[00:00:00] Speaker 01: Case for argument is 162707, Vanda Pharmaceuticals versus West Ward Pharmaceuticals. [00:00:33] Speaker 03: May it please the court? [00:00:35] Speaker 03: Yeah, Ken Shuler on behalf of Westward. [00:00:39] Speaker 03: I may also refer to Roxanne Laboratories. [00:00:42] Speaker 03: That was the entity that owned the ANDA at the time of the trial. [00:00:46] Speaker 03: As set forth in our supplemental letter brief, we believe this court has jurisdiction to reach the merits. [00:00:51] Speaker 02: Can I just ask you about that? [00:00:53] Speaker 02: And thanks for the supplemental briefing from both of you. [00:00:55] Speaker 02: It was really helpful. [00:00:57] Speaker 02: But I'm still a little confused. [00:01:00] Speaker 02: So they file and they list [00:01:03] Speaker 02: several patents. [00:01:05] Speaker 02: Or they list some patents. [00:01:07] Speaker 03: The NDA. [00:01:07] Speaker 02: Right. [00:01:09] Speaker 02: Not including the 610 obviously because it hasn't been issued and you haven't put it in the Orange Book. [00:01:14] Speaker 02: Correct. [00:01:15] Speaker 02: I understand that it later gets put. [00:01:17] Speaker 02: would have happened if they'd filed the ANDA with just the patents, and you'd never gotten the 610 patent, and everything else would have fallen out. [00:01:26] Speaker 02: Would there have been a lack of jurisdiction over their ANDA suit, or your suit against them under ANDA? [00:01:33] Speaker 02: Or would it have been a failure? [00:01:34] Speaker 02: I'm the ANDA applicant. [00:01:35] Speaker 02: I know who you are. [00:01:36] Speaker 03: OK. [00:01:37] Speaker 02: Can you run that story, please? [00:01:38] Speaker 02: Well, you're the one that filed suit, right? [00:01:40] Speaker 02: Because the ANDA is the act of infringement. [00:01:43] Speaker 02: So you filed suit based on that ANDA. [00:01:45] Speaker 03: No, we are the ANDA. [00:01:47] Speaker 02: Sorry. [00:01:48] Speaker 02: You're the ANDA applicant. [00:01:50] Speaker 03: Correct. [00:01:51] Speaker 03: So we had been sued. [00:01:52] Speaker 02: Do you agree that there's jurisdiction? [00:01:54] Speaker 02: Sorry, I got you backwards. [00:01:56] Speaker 03: You lost. [00:01:57] Speaker 03: Absolutely, Your Honor. [00:01:59] Speaker 02: But you still think that if they had never, they had never, sorry, I have lost, I've already lost where I was going on that. [00:02:10] Speaker 02: I'm trying to figure out why the 610 [00:02:17] Speaker 02: putting that in the orange book and then putting it in the certification was good enough to let this case go forward? [00:02:23] Speaker 03: Sure. [00:02:24] Speaker 03: The most straightforward way for, I think, me to address that is Rule 15D and the supplemental jurisdiction statute. [00:02:32] Speaker 03: And here's why. [00:02:33] Speaker 03: When we filed the certification, we had already been sued under the 198 patent. [00:02:38] Speaker 03: Everybody agrees that there's jurisdiction under E2 for that. [00:02:42] Speaker 03: The patent that's at issue had not issued [00:02:45] Speaker 03: as of the time that Roxanne filed its ANDA. [00:02:48] Speaker 03: So it can't be an E2 action. [00:02:50] Speaker 03: However, when we did our certification, that tied, in our minds, the certification, the ANDA at issue to what was already pending, which is the 198 patent action, therefore making it a common set nucleus. [00:03:07] Speaker 02: But if the 610 had never been filed, and you had never added it, and the 198 had dropped out. [00:03:14] Speaker 03: It's expired. [00:03:15] Speaker 02: It wouldn't have been a lack of jurisdiction. [00:03:17] Speaker 02: There would have just been no claim for infringement anymore. [00:03:20] Speaker 03: If the 610 patent didn't exist? [00:03:22] Speaker 02: Yeah. [00:03:22] Speaker 03: That's correct. [00:03:24] Speaker 03: OK. [00:03:24] Speaker 03: There would have been an action under the 198. [00:03:26] Speaker 03: That injunction would have expired because the patent expired. [00:03:29] Speaker 03: OK. [00:03:30] Speaker 04: But you're saying the 610 is properly, in effect, part of the Hatch-Waxman Act. [00:03:36] Speaker 03: Well, it can be appended to the Hatch-Waxman Act under 1367 under Rule 15. [00:03:42] Speaker 03: And our view is that that would allow the exercise of jurisdiction under two different sets of circumstances. [00:03:49] Speaker 03: I'm happy to explain why that is the case. [00:03:52] Speaker 03: But I think we agree with Vanda. [00:03:54] Speaker 03: Not on the mechanism to get there, but we agree that this panel has jurisdiction. [00:03:57] Speaker 04: Now, you've challenged claim one under section 101. [00:04:01] Speaker 03: Correct. [00:04:02] Speaker 04: Why isn't this plainly and simply, not simply, but in effect, a method of [00:04:09] Speaker 04: treatment claim. [00:04:10] Speaker 04: The method of treating a patient with Ila-Carabella, someone with schizophrenia, which is a predicate of it, consisting of administering the drug in a certain dose. [00:04:23] Speaker 04: Now, there are these portions of the claim, the if-then portions, but aren't those just predicates to justifying, to explaining to whom the drug should be administered, just like [00:04:38] Speaker 04: In the first two lines, it says a method of treating a patient where the patient is suffering from schizophrenia. [00:04:45] Speaker 04: That's a predicate. [00:04:47] Speaker 04: So why isn't this in effect a method of treatment claim? [00:04:51] Speaker 04: The Supreme Court has in effect blessed such a claim in Mayo. [00:04:58] Speaker 04: So what's the problem under 101? [00:05:01] Speaker 03: Well, I don't think that the Supreme Court has blessed it under Mayo. [00:05:03] Speaker 03: I think that Mayo actually highlights a straightforward application of the precepts in Mayo [00:05:08] Speaker 03: highlights that it's patent ineligible. [00:05:11] Speaker 03: Under the first step, first of all, let me highlight that if Vanda is correct that the claims only require dosing a normal metabolizer with a normal dose of the drug, that's quintessentially conventional activity and the only justification that they provided to the district court and that the district court embraced for allowing the claims as eligible would disappear. [00:05:34] Speaker 01: And so- I'm sorry, can you run the- [00:05:36] Speaker 03: Their claim construction says you only have to dose a normal metabolizer at a normal dose, and that it's an alternative to dose a... But it's also, the alternative is that you cut the dose in half for non-normal metabolizers, right? [00:05:50] Speaker 01: Correct. [00:05:50] Speaker 01: And under this court's precedent, if it's... And that's a method of treatment. [00:05:53] Speaker 01: How are we going to treat people who are PMs or whatever? [00:05:57] Speaker 01: Correct. [00:05:58] Speaker 01: Right? [00:05:58] Speaker 03: But if it's an optional claim element, in other words, [00:06:01] Speaker 03: If it's either or, as Vanda suggests, then for purposes of validity, that optional element, the dosing of the poor metabolizers, disappears from the claim for purposes of evaluating validity. [00:06:12] Speaker 03: And it's quintessentially conventional activity to give a normal dose to somebody who's got a normal metabolism. [00:06:17] Speaker 03: But our view is the claims are ineligible under our construction of the claims as well. [00:06:22] Speaker 03: in Mayo. [00:06:23] Speaker 04: But what you're saying is method of treatment claims are not permissible under Mayo. [00:06:29] Speaker 04: Mayo says, unlike, say, a typical patent on a new drug or a new way of using an existing drug, they exempted method of treatment, as they probably should have, under the prohibition in Mayo. [00:06:47] Speaker 03: Well, I think that [00:06:48] Speaker 03: Our view is that Mayo was a method of treatment. [00:06:51] Speaker 03: It talked about administering a thiopurine drug. [00:06:54] Speaker 04: But it was basically a diagnostic. [00:06:57] Speaker 02: It didn't have any methods of treatment. [00:06:59] Speaker 02: It just said, [00:07:01] Speaker 02: perform this analysis and adjust accordingly. [00:07:05] Speaker 02: If you have the same thing here, run the genetic test, and then adjust accordingly, you might be correct that Mayo covers it, but it has more specificity of use different dosage levels. [00:07:18] Speaker 03: It does, but I think that's a distinction without a difference. [00:07:20] Speaker 02: I mean, all of the dosage levels... Is that exactly what the distinction Mayo made? [00:07:25] Speaker 03: I don't think so. [00:07:26] Speaker 03: I think that Mayo said that all of the doses that a physician could adjust to [00:07:30] Speaker 03: are patented eligible. [00:07:31] Speaker 03: In other words, because it's conventional activity for a physician to adjust the dose with regard to potential side effects, that's conventional activity. [00:07:41] Speaker 02: I mean, I don't understand how you can make that argument so broadly. [00:07:44] Speaker 02: We have dozens of cases where we've held [00:07:49] Speaker 02: dosing patents eligible or valid for various reasons where the drug is known, side effects are known, and they come up with new methods of treatment or dosages to counteract those side effects. [00:08:04] Speaker 02: If you're otherwise correct, then any possible combination or any method of dosing is just ineligible if the drug is known and it's conventional to know to adjust. [00:08:19] Speaker 03: I think that the distinction is, for instance, the 198 patent, we did not contend was ineligible under 101. [00:08:24] Speaker 03: And it had methods of treating schizophrenia by giving iloperidone. [00:08:29] Speaker 03: Those are exactly what your honor is talking about, a new way of using a drug. [00:08:34] Speaker 04: But that's it. [00:08:34] Speaker 04: What you're getting to is, in effect, double patenting or obviousness. [00:08:40] Speaker 04: But those issues aren't before us. [00:08:42] Speaker 03: Well, what I'm saying is, I think that when a drug is known and it's known to adjust the dose, [00:08:48] Speaker 03: simply adding genotyping, which is under myriad, clearly natural law. [00:08:52] Speaker 03: The inherited genetic status of somebody, whether you're a poor metabolizer or a normal metabolizer, is an inherited genetic trait. [00:09:00] Speaker 03: And merely appending to that, based on that status and your potential propensity for side effects, you should give a lower dose within a certain range. [00:09:11] Speaker 03: Under Mayo, Mayo said dosing to address side effects is conventional and was conventional in 1998. [00:09:18] Speaker 03: as of the priority date of those patents. [00:09:19] Speaker 03: It clearly was conventional in 2004 as of these. [00:09:23] Speaker 01: But Mayo didn't have any specificity into what the treatment method of treatment was, right? [00:09:28] Speaker 01: I mean, I don't think we can get Mayo here. [00:09:31] Speaker 03: It was a method of treating a certain condition with a thought. [00:09:34] Speaker 01: But it didn't go to the dosing. [00:09:35] Speaker 01: It didn't say, and you're going to treat them for providing. [00:09:38] Speaker 01: Therefore, this group is going to get this much, and this group is going to get this much. [00:09:41] Speaker 03: Agreed. [00:09:42] Speaker 03: And my point is simply it said either [00:09:45] Speaker 03: upward with the dose or downward with the dose, it didn't say that any of those precise doses would be patent-eligible. [00:09:51] Speaker 03: Well, let me turn to our primary argument, I think, which is non-impringement, which is the record below showed that the potential rate of infringement was so low as a matter of law that one cannot infer or intend to induce infringement. [00:10:08] Speaker 01: I'm a little confused. [00:10:09] Speaker 01: I understand your argument, but it seems like you've got a two-part argument. [00:10:12] Speaker 01: And in my brain, it's easier to separate. [00:10:14] Speaker 01: Because it seems like part of your argument is there's no direct here. [00:10:18] Speaker 03: Correct. [00:10:19] Speaker 01: So it can't be indirect because there's no direct. [00:10:21] Speaker 03: Don't need to reach inducement, correct. [00:10:23] Speaker 01: And then there are other arguments that are made that kind of don't deal with the direct, but say there's no specific intent because of what the label says. [00:10:31] Speaker 01: Am I right that they're really two separate things you're arguing? [00:10:33] Speaker 03: That's right. [00:10:34] Speaker 03: And they're independent bases for reversing. [00:10:36] Speaker 03: With regard to the lack of intent to induce, the trial record showed that even under Vanda's construction of the claim, that a normal metabolizer being dosed at a normal dose is sufficient to satisfy the claim. [00:10:49] Speaker 03: only a single patient in the six years that the language they accused of inducement was in the label was treated in such a fashion. [00:10:56] Speaker 04: But that sounds like an ordinary infringement claim, inducement claim, when you have to show direct infringement here. [00:11:05] Speaker 04: You can see that it's under Hatch-Waxman, because there was an amendment to the ANDA. [00:11:13] Speaker 04: And so you don't have to prove. [00:11:15] Speaker 04: I mean, the whole point of E2 under Hatch-Waxman is you don't have to [00:11:26] Speaker 04: show acts of infringement. [00:11:28] Speaker 04: It's the filing of the ANDA, or the amended ANDA, which is the act of infringement. [00:11:34] Speaker 03: Well, that's the act of infringement that gives the court jurisdiction. [00:11:36] Speaker 03: That's not the act of infringement they have to prove to get the, an injunction. [00:11:41] Speaker 03: And so this, and by the way, this is not an action. [00:11:43] Speaker 04: The injunction is built into the act, you know. [00:11:46] Speaker 03: But this is not an action under E2, because the patent didn't exist at the time that [00:11:53] Speaker 03: at the time that the ANDA was filed. [00:11:55] Speaker 03: So there can't be an active infringement under E2 for the 610 patent. [00:11:59] Speaker 03: Congress was very clear that it's got to be a patent, a use claimed in a patent. [00:12:03] Speaker 03: They could have provided for jurisdiction for uses claimed in a patent application, but they didn't. [00:12:08] Speaker 03: It's limited to a patent. [00:12:09] Speaker 03: But let me get back to the inducement. [00:12:11] Speaker 03: We think this is just like Warner-Lambert. [00:12:13] Speaker 03: This has to be a traditional 271B claim, and that's what they asserted at trial. [00:12:17] Speaker 03: But the rate of infringement is one instance of one patient potentially being dosed in an infringing fashion [00:12:23] Speaker 03: in the six years that the brand label had the same language that they accused us of inducing infringement. [00:12:28] Speaker 02: I'm confused, because when you were talking about jurisdiction, you agreed that your ANDA, I'm going to get the party throwing again, I guess. [00:12:40] Speaker 02: Did you file the ANDA? [00:12:41] Speaker 02: Yes. [00:12:42] Speaker 02: OK. [00:12:42] Speaker 02: Your ANDA was an act of infringement. [00:12:45] Speaker 03: Under the 198 patent, which has expired. [00:12:49] Speaker 03: That was a separate action. [00:12:50] Speaker 02: So why do we have, if we don't have jurisdiction under ANDA over the 610, how do we have jurisdiction over the 610? [00:12:57] Speaker 02: Because what... I thought your argument was because it was then listed and you updated your certification that that brought it into the ANDA. [00:13:08] Speaker 03: What it does is it makes it a common set of operative fact under [00:13:12] Speaker 03: 1367. [00:13:13] Speaker 02: When you're getting to 15D, I think they're arguing differently. [00:13:17] Speaker 03: I think they are too. [00:13:18] Speaker 02: So if we disagree with you that it brings it in under 15D, but that it becomes part of the ANDA, then your argument that there's no direct act of infringement falls away because we have ANDA. [00:13:32] Speaker 03: You have jurisdiction, but the act of infringement for jurisdictional purposes is the filing of the ANDA. [00:13:40] Speaker 03: That doesn't mean [00:13:41] Speaker 03: that that's an act of infringement. [00:13:43] Speaker 03: They still have to show infringement under some section 271 A, B, or C. Not under ANDA. [00:13:49] Speaker 03: Yes, I think they do. [00:13:50] Speaker 03: That's this court's jurisdiction. [00:13:52] Speaker 02: Is it the filing of the ANDA, the act of infringement? [00:13:55] Speaker 02: So we file an ANDA, they don't have to show that they're selling the drug because they usually aren't selling the drug. [00:14:02] Speaker 03: That's correct. [00:14:03] Speaker 03: What the analysis does is it said hypothetically, would this label induce infringement if [00:14:09] Speaker 03: the drug were to be sold. [00:14:10] Speaker 03: But here, we know that the same label has been on the market for six years. [00:14:14] Speaker 03: And nobody has practiced the claims. [00:14:16] Speaker 03: And so just like Warner Lambert, the rate of potential infringement is so low that it's a matter of what. [00:14:22] Speaker 01: Warner Lambert was an off-label case. [00:14:24] Speaker 01: And one could argue that there's a distinction to be made here between an on-label and an off-label. [00:14:29] Speaker 01: And secondly, and so you can respond to both points at once, I assume you're familiar with our recent opinion in Sanofi, which dealt with an analogous issue. [00:14:38] Speaker 01: And they're right. [00:14:39] Speaker 01: I mean, Sanofi, part of what the majority relied on there was the 77% use. [00:14:44] Speaker 01: And they relied heavily on that. [00:14:46] Speaker 01: On the other hand, they go on to cite Eli Lilly as saying that, depending on the clarity of the drug's label instructions, the decision to continue seeking FDA approval of those instructions may be sufficient evidence of specific intent to induce infringement. [00:15:02] Speaker 01: So they seem to rely more heavily on what the label says. [00:15:05] Speaker 03: Right. [00:15:06] Speaker 03: we believe that, effectively, that Warner-Lambert and Sanofi are goalposts. [00:15:10] Speaker 03: Where the majority of the sales, as in Sanofi, are, you know, pursuant to the label, it makes economic sense that the engineering company intends for physicians to practice according to that, you know, level of sales. [00:15:24] Speaker 03: But as in Warner-Lambert, where the purported sales are so low, it makes no, it defies common sense, I think this court said, to say that somebody would intend to induce aberrant behavior. [00:15:34] Speaker 01: And I think that's the distinction we see, is that when we're far below the two- But don't you think our cases like Eli Lilly sort of say, if you're talking about an unlabeled case and the label is clear enough and explicitly, whether it recommends or instructs or whatever word we want to use, then that is sufficient? [00:15:51] Speaker 03: It all comes down to the circumstances. [00:15:53] Speaker 02: Hypothetically, I know you have quibbles about the clarity of this label, but if we read this label to instruct [00:16:01] Speaker 02: lower dosage based upon the genotype testing, isn't that enough for inducement? [00:16:07] Speaker 03: No, because there's a separate element that says you have to recommend genotyping. [00:16:11] Speaker 03: That's a separate step. [00:16:12] Speaker 02: The district court cited... No, but my hypothetical said we read this label as requiring genotypes. [00:16:18] Speaker 03: Oh, I'm sorry. [00:16:20] Speaker 03: I'm not sure, because my view is that under this court's case law, the question is whether it instructs the direct infringer. [00:16:27] Speaker 03: And so the salient inquiry is whether the physician regards it as a recommendation to do genotyping, not whether a judge reads it as such. [00:16:34] Speaker 01: So you just say that's evidence to show that there was no intent of the physicians, if there's no evidence of physicians doing it. [00:16:41] Speaker 01: What you have here, though, are fact-bindings by the district court. [00:16:45] Speaker 01: And we've got to defer to those fact-bindings. [00:16:47] Speaker 01: That's not to say if he had read the label differently or the experts had been differently. [00:16:52] Speaker 01: But he relied on explicit expert testimony. [00:16:55] Speaker 01: He credits some experts over others. [00:16:57] Speaker 03: if I may address that question. [00:16:58] Speaker 03: There was, that's exactly the problem. [00:17:00] Speaker 03: The court did not cite any expert testimony, any physician testimony, on whether the label recommends genotyping. [00:17:07] Speaker 03: He cited only the label language that says, laboratory tests to identify CYP2D6 PMs exist. [00:17:13] Speaker 03: Okay? [00:17:15] Speaker 03: In fact, all of the physicians tested... I know I'm running you over your time, if you don't mind. [00:17:19] Speaker 00: That's okay. [00:17:19] Speaker 02: Is there... What kind of laboratory tests are there to identify [00:17:27] Speaker 02: However you say that, besides genotype testing. [00:17:33] Speaker 03: I think that there are only genotyping testing. [00:17:36] Speaker 03: But there's two salient questions. [00:17:39] Speaker 03: The first is whether it refers to genotyping. [00:17:41] Speaker 02: The second... So you agree that the only way to identify this is through genotype testing. [00:17:47] Speaker 02: And the label says, use laboratory tests to identify this. [00:17:51] Speaker 03: It doesn't say use laboratory tests. [00:17:53] Speaker 03: It says they're available. [00:17:56] Speaker 03: All of the expert physicians, Your Honor, all of them testify that it was not a recommendation. [00:18:00] Speaker 03: You also have Vanda's own Dr. Wyden, who wrote an article saying that there are no recommendations in the label to test variants for CYP2D6. [00:18:11] Speaker 03: Now, that language from a published article outside of the context of litigation, which parallels the infringed inquiry, alone shows clear error. [00:18:19] Speaker 03: Because the question isn't whether a judge views it as recommending. [00:18:22] Speaker 03: The question is whether the physicians view it as recommending. [00:18:26] Speaker 03: There was a wealth of other evidence. [00:18:27] Speaker 03: It's detailed in our briefs, and I'm happy to continue on. [00:18:32] Speaker 03: That evidence, so Dr. Retain testified that it wasn't a recommendation. [00:18:35] Speaker 03: That's at A7043. [00:18:36] Speaker 03: Dr. Kay also testified that the language at issue, that tests are available, is not a recommendation. [00:18:42] Speaker 03: That's at 7019. [00:18:44] Speaker 03: And Vanda's own expert, Dr. Prescorn, conceded that this was- Maybe we'll talk about apples and oranges. [00:18:50] Speaker 01: What the district court relied on, I mean, we're parsing the language in the label. [00:18:54] Speaker 01: But the district court relied on the language should have their dose reduced by half. [00:19:02] Speaker 03: That's for a separate step. [00:19:03] Speaker 03: The step of recommending genotyping, the district court solely relied on the language in the label and did not cite any testimony from any physician and none existed. [00:19:13] Speaker 02: How can you lead those out of context? [00:19:15] Speaker 02: Because the prior step is dependent upon identifying that specific [00:19:24] Speaker 02: Genotype. [00:19:26] Speaker 02: Dosage adjustments for patients taking this who are poor metabolizers of whatever that, however you're saying that, should be reduced by half. [00:19:35] Speaker 02: And the only way to identify the people that have that are by doing genotype testing. [00:19:40] Speaker 02: So if the instruction is reduce it by half for these people, how else are you going to know to reduce it by half unless you do the genotype test? [00:19:48] Speaker 03: Well, the two answers to that are, first of all, it's informative. [00:19:51] Speaker 03: It's not a recommendation. [00:19:53] Speaker 03: There's another organization called the PharmaGKB that summarizes all the drug labels information about genetics. [00:19:58] Speaker 03: They can concur that this label does not recommend genotyping. [00:20:02] Speaker 03: There are other labels that the FDA specifies when dosing CYP2D6 genotyping is recommended. [00:20:08] Speaker 03: For instance, the tetrabenazine label says patients should be genotyped. [00:20:13] Speaker 02: So you're arguing the district court's decision on this was clear error? [00:20:15] Speaker 03: Clear error because two reasons. [00:20:17] Speaker 03: First of all, it did not account for it. [00:20:20] Speaker 03: It did not look at the proper prism, which is [00:20:23] Speaker 03: would a physician view it as a recommendation, the direct infringer. [00:20:26] Speaker 03: Secondly, the evidence overwhelmingly says, and we're talking about information that literally parallels the infringement inquiry, there is evidence, a wealth of evidence saying that the statement at issue is not a recommendation of genotype. [00:20:40] Speaker 03: The PharmaGKB, Dr. Wyden's article, there was another blinded article that is at A698586, Vanda's own statement to the EMA where they said, [00:20:51] Speaker 03: that FNAPT has been used for years in the United States, quote, in the absence of genotyping. [00:20:57] Speaker 03: And we asked Dr. Presquorn, and he conceded. [00:21:00] Speaker 01: A fair reading of that admission is that they did have one expert that said that laboratory tests available refers only to genotyping. [00:21:07] Speaker 03: They had that. [00:21:08] Speaker 03: They never had anyone say that laboratory tests are available is a recommendation to genotype. [00:21:15] Speaker 03: Dr. Presquorn was their expert. [00:21:16] Speaker 03: He conceded that that is not a recommendation. [00:21:18] Speaker 03: He conceded that it was merely informative. [00:21:20] Speaker 03: He also conceded that it was a fair reading of Vanda's statement to the EMA that the label does not recommend genotyping. [00:21:28] Speaker 02: Am I missing the context of this? [00:21:29] Speaker 02: I thought this drug was not allowed on the market or had to be taken off because for people with this genotype, it killed them. [00:21:38] Speaker 03: No. [00:21:39] Speaker 02: You're saying that the people with this genotype don't have susceptibility to cardiac arrest and that's why it wasn't approved again until [00:21:48] Speaker 03: I don't think it's people. [00:21:49] Speaker 02: These labels were put on? [00:21:50] Speaker 03: I don't think it's limited to people with this genotype. [00:21:52] Speaker 03: There's just a general concern that the drug may prolong the QTC interval. [00:21:59] Speaker 03: But I don't think that it was taken off the market because of genotyping. [00:22:04] Speaker 02: But why wasn't it on the market? [00:22:06] Speaker 02: Why wasn't it on the market? [00:22:07] Speaker 03: I think it wasn't up. [00:22:08] Speaker 03: Its approval was delayed, I think, because of. [00:22:11] Speaker 02: Because people died when they took it. [00:22:13] Speaker 03: I don't know if they. [00:22:14] Speaker 02: They had cardiac arrest. [00:22:16] Speaker 03: I don't know that, Your Honor. [00:22:18] Speaker 02: The testimony at trial was... Okay, I mean, if that's your view of the record. [00:22:24] Speaker 01: Well, if the label instructs that you should give a lower dosage to people who have this, and the only way to do it is through... The only way to discover whether or not you have this or not is genotyping, right? [00:22:37] Speaker 01: Are there other ways that are available? [00:22:40] Speaker 03: Yes, you can phenotype somebody. [00:22:41] Speaker 01: You can... Are there laboratory tests? [00:22:44] Speaker 01: I mean, I know you can phenotype, but, I mean, [00:22:46] Speaker 03: So Mayo would be a laboratory test to phenotype. [00:22:50] Speaker 03: So in Mayo, they looked at the metabolite in the blood, and that's phenotyping. [00:22:55] Speaker 03: Regardless of whether I have genotypically poor metabolizer status, if I have a certain metabolite level, that'll show that I'm metabolizing the drug at a certain level. [00:23:03] Speaker 03: It could be because I'm a smoker. [00:23:04] Speaker 03: It could be because I'm taking a concomitant drug that interferes with the ability to metabolize the drug. [00:23:10] Speaker 03: So you can phenotype somebody with looking at their drug levels phenotypically. [00:23:15] Speaker 01: That shows how you metabolize the drug physically as opposed to your genetic predisposition to doing so, which is... So what is your argument that if the laboratory tests that nobody is saying that's a recommendation, so where does that take you in the inducement analysis? [00:23:29] Speaker 03: That means that A, that they have to prove every element, and they have to prove that the label recommends every element. [00:23:37] Speaker 03: of the steps of the method, and they have no evidence of inducement, so that would be A. B, they have no evidence because there's no genome. [00:23:44] Speaker 03: There's no recommendation to genotype as, again, the corroborative evidence from outside of the litigation, which is their own advisory board member saying it doesn't recommend the pharma GKB, the fact that it's not reimbursed by Medicare, it's deemed investigatory, not necessary. [00:24:02] Speaker 03: All of that evidence shows clear. [00:24:04] Speaker 03: In addition, it corroborates the lack of intent. [00:24:07] Speaker 03: Right? [00:24:08] Speaker 03: I mean, it corroborates that Roxanne doesn't subjectively intend for people to engage in what's basically aberrant behavior, as Dr. Alva indicated. [00:24:16] Speaker 03: And remember, at the end, there are only evidence. [00:24:19] Speaker 01: He indicated it was aberrant behavior. [00:24:20] Speaker 01: They used genotyping. [00:24:22] Speaker 03: To genotype and then put the dose within the level that's specified in the claims. [00:24:27] Speaker 03: Dr. Alva gave the same dose to the poor metabolizer that he genotyped as the normal metabolizer. [00:24:34] Speaker 03: And the claims, as Vanna concedes, require differential dosing based on genotype. [00:24:39] Speaker 01: I thought at least there was one person that was identified by Dr. Alva where it was that he at some point, Easton, I know you argue that it was a year and a half later, but that he prescribed he was taking it at 12 and he upped his dosage to 16 because he wasn't identified through genotyping as being a P, whatever. [00:25:01] Speaker 03: Right. [00:25:01] Speaker 01: And he also... So there is a person that he used that he prescribed based on genotyping, right? [00:25:06] Speaker 03: Wasn't based on genotyping. [00:25:08] Speaker 03: And the point is, he dosed the poor metabolizer and the normal metabolizer at the same rate. [00:25:14] Speaker 03: That's at A7000. [00:25:15] Speaker 01: And so... For a while, right? [00:25:19] Speaker 01: Is that what you're saying? [00:25:20] Speaker 03: No. [00:25:20] Speaker 03: The poor metabolizer always got 24 milligrams. [00:25:24] Speaker 03: That's at A7000. [00:25:25] Speaker 03: The normal metabolizer was at [00:25:31] Speaker 03: lower rate, and then was elevated based on his symptomology, he needed a higher dose. [00:25:36] Speaker 03: And that was, our view is not an active direct infringement. [00:25:45] Speaker 03: It wasn't predicated on the fact that he was a normal tantalizer. [00:25:47] Speaker 03: It was predicated on the need to dose or titrate. [00:25:51] Speaker 02: Was there any genotyping done on that patient? [00:25:54] Speaker 02: Sorry? [00:25:55] Speaker 02: Was genotyping done on that patient? [00:25:59] Speaker 03: Yes. [00:25:59] Speaker 03: And it also bears emphasis on the [00:26:01] Speaker 02: Do you have any, is there any evidence in the record of how, what percentage of the population has this? [00:26:09] Speaker 03: I think the label says around 6%. [00:26:11] Speaker 03: It depends on your ethnicity. [00:26:16] Speaker 03: Okay. [00:26:17] Speaker 03: Um, but you know, in our view, there's a failure proof on direct infringement. [00:26:24] Speaker 03: They didn't prove that, uh, under the appropriate construction of the claims that, that a poor metabolizer has ever been given a dose. [00:26:30] Speaker 03: of 12 milligrams a day or less. [00:26:32] Speaker 03: And the wear-in clause specifies that it's the poor metabolizer who we're concerned about. [00:26:38] Speaker 03: Because the wear-in clause says, wear-in, the risk of QTC prolongation for the poor metabolizer is lower because they got a lower dose. [00:26:46] Speaker 03: And if no poor metabolizer has ever gotten that dose, then the wear-in clause can't work. [00:26:51] Speaker 03: And they haven't proven any instance of direct infringement. [00:26:53] Speaker 03: And as in Takeda, that, oh, I'm sorry, as in Takeda, [00:26:58] Speaker 03: You wouldn't need to reach the question of inducement. [00:27:00] Speaker 03: There's just insufficient evidence of direct infringement. [00:27:04] Speaker 03: Thank you. [00:27:09] Speaker 00: Good morning. [00:27:10] Speaker 00: May it please the court? [00:27:12] Speaker 00: I'll start with infringement since that's perhaps fresh in our minds. [00:27:16] Speaker 00: So the district court did make fact findings. [00:27:20] Speaker 00: And the question for this court is whether those are clearly erroneous. [00:27:23] Speaker 00: The district court found that poor metabolizers in the label [00:27:28] Speaker 00: refers to genotypic poor metabolizers. [00:27:30] Speaker 00: In other words, people who have these genetic mutations. [00:27:34] Speaker 00: The district court found that the label is the recommendation to reduce the doses for those genotypic poor metabolizers. [00:27:42] Speaker 01: Well, you heard your friend. [00:27:43] Speaker 01: I mean, didn't he say that all the evidence that nobody testified that this was a recommendation? [00:27:49] Speaker 01: That the laboratory test sentence, laboratory tests are available, is not a recommendation. [00:27:54] Speaker 00: I think there's some fine wording here going on, Your Honor. [00:27:57] Speaker 00: OK. [00:27:57] Speaker 00: are Roxanne, I'll call them Roxanne because that's what they were in the district court. [00:28:01] Speaker 00: Roxanne's expert conceded on the stand. [00:28:04] Speaker 01: Which, can you name the expert? [00:28:06] Speaker 00: Yes, Dr. Retain, right? [00:28:08] Speaker 00: Two things, that the laboratory tests referred to are genotyping tests and that the label is a recommendation to reduce the dosage for people who have that genotype. [00:28:19] Speaker 00: Now, what the argument that I think I'm hearing is that even though the label recommends [00:28:27] Speaker 00: reducing the dosage for people with this genotype. [00:28:30] Speaker 00: It doesn't actually recommend using a genotyping test to identify those people. [00:28:37] Speaker 00: That because it uses the words is available. [00:28:40] Speaker 00: And what I'm, I think I'm hearing is an argument that has teased this apart to the point of destruction of all meaning, right? [00:28:47] Speaker 00: The term in the label, laboratory tests are available to identify poor metabolizers immediately follows language [00:28:56] Speaker 00: Talking about poor metabolizers being those who are genotypically incapable of metabolizing this material. [00:29:03] Speaker 00: It clearly in context refers to is telling the physician, if you want to identify the population for whom we are recommending a reduced dose, you can order a commercially available test. [00:29:16] Speaker 00: As the district court found and as the experts agreed, the only such test that exists commercially available is the genotyping test. [00:29:23] Speaker 00: And I think what we have here is a semantic argument [00:29:27] Speaker 00: that even though the label recommends reducing the dose genetic port metabolizers and even though it because it's it merely uses the words tests are available that that is not a quote recommendation and therefore there is a failure of proof uh... we would submit that that is uh... arm a an argument that only a lawyer could love that and in in the question for this court is one of clear error [00:29:53] Speaker 00: The district court reviewed this. [00:29:55] Speaker 00: It's a matter of fact. [00:29:56] Speaker 01: So if genotyping tests are what everybody is using to do this, why is there so little proof, if any, that there's any direct infringement here? [00:30:05] Speaker 01: I know you say, well, this label was out there for six years. [00:30:09] Speaker 00: I'm happy to address that, Your Honor. [00:30:11] Speaker 00: In our view, the entire issue of whether there be proof that people have used this out in the real world with the patent-owners product is not something that's legally required. [00:30:22] Speaker 00: And we didn't set out when we were putting our proofs together to address that. [00:30:25] Speaker 00: This is an under case. [00:30:27] Speaker 00: The way we look at infringement is we look at what the label says and we say, what would happen? [00:30:31] Speaker 00: What does this label instruct people? [00:30:33] Speaker 00: I don't have to prove direct infringement. [00:30:36] Speaker 04: In other words, does the label authorize that activity? [00:30:41] Speaker 04: But if it's an under case, then you don't need to prove infringement, right? [00:30:47] Speaker 00: it exactly what it is it is a hatchback to the case and let me come to this wasn't patented uh... at the time the india was fine at that that's absolutely correct but the a and a d a was then amended factors amended a number of times after the law uh... after the patent issue uh... and it was amended ultimately to include a paragraph four certification against this patent and under the law of this court that is absolutely [00:31:17] Speaker 00: an act of infringement under 271E2. [00:31:20] Speaker 00: And therefore, it just brings the case into the under-context and all the normal under-law applies. [00:31:25] Speaker 00: And this Court has been unequivocal. [00:31:29] Speaker 00: And the strongest statement is in the Fearing case, Fearing v. Watson at 764F1382, and specifically at 1390-91, where the Court says repeatedly that our precedent, I'll just pick one statement, [00:31:46] Speaker 00: Our own precedent conclusively establishes that sections 271E2 and 4 require consideration of the amended ender. [00:31:54] Speaker 00: And there are a number of similar statements like that. [00:31:57] Speaker 00: So following the law of this court, it is undoubted that really in our view can be no doubt that there was an active infringement under 271E2, certainly no later than the time during the pendency of the lawsuit when they amended. [00:32:12] Speaker 00: to include a paragraph for certification. [00:32:15] Speaker 01: But when we're looking at inducement, cases have, most recently, Sanofi referred to the fact. [00:32:21] Speaker 01: Because whether you say it's a lawyer's argument or whatever, there's been testimony and we're struggling here to conclude how clear the label is. [00:32:30] Speaker 01: So as in Sanofi, there was a clarity problem or a clarity issue, and they relied on the fact that in 77% of the cases, this was being applied. [00:32:39] Speaker 01: So it's probative of inducement, is it not? [00:32:42] Speaker 00: It could be under some circumstances, Your Honor. [00:32:44] Speaker 00: I wouldn't say that it's always probative. [00:32:45] Speaker 00: I would say there's a quartet of cases of this Court, Sanofi being the last one, that lay out the law for circumstances like this. [00:32:54] Speaker 00: And those cases are AstraZeneca v. Apotex from 2010, Takeda from 2015, Eli Lilly v. Teva Perentoril from January of this year, and most recently Sanofi. [00:33:09] Speaker 00: And what they say [00:33:10] Speaker 00: is we look at the label language, and if the label instructs, recommends, promotes, or encourages the practice of the method, then that's an infringement under 271E2. [00:33:24] Speaker 00: Now, in Eli Lilly, there is a specific, from January of this year, there is a specific statement that we have not required, we the court, has not required evidence of prevalence of the induced behavior, the infringement. [00:33:39] Speaker 00: and that is an actual absolutely accurate statement of the law what happened here we in fact called doctor alpha primarily a trial for the reason that uh... of showing that people do genotype argument was made below nobody cheetah types we called up to alpha who testified that he had genotype over about a four-year period some three hundred patients uh... since doctor alpha was there we said also have you practiced the method and he said yes i have but we weren't doing that to try and prove prevalence not [00:34:09] Speaker 00: Not necessarily for the 300 cases, but we wanted to, since he was there, to at least show that he was following the method with at least some patients. [00:34:19] Speaker 00: But we didn't set out to prove, nor is there evidence below, I suggest, of overall prevalence of the method. [00:34:27] Speaker 00: What we have is the happenstance that one doctor who came along said he had practiced the method, and the district court so found. [00:34:33] Speaker 04: Why isn't claim one invalid from the 101 [00:34:38] Speaker 04: according to Mayo? [00:34:40] Speaker 00: Because I would agree, or well, my view is that it's a method of treatment, that Mayo specifically says that methods of treatment are not within the ambit of what it's talking about. [00:34:53] Speaker 00: It is a method of treating schizophrenia wherein you identify the population, the people to be treated and divide them into two groups, and that [00:35:04] Speaker 00: is it it fails both steps of in our view it fails both steps of the alice test that it is not uh... directed to a law of nature as this court found itself direct the uh... there is a big difference between the claim that we are saying that we we believe that the district court was wrong and that in fact this this claim involves the application of three [00:35:30] Speaker 00: principles that could be characterized as laws of nature if you wanted to try to apply that. [00:35:35] Speaker 00: But there are three of them, not one. [00:35:37] Speaker 00: It's not directed to a law of nature. [00:35:40] Speaker 00: It involves the application. [00:35:41] Speaker 01: That's because it has the dosing required. [00:35:43] Speaker 01: So you agree if this patent ended where you just said that you identify who's got this PM and use a test to do that, that that would be insufficient. [00:35:54] Speaker 01: That would be a male case, right? [00:35:56] Speaker 00: i actually don't agree with that you're on a bit but i because i think that what is going on is that this uh... we have and not an issue that this court need resolve here but we have a situation with this patent where it involves the intersection of three separate use of laws of nature and that that then leads us to a place where we could have a very elaborate debate as to whether that is or isn't claim that's quote directed to a law of nature want to take an action that utilizes law of nature i'm sorry [00:36:25] Speaker 04: Every action utilizes a law of nature. [00:36:28] Speaker 04: 100%, Your Honor, and in our view, the 101... If you're treating pain with aspirin, the aspirin interacts with whatever receptor it does through a law of nature. [00:36:41] Speaker 04: That is exactly... That's not ineligible. [00:36:43] Speaker 04: At least it wasn't. [00:36:44] Speaker 00: That's exactly how we view this. [00:36:46] Speaker 00: And to come back to the Chief Judge's question, we think, though, that turning to the second step of ALICE, that the dosing absolutely [00:36:54] Speaker 00: is a practical application of this that would confer patentability. [00:36:58] Speaker 01: And why is that not routine? [00:37:00] Speaker 01: I mean, there's a debate on this as to whether or not it's routine. [00:37:04] Speaker 01: I know the district court said it wasn't routine, but there's not that much analysis there. [00:37:08] Speaker 00: Because I think, Your Honor, that the right question is not whether dosing of any drug to any patient or patient population is routine. [00:37:14] Speaker 00: It's whether the dosing of this required by this claim is routine. [00:37:20] Speaker 00: Here, nobody had ever done this. [00:37:22] Speaker 00: right? [00:37:23] Speaker 00: And in fact, to Judge Hsu's question... Does what? [00:37:25] Speaker 01: Now, what are you referring to when you say nobody had ever done this? [00:37:28] Speaker 01: Nobody cut the dosing in half? [00:37:29] Speaker 01: I mean, what this patent does is cut the dosing. [00:37:32] Speaker 00: Nobody had ever reduced the QT risk, as far as we know for any drug, but certainly for eloperidone, by cutting the dose in half. [00:37:41] Speaker 00: And in order to understand why this invention would work, you have first of all to learn a very important fact, which is one of the things that the patent specification teaches the world, which is [00:37:52] Speaker 00: that there is a major difference when you look at the two metabolites, which are called P-88 and P-95. [00:37:59] Speaker 00: It turns out, and the inventors of this patent were the ones who found this, that P-88 has the characteristic that causes QT prolongation, and P-95 does not. [00:38:11] Speaker 04: But you're dealing now with Alice Step 2. [00:38:14] Speaker 04: Yes. [00:38:15] Speaker 04: But you wouldn't get to Alice Step 2. [00:38:17] Speaker 04: You think it's not claiming a law of nature. [00:38:21] Speaker 00: Your Honor. [00:38:22] Speaker 00: we vanda think that it's not that claim that is directed to a law of nature because because it is a claim that involves the application of three separate laws of nature and that is a legal matter that is not the same as a claim that is directed to a law of nature [00:38:38] Speaker 01: But not because it's a specific treatment? [00:38:42] Speaker 01: You were talking before about this is the method of treatment. [00:38:46] Speaker 01: That's not your answer. [00:38:47] Speaker 01: So you think even the method of treatment puts it in a step two analysis? [00:38:51] Speaker 00: I think that, Your Honor, that the step two analysis does involve the method of treatment, that it is about the specific dosage recommendations, which are determined based on the experimental work described in the patent, and that that is what causes it to pass step two. [00:39:07] Speaker 00: I also think, though the district court did not agree with us on this, that it passes step one as well, so that it would pass both steps. [00:39:17] Speaker 04: In effect, it fails step one in that it's not a law of nature. [00:39:21] Speaker 00: That's correct, in our view, Your Honor. [00:39:23] Speaker 01: But not because it's a treatment. [00:39:27] Speaker 01: Not because it includes the dosing requirements. [00:39:31] Speaker 00: That's right, Your Honor. [00:39:31] Speaker 00: In our view, the inclusion of the dosing requirements is relevant to step two of the ALICE test. [00:39:36] Speaker 00: uh... and does precisely part of the house again briefly i'm sorry to repeat why fields uh... why it is not routine here's the reason that when you give someone in the paradigm their body converts it into two different metabolites one of them is called p eighty eight one of them is called p ninety five now before the work that's described in this patent nobody knew [00:40:06] Speaker 00: P95 turns out to be approximately 10,000 times less potent in terms of causing the cardiac side effect, the QT prolongation. [00:40:16] Speaker 00: If you didn't know that, you would have no reason to adjust the dosing because it would be, some people have analogized it to moving deck chairs around on the Titanic. [00:40:26] Speaker 00: If both of the metabolites equally cause QT prolongation, the fact that somebody has more of one or less of the other doesn't matter. [00:40:35] Speaker 00: right? [00:40:35] Speaker 00: They've got the same amount of both of them in their body, and they're going to have the same amount of QT prolongation. [00:40:40] Speaker 00: And what these inventors did, and this is precisely what's referred to in the patent and what the district court referred to when referencing intermediate biomarkers, was they looked at the ratio of the two metabolites, and they correlated that to the genetic polymorphisms. [00:40:59] Speaker 00: And they, from that, they for the first time were able to understand that the [00:41:04] Speaker 00: The effect of the polymorphisms was to expose you to a greater QT risk, and that you could mitigate that by reducing the dose for people who had these polymorphisms. [00:41:14] Speaker 00: That was not known anywhere. [00:41:16] Speaker 00: And therefore, it is not routine in any sense of the word. [00:41:21] Speaker 00: And to Judge Hughes' question, by the way, the patent, Judge Hughes says that about 15% of the population have polymorphisms like this. [00:41:29] Speaker 00: The label says that it varies depending on what ethnic group you're from. [00:41:34] Speaker 00: but that for Caucasians I think it's something like 8 to 11 percent. [00:41:38] Speaker 00: So it's a minority but a non-trivial amount of the overall population. [00:41:44] Speaker 00: And what they, and Judge Hughes to your questions earlier, it was absolutely as the district court found that the thing that stood in the way of this drug being approved when it was owned by Novartis was they could not find a way to overcome this side effect and FDA [00:42:01] Speaker 00: is very reluctant to approve things that have this side effect and so it was not until the inventors were able to come up with this that they went back and got the approval and as we pointed out in the brief Novartis paid, they sold the product for an amount and bought it back for 400 times that amount which we thought was extremely strong evidence and the district court found it was strong evidence that this was anything but routine and so [00:42:31] Speaker 00: That's the way the landscape looks to us on the one-on-one issue. [00:42:34] Speaker 00: It's a method of treatment. [00:42:36] Speaker 00: We could debate. [00:42:37] Speaker 00: We don't think this court needs to engage on the step one question. [00:42:42] Speaker 00: The simpler way forward is simply to say, as the district court found, it certainly passes step two. [00:42:47] Speaker 00: It wasn't routine. [00:42:48] Speaker 00: The dosing absolutely is a concrete application of this. [00:42:52] Speaker 00: These inventors, in the words that Judge Bryson used in the, I guess, the Myriad case and have been repeated a lot since, as the people who discovered [00:43:01] Speaker 00: this effect they were in an excellent position to write method claims and that's exactly what we did here and the uh... uh... so what we have then is a method of treatment that enabled this medication to come to market uh... and serve a patient population that needs it uh... which could be done before and that that is we would say what i mean it it's excellent evidence of [00:43:23] Speaker 00: The fact that step two was anything but routine. [00:43:26] Speaker 04: Has this label changed at any time in relation to when the 610 certification was made? [00:43:36] Speaker 00: It has not changed. [00:43:37] Speaker 00: The certification was made, Your Honor, in May of 2015. [00:43:40] Speaker 00: It has not changed since then. [00:43:43] Speaker 00: The label has been the same, I believe, at all material times for purposes of this litigation. [00:43:49] Speaker 01: Well, for six years, right? [00:43:51] Speaker 01: About six years? [00:43:52] Speaker 00: It wasn't the same. [00:43:54] Speaker 00: When it was initially approved, the language was somewhat different. [00:43:59] Speaker 00: And then the FDA asked that this language, a more specific form of language about reducing the dosage by half for metabolizers be added, and that was added. [00:44:10] Speaker 00: I think that that precedes any involvement by Westwood or Roxanne. [00:44:16] Speaker 00: But that happened during the course of the period of time that Vander was selling the drug. [00:44:23] Speaker 00: And if there are other questions, I would be more than happy to answer them. [00:44:26] Speaker 00: Thank you. [00:44:30] Speaker 01: Three minutes. [00:44:36] Speaker 03: On the question of direct infringement, I think that counsel made an interesting point. [00:44:41] Speaker 03: He said one of the reasons that the claims are non-conventional is that they had solved the issue of reducing the risk of QT's prolongation for these poor metabolizers. [00:44:49] Speaker 03: That's the wherein clause. [00:44:51] Speaker 03: That proves that for direct infringement, you have to reduce the dose to a more metabolizer. [00:44:56] Speaker 03: And they haven't shown that anyone's ever done that. [00:44:59] Speaker 03: Now, their suggestion that they don't have to, I think, is misguided. [00:45:02] Speaker 03: As this court found in Lilly, the Supreme Court in Akamai said that, and Lilly is in the Hatch-Waxman context, of course, liability for induced infringement under Section 271B must be predicated on direct infringement. [00:45:15] Speaker 01: That obviously wasn't in the end the Hatch-Waxman context. [00:45:19] Speaker 03: Akamai was not, but I'm saying Lilly [00:45:21] Speaker 03: said in the Hatch-Waxman context, citing Akamai that for inducement, there must be evidence of direct infringement. [00:45:28] Speaker 03: And here there was a failure of proof. [00:45:31] Speaker 03: Council effectively conceded they didn't set out to prove that there was direct infringement and that's a failure of proof. [00:45:37] Speaker 03: Just like in Takeda, the court doesn't have to even get to the issue of inducement. [00:45:41] Speaker 03: Now on inducement, I don't think it is a matter of semantics. [00:45:45] Speaker 03: When the language has been in the label for six years and [00:45:48] Speaker 03: Physicians say they do not regard it as a recommendation. [00:45:51] Speaker 03: That's not semantic. [00:45:53] Speaker 03: That is action or inaction. [00:45:56] Speaker 03: And what I think is pertinent is the reason that people aren't doing it is it's not reimbursed. [00:46:02] Speaker 03: It's not a recommendation. [00:46:03] Speaker 03: They'd be violating the standard of care. [00:46:05] Speaker 03: If the standard of care truly was that the drug should only be given after genotyping and the label recommends genotyping, they'd be violating the standard of care when they don't do that. [00:46:13] Speaker 03: And that's why Dr. Retain testified without rebuttal. [00:46:17] Speaker 03: that people simply aren't genotyping. [00:46:20] Speaker 03: It's not a matter of semantics when their own advisory board member says the label contains no recommendations. [00:46:26] Speaker 01: But didn't Mr. Gruberidge tell us about Dr. Alva saying he had done this genotyping 300 times? [00:46:32] Speaker 03: But only four times for patients that he had treated with iloperidone. [00:46:37] Speaker 03: So he may make it a practice to genotype all of his patients. [00:46:40] Speaker 03: I don't know. [00:46:41] Speaker 03: But the point is all of the physicians that testified [00:46:47] Speaker 03: Dr. K, Dr. Retain, Dr. Prescorn, all of them said they had never seen the method practiced. [00:46:53] Speaker 03: They had never seen anybody genotyped on isla peridone. [00:46:55] Speaker 03: Those citations are in our brief, and I'm happy to supplement that, but simply it's not being practiced. [00:47:00] Speaker 03: And our concern is, affirming here, simply because of the subjective views of a judge as to what a label recommends, when there's no evidence that physicians view it as a recommendation, would be dangerous, in the sense that you would have [00:47:15] Speaker 03: extension of the patent monopoly of the patent on the compound and the method of use, because you could always find a subpopulation that should be treated slightly differently and amend your label and then patent it. [00:47:26] Speaker 03: And that's not what Hatch-Waxman is for. [00:47:27] Speaker 03: Hatch-Waxman is to allow the entry of generic drugs as soon as the pioneering patents expire. [00:47:34] Speaker 03: And, you know, affirm it's here. [00:47:36] Speaker 03: When there's no evidence of direct infringement that anyone's ever practiced the claims as written, we think there was a failure of proof. [00:47:43] Speaker 01: Thank you. [00:47:44] Speaker 01: We thank both sides of cases submitted. [00:47:46] Speaker 01: That concludes our procedure for this morning.