[00:00:03] Speaker 00:
We have two argued cases today.

[00:00:08] Speaker 00:
Council, ready to proceed on the first one?

[00:00:12] Speaker 00:
Yes, Your Honor.

[00:00:12] Speaker 00:
You're reserving three minutes.

[00:00:15] Speaker 03:
Yes, Your Honor.

[00:00:16] Speaker 00:
I'll let you know when you run up against it.

[00:00:22] Speaker 03:
May it please the court, the examiner rejected appellant's claims in this case as obvious on the ground that the senior reference

[00:00:32] Speaker 03:
disclosed an enzyme that inherently possesses low maltose activity.

[00:00:38] Speaker 03:
The ward affirmed on the ground that the examiner established a reasonable basis for inferring inheritance, thereby shifting the burden to repellent to disprove inheritance.

[00:00:49] Speaker 00:
In the red brief at 45 and 46, in response to Akita's assertion regarding Tsuji's disclosure, Apley notes the omission by Akita that

[00:01:02] Speaker 00:
SUGI's AOG-DH preparation shows 0.4% enzymatic reactivity to maltose relative to glucose 100%.

[00:01:12] Speaker 03:
Yes, Your Honor.

[00:01:13] Speaker 00:
Doesn't that meet the claim relative glucose over maltose specificity?

[00:01:17] Speaker 03:
Yes, it does, Your Honor.

[00:01:18] Speaker 03:
But SUGI is not prior art.

[00:01:21] Speaker 03:
And SUGI was, like the enzyme preparation in applicants'

[00:01:31] Speaker 03:
application, an appellant's application, was a highly purified enzyme preparation.

[00:01:39] Speaker 03:
So what SUGI shows in example two is that there is in fact an impurity in these enzyme preparations and that impurity does react with maltose.

[00:01:52] Speaker 03:
But you are correct in pointing out that in example one, in the highly purified SUGI preparation,

[00:02:00] Speaker 03:
there was low maltose activity that would be within scope of the claims that would be prosecuted.

[00:02:06] Speaker 02:
And that was both the highly purified natural one and the recombinant one?

[00:02:11] Speaker 02:
That is correct.

[00:02:11] Speaker 03:
The recombinant showed no maltose activity.

[00:02:17] Speaker 03:
The purified form showed

[00:02:22] Speaker 03:
a low amount of activity relative to maltose.

[00:02:26] Speaker 02:
Well, can you keep focusing on this purification issue?

[00:02:29] Speaker 02:
I would just assume for these purposes that you've made an awfully good point about the board being wrong about inherency.

[00:02:38] Speaker 02:
But they have this alternative ground, the board, that at least with some legal background like Aventis, there would have been a motivation to purify

[00:02:52] Speaker 02:
the senior FAD GDH.

[00:02:56] Speaker 03:
Yes, Your Honor.

[00:02:57] Speaker 02:
And sufficient motivation and a sufficient reasonable expectation that you would get the desired 20 to 1 ratio of glucose to maltose.

[00:03:09] Speaker 03:
Yes, Your Honor.

[00:03:10] Speaker 02:
So talk about that.

[00:03:12] Speaker 03:
My response to that is twofold.

[00:03:16] Speaker 03:
First,

[00:03:18] Speaker 03:
I do not believe that the examiner has established a basis for suggesting that.

[00:03:31] Speaker 03:
Excuse me, I lost my train of thought.

[00:03:34] Speaker 02:
I think if I remember your argument, at least the part that sticks in my memory is the idea that nobody would have expected that purification would do more for

[00:03:47] Speaker 02:
for relative maltose reduction than it did for PQQ.

[00:03:52] Speaker 03:
Now, the first point is that I don't believe that the examiner has established motivation to purify.

[00:03:59] Speaker 03:
Certainly, there is no prior art that the examiner cites for that proposition.

[00:04:04] Speaker 03:
And Sugi says, I'm not Sugi, but Senior says,

[00:04:07] Speaker 03:
expressly that its enzyme preparation need not be extensively purified.

[00:04:12] Speaker 03:
In fact, senior suggests that you can use its enzymes even if they haven't been purified at all.

[00:04:20] Speaker 03:
So certainly senior, there's nothing in senior to suggest that you should purify its enzyme preparation.

[00:04:28] Speaker 02:
But then as you point out, for other purposes, a quite long period elapses after senior to the priority date.

[00:04:36] Speaker 02:
Is there some

[00:04:37] Speaker 02:
point in that period at which there would have emerged a reason for a skilled artisan recognizing some misreading problem with PQQ to go and purify the FAD?

[00:04:55] Speaker 03:
The Solicitor has argued that by the time of 1997, when it was reported that PQQ glucose dehydrogenase

[00:05:06] Speaker 03:
was creating problems because it reacted with maltose, has suggested that at that time, one skilled New Yorker would have known that maltose was a potential problem and would have purified.

[00:05:21] Speaker 03:
But the PQQ enzyme that was having the maltose activity is the second enzyme disclosed in senior.

[00:05:31] Speaker 03:
And the PQQ enzyme inherently has activity to maltose.

[00:05:37] Speaker 03:
So the fact that there was a concern that this PQQ enzyme displayed activity to maltose, I don't think would have motivated somebody to purify the FAD enzyme.

[00:05:52] Speaker 03:
Because if you looked at what was causing the maltose activity in PQQ, it was the enzyme.

[00:06:00] Speaker 03:
It wasn't the impurity.

[00:06:02] Speaker 02:
So was there anything in prior art or any evidence of record here

[00:06:07] Speaker 02:
that indicated after 1983 up to 2003, I think your priority date or four, something like that, that told skilled artisans that FAD might not have the Malta's problem that PQQ did?

[00:06:27] Speaker 03:
Nothing in the record, Your Honor.

[00:06:31] Speaker 00:
Am I correct that IKEA agrees with the PTAB that

[00:06:36] Speaker 00:
enzymes that share the same EC numbers necessarily share the same substrate specificity?

[00:06:44] Speaker 03:
For purposes of this appeal, yes, your honor.

[00:06:46] Speaker 03:
That's correct.

[00:06:47] Speaker 03:
Because you sort of say that in your blueberry.

[00:06:50] Speaker 03:
The discrete enzyme in one preparation will have the same activity as that enzyme in another preparation.

[00:07:00] Speaker 00:
So what I think the issue is,

[00:07:03] Speaker 00:
is that Ikea disputes, as it relates to EC numbers, is how identical or not are discrete versus impure enzyme preparations.

[00:07:15] Speaker 03:
Is that right?

[00:07:16] Speaker 03:
We're disputing, yes.

[00:07:17] Speaker 03:
We're saying that what Senior discloses is not the discrete enzyme, does not the enzyme per se.

[00:07:24] Speaker 03:
What it describes is an impure preparation.

[00:07:27] Speaker 03:
And in that preparation,

[00:07:30] Speaker 03:
We believe that there are impurities that could well have activity to maltose, almost certainly does have some level of activity to maltose, but certainly we don't think on this record there's a basis to infer that the low maltose activity is inherent.

[00:07:52] Speaker 03:
And going back to your other point, Judge Toronto, I don't think there's any, beyond there not being any motivation,

[00:08:00] Speaker 03:
for purifying the senior enzyme.

[00:08:07] Speaker 03:
I don't believe there's anything in the record that would suggest a reasonable expectation of success that would tell you that if you did purify it, you would get this enzyme that has low maltose activity.

[00:08:19] Speaker 03:
And I think that's part and parcel of the prima facie case of obviousness.

[00:08:23] Speaker 02:
Can I ask you a very specific question that at least

[00:08:28] Speaker 02:
You have the 2009 FDA report, I think it's 2009, that says from 1997 to 2009, we've had, was it 13 or something, reports of deaths from PCQ sensor basically because of misreadings.

[00:08:49] Speaker 02:
What I couldn't tell from that, and you may know, were those reports publicly known?

[00:08:58] Speaker 03:
There's nothing in the record to suggest that they were publicly known.

[00:09:01] Speaker 02:
Dr. Turner's declaration reads to me like he thinks this was publicly known, but I couldn't quite tell.

[00:09:08] Speaker 03:
Well, but there's nothing in the record to suggest that those deaths were publicly reported.

[00:09:15] Speaker 03:
There was reported in 1997.

[00:09:17] Speaker 03:
There was a report.

[00:09:20] Speaker 03:
That's the Dr. DOK T.E.R.

[00:09:24] Speaker 03:
publication.

[00:09:28] Speaker 03:
No, it's not the doctor publication.

[00:09:30] Speaker 03:
It's the Wynn publication.

[00:09:32] Speaker 03:
There was a report that the PQQ enzyme was giving misreading information in patients that were given transfusion with isodextin.

[00:09:50] Speaker 03:
And it suggested that that was potentially dangerous.

[00:09:54] Speaker 03:
So there was certainly a report in 1997

[00:09:58] Speaker 03:
that this is a problem and it's potentially dangerous.

[00:10:04] Speaker 03:
But as to the actual deaths, we know that they first started, the FDA first started receiving those deaths in 1997, but we don't, I don't, there's nothing in the record to indicate that those are actual.

[00:10:19] Speaker 00:
Let me take you back to where Judge Toronto started his questioning with the alternative PTAB finding.

[00:10:27] Speaker 00:
It says

[00:10:28] Speaker 00:
that even if senior's FAD-dependent GDH enzyme preparation includes contaminants, it would have been obvious for a posita to modify senior's purification to obtain better purity, yield of GDH, etc.

[00:10:46] Speaker 00:
Aikita argues that the PTAP, quote, failed to explain why a posita would have expected the purified preparation of low activity against maltose.

[00:10:55] Speaker 00:
But in the hearing, Aikita

[00:10:58] Speaker 00:
Kida conceded that at most there is evidence that the material activity may not always be less than 5%.

[00:11:06] Speaker 00:
And it seems to me to be reasonable for a person of skill to expect success given this hearing transcript concession combined with the Tsuji reference purification method results.

[00:11:21] Speaker 00:
How is the fact achieving under 5% may not always occur?

[00:11:26] Speaker 00:
evidence of no expectation of success.

[00:11:30] Speaker 00:
You see what I'm saying?

[00:11:32] Speaker 03:
Well, I don't believe that... Well, first off, I think what you're assuming is that somehow a person of ordinary skill in the art would know that maltose is a problem and would know that they should

[00:11:55] Speaker 03:
purify the composition to remove maltose.

[00:11:59] Speaker 03:
There's nothing in the prior art that indicates that.

[00:12:03] Speaker 03:
So even if one was going to sit down and purify, unless you're saying that one normally just routinely would purify it and get all impurities out, I don't think that you necessarily would purify it in order to get low activity to maltose.

[00:12:24] Speaker 00:
Your yellow light's on, just so you know.

[00:12:26] Speaker 03:
OK.

[00:12:26] Speaker 03:
But the other point is, as I mentioned a few minutes ago, as far as the reasonable expectation of success, PQQ enzyme had been purified.

[00:12:39] Speaker 03:
It was being used in commercial products.

[00:12:43] Speaker 03:
And clearly, they would have done everything they could to try and remove any impurities from that under the hypothetical that you're suggesting.

[00:12:53] Speaker 03:
And in PQQ, that didn't remove the maltose activity.

[00:12:56] Speaker 01:
But why does the fact that purification didn't work with PQQ suggest that overall purification wouldn't be tried?

[00:13:05] Speaker 03:
Well, it may have been tried.

[00:13:07] Speaker 01:
It may have been, I mean, I think that- Are you saying that there's nothing in the prior art to suggest that this maltose sensitivity problem was unknown altogether and that it led to

[00:13:23] Speaker 01:
this problem of false results from the maltose sensitivity was unknown?

[00:13:29] Speaker 03:
No.

[00:13:29] Speaker 03:
I mean, the problem with PQQ and its maltose, the fact that it reacted with maltose, was known for a long time, from 1986.

[00:13:40] Speaker 03:
But I don't see how you can, the examiner can simply say that it would have been obvious to purify

[00:13:47] Speaker 01:
in the face, and you would somehow... Was there a general understanding, not just with regard to PQQ, but other types of sensors, that there was a potential problem of false readings due to maltose sensitivity?

[00:14:07] Speaker 03:
Other than PQQ, no, as far as I know.

[00:14:11] Speaker 03:
But again, the senior itself says

[00:14:17] Speaker 03:
You don't need to purify it.

[00:14:18] Speaker 03:
So you have an express teaching that you don't need further purification.

[00:14:21] Speaker 03:
And then it seems to me that if you're going to say, well, it just would have been obvious to purify it, there has to be something more than just the examiner saying, everyone knows that you would want to purify it to get out the impurities.

[00:14:33] Speaker 03:
When the principal reference that you're relying on says, it's not necessary in this particular application, which is measuring glucose

[00:14:42] Speaker 02:
And just so I'm clear, there are two points about motivation and then reasonable expectation.

[00:14:48] Speaker 02:
Even if you are motivated, you have a separate, though obviously related, point that there's no reason, you say, to have expected success for NAD any more than for PQQ.

[00:14:59] Speaker 00:
Correct.

[00:15:01] Speaker 00:
Thank you.

[00:15:02] Speaker 00:
We have your time.

[00:15:03] Speaker 00:
I'll give you two minutes.

[00:15:05] Speaker 00:
Thank you.

[00:15:11] Speaker 00:
Counsel?

[00:15:15] Speaker 04:
Good morning, Your Honors, and may it please the court.

[00:15:18] Speaker 04:
Aikita seeks to withdraw from the public seniors' disclosure of using a purified FAD GDH enzyme in a glucose biosensor, because Aikita is now claiming an inherent property of a purified FAD GDH enzyme preparation.

[00:15:33] Speaker 04:
For at least three reasons, we're asked this court to affirm the board's decision.

[00:15:38] Speaker 04:
One's based on just seniors' disclosure, what it discloses as a whole, seniors' specific enzyme prep, and also then the third,

[00:15:45] Speaker 04:
is the obvious to purify.

[00:15:47] Speaker 00:
In the blue brief, Aikita says at 28, quote, no prior art suggested that purifying senior's EC1.1 99.10 enzyme preparation would yield an enzyme preparation with low activity against maltose.

[00:16:05] Speaker 00:
How do you respond, and what's your best evidence to the contrary?

[00:16:10] Speaker 04:
So I take it that there was a motivation to purify at the time of Aikita's

[00:16:16] Speaker 04:
filing date, seniors 1986 or 83.

[00:16:20] Speaker 04:
And by the time Akita's filing date, there's a motivation to purify because we now know that there's patients taking drugs that results in maltose in their bloodstream.

[00:16:29] Speaker 04:
And that you have a problem, whether you have an enzyme that has intrinsic activity to maltose or if you have a contaminant to maltose, you're going to have a problem for that patient population.

[00:16:39] Speaker 04:
So based on the evidence that Akita put forth... What's the evidence for that?

[00:16:44] Speaker 01:
I mean, I understand that argument, but when I looked at the board's reasoning on this, I think we're talking about the alternative ground, it kind of just says it.

[00:16:53] Speaker 01:
It doesn't really cite to a whole lot.

[00:16:55] Speaker 04:
Well, I think the examiner first relied on it in the answer, and the examiner was relying on what Akita was presenting for a long felt need.

[00:17:05] Speaker 04:
At the time, the Aikida is saying there's a long felt need for a new enzyme that doesn't have this activity to maltose.

[00:17:12] Speaker 04:
So by the time of their priority date, the examiner is essentially relying on that.

[00:17:17] Speaker 04:
At that time, we have this evidence that PQQ GDH enzyme has activity to maltose.

[00:17:23] Speaker 04:
And then we have reports that are a decade after senior, but reports of

[00:17:29] Speaker 04:
maltose in the bloodstream of certain patients who are taking drugs.

[00:17:33] Speaker 04:
And that evidence that they're essentially putting forward for a long felt need, though wouldn't support a finding of a long felt need, did support a motivation to purify an enzyme.

[00:17:44] Speaker 02:
And I think even the six- Can I just ask on this report, do you have any different information about whether an ordinary skilled artisan knew about these reports of the PKQ death problem?

[00:17:57] Speaker 04:
There was an article that was published in 1998, which talked about the problem of having this higher maltose activity in the patient, suggesting that there could be a death problem.

[00:18:09] Speaker 02:
This is the Wens article?

[00:18:10] Speaker 04:
I think it is the Wens article, yes.

[00:18:12] Speaker 04:
So there's no evidence that the FDA reports of death starting in 1997 in public.

[00:18:17] Speaker 04:
But there is public data that was put forth for the long felt need that there was this risk to particular patients that were taking

[00:18:26] Speaker 04:
drugs that put maltose in their bloodstream.

[00:18:29] Speaker 04:
So that supports a motivation to purify away any maltose activity.

[00:18:34] Speaker 04:
I think Aventus and Spectrum support a motivation to purify a mixture, regardless of whether there's anything more explicit about it, because we have this known, desired property of the mixture, this enzyme activity.

[00:18:49] Speaker 01:
But that can't be kind of a blanket rule.

[00:18:52] Speaker 01:
There may be some times where purification

[00:18:54] Speaker 01:
is completely unnecessary.

[00:18:56] Speaker 01:
And so it would be added steps, added cost.

[00:18:59] Speaker 01:
And I mean, I don't think you can assume that purification is always obvious for somebody, a skilled artist, to do, can you?

[00:19:07] Speaker 01:
I think that's true.

[00:19:08] Speaker 01:
You have to have some reason to do it.

[00:19:09] Speaker 04:
I think that's true.

[00:19:10] Speaker 01:
And there has to be some level.

[00:19:13] Speaker 04:
To some level, when you're talking about using something in a glucose biosensor for patients, and you know out there that there's a problem with other sugars that could occur in the bloodstream, I think that is definitely sufficient.

[00:19:23] Speaker 04:
for motivation to purify the enzyme away if you were going to use it to then treat patients.

[00:19:31] Speaker 02:
Can I just ask on the Aventus point, why wouldn't one read Aventus as applied here to say that the crucial premise of a property in a substance, that the crucial property here is not sensitivity to glucose, but comparative

[00:19:50] Speaker 02:
20 to 1 sensitivity of glucose to maltose.

[00:19:53] Speaker 02:
And that, there just wasn't a reason to know.

[00:19:56] Speaker 04:
There wasn't a reason to know.

[00:19:59] Speaker 04:
But I guess that goes back to there wasn't a reason to know.

[00:20:05] Speaker 04:
But there was a reason to be worried about maltose.

[00:20:07] Speaker 04:
And there was a reason to know that there's maltose hydrolyzing enzymes.

[00:20:11] Speaker 02:
But very specifically on the Aventis case, which you place a fair bit of reliance on,

[00:20:16] Speaker 02:
a sentence that says, when you know that something has a particular property, it's sort of presumed that you would have a reason to purify.

[00:20:24] Speaker 02:
But the particular property here is a relative one.

[00:20:27] Speaker 02:
And I don't remember that there's anything that tells us that the world of public knowledge included knowledge of the relative 20 to 1 property of the FAD.

[00:20:41] Speaker 04:
That's true.

[00:20:42] Speaker 04:
until IKEDA shows the inherent property of the purified enzyme preparation in table 1, we don't know about the enzyme's activity to maltose.

[00:20:50] Speaker 04:
We do know that it's been given an EC number that defendifies it as a glucose dehydrogenase.

[00:20:56] Speaker 04:
And that fourth number, the 1, 0, is the substrate specificity that has been characterized for that enzyme.

[00:21:03] Speaker 04:
So reasonably, we expect that it

[00:21:07] Speaker 04:
would have glucose specificity.

[00:21:09] Speaker 02:
And if we're worried about... I'm sorry, but specificity does, I think, tell me if I'm wrong, not include information about whether it's also reacting to an unfortunate degree with something other than glucose.

[00:21:25] Speaker 04:
That's true.

[00:21:26] Speaker 04:
But I guess the art didn't know about this maltose property, about whether this enzyme or not had activity to maltose relative to glucose.

[00:21:36] Speaker 04:
But the senior did disclose using a purified fad GDH enzyme.

[00:21:41] Speaker 04:
And it's tracking a specific property, which is the EC number, which is an activity to glucose.

[00:21:51] Speaker 04:
And I think not only based on that disclosure and the knowledge, the enablement in the art that you could purify it to the level

[00:22:00] Speaker 04:
of purity that would give you this inherent property.

[00:22:03] Speaker 04:
But that senior particularly purified its enzyme and said it had this, you know, the ability to use it in a glucose biosensor.

[00:22:13] Speaker 04:
Ikea is now claiming an inherent property of that purified enzyme.

[00:22:19] Speaker 04:
And the inherent property doesn't have to be known in the prior art.

[00:22:23] Speaker 02:
Can you just clarify what you mean by senior discloses a

[00:22:29] Speaker 02:
purified FADGDH.

[00:22:33] Speaker 04:
CMEA just closes using a purified FADGDH enzyme preparation.

[00:22:38] Speaker 02:
What are you pointing to?

[00:22:39] Speaker 02:
I thought the kind of whole point here is that the... It says, so this is an APPX287.

[00:22:48] Speaker 04:
It's the first full paragraph where it starts when

[00:22:55] Speaker 04:
I mean, when used in the method of the invention, the enzyme may be in any form, e.g.

[00:23:01] Speaker 04:
a purified enzyme.

[00:23:03] Speaker 04:
And there's no dispute that one of skill and the art could have purified.

[00:23:07] Speaker 02:
But why is that anything other than saying, we've got this, forgive the expression, soup.

[00:23:16] Speaker 02:
It includes this enzyme.

[00:23:20] Speaker 02:
We say, we don't think it matters very much how pure it is.

[00:23:24] Speaker 02:
And you're taking from that a disclosure of the purified because it has mentioned that no matter how pure it will have a beneficial property?

[00:23:36] Speaker 04:
There was no testing or anything?

[00:23:40] Speaker 04:
There's no testing, but you don't have to have testing if it's an inherent property.

[00:23:45] Speaker 04:
You can't make a patentable distinction between

[00:23:48] Speaker 04:
what you're claiming now and what was in the prior art based on an inherent property, even if that inherent property isn't known.

[00:23:54] Speaker 04:
And here we have a disclosure of an EC enzyme preparation.

[00:23:59] Speaker 04:
And Aikida also is disclosing not the enzyme per se, not telling you anything about what that enzyme per se is activity, but an enzyme preparation.

[00:24:08] Speaker 04:
And so there's no way that the board or the examiner relied on an enzyme per se.

[00:24:13] Speaker 04:
They were relying on the fact that the prior art teaches purifying

[00:24:18] Speaker 04:
a fad GDH enzyme from this gamish of fungi cells, and then characterizing it as having this glucose dehydrogenase activity.

[00:24:29] Speaker 04:
And that is a reasonable basis to think that these two gamishes, either just the disclosure and an enablement of using a purified enzyme, or senior's particular preparation, inherently has the substrate specificity, the low maltose to glucose claimed activity,

[00:24:48] Speaker 04:
as senior's preparation.

[00:24:50] Speaker 04:
And senior's only answer is this maltose hydrolyzing contaminant.

[00:24:55] Speaker 04:
And that Shuji tells you that there's this contaminant in the preparation.

[00:25:00] Speaker 04:
But as Judge Wallach noted, that contaminant does not result in a high maltose activity relative to glucose.

[00:25:07] Speaker 04:
You still have lower than 5% activity of maltose relative to glucose in these preparations.

[00:25:14] Speaker 04:
So the board said there's no evidence of this contaminant.

[00:25:17] Speaker 04:
And even if there was evidence of this contaminant, it still then would inherently have this low activity to maltose relative to glucose.

[00:25:26] Speaker 04:
And so the PTO doesn't have the ability to test prior compositions and compare them to Iquitas.

[00:25:33] Speaker 04:
So the only thing the PTO can do is say we have these substantially similar preparations.

[00:25:39] Speaker 04:
They've both been classified as known

[00:25:43] Speaker 04:
enzymes based on their EC numbers.

[00:25:45] Speaker 02:
I guess I'm confused about this.

[00:25:48] Speaker 02:
Sometimes you're talking about the preparation used in senior, which I actually took it to be what the board was focused on.

[00:25:58] Speaker 02:
But at times you seem to be making an argument that says, senior mentions NADGDH.

[00:26:05] Speaker 02:
It uses the term purity.

[00:26:07] Speaker 02:
So it thereby teaches a pure NADGDH

[00:26:12] Speaker 02:
under sharing and the Claritin case, it doesn't matter when you discover an inherent property, if it's inherent, then all done anticipation.

[00:26:25] Speaker 02:
Are you making that as a separate point?

[00:26:27] Speaker 04:
There's two separate arguments.

[00:26:29] Speaker 04:
I'm saying that senior discloses using a purified fad GDH enzyme preparation, because there's no enzyme to teach at this point, because there's no recombinant enzyme.

[00:26:37] Speaker 04:
So when I say enzyme, I mean enzyme preparation, even if I don't say preparation, because that's all there is.

[00:26:42] Speaker 04:
He said senior teaches using this fad GDH enzyme preparation.

[00:26:47] Speaker 04:
And even if they're, if seniors particular embodiment is an operative or something's wrong with it, it doesn't take that disclosure using this purified fad GDH enzyme out of the prior art, as long as it's enabled.

[00:27:01] Speaker 04:
So the Purdue Pharma case where you have a one day, a 24 hour tramadol treatment and

[00:27:09] Speaker 04:
The prior art didn't actually show this particular 24-hour treatment with tramadol, but it would have been enabled because one of skill in the art could have done it.

[00:27:19] Speaker 04:
One of skill in the art could have purified it.

[00:27:21] Speaker 04:
All of these protein purification methods that are being used are well-known, ordinary methods.

[00:27:27] Speaker 04:
And so therefore, Senior discloses the FAD-GDH enzyme in two ways.

[00:27:31] Speaker 04:
By saying use the purified enzyme, if it had never done an enzyme preparation,

[00:27:37] Speaker 04:
That disclosure is not taken away from the prior art, but he also then purified the bad GVH enzyme and characterized it based on it having this EC number.

[00:27:47] Speaker 04:
An EC number already tells you that this enzyme is an enzyme that's been published and characterized in the prior art.

[00:27:54] Speaker 04:
And what Akita is doing is claiming this inherent property

[00:27:58] Speaker 04:
of that purified GDH, and so I'm trying to get a claim on it.

[00:28:01] Speaker 02:
So on that theory, could the case here of anticipation have been made without Senior just saying, look at this EC classification?

[00:28:12] Speaker 04:
I think so, yes.

[00:28:13] Speaker 04:
But Senior gives you the motivation to use it in a glucose biosensor.

[00:28:17] Speaker 04:
So the particular use that's being claimed now is the use of this enzyme to

[00:28:24] Speaker 04:
Calculate the amount of glucose in a blood sample.

[00:28:27] Speaker 04:
It isn't an anticipation rejection.

[00:28:29] Speaker 04:
It's obviousness because there's a bit of a structure that's relied on by UGAWA, but it's essentially a 102 for the enzyme preparation.

[00:28:38] Speaker 02:
Can I ask you to return to, I'm sorry, this was kind of a long detour from, I think, a discussion that began to focus on the purification.

[00:28:47] Speaker 02:
pair of issues.

[00:28:48] Speaker 02:
One is motivation and the second is a basis for reasonably expecting success that purifying FAD would be better than for these purposes, namely reducing maltose reactivity than purifying PQQ.

[00:29:05] Speaker 02:
What evidence in the real world known to skilled artisans would have generated such an expectation?

[00:29:12] Speaker 04:
So the reasonable expectation of success comes from the fact that it is classified as a

[00:29:16] Speaker 04:
glucose dehydrogenase.

[00:29:18] Speaker 04:
Other glucose enzymes have been purified and don't have any intrinsic activity to maltose.

[00:29:24] Speaker 04:
Glucose oxidase, the NADH FGAD that was used prior that had the separate cofactor also has no intrinsic activity to maltose.

[00:29:36] Speaker 04:
PQQ GDH does.

[00:29:38] Speaker 04:
But just because one of the enzymes does doesn't mean you wouldn't have a reasonable expectation of sex.

[00:29:43] Speaker 04:
success of purifying it and it not having intrinsic activity, it's not 100%, but it doesn't have to be 100% for as a reasonable expectation of success.

[00:29:52] Speaker 02:
And in fact, the activity of PQ2... I mean, our law just tells us almost nothing about where south of 100% reasonable is.

[00:29:59] Speaker 04:
But it's not like there's one GADH enzyme.

[00:30:03] Speaker 04:
It has been purified and it has activity to maltose.

[00:30:05] Speaker 04:
You have other enzymes that have been used

[00:30:08] Speaker 04:
for glucose biosensors, and they don't have intrinsic activity to maltose.

[00:30:12] Speaker 04:
They were purified, and if there was any, it was a contaminant.

[00:30:15] Speaker 04:
And here, the PQQGDH enzyme was never certainly tested for maltose until later, indicating it's sort of a surprise, perhaps, that this enzyme had this activity, because no one was looking for it when they initially isolated.

[00:30:29] Speaker 04:
See, I'm out of time, so unless there's any other questions, we'd ask this court to affirm the board's decision.

[00:30:35] Speaker 04:
Thank you, Your Honor.

[00:30:41] Speaker 00:
I like the way you think, counsel.

[00:30:43] Speaker 00:
Not what you think, but you think in paragraphs.

[00:30:47] Speaker 00:
I like it.

[00:30:48] Speaker 04:
Thank you, Your Honor.

[00:30:52] Speaker 00:
I'm not saying I dislike what you think.

[00:30:54] Speaker 00:
I'm just saying.

[00:31:00] Speaker 03:
Just a couple of points, Your Honor.

[00:31:02] Speaker 03:
The claims that are pending are not removing anything from the prior art, as Solicitor has argued.

[00:31:11] Speaker 03:
Claims are for a particular type of biosensor.

[00:31:14] Speaker 03:
It's a different type of biosensor than what was in senior.

[00:31:18] Speaker 02:
Can you focus very specifically on that?

[00:31:20] Speaker 02:
Because I guess I think I was learning something about what might be a couple of different arguments that maybe before today's argument I had been joining.

[00:31:33] Speaker 02:
Forget about the preparation that senior actually did experiments on and used.

[00:31:41] Speaker 01:
Yes.

[00:31:41] Speaker 02:
I understand the government to be saying that in addition, senior said biosensor with a said that didn't make or test or yet didn't make or test a FAD GDH in pure form.

[00:31:58] Speaker 02:
And as long as it disclosed it in a biosensor, you are doing nothing but identifying a leader discovered inherent property, namely a 20

[00:32:10] Speaker 02:
20 to 1 ratio of glucose to maltose reactivity.

[00:32:13] Speaker 02:
Tell me what your answer is to that.

[00:32:16] Speaker 03:
Well, the senior doesn't disclose using the enzyme.

[00:32:24] Speaker 03:
It discloses using an enzyme preparation.

[00:32:29] Speaker 02:
And I think I take it, and maybe I've misunderstood, that at page 289,

[00:32:40] Speaker 02:
Is it 289 or 287?

[00:32:42] Speaker 02:
287, I'm sorry.

[00:32:45] Speaker 02:
When used in the method of the invention, the enzyme may be in any form, e.g.

[00:32:50] Speaker 02:
purified enzyme in a crude cellular extract or contained in whole micro.

[00:32:57] Speaker 02:
And I think the government was saying that discloses something that Senior and his people never actually did, but it discloses using a pure

[00:33:10] Speaker 02:
FAD GDH in a biosensor.

[00:33:14] Speaker 02:
If you read the senior... So did the board find that?

[00:33:19] Speaker 03:
No.

[00:33:19] Speaker 03:
If you read the senior in its entirety, I think what the purification they're talking about there is the purification that took place in their example, which was an eight-fold purification.

[00:33:36] Speaker 03:
Later on, on

[00:33:40] Speaker 02:
I see.

[00:33:40] Speaker 02:
So purified is not an either-or kind of thing.

[00:33:44] Speaker 03:
No.

[00:33:45] Speaker 03:
The example in the application took ruptured cells, and then it centrifuged them out, and then it passed them over a one-stage column to purify it.

[00:34:00] Speaker 03:
And it increased the amount of GDH by about eightfold, it said.

[00:34:08] Speaker 03:
That is still a very crude preparation.

[00:34:12] Speaker 03:
It is somewhat purified.

[00:34:14] Speaker 03:
I'm letting you run over a bit.

[00:34:18] Speaker 03:
OK.

[00:34:18] Speaker 03:
But as we explained in our brief, the preparation that we've used is that has seven, the senior preparation has 7,000 times more protein impurity than the one that we use, demonstrating that the senior enzyme preparation that is actually disclosed

[00:34:36] Speaker 03:
is very different from the enzyme preparation in our application that was relied on by the examiner as the basis for the inherency argument.

[00:34:47] Speaker 00:
Time's up.

[00:34:48] Speaker 00:
Thanks.