[00:00:00] Speaker 02:
Our next case is Mylan Pharmaceuticals and MSN Laboratories versus Bosch Health Ireland, 2024, 1011, and 1053.

[00:00:11] Speaker 02:
All right, please proceed.

[00:00:18] Speaker 00:
Thank you, your honor.

[00:00:19] Speaker 00:
Good morning.

[00:00:20] Speaker 00:
May please the court.

[00:00:21] Speaker 00:
A single conservative substitution at a known finite point of interest in a peptide to create another peptide that has the same essential function is about as straightforward and easy as it gets when it comes to peptide chemistry.

[00:00:36] Speaker 02:
But it's a different compound.

[00:00:38] Speaker 00:
It's a different peptide, yes.

[00:00:40] Speaker 00:
It's a different compound.

[00:00:41] Speaker 00:
It is a different peptide with one single solution that was pointed out in the prior art.

[00:00:46] Speaker 02:
All right.

[00:00:47] Speaker 02:
So there is perhaps a prima facie case, as was found by the board.

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

[00:00:54] Speaker 02:
And then the board found that there were unexpected properties.

[00:01:01] Speaker 02:
And that's sort of a basic aspect of pharmaceutical patent law.

[00:01:06] Speaker 00:
It is.

[00:01:07] Speaker 00:
And if I could dig into those unexpected properties, Your Honor, the data set provided by Bausch is incomplete.

[00:01:13] Speaker 00:
And it led to a number of legal errors committed by the board, some of which they erred upon, some of which they didn't address.

[00:01:19] Speaker 00:
But when those issues are sorted out, what it boils down to is a failure by Bausch to meet their burden of production regarding that data set.

[00:01:26] Speaker 00:
Among the holes that exist in that data set,

[00:01:29] Speaker 00:
There's no information regarding the amount of Form A that was used in the Uruguayan sample.

[00:01:35] Speaker 00:
And Form A, of course, is the active topoisomer.

[00:01:37] Speaker 00:
Form B is inactive.

[00:01:38] Speaker 00:
So the more A isomer you have in your sample, the more potency you're going to see in the results.

[00:01:44] Speaker 00:
But we don't know what was the composition of those samples because they didn't produce that data.

[00:01:50] Speaker 02:
So we should be fact-finders and probe into all the details.

[00:01:56] Speaker 02:
of their determination?

[00:01:58] Speaker 00:
No, Your Honor, I'm not saying that.

[00:01:59] Speaker 00:
What I was about to pivot to was that the board let them off the hook with that failure to meet their burden of production.

[00:02:06] Speaker 00:
And one of the ways they did that was to define the closest prior art as being any mixture of A and B Uruguayan, as it naturally exists.

[00:02:15] Speaker 00:
And by allowing any mixture of A and B Uruguayan to be a comparator, what they allowed, the board allowed, was a comparison to lesser prior art.

[00:02:24] Speaker 00:
As I mentioned before, that the more form A you have in a sample, the more potent it's going to be.

[00:02:28] Speaker 00:
The less form A you have in a sample, the less potent it's going to be.

[00:02:32] Speaker 00:
But because that definition of the closest prior art includes inferior versions of Uruguayan that are known to be less potent,

[00:02:39] Speaker 00:
the board erred, because this court's precedent clearly holds that any comparison must be to the closest prior art, not to inferior prior art.

[00:02:48] Speaker 01:
Did Bouch below, I don't recall, argue that the closest prior art would just be the wild-type human uroguanilin, or did it argue that, or acknowledge that a-form version of human uroguanilin

[00:03:08] Speaker 01:
ever really get a clean test on pure A-form human guanulin, because even during the testing process, there's going to be some instability where it inter-converts into B-form.

[00:03:22] Speaker 00:
And that was the argument below, was that interconversion means that you can't have pure A-form as the comparator.

[00:03:28] Speaker 00:
But interconversion can be controlled.

[00:03:30] Speaker 00:
And the board found as much in its motivation analysis.

[00:03:32] Speaker 00:
Interconversion can be controlled by stabilizing the, first of all, you isolate the isomer to 99% purity.

[00:03:40] Speaker 00:
And you can store it in powder form for up to a year and keep it stable.

[00:03:45] Speaker 00:
And so, go ahead.

[00:03:47] Speaker 01:
Another question I have is then, it seems like everybody agrees that

[00:03:52] Speaker 01:
SP304, as it's reported out in table four of the patent in column 16, SP304 is a purified up to 95% A form of the GLUE III claimed invention.

[00:04:12] Speaker 01:
And if that's right, then why wouldn't the SP301 that's also reported in table

[00:04:19] Speaker 01:
likewise be a greater than 95% purified form, A-form of hemoglobin?

[00:04:26] Speaker 00:
Sure.

[00:04:27] Speaker 00:
So the SP304, what we've said, and this is based on Bausch's statements to the EPO, is that the SP304 was purified A-form plecanotide.

[00:04:37] Speaker 00:
So we weren't relying on that statement regarding purity in the patent, because you're looking at column 15 right now, I think.

[00:04:43] Speaker 00:
And that statement regarding purity doesn't say topoisomeric purity.

[00:04:47] Speaker 00:
It just says purity.

[00:04:48] Speaker 00:
And so they're excluding other peptides.

[00:04:50] Speaker 00:
They're not isolating a particular topoisomer of a single peptide.

[00:04:54] Speaker 00:
And if your honor looks at the footnote to that sentence, they refer to the clot reference.

[00:04:59] Speaker 00:
And this is important because clot discusses a method of synthesizing peptides and purifying them.

[00:05:04] Speaker 00:
And one of the peptides that he synthesized and purified was human uroguanilin.

[00:05:08] Speaker 00:
That's peptide 14 in Clot.

[00:05:10] Speaker 00:
And what Clot says after his discussion of synthesis and purification is that he found two topoisomers of human uroguanilin.

[00:05:18] Speaker 00:
And so that word purify in the specification, as it refers to Clot, it does not mean isolating a topoisomer.

[00:05:27] Speaker 00:
It means excluding the presence of other peptides.

[00:05:38] Speaker 01:
of the SB301 human guanulin version, it's a synthesized form of it.

[00:05:43] Speaker 01:
It's not just graphed from nature.

[00:05:45] Speaker 00:
It's not removed from urine or plasma.

[00:05:46] Speaker 00:
That's correct.

[00:05:47] Speaker 01:
And then it further says it's not only custom synthesized, but it was purified at greater than 95% purity.

[00:05:54] Speaker 00:
Of the peptide.

[00:05:55] Speaker 00:
It says nothing about topoisomeric purity.

[00:05:58] Speaker 00:
The word topoisomer or confirmor is nowhere near that sentence.

[00:06:01] Speaker 01:
But I'm just trying to understand if we all agree that the SB304 report in table

[00:06:09] Speaker 01:
on APORN, then why wouldn't it be true for the SP301?

[00:06:14] Speaker 00:
Because, like I just said, if you look at the clot reference, which is what that sentence is referring to, it was synthesized in accordance with a disclosed method.

[00:06:22] Speaker 00:
That's the clot paper.

[00:06:24] Speaker 00:
What clot discusses is that after he synthesized and after he purified, he found both topoisomers.

[00:06:30] Speaker 00:
And so he can't be referring to topoisomer purity, because clot doesn't discuss that, nor does the patent itself.

[00:06:39] Speaker 01:
You know, I think greater than 95% purity accounts for the fact that there's going to be a little bit of something else in there.

[00:06:48] Speaker 00:
Impurities or other peptides, yes.

[00:06:52] Speaker 01:
So, I mean, just because some B-form is found after the testing, I mean, I think that goes to the point of the other side on the board, which is, as a practical matter, you're not going to undertake these tests

[00:07:07] Speaker 01:
And if we accept that as being true and we use your 95% figure, Your Honor, that doesn't sync with what the board found regarding what the closest prior art is.

[00:07:25] Speaker 00:
They said it's any mixture.

[00:07:27] Speaker 00:
And so any mixture could include a very little bit of A form and a lot of B form or half and half.

[00:07:33] Speaker 00:
And that's far below the 95% standard yarn are just laid out.

[00:07:36] Speaker 00:
And so by defining the prior art, the closest prior art that broadly as a practical matter, what the board allowed is a comparison to inferior prior art.

[00:07:46] Speaker 01:
Well, the one thing I'll agree with is that it's a little less than clear whether the board said it's definitely gotta be a pure

[00:07:59] Speaker 01:
But I don't think it went so far to say any version of human guanlin, even a 50-50 A-form, B-form is good enough.

[00:08:10] Speaker 01:
That I don't think it's fair.

[00:08:13] Speaker 00:
I would push back on that respectfully, Your Honor.

[00:08:15] Speaker 00:
And that's because what the board said was, as it naturally exists, and it naturally equilibrates to a one-to-one ratio of A to B. And so I think they did have that in mind.

[00:08:23] Speaker 00:
And if you look at the citations that they included in the evidence that they looked at,

[00:08:28] Speaker 01:
including table four, SP301, is showing something else about this purification.

[00:08:36] Speaker 00:
Something else about the purification?

[00:08:37] Speaker 01:
I apologize, John, I don't follow up.

[00:08:57] Speaker 01:
hot reference in this patent.

[00:09:02] Speaker 00:
What I would say to that, Your Honor, is if the question of what is the closest prior art is addressed correctly, because the board did err on that, to be the purest form, A-form, you can get of your guanolin, then that shines a spotlight on this burden of production, because there is no information that they produce that allows us to conclude that the sample they used met that standard.

[00:09:25] Speaker 02:
You had argued in your brief that the difference here was a CH2, a methylene group, which is quite a small difference.

[00:09:35] Speaker 02:
And now you're saying that's not the closest prior art?

[00:09:38] Speaker 00:
No, I'm saying your guanidine is the closest prior art.

[00:09:41] Speaker 00:
But there are different mixtures of the A and B form of your guanidine.

[00:09:45] Speaker 00:
The A form has the activity.

[00:09:46] Speaker 00:
So the higher the concentration of the A form in the sample that you're testing, the more potency you're going to see.

[00:09:51] Speaker 02:
They both have the same structure.

[00:09:53] Speaker 00:
They both have the same structure that is correct, Your Honor.

[00:09:57] Speaker 00:
They're just configured differently in a three-dimensional space, and that apparently has a difference with regard to how they interact with the receptor here.

[00:10:05] Speaker 00:
And so if we were to redefine the closest priority as being pure form A, or as close as you can get to it, again,

[00:10:11] Speaker 00:
It's their burden to produce information that will allow us to tell that their sample met that.

[00:10:16] Speaker 00:
And they can't do that.

[00:10:17] Speaker 03:
I think Your Honor pointed out that the one sentence... So we don't know what the comparison was that they made.

[00:10:21] Speaker 00:
Yes, Your Honor.

[00:10:22] Speaker 00:
That's exactly right.

[00:10:23] Speaker 00:
The one sentence they leaned on was what Judge Chen pointed out, was the word purity.

[00:10:28] Speaker 00:
And they leaned very heavily into that sentence.

[00:10:29] Speaker 00:
But again, the word purity refers to the exclusion of other peptides.

[00:10:33] Speaker 00:
It doesn't refer to topoisomeric purity.

[00:10:36] Speaker 00:
There's no reason to think that it does.

[00:10:37] Speaker 00:
And I also add the board did not make that finding below that that's what that sentence means.

[00:10:42] Speaker 00:
That's what they're urging.

[00:10:44] Speaker 01:
When you say there's no reason to think that it does refer to A-form purity, why would you say that?

[00:10:53] Speaker 00:
because there's no mention of isolating a topoisomer in that patent.

[00:10:57] Speaker 00:
And I point out that Bausch received a later patent that claimed a pure form A plecanotide.

[00:11:05] Speaker 00:
And so in this patent, they can't be discussing that because they later claimed it.

[00:11:08] Speaker 00:
And that patent has a later expiration date as well.

[00:11:11] Speaker 00:
And so the purification process they're talking about was not what they discussed in the later patent.

[00:11:16] Speaker 00:
It's what was discussed in Klopp.

[00:11:19] Speaker 02:
You're into your rebuttal.

[00:11:21] Speaker 02:
You can use it or save it.

[00:11:23] Speaker 00:
I apologize.

[00:11:23] Speaker 00:
I'll save it, Your Honor.

[00:11:24] Speaker 00:
Thank you.

[00:11:34] Speaker 02:
Mr. Haskell.

[00:11:35] Speaker 04:
Thank you very much, Judge.

[00:11:38] Speaker 04:
May it please the Court, Your Honors, Myland's arguments regarding closest prior art commensurate in scope and unexpected superior properties do not warrant reversal of the Board.

[00:11:49] Speaker 03:
What was the comparison that was made?

[00:11:52] Speaker 03:
Was it A-form to A-form or not?

[00:11:54] Speaker 04:
The comparison, Your Honor, that was made was to human uroguanilin as it naturally exists and the Board correctly considered, Your Honor, that human uroguanilin naturally interconverts between

[00:12:05] Speaker 04:
and exists as a mixture of two total licenses.

[00:12:08] Speaker 03:
So in other words, we don't know what the mixture was that was involved in the comparison.

[00:12:12] Speaker 04:
We don't know the exact number, but irrespective of that, it represents the closest prior art.

[00:12:18] Speaker 04:
Had it been a 50-50 mixture, Your Honor?

[00:12:20] Speaker 03:
So in other words, if we were to say that the closest prior art is the A mixture, no such comparison was made.

[00:12:28] Speaker 04:
If Your Honor were to say that the closest prior art were purified human urine, is that your question?

[00:12:35] Speaker 03:
If it were A-form, yes.

[00:12:36] Speaker 04:
Yes, then Bausch did test against purified human urogonilum because the peptides, all those peptides were purified to 95% or greater.

[00:12:46] Speaker 03:
Okay, but let's assume for a moment that they're right.

[00:12:48] Speaker 03:
Purified doesn't mean purified 95% A-form, it just means purified human urogonilum peptide.

[00:12:57] Speaker 03:
So let's assume that purified doesn't mean purified 95% A-form.

[00:13:03] Speaker 03:
It just means that purified doesn't include other peptides.

[00:13:09] Speaker 04:
Then Bausch still tested against the closest prior art because it is a purified form of human uroguana.

[00:13:15] Speaker 03:
Wait, wait, wait.

[00:13:17] Speaker 03:
But we don't know, other than the use of the word purified here, whether the comparison was A-form to A-form, right?

[00:13:26] Speaker 04:
We know that the comparison was to a purified version.

[00:13:30] Speaker 03:
You know, I'll answer my question.

[00:13:32] Speaker 03:
We don't know whether the comparison was A-form to A-form.

[00:13:36] Speaker 04:
You mean A-form of plecanotide to A-form of human urine?

[00:13:39] Speaker 03:
Yes.

[00:13:40] Speaker 04:
So that is ultimately what the test is getting at.

[00:13:45] Speaker 01:
What's the test when you say that test is getting it?

[00:13:48] Speaker 04:
So the test that Bausch conducted, Your Honor, the test for T. And that's what we're trying to figure out.

[00:13:55] Speaker 01:
Right.

[00:13:55] Speaker 01:
We're trying to figure out two things.

[00:13:58] Speaker 01:
One is, did Bausch actually use a purified aid form of human guanine to put up against a purified aid form of tecanotide?

[00:14:12] Speaker 01:
And then, if so, did the board appreciate that?

[00:14:16] Speaker 01:
Did the board make a fact-finding?

[00:14:18] Speaker 01:
I mean, it's unclear to me from what the board said whether

[00:14:23] Speaker 01:
it understood that the closest prior art that needed to be examined was the purified A-form.

[00:14:34] Speaker 04:
The factual finding, respectfully, that the board made was that the closest prior art is human uroguanilin as it naturally exists.

[00:14:43] Speaker 01:
OK, but stop right there.

[00:14:45] Speaker 01:
As it naturally exists, that sounds like wild type.

[00:14:50] Speaker 04:
So Bausch did not test against wild-type human uroguanlina.

[00:14:54] Speaker 01:
However, had Bausch tested against wild-type human uroguanlina with... Well then, you would agree, wouldn't you, that testing against wild-type human guanlina would not be the closest prior art?

[00:15:05] Speaker 04:
That actually would reflect the closest prior art as well, Your Honor.

[00:15:26] Speaker 01:
saying that you agreed with that, that that is the closest prior art.

[00:15:30] Speaker 01:
With the recognition that there's going to be some interconversion to B form during the testing process, blah, blah, blah.

[00:15:36] Speaker 01:
But nevertheless, the starting material you would use as the closest prior art would be a purified A form of human guanine.

[00:15:45] Speaker 01:
That's what I remember hearing you say before.

[00:15:47] Speaker 01:
Then 40 seconds ago, I heard you say something else, that just as it exists in nature, human guanine would be the closest prior art.

[00:15:56] Speaker 01:
Those are two different things, though.

[00:15:57] Speaker 01:
Which one is it?

[00:15:58] Speaker 04:
So either could reflect the closest prior art, your honor, and as the tests are conducted, you're determining the difference.

[00:16:05] Speaker 01:
So then now you're making it even less clear to me which version did the board think was the closest prior art.

[00:16:12] Speaker 01:
Maybe the board thought it could have been either one of them.

[00:16:15] Speaker 01:
And then if that's the case, the question becomes, is it correct to think a wild type, naturally existing human guana could be regarded as a

[00:16:26] Speaker 01:
when it was known in New York that you could get an extra purified A-form version of human guanolin.

[00:16:33] Speaker 01:
And maybe that would be the true apples to apples comparison to a purified A-form with a chemical.

[00:16:40] Speaker 04:
So respectfully, Your Honor, the issue with trying to get human-era guanolin perfectly pure, it would be chemically difficult, if not impossible, to get it 100% pure.

[00:16:50] Speaker 01:
But at least they're trying to.

[00:16:52] Speaker 01:
People had done that.

[00:16:54] Speaker 01:
in the art and the fact that those attempts did produce some close to purely purified versions, but nevertheless it's altered and synthesized and different from how it was initially.

[00:17:09] Speaker 04:
Only at certain temperatures, Your Honor, would it be able to resist interconversion at really low temperatures.

[00:17:14] Speaker 04:
It could resist interconversion, but naturally there will be some interconversion on the board at appendix.

[00:17:20] Speaker 03:
Look, what was the comparison?

[00:17:22] Speaker 03:
Was the comparison

[00:17:24] Speaker 03:
between the wild type A to the gluten A, or was the comparison something else?

[00:17:33] Speaker 03:
How do we know what the comparison was?

[00:17:35] Speaker 04:
The comparison, your honor, as the tests were conducted, the peptides were purified to greater than 95% purity.

[00:17:41] Speaker 03:
OK, but what does purified to 95% mean, is the question.

[00:17:47] Speaker 03:
How do we know that that's A-form to A-form?

[00:17:51] Speaker 04:
Because that's how human uroguanlone, when human uroguanlone naturally exists, it interconverts.

[00:17:57] Speaker 04:
And the board made that finding based on the prior art and the testimony of Dr. Davis and Dr. Walden, and credited that the prior art, including the Chino reference, appendix 4293.

[00:18:06] Speaker 03:
Did those witnesses testify that the test was run on the

[00:18:13] Speaker 04:
those witnesses testified that no no answer the question yes no they did not testify that the test will run against 100 percent pure human you're a did they testify that was 95 percent if that they test where did they testify that that the uh... those uh... that appendix thirty eight to thirty nine it cites their testimony

[00:18:53] Speaker 04:
Their testimony, Your Honor, is going to be at paragraphs 67 through 68 of one of...

[00:19:15] Speaker 04:
Dr. Davis's testimony is paragraphs 67 through 68.

[00:19:20] Speaker 03:
What page are we talking about?

[00:19:21] Speaker 04:
So that's going to be joint appendix 4812 to 4813, Your Honor.

[00:19:25] Speaker 03:
4812?

[00:19:27] Speaker 03:
Okay.

[00:19:29] Speaker 04:
And Dr. Waldman's testimony in that regard.

[00:19:33] Speaker 03:
Wait, wait, wait.

[00:19:35] Speaker 03:
Okay.

[00:19:36] Speaker 03:
4812, where does he say that it's purified to 95% of the page?

[00:19:59] Speaker 03:
can't even find the testimony that supports them.

[00:20:03] Speaker 04:
He's testifying at paragraphs 67 and 68, your honor, about the interconversion.

[00:20:09] Speaker 03:
Where does he say it's purified to 95% type A?

[00:20:15] Speaker 04:
So the patent respectfully says that.

[00:20:17] Speaker 03:
No, no, no.

[00:20:18] Speaker 03:
You said that your witness has said that.

[00:20:53] Speaker 01:
Could it be 95% A-form versus 5% or less of A-form?

[00:21:02] Speaker 01:
Or does it mean something more broadly?

[00:21:11] Speaker 01:
points, vis-a-vis other possible peptides.

[00:21:15] Speaker 04:
Respectfully, Your Honor.

[00:21:18] Speaker 04:
Bausch's own tests show that the purification process will remove the topoisomers.

[00:21:22] Speaker 04:
And that was part of the unexpected results that Bausch showed.

[00:21:26] Speaker 04:
So when these peptides are purified by HPLC.

[00:21:29] Speaker 01:
I'm just trying to understand how to interpret this test at problem 15.

[00:21:35] Speaker 01:
How do we know?

[00:21:36] Speaker 01:
It's either one or the other.

[00:21:39] Speaker 01:
How do we know it's 95% A-form versus 5% or less B-form?

[00:21:47] Speaker 04:
It's at least 95% A-form because the HPLC process does remove the inactive topoisomeric purity.

[00:21:53] Speaker 03:
But you testified.

[00:21:56] Speaker 03:
No, you testified.

[00:21:57] Speaker 03:
I asked you where the testimony was, and you couldn't find it.

[00:22:01] Speaker 04:
So the topoisomeric purity, Your Honor,

[00:22:11] Speaker 04:
It was the Stability Against Interconversion test that Bausch ran, and they were able to, in fact, the board copy-pasted in the opinion a graph that shows separation of the cuban uroguano and the inactive topoisomer.

[00:22:44] Speaker 04:
That's Appendix 41.

[00:22:45] Speaker 04:
So Appendix 41 shows a graph where

[00:22:52] Speaker 04:
HPLC was run on samples of human urine and sp304 plecanotide.

[00:22:58] Speaker 04:
And the inactive fraction there represents the inactive topoisomer.

[00:23:04] Speaker 04:
And that shows that the HPLC process, in fact, does separate the inactive from the active topoisomer.

[00:23:11] Speaker 04:
And they ran HPLC.

[00:23:13] Speaker 02:
There's more than one set of data showing purportedly unexpected activity.

[00:23:21] Speaker 02:
Were all of those sets of data based on one standard?

[00:23:29] Speaker 02:
Were they based on different things?

[00:23:32] Speaker 04:
They were.

[00:23:32] Speaker 04:
They were based, Your Honor, on the procedure that is set forth in columns 15 and 16 of the patent, and the data there are shown in Table 4.

[00:23:44] Speaker 03:
Well, we're just looking at 41 in this rep.

[00:23:47] Speaker 03:
We don't know what the starting material was, right?

[00:23:49] Speaker 04:
the starting material would have been human uroguana as it naturally existed.

[00:23:54] Speaker 01:
And what does that mean?

[00:23:55] Speaker 04:
50-50 wild times?

[00:23:57] Speaker 04:
Depending on the temperature, depending on the pH, it could be as low as 50-50 or it could be... So then the starting material was not a purified version?

[00:24:06] Speaker 04:
Well, so I apologize, your honor.

[00:24:09] Speaker 04:
So the starting material in this particular experiment, they did custom synthesize them.

[00:24:14] Speaker 01:
Custom synthesize to create what?

[00:24:17] Speaker 04:
To create human uroguanlum.

[00:24:19] Speaker 01:
To create, well, an A-form, a purified A-form?

[00:24:23] Speaker 04:
To 95% or greater, yes.

[00:24:25] Speaker 01:
And how do we know that?

[00:24:27] Speaker 04:
Because they showed through HPLC that it was 95% or greater.

[00:24:31] Speaker 04:
They ran them through HPLC.

[00:24:34] Speaker 01:
The HPLC separates the... And where can we find that in the record, where it's like, I did an HPLC test, and voila, look what I did.

[00:24:47] Speaker 01:
I created a 95% purified A-form version of human quality.

[00:24:50] Speaker 04:
And so the inventor did put in a declaration, your honor, to that effect.

[00:24:54] Speaker 04:
And that inventor declaration is...

[00:25:00] Speaker 04:
I believe appendix 5599.

[00:25:05] Speaker 04:
5599.

[00:25:06] Speaker 03:
Yes.

[00:25:13] Speaker 04:
Yes, it is, Your Honor.

[00:25:15] Speaker 04:
Appendix 5599, paragraph 9.

[00:25:17] Speaker 03:
Yeah, but he doesn't say that 95% purity means 95% A4.

[00:25:30] Speaker 01:
based on the use of htlc that would be if that would be what was understood how do i know that where is he saying he didn't spell it out in that level of detail here i apologize argument one is yes you agree the closest prior art would be starting with a

[00:25:58] Speaker 01:
a very purified, maybe not completely purified, but a very purified, A-form version of human quantum.

[00:26:05] Speaker 01:
And you have the evidence to back that up.

[00:26:08] Speaker 01:
But it also sounds like you have some kind of backup argument that even if it's not a starting material of a very purified version of A-form human quantum,

[00:26:28] Speaker 01:
Is that your backup argument?

[00:26:30] Speaker 04:
Those both could reflect the closest prior argument, Your Honor.

[00:26:33] Speaker 01:
Yes.

[00:26:34] Speaker 01:
And so what would be the case for why the backup argument makes sense?

[00:26:40] Speaker 04:
I see that I'm out of time.

[00:26:40] Speaker 04:
May I answer your question?

[00:26:42] Speaker 04:
Please.

[00:26:43] Speaker 04:
Your Honor, had Bausch actually tested against wild-type human uroguanilin, the 50-50, having topoisomeric purity of only 50%, their results would have actually shown a much greater difference against human uroguanilin, as the inactive portion of human uroguanilin does not have activity.

[00:27:02] Speaker 01:
OK.

[00:27:02] Speaker 01:
But it also sounded like you had agreed that it was already known in the prior art that you could make

[00:27:13] Speaker 01:
very purified eight-form versions of human guan.

[00:27:18] Speaker 04:
Only at certain low temperatures, because it's going to naturally interconvert.

[00:27:22] Speaker 04:
Depending on the temperature, depending on the pH, it will interconvert between the active and the inactive totals.

[00:27:27] Speaker 03:
It's stable in the powder form, right?

[00:27:29] Speaker 04:
Excuse me.

[00:27:30] Speaker 03:
It's stable in the powder form, right?

[00:27:33] Speaker 04:
There would be potentially even some interconversion there.

[00:27:36] Speaker 04:
It would have to be at an extremely low temperature, presumably.

[00:27:47] Speaker 01:
Was that mentioned in the briefing below?

[00:27:50] Speaker 01:
I just don't remember.

[00:28:12] Speaker 04:
The way I would characterize it, Your Honor, is this is a compound that naturally interconverts.

[00:28:17] Speaker 04:
And there was evidence of pH sensitivity to that.

[00:28:24] Speaker 04:
In fact, that was part of the evidence of unexpected results.

[00:28:29] Speaker 03:
Where's the evidence that it interconverts in powder form?

[00:28:34] Speaker 04:
I don't believe it was tested in powder form, Your Honor.

[00:28:38] Speaker 02:
Is this patent expired?

[00:28:40] Speaker 04:
No, Your Honor.

[00:28:41] Speaker 04:
This patent has, with extension and patent term adjustment, an expiration date of January 30, 2028.

[00:28:49] Speaker 04:
I see.

[00:28:51] Speaker 02:
Which doesn't show in the face of the patent.

[00:28:54] Speaker 04:
Correct, Your Honor.

[00:28:55] Speaker 01:
You've got PTA?

[00:28:56] Speaker 01:
Correct, Your Honor.

[00:28:57] Speaker 01:
Oh, OK.

[00:28:59] Speaker 01:
PTA of 362 days.

[00:29:00] Speaker 04:
Correct.

[00:29:01] Speaker 04:
And PTE of...

[00:29:05] Speaker 04:
Don't have it memorized.

[00:29:06] Speaker 04:
I'll stop in my head, but get a little close to it.

[00:29:09] Speaker 04:
It goes out to January 2028, Your Honor.

[00:29:12] Speaker 02:
Thank you, counsel.

[00:29:13] Speaker 04:
Thank you very much, Your Honor.

[00:29:20] Speaker 02:
Mr. Kong has some rebuttal time.

[00:29:24] Speaker 02:
Almost four minutes if you need it.

[00:29:26] Speaker 00:
Yes, Your Honor.

[00:29:26] Speaker 00:
Thank you.

[00:29:27] Speaker 00:
I wanted to respond, Judge, to your two questions.

[00:29:30] Speaker 00:
Number one, did Bausch use pure form A uroguanulin?

[00:29:34] Speaker 00:
The answer we just heard is nobody knows.

[00:29:36] Speaker 00:
Nobody knows.

[00:29:37] Speaker 00:
Because they didn't provide that data.

[00:29:39] Speaker 00:
And any ambiguity on that falls in their lap.

[00:29:41] Speaker 00:
It was their burden of production.

[00:29:42] Speaker 00:
They needed to produce that evidence.

[00:29:44] Speaker 00:
They're leaning heavily on this word purity in the patent and in this declaration.

[00:29:48] Speaker 00:
Again, I won't repeat this.

[00:29:50] Speaker 00:
The word topoisomer, the word confirmor, there's no reason to believe that that purity is referring to topoisomeric purity.

[00:29:57] Speaker 00:
Again, if you follow the clot reference, which you can because the board did not make any findings on this, there's no substantial evidence standard here.

[00:30:02] Speaker 00:
If you follow the clot reference, he discusses finding two topoisomers of human urine or guanulin.

[00:30:08] Speaker 00:
So if that's the synthesis method that they used to make what they tested, it was a mixture of A and B. It wasn't pure form A. The second question is, did the board make that finding?

[00:30:18] Speaker 00:
I think I just answered that.

[00:30:19] Speaker 00:
The board did not make that finding in terms of what they did.

[00:30:21] Speaker 00:
Rather, the board had a broad definition for what was the closest prior art and that obviated their need to make that finding.

[00:30:28] Speaker 00:
Lastly, I want to point to the data that my friend on the other side pointed to.

[00:30:32] Speaker 00:
This is page 41, appendix 41.

[00:30:36] Speaker 00:
This is the acid stability test.

[00:30:38] Speaker 00:
This is the data from time point 16 hours.

[00:30:41] Speaker 00:
And as your honor pointed out, there's no data from time point zero.

[00:30:45] Speaker 00:
So we don't know what the starting material was or how to interpret this data.

[00:30:49] Speaker 00:
Because absent data at time point zero, we don't know what this means.

[00:30:53] Speaker 00:
We have to compare this to something to see how much interconversion actually occurred.

[00:30:56] Speaker 00:
And we can't do that.

[00:31:02] Speaker 01:
They didn't use wild-type natural uroguanilin of a one-to-one A to B ratio, because it's a 70 to 30 ratio, A-form to B-form.

[00:31:13] Speaker 01:
So, given that we know that uroguanilin does interconvert, you know, and here we've got a 16-hour test, it's probably, it stands to reason that it could be 80 or 90 percent, you've got A-form uroguanilin.

[00:31:30] Speaker 00:
If we assume the test worked as it was supposed to work, which there's no evidence that it did, because all we have is data at time point 16, if we make that assumption, then I hear your honor's point, then they probably started something higher than 7030, or maybe they started with 7030, and nothing changed.

[00:31:47] Speaker 00:
We don't know.

[00:31:48] Speaker 00:
So that doesn't solve the problem.

[00:31:50] Speaker 01:
That's some version of purification, I would think.

[00:31:54] Speaker 01:
7030?

[00:31:55] Speaker 01:
Not to the extent you would want it, obviously.

[00:31:58] Speaker 00:
I would argue that is inferior prior art because it is going to be less potent than the more potent, as pure as you can get at format.

[00:32:07] Speaker 00:
There are further questions, I see the remainder of my time.