[00:00:21] Speaker 03: Next case for argument is 15-2067, Eli Lilly and Company versus Teva Medicine. [00:00:33] Speaker 03: Court, Your Honors. [00:00:34] Speaker 03: Why don't we give everybody a chance to settle it? [00:00:37] Speaker 03: I apologize now. [00:00:38] Speaker 03: No, that's all right. [00:00:48] Speaker 00: Okay, Mr. Jay, I think we're good to go. [00:00:50] Speaker 00: Thank you, your honor. [00:00:52] Speaker 00: Good morning. [00:00:53] Speaker 00: This case, as the court knows, presents three issues. [00:00:56] Speaker 00: One, infringement question, and we presented two in validity questions on appeal. [00:01:01] Speaker 00: I'd like to begin with the infringement question, the issue on which there are a number of amicus briefs, and on which the district court's decision is novel, legally erroneous, and should be reversed. [00:01:13] Speaker 00: The divided infringement question here is whether [00:01:16] Speaker 00: the doctors exercise enough control over the actions of their patients that the doctors and the patients should be considered a single unit for purposes of infringement, that the doctors should be held legally responsible for the actions of the patients. [00:01:30] Speaker 00: The district court held that there was enough control here. [00:01:33] Speaker 00: But on these facts, instructing a patient to take an over-the-counter pill in one of many forms, either a multivitamin or any of the various commercially available folic acid supplements, [00:01:45] Speaker 00: on any five days within a period and within a wide range of amounts prescribed in the patient information. [00:01:57] Speaker 00: That's not enough control to attribute the actions of the patients to the doctors. [00:02:02] Speaker 00: And if the patient... Why not? [00:02:03] Speaker 03: What would be enough control? [00:02:05] Speaker 03: I mean, we here lived through years of Akamai and the discussion of what direction and control meant. [00:02:11] Speaker 03: Why isn't it enough? [00:02:13] Speaker 03: I mean, both experts, I think experts on both sides, testified that it was standard practice for doctors to withhold the treatment if patients didn't take the folic acid. [00:02:23] Speaker 03: And I think there's lots of evidence. [00:02:25] Speaker 03: These were instructions. [00:02:26] Speaker 03: This was what they were required to do. [00:02:27] Speaker 03: They were compelled to do it. [00:02:28] Speaker 03: The doctors wouldn't provide the treatment if they didn't do it. [00:02:31] Speaker 03: I mean, unless we're going to have some requirement of a contractual relationship, seems to me this is pretty strong direction and control. [00:02:38] Speaker 00: Well, we don't think so, Your Honor, but we're not here advocating for a contractual relationship and nothing else, as a bright line. [00:02:45] Speaker 00: But what we are arguing for is that you should apply the same standard in the doctor-patient context that you would apply in other patent cases. [00:02:52] Speaker 00: You look at whether there is a legally sufficient [00:02:55] Speaker 00: Let me go right to what your question was about, which is the withholding of treatment. [00:03:00] Speaker 00: I want to point out that is not what the district court made findings on. [00:03:04] Speaker 00: That is not what the district court premises decision on. [00:03:06] Speaker 00: If you look at A27, the district court says it was going to look at three things. [00:03:10] Speaker 00: The district court was going to look at the patent itself. [00:03:13] Speaker 00: That's the first legal error that the district court made, and I'm going to come back to that. [00:03:17] Speaker 00: but also the patient information and the prescribing information. [00:03:21] Speaker 00: There's nothing in either of those documents that talks about withholding treatment. [00:03:26] Speaker 03: Wait a minute. [00:03:26] Speaker 03: I mean, I don't know. [00:03:28] Speaker 03: Obviously, there's a lot of paper here. [00:03:29] Speaker 03: I'm looking. [00:03:30] Speaker 03: Didn't you call out A27? [00:03:31] Speaker 03: Yes, you're right. [00:03:33] Speaker 03: All right. [00:03:33] Speaker 03: Well, A27. [00:03:34] Speaker 03: Maybe I'm looking at the wrong thing. [00:03:36] Speaker 03: But it does say on that page, reading quickly, if the patient fails to carry out the step, he or she will not receive the benefit of the patented method. [00:03:44] Speaker 00: The benefit of the patented method. [00:03:45] Speaker 00: Now what the court is saying there is not the doctor won't give you the treatment. [00:03:51] Speaker 00: The court is saying you won't get a reduction of potentially life-threatening toxicities. [00:03:56] Speaker 00: In other words, that's just saying if you don't take folic acid, not whether you follow the patented steps, [00:04:03] Speaker 00: But if you don't take folic acid, you'll be at risk of toxicity. [00:04:07] Speaker 00: That's just assuming the conclusion. [00:04:08] Speaker 00: That's saying that here's a step in a patented method. [00:04:12] Speaker 00: And if you, actor number one, hear the patient, don't perform this step, well, then you won't share in the benefits of performing the patented method. [00:04:19] Speaker 03: And it goes on to say the physician, based on the patented method, directs the manner and timing of the patient's ingestion of folic acid. [00:04:25] Speaker 00: And that's what the court said. [00:04:27] Speaker 00: That's right. [00:04:27] Speaker 00: Which is not about the doctor withholding treatment. [00:04:31] Speaker 02: Well, suppose the court had found [00:04:33] Speaker 02: Suppose the court had found that physicians withhold the treatment unless the patient takes folic acid. [00:04:42] Speaker 02: Is that direction in control? [00:04:44] Speaker 00: If I may vary the question a little bit, if they'd said that the doctors withhold treatment unless the patients take folic acid, [00:04:53] Speaker 00: within the range claimed in the patent, or within the specified range. [00:04:58] Speaker 00: But we don't have a finding to that effect. [00:05:01] Speaker 00: I think the answer is yes. [00:05:02] Speaker 00: That is direction of control. [00:05:05] Speaker 00: I think we're not disputing that. [00:05:07] Speaker 00: But we don't have that here. [00:05:11] Speaker 02: There seems to have been a lot of testimony that that's what doctors do, even if there's no finding here by the district court. [00:05:20] Speaker 02: The record suggests that that's the only finding that could be made with respect to that. [00:05:26] Speaker 00: Respectfully, I don't think so, Your Honor, because of the qualifier that I wanted to insist on in response to your question. [00:05:32] Speaker 00: And that while there is testimony about doctors insisting that their patients take folic acid, [00:05:38] Speaker 00: There is no evidence about insisting on the range in particular and saying, for example, if you've come in and you've taken 1,001 micrograms of folic acid, go away. [00:05:52] Speaker 00: I won't give you the treatment. [00:05:55] Speaker 00: That's the level of direction and control that might satisfy this court's cases. [00:06:01] Speaker 00: and hold one actor legally responsible for the other. [00:06:04] Speaker 03: Well, the prescribing information, and clearly we're back to page 827 with the conclusions of the district court where the prescribing information clearly directed them to do that specifically. [00:06:17] Speaker 03: to take a specific amount, instruct the patients to initiate a certain amount of folic acid, et cetera. [00:06:22] Speaker 00: Well, it's a certain amount of folic acid. [00:06:25] Speaker 00: In the prescribing information, it's 400 micrograms to 1,000, which is slightly different from the patented range. [00:06:32] Speaker 00: But we don't think that that broad range, in a sense, you can take [00:06:41] Speaker 00: you can take any amount within a wide range. [00:06:44] Speaker 00: First of all, directing the patient to do that isn't enough direction or control because of the other aspects of this case that [00:06:52] Speaker 00: give the patient a lot of freedom about what to take. [00:06:55] Speaker 00: Do you take a multivitamin? [00:06:57] Speaker 00: Do you take one of the many commercially available alternatives? [00:07:01] Speaker 00: When do you take it? [00:07:03] Speaker 00: And what this court's cases have said is that direction has to be over the manner and timing of performance. [00:07:10] Speaker 00: We don't think that just saying, take somewhere between 400 and 1,000 micrograms is enough. [00:07:15] Speaker 00: Doctors give an awful lot of advice to patients. [00:07:20] Speaker 00: Take two over-the-counter aspirin. [00:07:22] Speaker 00: Take with food. [00:07:24] Speaker 00: Take on an empty stomach. [00:07:26] Speaker 00: Take after a good night's sleep. [00:07:27] Speaker 04: So if the doctor gives conflicting advice or advice outside of the label, why does that invalidate the patent? [00:07:35] Speaker 04: That's my question. [00:07:37] Speaker 00: If the doctor gives advice outside the label, in other words, the doctor says, my practice is to do something more than the label requires me to do. [00:07:45] Speaker 04: I think you are telling us that there are limits that may or may not be respected. [00:07:52] Speaker 00: If I'm understanding your honor's question. [00:07:56] Speaker 00: I'm trying to understand your argument. [00:07:58] Speaker 00: I'm saying that the doctor would have no reason to insist on performance within the patented range, the point that I made about 1,001 micrograms. [00:08:08] Speaker 04: Yes, exactly. [00:08:09] Speaker 04: But why does that invalidate the patent? [00:08:10] Speaker 00: We're not saying it invalidates the patent. [00:08:12] Speaker 00: We're saying that the fact that if the doctor wouldn't care if the patient comes in having taken 1,001 micrograms or 1,002 micrograms or 1,100 micrograms, [00:08:22] Speaker 00: then the doctor isn't exercising the level of control over how much the patient takes, which is necessary for the patient's selection of a particular amount within the range, which would be necessary for infringement to be attributable to the doctor. [00:08:38] Speaker 00: This whole exchange is turned on whether the doctor is insisting that the patient do very specific things or giving advice that's much further along the continuum, closer to [00:08:53] Speaker 00: you know, take two aspirin or take on an empty stomach. [00:08:56] Speaker 02: I'm not following this. [00:09:00] Speaker 02: Suppose the doctor tells the patient, I won't give you this medication unless you take folic acid 400 to 1,000 milligrams orally once a day beginning seven days before the first dose of LTE. [00:09:18] Speaker 02: If that instruction were given, [00:09:21] Speaker 02: by the physician to the patient, would that satisfy the infringement requirements? [00:09:30] Speaker 00: I won't give you Pematrexid. [00:09:33] Speaker 00: I think the doctor would have to say that and to follow through on it. [00:09:39] Speaker 00: In other words, to verify not only did you take some folic acid. [00:09:45] Speaker 00: but also to verify the amount. [00:09:47] Speaker 00: That, I think, would be necessary for the relevant level of control to be exercised. [00:09:51] Speaker 02: But if he did say that and verified it, that would be infringement? [00:09:55] Speaker 00: I think that could be the right level of control, yes. [00:09:59] Speaker 00: We're not arguing with that. [00:10:01] Speaker 00: We are saying that that's not what was established here. [00:10:08] Speaker 00: It was the other side's burden to establish not only that, but also that even if they could find a doctor who exercised that level of control over the particular amount, that they would have to show that our clients are responsible for that, that they've induced the doctors to do that. [00:10:26] Speaker 00: And the district court found that inducement in the labeling and nowhere else. [00:10:32] Speaker 00: The mere fact that you say in the labeling. [00:10:35] Speaker 02: Why can't we assume that the doctors would follow through on the what they're told to do in the label? [00:10:42] Speaker 00: I don't think that the labeling directs them to the labeling certainly doesn't direct them to withhold hematrexit treatment the labeling in particular if someone has has a healthy folate level in their blood, but they've taken slightly too little or slightly too much and [00:11:01] Speaker 00: Folic acid and there are lots of other ways to get folate. [00:11:05] Speaker 00: It's It's in a lot of food. [00:11:09] Speaker 00: It's in you know. [00:11:10] Speaker 00: It's supplemented and preserved foods There are reasons why a doctor would not say I'm not going to give you this life Make sure I got all my knots right the doctor would not say I'm not going to give you this life-threatening life-saving treatment because you took just a little bit too much folic acid the doctors there's no evidence the doctors are so focused on on the amounts and [00:11:31] Speaker 00: If I may, I'd like to say a bit about the indefiniteness issue in my time here. [00:11:38] Speaker 00: So the question here is whether vitamin B12 has a sufficiently definite meaning to a person of skill in the art. [00:11:46] Speaker 00: And the other side, the patentee defines [00:11:52] Speaker 00: Sorry the patent uses vitamin b12 in different ways and it is common ground I think that there are different ways accepted in the art of [00:12:03] Speaker 00: that different things that vitamin B12 can mean. [00:12:05] Speaker 00: It can mean either specifically cyanocobalamin, or it can mean something broader. [00:12:11] Speaker 03: Yeah, but it's true of this issue, and it's true of a lot of issues. [00:12:16] Speaker 03: The district court made findings. [00:12:18] Speaker 03: There were experts that testified she credited some and not others. [00:12:22] Speaker 03: On this issue, I recall that the experts did agree that B12 is used as a vitamin supplement for use in medical contexts. [00:12:31] Speaker 03: B12 was synonymous with [00:12:33] Speaker 03: That word I can't pronounce. [00:12:36] Speaker 00: And no, Your Honor. [00:12:37] Speaker 00: This is a very important point. [00:12:39] Speaker 00: I'm glad you brought it up. [00:12:41] Speaker 00: But the findings, first of all, the other side's expert testified not just about what the ordinary meaning was. [00:12:48] Speaker 00: If you look at 3821 of the appendix, you'll see that the expert was declaring what he thought the meaning in the claims to be. [00:12:54] Speaker 00: In other words, he was being an expert not about [00:12:58] Speaker 00: just ordinary meaning, but he was actually trying to interpret the patent. [00:13:02] Speaker 00: And that's just the kind of extrinsic evidence that this court does not defer to, especially when our argument about indefiniteness is based squarely on the intrinsic record, on the specification itself. [00:13:13] Speaker 03: Well, I know you may know more about Tevin than I do. [00:13:16] Speaker 03: But it seems to me that her accepting Dr. O'Dwyer's representation that a person of ordinary skill, how we would understand B12 to mean it, [00:13:28] Speaker 03: is maybe come under the bucket of extrinsic evidence, right? [00:13:32] Speaker 00: It's extrinsic, but after all, in TEVA itself, the debate in TEVA itself was whether there are different ways to determine the meaning of a particular testing method, and you couldn't tell based on the intrinsic [00:13:48] Speaker 00: record, this court said, which one was to be used. [00:13:52] Speaker 00: And there was a finding, there was an expert, and this is explained in the court's opinion in Dow just recently. [00:13:58] Speaker 00: There was a finding by the district court that a person of skill and the art could, in fact, tell by looking at the specification which one was meant. [00:14:05] Speaker 00: And this court said, that's not a proper use of extrinsic evidence. [00:14:09] Speaker 00: We will not defer to it. [00:14:10] Speaker 00: We will instead, because [00:14:11] Speaker 00: Because the intrinsic evidence is in conflict, we will hold the patent fatally indefinite. [00:14:16] Speaker 00: That was this court's holding on remand in Teva and further explained in Dow, where likewise the patent was found indefinite. [00:14:24] Speaker 00: And your other question, Chief Judge, was about whether cyanocobalamin is the only one used as a supplement. [00:14:30] Speaker 00: And that simply is not so. [00:14:32] Speaker 00: Hydroxocobalamin is also used as a supplement. [00:14:35] Speaker 00: Not only that, as an injectable supplement. [00:14:37] Speaker 00: And this, after all, is a patent that specifically says that the B12 [00:14:40] Speaker 00: will be injected. [00:14:41] Speaker 00: And actually if you look at A750-51, this is after the claim construction as a testimony from the trial, but it is about the use of hydroxocobalamin as a supplement in the UK and in Europe. [00:14:53] Speaker 00: So there certainly is no basis for saying that [00:14:55] Speaker 00: If supplement, then cyanocobalamin. [00:14:58] Speaker 00: Certainly nothing that could overcome the conflict in the intrinsic record itself. [00:15:02] Speaker 00: If you look at the claims, there's B12 and there's cyanocobalamin, which would tell someone reading the claims that these are different things. [00:15:11] Speaker 00: They're not synonymous. [00:15:12] Speaker 00: And that is backed up by the lengthy discussion, I think, in, I guess, column six, where it says vitamin B12 refers to, and there's a long list of substances. [00:15:24] Speaker 00: and refers to the chemical derivatives as well. [00:15:27] Speaker 00: And what a person of skill in the art needs to know is can they design around this claim by using a vitamin B12 variant that is not one of the ones specified but that would be picked up by that broader meaning? [00:15:39] Speaker 00: Or is vitamin B12 just cyanocobalamin? [00:15:42] Speaker 00: There's no way to tell that from the intrinsic record here. [00:15:44] Speaker 03: You've gotten to your rebuttal time. [00:15:46] Speaker 03: I'll restore three minutes for rebuttal. [00:15:48] Speaker 03: Thank you. [00:16:01] Speaker 01: Good morning, your honor. [00:16:02] Speaker 01: May it please the court, Adam Perlman on behalf of Eli Lilly. [00:16:05] Speaker 01: Let me start with the question that Judge Prost asked about the district court's findings on infringement. [00:16:10] Speaker 01: And it is, in fact, the sentence immediately before the one that Judge Prost read aloud on page A27. [00:16:15] Speaker 01: The court says it is clear from the patent, the prescribing information, and the patient information that taking folic acid in the manner specified is a condition of the patient's participation in Pembitrexib treatment as described in the patent. [00:16:29] Speaker 01: That is a finding based on the undisputed evidence [00:16:32] Speaker 01: at trial that if the patients do not take folic acid as directed by their physician, the physician will not provide them with Pematrexid. [00:16:41] Speaker 01: That is supported exactly by the label, which I will take you through in a moment, and it's also undisputed that that is the uniform way in which medicine is practiced in this country with Pematrexid. [00:16:52] Speaker 03: Is there necessarily inducement if the product labeling for a drug and nothing more contains instructions as to the steps? [00:17:01] Speaker 03: Is that enough? [00:17:02] Speaker 01: Yeah, in the end of context, because there's been no actual sales, if the label, this is the court's AstraZeneca opinion, which I believe your honor author, if the label encourages or recommends steps that would cause at least some users to infringe, from that we infer intent to induce infringement by the party using that label and selling the product. [00:17:24] Speaker 01: And in this case, if you look at the physician label, [00:17:29] Speaker 01: multiple times in the label. [00:17:30] Speaker 01: It's on the first page twice. [00:17:31] Speaker 01: But I'll take you to A11258, section 5.1 of the label. [00:17:37] Speaker 01: The heading is, requirement for pre-medication and concomitant medication to reduce toxicity. [00:17:44] Speaker 01: And it's undisputed. [00:17:45] Speaker 01: This is directed to the physician and is the instructions to the physician about how to administer the drug. [00:17:50] Speaker 01: And it says, prior to treatment with olymptah, initiate supplementation with oral folic acid and also B12. [00:17:57] Speaker 01: I'll skip that. [00:17:57] Speaker 01: to reduce the severity of hematologic and gastrointestinal toxicity of olymptum. [00:18:02] Speaker 01: And it goes on and says, in clinical studies, where people didn't do that, very severe toxicities occurred, including death. [00:18:09] Speaker 02: And what that is saying to the doctor. [00:18:11] Speaker 02: I guess the problem here is, it seems to me, in reading Akamai, whether just a direction to the physician to get the patients to do this is sufficient, or does there have to be evidence of some sort of enforcement [00:18:24] Speaker 02: mechanism or practice by the physicians with respect to that, and the argument is that there isn't evidence here of an enforcement mechanism with respect to the specific doses and schedule, right? [00:18:38] Speaker 01: Well, that is the argument, and the Gister court made findings on this, and the evidence at trial was undisputed on this, that based on the label, [00:18:47] Speaker 02: The label says, as a physician, you must... I guess what I'm asking is, is the label alone sufficient to bring about direction? [00:18:55] Speaker 01: So in this case, the label alone is sufficient for us to prevail. [00:19:00] Speaker 01: But in this case, we have both the label and undisputed evidence about what happens in the real world in response to this label. [00:19:06] Speaker 01: Because unlike some of this court's cases that the defendants have cited, where the generic had carved something out of the label, and the question was, was there some sort of vague intimation that would sort of bring in the thing that was carved out? [00:19:17] Speaker 01: The defendant's label is identical to the Olymptal label. [00:19:20] Speaker 01: That's why the trial was conducted on the basis of the Olymptal label. [00:19:23] Speaker 01: And we have years of real-world experience about what the label induces physicians to do in treating patients with Pematrexid. [00:19:31] Speaker 01: Both sides experts agree that all physicians uniformly require patients to take folic acid as a condition of receiving Pematrexid. [00:19:38] Speaker 02: And just like in Akamai, you could not necessarily in the doses on the label. [00:19:44] Speaker 01: Yes, in the doses on the label. [00:19:46] Speaker 02: Where does it say that? [00:19:47] Speaker 01: Well, it says, where does the label say that, or where does the evidence say that? [00:19:51] Speaker 01: Where does the evidence say that? [00:19:55] Speaker 01: The evidence is at, this report cited this on A28, but at A2196 to 97, Dr. Chavner essentially says that the physician is in control and tells the patient what dose to take. [00:20:11] Speaker 01: The patient does not do what the doctor says in terms of taking the folic acid as directed. [00:20:16] Speaker 01: The doctor will not give the pemotrexate. [00:20:18] Speaker 02: And I will say that in an and a case... It seems to me a bit different than saying that physicians make a practice of telling them, if you don't take this specific dose, you won't get the pemotrexate. [00:20:29] Speaker 01: Well, one, we look at the label and presume that the physicians and the patients follow the label. [00:20:37] Speaker 01: The evidence is that they do, but we presume that in the Ande case. [00:20:39] Speaker 02: Well, that comes back to my question. [00:20:42] Speaker 02: Is the label alone enough? [00:20:44] Speaker 02: Because it doesn't seem to me that there is evidence that physicians require the kind of specific compliance as a condition that would bring their actions within the limits of the patent. [00:20:58] Speaker 01: Well, I think there is that testimony. [00:21:00] Speaker 01: I think it's on the pages that I cited. [00:21:02] Speaker 01: But I think the label is sufficient here because in an Ande case, [00:21:06] Speaker 01: The point is that if the acts on the label are performed, would there be infringement? [00:21:12] Speaker 01: Here the label says, the patient has to take 400 to 1,000 on the schedule set forth in the label. [00:21:20] Speaker 01: And if they do that, and if the doctor tells them to do that, they can have Pematrexit. [00:21:25] Speaker 01: And if they don't, they can't have Pematrexit. [00:21:26] Speaker 01: And in Akamai, remember, it was condition participation in the activity and, I forget the exact word, but essentially direct [00:21:36] Speaker 01: the manner or the timing of the practice of that step. [00:21:41] Speaker 01: And here, we have the doctor telling the patient, take folic acid orally, starting seven days before. [00:21:47] Speaker 01: Take folic acid in this dose. [00:21:50] Speaker 01: I mean, there's a bit of a red herring going on here about whether the doctor says a specific dose within the label range of 400 to 1,000, or whether the doctor says, go ahead and take anything within the range of 400 to 1,000. [00:22:03] Speaker 03: What's the range in the patent? [00:22:06] Speaker 01: The range in many of the claims of Patent is 350 to 1,000. [00:22:09] Speaker 01: So it's completely, most of the claims are completely subsumed by the entire range. [00:22:13] Speaker 01: We have a couple, three claims that say 350 to 600. [00:22:17] Speaker 01: But under Synovian, they are seeking approval for doses within that range, 350 to 600. [00:22:22] Speaker 01: And lost my thought for a moment. [00:22:26] Speaker 01: Sorry. [00:22:27] Speaker 01: No, no, Your Honor. [00:22:32] Speaker 01: It doesn't matter for infringement. [00:22:33] Speaker 01: The only relevant, I heard Mr. J talk about all the things that you go to the pharmacy, you get a multivitamin. [00:22:39] Speaker 01: The only thing you have to control under Akamai, or direct under Akamai, is the practice of the claim element. [00:22:45] Speaker 01: You don't have to control the rest of the patient's life in relation to that element. [00:22:50] Speaker 01: And here, the requirement is that they take a certain amount of folic acid on a particular schedule as directed by the doctor. [00:22:57] Speaker 03: Well, how do they enforce that requirement? [00:22:59] Speaker 03: That's part of Akamai. [00:23:00] Speaker 03: You can't just... Absolutely. [00:23:01] Speaker 01: And they enforce that requirement because they inquire of the patient, have you done this? [00:23:06] Speaker 01: And the label tells them to do that. [00:23:08] Speaker 01: It says, you have to initiate folic acid before you, the doctor, who are in unique control of giving pembitrexid, because it's prescription and it's by infusion, before you give that pembitrexid, you must initiate folic acid. [00:23:21] Speaker 01: The testimony was, and the district court found, that the inverse of that is equally true from the label. [00:23:26] Speaker 01: That if you haven't successfully initiated folic acid, if the patient hasn't taken it, don't give the Pematrexin. [00:23:32] Speaker 01: And the reason for that is very logical. [00:23:34] Speaker 01: The whole reason anyone is doing this, and it's set forth right in the label, is that patients were dying in the phase three clinical trial when they were not supplemented in advance with Pematrexin. [00:23:46] Speaker 02: Where is the testimony that they condition it on a specific dose? [00:23:51] Speaker 01: I believe, if it's not at the page I cited to you, I believe it. [00:23:53] Speaker 02: I didn't look at the page. [00:23:55] Speaker 01: This report cites it at A28, and she cites to 2196 to 97 in the appendix. [00:24:02] Speaker 01: And I think we have other citations probably in our brief. [00:24:04] Speaker 01: That is the one I brought to the podium with me. [00:24:06] Speaker 01: But Your Honor, the idea that- Wait, wait, wait. [00:24:14] Speaker 01: Let's see. [00:24:15] Speaker 01: 2196 to 2197. [00:24:16] Speaker 01: So we're- OK. [00:24:26] Speaker 02: use a standard dose, that's 1,000. [00:24:28] Speaker 02: And that's within the patented range of 1,000? [00:24:35] Speaker 01: Yes, sir. [00:24:36] Speaker 01: We have claims that go 350 to 1,000. [00:24:40] Speaker 01: We have other claims that go 350 to 600, which, as I say, the former claims all completely subsume the label range. [00:24:47] Speaker 01: And the 350 to 600 claims overlap with the label range. [00:24:51] Speaker 01: And so the label is inducing the practice of those claims. [00:24:55] Speaker 03: I didn't get that last one. [00:24:58] Speaker 03: If the range in certain claims is 350 to 600, and they're prescribing 1,000, that comes within the range? [00:25:06] Speaker 01: No, so Your Honor, the question in the end of the case is, this is under Synovian, what is the label seeking approval for? [00:25:13] Speaker 01: And the label is seeking approval for a regimen in which doctors can say 400 up to 1,000. [00:25:20] Speaker 01: Because 400 is within the label, 450, 500 are in the label, and that overlaps with the claim, that is infringement of the claim under this court's synonym. [00:25:28] Speaker 02: But if we conclude that the 400 to 600 claims aren't infringed, does that make a difference in the outcome? [00:25:34] Speaker 01: Makes absolutely no difference. [00:25:35] Speaker 01: The 350 to 1,000 claims are absolutely infringed, and it makes absolutely no difference. [00:25:42] Speaker 01: Let me just say I want to make one final point on infringement, and then I want to move to the Nautilus issue. [00:25:51] Speaker 01: We heard a couple arguments about how doctors say, go ahead, take an aspirin, eat better, give all kinds of instructions. [00:25:56] Speaker 01: This is not that kind of instruction. [00:25:59] Speaker 01: People were dying in the clinical trial. [00:26:01] Speaker 01: And the way that the FDA and Lilly agreed to address that was to say, doctors, you have to give them folic acid and B12 before they get this medicine. [00:26:09] Speaker 01: And you have to instruct the patients. [00:26:10] Speaker 01: They have to do it. [00:26:11] Speaker 01: And the label tells both patient and doctor, you have to do it. [00:26:14] Speaker 01: And the idea that the argument that we're getting from the defendants is what all the label really induces is for the doctor to say to the patient, [00:26:20] Speaker 01: Take some folic acid, and I otherwise wash my hands of the situation. [00:26:23] Speaker 01: I think it's not a credible reading of the label. [00:26:25] Speaker 01: The district court made a fact finding regarding the label. [00:26:29] Speaker 01: There was testimony about the label. [00:26:31] Speaker 01: I don't think there's any error at all. [00:26:33] Speaker 01: But even if there were errors, certainly not clear error. [00:26:35] Speaker 01: The label and the undisputed testimony support infringement. [00:26:40] Speaker 01: Let me turn to Nautilus. [00:26:42] Speaker 01: And let me clear something up. [00:26:45] Speaker 01: Chief Judge Prost was absolutely correct. [00:26:48] Speaker 01: The evidence before the trial court [00:26:50] Speaker 01: was that in the context of giving a vitamin supplement to a patient, when physicians say vitamin B12, they mean synocobalamin. [00:27:01] Speaker 01: There is one established meaning. [00:27:03] Speaker 01: The fact that hydroxocobalamin might be given as a supplement is irrelevant. [00:27:07] Speaker 01: No one calls it B12. [00:27:09] Speaker 01: They call it hydroxocobalamin. [00:27:12] Speaker 01: The district court made that finding at page A85 of the appendix. [00:27:16] Speaker 01: The argument was, well, if you look back at the expert's report, he testified as to both [00:27:20] Speaker 01: the ordinary understanding of the term and the art, and also the ultimate conclusion of what the construction of the claim should be. [00:27:28] Speaker 01: That's a true statement. [00:27:30] Speaker 01: The district court, though, accepted the factual testimony regarding what the ordinary meaning of the art is, as is clear from her opinion. [00:27:36] Speaker 01: The fact that his testimony on the ultimate issue may not be entitled to deference, the testimony that led to the finding that [00:27:44] Speaker 01: The ordinary meaning in this context is Sino-Kobalaman was made by the district court and is entitled to clear error review and they've established no clear error. [00:27:52] Speaker 01: Now that distinguishes this case from both Dow and Teva, both of which were about terms of measurement that could have different meanings in the art and in neither case was there an established default meaning [00:28:05] Speaker 01: to the person of ordinary skill. [00:28:07] Speaker 01: And the evidence in this case is that there is such an established default meaning, and it is Sinoquibalamin and the district court made a finding in that regard. [00:28:17] Speaker 01: Let me briefly touch on this issue about the specification and column five and vitamin B12 referred to paragraph that Mr. Che mentioned. [00:28:30] Speaker 01: And no one is arguing that this is an express redefinition [00:28:35] Speaker 01: of the term vitamin B12. [00:28:37] Speaker 01: The district court found that it wasn't, and the defendants aren't arguing on appeal that it was, such that it should be applied. [00:28:42] Speaker 01: And looking at the patent, that's obviously correct. [00:28:48] Speaker 01: Because one, as the district court held, for other terms, it says as used herein, it means this. [00:28:53] Speaker 01: As used herein, it means this. [00:28:55] Speaker 01: Doesn't do that for B12. [00:28:56] Speaker 01: But more importantly, [00:28:57] Speaker 01: This paragraph doesn't purport to define what vitamin B12 means. [00:29:01] Speaker 01: It says vitamin B12 refers to vitamin B12 and its pharmaceutical derivatives. [00:29:05] Speaker 01: And that is putting the reader on notice on what was accepted by everyone in the trial court that the term has different meanings depending on the context that it is used, either broader or narrower. [00:29:17] Speaker 01: But in the context of the patent, which is about administration of a supplement to a patient, it has one [00:29:25] Speaker 01: and only one meaning, and that is cyanocobalamin. [00:29:28] Speaker 01: And that is supported by the structure of the claim itself. [00:29:31] Speaker 01: Claim one says B12 and a variety of other listed agents. [00:29:36] Speaker 01: And then claim two says wherein the agent is vitamin B12. [00:29:40] Speaker 01: It is entirely consistent with vitamin B12 meaning cyanocobalamin. [00:29:44] Speaker 01: And claim two is therefore narrower than claim one. [00:29:49] Speaker 01: The argument that we saw in the brief, and I suspect we're going to hear on rebuttal, is well, [00:29:54] Speaker 01: There's a redundancy in claim one, because sano cobalamin is also there. [00:29:58] Speaker 01: Under either established meaning in the art, either sano cobalamin or all cobalamins, there's a redundancy in claim one. [00:30:06] Speaker 01: That's a fact. [00:30:07] Speaker 01: It just is. [00:30:08] Speaker 01: And while this court's cases say we prefer that claim terms have distinct meanings, it also holds that when two terms are properly construed to mean the same thing, then so be it. [00:30:17] Speaker 01: That's what they mean. [00:30:18] Speaker 01: Here, there are two established meanings. [00:30:21] Speaker 01: No one has ever suggested that there is a third meaning. [00:30:24] Speaker 01: And they both lead to a redundancy, which tells you that looking for a redundancy isn't going to resolve this question for you. [00:30:29] Speaker 01: But looking at claim two does resolve this question for you, because it couldn't be the broad meaning. [00:30:33] Speaker 01: It has to be the narrow meaning, or otherwise claim one is not narrower than claim two. [00:30:39] Speaker 01: I'm coming to the end of my time. [00:30:40] Speaker 01: There was also an obviousness and obviousness to all the patent issues raised. [00:30:43] Speaker 01: I don't have anything to say on that if there aren't any questions on that. [00:30:46] Speaker 01: And if there are no further questions from the court, I will sit down. [00:30:49] Speaker 01: Thank you. [00:30:57] Speaker 00: Thank you, Your Honors. [00:30:58] Speaker 00: I want to correct one page reference that I gave you before. [00:31:00] Speaker 00: 3621 is where the expert always made clear he was opining on what's in the claims, what the meaning is of the claims. [00:31:08] Speaker 00: Mr. Perlman, to go back to the divided infringement point about the labeling, Mr. Perlman relied on the word requirement in the prescribing instructions. [00:31:20] Speaker 00: But if the argument were that everything in the prescribing instructions is telling you [00:31:26] Speaker 00: that if this isn't precisely followed, withhold Pematrexid, including the quantity and everything else, then you wouldn't have what you have in the patient instructions because the prescribing instructions say take it every day. [00:31:41] Speaker 00: The patient instructions say take it five out of every seven days. [00:31:44] Speaker 00: That's in there because patients miss doses. [00:31:47] Speaker 00: And so you just can't get out of the prescribing instructions that absolutely everything in here is a cynical unknown. [00:31:53] Speaker 00: It has to be followed exactly or you will withhold treatment. [00:31:56] Speaker 00: You certainly can't say that if there are individual doctors who go overboard and do what is quoted on the page that Mr. Perlman relied on, do things like require patients to have pill diaries, bring in empty bottles, and prove that they've taken their pills. [00:32:14] Speaker 00: Even if there are doctors who do that, that is not required by the labeling. [00:32:18] Speaker 00: That's not something that is induced by TEVA, and it's not something that can be [00:32:23] Speaker 00: attributed to the alleged induced infringer. [00:32:28] Speaker 00: It's certainly true that you don't have to control the other person's entire life in order to be deemed the same unit for direction and control purposes under divided infringement. [00:32:39] Speaker 00: What you do have to control is the manner and timing of what the person does. [00:32:44] Speaker 00: That's why the court in Akamai, for example, was emphasizing that [00:32:47] Speaker 00: Limelight was directing its customers to follow these precise steps. [00:32:51] Speaker 00: If there isn't that level of direction, then they aren't going to be considered the same unit for purposes of divided infringement. [00:33:00] Speaker 00: The thing to remember on divided infringement really is that this is a drafting issue. [00:33:04] Speaker 00: It's a drafting issue and an assertion issue as well. [00:33:07] Speaker 00: We wouldn't be talking about the quantities. [00:33:09] Speaker 00: I think Judge Dykes Colloquy with my friend brought out the importance of the quantities in the claims that Lilly chose to assert. [00:33:16] Speaker 00: They could have tried to go to trial on claim one, which doesn't have the quantities in it, but they chose instead to go to trial on the claims, perhaps for validity reasons, that have a specific quantity in it. [00:33:26] Speaker 00: They have to live with that choice. [00:33:28] Speaker 00: If they wanted to, if they're concerned about divided infringement, there are ways to draft claims that avoid the divided infringement question. [00:33:35] Speaker 00: That's something that this court has emphasized in all of its method claim cases. [00:33:39] Speaker 00: And the same is true here. [00:33:41] Speaker 00: They focus on it. [00:33:42] Speaker 00: If you focused on the advice of the doctor rather than the patient administering the folic acid, then you wouldn't have this issue. [00:33:51] Speaker 00: To switch gears and go to the [00:33:54] Speaker 00: indefiniteness issue. [00:33:55] Speaker 00: I'll just say that my friend said that column 5 doesn't redefine B12. [00:34:00] Speaker 00: Well, that's exactly the point. [00:34:02] Speaker 00: Column 5 recognizes that B12 has another meaning, a broader meaning that includes all of these pharmaceutical derivatives. [00:34:09] Speaker 00: And that is where, for example, hydroxycobalamin [00:34:12] Speaker 00: is called B12, right there in the patent. [00:34:15] Speaker 00: And the very fact that there are two meanings and the intrinsic record doesn't allow you to select between them and the redundancy, if anything, suggests that the narrower meaning isn't correct, that's why this patent is indefinite. [00:34:29] Speaker 00: It doesn't give enough information to design around the claimed invention and figure out whether you could use a different derivative of B12. [00:34:38] Speaker 00: Thank you very much. [00:34:38] Speaker 03: Thank you. [00:34:39] Speaker 03: We thank both parties and the cases submitted.