[00:00:00] Speaker 04:
The next argued case this morning is number 22, 1595, Genentech Incorporated against Sandoz Incorporated.

[00:00:12] Speaker 01:
Thank you, Your Honor, and may it please the court.

[00:00:18] Speaker 01:
Sandoz has cited no case in which a court refused to find infringement in an and a case.

[00:00:26] Speaker 01:
where the label instructs a physician to infringe, as is the case here.

[00:00:32] Speaker 01:
And let me begin with the DDI patents.

[00:00:36] Speaker 03:
Well, Ms.

[00:00:37] Speaker 03:
Dury, even if you're right that something in the label amounts to inducement, aren't these patents invalid as being obvious?

[00:00:50] Speaker 03:
They claim a dose for an old drug

[00:00:56] Speaker 03:
and lowering the dose if side effects are noticed.

[00:01:04] Speaker 03:
Isn't that sort of medication 101?

[00:01:07] Speaker 03:
If you have a headache and ask me what to do, I say take two aspirin and then you come back and you say I get a belly ache and I say well lower the dose.

[00:01:17] Speaker 03:
Isn't that standard practice?

[00:01:19] Speaker 01:
With respect to the DDI patents, the drug-drug interaction patents,

[00:01:24] Speaker 01:
The district court found those patents to be not obvious, and found that it was not obvious that there would be a drug-drug interaction through the concomitant use of flovoxamine and profanidone, and that the claims at issue here, which would be either to discontinue flovoxamine...

[00:01:55] Speaker 03:
is in package circular, that amounts to inducement.

[00:01:59] Speaker 03:
And I'm saying maybe you're right, but those patents are invalid.

[00:02:03] Speaker 01:
With respect to the LFT patents, the liver function test patents, the court did find those patents to be invalid as obvious.

[00:02:13] Speaker 01:
We think the district court misread the prior art in so finding because the prior art did not identify any instance in which a patient

[00:02:25] Speaker 01:
presenting with indications of abnormal liver function, which potentially could lead to very serious liver injury and even the need for a liver transplant, would still be prescribed the drug that was presumptively causing that incipient liver failure, rather than having that drug be discontinued.

[00:02:45] Speaker 01:
And we think the patent examiner correctly concluded reviewing that same prior art that the prior art taught away from the invention,

[00:02:54] Speaker 01:
by saying in straight terms that the drug should be discontinued.

[00:02:58] Speaker 01:
Having said that, I wanted to focus my argument in the first instance on the DDI patents, because with respect to those patents, there is only one issue for the court to resolve.

[00:03:08] Speaker 01:
And that is the question of direct infringement.

[00:03:11] Speaker 01:
And there, I would suggest that Sandoz has not cited any case where a court has found where there is a clear instruction in the label to infringe

[00:03:23] Speaker 01:
that there is nevertheless no direct infringement.

[00:03:26] Speaker 01:
And that is because, under this court's precedence, that analysis of hypothetical infringement takes place with respect to the language of the label, where the language of the label- Well, you're right, it's with the label.

[00:03:38] Speaker 02:
And so maybe different labels carry different weight with regard to the question you're posing.

[00:03:44] Speaker 02:
But in this particular, let's look at the 383, Claim 6.

[00:03:51] Speaker 02:
We're talking about a method, and maybe there's so many claims in this case that I may have the wrong one.

[00:03:56] Speaker 02:
But this seems like what I call an if claim.

[00:03:59] Speaker 02:
If you're doing something, stop doing it.

[00:04:02] Speaker 02:
So why is it not fair, correct, under Hatt Swaxman and maybe any other regime, that if there's an if claim, so it may never happen, that now I don't want to get into a burden argument.

[00:04:18] Speaker 02:
Because maybe it's the case that you have

[00:04:20] Speaker 02:
you've satisfied your burden because they're using the claim language in the label.

[00:04:25] Speaker 02:
But the district court said here there was evidence, overwhelming evidence on one side, nothing on the other, that nobody ever did this.

[00:04:35] Speaker 02:
So why in this, we're not talking about globally with respect to every claim and what it might require.

[00:04:40] Speaker 02:
We're talking about this particular type of claim

[00:04:44] Speaker 02:
And why, if it's kind of what I call, as I said, an if claim, to repeat myself, why it shouldn't, whether it's their burden or your burden, clearly whoever had the burden, their evidence was overwhelming.

[00:04:58] Speaker 02:
And we're deferring to the district court's fact finding.

[00:05:01] Speaker 01:
So it is an if claim in the sense that the claim is addressed to a situation where a patient is on fluvoxamine.

[00:05:10] Speaker 01:
And if a patient is on flovoxamine, what do you then do?

[00:05:14] Speaker 01:
You either discontinue the flovoxamine or you reduce the dose of the perfunadome.

[00:05:19] Speaker 01:
The district court did not find that there are no patients that take flovoxamine.

[00:05:24] Speaker 01:
And in fact, there was evidence in the record that it's widely prescribed.

[00:05:28] Speaker 01:
The district court did look outside the label

[00:05:32] Speaker 01:
to conclude that in his assessment of the evidence, a physician confronted with a patient who was taking fluvoxamine would prescribe a different drug rather than discontinue fluvoxamine.

[00:05:46] Speaker 01:
Now, we think that factual finding would be clear error, but we also don't think the court should get to that question because the language of the label is dispositive.

[00:05:56] Speaker 01:
And that is what follows from Sinovian.

[00:05:58] Speaker 01:
I think

[00:05:59] Speaker 01:
In its response to Genentech's 28-J letter, I think Sandoz agreed that if we were looking at a product claim, it would be error to look outside the label to determine whether there would be infringement in the real world.

[00:06:14] Speaker 01:
And that's because in Sinovian, the ANDA applicant came forward and said, notwithstanding the product specifications, here is conclusive evidence that our product never will infringe.

[00:06:26] Speaker 01:
There will never be direct infringement.

[00:06:28] Speaker 01:
And this court said,

[00:06:29] Speaker 01:
That doesn't matter because the applicant is stuck with the representations that they made in order to get the product on the market and said that what a generic applicant asks for and receives approval to market, if within the scope of a valid claim is an infringement,

[00:06:52] Speaker 01:
Now, it is true that in Sinovian, the claim at issue was a product claim.

[00:06:58] Speaker 02:
Right.

[00:06:58] Speaker 02:
And I'm suggesting there might be a difference.

[00:07:00] Speaker 02:
OK, even assuming that if you're talking about a tabular formulation that meets the claims and the label might resolve the dispute.

[00:07:10] Speaker 02:
But on the other hand, if the label requires some factual predicate,

[00:07:16] Speaker 02:
a rare disease patient also being prescribed another specific drug, then the label might be enough on its own in the absence of other evidence.

[00:07:26] Speaker 02:
But it might not be in light of evidence that the factual predicate wouldn't occur.

[00:07:32] Speaker 02:
Why is what I said wrong?

[00:07:34] Speaker 02:
And what case says that what I'm saying is wrong?

[00:07:36] Speaker 01:
I think I have two responses to that, Your Honor.

[00:07:39] Speaker 01:
My first response is that I think Par Pharma and the Federal Discourse 2020 decision in Par Pharma indicates that that is wrong at least in part.

[00:07:49] Speaker 01:
Because Par Pharma had method claims as well as product claims and didn't distinguish in its analysis.

[00:07:55] Speaker 01:
So I would say as a threshold matter, the Sanobian rule is not limited to

[00:07:59] Speaker 01:
product cases, it was applied to method places in Par-Pharma.

[00:08:03] Speaker 01:
And then I would say, more generally, if there were some basis to say that the if condition never could happen, maybe we would be in a different situation.

[00:08:14] Speaker 01:
But here, where the ANDA applicant has requested permission to give physicians that instruction, if it thinks it is an instruction that doesn't need to be given, the correct audience for that argument is the FDA.

[00:08:28] Speaker 01:
not this court after the fact.

[00:08:30] Speaker 01:
in an effort to suggest that there was no need to have given the instruction in the first place.

[00:08:35] Speaker 01:
And I think that is what comes out of Sinovian, that the policy rationale that underlies this court's decision in Sinovian, 271e infringement has been sort of set up statutorily to be a narrow argument.

[00:08:49] Speaker 01:
And the basis for this court's conclusion in Sinovian was that this sort of real world inquiry into what the hypothetical infringement would be

[00:08:59] Speaker 01:
would unnecessarily defer and complicate resolution of this infringement issue that the Hatch-Waxman framework was intended to address earlier.

[00:09:08] Speaker 01:
I would also say, Your Honor, this court's precedent in Vanda makes clear that even in a situation where there is an if condition, and obviously there there was this sort of if, are you going to genotype or not, as a predicate to administering the therapy, there the court said unambiguously, there's no requirement to prove any instance of past infringement.

[00:09:28] Speaker 01:
There's no, and this court in affirming, and there's no particular quantum of infringement that is required.

[00:09:35] Speaker 01:
And this court, in affirming the district court's judgment in Vanda, did not attempt to parse the claim construction issues that would have gone to the question whether past infringement in fact had occurred, and did not attempt to evaluate the court's weighing of the evidence.

[00:09:52] Speaker 01:
And notably, the district court

[00:09:54] Speaker 01:
indicated there were reasons to think this would never happen, that in practice, physicians would not genotype.

[00:10:01] Speaker 01:
But this court did not wade into that question and instead simply said the district court's analysis of the label was proper under this court's precedence.

[00:10:12] Speaker 01:
And so.

[00:10:13] Speaker 02:
Can I just ask you, this is just a not a substantive question, but since the case you've been citing repeatedly here is Sinovian.

[00:10:22] Speaker 02:
And I just checked, and it was

[00:10:24] Speaker 02:
pass them in gray.

[00:10:26] Speaker 02:
But I don't see it in cited.

[00:10:30] Speaker 02:
I don't think red engaged in it.

[00:10:32] Speaker 02:
And I might be entirely wrong on this.

[00:10:33] Speaker 02:
I've got too many cases this week.

[00:10:35] Speaker 02:
But I don't think red engaged.

[00:10:37] Speaker 02:
And then that raised my question of, well, did you cite it in blue?

[00:10:40] Speaker 02:
And I don't see it in the table of contents in blue.

[00:10:42] Speaker 01:
I don't believe this particular case was cited in the blue brief.

[00:10:47] Speaker 01:
But certainly, the argument has consistently been made.

[00:10:50] Speaker 01:
And we relied heavily on Vanda for these purposes.

[00:10:54] Speaker 01:
But I think the thesis of the argument is the same, that it is the label that controls the analysis.

[00:11:00] Speaker 02:
So does Sinovian give you anything more than Vanda does in terms of your arguments?

[00:11:03] Speaker 02:
I'm just trying to put it together now because I've got a lot of paper.

[00:11:06] Speaker 01:
Right.

[00:11:06] Speaker 01:
I think Sinovian makes it even more clear.

[00:11:09] Speaker 01:
I think Vanda makes it clear.

[00:11:11] Speaker 02:
Well, I'll ask the other side.

[00:11:13] Speaker 02:
Obviously, Nietzsche is entitled to an opportunity to respond to that.

[00:11:17] Speaker 01:
Of course.

[00:11:18] Speaker 01:
But let me try to explain how I think the two decisions relate to each other.

[00:11:21] Speaker 01:
And I think part pharma is sort of yet another in this string.

[00:11:24] Speaker 01:
I think Vanda makes it clear that the ANDA controls, and that's obviously in the context of a method claim, but the argument has been made that Vanda does not control because in Vanda the district court did discuss evidence outside the label, although in our reading of this court's Vanda opinion that was not required for this court's affirmance.

[00:11:46] Speaker 01:
So Novian makes the point that our reading of Vanda we think is correct.

[00:11:51] Speaker 01:
And that there are circumstances where the label language itself is dispositive and simply ends the inquiry.

[00:11:59] Speaker 01:
I would also note that the Redbrief and Sandoz had cited other cases that are distinguished in the Sinovian opinion, because they are cases in which the label was broad enough to encompass the possibility of infringement, but did not itself specify that infringement would occur.

[00:12:21] Speaker 01:
In those cases, the court has looked to evidence outside the label in order to determine whether infringement, in fact, will occur.

[00:12:31] Speaker 01:
But Sinovian makes clear that that inquiry is not appropriate where the label itself disposes of the infringement question by calling for infringement within its four corners.

[00:12:44] Speaker 01:
And that's why we think that the Sinovian and Parforma line of cases are those that should control here.

[00:12:53] Speaker 04:
All right, let's hear from the other side.

[00:12:55] Speaker 04:
Thank you.

[00:12:56] Speaker 04:
Mr. Jay.

[00:12:57] Speaker 00:
Good morning, Your Honors.

[00:12:59] Speaker 00:
May it please the Court?

[00:13:00] Speaker 00:
As my friend did, I'd like to focus on the DDI patents and respond in particular to the reliance on this Synovian line of cases, which we think, I think your colleague, Judge Prost, with my friend brought this out.

[00:13:15] Speaker 00:
Where the ANDA, what the ANDA controls is what's in the generic product.

[00:13:19] Speaker 00:
And Sinovian says specifically that where it defines a compound, the ANDA defines the compound.

[00:13:27] Speaker 00:
That echoes what the court also said in Ferring and in Vanda itself, that the ANDA defines the proposed generic product.

[00:13:36] Speaker 00:
We're not disagreeing with the proposition that where the ANDA defines the proposed generic product and then making, using, or selling that generic product would infringe

[00:13:45] Speaker 00:
a claim that that's dispositive if the ANDA answers the infringement question.

[00:13:50] Speaker 00:
Now my friend on the other side said that PAR, now there are two PAR cases, there's the recent one and there's the 2021, but relying on the unpublished 2021 for the proposition that this also applies to method claims.

[00:14:02] Speaker 00:
But if you look at the method claim in that case, it is simply administer the compound, administer the claimed compound.

[00:14:07] Speaker 00:
So as you'll see, the opinion goes through why is there not infringement?

[00:14:11] Speaker 00:
It's because the compound doesn't infringe.

[00:14:14] Speaker 03:
With respect to the DDI patents, the court found that these were not infringed, that there was no evidence that these two compounds were administered together.

[00:14:26] Speaker 03:
You're asserting that

[00:14:27] Speaker 03:
Correct.

[00:14:28] Speaker 03:
And since there's no direct infringement, there could be no inducement.

[00:14:33] Speaker 00:
That is exactly our argument, that there's no clearer in that finding.

[00:14:35] Speaker 03:
And is it also your view that the filing of the ANDA provides jurisdiction only for the conduct of the lawsuit, rather than serving as the predicate for an inducement finding?

[00:14:51] Speaker 00:
That's exactly right.

[00:14:54] Speaker 00:
You can't prove inducement without proving direct infringement.

[00:14:57] Speaker 00:
And the burden is always on the plaintiff to establish that if the ANDA was approved and the product was marketed, that infringement would result.

[00:15:08] Speaker 00:
In an inducement case, that includes direct infringement.

[00:15:11] Speaker 00:
And you can't, from the label,

[00:15:16] Speaker 00:
just presume conclusively that out there in the real world, the if part of an if claim is going to be satisfied.

[00:15:23] Speaker 02:
The reason, I mean, I guess you and I may part company.

[00:15:26] Speaker 02:
I don't know.

[00:15:27] Speaker 02:
But it seems to me you don't really need to answer the burden question in this case because I can't recall, but I don't think the district court relied heavily.

[00:15:36] Speaker 02:
or whatever.

[00:15:37] Speaker 02:
And here, the evidence was one sided.

[00:15:41] Speaker 02:
So I was going to ask, my question to you is, hypothetically, if you had put on all your three experts and they had said what they said, and it's very persuasive, and they come in and they have one doctor, one expert that says, yes, I've done this, and yes, I believe it will be done in the future based on my 50 years experience, would that be sufficient?

[00:16:01] Speaker 00:
That's a question for the fact finder.

[00:16:03] Speaker 00:
So it certainly could be.

[00:16:04] Speaker 00:
Uh, and that is, uh, what I take, uh, the, the lesson of all these cases to be that whether the, whether direct infringement has been proved as an element of induced infringement is a factual question for the fact finders.

[00:16:19] Speaker 04:
Isn't it really a Hatch-Waxman question to get into, to achieve jurisdiction?

[00:16:27] Speaker 04:
Under Hatch Waxman, when everyone knows that there is an actual infringement, no matter how it's construed, you have to have a premise, not as a question of fact, but as a jurisdictional premise of infringement.

[00:16:42] Speaker 00:
Respectfully, Your Honor, infringement is not the jurisdictional premise of a Hatch-Waxman filing.

[00:16:47] Speaker 00:
The filing of the ANDA with the Paragraph 4 certification is the Artificial Act.

[00:16:51] Speaker 00:
But one of the things that Paragraph 4 certification can say is we certify that we don't infringe the Orange Book listed patent.

[00:16:57] Speaker 00:
So you don't concede infringement by filing the certification.

[00:17:03] Speaker 00:
And in any event, whether infringement would result following marketing, that's always the question.

[00:17:11] Speaker 04:
Now, my friend relied on- I don't think that that's how it works.

[00:17:15] Speaker 04:
You have to have a live controversy for federal jurisdiction.

[00:17:20] Speaker 04:
There is a statutory presumption under certain circumstances.

[00:17:26] Speaker 04:
You're telling us, don't bother me with circumstances, those are questions of fact?

[00:17:31] Speaker 00:
I'm saying, Your Honor, that the certification, this court has said in all of its cases, Farring, Sanovian, Vanda, and Glaxo, I think, is the first of this line of cases.

[00:17:43] Speaker 00:
that the filing of the ANDA doesn't allow you to conclusively presume, nor does it concede on the part of the generic, that infringement, whether induced or direct, would result?

[00:17:54] Speaker 04:
That's not my understanding of Hatch-Waxman.

[00:17:57] Speaker 04:
I'll double check that understanding.

[00:17:59] Speaker 04:
But all these years that it has been working, it seems to me that parties in your position have felt that they were compelled to concede infringement.

[00:18:13] Speaker 04:
In order to have jurisdiction that artificial infringement can be challenged, you say there is no artificial infringement, you're out of court.

[00:18:25] Speaker 00:
You're not out of court because it's the threat of the assertion of the patent because you want to market the generic during the lifetime of the patent and you're certifying to the generic, I'm sorry, to the brand and to the FDA that the patent either is invalid or will not be infringed.

[00:18:43] Speaker 03:
In other words, infringement on the merits is to be decided

[00:18:48] Speaker 03:
separately from the fact that as a matter of law, the filing of the ANDA creates jurisdiction for the issue to be considered.

[00:19:02] Speaker 00:
That's exactly right, Your Honor.

[00:19:03] Speaker 00:
The court, starting in Glaxo and in a whole series of cases, has rejected the idea that by filing the Paragraph 4 certification, you are agreeing that infringement would result, that there's a conclusive or even a rebuttable presumption.

[00:19:19] Speaker 00:
The court has rejected that roundly.

[00:19:21] Speaker 03:
That's clear from the statute.

[00:19:22] Speaker 00:
It is clear from the statute.

[00:19:23] Speaker 00:
You couldn't have a certification of non-infringement under Paragraph 4 if by certifying you were exceeding to infringement.

[00:19:31] Speaker 00:
And so I think the question on these facts really goes back to Judge Prost's point that this is an if patent.

[00:19:38] Speaker 00:
And nothing in the specification of the ANDA tells the court whether that if condition will ever be satisfied.

[00:19:45] Speaker 00:
Now in Vanda, the patent is different because what the labeling in Vanda tells the doctor is that in all cases, you should figure out whether your patient is a poor metabolizer or not.

[00:19:56] Speaker 00:
You can't determine the correct dosage without doing that genotyping test first.

[00:20:01] Speaker 00:
And so in all cases, the labeling the district court found directed performing the genotyping test.

[00:20:11] Speaker 00:
This court found that that finding was not clearly erroneous, but it treated it specifically as a fact question.

[00:20:18] Speaker 00:
And I think that that is the right way of approaching it.

[00:20:21] Speaker 00:
And I think my friends on the other side haven't really dealt with the

[00:20:25] Speaker 00:
finding a fact on its own terms, they want the court to look past this evidence and say that the ANDA is conclusive.

[00:20:32] Speaker 00:
But when you look at the evidence on which the district court relied, not only is there a complete absence of evidence that these drugs were prescribed together into the same patient, that, of course, is not dispositive.

[00:20:46] Speaker 00:
But it is permissible for a finder of fact to draw an inference from that, especially when you combine it with what the experts said about the warnings

[00:20:55] Speaker 00:
in paragraph 7.1 of the labeling, that because of the warnings and because of the availability of another alternative that doesn't raise the same risk with fluvoxamine, and the fact that the person who's going to be prescribing this drug is a pulmonologist, pulmonologist that our expert testified and the district court credited, is not going to take someone off of their psychiatric medication when they can instead prescribe a different

[00:21:22] Speaker 00:
treatment for their IPF.

[00:21:24] Speaker 00:
That here is OFEV, which is a non-infringing alternative.

[00:21:28] Speaker 00:
That's what the district court found, as a fact, would happen.

[00:21:31] Speaker 00:
And I think that because that factual finding is not clearer, and the ANDA doesn't override the evidence about the real world, I think that really is dispositive on the TDI patents.

[00:21:44] Speaker 04:
I have another policy problem.

[00:21:47] Speaker 04:
And that is, here, this patentee

[00:21:50] Speaker 04:
put this system of withdrawal and so on and retitration through clinical trials, all three phases.

[00:21:59] Speaker 04:
We know it's expensive, whatever it is.

[00:22:03] Speaker 04:
And you're telling us, nevermind, that's not patentable.

[00:22:06] Speaker 04:
You can't control it.

[00:22:07] Speaker 04:
That's a gift to the public.

[00:22:09] Speaker 04:
You can't recover your investment in this development, although the FDA requires that it be on the label.

[00:22:18] Speaker 04:
Therefore, we're required to put it on the label.

[00:22:21] Speaker 04:
Therefore, we cross this bridge that I was concerned with of getting into court to challenge validity and infringement.

[00:22:30] Speaker 04:
Why would any of this take place on the position that you now tell us is required?

[00:22:38] Speaker 04:
And who's the loser?

[00:22:41] Speaker 04:
The patient.

[00:22:42] Speaker 04:
The patient isn't going to have the benefit of phase three.

[00:22:47] Speaker 04:
for the trials and the experience.

[00:22:51] Speaker 04:
So who wins?

[00:22:52] Speaker 04:
Nobody.

[00:22:55] Speaker 00:
We disagree with that.

[00:22:56] Speaker 00:
And we certainly don't dispute the value of innovative medicines and the clinical trials that underlie them.

[00:23:02] Speaker 00:
But this patent and this labeling indication are somewhat unusual for a couple of reasons.

[00:23:09] Speaker 00:
One thing I want to point the court to is the fact that the

[00:23:12] Speaker 00:
FDA directs using fluvoxamine as a stand-in for a whole class of inhibitors of the same type, CYP1A2 inhibitors.

[00:23:24] Speaker 00:
And the evidence in the record is that, and this is at 73, 42 to 43, that FDA is, this is the only one in this class that FDA recommends using in a clinical trial.

[00:23:39] Speaker 00:
But it does so as a stand-in for the entire class.

[00:23:41] Speaker 00:
That is why, if you look in the labeling, you will see that each time fluvoxamine is mentioned, it is prefaced with EG.

[00:23:48] Speaker 00:
EG fluvoxamine, this is just one example.

[00:23:50] Speaker 00:
But their patent is only on that one, only on the administration of that one specific compound.

[00:23:56] Speaker 03:
Is it also your point that perfenedone for IPF, this patent did not

[00:24:06] Speaker 03:
claim the first use and discovery of that treatment.

[00:24:12] Speaker 03:
That was in the prior art.

[00:24:14] Speaker 00:
It certainly was and these are very narrow method claims well into the lifetime of this compound.

[00:24:21] Speaker 03:
They just changed the dosage and then recited lowering the dose if there were side effects and then manipulating and this is sort of within the skill of the art.

[00:24:33] Speaker 03:
trial court said this was standard medical practice.

[00:24:39] Speaker 00:
That's exactly right and now there is this language in the label that they've gotten a patent on and my friend on the other side said that you should infer intent to infringe and indeed you should infer that direct infringement will occur and that if Sandoz didn't like that Sandoz should talk to the FDA but of course the generics duty in a Hatch-Waxman case

[00:25:01] Speaker 00:
is to replicate the brand's labeling verbatim.

[00:25:05] Speaker 00:
The duty of sameness obliges it to do that.

[00:25:08] Speaker 03:
How old was the use of perphenidone to treat IPF?

[00:25:15] Speaker 00:
Certainly before the prior date of these patents.

[00:25:20] Speaker 00:
That's right, because the product was being used for that purpose in Japan.

[00:25:27] Speaker 00:
That's Perespa, the prior product, whose label is in the prior art.

[00:25:33] Speaker 00:
The only other point I wanted to make, which is on the other topic that my friend covered in the top side of the argument, is about the obviousness of the LFT patents.

[00:25:44] Speaker 00:
And I really just want to make one point, which is that even in addition to the Azuma reference and the Perespa label, the district court made an important finding about the common medical knowledge at the time, and in particular, the HHS guidelines for drug-induced liver injury.

[00:26:01] Speaker 00:
And you will find that finding at page A26, which explains why, even if you took both of the references off the table, the state of the art was that grade two liver levels elevated at the grade two level,

[00:26:19] Speaker 00:
was not serious enough to definitively require withholding what might be a very important treatment.

[00:26:26] Speaker 00:
And the HHS guidance says to medical professionals to consider continuing to administer, perhaps at a reduced dosage, perhaps at the original dosage.

[00:26:38] Speaker 00:
And that's exactly what the supposed innovation is here.

[00:26:42] Speaker 00:
The district court's findings on that and on the

[00:26:45] Speaker 00:
scope and content of the prior art, Azuma and the Perespa label were not clearly erroneous.

[00:26:49] Speaker 00:
Unless the court has any further questions about anything else in the case, we're prepared to submit our case.

[00:26:56] Speaker 04:
Thank you.

[00:26:56] Speaker 04:
Thank you, counsel.

[00:27:01] Speaker 01:
Thank you.

[00:27:02] Speaker 01:
Your Honor, it is true that perfunadone was available in Japan before Genentech did the work that led to the patents in suit, but FDA had refused to approve it in the United States and it was not available to patients because of concerns about safety and efficacy.

[00:27:20] Speaker 02:
Approximately how many patents are out there or have been issued related to this drug?

[00:27:26] Speaker 01:
I don't know the answer to that question, Your Honor.

[00:27:29] Speaker 01:
I know that it was an old composition.

[00:27:32] Speaker 01:
So that long ago expired?

[00:27:36] Speaker 01:
Absolutely.

[00:27:37] Speaker 01:
The composition.

[00:27:37] Speaker 01:
And it was not being used to treat patients for IPF because it had not been determined to be safe and effective.

[00:27:43] Speaker 01:
And Genentech did the work to establish that it could be prescribed safely for IPF and was then able to bring this therapy to market.

[00:27:50] Speaker 01:
Now, I want to start with Vanda.

[00:27:53] Speaker 01:
It is true that there was a factual question in Vanda.

[00:27:56] Speaker 01:
The factual question was whether the label encouraged genotyping because the label did not specifically call out genotyping.

[00:28:05] Speaker 01:
It simply talked about the possibility of testing generally.

[00:28:08] Speaker 01:
And there was a factual question as to whether that would direct a physician to genotype that was resolved in the plaintiff's favor as a factual question.

[00:28:18] Speaker 01:
But that does not mean that the question of what force the ANDA label has in an ANDA case is not a legal question, and it is.

[00:28:26] Speaker 01:
And in Vanda, this court was very clear.

[00:28:29] Speaker 01:
We did not have the burden to come forward with an instance of past infringement.

[00:28:34] Speaker 01:
And no particular quantum of infringement is required, such that even an individual patient would be sufficient.

[00:28:41] Speaker 01:
Now, there was ample evidence in the record that flovoxamine is prescribed for depression and anxiety and a variety of disorders.

[00:28:48] Speaker 01:
And there was not a suggestion that it's not widely prescribed.

[00:28:51] Speaker 01:
The actual testimony in the record, and this is at appendix 71, 46 to 47, is that the individual physicians who testified as experts for both sides had not seen a patient who had been prescribed fluvoxamine, but observed that they had only seen 0.2% of patients who had presented with IPF during the relevant period of time.

[00:29:12] Speaker 01:
So this was a tiny, tiny sample.

[00:29:15] Speaker 01:
The district court nevertheless criticized Genentech and said the information that it proffered about

[00:29:21] Speaker 01:
The fact that flovoxamine was widely prescribed and the fact that it was going to potentially be used widely as a treatment for COVID does nothing to lessen the persuasive impact of plaintiff's inability to cite a single example of a patient being prescribed both perfunadone and flovoxamine.

[00:29:38] Speaker 01:
That evidence was not adduced because it was not our burden to adduce it.

[00:29:42] Speaker 01:
Because Vanda was very clear that we did not have that burden.

[00:29:46] Speaker 01:
And the district court aired as a matter of law in finding that we had not met our burden because we had failed to provide that evidence.

[00:29:54] Speaker 01:
Vanda says we don't need it.

[00:29:57] Speaker 01:
There is no quantum of infringement that is required.

[00:30:00] Speaker 01:
And the district court speculation that instead a physician might prescribe this alternative treatment, OFEV, I would suggest would be clear error, because the same expert who mentioned that possibility also testified that the treatment modality is determined by side effects, which are different between the two different treatment regimes and price.

[00:30:23] Speaker 01:
And in this situation, OFEV would cost $100,000 a year.

[00:30:26] Speaker 01:
and perfunadone would be generic.

[00:30:28] Speaker 01:
Nobody testified that in that circumstance, a physician would always choose Ofev at $100,000 rather than discontinuing fluvoxamine, which is one of many drugs that are available to treat depression and anxiety.

[00:30:42] Speaker 01:
So again, I would return to the predicate point, Your Honor, that we think this court's jurisprudence has been clear that, yes,

[00:30:51] Speaker 01:
The applicant in some circumstances must copy the label language, but the applicant also has the option to go back to FDA and seek a carve out of that language if it thinks that language is not important and make its argument to FDA for while that language would not have any real world impact.

[00:31:08] Speaker 01:
Sandoz could have done that here.

[00:31:10] Speaker 01:
It made the election not to do that.

[00:31:13] Speaker 01:
And it made the election to include these unambiguous instructions in its label.

[00:31:18] Speaker 01:
And in that circumstance, we think

[00:31:21] Speaker 01:
that Synovian and Parpharma and this court's precedents mean that where the label is explicit on the question of infringement and directs the physician unambiguously to infringe, that the applicant cannot avoid the force of the instructions that it is given by saying, as the applicant tried to do in Synovian, well, it's never going to really happen, but instead must be bound by those representations that it made in order to be able to bring a generic product to work.

[00:31:50] Speaker 04:
Okay, thank you.

[00:31:51] Speaker 01:
Thank you.

[00:31:55] Speaker 04:
Any more questions?

[00:31:55] Speaker 04:
Thank you.

[00:31:56] Speaker 04:
Thank you to both counsel.

[00:31:58] Speaker 04:
The case is taken under submission.

[00:32:00] Speaker 04:
That concludes this panel's argued cases for this morning.