[00:00:00] Speaker 04: Our last case for argument today is 24-1346, Corseptherapeutics versus Teva Pharmaceuticals, Mr. Cannon. [00:00:12] Speaker 00: May I begin? [00:00:12] Speaker 00: Yes. [00:00:15] Speaker 00: May I please record? [00:00:16] Speaker 00: Brian Cannon for Corseptherapeutics. [00:00:19] Speaker 00: Your Honours, Teva chose to copy the exact label with the exact patented infringing doses, but now says, don't worry, we have extrinsic evidence that shows that doctors, it's unlikely that doctors will do what the label tells them to do. [00:00:36] Speaker 00: Hatchwax from precedent does not permit Teva to have it both ways. [00:00:40] Speaker 00: They can't copy the exact label with the exact patented methods and say, don't worry, doctors are not going to follow those methods. [00:00:48] Speaker 00: Once you copy a label, Your Honors, the generic, in this case Teva, is bound by that label. [00:00:54] Speaker 00: The FDA anticipated there would be co-administration of these drugs. [00:00:59] Speaker 00: The invention showed a safe dosage regimen for co-administration of these drugs. [00:01:04] Speaker 00: The label provides the patented method [00:01:06] Speaker 00: And the evidence undisputably shows that in some instances, in the past and in the future, doctors will want to co-administer these drugs for the sickest of patients. [00:01:16] Speaker 04: But not necessarily co-administer them at the claimed dosages. [00:01:20] Speaker 00: Well, Your Honor, the claimed dosages are on the label. [00:01:22] Speaker 04: And I think I would like to- Yes, but that's not what- I didn't ask you if the claimed dosages were on label. [00:01:26] Speaker 04: You've introduced no evidence that anyone has ever administered the CYP3A alongside a 600 or 900 milligram dose of Mifepristone, and that's all you have claimed. [00:01:38] Speaker 04: So for all I know, the co-administration, the only co-administration that you've established was at 300 milligrams, which is not claimed. [00:01:44] Speaker 00: Your Honor, I'd like to respond two ways to that. [00:01:47] Speaker 00: First, under the Vanda precedent, a corset does not have to show instances of past infringement. [00:01:53] Speaker 00: We look at the link. [00:01:54] Speaker 03: Right. [00:01:54] Speaker 03: It doesn't have to. [00:01:56] Speaker 03: But under Genentech and under Vanda, the court may. [00:02:00] Speaker 03: And so once the court looks at all relevant evidence, can it not simply credit the fact that even though the label says one thing, there is no evidence of direct infringement in the past? [00:02:14] Speaker 03: And in weighing that, then conclude that there's no direct infringement. [00:02:21] Speaker 00: Well, Your Honor, [00:02:22] Speaker 00: I think if we start with the label, it has both infringing doses and non-infringing doses. [00:02:27] Speaker 00: And also, a doctor may choose not to co-administer at all. [00:02:30] Speaker 00: Correct. [00:02:30] Speaker 00: This is one of those cases where the pills are sold, and then a doctor makes a prescription. [00:02:35] Speaker 00: The doctor could choose to just prescribe just Mifepristone. [00:02:39] Speaker 00: The doctor could choose to prescribe Mifepristone with the strong inhibitor. [00:02:44] Speaker 00: And the issue on demand is, we do not need to show that all patients must receive co-administration. [00:02:51] Speaker 03: You do not need to show that, but the district court, even under Vanda, can look at all relevant evidence, which is what the district court did here. [00:03:00] Speaker 00: The district court did, Your Honor, but the district court erred in a couple of foundational ways. [00:03:04] Speaker 00: The district court looked at the extrinsic evidence and decided and ruled, as a matter of fact, indisputably co-administration had happened in the past and it will happen in the future. [00:03:14] Speaker 00: But the district court found essentially there was not enough co-administration to meet what we believe the district court applied was a prevalence standard. [00:03:23] Speaker 04: No, the district court did exactly what I just asked you about. [00:03:26] Speaker 04: It expressly said, while co-administration has occurred in the past and may occur in the future, that there's no proof it wasn't occurring at non-infringing level dosages. [00:03:37] Speaker 04: That's what she said. [00:03:39] Speaker 04: Verbatim. [00:03:40] Speaker 04: Well, not verbatim. [00:03:41] Speaker 00: But I understand. [00:03:43] Speaker 00: Your Honor, the issue with proving exact, first of all, under Vanda, we did not have to prove there was exact infringement. [00:03:50] Speaker 01: What about, this is maybe a little bit different than Vanda, in that here there's non-infringing uses right on the label, right? [00:04:00] Speaker 01: And there's been evidence introduced that this [00:04:06] Speaker 01: method hasn't been used or is, I mean, in that circumstance, do we have to do more and go beyond the label? [00:04:16] Speaker 00: It's a great question. [00:04:17] Speaker 00: Can I start with Vanda and then also address the question? [00:04:19] Speaker 00: In Vanda, the issue in Vanda was very, very similar to our case. [00:04:24] Speaker 00: In Vanda, it was a drug, I believe, for schizophrenia. [00:04:28] Speaker 00: And the drug had about 3% to 10% of patients were poor metabolizers of the drug. [00:04:34] Speaker 00: So the drug was sold. [00:04:36] Speaker 00: And on the label, it said, doctors test patients. [00:04:39] Speaker 00: And if the patient is a poor metabolizer, then you do a lower dosage. [00:04:42] Speaker 00: So, in Vanda, there was non-infringing dosages on the label because most patients who received the Vanda drug were not poor metabolizers. [00:04:50] Speaker 00: So, they would receive the drug at the high dosages. [00:04:52] Speaker 00: It was only those 3 to 10 percent of patients in Vanda who were tested, genotypically tested. [00:04:58] Speaker 01: It was determined that there was 3 to 10 percent. [00:05:01] Speaker 00: Right. [00:05:01] Speaker 00: So, for that 3 to 10 percent, they may get the lower doses. [00:05:04] Speaker 00: So, it's similar to our case. [00:05:05] Speaker 00: The majority of Cushing syndrome patients may not [00:05:08] Speaker 00: But there is no percent here. [00:05:10] Speaker 01: There is nothing indicating that anybody would fall within this regimen. [00:05:16] Speaker 01: I mean, I could be wrong. [00:05:18] Speaker 00: Well, in the record, Dr. Adrienne Dobbs was an expert for Teva. [00:05:23] Speaker 00: And at the appendix 1059, 1060, that is the testimony from Dr. Dobbs. [00:05:28] Speaker 00: And she testified that she had approximately five to six Cushing syndrome patients. [00:05:33] Speaker 00: to whom she prescribed methopristone. [00:05:37] Speaker 00: And for about two to three of those patients, she also co-administered a strong CYP3 inhibitor. [00:05:43] Speaker 01: But was it the co-administration at the dosage levels in the claims? [00:05:47] Speaker 00: The exact dosage levels were not set forth by Dr. Dobbs. [00:05:51] Speaker 03: So that's not infringement. [00:05:53] Speaker 03: I mean, the infringement of the claim requires [00:05:57] Speaker 03: a certain dosage. [00:05:59] Speaker 03: So the fact that she testified that you could co-administer isn't sufficient to meet the limitations of this claim. [00:06:07] Speaker 00: But I think, Your Honor, as a Hatch-Waxman case, it's almost like a statistical case. [00:06:12] Speaker 00: We look forward to the future in the hypothetical. [00:06:15] Speaker 00: It's not proving, did it happen in the past? [00:06:17] Speaker 00: Is it likely to happen? [00:06:19] Speaker 00: Is it possible to happen in the future? [00:06:21] Speaker 00: And here, since it's on the label, just like in Vanda, the infringing method of genotypically testing and giving a lower dose is on the label here. [00:06:31] Speaker 04: But if you succeed, [00:06:34] Speaker 04: If we conclude that because it's on the label, you have sufficed under our precedent to meet whatever is necessary to establish this induced infringement concept, what is the consequence then? [00:06:51] Speaker 00: The consequence is that Teva cannot market the drug. [00:06:54] Speaker 00: with this label. [00:06:55] Speaker 00: They could market the drug with a different label. [00:06:57] Speaker 00: They could do a carve out and not include the patented method. [00:07:01] Speaker 00: I think a very bottom line fact is Teva wants this entire label. [00:07:05] Speaker 00: They have chosen to copy the entire label. [00:07:07] Speaker 00: And the Sinovian case we cited speaks to that, which is the generic company does not have to copy the entire label. [00:07:14] Speaker 00: They could carve out [00:07:15] Speaker 00: the patented method but here they want to have it both ways. [00:07:18] Speaker 00: They want to have the full label with the patented dosages but also say don't worry no one's going to use it. [00:07:26] Speaker 04: So here's the deal. [00:07:27] Speaker 04: The evidence here establishes that [00:07:30] Speaker 04: If anybody uses this at the patented dosages, it seems to be very few people. [00:07:35] Speaker 04: Number one, it hasn't been happening. [00:07:37] Speaker 04: Number two, there's a new drug that might obviate the need for co-administering these things altogether, but whatever. [00:07:44] Speaker 04: So if there's no doubt that Mifepristone has lots of non-infringing uses, if there's no doubt that Mifepristone can be administered with 300 milligrams, [00:07:52] Speaker 04: without infringing this. [00:07:54] Speaker 04: So let me just assume, whether you agree or not, that only a tiny or miniscule portion of those people to whom Mipha per Stone is actually prescribed will also be co-prescribed 600 or 900 milligrams. [00:08:10] Speaker 04: What in the world is the incentive for Teva to keep this on the label if they could so easily carve around this [00:08:18] Speaker 04: Why do they want, which is what you just said, this label that has these infringing [00:08:24] Speaker 04: recommendations on it. [00:08:26] Speaker 04: What is the logic behind that? [00:08:28] Speaker 00: I agree with that, Your Honor. [00:08:30] Speaker 00: The logic is they want to have the ability to have this label. [00:08:35] Speaker 04: But why do they want the ability to have this label? [00:08:38] Speaker 00: Because the FDA certainly anticipated, and we have evidence in the record, the FDA anticipated that co-administration will happen for the sickest of patients. [00:08:47] Speaker 00: That's what led to the clinical trials, which led to the invention. [00:08:50] Speaker 00: In fact, this court affirmed the validity of the invention, saying [00:08:54] Speaker 04: Yeah, but the fact that it might happen for the worst patients, I mean, I'm not even going to ask how much you bill per hour. [00:09:02] Speaker 04: I'm not going to ask how much he bills per hour. [00:09:04] Speaker 04: But if they could have so easily carved around these two administrations, I bet that as a company, honestly, it would have cost them less. [00:09:16] Speaker 04: than this litigation did. [00:09:18] Speaker 04: So I'm wondering, what in the world is really going on here? [00:09:22] Speaker 04: Why did they not just carve around that? [00:09:25] Speaker 00: Well, I mean, I can speculate. [00:09:28] Speaker 00: I'm not Teva. [00:09:29] Speaker 00: Obviously, I don't represent Teva. [00:09:31] Speaker 00: I think, to me, it's [00:09:34] Speaker 00: There's at least 10 more years left on the patent. [00:09:36] Speaker 00: And I think it's highly likely lots of doctors will want to co-administer these drugs together because ketoconazole, which was the tip three inhibitor that was the subject of the FDA memo. [00:09:46] Speaker 01: So you're saying the fact that they didn't carve out is some sort of circumstantial evidence that they would think that it would be used. [00:09:53] Speaker 00: Correct. [00:09:54] Speaker 01: Let me ask you one other thing. [00:09:57] Speaker 01: Is there some sort of procedural reason why they wouldn't have a carve out or why they wouldn't have [00:10:03] Speaker 01: copy the original label. [00:10:06] Speaker 00: I'm not aware, Your Honor, they could have copied the original label. [00:10:10] Speaker 00: That's not in the record that we have. [00:10:11] Speaker 00: The original label did not have these reduced doses of the 2012 label. [00:10:16] Speaker 00: It's the 2019 label, section 2.5, which is in page 16 of the blue brief, which has the doses. [00:10:24] Speaker 00: I will say, when this came up, Your Honor, at trial below, and the issue of, hey, you haven't, when the district court judge said, of course, that, hey, you haven't given me specific examples of [00:10:35] Speaker 00: of actual infringing uses. [00:10:37] Speaker 00: Teva did submit declarations to the court. [00:10:39] Speaker 00: Now, this was after the bench trial. [00:10:41] Speaker 00: So what happened was the district court said, that's too late, I'm not going to consider it. [00:10:45] Speaker 00: But when the issue came up below, Teva did provide declarations. [00:10:49] Speaker 03: The district court has discretion to preclude evidence that wasn't provided at the time of trial. [00:10:55] Speaker 00: That is correct. [00:10:56] Speaker 00: We are not appealing that issue, Your Honor. [00:10:58] Speaker 03: So tell me, counsel, how this case is any different than Genente. [00:11:01] Speaker 00: Thanks for that question, Your Honor. [00:11:03] Speaker 00: There's three ways I would like to discuss Genentech. [00:11:06] Speaker 00: First, a label is very different. [00:11:08] Speaker 00: In the Genentech case, the label said, avoid the two drugs, discontinue using the two drugs. [00:11:14] Speaker 00: And that is on page [00:11:18] Speaker 00: 1375 of the Genentech decision. [00:11:20] Speaker 00: The Genentech label had a prohibition on using the drugs together. [00:11:24] Speaker 00: There is no prohibition in our label of using the drugs together. [00:11:28] Speaker 00: And I'd like to add that our label for other situations does have the prohibitory avoid language. [00:11:34] Speaker 00: In appendix 4254, [00:11:37] Speaker 00: Our label says, do not use Mifepristone if the patient is pregnant, or do not use Mifepristone if the patient has type 2 diabetes not caused by Cushing's. [00:11:46] Speaker 00: So our label has prohibitory language for some situations, but not for co-administration with CIP3A. [00:11:52] Speaker 00: The Genentech label had prohibitory language, the outset, for the dosages. [00:11:58] Speaker 00: Second, in Genentech, the evidence was doctors had never combined the drugs, despite decades of practice. [00:12:05] Speaker 00: The evidence in our case, and I hear your Honor's question and point about the specific dosages, but the undisputed evidence in our case is doctors have combined these drugs. [00:12:13] Speaker 00: And I will say, the dosages are not that complicated. [00:12:16] Speaker 00: Each pill is 300 milligrams. [00:12:18] Speaker 00: We're talking one, two, three, or four pills. [00:12:20] Speaker 04: Complicates or not? [00:12:21] Speaker 04: There's no evidence in this record. [00:12:22] Speaker 04: Anybody's ever combined it at the claimed dosages, which is all that matters. [00:12:26] Speaker 04: So I don't see how you've distinguished yourself from Genentech at all on your second point. [00:12:29] Speaker 00: Well, Your Honor, before I get to my third point, I will say I believe Banda does not require us to prove. [00:12:35] Speaker 00: And I understand Judge Wang's point about, hey, why can't the judge look at all the evidence? [00:12:40] Speaker 00: And yes, the district court judge, of course, can holistically look at all the evidence. [00:12:44] Speaker 00: But we have to start with the label. [00:12:46] Speaker 00: And in Banda, there was a lot of non-infringing uses. [00:12:49] Speaker 00: In fact, if you go with the 3% to 10%, there was up to 97% non-infringing uses. [00:12:54] Speaker 00: But here, we do have record evidence, in fact, that the trial court found that... So this is a completely different point. [00:13:01] Speaker 04: I want you to answer her question, Judge Wang's question about Genentech. [00:13:05] Speaker 04: You've now pivoted and you're trying to basically beat a straw man to death. [00:13:09] Speaker 04: Can you please go through number one, two, and now you're at number three. [00:13:12] Speaker 00: Number three. [00:13:12] Speaker 00: Thank you, Your Honor. [00:13:14] Speaker 00: The third difference from Genentech is in Genentech there was no FDA evidence. [00:13:18] Speaker 00: Here we have the FDA, and the Lee memo is sort of the key memo here. [00:13:23] Speaker 00: That's, I believe, let me get that site accurately, 4450, appendix 4450. [00:13:28] Speaker 00: In 2012, the FDA said, told Corsep, there is a high potential of concomitant use, and the study will help provide more therapeutic options available to Cushing's patients. [00:13:39] Speaker 00: That FDA evidence did not appear in Genentech whatsoever. [00:13:43] Speaker 00: In fact, Genentech said, the Genentech panel said, you know, that Genentech was speculating about the FDA, what the FDA wanted on the label. [00:13:51] Speaker 00: Here we don't have speculation. [00:13:53] Speaker 00: We have the FDA themselves telling Corecept there's a high potential, there's a likelihood [00:13:58] Speaker 00: And then in Appendix 4300 and 4468, the FDA told Corsep there is a likelihood of co-administration. [00:14:09] Speaker 00: Therefore, Corsep, please go out, run this trial, check out the drug-drug interactions. [00:14:13] Speaker 04: But again, you're missing the key thing, which is a likelihood of co-administration. [00:14:19] Speaker 04: That was of [00:14:20] Speaker 04: It was the 300 milligrams. [00:14:22] Speaker 04: The FDA said, go investigate this for safety and efficacy. [00:14:26] Speaker 04: But those statements the FDA made at that time were all in the guise of only approving a label at 300 milligrams, which doesn't impringe. [00:14:35] Speaker 00: That's true, but the FDA asked Corset to do that because it was likely, the FDA understood it was likely there would be co-administration. [00:14:42] Speaker 00: Corset did that, did the trials, made unexpected discoveries, unexpected results, filed for patents. [00:14:49] Speaker 00: And I will say, the patent system incentivized exactly what happened here, which was to give Corset protection, and Corset discovered and patented [00:14:58] Speaker 00: this dosing regimen that helps the absentee. [00:15:00] Speaker 04: Do you want to save some time for about a minute? [00:15:01] Speaker 00: I would like to, Your Honor. [00:15:02] Speaker 04: You've got 16 seconds left. [00:15:03] Speaker 04: Yeah, I'll give you some more, but I'll sign back. [00:15:04] Speaker 04: I'll restore it. [00:15:05] Speaker 04: Thank you. [00:15:05] Speaker 04: Let's hear from the opposing counsel. [00:15:09] Speaker 04: Is it Mr. Rosendahl? [00:15:11] Speaker 02: Yes, Your Honor. [00:15:12] Speaker 01: Thank you. [00:15:20] Speaker 01: Could you start by addressing why there was no attempt to have a carve out or copy the original label? [00:15:27] Speaker 02: Your Honor, the FDA regulations require, as a general matter, that a generic drug have an identical label, apart from the name of the drug, of course, to the branded drug. [00:15:38] Speaker 02: What we're talking about here is [00:15:40] Speaker 02: essentially safety information, their warnings and precautions. [00:15:43] Speaker 02: And this was not an issue that was explored at trial, but I think my understanding is that it's pretty tough to get the FDA to allow one to carve warnings or precautions out of a label once the FDA has determined that they're appropriate. [00:15:58] Speaker 02: So I think that the background rule here is that the generic needs to have the same label [00:16:03] Speaker 02: as the branded drug. [00:16:07] Speaker 01: You can have a skinny label, you can have a carve out and the original label which was approved by the FDA didn't have the specific table with the dosages that are recited in the claims, right? [00:16:21] Speaker 02: It's true that the 2012 label as originally approved did not have the specific dosages in the claim. [00:16:27] Speaker 02: I think this is different from a so-called skinny label or carve-out situation, though, because in the carve-out situation, you typically have a drug that can be used for more than one indication. [00:16:37] Speaker 02: And what gets carved out of a label is one of the indications. [00:16:41] Speaker 02: So, you know, if a drug can be used to treat cancer and rheumatoid arthritis, [00:16:45] Speaker 02: there's a patent on rheumatoid arthritis, a generic has the option to say, well, we're not going to pursue that indication. [00:16:52] Speaker 02: We'll only seek a label that has the unpatented use on it. [00:16:57] Speaker 02: But that's different from the indication and usage section of the label. [00:17:01] Speaker 02: That's not the same thing as the warnings and precautions section of the label. [00:17:06] Speaker 04: The warnings and precaution concept that you just threw out there is the FDA won't let us use the original label because, you know, warnings are important. [00:17:14] Speaker 04: The original label had more warnings, not fewer warnings. [00:17:17] Speaker 04: The 2012 label gave people many more warnings about mixing misoprostone, especially at any higher dosages, along with the CY3PA inhibitor. [00:17:29] Speaker 04: So I don't see how your argument makes sense. [00:17:31] Speaker 04: If your argument was, [00:17:33] Speaker 04: The FDA doesn't want you to modify warnings, because warnings are so important. [00:17:38] Speaker 04: The original label had more warnings, stronger warnings, not less warnings. [00:17:42] Speaker 04: So why would the FDA have prohibited you from using the 2012 label, which would have allowed you to avoid encouraging infringement and, at the same time, contained warnings? [00:17:52] Speaker 02: But Your Honor, first of all, the question of a carve-out was not something that was litigated below. [00:17:56] Speaker 02: And I'm not prepared to make representations on exactly what the FDA would or would not have allowed. [00:18:01] Speaker 02: I think that the whole premise of the question, though, kind of turns the inquiry on its head. [00:18:06] Speaker 02: It's not up to Teva to avoid. [00:18:08] Speaker 01: Forget about the carve out question. [00:18:10] Speaker 01: We've got a separate question. [00:18:11] Speaker 01: We've heard your answer to carve out, but you haven't yet answered why you didn't copy the original 2012 label. [00:18:18] Speaker 02: That's not an option, Your Honor. [00:18:19] Speaker 02: The rule is that the label. [00:18:20] Speaker 02: The label for the generic needs to mirror the current label as a background matter. [00:18:25] Speaker 02: It needs to mirror the label. [00:18:27] Speaker 01: The current label. [00:18:27] Speaker 02: The current label. [00:18:28] Speaker 02: Yeah. [00:18:28] Speaker 02: I don't think it's an option to go back to some previous label and say that I like that form of words better. [00:18:34] Speaker 02: I think the current version of the label. [00:18:35] Speaker 01: What law do you have on that? [00:18:36] Speaker 01: I'm just asking because I really don't know. [00:18:39] Speaker 01: I'm not trying to trip you up or anything. [00:18:42] Speaker 01: I'm just, I want to know why it wasn't done. [00:18:44] Speaker 01: So if you can help me understand the legality of that, I would appreciate it. [00:18:48] Speaker 02: So I do not have a specific statutory site for Your Honor standing here today. [00:18:52] Speaker 02: I would be happy to submit a letter with the relevant statutory reference. [00:18:56] Speaker 02: But it is a background principle of Hatch-Waxman cases that the label of the generic as a general matter needs to be the same as the label on the branded drug. [00:19:08] Speaker 02: I don't think there was any dispute about that. [00:19:10] Speaker 01: You said current before. [00:19:11] Speaker 02: Yes. [00:19:13] Speaker 02: Yes. [00:19:13] Speaker 02: I think the point, though, is that the burden at trial was on corecept to prove both direct infringement and indirect infringement. [00:19:25] Speaker 02: carefully reasoned 47 page long opinion, the district court made factual findings that CORCEP simply failed to carry its burden of proof on two important elements of its case. [00:19:36] Speaker 04: One of the problems is this is a hypothetical scenario, this ANDA scenario, because the product hasn't launched. [00:19:43] Speaker 04: So it's hypothetical. [00:19:45] Speaker 04: So why would we assume there has to be proof of an actual direct infringement having already occurred? [00:19:55] Speaker 02: That is not required, of course. [00:19:56] Speaker 02: It's not necessary to prove that there's been an actual infringement in the past in order to establish that there will be an infringement in the event that the generic is put onto the market. [00:20:07] Speaker 02: However, the question of past practice, as this court has recognized in Genentech, is directly relevant to the question of how physicians are likely to behave in the future. [00:20:19] Speaker 02: And here, we had the additional issue that there is a new drug on the market in the form of Acylidrostat, and the district court credited expert testimony to the effect that whatever people may have thought about the benefits of co-administration of these two kinds of drugs back in the 2012 time frame when Mifepristone was first approved, [00:20:40] Speaker 02: Now, as of 2020, there is another alternative available for treating pushing syndrome, which is superior for co-administration to myphopristone because the dosage of the two drugs can be controlled by monitoring the level of cortisol in the body, which is something that cannot be done with myphopristone. [00:21:01] Speaker 02: And so with myphopristone, you have a problem. [00:21:03] Speaker 02: that if the level of myphopristone in the body gets too high, you have very serious life-threatening side effects, including very low blood pressure, potassium problems. [00:21:13] Speaker 02: And you can't tell by measuring the amount of cortisol in the blood if the myphopristone level is too high, because myphopristone doesn't reduce the level of cortisol. [00:21:22] Speaker 02: It simply blocks the effect of the cortisol on the body by blocking the receptors that cortisol would attach to. [00:21:28] Speaker 02: And so you actually even have the perverse effect that when you take Mifopristone, people's cortisol levels tend to go up rather than down because the signal to the body that the cortisol levels are too high gets blocked by the Mifopristone. [00:21:40] Speaker 01: I'd like to ask you a legal question. [00:21:41] Speaker 01: I mean, I see our cases. [00:21:43] Speaker 01: We've got cases like Vonda, and we've got cases like Genentech on the other hand. [00:21:48] Speaker 01: I want to know, what statutory support is there for when you're looking at direct infringement for looking at more than the label? [00:21:59] Speaker 02: for looking at more than the label. [00:22:00] Speaker 01: Right, where the statute itself says that the filing of the enda itself is the act of infringement. [00:22:08] Speaker 02: Yes. [00:22:10] Speaker 02: 271E says that it's an act of infringement to file an ANDA for a product that infringes the patent or the use of which infringes the patent. [00:22:22] Speaker 02: And so in this court's cases, when the question is, what is the product for which approval is being sought? [00:22:30] Speaker 01: For the use here of the use. [00:22:31] Speaker 02: Well, I'd like to distinguish between those two, if I may. [00:22:35] Speaker 02: I think in this court's cases where the question is, what is the proposed product, the court has given controlling weight to the ANDA as the description of the thing for which approval is being sought. [00:22:46] Speaker 02: And every one of the cases that Corsept relies on for the proposition that one needs to start with the label or that the label is controlling was a product claim. [00:22:56] Speaker 02: So Sinovian and Brahmanidine and Bayer and Parr, all of those [00:23:01] Speaker 02: involved infringement by the product that was going to be sold. [00:23:06] Speaker 02: And the question was, what product have you sought approval for? [00:23:10] Speaker 02: However, in cases where the question isn't, what is the product, when the question is, how is the product going to be used, this court has never hesitated to go beyond the label to answer that question. [00:23:23] Speaker 02: And that's because, of course, not the label, the end up. [00:23:26] Speaker 04: Is there any case that you can point to [00:23:30] Speaker 04: where the court went beyond the label when the label itself nonetheless instructed the infringing use? [00:23:39] Speaker 02: Well, again, I don't want to fight the hypothetical. [00:23:44] Speaker 04: You're not going to be able to fight the hypothetical because I'm asking you that question. [00:23:49] Speaker 04: So is there any case [00:23:51] Speaker 04: that's a use case, because you're saying let's distinguish between products and uses. [00:23:55] Speaker 04: You've sort of given in on the product part, but you're trying to hold it out that this is a use case. [00:24:00] Speaker 04: So is there any case that you know of where it involved a use and the actual ANDA instructed the infringing use right on the label? [00:24:10] Speaker 02: I think Genentech essentially was... No, Genentech said don't do it. [00:24:14] Speaker 04: It didn't say do it, it said don't do it. [00:24:20] Speaker 02: I think there was more than one claim at issue in Genentex. [00:24:22] Speaker 02: Some of them required adjustment of dosages, and some of them required discontinuance of the usage. [00:24:28] Speaker 04: I'll read you Genentex label because I've got it right here. [00:24:31] Speaker 04: Use of fluoxamine or other strong CYP1A2 inhibitors should be discontinued prior to administration and avoided during perfenedone treatment. [00:24:43] Speaker 04: So Genentech's label actually instructed you not to do it. [00:24:47] Speaker 04: This label instructs you to do it. [00:24:48] Speaker 02: Well, but the claim in Genentech, one of the claims that was at issue in Genentech was an instruction to discontinue, was an instruction not to give them together. [00:24:57] Speaker 01: So that was a way of... But do you know of any cases other than Genentech in answering the question? [00:25:04] Speaker 01: Is Genentech your only case you have? [00:25:06] Speaker 02: Well, I think that Takeda and Genentech are both cases that were drug-drug interaction patents. [00:25:12] Speaker 02: And so they're quite close, factually, to what we have here. [00:25:15] Speaker 01: Again, the question is whether you know of any case that involves a use where the ANDA on its face instructs the use, but yet the court went beyond the plain language of the label to assess whether it would, in fact, be used if the generic were to go on the market. [00:25:35] Speaker 02: Well, I don't specifically recall exactly what the instructions were in those two cases. [00:25:40] Speaker 02: What I can tell you is on the label. [00:25:42] Speaker 02: What I can tell you is that Genentech and Takeda are two cases where the question about how physicians were going to use the product was answered by looking at physician practice and was not restricted to the label. [00:25:56] Speaker 02: And I think that's the closest thing that we have here. [00:25:58] Speaker 02: And I think that what distinguishes those cases from [00:26:01] Speaker 02: The other cases that Corset attempts to rely on, such as AstraZeneca, the downward titration case, or Vanda, the poor metabolizer case, or even Janssen, the recent subject of their 28-J letter. [00:26:15] Speaker 02: In each of those cases, unlike here, there was evidence in the record that the infringing use would be inevitable if the instructions on the label were followed. [00:26:27] Speaker 04: And here, we have said- Wait, are you suggesting you have to have evidence? [00:26:30] Speaker 04: Are you now saying that we need a rule of law that you have to have evidence that infringing use will be inevitable? [00:26:38] Speaker 02: No. [00:26:39] Speaker 02: I'm not saying that. [00:26:40] Speaker 02: What I'm saying is that one way that one can satisfy the burden of showing that infringement is going to happen in the future is to demonstrate that it is inevitable when the instructions are followed. [00:26:51] Speaker 02: This is not just an issue of Hatch-Raxman law. [00:26:53] Speaker 02: This comes up also. [00:26:54] Speaker 04: Here, I mean, 271E says the filing of the ANDA is an act of infringement. [00:26:59] Speaker 04: And if on the filing of the ANDA, if your label actually tells people to administer things in exactly the infringing dosages that are subject to the patent, [00:27:09] Speaker 04: I don't know why that doesn't just end the inquiry. [00:27:11] Speaker 02: Well, because this court has said over and over again that although the artificial act of infringement in 271E is enough to create jurisdiction, we don't answer the infringement question by asking solely what does the ANDA say. [00:27:25] Speaker 02: We ask the question of, if the drug is marketed, will it result in infringement? [00:27:32] Speaker 02: There's a long line of cases saying that. [00:27:34] Speaker 04: You've already acknowledged that if it was a product, we can look at just the label. [00:27:38] Speaker 04: that Vanda and others, if it's a product, you can look at just the label. [00:27:42] Speaker 04: You've carved out this distinction. [00:27:44] Speaker 04: So you've already sort of admitted that the large swath of cases to have addressed this, which are product cases, are not consistent with what you just said. [00:27:56] Speaker 02: The question, if the question, right, we don't have a product to look at yet because there isn't a product that's being marketed. [00:28:02] Speaker 02: And so we have to put ourselves in the hypothetical future world in which the product is being marketed. [00:28:07] Speaker 02: And then we ask ourselves does that, in that future world, does the product infringe or is it used in an infringing matter? [00:28:14] Speaker 02: And the question, does the product infringe simply by being sold? [00:28:18] Speaker 02: can be answered by answering the question, what is the product? [00:28:22] Speaker 02: And the answer to the question, what is the product for which approval is being sought, can be answered by looking at the product specification in the ANDA. [00:28:30] Speaker 02: And so that has been given controlling weight on that question. [00:28:33] Speaker 02: But as to the question of how is the product going to be used in this hypothetical future world, the court has always looked at physician practice. [00:28:41] Speaker 02: And the important point of Genentech, the key holding of Genentech, is that the burden is on [00:28:47] Speaker 02: the patentee to establish that there's going to be future infringement if the product is marketed. [00:28:53] Speaker 02: They cannot simply assume that there's going to be infringement if the product is marketed. [00:28:57] Speaker 02: And that is the error, the course that makes here. [00:28:59] Speaker 02: And you can see it on page 33 of this. [00:29:02] Speaker 04: What is the best evidence that you have that the district court found in terms of fact findings that would indicate the product is not going to be used in an infringing manner as the label otherwise instructs people to do? [00:29:17] Speaker 02: Well, I could point, Your Honor, to Appendix Page 34, where the Court credits the testimony of Teva's expert, Dr. Snyder, that the risks of co-administration outweigh the benefits, especially since the introduction of Acylodrostat. [00:29:38] Speaker 04: I'm sorry, where is the fact-finding? [00:29:40] Speaker 02: For example, on Page 34 of the Appendix, [00:29:50] Speaker 04: I don't see any fact-findings. [00:29:51] Speaker 04: I see her sort of methodically in this page going through the arguments and what various experts testify to. [00:29:59] Speaker 04: There might be a fact-finding not on 34. [00:30:01] Speaker 02: Well, she's crediting the testimony that the benefits of co-admission. [00:30:06] Speaker 04: Show me a page and a line number, or which paragraph, where. [00:30:12] Speaker 01: I think you might be referring to the last sentence of the first paragraph. [00:30:17] Speaker 02: Yes. [00:30:18] Speaker 02: The court finds this testimony credible and persuasive that the benefits of code ministering never outweigh the risks, especially since the introduction of acyldorostat. [00:30:27] Speaker 02: Thank you, Your Honor. [00:30:28] Speaker 02: That is the key point. [00:30:30] Speaker 02: And that shows a conclusion on the part of the district court that doctors in the future, especially since the advent of acyldorostat, [00:30:38] Speaker 02: are not likely to use the two drugs together, the Mifopristone and a strong 6-3-A inhibitor. [00:30:44] Speaker 02: That is a key finding. [00:30:45] Speaker 02: And the point I was trying to make about inevitability, Your Honor, was simply that. [00:30:50] Speaker 04: And I could also point, Your Honor, to- So one problem, this doctor concluded in his personal experience, benefits don't outweigh the risks. [00:30:59] Speaker 04: Is that really sufficient? [00:31:01] Speaker 04: And she finds that credible and persuasive. [00:31:02] Speaker 04: I get it, that he personally would do that. [00:31:06] Speaker 04: I don't see her explaining that he goes further to say that doctors would not do that, as opposed to he personally wouldn't. [00:31:12] Speaker 02: Well, I think that when one views that statement in the context of the whole opinion, it's pretty clear that she is crediting the point that the fact of the matter, that the benefits are not going to outweigh [00:31:28] Speaker 02: the risks. [00:31:29] Speaker 02: And we have other statements, for example, just two pages earlier on appendix page 32, at the beginning of the second paragraph, Dr. Snyder persuasively testified that physicians should be very afraid of co-administration and that it could cause a problem. [00:31:45] Speaker 04: So here we have... So here's my problem. [00:31:47] Speaker 04: Let me just walk you through my chronology that's bothering me about this. [00:31:50] Speaker 04: As of 2012, nobody would consider giving more than 300 milligrams of Mephepristone alongside a CY3PA inhibitor [00:31:58] Speaker 04: because of the extraordinarily dangerous co-administration side effects. [00:32:03] Speaker 04: So, and that continued, FDA said go do a study. [00:32:06] Speaker 04: They went and they did an expensive study and they came back and in 2019, they sought and obtained approval for a label. [00:32:13] Speaker 04: But when did your discovery in this case close? [00:32:14] Speaker 04: Because I'll tell you when, I know exactly when. [00:32:16] Speaker 04: When did it close? [00:32:17] Speaker 04: Do you know? [00:32:18] Speaker 02: There was an initial close of fact discovery in late 2020, and then they added a new patent to the case in 2023, and there was an additional round of discovery with the final round of expert reports coming in in May of 2023. [00:32:34] Speaker 04: So all these Dr. Snyders, did they come in in May of 2023 or May of 2020? [00:32:39] Speaker 02: 2023, I believe, Your Honor. [00:32:41] Speaker 04: Dr. Snyder says somebody came in in 2023 because I thought it was 2020. [00:32:44] Speaker 02: No, Your Honor. [00:32:46] Speaker 04: Okay, I'll certainly look that up afterwards. [00:32:49] Speaker 04: No, there were supplemental reports that were... Because what bothered me a lot was the idea that, that clearly everyone, including the brand, was saying don't use Mifflin Pristone in more than 300 milligrams until at the earliest 2019. [00:33:04] Speaker 04: So it's not surprising that people would be afraid of co-administration. [00:33:07] Speaker 04: They were saying in their earlier 2012 label there could be extraordinary problems with co-administration. [00:33:13] Speaker 04: And all that went away after 2019, up to 900 milligrams. [00:33:17] Speaker 02: Right, but I think there was three and a half or four years between the time of the new label and the testimony at issue. [00:33:27] Speaker 02: And of course, acyldrosat itself didn't come onto the market until 2020. [00:33:31] Speaker 02: And so that was, I think the district court clearly found, was a game changer and made it less likely than it would have been before for doctors to consider co-administering the pristone with a strong 6-3-8 inhibitor. [00:33:46] Speaker 02: Dr. Snyder, looking at the label, said that the label actually discourages the co-administration. [00:33:54] Speaker 04: Yeah, but I don't agree with that at all, and I would find that clear error. [00:33:59] Speaker 02: Well, I would submit for the court's consideration, and your honors can find that in the district court's opinion, that the changes between 2012 and 2019 to the label [00:34:12] Speaker 02: were quite minimal in view of the testimony from Corsept and the inventor that the 2012 label was a forceful warning against co-administration. [00:34:21] Speaker 04: Yeah, because it said you can't go higher than 300 milligrams, and it had extremely serious and all these other adverbs and adjectives in it that were almost all removed entirely, and it expressly instructed to go to 600 and 900 milligrams. [00:34:33] Speaker 04: Wildly different labels. [00:34:37] Speaker 02: I think the record speaks for itself on what the differences in the label are. [00:34:40] Speaker 02: I won't belabor the point. [00:34:41] Speaker 02: But I do think if I can draw the court's attention to page 33 of Corsep's opening brief, I think that this kind of crystallizes the problem with Corsep's approach to the case. [00:34:55] Speaker 02: This is where they call out what they say is the very best evidence that they have from their expert on why there's infringement, supposedly on the basis of the label alone. [00:35:06] Speaker 02: The question that's asked on page 33 in the block quote is, in your opinion, doctor, in instances where medical professionals determine that it's necessary to co-administer Mifopristone and a strong CIP3A inhibitor to a patient who is already taking 1,200 milligrams or 900 milligrams of Mifopristone, would a medical professional follow the instructions on TEFA's label? [00:35:27] Speaker 02: And the answer given by their expert was yes. [00:35:29] Speaker 02: And our point is the district court found that that was not enough. [00:35:33] Speaker 02: to meet their burden on direct infringement or on indirect infringement. [00:35:36] Speaker 02: And the district court was correct about that. [00:35:38] Speaker 04: OK, counsel, we're way over your time. [00:35:40] Speaker 04: I thank you for your argument. [00:35:41] Speaker 04: We're going to give Mr. Cannon a full five minutes of rebuttal time because that's how much Mr. Rosendahl went over. [00:35:50] Speaker 00: Thank you. [00:35:56] Speaker 00: Thank you very much, Your Honors. [00:35:59] Speaker 00: I would like to address some of the points my colleague made, unless you had questions you wanted to start off with right away. [00:36:06] Speaker 00: Judge Moore, you are correct that discovery, fact discovery closed on October 15, 2020. [00:36:12] Speaker 00: Now, there was a round of expert discovery. [00:36:14] Speaker 00: because the 800 patent was added to the case after the 214 patent. [00:36:19] Speaker 00: But in the underlying district court docket, docket 180, fact discovery closed in 2020. [00:36:26] Speaker 00: And you are correct that there was not, it wasn't like there was years and years of fact discovery in order to determine in these rare instances, let's find specific instances of doctors prescribing these drugs, co-administrating these drugs at the infringing dosages. [00:36:42] Speaker 00: One of the points I wanted to raise was the difference between product and method claims because I believe council has conceded that for at least product claims [00:36:50] Speaker 00: The label absolutely controls. [00:36:51] Speaker 00: And Sunovion, I think, is probably one of the best cases for that. [00:36:55] Speaker 00: I would like to point out that Vanda is a method case. [00:36:59] Speaker 00: It was a method of treatment case. [00:37:00] Speaker 00: So I do believe Vanda is a very strong case for us. [00:37:04] Speaker 00: In fact, it controls our situation. [00:37:06] Speaker 00: And I don't see a principal difference with respect to looking at a label between a method claim and a method of treatment. [00:37:13] Speaker 04: Look, if you're right, we just look at the label UN. [00:37:16] Speaker 04: But the district court did not confine herself to just the label. [00:37:19] Speaker 04: And... [00:37:21] Speaker 04: I mean, he pointed to the very best sentence in the opinion, or one of them, about Mr. Snyder and her saying, people will not give Mifepristone at 600 or 900 milligrams plus a CYP3 inhibitor now in light of this new drug that she finds credible that the risks outweigh the benefits. [00:37:42] Speaker 04: And so it's not going to happen. [00:37:44] Speaker 04: And so she's making an affirmative finding based on a precise set of facts [00:37:50] Speaker 04: That this is, I mean, this is where all the marbles are for me. [00:37:53] Speaker 04: I don't know how I'm going to decide this case. [00:37:54] Speaker 04: I've given you both a hard time today. [00:37:56] Speaker 04: Hopefully he didn't get up thinking super confident after he heard me question you hard because I think I went at him harder. [00:38:02] Speaker 04: I truly don't know how I'm going to decide this case as I sit here. [00:38:04] Speaker 04: That's why I'm asking you both really hard questions. [00:38:06] Speaker 04: But that's what it comes down to. [00:38:08] Speaker 04: If the label controls, you win. [00:38:10] Speaker 04: No way it was a warning not to do it. [00:38:11] Speaker 04: But if the label's not all the controls and I look at the whole [00:38:15] Speaker 04: of the record, I don't know what to do with all her precise fact findings. [00:38:19] Speaker 04: I'm not sure what to do with that. [00:38:20] Speaker 04: To the extent she said the labels of warning clear error as far as I'm concerned. [00:38:23] Speaker 04: But the other pieces where she said doctors will not do this, I've concluded that. [00:38:28] Speaker 04: I don't know what to do with that. [00:38:30] Speaker 00: May I point you to a couple of other places in the judge's decision, Your Honor? [00:38:34] Speaker 00: Because I believe the judge's fact-finding is not quite as clear and definitive as counsel says. [00:38:39] Speaker 00: Counsel pointed you to, I believe, the page, I believe it was 32, where the court credited Dr. Snyder saying in his personal experience he wouldn't do it. [00:38:49] Speaker 00: That's not testimony that no doctor would ever do it, never not do it, excuse me. [00:38:53] Speaker 00: That's Dr. Snyder. [00:38:55] Speaker 00: And I think the sentence I want to show you, Your Honor, is first on past infringement, because the district court judge made a finding on past infringement and a finding on future infringement. [00:39:07] Speaker 04: I know, but the past infringement was the people co-administered, but she never made any finding that they co-administered at these dosages. [00:39:13] Speaker 04: And so, I mean, unless you're going to show me this, I feel like this is what you beat your head against the wall on in the opening argument. [00:39:20] Speaker 04: You couldn't get past the specific dosages requirement. [00:39:23] Speaker 04: And you kept thinking co-administration wins you the ball game when it does not win you the ball game. [00:39:27] Speaker 00: Well, I think statistically, Your Honor, if there's only four possible doses that you can have, 300, 600, 900, or 1,200. [00:39:34] Speaker 00: So if we're looking to the future, I don't think the burden is on us to have a crystal ball to say, absolutely, these are the exact dosages that the doctors will have in the future. [00:39:43] Speaker 00: And there is evidence in the record. [00:39:44] Speaker 03: Isn't it your burden to prove direct infringement? [00:39:47] Speaker 03: So if both Vanda and Genentech direct a district court in saying the infringement determination is thus based on the consideration of all relevant evidence, and because the drug manufacturers are bound by the strict statutory provisions to sell only those products that comport in Anda's description of the drug, and Anda itself dominates the analysis, [00:40:09] Speaker 03: Isn't that telling, even Banda telling a district court, you look at all relevant evidence, the district court determines what that relevant evidence is, how to weigh that relevant evidence. [00:40:20] Speaker 03: So once she has done that, how can you find clear error? [00:40:23] Speaker 00: Your Honor, may I point you to the fact finding that the district court made on bottom of page 30 across to 31. [00:40:30] Speaker 00: And this is what the district court said. [00:40:32] Speaker 00: Crediting Dr. Snyder's testimony, this court finds that while clinicians may exercise their medical judgment to co-administer mephepristone with a strong CYP3A inhibitor in isolated instances when necessary, it is highly unlikely that physicians will practice the claimed methods. [00:40:49] Speaker 00: Your Honor, this is not a finding that it will never happen. [00:40:52] Speaker 00: This is a finding that the district court found, as a matter of fact, that in rare cases, it will be necessary, medically necessary, that some doctors may do it. [00:41:02] Speaker 01: Wait, wait. [00:41:02] Speaker 01: That's saying medically necessary to co-administer. [00:41:05] Speaker 01: It doesn't say medically necessary to co-administer at the dosage levels. [00:41:10] Speaker 01: That's correct, Your Honor. [00:41:11] Speaker 01: Instead, with the, I think the next clause is the one that relates to the dosage levels, which says it's highly unlikely that physicians will practice the claimed methods. [00:41:22] Speaker 01: Do you agree with that? [00:41:24] Speaker 00: I don't fully agree with that, Your Honor, because co-administration of these drugs will necessarily lead to infringement, because the record evidence was the majority of the patients are on either 900 or 1,200 milligrams of Mifoprispon. [00:41:38] Speaker 04: them to, by itself. [00:41:40] Speaker 04: There's no record evidence here. [00:41:41] Speaker 04: The majority of people taking CYPA3 inhibitors are on 900 milligrams of MIP of per stone. [00:41:46] Speaker 04: Show me where that evidence is. [00:41:47] Speaker 04: That is a blatant misrepresentation. [00:41:49] Speaker 00: I believe Dr. Belanoff, Appendix 1164, 65. [00:41:52] Speaker 04: You better be right, or you're going to have a show of cause order coming your way. [00:41:55] Speaker 00: I'm sorry. [00:41:56] Speaker 04: You better revise what you just said. [00:41:57] Speaker 04: Those are your two choices in front of me. [00:41:59] Speaker 00: If I wasn't clear, I deeply apologize. [00:42:03] Speaker 00: I believe Dr. Belanoff's testimony was that the majority of, putting aside CYP3A inhibitors, just Mifopristone, the majority... Yeah, just Mifopristone, exactly. [00:42:13] Speaker 01: Is this the testimony, you say it's at 1164 to 65? [00:42:17] Speaker 00: Yes. [00:42:27] Speaker 00: And I really did not... [00:42:29] Speaker 00: intend to imply that it was the majority on both. [00:42:32] Speaker 00: It's putting aside Sipteria, if you have all of the patients, the Cushing Syndrome patients who are on with the Cris done. [00:42:52] Speaker 00: It's 1164, lines 25 to 1165, line 6. [00:43:00] Speaker 00: That's the testimony of the head of mine, Your Honor. [00:43:02] Speaker 00: And I apologize if I implied that it was an exact infringing claim there, because this is not demonstrated infringement. [00:43:10] Speaker 04: Is there anything else in her opinion you want to point me to that suggests that she somehow scaled back on her later statements about the likelihood of Mifflipristone at the claim dosages? [00:43:22] Speaker 04: being prescribed alongside a CYP3A. [00:43:26] Speaker 00: From my notes, your honor, the other part of the record is in the past infringement, Appendix 29, and these are not infringing doses, just co-administration, that the record indisputably reveals that physicians have co-administered the fipristone with strong citric acid in their cases. [00:43:43] Speaker 04: Anything further, Dr. Stone? [00:43:45] Speaker 04: Anything further, Dr. Twain? [00:43:46] Speaker 04: Okay. [00:43:47] Speaker 04: That's all the time we have for today. [00:43:48] Speaker 04: Thank you.