was concerned with the level of precision that we were concerned with in the litigation.

[00:19:09] Speaker 05:
And so one thing that is not evident from the literature is whether they did an ONPG control, which is what takes into account

[00:19:23] Speaker 05:
spontaneous hydrolysis of OMPG.

[00:19:26] Speaker 03:
But as I understand it, you agree that that type of OMPG control, that's part of Miller's protocol, correct?

[00:19:35] Speaker 05:
Not necessarily, Your Honor, because the Miller Protocol says you may want to do the OMPG control, but the scientific literature, if they're not concerned with the level of precision that we were concerned with, they may not necessarily do that.

[00:19:54] Speaker 05:
And I haven't seen that they've done that.

[00:19:56] Speaker 05:
And Genewine itself, Appendix 51324, shows that

[00:20:02] Speaker 05:
Their blank was just the Z-buffer.

[00:20:05] Speaker 05:
At Appendix 29699, glycosine experts expressly testified that you have to have OMPG in the blank if you want to account for the spontaneous hydrolysis of OMPG.

[00:20:23] Speaker 05:
So there could be reasons why those negative strains generate Miller units.

[00:20:28] Speaker 05:
But glycosine showed by a preponderance of the evidence

[00:20:32] Speaker 05:
that the Miller units were beta-galactosidase activity, because there was no evidence that any other gene could cause beta-galactosidase activity.

[00:20:43] Speaker 05:
Even GenYne's experts admitted to that at authentic 29H22.

[00:20:49] Speaker 05:
As to other sources of noise, glycogen testing accounted for that.

[00:20:54] Speaker 05:
They did the centrifugation to account for fermentation media and cellular debris, and they followed

[00:21:01] Speaker 05:
the ONPG control that was called for in the Miller assay.

[00:21:06] Speaker 05:
And actually the commission specifically found that Genouine's ONPG control was flawed because it included cells when it was not supposed to.

[00:21:20] Speaker 05:
And I'd like to also point to

[00:21:25] Speaker 05:
Here, it is undisputed that the Miller Protocol does not disclose the use of a negative control strain.

[00:21:35] Speaker 05:
The commission credited expert testimony by glycogen, you don't subtract the negative control strain from the tested strain.

[00:21:44] Speaker 05:
That is Appendix 111 citing Appendix 33983.

[00:21:47] Speaker 05:
So there was substantial evidence to support the commission's determination.

[00:21:52] Speaker 05:
And certainly we should not, the court should not allow General Wine to escape the substantial evidence standard by arguing that this is a claim construction dispute.

[00:22:01] Speaker 05:
It is not.

[00:22:02] Speaker 05:
The issue concerns the proper testing methodology and it is squarely factoring in nature.

[00:22:08] Speaker 05:
And furthermore, General Wine never presented this issue to the commission as a matter of claim construction and the court should not allow them to do that on appeal.

[00:22:19] Speaker 05:
If there are no further questions, I conclude my argument.

[00:22:25] Speaker 03:
And thank you, Your Honor.

[00:22:28] Speaker 03:
One of the accused strains was found by the Commission to be not infringing the claims.

[00:22:34] Speaker 03:
Is that right?

[00:22:39] Speaker 05:
Both accused, actually, yes, Your Honor, I see what you're saying.

[00:22:45] Speaker 05:
You're pointing to the CTFL-12 strain, correct?

[00:22:48] Speaker 03:
Yes.

[00:22:50] Speaker 05:
Yes, that strain was found to lack a functional beta-GADAC 30-day chain, and so it was found not to infringe.

[00:22:58] Speaker 05:
In addition, I know that GenWine went to Customs and further had a ruling from them that the 1242 strain also was found to be non-infringent for the same reasons as CTFL-12, and the 1242 strain has FDA approval.

[00:23:22] Speaker 00:
Thank you, Counsel.

[00:23:24] Speaker 00:
Let's hear from Mr. Newman.

[00:23:27] Speaker 05:
Thank you.

[00:23:39] Speaker 00:
Mr. Newman, are you there?

[00:23:40] Speaker 04:
Thank you, Your Honors, and may it please the Court.

[00:23:47] Speaker 04:
I'd like to go right to the issue of background noise.

[00:23:51] Speaker 04:
And note that Miller has two different procedures, one for testing high levels of beta-galactosidase and one for testing low levels.

[00:24:00] Speaker 04:
When testing for low levels, there's the ONPG step and not for high levels.

[00:24:07] Speaker 04:
And the articles that Genovine points to that are showing background noise are tests that are testing for beta-galactosidase activity up to 20,000 units.

[00:24:21] Speaker 04:
And so these tests are not interested whatsoever at the low level of beta-galactosidase.

[00:24:26] Speaker 04:
And I think it could be presumed that those do not include the standard controls that you would use in the Miller Protocol for testing low levels of beta-galactosidase activity.

[00:24:39] Speaker 04:
I would also take a bit of an exception to Yennebine stating that there is, it's undisputed that the,

[00:24:50] Speaker 04:
Beta-galactosidase activity needs to be attributed to the beta-galactosidase gene that was inserted.

[00:24:56] Speaker 04:
Genoine's pre-hearing brief was clear that the claim required measuring the strains beta-galactosidase activity.

[00:25:04] Speaker 04:
And specifically, they said the units must reflect the beta-galactosidase activity of the bacterium.

[00:25:11] Speaker 04:
Genoine's expert also testified along the same line.

[00:25:14] Speaker 04:
that the asserted claims require the measured units reflect beta-galactosidase activity of the E. coli bacterium, opposed to the gene itself.

[00:25:23] Speaker 04:
That's at appendix 60658.

[00:25:27] Speaker 04:
During the Markman proceedings, Yenovine contended that the Miller units must be measured by strictly adhering to the Miller assay.

[00:25:34] Speaker 04:
For example, at appendix 204, Yenovine faulted glycosin for wanting to adopt the Miller assay.

[00:25:41] Speaker 04:
the method of calculating units, but not the expressed description of how the assay should be performed.

[00:25:47] Speaker 04:
So over and over again, Yennevarin took the position that the Miller test needed to be performed to the letter of Miller as described in the Miller assay.

[00:26:01] Speaker 04:
And so the first we heard of the idea that the activity needed to be,

[00:26:10] Speaker 04:
corresponding to the gene that was inserted was in the post-hearing brief, and therefore, I mean, I think their argument is waived under Broadcom Corp.

[00:26:21] Speaker 04:
But regardless, even if the claim did require that the activity be attributable to the inserted beta-glacosidase gene, the ALJ found that it did.

[00:26:29] Speaker 04:
In Appendix 106, the ALJ found that the limitation was still met.

[00:26:34] Speaker 04:
since the strain produced beta-galactosidase activity in the range and no other source of beta-galactosidase activity other than the functional beta-galactosidase gene was identified.

[00:26:44] Speaker 04:
There was a finding of fact that Miller units from glycosine tests were beta-galactosidase activity.

[00:26:51] Speaker 04:
That's appendix 116117.

[00:26:54] Speaker 04:
There was a finding of fact that the only known source of beta-galactosidase in the accused strain was the inserted beta-galactosidase gene.

[00:27:01] Speaker 04:
That's appendix 109.

[00:27:04] Speaker 04:
There was a finding fact that repressors leak, and that's Appendix 102.

[00:27:09] Speaker 04:
And there was a finding of the fact that Inovine's tests were not credible and were not reliable.

[00:27:15] Speaker 04:
That's at Appendix 106, Appendix 116.

[00:27:18] Speaker 03:
Mr. Newman, you were saying that Miller uses ONDG controls for low levels of activity, but not high levels of activity, and then generalized cited literature

[00:27:32] Speaker 03:
deals with cases of high levels of activity, is that right?

[00:27:37] Speaker 03:
Yeah, I understand you're correct.

[00:27:40] Speaker 03:
Where in the records do you have evidence of all this?

[00:27:45] Speaker 04:
At appendix 53964, you can see that the test being performed is for a plasmid that includes a beta-galactosidase gene that expresses Miller units at 20,000

[00:28:02] Speaker 04:
Miller units?

[00:28:06] Speaker 01:
It would have been helpful if this issue had been briefed on your side.

[00:28:11] Speaker 01:
I didn't see anything in the briefs that raised the issue you've raised here at argument.

[00:28:17] Speaker 04:
Did I miss something?

[00:28:29] Speaker 01:
I guess I don't remember, Your Honor, exactly if we... I don't remember it either, and I read the brief several times, so I don't think there's anything at least as explicit as what you're saying now about the problem with the literature.

[00:28:45] Speaker 04:
Yes, Your Honor, it very well may be that this is in response to the reply brief that we got.

[00:28:59] Speaker 00:
Anything further, Mr. Newman?

[00:29:02] Speaker 04:
No, Your Honor, unless there are any questions.

[00:29:07] Speaker 00:
Thank you.

[00:29:08] Speaker 00:
Ms.

[00:29:08] Speaker 00:
Sikorski has some rebuttal time.

[00:29:10] Speaker 00:
We'll give you three minutes.

[00:29:13] Speaker 02:
Thank you, Your Honors.

[00:29:13] Speaker 02:
I'd like to start with a negative control strain issue.

[00:29:15] Speaker 02:
And first, I'd like to start with, I think, a question Judge Chen asked

[00:29:19] Speaker 02:
I'm afraid I misunderstood that question and gave the wrong answer, so I want to correct that.

[00:29:23] Speaker 02:
I think the question was whether the strains we used had the limitations Romanet 3 and Romanet 4 in the patents, and the strains did not.

[00:29:33] Speaker 02:
I just checked the record on that, but I'd say that Glycosine never provided a different negative control.

[00:29:38] Speaker 02:
In fact, they had planned to use our negative control and then inexplicably decided not to use it.

[00:29:44] Speaker 02:
And I think the question here is what the claim requires.

[00:29:46] Speaker 02:
Does it require a negative control?

[00:29:48] Speaker 02:
Not exactly how should the test be run or what is the right negative control.

[00:29:53] Speaker 02:
And now glyphosin is coming in and saying the claim doesn't even require use of or measuring the activity of the gene.

[00:29:59] Speaker 02:
But that comes right from the claim language.

[00:30:01] Speaker 02:
It says that there's an exogenous functional gene comprising a certain level of activity.

[00:30:07] Speaker 02:
And that's what needs to be measured.

[00:30:09] Speaker 02:
I guess the second point would be this evidence that we talked about, and I'm happy that the court has looked closely at it, this evidence in the literature from Italy, from the UK, and from the US.

[00:30:18] Speaker 02:
These are three different sets of tests, more than one test in each one, peer-reviewed, that talk about there being Miller unit activity for cells that completely lack the gene.

[00:30:30] Speaker 02:
And there's this new attempt by Glycosin, an argument that wasn't in any of the briefs about, oh, these are just for high levels.

[00:30:36] Speaker 02:
But that's not, I would take a look at this literature.

[00:30:38] Speaker 02:
That's not what it says.

[00:30:40] Speaker 02:
And plus, there's still the other evidence of the co-inventor of this very patent that said that he tested bacterium that didn't have the gene and got up to 0.2 Miller units, which is well within the level of activity here.

[00:30:53] Speaker 02:
And I guess I understand the arguments that the ITC and the Glycosin are making about, oh, the ALJ found some issues with the way that Yenowine conducted its test.

[00:31:02] Speaker 02:
But I would say you can put all that evidence aside, all of the evidence of how Yenowine conducted its test, and you still have this evidence from the literature and from the co-inventor of the patent.

[00:31:12] Speaker 02:
And by the way, to the extent that there are criticisms of how we conducted our test,

[00:31:17] Speaker 02:
Yenowine also conducted tests of the negative control following Glycosine's protocol exactly to the letter and found Miller unit readings for a cell that lacks the gene of up to 2.24 units.

[00:31:30] Speaker 02:
And the point, Your Honors, is that this negative control really matters because our strains don't have the ability to make beta-galactosidase activity.

[00:31:40] Speaker 02:
Everything that's being reported is just this background noise, and we're talking about the absolute lowest limits of what can be detected in the Miller Protocol.

[00:31:48] Speaker 02:
And I would also just point, Your Honors, to our other arguments related to the fact that there's not an exogenous functional gene here, because it's only part of it that's exogenous.

[00:31:58] Speaker 02:
and the timing issue.

[00:32:00] Speaker 02:
The long and short of it here is that what our strains do is just not what's claimed in the patent.

[00:32:05] Speaker 02:
And Glycosin is trying to stretch and stretch and stretch the terms of this patent to try to get it covered.

[00:32:11] Speaker 02:
But it's fundamentally different, because we just don't have the genes that are functional during this process.

[00:32:18] Speaker 02:
So we respectfully urge that you reverse the decision of the IPC.

[00:32:24] Speaker 01:
Could I ask just a purely procedural question

[00:32:28] Speaker 01:
There are a couple of citations in the appendix.

[00:32:33] Speaker 01:
Well, they're in your briefs to things in the appendix that I found missing.

[00:32:40] Speaker 01:
You cite, and I think this is on about pages 39 to 40 or so of your opening brief, you cite pages 48, oh, 38 I think it is, and 54, 368.

[00:32:56] Speaker 01:
both of which are blank pages.

[00:32:59] Speaker 01:
They are followed by a gap in the appendix, which I assume was, these are Yenavine's test results, but I assume those were intended to be the inclusion of the test results from Yenavine.

[00:33:14] Speaker 01:
Should we have those or what is the story with those citations?

[00:33:20] Speaker 02:
Your Honor, I'm going to need to take a look at those citations.

[00:33:25] Speaker 01:
I think you'll find that the page is indicated placeholder and there's nothing, there's a skip then which appears just to be material that was either intentionally or unintentionally omitted.

[00:33:42] Speaker 02:
Yes, Your Honor.

[00:33:44] Speaker 02:
We will take a look at that and then update the court as appropriate.

[00:33:47] Speaker 03:
Thank you.

[00:33:48] Speaker 03:
I've got a procedural question, too.

[00:33:52] Speaker 03:
Your 1242 strain has received FDA approval.

[00:33:57] Speaker 03:
How about your TTFL strain?

[00:34:02] Speaker 02:
I think so, but I don't have that in front of me, Your Honor, to double-check.

[00:34:08] Speaker 01:
One wonders why are we here, other than perhaps damages?

[00:34:14] Speaker 02:
Sorry, Your Honor.

[00:34:16] Speaker 02:
We provided the native Excel files through USB drives on the other sites that Your Honor was asking about.

[00:34:24] Speaker 02:
I think it was Judge Bryson.

[00:34:25] Speaker 02:
I'm sorry.

[00:34:26] Speaker 02:
Just to clarify this, this is pages 48038, 54368, et cetera.

[00:34:33] Speaker 02:
Those were provided to the court through USB drives.

[00:34:36] Speaker 02:
So they're not in paper, but they were provided in that way.

[00:34:41] Speaker 01:
Yeah, for a person that uses paper, relies on paper, that puts me at a something of a disadvantage, but thank you.

[00:34:48] Speaker 02:
Yeah, sorry about that confusion.

[00:34:51] Speaker 03:
If you could let us know about the FDA approval status of TTFL, I'd appreciate it in a short letter.

[00:34:58] Speaker 02:
Yes, will do, Your Honor.

[00:35:00] Speaker 02:
I'm sorry, I just want to double check that I don't want to misspeak.

[00:35:02] Speaker 02:
Thank you.

[00:35:05] Speaker 00:
Anything further?

[00:35:08] Speaker 00:
If not.

[00:35:09] Speaker 00:
The case is taken under submission.

[00:35:12] Speaker 00:
Thank you to both counsel.

[00:35:16] Speaker 04:
The Honorable Court is adjourned until tomorrow morning at 10 a.m.