[00:00:04] Speaker 03:
The first case for argument this morning is 19-1011 Halizan versus Yanko.

[00:00:11] Speaker 03:
Mr. Gady?

[00:00:12] Speaker 00:
Gady, yes, Your Honor.

[00:00:14] Speaker 03:
Good morning.

[00:00:16] Speaker 00:
Good morning.

[00:00:17] Speaker 00:
May it please the court?

[00:00:19] Speaker 00:
I'll get right to the chase here.

[00:00:20] Speaker 00:
The district court committed clear errors of law, and I wish to focus on four of them.

[00:00:25] Speaker 00:
First, I'll focus primarily on the court legally airing by applying the doctrine of routine optimization to overcome

[00:00:33] Speaker 00:
the legal requirements of motivation to combine and reasonable expectation of success for obvious and ODP.

[00:00:41] Speaker 00:
Specifically, there is no disclosed range of pegulation in the cited prior art for the specific hyaluronidase.

[00:00:50] Speaker 00:
And B, the Braxton and Thompson references that form the grounds for rejection for the claims only point to uncertainties and different techniques

[00:01:01] Speaker 00:
inapplicable to this particular pharmaceutical composition.

[00:01:06] Speaker 00:
Secondly, for ODP, the discord compounded its errors by consulting and relying on the 431 and 081 reference patent specification, and by finding that there is, in essence, a presumption that where there's a broader genus claim, a species claim cannot be patentable.

[00:01:24] Speaker 00:
Third,

[00:01:25] Speaker 00:
The district court erred by finding and creating a rule of law that commercial success and long-felt need can never be shown for our product until it is approved by the FDA, creating a bright line test that would undermine the enforceability of patents by life science companies in the United States.

[00:01:47] Speaker 00:
And then finally, the district court, with respect to Bookbinder, errs by saying there's no

[00:01:55] Speaker 00:
beginning and end point in the amino acid sequences.

[00:01:58] Speaker 00:
I don't want to spend really any time on that.

[00:02:00] Speaker 00:
I just want to make one point on that briefly for the court.

[00:02:03] Speaker 00:
The court says there's no beginning and end point.

[00:02:06] Speaker 00:
But if you look at the decision at page 11, appendix 12, right there, the court says that the application discloses seek ID number one, which it identifies as the polypeptide sequence of human hyaluronase

[00:02:23] Speaker 00:
seek ID number four which corresponds to amino acids 36 to 43 of seek ID number one So later on the opinion the court says that the disclosure provides no beginning endpoint But is undermined not only by the record that is briefed here But also by the very statement in its decision at page 11 that there is a beginning point all the pending claims have 36 as the beginning point and

[00:02:52] Speaker 00:
All except one claim have it as an endpoint, 43.

[00:02:56] Speaker 00:
So it's right there in the district court's decision.

[00:02:59] Speaker 00:
Let's turn first, though, to what I think is the main issue here, which is the routine optimization that was used to overcome the legal requirements of a proper conclusion under obviousness for motivation to combine and reasonable expectation of success.

[00:03:18] Speaker 00:
There is no ratio here.

[00:03:20] Speaker 00:
There is no range that is provided here.

[00:03:23] Speaker 00:
PTO and the court in their decision do not point to any language in the Braxton or the Thompson references that provide a specific range.

[00:03:35] Speaker 00:
Why is that important?

[00:03:37] Speaker 00:
That's important because it's the range in the court case law, such as in the Peterson case, which had 0% to 7% that provide the framework for motivation and provide the framework for a reasonable expectation of success

[00:03:52] Speaker 00:
in the Peterson claim that had 1% to 3%.

[00:03:55] Speaker 00:
We don't have that here.

[00:03:57] Speaker 00:
We have no guidance in Braxton as to a specific range that this court has used in the past, for example, in the Peterson case.

[00:04:07] Speaker 00:
Also, other ranges are not broadly applicable here.

[00:04:11] Speaker 00:
As was admitted by their expert, peggalation is, quote, specific to each protein, close quote.

[00:04:19] Speaker 00:
That's appendix 7981 at line 6 to 8.

[00:04:23] Speaker 00:
So no broad applicable ranges can be transferred from one protein to another.

[00:04:30] Speaker 00:
Without the range, it's improper to, in essence then, use the doctrine of routine optimization because there's nothing in the art.

[00:04:40] Speaker 00:
And effectively, what the court did was use hindsight bias by looking at the range in the claim of three to six.

[00:04:48] Speaker 00:
And then saying, well, that one would get to with routine optimization.

[00:04:53] Speaker 00:
But how does one know that?

[00:04:54] Speaker 00:
There's no guidance in the art.

[00:04:56] Speaker 00:
There's no range in the art.

[00:04:57] Speaker 00:
There's nothing that guides one.

[00:04:59] Speaker 00:
to a person of ordinary skill, to that three to six solution.

[00:05:03] Speaker 03:
Your argument's about range.

[00:05:05] Speaker 03:
So what you're looking is a range what?

[00:05:07] Speaker 03:
A larger range?

[00:05:09] Speaker 03:
There would have needed to be a larger range in the prior art, and this would be a species of that?

[00:05:15] Speaker 03:
Is that what you're arguing for?

[00:05:17] Speaker 00:
Exactly.

[00:05:18] Speaker 00:
It has a range that provides the teaching that then one of skill can use routine optimization

[00:05:25] Speaker 00:
to get to the species within that range, such as in the Peterson case, where there is 0% to 7% versus what was ultimately done?

[00:05:33] Speaker 03:
Well, there might be cases where the range is included.

[00:05:36] Speaker 03:
But which of our cases say that's necessary in order to apply the optimization analysis?

[00:05:43] Speaker 00:
Well, I think it becomes to the point then, it's necessary when you go to your other cases, such as in the Step-On case, where there wasn't a precise range that was provided.

[00:05:54] Speaker 00:
In fact, there the claim was at 70 degrees centigrade.

[00:05:58] Speaker 00:
And there was a suggestion in the Step-On case up to 65 degrees centigrade.

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And the court found in that case that there was no guidance as to the why to go to the 70 degrees centigrade.

[00:06:12] Speaker 00:
So that's an example right there in the Step-On case.

[00:06:16] Speaker 00:
I think also you could look to the Genetics Institute case

[00:06:20] Speaker 00:
where there are multiple different species within the scope of the genus claim, just as there are here.

[00:06:25] Speaker 00:
And there again.

[00:06:27] Speaker 03:
Well, it seems to me we have a number of cases.

[00:06:31] Speaker 03:
And the test they rely on is whether or not there's just an enormous number of variables to choose from.

[00:06:40] Speaker 03:
That's not the argument you're making here.

[00:06:42] Speaker 03:
You're not saying the range is so enormous that it would have taken more than routine optimization to select the three to six range.

[00:06:51] Speaker 00:
Well, I'm making a couple of different points, Your Honor.

[00:06:55] Speaker 00:
The range here is, first of all, there is no range.

[00:06:59] Speaker 00:
So we're not limiting down the number of potential embodiments by the prior art range.

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Secondly, left with the fact that you just have

[00:07:08] Speaker 00:
the general guidance in the reference claims of a pegulated or dextran modified hyaluronidase, but no range within that.

[00:07:19] Speaker 00:
Then within that, given the number of amino acids within hyaluronidase, there are a multitude of potential different structures.

[00:07:29] Speaker 00:
And importantly, Your Honor, it's not just that you can attach a peg.

[00:07:33] Speaker 00:
It's that you will have in this claim for this pharmaceutical composition

[00:07:39] Speaker 00:
a hyaluronidase that is pegulated that has activity systemically, that is formulated for systemic administration.

[00:07:48] Speaker 00:
That's the purpose, and that's the property that specific hyaluronidase must have.

[00:07:54] Speaker 00:
It must have that property.

[00:07:57] Speaker 00:
And among all the multitudes and the myriads of different possibilities that exist, there's nothing that guides one of ordinary skill and the art through a range where the routine optimization could apply.

[00:08:11] Speaker 00:
I think then, secondly, when we're looking at the range issue, then I think then that brings us to the second fundamental error.

[00:08:20] Speaker 00:
So to find the motivation and to find the reasonable expectation of success, the court relies on the Braxton and the Thompson references.

[00:08:31] Speaker 00:
And it's clear that you can't just cherry pick words in a reference for the combination for obviousness.

[00:08:39] Speaker 00:
That was held in the Bausch and Lomb case.

[00:08:42] Speaker 00:
that's cited in our briefs.

[00:08:44] Speaker 00:
And what did the district court do?

[00:08:47] Speaker 00:
It relied on one sentence in the background of the invention, and it ignored the entire thrust of the references themselves, which was undisputed.

[00:09:01] Speaker 00:
They relate to a technique that, if used, one skill would understand would destroy

[00:09:09] Speaker 00:
the activity of the hyaluronidase, clearly teaching away.

[00:09:13] Speaker 00:
More importantly, even in the background section that the court relies upon, there are two key points in there as well.

[00:09:23] Speaker 00:
First, it says that if you use sort of random lysine modification, which is an approach, it's not suitable for pharmaceutical compositions.

[00:09:36] Speaker 00:
And that's at 101, 143, 32 through 34.

[00:09:43] Speaker 00:
And also, in Braxton in the background section, it says, it is, quote, unsuitable where certain lysine residues are essential for biological activity.

[00:09:56] Speaker 00:
That's at lines column two, line 62 to 65 in Braxton.

[00:10:01] Speaker 00:
So two warning points are in Braxton.

[00:10:05] Speaker 00:
First, it's not suitable to use random lysine pegalation for pharmaceutical compositions, which is a limitation of the claim.

[00:10:15] Speaker 00:
Second, it's unsuitable where suit and lysine residues are essential for biological activity.

[00:10:22] Speaker 00:
And those were clear unknowns in the art as to what specific amino acids, what specific lysines would, in fact, if pegulated, have an impact on the activity.

[00:10:35] Speaker 00:
And the ODP claims, the reference claims, where they just talk about dextran or pegulated modified hyaluronidase, don't provide that specific teaching necessary for the systemic use where you have all the clearance mechanisms of the body in play.

[00:10:51] Speaker 00:
And secondly, don't point you in any way that is suitable for a pharmaceutical composition, which Braxton clearly warns against.

[00:11:02] Speaker 00:
And then Braxton says, go to another technique which one of ordinary skill in the art understands would be inapplicable.

[00:11:09] Speaker 00:
So there's no clear guidance or direction within Braxton and Thompson pointing the person of ordinary skill in the art towards the invention

[00:11:20] Speaker 00:
which is three to six pegs that is formulated for systemic application.

[00:11:29] Speaker 00:
And by relying on the single sentence in the background to the invention, the court erred and cherry picked in violation of the Bausch and Lomb case that is cited in our briefs at 796 Fed 2nd, 448.

[00:11:44] Speaker 00:
And otherwise, the doctrine of teaching away is undermined.

[00:11:49] Speaker 00:
If you can find the motivation or the reasonable expectation of success in a single sentence in the background to an invention, which, in fact, disparages the very technique, now the doctrine of teaching away of the reference, which must be considered as a whole, is undermined.

[00:12:08] Speaker 00:
Because the references, undisputably, as a whole, there's no doubt about it, teach a technique that, if used, would destroy the activity, that would not be suitable

[00:12:21] Speaker 00:
The other FDA-approved drugs that the PTO points to do not help them, because there is no range pointing to 3 to 6.

[00:12:31] Speaker 00:
Most of them are mono-pegalated, which doesn't point to 3 to 6.

[00:12:35] Speaker 00:
The one that they rely on, adigen, which is 11 to 17, isn't the range.

[00:12:41] Speaker 00:
And also, in one of the other FDA-approved drugs, it actually talks about pegalating the histidine, which is different.

[00:12:50] Speaker 00:
So there are multiple different ways that these products can be pegalated.

[00:12:55] Speaker 00:
It is specific to each and every one.

[00:12:59] Speaker 00:
And it's not transferable from one to the other.

[00:13:02] Speaker 00:
And just simply stating that there is a reference claim to modifying hyaluronidase by pegalation or dextrin doesn't get you through Braxton and Thompson

[00:13:19] Speaker 00:
to the clear invention here, which is to develop a new drug that would be used for systemic use, never before application, that had been identified, and that there's no clear guiding or teaching in the art around it.

[00:13:35] Speaker 03:
You're into your rebuttal time.

[00:13:37] Speaker 00:
I'll reserve the rest.

[00:13:37] Speaker 00:
Thank you.

[00:13:46] Speaker 02:
May it please the court, for Helizine to prevail, it must establish that all four of the board's rejections were in error.

[00:13:54] Speaker 02:
The correct starting point for the board's rejections is not an unpagulated hyaluronidase.

[00:14:01] Speaker 02:
It's a pagulated hyaluronidase, which is claimed by each of the reference patents and disclosed by Bookfinder.

[00:14:09] Speaker 02:
Using these starting points, the district court did find motivation to optimize in a reasonable

[00:14:17] Speaker 02:
expectation of success.

[00:14:18] Speaker 01:
In fact, isn't it the case that bookbinder is only missing the three to six?

[00:14:22] Speaker 01:
Nothing else.

[00:14:22] Speaker 01:
Everything is there.

[00:14:23] Speaker 01:
So I don't know how to say all those words, lysine, pegulation.

[00:14:28] Speaker 01:
It's all disclosed in there, right?

[00:14:29] Speaker 01:
Everything is in there.

[00:14:31] Speaker 03:
Right.

[00:14:31] Speaker 03:
Okay.

[00:14:32] Speaker 03:
But the rain, I mean, your friend, you heard him and he made the same argument in his briefs.

[00:14:37] Speaker 03:
that routine optimization does not get you there.

[00:14:41] Speaker 03:
There's just no range disclosed in the prior art.

[00:14:45] Speaker 03:
And so this isn't an issue, a case where you can apply routine optimization.

[00:14:50] Speaker 02:
Well, actually there is a range disclosed in the prior art because a person of ordinary skill knew that there were only 31 license.

[00:14:57] Speaker 02:
So the largest number that could be pagulated was 31.

[00:15:01] Speaker 02:
And all of the experts explained

[00:15:04] Speaker 02:
that a person of ordinary skill in the art knew how to pegulate.

[00:15:07] Speaker 02:
They knew how to attach pegs.

[00:15:09] Speaker 02:
They knew how to figure out how many pegs were there.

[00:15:11] Speaker 02:
And so it would just be narrowing the 31 possible sites down to what Hellezheim says is a weighted average to about 3 to 6.

[00:15:22] Speaker 02:
So there is a range there.

[00:15:23] Speaker 02:
I do want to mention something about the formulated for systemic administration because Hellezheim talks about that a lot.

[00:15:30] Speaker 02:
That claim term is actually just redundant of the other claim terms in the claims.

[00:15:37] Speaker 02:
The only evidence Halizan presented on why formulated for systemic administration is a patentable distinction was Dr. Flamion saying that the term is important because it must have the properties to be injected as a systemic administration.

[00:15:51] Speaker 02:
And that was at 7719.

[00:15:52] Speaker 02:
And he explained that those properties are twofold, solubility and a relatively long half-life.

[00:15:59] Speaker 02:
That's at 7683.

[00:16:01] Speaker 02:
Both of those properties are already achieved by modification of the protein.

[00:16:06] Speaker 02:
Solubility is achieved by truncation, and the long half-life is achieved by pegulation.

[00:16:12] Speaker 02:
So the claims of all of the ODP reference patents already claim a truncated, pegulated hyaluronidase.

[00:16:19] Speaker 02:
So they are already formulated for systemic administration.

[00:16:23] Speaker 01:
You moved away, though, from the argument that he spent the bulk of his time on, and you really didn't respond in any significant way to the 3 to 6 limitation.

[00:16:34] Speaker 01:
Even if a skilled artist would know there are only 31 choices, how do you get from 31 to 3 to 6?

[00:16:40] Speaker 01:
What's the evidence?

[00:16:42] Speaker 02:
So the evidence is that a person of ordinary skill knew how to do so, right?

[00:16:46] Speaker 02:
Nectar, salt, pegalation, reagents.

[00:16:50] Speaker 02:
Halizam's own expert said a person would make a pegolated hyaluronidase, test it for activity and longevity, and if the result didn't meet your desired criteria, you could vary the degrees of pegolation.

[00:17:01] Speaker 02:
That's at 78.53.

[00:17:03] Speaker 02:
That's Dr. Zalewski.

[00:17:04] Speaker 02:
Their other expert, Dr. Flamion, said that if you have no effect on half-life with one peg, your natural response would be to put on three, four, or five pegs until you have some effect.

[00:17:15] Speaker 02:
That's at 7742.

[00:17:15] Speaker 02:
So a person of ordinary skill knew what the variables were, knew how to pegulate, and would simply put pegs on, test it for activity and longevity.

[00:17:26] Speaker 02:
And if the result didn't meet your desired criteria, you would vary the degrees of pegulation.

[00:17:33] Speaker 02:
Halizam's argument, moving on to bookbinder,

[00:17:39] Speaker 01:
Varying the degrees, though, I mean, how many choices is it?

[00:17:43] Speaker 01:
It's not 31 choices, right?

[00:17:46] Speaker 01:
And it's infinitely more than that.

[00:17:48] Speaker 02:
So they make an argument that there's a million variants.

[00:17:51] Speaker 02:
But that's incorrect, because the claims don't require pegulation at any particular points.

[00:17:57] Speaker 02:
All they require is about three to six pegs.

[00:18:01] Speaker 02:
Halizime actually says it's a weighted average of about three to six pegs.

[00:18:05] Speaker 02:
So some of the proteins could actually have eight pegs.

[00:18:07] Speaker 02:
Some of the proteins could have one.

[00:18:09] Speaker 02:
So it's actually quite a long range.

[00:18:12] Speaker 02:
And our expert, Dr. Joe, said that that would be easy for a person of ordinary skill to achieve.

[00:18:17] Speaker 02:
And there was no rebuttal testimony to that.

[00:18:22] Speaker 02:
It would be easy why and how?

[00:18:25] Speaker 02:
It would be easy because you only have 31 possible choices.

[00:18:31] Speaker 02:
And a person would know, like I said, what the variables are.

[00:18:34] Speaker 02:
One of the variables is pH.

[00:18:36] Speaker 02:
One of the variables is the concentration of pegs per protein.

[00:18:39] Speaker 02:
So you would just put that on.

[00:18:41] Speaker 02:
You would test it.

[00:18:42] Speaker 02:
And as Dr. Fleming said, if you didn't see an increase in half-life, you would add more pegs.

[00:18:47] Speaker 02:
And you could do that by changing the pH or changing the concentration until you got to the range where it was the optimal balance.

[00:18:54] Speaker 02:
A person of ordinary skill knew that pegulation increased half-life and decreased activity.

[00:19:01] Speaker 02:
And they would be motivated to find that optimal point.

[00:19:05] Speaker 03:
What about your friend's argument with respect to the other?

[00:19:08] Speaker 03:
I guess it was the Thompson reference, and that it taught away, and he kept using the word cherry picking in terms of one sentence from the background.

[00:19:16] Speaker 02:
Right.

[00:19:17] Speaker 02:
So first of all, their teaching away argument is actually asking, it's actually ignoring the primary reference, which is Bookbinder, which already teaches to use lysine pegulation.

[00:19:31] Speaker 02:
What they're asking

[00:19:32] Speaker 02:
the district court to do was ignore bookbinder.

[00:19:36] Speaker 02:
Pretend bookbinder doesn't exist.

[00:19:38] Speaker 02:
And pretend you have an unpagulated hyaluronidase and only Braxton and Thompson in hand.

[00:19:45] Speaker 02:
And then would you choose lysine paglation?

[00:19:48] Speaker 02:
But the starting point is already, with bookbinder, a pagulated hyaluronidase with lysine.

[00:19:55] Speaker 02:
But even if we were to go down that road and figure out whether the prior art

[00:20:00] Speaker 02:
whether Braxton and Thompson teach away from lysine pigilation.

[00:20:04] Speaker 02:
They don't.

[00:20:05] Speaker 02:
Palazim is the one that's cherry picking the one sentence, which says, such mixtures of diversely modified proteins are not suitable as pharmaceutical compositions.

[00:20:14] Speaker 02:
Diversely modified proteins means lysine pigilated.

[00:20:18] Speaker 02:
But the very next sentence, Braxton tells you how to solve that.

[00:20:22] Speaker 02:
He tells you to use purification and characterization.

[00:20:27] Speaker 02:
And Dr. Joe testified that both of those techniques had improved tremendously since Braxton was filed in 1995.

[00:20:37] Speaker 02:
The other thing is Braxton is self-contradictory when it says these mixtures are not suitable as pharmaceutical compositions, because the example Braxton is using is adesine diaminase, which is adenogen, which actually was approved by the FDA

[00:20:54] Speaker 02:
as a lysine-pegalated pharmaceutical composition.

[00:20:58] Speaker 02:
And Halizam's own expert, Dr. Zalipsky, admitted that and said it was ironic.

[00:21:03] Speaker 03:
So let me just ask you about the play in this case, because you've got at least two separate ways to go here, on a 103 straightforward obviousness and then on a double patenting.

[00:21:14] Speaker 03:
Is there any reason for us to decide

[00:21:18] Speaker 03:
on both of those grounds or to pick one or another?

[00:21:22] Speaker 03:
Are there any consequences to how we decide to resolve this case if we are interested in affirming it?

[00:21:29] Speaker 02:
So if you were, since all the claims were rejected under all four rejections, if you affirm any one of them, that will end this dispute.

[00:21:39] Speaker 02:
In other words, Halizime has to show error.

[00:21:41] Speaker 03:
And there's no consequence.

[00:21:43] Speaker 03:
There are no other pending cases or things or reason to resolve a double patenting issue on these claims or anything like that.

[00:21:50] Speaker 02:
Not that I know of.

[00:21:52] Speaker 02:
I think Halizam also made the argument about the ODP rejection that the district court looked at the specification of the reference patents, but that was an alternative.

[00:22:07] Speaker 02:
So if this court were to affirm the district court

[00:22:10] Speaker 02:
analysis without looking at the specifications of the 431 and 081 patents, it would not even have to look at that legal issue.

[00:22:17] Speaker 03:
Going back to the first argument, and he did raise this point about under the 103 rejection, whether the board rejected it having not sufficient written description because it had no starting point.

[00:22:32] Speaker 03:
You know what I'm talking about.

[00:22:33] Speaker 03:
And he's arguing that there is a starting point.

[00:22:35] Speaker 03:
And he referred to us to a page in the board's opinion where the board itself

[00:22:40] Speaker 03:
acknowledge that.

[00:22:41] Speaker 03:
So could you respond to that point?

[00:22:43] Speaker 02:
Sure.

[00:22:43] Speaker 02:
So it was their, they were trying to show priority to the 171 application at the district court, so it was their burden to show written description.

[00:22:52] Speaker 02:
This is actually a new argument that their expert didn't make.

[00:22:55] Speaker 02:
Their expert at trial only relied on paragraph 39 of the 171 application.

[00:23:01] Speaker 02:
The district court did not let them, did not let the expert rely on another paragraph, paragraph 704, because it had not been disclosed during discovery.

[00:23:09] Speaker 02:
Halizam is now trying to rely on 704 again, even though the district court didn't let their expert rely on it.

[00:23:17] Speaker 02:
And they're actually raised two additional paragraphs for the first time in their appeal brief that they're trying to rely on, paragraphs 114 and 44.

[00:23:25] Speaker 02:
And now they're trying to rely on sequence ID number four.

[00:23:29] Speaker 02:
So all those arguments are waived.

[00:23:32] Speaker 02:
Their expert had every opportunity to rely on them at trial in their expert reports and did not.

[00:23:40] Speaker 03:
But my recollection is, what about he pointed us to Appendix 11 at the start of his argument?

[00:23:48] Speaker 03:
I think it was Appendix 11, or the board's opinion.

[00:23:56] Speaker 03:
I'm sorry, it's a district question.

[00:23:58] Speaker 02:
Yeah, it's actually Appendix 12.

[00:24:01] Speaker 03:
OK.

[00:24:02] Speaker 02:
So that does say that seek ID number 4 corresponds to those amino acids.

[00:24:09] Speaker 02:
But first of all, the claims aren't limited to just 36 to 483.

[00:24:12] Speaker 02:
They have other starting points.

[00:24:14] Speaker 02:
And second of all, their expert never relied on seek ID number four.

[00:24:17] Speaker 02:
He generally pointed and said, there are 30 pages of sequences.

[00:24:22] Speaker 02:
There are 53 sequences.

[00:24:23] Speaker 02:
It's in there somewhere.

[00:24:24] Speaker 02:
But he did not point to seek ID number four to support this.

[00:24:33] Speaker 02:
If there's nothing further, I'll yield the rest of my time.

[00:24:36] Speaker 02:
Thank you.

[00:24:43] Speaker 00:
Just very briefly, Your Honor.

[00:24:45] Speaker 00:
First, with respect to the routine optimization, it also includes the requirement formulated for systemic activity to have activity.

[00:24:55] Speaker 00:
It's not just half-life.

[00:24:56] Speaker 00:
It also has to have activity in the systemic context.

[00:25:00] Speaker 00:
That was unknown.

[00:25:03] Speaker 00:
Second, turning to bookbinder, as we've argued, bookbinder, of course, is not prior art, so relying specifically upon

[00:25:11] Speaker 00:
Disclosure in bookbinder is part of the obviousness that the PTO does is improper because bookbinder itself does not qualify under as prior art because it relates back the 171 application relates back to the 716 application and Therefore bookbinder is not prior art so the contents of bookbinder should not be properly considered as part of the obviousness finally with respect to bookbinder itself again

[00:25:42] Speaker 00:
One, PTO points out that we didn't raise a specific point about seek ID number four that the court's opinion relies upon at page 11.

[00:25:51] Speaker 00:
But of course, we didn't have the court's opinion at trial.

[00:25:54] Speaker 00:
This is what came out afterwards.

[00:25:56] Speaker 00:
This shows the contradictory nature of the clear evidence that was before the court.

[00:26:03] Speaker 00:
The beginning and the end points were all disclosed in the application that was in evidence.

[00:26:10] Speaker 00:
And the court said there's no beginning and end point, and that is completely contradicted by its earlier point in its decision at page 11.

[00:26:17] Speaker 03:
Thank you.