[00:00:04] Speaker 02:
Councilman Blackmon, you said you reserved six minutes of your time, correct?

[00:00:08] Speaker 02:
Yes, sir.

[00:00:09] Speaker 02:
All right, you may proceed.

[00:00:10] Speaker 02:
Thank you.

[00:00:12] Speaker 01:
Good morning.

[00:00:12] Speaker 01:
May it please the court?

[00:00:15] Speaker 01:
I think the ultimate issue before this court in this case is whether the cited combination of prior art references genuinely discloses or suggests every claimed feature as required by each of the pending claims.

[00:00:29] Speaker 01:
We believe the answer is no.

[00:00:32] Speaker 01:
I hope to establish the following three points.

[00:00:36] Speaker 01:
The critical prior art document cited is the pharmacopoeia disclosure, an excerpt from the pharmacopoeia that sets multiple general safety standards for all parental products.

[00:00:47] Speaker 01:
All products are intended to be injected into a patient rather than administered by another mode.

[00:00:52] Speaker 01:
There are hundreds or thousands of treating agent formulations designed for injection to a patient for one reason or another.

[00:01:04] Speaker 01:
Our second point is

[00:01:06] Speaker 01:
that the specific claims, the pending claims at issue, all require a specific narrow combination.

[00:01:14] Speaker 01:
Among a few other elements in the claims, they all require treatment, a container of treatment where the treating agent is one of a small specific class of treating agents.

[00:01:28] Speaker 01:
And they also require that extractable zinc from the closure be zero parts per million.

[00:01:34] Speaker 01:
The pharmacopoeia, the general disclosure, is five parts per million as a safety measure.

[00:01:40] Speaker 01:
And our third point is that nothing in the combined disclosures of the prior art genuinely suggests the specific claim combination.

[00:01:50] Speaker 01:
The prior art discusses a safety limit of five parts per million of extractable zinc from rubber closures for these types of containers.

[00:01:59] Speaker 01:
The claims require for specific treaty agents for

[00:02:03] Speaker 01:
acid labile proton pump inhibitors, of which Pantoprazole is one, the extractable zinc should be zero parts per million.

[00:02:12] Speaker 03:
But the reference is disclosure of five parts per million as a safety limit encompasses zero parts per million.

[00:02:20] Speaker 01:
We would disagree with that, sir.

[00:02:23] Speaker 01:
Safety limit says that you cannot exceed five parts per million.

[00:02:27] Speaker 01:
Not only does the pharmacopeia not teach you how to achieve the five,

[00:02:31] Speaker 01:
It doesn't discuss less.

[00:02:32] Speaker 01:
All it says is that anything higher than five is no good.

[00:02:36] Speaker 01:
There's nothing that affirmatively teaches or discloses even five, let alone anything less.

[00:02:41] Speaker 01:
So for example, there are three cases cited for ranges.

[00:02:51] Speaker 03:
We're not talking about anticipation.

[00:02:53] Speaker 03:
We're talking about obviousness.

[00:02:55] Speaker 03:
So the question is, is this statement of a limit of teaching

[00:03:00] Speaker 03:
on an ordinary skill in the art would understand encompasses, obviously it encompasses things that are less than five parts per million.

[00:03:09] Speaker 03:
It's an upper limit.

[00:03:11] Speaker 03:
And even in your argument, you point out fairly clearly that even the recitation zero part per million, it's really not zero.

[00:03:21] Speaker 01:
Right.

[00:03:22] Speaker 01:
And in fact, the specification defines zero parts per million as no detectable amount of zinc.

[00:03:27] Speaker 01:
The critical point, though, is that the combination, the particular combination, of this family of treating agents with zero, as opposed to the pharmacopoeia's limit of five, the application itself points out that that gives us an unexpected result.

[00:03:42] Speaker 03:
And what is it about that combination that provides this unexpected result?

[00:03:48] Speaker 01:
Yeah, as far as understanding why it works, I'm not sure.

[00:03:52] Speaker 01:
But what happens is with acid-laborol proton pump inhibitors, the inventors found

[00:03:57] Speaker 01:
And it's in the appendix and the application at pages 18 and 19.

[00:04:06] Speaker 01:
The inventors found that surprisingly, by using the closure container system, which essentially does not release zinc ions, then in Pantoprazole and related injection solutions.

[00:04:18] Speaker 04:
What are you reading from?

[00:04:19] Speaker 01:
I'm sorry, appendix page 18.

[00:04:22] Speaker 01:
The third paragraph starts surprisingly.

[00:04:24] Speaker 01:
Thank you.

[00:04:27] Speaker 01:
And it says that the formation of particles can be suppressed or completely avoided.

[00:04:33] Speaker 01:
So even more than the general limit, the pharmacopoeia sets forth a general limit for all parenteral products.

[00:04:38] Speaker 01:
And the general limit for zinc is five parts per million.

[00:04:42] Speaker 01:
Anything higher than that is not permitted, is not deemed safe.

[00:04:46] Speaker 01:
It's a maximum of five parts, correct?

[00:04:49] Speaker 01:
Yes, sir.

[00:04:50] Speaker 01:
It has to be no higher than five.

[00:04:55] Speaker 02:
part per million wouldn't satisfy you.

[00:05:01] Speaker 01:
Yes.

[00:05:01] Speaker 02:
So you would say that's within the range.

[00:05:03] Speaker 02:
One, two, three, four, not zero.

[00:05:05] Speaker 02:
Right.

[00:05:07] Speaker 01:
And if our claims went to all parental products and simply lowered the amount of zinc, I would agree that that's significant.

[00:05:15] Speaker 01:
But there's nothing in the record that points to zero parts per million as having special significance with this particular

[00:05:21] Speaker 01:
treating agent family.

[00:05:23] Speaker 01:
All the claims require that the treating agent be an acid lay-by-all proton pump inhibitor.

[00:05:30] Speaker 02:
But wouldn't a person skilled in art say, well, if one part satisfies it, let me try zero?

[00:05:37] Speaker 01:
Well, I understand, and there's certainly an initial attraction to that type of an argument.

[00:05:46] Speaker 01:
But for example, the pharmacopeia generally is... Well, it seems like a practical step.

[00:05:51] Speaker 01:
Well, except that I would point out that even in the two pages of the pharmacopoeia that are cited in the appendix at 495 to 496, even with regard specifically to rubber closures for aqueous parenteral preparations, the pharmacopoeia sets forth a number of limitations, a number of safety limitations.

[00:06:10] Speaker 01:
It deals with the elasticity of the closure.

[00:06:14] Speaker 01:
It deals with solubility, acidity, absorbance,

[00:06:17] Speaker 01:
the presence of reducing substances.

[00:06:19] Speaker 01:
There's a whole slew of issues, even just specifically for this one factor.

[00:06:23] Speaker 01:
And obviously, when you're talking about a treating agent solution, the nature of the rubber closure is only one small part of the whole picture.

[00:06:31] Speaker 01:
You've got the container.

[00:06:32] Speaker 01:
You've got the closure.

[00:06:33] Speaker 01:
You've got the needle that's going to be involved.

[00:06:34] Speaker 01:
You've got what goes into the solution.

[00:06:37] Speaker 01:
And even still, even as far as contaminants, the pharmacopoeia talks about

[00:06:42] Speaker 01:
impurities, ammonium is limited to two parts per million, extractable heavy metals are limited to two parts per million, volatile sulfide is limited against a standard solution, and then there's an extractable zinc at five parts per million.

[00:06:56] Speaker 01:
We're saying the inventors are claiming that this particular combination, zero parts per million of zinc, that one combination with these particular treating agents makes a difference.

[00:07:10] Speaker 01:
And frankly,

[00:07:11] Speaker 01:
When you take it in context, that's one limitation out of a slew of limitations for the rubber stoppers.

[00:07:18] Speaker 01:
And it's, of course, one of even myriad other sets that this applies to when you're looking at all formulations, all kinds of treating agents.

[00:07:33] Speaker 01:
So that leads to the third point.

[00:07:35] Speaker 01:
Our position is that nothing in the combined disclosures genuinely teaches this combination.

[00:07:39] Speaker 01:
It's a very specific combination in the claims.

[00:07:41] Speaker 01:
It requires an acetyl-avial proton pump inhibitor and zero parts per million, no detectable amount of zinc.

[00:07:49] Speaker 01:
And the application itself also goes on to explain that that was an unexpected result, that if you limit that particular parameter in the solution, in the closure of the solution, that

[00:08:04] Speaker 01:
That particular parameter is enough to typically avoid precipitate in the solution.

[00:08:16] Speaker 02:
Thank you.

[00:08:26] Speaker 02:
OK.

[00:08:26] Speaker 02:
Mrs. Caprion.

[00:08:29] Speaker 00:
Good morning, Your Honors, and may it please the court.

[00:08:31] Speaker 00:
Here, substantial evidence supports the board's finding

[00:08:35] Speaker 00:
that Lippert's claimed closure, which basically discloses a mate of material where there's zero parts per million extractable zinc, as determined by the European Pharmacopeia, is obvious in view of the standard that is set forth in that pharmacopeia itself.

[00:08:51] Speaker 00:
And as your honors acknowledged, the pharmacopeia sets a standard of no more than a maximum of five parts per million of extractable zinc.

[00:09:00] Speaker 00:
Now what this discloses is a range

[00:09:02] Speaker 00:
of allowable extractable zinc within the closures and that range encompasses the range that is claimed in this claim.

[00:09:10] Speaker 04:
So sometimes the, I don't know, let's call it a presumption of picking something within a previously disclosed range can be overcome.

[00:09:19] Speaker 04:
What is the kind of evidence, I know you think that there wasn't sufficient, but what is the kind of evidence

[00:09:26] Speaker 04:
that the applicant here should have tried to come up with that might have overcome that presumption.

[00:09:35] Speaker 00:
Well, the case law makes clear that when you are claiming a specific point within a disclosed range or within a taught range, what you have to show is criticality of that.

[00:09:45] Speaker 04:
Yeah, I will say I've never understood what that means in a concrete way.

[00:09:50] Speaker 04:
That's kind of my question.

[00:09:51] Speaker 04:
What does it mean to be critical?

[00:09:52] Speaker 00:
So in this case, Lipper could have submitted data

[00:09:56] Speaker 00:
showing that the particular combination here of the pharmaceutical product as well as having no detectable zinc greatly increased or rather greatly reduced the number of particles in solution.

[00:10:12] Speaker 00:
Because that's really at the end of the day, that's what they're saying, that this surprising event is what's taught here.

[00:10:18] Speaker 04:
So in order for them to actually overcome that... Doesn't the application that the pages we were talking about before, I guess, Joint Appendix 18 and 19, say that by doing this you can reduce or eliminate formation of certain kinds of undesirable particles?

[00:10:38] Speaker 00:
At APPX 18, what the inventor says is that it was surprising that this event occurs.

[00:10:46] Speaker 00:
But what

[00:10:47] Speaker 00:
a liberate has to show here is that not only was it surprising that this event occurred, but that it was surprising within the scope that's taught in the prior art as well as within what's claimed.

[00:10:59] Speaker 00:
And here what's taught in the prior art is that it is preferable to have five parts per million or less of extractable zinc.

[00:11:06] Speaker 00:
And the reason that's preferable is because the pharmacopoeia standard sets forth standards to not only improve the safety of the closures

[00:11:15] Speaker 00:
that are contained within these parenteral pharmaceutical products but also to protect the actual pharmaceutical product that's contained within.

[00:11:24] Speaker 00:
And what it taught was that it's preferable not to have contaminants go from the closure to the pharmaceutical product that's contained.

[00:11:32] Speaker 00:
And so because that is taught within the prior art,

[00:11:35] Speaker 00:
It is not invented to discover a particular value within that disclosed range, where they haven't shown that at five parts per million of extractable zinc, the amount of particles and product is significantly more than at zero parts per million of extractable zinc.

[00:11:53] Speaker 04:
Did they make any kind of case of no reasonable expectation of success?

[00:11:59] Speaker 04:
I guess I heard an echo of that.

[00:12:01] Speaker 04:
in the suggestion that even the European Pharmacopeia didn't teach you how to do the five, let alone how to get significantly below that.

[00:12:11] Speaker 00:
Before the board, they did raise that argument that there was no reasonable expectation of success here.

[00:12:16] Speaker 00:
But what the board and the examiner found is that the European Pharmacopeia itself teaches the testing that's used to determine whether or not a closure actually meets those limitations.

[00:12:26] Speaker 00:
And so because the European Pharmacopeia

[00:12:28] Speaker 00:
teaches, one of skill in the art, what tests to use to determine whether a particular closure meets the five parts per million of extractable zinc limit.

[00:12:37] Speaker 00:
It would also teach whether or not a particular closure had no detectable zinc here.

[00:12:42] Speaker 00:
And so what the board found is that there was a reasonable expectation.

[00:12:44] Speaker 02:
Does the pharmacopoeia reference teach the benefit of eliminating particle formation by reducing the zinc?

[00:12:52] Speaker 00:
What it does teach is that by limiting the amount of contaminants, you actually

[00:12:57] Speaker 00:
promote the safety and reduce the toxicity of the pharmaceutical product contained therein.

[00:13:03] Speaker 00:
And that's taught at page 495.

[00:13:07] Speaker 00:
But that's not the only prior art here of record.

[00:13:10] Speaker 00:
The other prior art also teaches that it is preferable to reduce the amount of contaminants that go from the disclosure into any pharmaceutical products that contain within the container closure system.

[00:13:23] Speaker 00:
If there are no further questions.

[00:13:24] Speaker 04:
Can I just actually follow up on something?

[00:13:28] Speaker 04:
I may well be confused at the moment.

[00:13:32] Speaker 04:
The following two things do not seem to me logically equivalent.

[00:13:35] Speaker 04:
One is if I give you something, you know how to test how much zinc is in it.

[00:13:41] Speaker 04:
And the other is I know how to make something with a particularly low level of zinc.

[00:13:49] Speaker 04:
And it isn't the reasonable expectation of success inquiry, the latter, and therefore not answered by saying,

[00:13:57] Speaker 04:
Here's a test that can tell you how much zinc there is.

[00:14:01] Speaker 00:
Well, I think first we have to look back and see what is claimed here.

[00:14:04] Speaker 00:
And what is claimed is a closure that is made of material with zero parts per million of extractable zinc.

[00:14:11] Speaker 00:
And that closure that they have disclosed in their application is not made of any particular material.

[00:14:19] Speaker 00:
They've disclosed various different embodiments, but those embodiments are taught in the prior art.

[00:14:24] Speaker 00:
And so it's not

[00:14:26] Speaker 00:
inventive to discover that a particular point within this range that's disclosed within the pharmacopoeia would have these beneficial properties.

[00:14:36] Speaker 00:
And second, what is claimed here is a closure where it's zero parts per million as determined by the European pharmacopoeia.

[00:14:45] Speaker 00:
And the European pharmacopoeia discloses the tests that one would use to determine whether a particular closure has zero parts per million of extractable

[00:14:54] Speaker 04:
But if you still couldn't make it, doesn't that?

[00:14:58] Speaker 04:
I mean, I guess I'm still not hearing you say prior art taught you how to get a closure down around the zero.

[00:15:08] Speaker 00:
Well, the prior art recognized that it is preferable to reduce the amount of contaminants that could flow from the closure into the pharmaceutical product.

[00:15:17] Speaker 00:
That's clear.

[00:15:18] Speaker 00:
That's taught by Meraki.

[00:15:19] Speaker 00:
That's taught by Lippert.

[00:15:20] Speaker 00:
And Meraki actually discloses, one of the embodiments disclosed in Meraki

[00:15:24] Speaker 00:
is a sealed closure.

[00:15:27] Speaker 00:
And the objective of Meraki, and I think we'll point that to you.

[00:15:34] Speaker 00:
If you turn to page 488 of the appendix, well, if you look at the figure on page 487, it shows a stopper and it shows a laminated layer of the stopper.

[00:15:46] Speaker 00:
And then at 488, one of the objectives or one of the problems that they were trying to overcome in the prior art was they wanted to reduce the contamination that takes place.

[00:15:55] Speaker 00:
due to fine particles from the rubber materials during production steps of storage and medikins.

[00:15:58] Speaker 00:
So they didn't want any fine particles falling from the rubber closures into the farm school product container in.

[00:16:05] Speaker 00:
So the prior art recognized that this was a problem.

[00:16:08] Speaker 00:
This is not a new problem.

[00:16:09] Speaker 00:
And the prior art also recognized ways to achieve that, or ways to solve that problem.

[00:16:15] Speaker 00:
I think another also telling thing here is that within the inventor's specification, they disclosed various embodiments.

[00:16:23] Speaker 00:
that would encompass this invention.

[00:16:26] Speaker 00:
And at APPX, I believe it's 19.

[00:16:31] Speaker 02:
What was that slide?

[00:16:33] Speaker 00:
APPX 19.

[00:16:34] Speaker 00:
It's the inventor's disclosure, or specification, rather.

[00:16:39] Speaker 00:
And they talk about various types of closures that would meet the claimed invention.

[00:16:45] Speaker 00:
And one of the embodiments they disclose is a type 1 rubber closure

[00:16:49] Speaker 00:
as according to the European pharmacopeia itself.

[00:16:52] Speaker 04:
About 10 lines up from the bottom?

[00:16:53] Speaker 00:
Correct.

[00:17:00] Speaker 00:
And that type 1 closure would meet the strictest requirements of the European pharmacopeia.

[00:17:05] Speaker 00:
And yet, I think another telling thing is that in their reply break at page 10, the Lippert in fact concedes and acknowledges that there were options available that would likely produce closer to zero parts per million of extractable things.

[00:17:19] Speaker 00:
So not only is this taught in the prior art, but appellants here can see that it would not be difficult to do.

[00:17:30] Speaker 00:
Any questions?

[00:17:30] Speaker 00:
If there are no further questions, I yield.

[00:17:31] Speaker 01:
Thank you.

[00:17:36] Speaker 01:
Mr. Pesce?

[00:17:36] Speaker 01:
Yes, sir.

[00:17:40] Speaker 01:
At page 19 of the appendix, in the section that was just being discussed,

[00:17:47] Speaker 01:
The claims focus on zero parts per million.

[00:17:50] Speaker 01:
The disclosure discusses less than five, less than four, less than three, less than two, less than one.

[00:17:55] Speaker 01:
The claims are the most preferred embodiment and the strictest of these in order to most minimize and avoid detectable amounts of zinc.

[00:18:04] Speaker 01:
The zero is the only one that's defined as a non-detectable amount of zinc.

[00:18:09] Speaker 04:
So does your written description enable zero?

[00:18:19] Speaker 04:
Yes, there are.

[00:18:23] Speaker 04:
And it seems to me there are only two possibilities that enables it.

[00:18:26] Speaker 04:
One is you say, here's something new, nobody did before, and it's zero.

[00:18:30] Speaker 04:
And the other is something off the shelf, zero.

[00:18:34] Speaker 01:
The point is that it's a new closure, necessarily.

[00:18:38] Speaker 01:
The point is that, I mean, first off, for example, Meraki itself, they use a laminated closure.

[00:18:45] Speaker 01:
But the closure itself, if you look at Meraki in the appendix of 492,

[00:18:49] Speaker 01:
The rubber itself is made using a zinc compound.

[00:18:52] Speaker 01:
So when you insert a needle through that closure, without being tested, there's no way to know whether any zinc can still leach through the hole that's made by the needle or that may come out, maybe enter into the solution when the needle is inserted.

[00:19:06] Speaker 01:
The specification has a broad range, but the claims focus on zero.

[00:19:12] Speaker 01:
And the important thing is,

[00:19:13] Speaker 01:
Not so much that the stoppers are new.

[00:19:15] Speaker 01:
I mean, if you use a stopper that simply is produced without any zinc in the process, then there can't be any zinc.

[00:19:21] Speaker 01:
The key here is recognizing that reaching the zero parts per million, which is more expensive and not typical in the industry, but reaching zero parts per million of zinc with this particular set of treating agents.

[00:19:39] Speaker 01:
You don't have to worry about the other factors.

[00:19:41] Speaker 01:
that the pharmacopoeia sets forth, you don't have to worry about, we're not combining it with any particular extra limits on the ammonium, on heavy metals, anything else, but for this particular set of treating agents, zero detectable zinc makes a difference.

[00:19:57] Speaker 01:
And our position is not that we're combining, that we created something new with the closure, but it's this particular combination with the specific, very narrow set of treating agents makes a difference.

[00:20:09] Speaker 01:
And that's what was not known or disclosed in the prior argument.