[00:00:02] Speaker 00:
Morning, counsel.

[00:00:03] Speaker 00:
Ready to proceed?

[00:00:10] Speaker 03:
Yes, sir.

[00:00:11] Speaker 03:
Let's go.

[00:00:11] Speaker 03:
May I please support a point of order first?

[00:00:14] Speaker 03:
Should we switch tables?

[00:00:16] Speaker 03:
Yes, you should.

[00:00:19] Speaker 03:
This appeal, 101 appeal, was originally conceived by us to be perhaps seminal case to determine whether or not method of treatment claims in the pharmaceutical area

[00:00:31] Speaker 03:
were patentable under Maya.

[00:00:33] Speaker 03:
Since then, during the briefing, the Vanda decision came down, which decided the issue presented in this case definitively.

[00:00:40] Speaker 03:
The claims in Vanda are indistinguishable from those here.

[00:00:44] Speaker 03:
And frankly, Your Honor, unless you have questions, I know you have a very busy calendar today, and I would cede the floor to my opponent to explain Vanda and then reserve my time for rebuttal.

[00:00:57] Speaker 00:
That's fine.

[00:00:58] Speaker 03:
Thank you.

[00:00:58] Speaker 00:
Thank you for your candor.

[00:01:06] Speaker 02:
Good morning, Judge Wallach, and may it please the court.

[00:01:08] Speaker 02:
I guess I'll go straight to Mayo.

[00:01:10] Speaker 02:
And first of all, Vanda did not hold that any administering step will make the claims patent eligible.

[00:01:17] Speaker 02:
And this is our first opportunity to respond to Endo's take on Vanda.

[00:01:20] Speaker 02:
Endo's reply brief talks a lot about the administrative step.

[00:01:25] Speaker 02:
Supreme Court tells us in Benson, Mayo, and Alice that adding apply it or compute it to an ineligible claim won't save it under 101.

[00:01:32] Speaker 02:
Vanda didn't announce a different rule for administrative claims.

[00:01:35] Speaker 02:
Vanda turned on the specific administering step at issue in that case.

[00:01:39] Speaker 02:
And it's meaningfully different from Vanda's in two related ways.

[00:01:43] Speaker 02:
The last step of the claims in Vanda, the step

[00:01:55] Speaker 02:
The last, the administering step of Vanda is like a flow chart.

[00:01:58] Speaker 02:
It recites specific doses of a drug, and those specific doses are directly tied to the result of the diagnostic step, which is the previous step.

[00:02:06] Speaker 02:
The second step of Vanda claims a genotyping assay to check for specific mutations in the patient's DNA.

[00:02:11] Speaker 02:
And the final step says that if the patient has those mutations, give the patient 12 milligrams or less of iloperidone.

[00:02:17] Speaker 02:
And if not, give the patient 12 milligrams to 24 milligrams of iloperidone.

[00:02:21] Speaker 02:
End-dose claims don't recite specific doses and they don't have the direct tie to the diagnostic step that comes before.

[00:02:27] Speaker 02:
They just say, check the patient's kidneys and then reduce the dose if you need to.

[00:02:31] Speaker 00:
All end-dose claims... Doesn't it also, it measures, it has four different categories of the creatine clearance rate, right?

[00:02:40] Speaker 02:
Yes.

[00:02:41] Speaker 02:
Okay.

[00:02:42] Speaker 02:
Yes, and so two points about that.

[00:02:44] Speaker 02:
There is no tie between those categories and the last step.

[00:02:47] Speaker 02:
It doesn't say,

[00:02:49] Speaker 02:
So as a van, it tells you exactly what to do, depending on the result of the test.

[00:02:52] Speaker 02:
The last step in end-dose cleanse doesn't tell you what to do if it's in this category, that category, or a different category.

[00:02:56] Speaker 02:
It just says, check the patient's kidneys, put their creatinine clearance rate in one of these four boxes, and then just reduce the dose if you need to.

[00:03:06] Speaker 02:
And that's it.

[00:03:07] Speaker 02:
There's no direct tie.

[00:03:08] Speaker 02:
There's no specific dose, just that.

[00:03:11] Speaker 00:
What about the wearing clause language?

[00:03:13] Speaker 00:
How does that inform the dosage?

[00:03:17] Speaker 02:
Just one more point on the creatinine boxes before I get to that is that the creatinine boxes cover everything possible.

[00:03:23] Speaker 02:
You're not going to answer the questions?

[00:03:24] Speaker 02:
May I make one last quick point about... Why don't you answer my question and then you can go back to your point.

[00:03:31] Speaker 02:
Sorry, I had two of your questions in front of me.

[00:03:34] Speaker 02:
So the last step of the claims, the wear-in clause.

[00:03:41] Speaker 02:
All that does is tell the doctor, after you check the patient's kidneys, after you adjust the dose, at some later time, there's a certain level of oxymorphone in the patient's kidneys.

[00:03:49] Speaker 02:
It doesn't tell the doctor what to do.

[00:03:51] Speaker 02:
It just says there's anything there.

[00:03:53] Speaker 02:
And my other point, which actually also answers this question, is that the diagnostic covers every level of creatinine clearance from zero to infinity.

[00:04:01] Speaker 02:
The first box is a certain number or less.

[00:04:04] Speaker 02:
The last box is a higher number or more.

[00:04:06] Speaker 02:
And the two middle boxes are everything in between.

[00:04:08] Speaker 02:
So those categories aren't doing any work.

[00:04:11] Speaker 02:
The diagnostic stuff says, just classify the patient's creatinine clearance rate.

[00:04:15] Speaker 02:
And everyone agrees that tests for that are known in the art, not something Endo came up with.

[00:04:21] Speaker 02:
And the actual testing of a patient's creatinine clearance rate.

[00:04:25] Speaker 02:
And the last step doesn't tell you, if it's in this box, do this.

[00:04:29] Speaker 02:
If it's in that box, do that.

[00:04:30] Speaker 02:
It just says, adjust the dose if you need to adjust the dose.

[00:04:33] Speaker 02:
And the wherein clause just says, there's a certain level of oxymorphone that you can measure in the patient system later.

[00:04:40] Speaker 02:
It's not even a certain level.

[00:04:41] Speaker 02:
It's a certain range of levels.

[00:04:43] Speaker 02:
There's a maximum bound on the amount of oxymorphone in the system.

[00:04:47] Speaker 02:
In that sense, it's like the token post-solution activity that Supreme Court has rejected in cases like Mayo and Fluke.

[00:04:53] Speaker 02:
If the patent's otherwise ineligible, then saying, here's a maximum limit on oxymorphone you find in the patient system doesn't save it.

[00:05:05] Speaker 02:
And I think this is important, because Vanda is a much more nuanced decision than Endo gives it credit for.

[00:05:11] Speaker 02:
Vanda didn't say any administering step will save the claims.

[00:05:14] Speaker 02:
Vanda said this administering step will save the claims.

[00:05:17] Speaker 02:
There's the diagnostic step, there's the specific doses, and there's the mechanistic tie between the diagnostic step and the dosing step, where they tell the doctor exactly what to do.

[00:05:28] Speaker 02:
And if you don't need to take my word for it, Judge Bryson's opinion for the district of Delaware in Parnix, Ireland, versus Alvagen, 2018, Westlaw, 222-5113.

[00:05:37] Speaker 02:
at page 24 has two paragraphs about the district court's opinion in this case.

[00:05:41] Speaker 02:
And Judge Bryson said, quote, the representative claim in ENDO is more akin to the claim in Mayo than to the claims at issue in Cells Direct, Vanda, and this case.

[00:05:53] Speaker 02:
As in Mayo, the claim at issue in ENDO, in effect, simply stated the law of nature, i.e.

[00:05:58] Speaker 02:
renal impaired patients may be more sensitive to oxymorphone while adding the words apply it.

[00:06:04] Speaker 02:
Another important point about Mayo is it puts the lie to Endo's argument that an affirmance here would spell the end of method of treatment claims.

[00:06:11] Speaker 02:
Vando is an example of a patent that takes a naturally occurring phenomenon and actually adds something to it.

[00:06:16] Speaker 02:
After finding the correlation, you actually do something specific and it tells the doctor exactly what to do.

[00:06:21] Speaker 02:
Endo's claims claim a correlation and add a draft trick.

[00:06:26] Speaker 02:
So going back to Mayo, Vanda didn't overrule Mayo.

[00:06:30] Speaker 02:
Vanda didn't announce an exception to Mayo that you could drive a truck through.

[00:06:32] Speaker 02:
The district court and the magistrate judge were right that the claims in this case are just like the claims in Mayo.

[00:06:37] Speaker 02:
Mayo doesn't actually say administering, but the claims use the word administering, and they actually contemplate administering.

[00:06:43] Speaker 02:
They use the word administered twice.

[00:06:44] Speaker 02:
They state that certain metabolite levels, quote, indicate a need to increase the amount of said drug subsequently administered to said subject, and that another metabolite

[00:06:54] Speaker 02:
level indicates a need to decrease the amount of said drug subsequently administered to said subject.

[00:06:59] Speaker 02:
And the Supreme Court, paraphrasing those claims, described them as an instruction to doctors, in that they tell doctors to, quote, reconsider the dose in light of the natural law.

[00:07:09] Speaker 02:
And to be sure, Justice Breyer did say in Mayo that the claims don't actually require the doctor to administer the drug.

[00:07:15] Speaker 02:
But that was just a comment on how easy the case was.

[00:07:17] Speaker 02:
It wasn't the only weakness in the Patentees case.

[00:07:19] Speaker 02:
It's certainly not a holding that adding administer it would save the claims any more than adding apply it to otherwise patent-ineligible claims would save them.

[00:07:29] Speaker 02:
I think given the shortness of the opening argument, I'll make two more quick points.

[00:07:35] Speaker 02:
There's another case about administering steps that actually addresses this point directly.

[00:07:40] Speaker 02:
It's Hemopet versus Hills Pet Nutrition.

[00:07:42] Speaker 02:
It's 2014 Westlaw 1031-7302.

[00:07:47] Speaker 02:
which this court affirmed by Rule 36 in Appeal Number 15-1218.

[00:07:52] Speaker 02:
And in that case, independent claims recited methods of analyzing nutrition for cats and dogs based on their genetic information.

[00:07:59] Speaker 02:
And a dependent claim recited the method of Claim 1 further comprising preparing a nutritional diet based on the analyzed data.

[00:08:06] Speaker 01:
Did you cite that case in your brief?

[00:08:08] Speaker 02:
We did not.

[00:08:10] Speaker 02:
And Bryson's opinion?

[00:08:14] Speaker 02:
The one I mentioned earlier from Judge Bryson, we didn't cite in our brief.

[00:08:17] Speaker 02:
You didn't cite that either.

[00:08:18] Speaker 02:
This is another one, and this is, we didn't cite either.

[00:08:20] Speaker 01:
We've got some more cases you didn't cite in your brief.

[00:08:22] Speaker 01:
You want to unload it on us now?

[00:08:25] Speaker 02:
No, just these two.

[00:08:26] Speaker 01:
To be fair, Judge Bryson's opinion.

[00:08:27] Speaker 02:
Just two, right?

[00:08:28] Speaker 02:
Yes.

[00:08:28] Speaker 02:
Judge Bryson's opinion did come down after the brief.

[00:08:30] Speaker 02:
In this case, we can submit a 28-J, if that would be better.

[00:08:34] Speaker 02:
I guess the last point I'll say before I sit down is at page 22 of the reply brief in text in the footnote 21.

[00:08:40] Speaker 02:
And there accuses the district court of making a certain factual finding.

[00:08:44] Speaker 02:
saying that the correlation between renal impairment and oxymorphone was not unknown.

[00:08:49] Speaker 02:
What Endo refers to as the district judge at page 22 is the magistrate judge.

[00:08:53] Speaker 02:
And the magistrate judge makes a statement.

[00:08:56] Speaker 01:
Page 23, you're going pretty fast, Mr. Burgess.

[00:08:59] Speaker 01:
We're on page 23, and you're complaining.

[00:09:01] Speaker 01:
Reply brief.

[00:09:02] Speaker 02:
I'm sorry, Judge Clevenger.

[00:09:03] Speaker 02:
I'm referring to page 22.

[00:09:05] Speaker 01:
Page 22 of the gray brief?

[00:09:06] Speaker 02:
Page 22 of the gray brief, yes.

[00:09:09] Speaker 01:
Page 22.

[00:09:09] Speaker 01:
And what on page 22?

[00:09:12] Speaker 02:
Endo says in the main text and again in the footnote that the district court made a factual finding the correlation between renal impairment and oxymorphone was not unknown.

[00:09:23] Speaker 02:
And Endo cites APPX pages 246 to 247.

[00:09:28] Speaker 02:
That is the district court, not the magistrate judge.

[00:09:31] Speaker 02:
What the district court says is that APPX 229 where he says he's not relying on that statement by the magistrate judge because it's quote, not essential to the decision.

[00:09:40] Speaker 02:
And Judge Andrews was right, it's not essential to the decision, because the Supreme Court tells us in Myriad that groundbreaking, innovative, or even brilliant discovery does not by itself satisfy the 101 inquiry.

[00:09:51] Speaker 02:
Nothing turns on that.

[00:09:52] Speaker 02:
And at APPX 229, that's the district court saying that nothing turns on that.

[00:09:58] Speaker 02:
So unless the court has further questions, we ask the court to approve.

[00:10:02] Speaker 02:
It may have spilled a lot, and then it didn't even rule it, and then that's a massive exception.

[00:10:09] Speaker 02:
Thank you, counsel.

[00:10:18] Speaker 03:
We submit that Vanda decided this case.

[00:10:21] Speaker 03:
There are, in fact, two administration steps in the claims.

[00:10:24] Speaker 03:
The first is orally administering two said patient in dependence on the creatinine clearance level, a lower dosage form.

[00:10:32] Speaker 03:
And that should be read as a lower dosage form than the subpopulation of patients which are healthy.

[00:10:38] Speaker 03:
There was then the wear-in clause, which Your Honor asked about, which is limiting.

[00:10:42] Speaker 03:
It says that after administration, the blood levels have to be at a certain level, below a certain level.

[00:10:48] Speaker 03:
And the reason for that is that's the level that will resolve pain but not harm the patient.

[00:10:55] Speaker 03:
The administration of opioids is a very big deal.

[00:10:58] Speaker 03:
And the problem that the inventors discovered was that even though this is metabolized in the liver, that it was surprising that renal

[00:11:07] Speaker 03:
insufficiency was causing blood levels of the opioid to rise.

[00:11:12] Speaker 03:
So they changed the label, which has been incorporated by reference into the patent, and advised the doctors, do not prescribe the regular dose of opioids to patients with renounced sufficiency.

[00:11:26] Speaker 03:
They said, you must lower the dose depending upon the adenine's clearance level.

[00:11:31] Speaker 03:
The doctors know how to do that.

[00:11:33] Speaker 03:
They apply the

[00:11:34] Speaker 03:
They can apply the test results from the patent specification and properly treat the patient.

[00:11:40] Speaker 00:
Can I ask you about that wearing clause?

[00:11:43] Speaker 00:
Am I correct in understanding that that wearing clause, in order to be satisfied, the dosage is going to change?

[00:11:50] Speaker 03:
That is absolutely correct.

[00:11:51] Speaker 03:
If you look at the figures, what you'll see is that for a normal patient, given oxymorphone, it goes up to this level and then eases down.

[00:12:02] Speaker 03:
But for a renally impaired patient, the dose spikes.

[00:12:04] Speaker 03:
And spiking doses of opioids are very bad news.

[00:12:08] Speaker 03:
And what the patentee discovered was that you can solve that problem and give practical advice to the doctors, reduce the dosage form.

[00:12:15] Speaker 03:
But they didn't stop where Mayo stopped by saying, just think about it.

[00:12:19] Speaker 03:
They said, administer it to the patient.

[00:12:22] Speaker 03:
And then they have a very narrow wherein clause that says you have to get the blood levels below a certain level.

[00:12:27] Speaker 03:
That's more than sufficient to narrow the claim

[00:12:31] Speaker 03:
to avoid any problems of the Rose and Maya.

[00:12:34] Speaker 03:
Now, if the court were not to reverse, were to create a conflict between the claim in this case and Van Dyke, you'd have a terrible situation.

[00:12:44] Speaker 03:
This issue has just been settled.

[00:12:48] Speaker 02:
It was a matter of- Or you'd have a fine distinction.

[00:12:50] Speaker 03:
What's that?

[00:12:51] Speaker 03:
Or you would have a fine distinction.

[00:12:52] Speaker 03:
Or you'd have a very fine distinction.

[00:12:54] Speaker 03:
And we believe that because of the last step, we are actually narrower.

[00:12:59] Speaker 03:
claims in Vanda did was really divide into two subpopulations and give 0 to 12 to 1 and 12 to 24 to the other.

[00:13:05] Speaker 03:
Our says you've got to titrate the dosage so that the patient's blood levels are below a specific cutoff.

[00:13:13] Speaker 03:
If you were to create a conflict between this decision and Vanda, you would upset what's now been recently settled law.

[00:13:20] Speaker 03:
There's new patent office guidance and the bar is moving forward.

[00:13:23] Speaker 03:
We don't believe that would be the appropriate decision.

[00:13:26] Speaker 03:
Judge Andrews obviously did not have the benefit of this decision when he ruled.

[00:13:30] Speaker 03:
And we believe that in light of that, the decision should be reversed.

[00:13:32] Speaker 01:
Do you take any comfort in Cells Direct?

[00:13:36] Speaker 03:
Yes, we do.

[00:13:38] Speaker 03:
Cells Direct also had a practical real-world step.

[00:13:42] Speaker 03:
They discovered a law of nature, as is often the case, in the pharmaceutical world.

[00:13:49] Speaker 03:
But then they had a practical application of that.

[00:13:52] Speaker 01:
Well, cells direct also was not available to the district court, as I understand it.

[00:13:58] Speaker 03:
I believe that's correct.

[00:13:59] Speaker 01:
That's by a matter of months.

[00:14:01] Speaker 03:
I believe that's correct.

[00:14:02] Speaker 03:
I believe that's correct.

[00:14:06] Speaker 03:
Thank you.

[00:14:07] Speaker 01:
Thank you, counsel.

[00:14:08] Speaker 01:
You've got to admit that in Vanda, there are more commands to the doctors than here.

[00:14:14] Speaker 03:
No, I wouldn't admit that at all.

[00:14:15] Speaker 03:
There's only one command to the doctor, which is once you've done the test, divide your treatment regimen

[00:14:20] Speaker 03:
And you have two treatment regimens.

[00:14:22] Speaker 03:
The algorithm is very, very simple, actually.

[00:14:24] Speaker 03:
It says give 0 to 12 to one group and give 12 to 24 to the other group.

[00:14:30] Speaker 03:
That's all there is.

[00:14:31] Speaker 03:
And that was sufficient.

[00:14:32] Speaker 03:
They discovered that administering medicine in a different dosage form for two subpopulations was sufficient.

[00:14:40] Speaker 03:
We actually have more specificity.

[00:14:41] Speaker 03:
A doctor has to titrate for an individual patient to get down below specific blood levels.

[00:14:48] Speaker 01:
So you argue you're even more specific?

[00:14:50] Speaker 03:
Yes, I am, Your Honor, because you have to actually titrate down for a particular patient.

[00:14:55] Speaker 03:
All they said was if the patient... It depends on the wearing clause.

[00:14:58] Speaker 03:
Because of the wearing clause.

[00:15:00] Speaker 01:
So if we take the wearing clause out, the big lady falls out from your stool.

[00:15:05] Speaker 03:
If you took the wearing clause out, we'd be much closer to where Vanda is, because then the difference would be there's still an administration step, which would take you outside of Mayo, because there's a practical effect on the patient.

[00:15:17] Speaker 03:
You give a lower dose to one population and a higher dose to the other population.

[00:15:22] Speaker 03:
But the wear and flaws makes us narrower than that.

[00:15:29] Speaker 03:
Thank you, Council.

[00:15:34] Speaker 00:
You'll have the time to do that, yes.