[00:00:04] Speaker 00:
All right, our final case today, 2019-1067, Amgen versus Haspera.

[00:00:12] Speaker 00:
Mr. Meloro, please proceed.

[00:00:14] Speaker 04:
Thank you, Your Honor, and may it please the court.

[00:00:21] Speaker 04:
The judgment of infringement of the 298 patent should be reversed because it was based on an erroneous claim construction

[00:00:29] Speaker 04:
I'd like to turn to the language of claims 24 and 27, going first to claim 24, and explain how the claim language is pieced together in a way which results in a single ISO form.

[00:00:44] Speaker 00:
As a general starting point, can I ask you, since claim 24 and 27 are predicated on different arguments in this case,

[00:00:54] Speaker 00:
If we were to affirm across the board on either one of them, that would end the case without the need to address the other.

[00:01:00] Speaker 00:
Is that right?

[00:01:02] Speaker 04:
If the affirmance across the board was on either claim 24 or claim 27, then yes, that would end the case on the 298 patent across the board, meaning not just the Markman issues, but the other J-Mall issues on infringement.

[00:01:17] Speaker 04:
The State Harbor or everything else, yeah.

[00:01:19] Speaker 04:
Exactly, with respect to those issues.

[00:01:23] Speaker 04:
Now, with respect to claim 24, there are three pieces to the claim that show that you get a single isoform.

[00:01:33] Speaker 04:
You start by the introductory clause, a method of preparing, and I'm just going to call it EPO today, a method of preparing EPO molecules.

[00:01:43] Speaker 04:
And so then the question is, how are those EPO molecules characterized and required in the claim?

[00:01:51] Speaker 04:
those EPO molecules having a predetermined number of sialic acids per molecule.

[00:01:58] Speaker 04:
And then there's an important Marcouche limitation, that those molecules have a predetermined number of sialic acids, said number, selected from the group consisting of 1 to 14.

[00:02:11] Speaker 04:
So that closed Marcouche language tells us that all of the molecules have a predetermined number, and that's one and only one number.

[00:02:21] Speaker 04:
we end up with a single isoform having a single number of sialic acids corresponding to it.

[00:02:29] Speaker 04:
And then the last part of the claim.

[00:02:31] Speaker 03:
Well, the claim doesn't say, I mean, first of all, let me just lead by saying this claim is not so clear.

[00:02:42] Speaker 03:
But the claim, as you understand it, would be that a method of preparing EPO modules

[00:02:52] Speaker 03:
having an identical predetermined number of sialic acids per molecule, and then said number selected from the group consisting of 1 to 14.

[00:02:59] Speaker 03:
The claim doesn't say that extra word identical before predetermined.

[00:03:04] Speaker 03:
So I mean, one, the alternative reading, which the judge below adopted, was that, yes, every molecule of the resulting EPO molecules have to have a predetermined number of sialic acids

[00:03:20] Speaker 03:
anywhere between 1 to 14 sialic acids.

[00:03:23] Speaker 03:
So what's wrong with that understanding of this language?

[00:03:29] Speaker 04:
The word identical, of course, is not in claim 24.

[00:03:34] Speaker 04:
But claim 24 does specify identical because of the Marcouche language that said number is selected from the group consisting of 1 to 14.

[00:03:43] Speaker 04:
Right.

[00:03:45] Speaker 03:
So I guess why doesn't that just mean, well,

[00:03:49] Speaker 03:
Every molecule has to have a particular number of sialic acids.

[00:03:54] Speaker 03:
It can't have both two sialic acids and eight sialic acids.

[00:03:58] Speaker 03:
It can only have one number, and that number consists of something between 1 and 14.

[00:04:06] Speaker 04:
Both because of the way the claim language is put together, that the molecules have a predetermined number.

[00:04:12] Speaker 04:
And if it was going to be mixtures of numbers, some molecules having one, some have two.

[00:04:17] Speaker 03:
It's a predetermined number per molecule.

[00:04:19] Speaker 03:
I guess that's what's hanging me up, is what work am I supposed to give to the phrase per molecule?

[00:04:28] Speaker 04:
Because the molecules are what's listed as having a predetermined number.

[00:04:34] Speaker 04:
And so if it were going to be that some molecules could have one number and some molecules could have another number,

[00:04:40] Speaker 04:
then what you would have is a situation where the claim would have to say, selected from the group consisting of 1 to 14 or mixtures thereof, or selected from the group consisting of one or more of the numbers from 1 to 14.

[00:04:54] Speaker 04:
As a practical matter, that would also mean the claim language wouldn't really carry any meaning, because EPO molecules always have a number of sialic acids.

[00:05:05] Speaker 04:
A particular molecule won't have 2 and 4.

[00:05:07] Speaker 01:
It struck me that there is a

[00:05:10] Speaker 01:
Contrast between the language used in claim 24 and the language used in claim 13 setting aside that 24 is a method claim claim 13 refers to EPO consisting essentially of EPO molecules having a single specific number of sialic acids per molecule said number selected from the group consisting of 1 through 14 and

[00:05:33] Speaker 01:
Whereas 24 does not have that single specific number language, which if it did, this wouldn't be a dispute.

[00:05:42] Speaker 01:
We wouldn't be here on this issue.

[00:05:44] Speaker 01:
That would be clear.

[00:05:45] Speaker 01:
And yet, the claim 24 specifically lacks that language, which would have been very easy to incorporate in 24 if the intent were to limit it to a single molecule, don't you think?

[00:06:02] Speaker 04:
Certainly the language single specific is not in claim 24 and is in claim 13.

[00:06:07] Speaker 01:
Doesn't that give rise to some suspicion at least that something different is intended?

[00:06:12] Speaker 04:
No, because the context of both the claim language and the prosecution history show that this claim was originally directed to mixtures, what became claim 24.

[00:06:23] Speaker 04:
And that claim was rejected over the prior art repeatedly.

[00:06:27] Speaker 04:
And ultimately, the word mixtures was taken out.

[00:06:32] Speaker 04:
It originally was mixtures of silicate.

[00:06:34] Speaker 03:
When I looked through the prosecution history, it was unclear why the mixtures, that word, was deleted from the claim.

[00:06:43] Speaker 04:
The mixtures word was deleted from the claim because of prior rejections over mixtures.

[00:06:49] Speaker 03:
But I didn't see anywhere in the prosecution history that explains that.

[00:06:55] Speaker 03:
I know that's what you believe, and I understand why you believe that, but I don't have anything in the prosecution history right now that necessarily forces me to think that way.

[00:07:07] Speaker 04:
Well, the examiner explained in rejecting the claim that the prior art taught mixtures.

[00:07:12] Speaker 04:
And the claim claimed mixtures.

[00:07:14] Speaker 04:
And then there was an amendment which deleted the term mixtures from the claim.

[00:07:19] Speaker 03:
Then there was also the addition of a reference to application claim 16, which really seems to drive home the idea that this claim, application claim 30, was devoted to the idea of a single and just a single isoform.

[00:07:36] Speaker 03:
But then that reference to application claim 16 got removed by the examiner and examiner's amendment.

[00:07:45] Speaker 03:
And then when you read the notice of allowance, the examiner states that the claims are direct to combinations of isoforms.

[00:07:58] Speaker 03:
you know, left me at a loss.

[00:07:59] Speaker 03:
I agree, you can find different statements by Amgen, the applicant, throughout the prosecution history that seem to make claim 30 sound like it's for just a single isoform.

[00:08:12] Speaker 03:
But then, by the time we get to the finish line,

[00:08:16] Speaker 03:
Amgen stopped talking like that, and then the examiner said what he said in the notice of allowance that these claims are all directed to combinations of isoform.

[00:08:25] Speaker 03:
So that made me wonder what exactly can we really take from any of those earlier statements if we arrive at a place that really seems to be talking

[00:08:35] Speaker 03:
about combinations of isoforms and not to just a single and only a single isoform.

[00:08:40] Speaker 04:
There are two things from the prosecution history towards the end, as that change was made from Claim 16 to the language that's issued in Claim 24 and the examiner's commentary.

[00:08:52] Speaker 04:
The change from the reference to Claim 16 to the language that was allowed was made at the same time that the Marcoosh, the closed Marcoosh language was added to the claim.

[00:09:04] Speaker 04:
And so therefore, the concept of a single number of sialic acids was incorporated specifically into the claim by the examiner at the time that the application was allowed.

[00:09:16] Speaker 04:
There is a reference in claim 27 where you can have mixtures of two or more

[00:09:25] Speaker 04:
EPO isoforms, but they are specifically isoforms of claim 1.

[00:09:30] Speaker 04:
So when the examiner allowed the application, the examiner understood that all of the claims went to single isoforms.

[00:09:40] Speaker 04:
And it's just that you could have a mixture in claim 27

[00:09:45] Speaker 04:
of two or more of those single isoforms, but you have to prepare single isoforms, or you don't ever meet the limitations of claim 27.

[00:09:54] Speaker 04:
Claim 27 says they are isoforms of claim 1, and claim 1 specifies that those are isolated isoforms.

[00:10:04] Speaker 04:
And that was the other markman error that the district court made.

[00:10:08] Speaker 04:
in not permitting the language of claim one to control, in reading out, essentially, the idea that isolated isoforms are required for claim 27.

[00:10:19] Speaker 01:
If I could just ask, I know you want to move on to claim 27, which is fine.

[00:10:24] Speaker 01:
But just one more question to follow up on Judge Chen's question.

[00:10:30] Speaker 01:
The last clause.

[00:10:32] Speaker 01:
of the examiner's notice of allowability refers to the instantly claimed combinations of isoforms.

[00:10:43] Speaker 01:
Is there an explanation for that that does not lead us to conclude that the examiner believed that the claim as revised reads on combinations of isoforms?

[00:10:57] Speaker 04:
Claim 27 is?

[00:10:58] Speaker 01:
This is claim 24.

[00:11:02] Speaker 04:
Correct, Your Honor.

[00:11:03] Speaker 01:
So if you turn to either 5614 of the appendix or page 28 of your brief at the bottom, there's that clause.

[00:11:16] Speaker 01:
And this puzzled me when I read it, where the examiner is saying, the prior act does not suggest isolation of single isoforms and does not suggest the instantly claimed combinations of isoforms that suggests

[00:11:31] Speaker 01:
to a casual reader, at least, that the examiner believed that the claim as revised read on a combination of isoforms.

[00:11:41] Speaker 04:
If you start at the bottom of 5613 of the appendix, the examiner states that there was an advantage that epo compositions with single isoforms in combination varying the number of sialic acids to control activity

[00:12:02] Speaker 04:
And he goes on at the sentence that bridges over 5613 to 14.

[00:12:07] Speaker 04:
Single isoforms are not taught by the prior art of record.

[00:12:13] Speaker 04:
That is the reason for allowance.

[00:12:15] Speaker 04:
And then he says the art does not suggest isolation of single isoforms and does not suggest the instantly claimed combinations.

[00:12:24] Speaker 01:
Right.

[00:12:24] Speaker 01:
And that's the part that is troubling me.

[00:12:26] Speaker 04:
Of single isoforms.

[00:12:28] Speaker 04:
The art doesn't suggest isolation of single isoforms or combining isoforms.

[00:12:35] Speaker 04:
Because the art's clearly taught.

[00:12:36] Speaker 04:
It was known all along.

[00:12:38] Speaker 04:
And the argument all throughout was that the art did come up with mixtures of isoforms.

[00:12:43] Speaker 01:
So what is your interpretation of that last clause in the examiner's assessment?

[00:12:52] Speaker 04:
So for example, claim 27 specifically claims

[00:12:58] Speaker 04:
combinations of single isoforms.

[00:13:01] Speaker 04:
So the instantly claimed combinations references, for example, claim 27.

[00:13:07] Speaker 01:
So you think this is a reference to claims other than just claim 24 or claim 30 that became claim 24?

[00:13:14] Speaker 04:
Correct.

[00:13:14] Speaker 01:
OK.

[00:13:15] Speaker 04:
Correct, Your Honor.

[00:13:17] Speaker 04:
With respect to claim 27, the requirement of isolated isoforms of claim 1 was read out by the district court in the Markman construction.

[00:13:27] Speaker 04:
And the second sentence of that Markman order that was given to the jury essentially specifically said you could prepare mixtures of isoforms without ever having an isolated isoform.

[00:13:41] Speaker 04:
The jury was never even shown Claim 1 at trial.

[00:13:43] Speaker 04:
There was no evidence put in at trial that the limitations of Claim 1 were met, because the jury was sent on the wrong mission with regard to

[00:13:54] Speaker 04:
whether mixtures of isoforms, repairing mixtures of isoforms without ever having a single isoform could be covered by the claims.

[00:14:05] Speaker 01:
I mean, I would assume that you would be arguing, pointing the jury to claim one.

[00:14:11] Speaker 04:
Were you not?

[00:14:11] Speaker 04:
The jury was told that mixtures of isoforms could be infringing.

[00:14:17] Speaker 01:
So you regard that argument as being foreclosed by the claim construction.

[00:14:23] Speaker 04:
So it was the plaintiff's burden to prove that the limitations of claim one were met.

[00:14:28] Speaker 04:
They didn't do that.

[00:14:30] Speaker 04:
They didn't go through claim one and show how claim one was met.

[00:14:32] Speaker 04:
They just simply said,

[00:14:34] Speaker 04:
Jaspier prepares mixtures of isoforms and went through the specific activity limitations that were in the claim without ever pointing that out.

[00:14:43] Speaker 04:
And the jury was specifically instructed that you could prepare mixtures of isoforms and meet claim 27.

[00:14:50] Speaker 04:
With regard to the safe harbor, the district court

[00:14:54] Speaker 04:
improperly focus the jury on the reasons for manufacture of the bachelors.

[00:14:59] Speaker 00:
I understand that you want to address a different one of the seven issues you appealed, and that is, in fact, undoubtedly the downside of raising seven separate appealable issues in briefs.

[00:15:08] Speaker 00:
But your time has definitely expired, and almost all your rebuttal time has expired.

[00:15:12] Speaker 00:
So if you continue, it's at the expense of any rebuttal time.

[00:15:15] Speaker 04:
Your Honor, then I will see the podium.

[00:15:32] Speaker 02:
May it please the court, John Labe on behalf of Plaintiffs, Cross Appellants, Amgen, Inc., and Amgen Manufacturing.

[00:15:39] Speaker 02:
Claim 24 is not limited to isolating a single isoform.

[00:15:45] Speaker 02:
Dr. Strickland discovered that EPO produced in cells is made up of isoforms of EPO with different numbers of sialic acids per molecule and different charges, and therefore different biological activities.

[00:16:01] Speaker 02:
This discovery allowed Dr. Strickland.

[00:16:03] Speaker 03:
We're trying to parse the language in Claim 24.

[00:16:06] Speaker 03:
So we understand Dr. Strickland invented a lot of things.

[00:16:10] Speaker 03:
But the exercise is trying to get into this claim language.

[00:16:13] Speaker 02:
Sure, Your Honor.

[00:16:14] Speaker 02:
So to focus on Claim 24, the key issue here, of course, is whether Claim 24 is limited to preparing a single isoform.

[00:16:22] Speaker 02:
And it's not.

[00:16:23] Speaker 02:
Nothing in the language of claim 24 limits the claim to a method of isolating a single isoform as Judge Bryson highlighted compare the claim to claim 13 which is directed to a composition of molecules with a single specific number of sialic acids per molecule also contrasts with claim 23 which is a method claim it's a very similar method claim to claim 24 and

[00:16:48] Speaker 02:
But that one requires eluting a single isoform of EPO.

[00:16:53] Speaker 02:
The Marcus group in claim 24 refers to a number of sialic acids per molecule in an isoform, as the district court found.

[00:17:03] Speaker 02:
It does not mean that every molecule prepared according to the method of the claim must have an identical number of sialic acids per molecule.

[00:17:12] Speaker 01:
Well, what do you say as to the superfluousness

[00:17:17] Speaker 01:
of the language of the claim, if in fact it reads the way you think it does, since all EPO molecules have a single number of sialic acids somewhere between 1 and 14.

[00:17:29] Speaker 02:
Your Honor, we disagree.

[00:17:30] Speaker 02:
An EPO molecule could have zero sialic acids per molecule.

[00:17:34] Speaker 02:
It's also possible that an analog of EPO, the claim defines EPO as including EPO analogs, which could have more than 14 sialic acids.

[00:17:42] Speaker 02:
We believe the examiner included this language 1 to 14 in the final claim simply to refer to those isoforms that are described in the specification and that the applicant was intending to cover by the claim.

[00:17:56] Speaker 02:
It's just being used as a shorthand to refer to isoforms, but it is limited to 1 to 14.

[00:18:01] Speaker 03:
I guess I was looking at the 298 spec at column 6, lines, I don't know, 38-39.

[00:18:10] Speaker 03:
And it says, in another embodiment, said numbers greater than 14, advantageously 16-23.

[00:18:18] Speaker 03:
And so to me, that just popped out of nowhere.

[00:18:24] Speaker 03:
And I was trying to understand, what is the specification communicating here about the possibility of having as many as 23 sialic acids?

[00:18:33] Speaker 02:
That's correct, Your Honor.

[00:18:35] Speaker 02:
In referring to other portions of the specification, it says that EPO, as used here, can refer to analogs of EPO.

[00:18:42] Speaker 02:
It's possible certain analogs of EPO could have more than 14 sialic acids.

[00:18:47] Speaker 02:
What I would point, Your Honor, to in column 6 is beginning at line 46.

[00:18:53] Speaker 02:
where it says that in another embodiment, the compositions comprise mixtures of isoforms having a predetermined number of sialic acids per epo molecule.

[00:19:04] Speaker 02:
For example, less than 12 or greater than 8, as in, for example, a mixture of 9, 10, and 11.

[00:19:10] Speaker 02:
And I highlight that language because it uses the phrase, a predetermined number of sialic acids per.

[00:19:17] Speaker 00:
It also uses the word mixture.

[00:19:18] Speaker 00:
My problem, and I'm just going to lay it out for you, is that you're representing the patentee on a claim that I don't think is very clear as to which way it should go.

[00:19:29] Speaker 00:
And I don't know, and that's a question of law that I have to decide.

[00:19:33] Speaker 00:
But throughout the prosecution, you made a number of changes.

[00:19:36] Speaker 00:
I can't necessarily say I understand the reason for all the changes, but the changes you made, you deleted the word mixture, you used to refer back to 16, which is now 13, which is undoubtedly directed to a single specific species or a single specific number of Xaelic.

[00:19:52] Speaker 00:
So it used to be that this is a method of preparing the things that are now identified in claim 13.

[00:19:57] Speaker 00:
And after a phone call with the examiner, the results of which I, of course, have no idea.

[00:20:00] Speaker 00:
No one memorialized it.

[00:20:02] Speaker 00:
That was eliminated, but I don't know that it was to make it broader necessarily.

[00:20:06] Speaker 00:
So you took out greater than.

[00:20:07] Speaker 00:
You took out mixture.

[00:20:08] Speaker 00:
Both of those would suggest to me you're moving away from the example in column six, which was a mixture and towards a group of epiomolecules, all of which would have exactly the same number of sialic acids attached.

[00:20:21] Speaker 00:
And then you add to that the fact that this

[00:20:23] Speaker 00:
You said in your prosecution history that Claim 24 is a method of making the molecules in Claim 13.

[00:20:29] Speaker 00:
Now granted, you took it out, but I have no idea why you took it out.

[00:20:32] Speaker 00:
So what do I do with all of that?

[00:20:35] Speaker 00:
A lot of your prosecution history points in the direction of we're moving this claim, Claim 24, away from a mixture claim and towards the same single isolated isoform that we have in the other claims.

[00:20:48] Speaker 00:
We're just using slightly different language to claim it.

[00:20:50] Speaker 02:
Your Honor, there were a number of amendments made during prosecution, but Amgen never said that it was amending the claims to limit it to isolating a single ISO form.

[00:21:00] Speaker 00:
That doesn't mean that a skilled artisan wouldn't read it.

[00:21:04] Speaker 00:
I'm not using the clear and unmistakable standard because I'm not using this for disclaimer purposes.

[00:21:09] Speaker 00:
I'm using it to try to understand what the claim means.

[00:21:11] Speaker 00:
which we're supposed to do as part of claim construction.

[00:21:14] Speaker 00:
So a lot of these amendments, though, moved the claim away from a claim that clearly covered multiple isoforms.

[00:21:24] Speaker 02:
The examiner's rejections were based on prior art references that were focused on purifying EPO by separating EPO molecules from non-EPO, by removing non-EPO contaminants.

[00:21:37] Speaker 02:
And that is what the examiner was concerned about.

[00:21:40] Speaker 02:
Now, some of the amendments are a little bit unclear, but that is what the amendments were intended to focus on.

[00:21:45] Speaker 03:
Well, you don't need to delete the word mixtures to overcome that kind of thing.

[00:21:49] Speaker 03:
You don't, but at the same time... So then why was that word deleted?

[00:21:53] Speaker 02:
It's not clear.

[00:21:54] Speaker 03:
As this court said of Phillips... Amgen doesn't know?

[00:21:57] Speaker 02:
We don't know.

[00:21:58] Speaker 03:
You represent the patent owner.

[00:21:59] Speaker 03:
You don't know why the word mixtures was removed.

[00:22:01] Speaker 02:
At the same time, the mixtures was... The answer to your question, Aaron, is we do not know.

[00:22:05] Speaker 02:
It's not indicated in the file history why mixtures was removed.

[00:22:08] Speaker 02:
At the same time mixtures was removed, however, the step of selective elution was added.

[00:22:13] Speaker 02:
The step of selectively eluding the isoforms was distinguished it from the prior art that the examiner was citing.

[00:22:19] Speaker 00:
Exactly.

[00:22:19] Speaker 00:
And I understood why that one was added, because that was the portion that distinguished it from the prior art based on the rejection.

[00:22:24] Speaker 00:
Exactly right.

[00:22:25] Speaker 00:
We can't figure out why the word mixture was added.

[00:22:27] Speaker 00:
And I guess in a scenario like this, with all due respect, when you have the patentee winnowing his claim down and then leaving it in what feels like a confusing state,

[00:22:37] Speaker 00:
It seems like, hmm, let's see, how should I construe that claim then in favor of the patentee who made a lot of amendments that took it away from the position he's arguing it now should extend to?

[00:22:48] Speaker 00:
Or should I give that all back to him, even though he took those things away without any clear reason for me in the prosecution history?

[00:22:54] Speaker 02:
I would just come back to the fact that by taking out the reference to mixtures,

[00:22:59] Speaker 02:
It didn't limit it to isolating a single isoform.

[00:23:01] Speaker 02:
It only meant that it encompassed both preparing a mixture and potentially preparing a single isoform.

[00:23:06] Speaker 02:
You could choose to use the method to elude a single isoform, or you could use the method to prepare a mixture of isoforms.

[00:23:13] Speaker 01:
Are you saying that by taking out mixture, you avoided the implication that single isoforms were excluded from the scope of the claim?

[00:23:24] Speaker 02:
that single isoforms were excluded?

[00:23:26] Speaker 01:
I mean, I didn't understand your last argument, but it sounded to me like you were saying, well, we took mixture out so that somebody would understand that both mixtures and single isoforms would be.

[00:23:37] Speaker 02:
I simply don't know why they took out mixtures from the language of the claim, except that there was no indication that it was to overcome the prior art.

[00:23:44] Speaker 02:
The prior art that was being cited was about purifying EPO by removing non-EPO contaminants, because Dr. Strickland's inventions

[00:23:54] Speaker 00:
But respectfully, it doesn't matter whether they were taking it out to overcome the particular piece of prior art that was the subject of the rejection.

[00:24:02] Speaker 00:
What matters is would a skilled artisan understand that the patentee is trying to signal something?

[00:24:06] Speaker 00:
about the scope of his claim by taking that word out.

[00:24:09] Speaker 00:
Because you can make an amendment for any reason you want.

[00:24:12] Speaker 00:
You can amend your claims even not in response to an examiner's rejection, right?

[00:24:16] Speaker 00:
And we're not going to say that amendment has no meaning, despite the fact that it wasn't made in response to an examiner's rejection.

[00:24:23] Speaker 00:
So I guess, what do we do with all that?

[00:24:27] Speaker 02:
Well, Your Honor, I think on balance, because they were not addressing an amendment,

[00:24:39] Speaker 02:
Yes, I would also like to highlight, in the prosecution history, when these amendments were made, if I could point to appendix 5557 through 58, the applicant, Amson, consistently referred to the method claim, it was prosecution claim 30, as referring to a preparation of isoforms, plural, and also specifically

[00:25:00] Speaker 02:
pointed to exhibit 5 as an example of practicing claim 30.

[00:25:06] Speaker 02:
Exhibit 5 is clearly directed to a method of preparing a mixture of isoforms using ion exchange chromatography to prepare a mixture of isoforms.

[00:25:15] Speaker 02:
And so I see you're looking at it.

[00:25:17] Speaker 03:
Exhibit 5 is in the specification?

[00:25:20] Speaker 02:
Exhibit 5 in the specification, correct.

[00:25:22] Speaker 02:
And this is referenced, Your Honor, at appendix 55, 57 to 58.

[00:25:30] Speaker 02:
Oh, I said exhibit five.

[00:25:32] Speaker 02:
I should have said example five, Your Honor.

[00:25:34] Speaker 02:
Sorry.

[00:25:35] Speaker 02:
Example five in the specification.

[00:25:38] Speaker 02:
There are two places in that office action response.

[00:25:41] Speaker 02:
It's at appendix 55, 57, to 58, as well as at 55, 62, to 63, that Amgen referred to prosecution claim 30, now claim 24, as a method of preparing ISA forms, plural, and specifically referred to

[00:26:00] Speaker 02:
Example 5.

[00:26:01] Speaker 00:
Can I ask you where it says that, the method of preparing isoforms, and where exactly?

[00:26:07] Speaker 00:
I'm on 5557 and 5558.

[00:26:09] Speaker 00:
If you don't have your appendix, take a minute and get it.

[00:26:16] Speaker 02:
So at 5557 to 58, it's at the top of page 5558, the paragraph there.

[00:26:26] Speaker 02:
The steps comprise applying EPO-containing material to an ion exchange column, claim 30.

[00:26:33] Speaker 02:
and selectively eluding EPO molecules having a predetermined number of sialic acids from the column.

[00:26:37] Speaker 02:
The method is fully described in examples four and five of the subject application.

[00:26:42] Speaker 00:
Yes, that doesn't say what you said it did.

[00:26:44] Speaker 00:
You stood there in front of us and insisted that it says isoforms plural, isoforms plural.

[00:26:48] Speaker 02:
It does say that elsewhere, Your Honor.

[00:26:49] Speaker 02:
Example five, I'm pointing to example five.

[00:26:52] Speaker 00:
No, you told me that on page 5557 to 5558, you read the little note that the guy ran up to you.

[00:26:57] Speaker 00:
You said it said isoforms.

[00:26:59] Speaker 00:
And so I'm looking, I don't see the word isoforms anywhere in there.

[00:27:02] Speaker 02:
This is the example five reference.

[00:27:03] Speaker 02:
It also refers to isoforms, Your Honor, several pages later.

[00:27:06] Speaker 02:
It refers to isoforms at APPX 5562 to 63.

[00:27:15] Speaker 00:
I'm sorry, where?

[00:27:21] Speaker 02:
So if I could just clarify, Your Honor, what I was just highlighting there was that it refers to example five.

[00:27:26] Speaker 02:
Example five is a method of preparing a mixture of isoforms.

[00:27:29] Speaker 02:
Okay, later at pages 55, 62 to 63, and this is also cited in our brief, it refers to the two-step processes of the amended claims are not

[00:27:56] Speaker 02:
Selectively eluding the desired isoforms.

[00:27:59] Speaker 02:
It's at the top of page 11 is appendix 5563 your honor Yes, your These two citations your honor are both from the same

[00:28:15] Speaker 02:
Office action response the applicants have amended claim 30 to recite a two-step process of applying material containing epo to an ion exchange column and Selectively eluding the desired isoforms plural.

[00:28:28] Speaker 02:
That's where it has the plural reference I actually think the reference to exhibit to example five is also compelling because example five is directed to a method of preparing a mixture of isoforms so

[00:28:43] Speaker 00:
OK, so maybe what I'll grant you is that you're all over the friggin' place in this prosecution.

[00:28:50] Speaker 00:
You have created a prosecution history that leaves a skilled artisan with a complete and utter lack of clarity regarding the scope of your claim.

[00:28:57] Speaker 00:
To whom should that detriment enter?

[00:28:59] Speaker 02:
Well, Your Honor, I would refer to this court's decision in Phillips that said that when the prosecution history is ambiguous, it doesn't provide much

[00:29:07] Speaker 02:
significance in interpreting the claims, and I would focus on the language.

[00:29:10] Speaker 00:
But the claim language also doesn't provide much significance in interpreting the claims in terms of this particular distinction.

[00:29:16] Speaker 00:
So suppose the court is truly confronted with a scenario where either of two equal possible definitions could apply to a claim.

[00:29:26] Speaker 00:
Which one should we choose?

[00:29:27] Speaker 00:
I think Paul Michelle in a case long ago, the name of which I don't remember, said the one that doesn't favor the patentee.

[00:29:35] Speaker 02:
I think here, Your Honor, the claim should be interpreted in the sense it doesn't have any language like other claims.

[00:29:43] Speaker 02:
It limits it to isolating or preparing a single isoform.

[00:29:47] Speaker 00:
It does.

[00:29:47] Speaker 00:
It says a predetermined number.

[00:29:49] Speaker 00:
Now, you want me to read that to apply only to a molecule, and then there could be lots of molecules that have their own predetermined numbers.

[00:29:57] Speaker 00:
But that claim could be read either way, as far as I'm concerned.

[00:29:59] Speaker 00:
Either way.

[00:30:00] Speaker 00:
I mean, I could flip a coin and read it either way.

[00:30:04] Speaker 02:
But Your Honor, with respect to the predetermined language, I would refer to the language in column six of the specification where it says that mixtures.

[00:30:10] Speaker 00:
Which is a mixture, right?

[00:30:11] Speaker 00:
It says mixtures.

[00:30:11] Speaker 00:
And you took that word out.

[00:30:13] Speaker 00:
You took the word mixture out of the claim during prosecution to purposefully make it confusing for the world.

[00:30:18] Speaker 02:
But it uses the term a predetermined number to refer to mixtures.

[00:30:23] Speaker 02:
And so the claim.

[00:30:24] Speaker 00:
So now you'd like me to read mixtures back in, even though you express it took it out during prosecution?

[00:30:29] Speaker 02:
No, Your Honor.

[00:30:29] Speaker 02:
Claim 24 could cover a single or it could cover a mixture of isoforms.

[00:30:34] Speaker 02:
The examiner was concerned with the method steps, and in particular the method of selectively eluding the isoforms.

[00:30:40] Speaker 00:
So now are you back to the argument that Judge Bryson questioned you on long ago, where you took the word mixture out in order to make it clear that Claim 24 applies to both mixtures and single isoforms?

[00:30:51] Speaker 02:
Again, Your Honor, I don't think it's clear why that language was taken out, except that I think the implication of it is that, yes.

[00:30:56] Speaker 00:
You're right.

[00:30:57] Speaker 00:
It's not clear.

[00:30:58] Speaker 00:
And so that's the problem.

[00:30:59] Speaker 00:
It leaves the world without clarity from the prosecution history, because for particular office actions or particular sections, I could, in the absence of the rest of the prosecution, absolutely read them to, quite frankly, favor limiting this

[00:31:15] Speaker 00:
to single isoforms, but then you add some complexity to that by pointing out other places where in arguments you added the word isoforms with a plural.

[00:31:26] Speaker 02:
I believe, Your Honor, that throughout the file history, Amgen consistently referred to the claim as a method of preparing isoforms plural.

[00:31:32] Speaker 02:
I pointed to that one office action.

[00:31:34] Speaker 02:
I apologize that there was some confusion about what I was pointing to there.

[00:31:38] Speaker 00:
You can't say that Amgen's invention is preparing isoforms plural, because more than half of your claims are directed to single isoforms.

[00:31:45] Speaker 00:
So it's not isoforms plural.

[00:31:47] Speaker 02:
Well, many of the claims are directed to isolating a single isoform, but not all.

[00:31:51] Speaker 02:
And the specification, throughout the specification, particularly the language at the bottom of column 6, makes it clear that the claims are directed to preparing both isolated as well as mixtures of isoforms.

[00:32:03] Speaker 00:
Is it your view that claim 1 would be limited to a single isoform?

[00:32:09] Speaker 02:
Yes, your honor judge the district court did construe claim one the isolated language and claim one is limiting claim one to preparing one and only one isoform That language doesn't appear in claim 24 the specification consistently refers to

[00:32:27] Speaker 02:
the invention as one of being able to select isoforms, not just one isoform, but Dr. Strickland's invention was that he could select specific isoforms to include in the composition to give the composition a specific biological activity.

[00:32:42] Speaker 02:
Prior to Dr. Strickland's inventions, it wasn't possible to separate

[00:32:47] Speaker 02:
of molecules of EPO to separate isoforms of EPO based on their charge.

[00:32:52] Speaker 02:
He made the correlation between content of sialic acid and isoforms in order to enable this method of selecting isoforms.

[00:33:01] Speaker 02:
But it's not just selecting a single isoform.

[00:33:03] Speaker 02:
It's potentially selecting a mixture of isoforms with a predetermined in vivo specific activity.

[00:33:09] Speaker 00:
Okay.

[00:33:09] Speaker 00:
You are well beyond.

[00:33:11] Speaker 03:
Can he get the claim 27?

[00:33:13] Speaker 03:
Sure.

[00:33:15] Speaker 03:
the failure to

[00:33:24] Speaker 03:
what to take away from the meaning of the word isolated in claim one and how that impacts, if at all, the preparation of the mixture as recited in claim 27.

[00:33:34] Speaker 02:
I can address both of those issues, Your Honor.

[00:33:35] Speaker 02:
And with respect to the first issue, I might just point you to page 28 of our brief where we cited the evidence that proved infringement of the remaining elements of claim one.

[00:33:45] Speaker 02:
It wasn't the focus of the trial, admittedly, but there was evidence before the jury with respect to the other elements of Claim 1.

[00:33:52] Speaker 02:
Haas-Pierre's point here really is about isolated, and whether isolated is part of Claim 27.

[00:33:58] Speaker 02:
Claim 27 is a method claim that the district court construed as an independent method claim, which Haas-Pierre doesn't dispute on appeal.

[00:34:05] Speaker 02:
The reference to EPO ISO forms of Claim 1

[00:34:09] Speaker 02:
is simply to describe the types of isoforms that can be included in the mixture prepared according to claim 27.

[00:34:18] Speaker 02:
Because it's a mixture, it doesn't mean that the isoforms need to be separately prepared.

[00:34:23] Speaker 02:
The district court simply said that the isoforms don't need to be separately prepared before preparing the mixture.

[00:34:28] Speaker 02:
At the bottom of column 6, the specification describes multiple ways of preparing a mixture.

[00:34:33] Speaker 02:
By first isolating the isoforms or by preparing the mixture using ion exchange chromatography,

[00:34:39] Speaker 02:
to prepare a mixture of isoforms with a certain number of sialic acids.

[00:34:43] Speaker 00:
But this says the mixture of the claim one things.

[00:34:46] Speaker 00:
So the claim one things are each individual, each have individual numbers of sialic acids, right?

[00:34:56] Speaker 02:
That is required by claim 27 that each have individual numbers of sialic acids.

[00:35:01] Speaker 02:
It has to be those isoforms.

[00:35:03] Speaker 02:
It has to be isoforms with between 1 and 14 sialic acids per molecule, for example.

[00:35:08] Speaker 02:
It has to be a mixture of those isoforms, not a mixture.

[00:35:11] Speaker 00:
It has to be a mixture of two different isoforms, each of which are starting out with a different number of sialic acids, doesn't it?

[00:35:20] Speaker 02:
I think I agree with that, Your Honor, except that they don't have to be separately prepared, because Claim 27 is a method claim, and it does not include a method step of separately preparing the isoforms, nor does Claim 1.

[00:35:31] Speaker 00:
If I said I was going to hand you a mixture of salt and pepper...

[00:35:36] Speaker 00:
Wouldn't you expect that to be salt and then pepper, and then I mixed them together and gave them to you?

[00:35:41] Speaker 02:
Yes, but Your Honor, it's a method claim.

[00:35:43] Speaker 02:
So if it were a method of preparing a mixture of salt and pepper, it wouldn't necessarily mean that you need to have salt and pepper purified in advance.

[00:35:51] Speaker 02:
You could prepare the mixture directly.

[00:35:53] Speaker 02:
If there were some method that skilled artists would know that you could prepare a mixture of salt and pepper,

[00:35:58] Speaker 02:
without first separating them, and that's what we have here, is that using ion exchange chromatography, you can prepare a mixture of isoforms without first separating them, and that's described between columns six and seven of the specification.

[00:36:10] Speaker 00:
But the Claim 27 doesn't require the method by which they're going to be made.

[00:36:13] Speaker 00:
It doesn't limit it to the

[00:36:15] Speaker 00:
I am chromatography.

[00:36:16] Speaker 02:
Well, that's correct, Your Honor.

[00:36:17] Speaker 02:
It doesn't require a particular method to be used.

[00:36:20] Speaker 02:
And so by that token, it doesn't require that they be separately prepared and then mixed.

[00:36:25] Speaker 02:
They could be, if there were some way, which there is, of preparing a mixture, it only requires the preparation of a mixture with a predetermined in vivo-specific activity, which was enabled by the invention.

[00:36:35] Speaker 02:
It only requires that that mixture be prepared.

[00:36:38] Speaker 02:
It doesn't have a method step of separating the isoforms, nor does claim one.

[00:36:42] Speaker 02:
Claim one doesn't have any method steps.

[00:36:45] Speaker 01:
Well, I was just going to ask about I think you referred to the bottom of column six, but I Didn't get your precise reference, but there is a sentence at the bottom of column six line 61 through about Line 63 and I wanted to to see if that's consistent with what you're saying now You you say well, let me read the sentence in order to produce mixtures of repo

[00:37:12] Speaker 01:
isoforms.

[00:37:13] Speaker 01:
This invention also provides methods of isolating selected EPO isoforms simultaneously.

[00:37:21] Speaker 01:
Is that what you're saying is that you can have isolation

[00:37:25] Speaker 01:
of more than one at a time?

[00:37:27] Speaker 02:
That's part of the language.

[00:37:28] Speaker 02:
It's really that entire paragraph that I would point to taken together.

[00:37:32] Speaker 02:
So it's that sentence followed by the techniques that are then described.

[00:37:36] Speaker 02:
It says the methods include isolation of individual isoforms or preparation of mixtures of isoforms continuing to the next column by techniques such as ion exchange chromatography.

[00:37:49] Speaker 01:
The second part of that paragraph seems to be not necessarily helpful to you.

[00:37:54] Speaker 01:
What I was focusing on was the use of the term isolating simultaneously, which suggests that this doesn't require that the one isoform be at any point in the discrete portion of the composition.

[00:38:11] Speaker 02:
We do understand it that way, Your Honor.

[00:38:13] Speaker 02:
And I only cite the rest of the paragraph as described in multiple ways.

[00:38:16] Speaker 02:
You could isolate and mix, or you could just prepare a mixture.

[00:38:20] Speaker 02:
But I agree, Your Honor, that the first sentence suggests that isolation could occur

[00:38:24] Speaker 01:
It's an unusual use of the term isolation, but the point of Claim 27 is to prepare a mixture where

[00:38:38] Speaker 02:
Those isoforms are separated from other isoforms, which enables you to prepare the mixture with a predetermined in vivo specific activity.

[00:38:46] Speaker 02:
You have to prepare the specific mixture to have the predetermined in vivo specific activity, which is what Dr. Strickland discovered and allowed him to prepare these to invent these methods.

[00:38:57] Speaker 00:
All right.

[00:38:58] Speaker 00:
I think that we need to bring this to a close.

[00:39:00] Speaker 00:
Thank you, Your Honor.

[00:39:00] Speaker 00:
Thank you.

[00:39:02] Speaker 00:
Mr. Meloro, I'm going to give you all five of your rebuttal minutes back because he

[00:39:07] Speaker 00:
went on and on at the response to questions, to be clear.

[00:39:10] Speaker 00:
But yes, he did eat up a lot of time.

[00:39:12] Speaker 00:
So we're going to give you all your rebuttal time back.

[00:39:15] Speaker 00:
But I do caution you that rebuttal is to respond to arguments that were addressed by the other side.

[00:39:21] Speaker 00:
So with all due respect, you are now limited to Claim 24 and 27.

[00:39:24] Speaker 00:
And since he never reached any of the other issues you appealed, those are off the table.

[00:39:29] Speaker 04:
Yes, Your Honor.

[00:39:30] Speaker 04:
Thank you very much.

[00:39:31] Speaker 00:
Unless one of my colleagues really wants to know the answer to one of them, in which case I'll defer to them.

[00:39:37] Speaker 04:
I'd like to start with the prosecution history and pick up where counsel left off, which was the amendment from October of 1993 and the elimination of the mixture term.

[00:39:52] Speaker 04:
And there were some references in that amendment to example five and to isoforms, which counsel pointed out.

[00:40:01] Speaker 04:
But what happened then was the claim was rejected again.

[00:40:05] Speaker 04:
And so the claim was then even more specifically directed in the next amendment to single isoforms, and that was by putting in the reference specifically to claim 16.

[00:40:18] Speaker 04:
So what we had at that point was any ambiguity about mixtures was gone.

[00:40:25] Speaker 04:
once the next amendment came in, after the next rejection came in.

[00:40:29] Speaker 04:
And we had a claim.

[00:40:30] Speaker 04:
And by the way, it was counsel's law firm that was prosecuting the application.

[00:40:35] Speaker 04:
We had a claim.

[00:40:36] Speaker 04:
that was specifically directed to a single isoform by the reference to according to claim 16.

[00:40:42] Speaker 04:
And then that reference got removed?

[00:40:45] Speaker 04:
And then that reference got removed with the examiner's amendment, and it was essentially swapped out for the closed Marcouche language, which has the same effect.

[00:40:54] Speaker 03:
But that's your interpretation of that.

[00:40:57] Speaker 03:
It's not so clear that

[00:40:59] Speaker 03:
It's this kind of one for one swap that you would make it out to be.

[00:41:05] Speaker 04:
We would submit that when you look at the claim language itself, and keeping in mind the admonitions about closed Marcouche language, and that if you want to say mixtures, you have to specify it in the claim language.

[00:41:20] Speaker 04:
There was no reference to putting mixtures in in the closed Marcoosh language.

[00:41:26] Speaker 04:
And in fact, the references which Judge Bryson pointed out in the examiner's reasons for allowance talked specifically about the single isoforms and the instantly claimed combinations.

[00:41:41] Speaker 04:
Not mixtures, combinations.

[00:41:44] Speaker 04:
Combinations is a different concept

[00:41:46] Speaker 04:
from mixtures.

[00:41:47] Speaker 04:
Claim 27, for example, does claim combinations of single isolated isoforms.

[00:41:55] Speaker 04:
And that reference, if there was to be a sea change.

[00:42:00] Speaker 03:
Well, I don't know.

[00:42:01] Speaker 03:
It says preparing a mixture.

[00:42:04] Speaker 03:
It doesn't say preparing a combination of isoforms.

[00:42:08] Speaker 04:
That's correct, Your Honor.

[00:42:09] Speaker 03:
So you're right that the

[00:42:11] Speaker 03:
examiner said combinations of isoforms, but I don't know if that means you can make a distinction between combinations and mixtures.

[00:42:20] Speaker 04:
Well, if there were to be a sea change at that moment, away from the CLAIM-16 language,

[00:42:27] Speaker 04:
which was, as everyone agrees, directed to a single isoform.

[00:42:31] Speaker 04:
If claim 30, which over all these years had been narrowed down to by May 3rd of 1994, be seriously and specifically claiming a single isoform, and then through examiner's amendment was going to be now broadened out to what had been rejected over all those years,

[00:42:53] Speaker 04:
One would have expected to have seen some clear, I've changed my mind.

[00:42:59] Speaker 04:
In fact, you are entitled to mixtures, and I'm reopening the claim to something that's not mixtures.

[00:43:06] Speaker 04:
Instead, what the examiner did was required this closed Marcouche language.

[00:43:12] Speaker 04:
Closed Marcouche language, which, if it were to be directed to mixtures, would have been required to either use the word mixture,

[00:43:22] Speaker 04:
or use some other phraseology, like one or more of, to make clear to the public, when they looked at that Marcouche language, that it was intended to cover more than one of the number of sialic acids.

[00:43:36] Speaker 04:
Having not done that, we're not just left with a record that's muddled and who should bear the burden, but we're left with case law that says it is absolutely incumbent on the patentee

[00:43:48] Speaker 04:
when they want to claim mixtures in a closed Marcoosh claim to put mixtures into that claim.

[00:43:56] Speaker 04:
Now, with respect to claim 27, claim 27 is directed to ISO forms of claim 1.

[00:44:05] Speaker 04:
ISO forms of claim 1 is a requirement for proving infringement of claim 27.

[00:44:13] Speaker 04:
Do not contest on this appeal the independent nature of Claim 27.

[00:44:19] Speaker 04:
But that does not mean that limitations of claims, independent claims, are optional in terms of proofs.

[00:44:26] Speaker 04:
And the isolated ISO forms of Claim 1 are what's required for proof on Claim 27.

[00:44:33] Speaker 04:
If they wanted to claim just mixing two or more isoforms, they had every opportunity to do that.

[00:44:39] Speaker 04:
Instead, they chose to claim two or more isolated isoforms.

[00:44:45] Speaker 00:
OK.

[00:44:45] Speaker 00:
Thank you, Mr. Meloro.

[00:44:46] Speaker 00:
I thank both counsel.

[00:44:48] Speaker 00:
The case is taken under submission.