[00:00:04] Speaker 02: The first case for argument this morning is 181691, Idenex Pharmaceuticals versus Gilead. [00:00:12] Speaker 02: Good morning. [00:00:13] Speaker 01: Good morning. [00:00:16] Speaker 01: Chief Judge Prost, and may it please the court. [00:00:19] Speaker 01: Idenex's patent was a game-changing invention for the treatment of hepatitis C. It's a method of treating that virus with a class of two-prime methyl-up ribonucleosides. [00:00:32] Speaker 01: The industry immediately followed in the wake of the disclosure of this patent by making different kinds of those two prime methyl up ribonucleosides. [00:00:40] Speaker 01: And it stopped hepatitis C's virus in its tracks. [00:00:44] Speaker 02: And what stops it is the two prime fluoro down? [00:00:48] Speaker 01: That is the commercial embodiment of Gilead's product. [00:00:51] Speaker 01: That's correct. [00:00:52] Speaker 01: But that's not the only embodiment that stops it. [00:00:54] Speaker 01: And in fact, what I'm going to tell the court, Chief Judge Prost, is that there are two paths to reversal in this case. [00:01:00] Speaker 01: And both of them show. [00:01:02] Speaker 01: that the quid pro quo of the patent system worked in this case. [00:01:05] Speaker 01: The first path has to do with the rule 50 violations that we set forth in our brief, and the second has to do with the district court's misapplication of the law as requiring a person of ordinary skill to make every embodiment within the claims. [00:01:20] Speaker 01: Now if I could start by begging the court's indulgence, because we have a jury verdict here, and Gilead had a clear and convincing evidence standard, [00:01:29] Speaker 01: We have to look to see what implied facts the jury found in this case that are supported by the evidence. [00:01:35] Speaker 01: There are eight. [00:01:37] Speaker 01: There's one sentence. [00:01:38] Speaker 02: I don't know how much time we have to cover the eight. [00:01:41] Speaker 02: Can you talk to me about the numbers? [00:01:43] Speaker 02: What is your number in terms of the potential number of compounds here? [00:01:47] Speaker 01: So first of all, that's a question you might better ask my friend on the other side because it was their burden to prove. [00:01:54] Speaker 01: The court said the number was unclear. [00:01:56] Speaker 01: To me, that should be enough with regard to the clear and clear evidence. [00:02:00] Speaker 02: It may have said it was unclear. [00:02:02] Speaker 02: It started at billions, and it whittled it down to tens of thousands. [00:02:06] Speaker 01: He starts with billions, and then whittles it down using what he calls the refined structural limitations to tens of thousands. [00:02:14] Speaker 01: But what do those numbers represent? [00:02:17] Speaker 01: Those represent which ones of the two prime methyl up ribonucleosides work. [00:02:22] Speaker 01: And that goes to one of the things that the jury could have found here. [00:02:26] Speaker 01: The jury could have found that every two prime methyl up. [00:02:29] Speaker 02: But can we go back to my question about the numbers? [00:02:31] Speaker 02: Sure. [00:02:31] Speaker 02: What is your position about what number the jury must have relied on or did rely on or could have relied on? [00:02:39] Speaker 02: What is the number we're talking about? [00:02:41] Speaker 01: Well, all I can tell you, Your Honor, is that the [00:02:43] Speaker 01: District Court in this case said that the number that the jury could have relied on was in the thousands. [00:02:51] Speaker 01: But he prefaced that with may and might language. [00:02:55] Speaker 01: And he said the number was unclear. [00:02:56] Speaker 01: And again, to the extent. [00:02:58] Speaker 03: But he said it was unclear as to whether it was a lot more than that, not a lot less than that. [00:03:03] Speaker 01: Well, and that's right. [00:03:04] Speaker 01: But here's the point. [00:03:06] Speaker 01: That's important. [00:03:07] Speaker 01: Well, it is important. [00:03:09] Speaker 01: But what's important about the number is which ones of them work. [00:03:14] Speaker 01: which ones of them actually work. [00:03:16] Speaker 03: Well, what's also important about the number is how fast you can get through them. [00:03:21] Speaker 01: Well, that's why I want to go to the facts, because I think that before I can have a coherent discussion with you, and I can do this very quickly. [00:03:29] Speaker 01: And I'm not going to overstate the record. [00:03:31] Speaker 01: I'll have citations for you if you'd like. [00:03:33] Speaker 02: But you said what matters is what it works. [00:03:35] Speaker 02: But you have to screen and synthesize to see what works. [00:03:39] Speaker 02: No, you don't have to. [00:03:40] Speaker 02: What do you mean what it works? [00:03:43] Speaker 02: What is claimed here? [00:03:44] Speaker 02: You have to enable the full scope of the claim. [00:03:48] Speaker 01: Yes, absolutely. [00:03:49] Speaker 01: I really am trying to answer the court's question. [00:03:51] Speaker 01: I'm not trying to avoid it at all. [00:03:52] Speaker 02: Okay, and I'm just still looking for a number. [00:03:55] Speaker 02: You're trying to defend a jury verdict, and we want to put ourselves in the place of the jury and see what number they were working with. [00:04:03] Speaker 02: Do you accept the judge? [00:04:05] Speaker 02: You said the district court said it was unclear. [00:04:07] Speaker 02: Yeah, as Judge Wallach pointed out, whether it was tens of thousands reaching up to billions. [00:04:12] Speaker 02: What number are you assuming the jury relied on? [00:04:16] Speaker 01: I can only go by what the [00:04:18] Speaker 01: what the judge said and say that it's in the thousands. [00:04:21] Speaker 01: If I accept that burden, I accept it for purposes of argument, because I don't believe we have any burden here whatsoever. [00:04:29] Speaker 02: From a matter of burden, we're trying to evaluate the basis for the jury's opinion. [00:04:34] Speaker 02: to jury's decision. [00:04:36] Speaker 02: They heard all of the evidence. [00:04:38] Speaker 02: We've got to credit your evidence in that regard. [00:04:42] Speaker 02: If we're trying to discern what number, what universe we're talking about, then we've got to have in our mind the number. [00:04:49] Speaker 02: If you agree with us that we can accept the discourse analysis in that regard, that's fine. [00:04:54] Speaker 02: That answers my question. [00:04:55] Speaker 01: Well, I will accept it for purposes of argument because then what we now know, if it's thousands, [00:05:00] Speaker 01: is that you can screen thousands instantaneously. [00:05:03] Speaker 01: And screening is not an impediment to enablement. [00:05:07] Speaker 01: Juan says that. [00:05:09] Speaker 01: Atlas Powder says that. [00:05:11] Speaker 01: Judge Bryson's Euro PEP opinion, which was affirmed by this court under Rule 36, says that. [00:05:18] Speaker 01: Screening, the question at that point is, is screening [00:05:21] Speaker 01: undue experimentation. [00:05:23] Speaker 01: The evidence in this case was that even if you assume that you were dealing with the universe of thousands, screening would have been quite easy. [00:05:29] Speaker 02: Are you also assuming they were all in the library? [00:05:31] Speaker 02: You don't have to do any synthesis? [00:05:33] Speaker 01: No, but let me again go to what the jury could have found here. [00:05:37] Speaker 01: The jury could have found that identics as patent directed a person of ordinary skill in the art to focus on the HCV polymerase. [00:05:45] Speaker 01: I'll give you citations to each of these if you want, but I'm just going to go through them quickly. [00:05:49] Speaker 01: The jury could have found [00:05:50] Speaker 01: that identix's patent directed a person of ordinary skill in the art that two methyl-up ribonucleosides, which is all we've claimed, the method using those ribonucleosides, predictably terminate the chain of the hepatitis C virus by attacking at the NS5B point. [00:06:08] Speaker 01: The jury could have concluded that all two prime methyl ribonucleosides were active against the hepatitis C virus, so that the numbers don't matter. [00:06:17] Speaker 01: Screening was irrelevant. [00:06:18] Speaker 01: In fact, the patent calls screening merely confirmatory. [00:06:22] Speaker 01: Fourth, if any screening... Can I just ask you about that? [00:06:25] Speaker 01: Sure. [00:06:25] Speaker 02: You're saying that they were all effective, and that's because they all could have been screened, because they all were screened? [00:06:32] Speaker 01: No. [00:06:33] Speaker 01: The reason for that is the testimony of Mr. Clark and Dr. Somadosi. [00:06:38] Speaker 01: Mr. Clark at A7311 said, and I quote, I can say for certain that I knew the two prime up methyl ribonucleosides were active against HCV. [00:06:49] Speaker 01: He also believed that his own embodiment, which is the fluorodone embodiment, would have anti-HCV activity. [00:06:55] Speaker 02: Well, wait a minute. [00:06:56] Speaker 02: There's some testimony at 37441 where your expert says you don't know whether or not a nucleoside will have activity against HCV until you make it and test it. [00:07:07] Speaker 01: That's right with regard to absolute confirmatory screening. [00:07:11] Speaker 01: Yes, that's the only thing that can be understood the same. [00:07:13] Speaker 02: Well, I don't mean use the word absolute confirmatory. [00:07:18] Speaker 02: You don't know whether or not it works. [00:07:20] Speaker 02: That's what we're supposed to be looking at. [00:07:22] Speaker 01: For clinical purposes, that's absolutely right. [00:07:25] Speaker 01: You've got to screen before you put anything into clinical trials. [00:07:29] Speaker 01: But that's not the enablement standard. [00:07:30] Speaker 01: The FDA clinical trial standard is not the enablement standard. [00:07:34] Speaker 01: The simple question is, does this patent enable a person of ordinary skill? [00:07:38] Speaker 01: And the answer is yes. [00:07:40] Speaker 01: We'll just give you a couple. [00:07:40] Speaker 02: And what is the connection between that and whether it works or not for the intended purpose and the claimed purpose, which is HCV? [00:07:49] Speaker 01: Right. [00:07:49] Speaker 01: The point is that the jury could have concluded that every two prime up ribonucleoside was effective against HCV. [00:07:57] Speaker 02: So you don't need any testing, any screening? [00:07:59] Speaker 01: Screening is only confirmatory and it only confirms so that you get it into the lab and you know it for certain. [00:08:04] Speaker 02: Okay, and can you tell me what that testimony is again? [00:08:06] Speaker 01: Sure. [00:08:06] Speaker 01: Let me start with Mr. Clark at A7311 where he says, and this is their witness, I can say for certain that I knew the two prime methyl nucleosides were active against HCV. [00:08:18] Speaker 01: He also says, [00:08:20] Speaker 01: three pages later, at A7314, that he believed his embodiment would have anti-HCV activity before he made it because, quote, that's what it's made for. [00:08:29] Speaker 01: This was, by the way, recognized as a fact dispute by Gilead's own lawyer, and that's at A37830. [00:08:37] Speaker 01: He says, in closing, Dr. Somadosi told you all [00:08:43] Speaker 01: two prime up methyl ribonucleosides would be effective. [00:08:46] Speaker 01: There's a conflict in the evidence. [00:08:47] Speaker 01: You should believe our witness. [00:08:50] Speaker 01: The jury didn't believe that. [00:08:52] Speaker 01: Dr. Sobodossi's testimony there, by the way, can also be found at A737-085. [00:08:57] Speaker 01: He testifies, quote, any two prime methyl ribonucleoside would be active against the hepatitis C virus, end quote. [00:09:09] Speaker 01: That's proposition three. [00:09:11] Speaker 01: was my point earlier. [00:09:12] Speaker 01: If any screening was necessary, it would have been quick and easy. [00:09:16] Speaker 01: Five, Identics's patent disclosed that substitutions could be made at any position, including the two prime down position, without affecting the expected activity. [00:09:27] Speaker 01: That's Appendix 80, column 22 of the patent. [00:09:31] Speaker 01: Also, Gilead's concession at the beginning of the Rule 50 motion in the trial court, where he said that all OH down embodiments [00:09:40] Speaker 01: were enabled. [00:09:42] Speaker 01: So the discussions about anything at any of the other positions other than two prime down should be out of this case. [00:09:49] Speaker 01: We're also in a very established art, nucleoside chemistry. [00:09:53] Speaker 01: Nucleoside chemistry had been established for over 30 years. [00:09:56] Speaker 01: Mr. Clark himself said, you could always make any compound you wanted to make. [00:10:01] Speaker 01: It was routine and a very developed science. [00:10:05] Speaker 01: Number seven, persons of ordinary skill knew that nucleosides were regularly used as chain terminators for other viruses like HIV, hepatitis B, and herpes. [00:10:15] Speaker 00: So we would have to conclude that based on the specification, which eventually if you work your way through, you finally get to the two prime F down substituent in a different context, that that aspect is, all of that is irrelevant as long as it's a two prime up methyl. [00:10:36] Speaker 01: That's our invention in this case is two prime methyl up. [00:10:40] Speaker 01: It doesn't matter what's at the down position. [00:10:41] Speaker 03: It doesn't matter how much you claimed. [00:10:43] Speaker 01: It matters exactly how much we claim because our specification and our enablement is absolutely commensurate with the full scope of that claim. [00:10:52] Speaker 01: This is what I'm trying to establish to you. [00:10:55] Speaker 00: But when you look at it, at all of the examples which include halogen, they don't include fluorine until you get to, at the very end, that it's just chlorine, iodine, bromine. [00:11:10] Speaker 00: And from that, can one draw some sort of inference that at least the two prime down F was not contemplated [00:11:20] Speaker 01: No, you can't draw that inference. [00:11:22] Speaker 01: As you yourself just said, Judge Newman, those are examples. [00:11:26] Speaker 01: Specification and the examples are not meant to be limiting. [00:11:29] Speaker 01: And the argument that identics had disclaimed fluorine at the down position was made and rejected at claim construction. [00:11:37] Speaker 01: It then became resurrected in the trial. [00:11:39] Speaker 01: But remember that the enablement here is not to enable a two-prime fluorodown embodiment. [00:11:45] Speaker 01: It's to enable the full scope of the claims. [00:11:47] Speaker 01: And the claims are two-prime methyl. [00:11:49] Speaker 02: Well, it must include the two-fluorodown, because that's the accused product. [00:11:55] Speaker 02: So it's got to include it, and it's got to enable it, right? [00:11:58] Speaker 01: Well, it's got to enable it in the sense that a claim to a genus like this one is, at least with regard to the chemical used in the method of treatment, has to enable the full scope. [00:12:08] Speaker 01: But it also does enable fluorine. [00:12:11] Speaker 01: And it enables fluorines for pretty much all the reasons, Judge Newman, that you pointed out. [00:12:15] Speaker 02: And in fact- So is it your view that all of the thousands were at least on the same, at least thousands? [00:12:21] Speaker 02: So all of those are effective for hepatitis C? [00:12:26] Speaker 01: It is my view that a jury could have concluded that based on the testimony here. [00:12:31] Speaker 01: And I want to remind the court of a couple of things here. [00:12:35] Speaker 03: Again- Well, hang on. [00:12:36] Speaker 03: OK. [00:12:38] Speaker 03: Because I have some questions. [00:12:39] Speaker 03: I'd let you run through your eight. [00:12:42] Speaker 03: On page 53 of the blue brief, you talk about phantom statements by the district court. [00:12:50] Speaker 03: On 53, you say, the district court also cited a purported admission from Dr. Meyer. [00:12:57] Speaker 03: And you discuss it. [00:13:01] Speaker 03: Quote, that not all compounds of interest were commercially available. [00:13:07] Speaker 03: The district court miscited a page. [00:13:09] Speaker 03: Did Dr. Meyer ever make that statement? [00:13:13] Speaker 01: We say that Dr. Meyer never made such a statement, and the source was actually from Gilead's Dr. Sechrist. [00:13:21] Speaker 03: You say it's from Gilead's lawyer. [00:13:24] Speaker 01: Well, it was the lawyer who misattributed it to Dr. Meyer. [00:13:28] Speaker 01: as we say here on the page that you've signed. [00:13:31] Speaker 03: But that statement was made, wasn't it? [00:13:32] Speaker 01: The statement was made, yes. [00:13:34] Speaker 01: But it was part of it. [00:13:36] Speaker 03: It wasn't a phantom statement. [00:13:39] Speaker 01: If the claim is made that we've overclaimed with regard to that being a phantom statement, I'll apologize to the court. [00:13:44] Speaker 03: I think you should. [00:13:45] Speaker 03: You should apologize to the district court for that. [00:13:47] Speaker 01: Well, but the larger point here is that the district court did, on Rule 50, resolve factual disputes. [00:13:56] Speaker 01: Chief Judge Prost, with regard to your previous question there about the, or actually, I think it was Judge Newman also, about the path through the patent, I also want to point you to Mr. Clark and Dr. Otto's testimony, where the district court said there was no evidence that a reasonable jury could have concluded that Clark actually used our patent in order to track right down to the floral embodiment. [00:14:18] Speaker 01: The evidence is actually to the contrary. [00:14:20] Speaker 01: Dr. Otto testified at page A. [00:14:22] Speaker 01: three seven three two two Not only that that doc that mr. Clark had the patent when he came to him with his idea to make a fluoro down embodiment But he showed him the path through They were looking for what they were calling a loophole and remember they had the specification But not the claims and they see that in these examples all of these other halogens But not fluorine are mentioned there so they go aha we think we found a loophole and [00:14:52] Speaker 01: They were wrong. [00:14:53] Speaker 01: And that shows, by the way, how the patent enables. [00:14:56] Speaker 01: It took this person of subordinary skill right to the embodiment that he actually made. [00:15:01] Speaker 02: Now, of course, you have to enable the entire scope. [00:15:04] Speaker 01: We are enabling the entire scope. [00:15:05] Speaker 02: But can I go back to make sure I understand your view was that based on this record, the jury could have concluded that every one of the thousands and thousands of compounds works effectively. [00:15:18] Speaker 02: Yes. [00:15:19] Speaker 02: But what about the expert testimony that I think we talked about, I mentioned earlier in the day, with your own expert saying that you'd have to test all of these? [00:15:30] Speaker 02: So even assuming testing is routine, so was the jury told, yes, we've tested all of these, and they all work? [00:15:37] Speaker 02: On what basis could the jury have concluded that they all work? [00:15:42] Speaker 01: Because of the mechanics of the two prime methyl [00:15:46] Speaker 01: molecule which attacks the RNA of the virus and causes the chain to terminate. [00:15:55] Speaker 01: It is that two prime methyl up. [00:15:56] Speaker 01: That was our invention. [00:15:57] Speaker 01: That's the thing that causes the chain to terminate. [00:16:00] Speaker 02: So no matter what else is there, that's what causes? [00:16:05] Speaker 02: Yes. [00:16:06] Speaker 01: There is evidence in the record of that. [00:16:07] Speaker 02: Without any screening? [00:16:10] Speaker 02: No testing, no screening, nothing. [00:16:12] Speaker 01: Only confirmatory, and that's the word. [00:16:14] Speaker 01: that the patent uses is confirmatory. [00:16:16] Speaker 01: Now, I think I'm already into my rebuttal time, but I want to be able to make sure that I'm answering the court's questions here because the factual record is so, so critical in this case. [00:16:26] Speaker 01: Even if I'm wrong, even if it was not reasonable, and I think it was based on the testimony I've given you, for the jury to conclude that Gilead had not met its burden on that particular factual issue, let me then assume that we're talking about the [00:16:42] Speaker 01: that there are some inoperable embodiments. [00:16:44] Speaker 01: Well, this court's case law, cases like Atlas Powder, cases like Wands, allow for a number of inoperable embodiments, and they can be screened, so long as the screening itself does not constitute undue experimentation. [00:17:00] Speaker 01: What's the record evidence in this case with regard to two-prime methyl up with activity? [00:17:07] Speaker 00: But it isn't just 2 prime methyl up, and this is the problem, and this is the problem that I have. [00:17:12] Speaker 00: You go through this patent specification, there is no generic formula that includes 2 prime methyl up, 2 prime F down. [00:17:23] Speaker 00: There's a generic formula for the other halogens down, but they're explicit. [00:17:32] Speaker 00: They don't mention fluorine. [00:17:34] Speaker 00: And this is a gap that you have to transcend, I think. [00:17:40] Speaker 01: Well, I think it's transcended, I think, by how a person of ordinary skill would and how a sub-ordinary [00:17:47] Speaker 01: skilled person of Mr. Clark actually did read the specification. [00:17:51] Speaker 00: It pointed him right to fluorine. [00:17:52] Speaker 00: If I were reading it, and if it says methylap, chlorine, fluorine, iodine down, I would say that includes fluorine? [00:18:01] Speaker 01: But it's just an example. [00:18:02] Speaker 01: It's an example. [00:18:03] Speaker 00: And when an example is giving you... Then why do they say halogen instead of mentioning 3 or 4? [00:18:08] Speaker 01: We don't know the actual reason. [00:18:11] Speaker 01: It could have been as simple as a typographical error, if that was what was intended. [00:18:14] Speaker 00: It's in several of the examples. [00:18:16] Speaker 00: It can't be a typographical error. [00:18:18] Speaker 01: It is the sort of thing that gets, if you look, the examples are exactly the same. [00:18:21] Speaker 01: They could have been just cut and pasted. [00:18:24] Speaker 01: But I don't know that for a fact. [00:18:26] Speaker 01: What I do know is that the claims include fluoro. [00:18:29] Speaker 01: And the patent points you to fluorine. [00:18:32] Speaker 01: Just the last point, Chief Judge Prost, because I want to get to the thing that you're stating concern about here. [00:18:39] Speaker 01: Let's say I'm wrong and that the jury was not allowed to conclude from the testimony, which is there, that all two prime methyl up compounds work. [00:18:53] Speaker 01: Two prime methyl. [00:18:54] Speaker 01: Two prime methyl up compounds work. [00:18:57] Speaker 01: Against the HCV virus let's say I'm wrong about that Let's take them a look at the testimony about what screening would have been necessary What other than other than general comments about you can't know and of course the understanding there is for certain Unless you've screened something because people are talking about making clinical embodiments and getting through the FDA Here's what Gilead's case was with regard to that the there was a list of [00:19:26] Speaker 01: 284 two prime methyl up Embodiments that is in the appendix And I don't I think it's I don't have the appendix site for the particular list But it is the it is a list that came from our client from identics Dr.. Seeger their expert put a demonstrative under [00:19:53] Speaker 01: The demonstrative is not part of the record. [00:19:55] Speaker 01: It's not in our record here. [00:19:57] Speaker 01: I'm informed that he's cherry-picked 40 inactive compounds from that list of 284. [00:20:03] Speaker 01: But he only talked about four in the record, and that's A37, 513, and 514. [00:20:12] Speaker 01: The only evidence the jury had was that most 2-prime methyl-up embodiments actually did have activity. [00:20:21] Speaker 01: or at least hadn't been shown by the party with the burden of proof to have inactivity. [00:20:27] Speaker 01: He didn't say all 284 don't work. [00:20:29] Speaker 01: And if you think about this, 40 inactive embodiments, if that's true, that's absolutely accepted as true after a jury considered this record, out of 284, that is well within what this court allowed in Wands with regard to screening out inoperative embodiments. [00:20:49] Speaker 01: That case had, depending on the version of the facts that the court accepted, either a 44% hit rate or a 2.8% hit rate, and both were acceptable. [00:20:58] Speaker 01: I know I'm into my rebuttal. [00:21:00] Speaker 01: Thank you. [00:21:00] Speaker 02: I'm going to move on. [00:21:00] Speaker 02: We'll save some time for rebuttal. [00:21:02] Speaker 02: Let's hear from the other side. [00:21:09] Speaker 04: Good morning. [00:21:10] Speaker 04: Good morning, Your Honors. [00:21:10] Speaker 04: May it please the court, Josh Rosencrantz representing Gilead. [00:21:15] Speaker 04: Let me go straight to the numbers, because that's where a lot of the court's questions were for the first half of Idenex's argument. [00:21:24] Speaker 04: There are three undisputed legal points. [00:21:30] Speaker 04: Excuse me. [00:21:30] Speaker 04: There are three undisputed facts that drive the entire enablement case and, by the way, written description, which I don't want to neglect to get to this morning, in our favor. [00:21:43] Speaker 04: And all of those facts came out of the witnesses of IDENIX, and in particular its experts, and IDENIX's lawyers' mouths. [00:21:54] Speaker 04: First, only a small portion of two prime methyl-up nucleosides are effective. [00:22:04] Speaker 04: The field was so unpredictable that you simply could not know, just from looking at a nucleoside, what would be active and what would not. [00:22:13] Speaker 04: And third, the universe of two prime methyl-up nucleosides that would have to be tested was vast. [00:22:22] Speaker 04: Now let me flesh out the numbers on each of this on the basis of undisputed testimony. [00:22:29] Speaker 04: So the court asked, [00:22:31] Speaker 04: on about the size of the candidate pool. [00:22:33] Speaker 04: So that's plank one of our argument. [00:22:36] Speaker 04: And this goes to Judge Prost's initial question. [00:22:40] Speaker 04: There was never a dispute that the universe of nucleoside. [00:22:43] Speaker 02: But I thought we got Mr. Kastanias to a point where we were talking about thousands. [00:22:48] Speaker 02: The district court was tens of thousands. [00:22:50] Speaker 02: So let's just assume we're in the same universe of numbers. [00:22:54] Speaker 02: What do you say to his remaining points? [00:22:56] Speaker 04: OK, so the next critical point [00:23:00] Speaker 04: question is, what proportion of those are active? [00:23:04] Speaker 04: He's now telling the court a jury could have concluded they were all active. [00:23:09] Speaker 04: Now, I'm surprised to hear this. [00:23:11] Speaker 04: This was never in dispute. [00:23:13] Speaker 04: It was actually a key piece of Idenex's argument that the universe of claimed compounds, that is, compounds that are active, was actually small. [00:23:24] Speaker 04: It said, and this is its Jamal opposition at pages three to four, [00:23:29] Speaker 04: It's docket 560, quote, that only a small number of compounds could be active against HCV. [00:23:36] Speaker 02: But he cited, what do you say? [00:23:38] Speaker 02: Didn't he give us a transcript site from your witness, Dr. Clark or Mr. Clark? [00:23:44] Speaker 04: He gave a site from Dr. Clark and from their founder, Somadosi. [00:23:49] Speaker 04: Both were talking about two prime methyl up, OH down, the compounds that are specifically identified and tested in the patent. [00:24:00] Speaker 04: So Medosi and Clark said, no question, those are all active. [00:24:04] Speaker 04: It's four. [00:24:05] Speaker 04: But identics repeats on appeal, their opening brief, page 46, the same point that the universe [00:24:15] Speaker 04: of active molecules was actually small and they got that from their own witness. [00:24:21] Speaker 04: Di Francesco was an identics witness. [00:24:23] Speaker 00: They teach that the universe is extremely large and on its face that seems to be the case. [00:24:32] Speaker 00: My concern [00:24:34] Speaker 00: is that it's hard to find a generic formula close enough to methyl up fluorine down. [00:24:42] Speaker 00: However, it goes all around. [00:24:46] Speaker 00: As your friend says, the typographical error, I'm not so sure about that. [00:24:50] Speaker 00: However, it turns out that it is active, just as all these pages of specification say. [00:24:58] Speaker 00: And so why was the jury wrong in accepting [00:25:03] Speaker 00: that principle when in fact actually it turns out that it's active. [00:25:09] Speaker 00: Whether it's superior activity or something else, the record doesn't say, but apparently it has something in its favor. [00:25:17] Speaker 04: Yes, Judge Newman. [00:25:18] Speaker 04: So two separate questions, and I'll address them separately. [00:25:21] Speaker 04: You started with the universe. [00:25:23] Speaker 04: There are two universes we're talking about. [00:25:26] Speaker 04: There's the universe of potential candidates. [00:25:30] Speaker 04: Everyone agrees that's huge and identics concedes it's in at least the thousands. [00:25:35] Speaker 04: Then, what proportion, what subset are active? [00:25:39] Speaker 04: which then triggers the need to do this iterative testing and screening. [00:25:44] Speaker 04: Identics now says they were all active. [00:25:46] Speaker 04: A jury could have found that. [00:25:48] Speaker 04: Their own witness, and I will quote from Dr. DiFrancesco, their own witness says, quote, this is 37,747. [00:25:59] Speaker 04: We use the screening because that is a way you actually cut down the number of compounds by removing all [00:26:07] Speaker 04: Inactive ones to a few interesting ones. [00:26:11] Speaker 04: Idenix's own logs that Mr. Costanius refers to prove the point. [00:26:17] Speaker 04: Dr. Seeger, whose testimony he mentioned, gave 40 examples of, quote, no activity in BBDV and yellow fever assays. [00:26:27] Speaker 04: They were not all effective. [00:26:29] Speaker 04: Now, you asked a separate question about nothing pointing to two-prime methylfluoro. [00:26:35] Speaker 04: That relates directly to our written description argument. [00:26:39] Speaker 04: But it also relates to how in the world do you figure out which of these billions or thousands of possible candidates, how do you figure out from the specification which ones are going to work? [00:26:52] Speaker 04: And that leads to a key legal principle that identics has not even discussed this morning. [00:27:00] Speaker 04: you have to get it from the specification. [00:27:03] Speaker 00: There is a teaching of a highly specific molecule with thousands of variations. [00:27:13] Speaker 00: And why isn't it routine just to give a robot the job? [00:27:18] Speaker 00: All right, start at the top. [00:27:20] Speaker 00: Start with page one, make these compounds, and see what happens. [00:27:23] Speaker 04: Well, Your Honor, the answer, I think the easiest way to see the answer is to look at page six [00:27:30] Speaker 04: of our brief because it describes what was claimed. [00:27:34] Speaker 04: And so there is a sugar with six possible variables, and then two bases, five more total variables, 11 variables. [00:27:45] Speaker 04: All that was claimed is, OK, we're going to fix one of those variables at methyl. [00:27:51] Speaker 04: Start at the top. [00:27:52] Speaker 04: The undisputed testimony was, even if what you are doing is focusing only on the things that identics' own inventor said you would put in place of these question marks, [00:28:04] Speaker 04: You're talking about billions. [00:28:06] Speaker 04: So start at the top. [00:28:07] Speaker 04: It would take forever to test each one of them. [00:28:10] Speaker 04: And then, to your point, you would never actually test 2-primethylfluoro because the SPAC points in the other direction. [00:28:20] Speaker 00: I think that is the strongest argument [00:28:24] Speaker 00: that where they do list the halogens, and only some of the examples do they include fluorine. [00:28:32] Speaker 04: Yes, right. [00:28:32] Speaker 04: This is not teaching toward. [00:28:34] Speaker 04: It's teaching away, not in the claim construction sense, but in the sense of not guiding anyone. [00:28:42] Speaker 04: So it goes both to written description. [00:28:45] Speaker 04: These are blaze marks in the wrong way, and to what a person of skill in the art would do with these candidates. [00:28:52] Speaker 03: OK, wait. [00:28:54] Speaker 03: take you back to your opposing counsel's universe argument. [00:29:00] Speaker 03: You referenced page 46 of the blue break. [00:29:03] Speaker 03: I'm going to take you to the next page, where the appellant says, the district court cited no evidence to support its purely factual determination that a very large number of compounds. [00:29:15] Speaker 03: This is where I'm bothered about the argument being made. [00:29:19] Speaker 03: Perhaps thousands, at least many thousands, they're quoting in different quotes. [00:29:22] Speaker 03: Or even millions satisfied their refined structural limitations. [00:29:27] Speaker 03: And they say the court cited no evidence for that conclusion. [00:29:32] Speaker 03: So my question is, is there, in fact, record evidence to support that millions number? [00:29:38] Speaker 03: And I think part of what you're going to answer me is I just answered that question. [00:29:43] Speaker 03: But do you have more of that? [00:29:46] Speaker 04: Well, you gave a part of the answer to that question, but yes, there is more. [00:29:49] Speaker 04: So first of all, on the structural limitations, their own expert, Dr. Meyer, said that he agreed that if you theoretically went through all of the variables, he was asked this question. [00:30:05] Speaker 04: Do you agree, this is 37-734, quote, do you agree with the view that we've heard from Gilead's side that the 597 patent discloses billions of compounds? [00:30:19] Speaker 04: He says, he agrees, of course, quote, of course, if you discuss all the structures that are mentioned in the 597 patent. [00:30:28] Speaker 04: So that brings you back to that page I was showing you. [00:30:31] Speaker 04: All that they did was to fix that one point. [00:30:34] Speaker 04: Now, he did not create a material dispute of fact by then saying vaguely that the number is significantly smaller. [00:30:44] Speaker 04: In reality, a person of skill would know it to be smaller for two reasons. [00:30:49] Speaker 04: First, significantly smaller is still, I mean, billions. [00:30:55] Speaker 03: That's where he said some of them could be poisonous. [00:30:57] Speaker 04: Well, no, no, no. [00:30:58] Speaker 04: He was just talking about activity, not about poisonous. [00:31:03] Speaker 04: Millions is significantly smaller than billions. [00:31:05] Speaker 04: It's a thousand times smaller. [00:31:07] Speaker 04: Thousands is a million times smaller than billions. [00:31:10] Speaker 04: And the second reason is he is pointing to a chain of logic that a person of skill in the art would have to adopt, starting with, we're focusing on NS5B. [00:31:23] Speaker 04: OK, so let's pause for a moment. [00:31:25] Speaker 04: Let's posit that the person of skill in the art would know that the claim is actually limited to NS5B. [00:31:33] Speaker 04: The patent doesn't teach you what to do with that. [00:31:35] Speaker 04: Why it was limited to one target, one actual enzymatic target. [00:31:44] Speaker 04: But the patent doesn't say the next steps. [00:31:46] Speaker 04: It doesn't say what you should do with that information is [00:31:51] Speaker 04: take the OH and replace it with something else. [00:31:54] Speaker 04: Nor does it tell you the thing you should replace it with is the flora. [00:31:57] Speaker 04: To Judge Newman's point, it actually points you away from the flora. [00:32:01] Speaker 00: But the patent makes a powerful contribution on the methyl-up substituent, and that's what's claimed. [00:32:11] Speaker 00: two prime ethyl doesn't say throughout, two time ethyl up. [00:32:16] Speaker 00: Why isn't that enough to cover, as the jury apparently believed, every compound with a two prime ethyl up substitute, whatever else you put on the two prime down position? [00:32:29] Speaker 00: Whether or not it's included explicitly in the specification [00:32:35] Speaker 04: Well, the answer, Your Honor, is twofold. [00:32:38] Speaker 04: First, it requires you to go through the iterative process of trying one compound at a time, first making whatever compound. [00:32:48] Speaker 00: That's how the system works. [00:32:50] Speaker 00: But their contribution, their inventive contribution, was the methyl [00:32:57] Speaker 00: Yes, you are. [00:32:59] Speaker 04: Their inventive contribution was a molecule. [00:33:01] Speaker 04: And I would give it to them. [00:33:03] Speaker 04: They invented a molecule with methyl at two prime up and hydroxy at two prime down and showed that it worked. [00:33:10] Speaker 04: That did not entitle them to claim every possible compound. [00:33:17] Speaker 00: Why not? [00:33:18] Speaker 00: I mean, this is a dilemma. [00:33:22] Speaker 00: Make an important contribution. [00:33:23] Speaker 00: It's elaborately explained. [00:33:27] Speaker 00: Let's agree, it seems to me, that they did not foresee this particular compound, methyl-up fluorine down, that it's almost conspicuous in its absence. [00:33:40] Speaker 00: However, the methyl-up seems to be [00:33:44] Speaker 00: critical, the foundation of their inventive contribution. [00:33:48] Speaker 04: Your Honor, methyl-up was an important contribution from which one then develops, and any normal company would then embark upon a research program to figure out what other changes to the molecule would work. [00:34:05] Speaker 00: And it might be separately patentable to whoever puts the fluorine down. [00:34:10] Speaker 00: But in terms of a dominating claim, [00:34:14] Speaker 00: which seems to be what the jury thought, the methyl-up is still there. [00:34:19] Speaker 04: Your Honor, what they are entitled to is a claim that is commensurate with what they actually discovered. [00:34:25] Speaker 04: And what they discovered was two-prime methyl-up works, but only a small portion of molecules with two-prime methyl-up will work. [00:34:34] Speaker 04: So now you have to figure out what other changes you're going to make. [00:34:37] Speaker 04: But I do want to get to this. [00:34:38] Speaker 04: This segue is directly to the point you were making earlier. [00:34:43] Speaker 04: that goes directly to written description. [00:34:45] Speaker 04: And in some ways, written description is a shortcut to the same result. [00:34:49] Speaker 04: You don't have to wrestle with how hard it is to make 2-primethyl-up nucleosides. [00:34:54] Speaker 04: By the way, that's part of the answer to your question. [00:34:56] Speaker 04: You've got to make all of these billions or thousands of compounds to use them. [00:35:01] Speaker 04: You don't have to wrestle with how hard it is to make 2-primethylfluoro. [00:35:06] Speaker 04: Even whether attaching a fluorine would have been obvious, you don't have to wrestle with. [00:35:11] Speaker 04: For one version of our written description argument, it doesn't even matter how many viable candidates there were. [00:35:17] Speaker 04: You can just focus on the spec itself. [00:35:19] Speaker 04: What does the spec say? [00:35:21] Speaker 04: Identics possessed? [00:35:23] Speaker 04: four specific nucleosides, and thousands of candidates for further research. [00:35:28] Speaker 04: Whether you think about it in terms of blaze marks or closed lists, you end up in the same place for exactly the reason you articulated, Judge Newman, the list of candidates points away from fluorine at 2 prime down, not toward it. [00:35:43] Speaker 04: And identics most certainly did not possess [00:35:46] Speaker 04: as in invent the molecule 2-primethylfluorine. [00:35:52] Speaker 04: They omitted it, and identics concedes that they never thought about 2-primethylopfluorodone until a year after the date. [00:36:02] Speaker 04: Now, there's a clear disconnect to your question, Judge Newman, between the specification and the claim. [00:36:08] Speaker 04: The patent declares, quote, the present invention is, quote, a nucleoside as described in. [00:36:17] Speaker 04: one of the 18 formulas. [00:36:19] Speaker 04: Those 18 formulas have very specific constituents. [00:36:22] Speaker 04: I mean, billions of them. [00:36:26] Speaker 04: But the universe of nucleosides captured by the formulas, however vast it is, doesn't include the one thing that is actually what the inventors were after, the drug that would actually work. [00:36:40] Speaker 04: So one thing obviously omitted is two prime fluorodone. [00:36:44] Speaker 04: The inventors omitted fluorine, a halogen, at 2 prime down, while including all four halogens at 2 prime up. [00:36:53] Speaker 04: In fact, even calling it halogens, it had to have been on purpose. [00:36:57] Speaker 04: And identics council admitted, this is at 25, 562, why the 597 patent doesn't include 2 prime fluorodown, quote, there is no factual dispute [00:37:10] Speaker 04: that IDENIX's folks only came up with a two prime methyl floral embodiment a year or so after the application was filed. [00:37:19] Speaker 04: Let me close with just this one minute of framing. [00:37:26] Speaker 04: And that is IDENIX is striving to identify disputed facts. [00:37:32] Speaker 04: But it cannot prevail unless it identifies material disputes of fact, disputes of fact that will actually change the result [00:37:40] Speaker 04: On both undue experimentation and written description, we prevail so long as we persuade this court that the universe of compounds, that is, candidate compounds, was at least thousands, which they've conceded. [00:37:55] Speaker 04: Many of these thousands were ineffective, which they conceded below and even in their brief on appeal. [00:38:01] Speaker 04: And the patent doesn't teach which ones are effective and which ones are not. [00:38:06] Speaker 04: The first two points are conceded, so all it comes down to is the patent. [00:38:11] Speaker 04: Identics never points to anything in the patent that teaches how you separate effective NS5B chain terminators from ineffective ones. [00:38:21] Speaker 04: It says NS5B, that's it. [00:38:24] Speaker 04: Identics does. [00:38:25] Speaker 04: But it doesn't tell you what to draw from that. [00:38:28] Speaker 04: For these reasons, the district court, after a thorough review of the record, came up with the correct conclusion [00:38:36] Speaker 04: None of the facts Idenex points to that it claims are disputed are actual material disputes, and many of them are actually undisputed. [00:38:46] Speaker 04: If there are no further questions, I thank the court for its attention. [00:38:51] Speaker 02: We'll restore two minutes of rebut. [00:39:00] Speaker 01: Thank you, Your Honor. [00:39:01] Speaker 01: The site I couldn't come up with before to Dr. Goslin's chart is A50155. [00:39:07] Speaker 01: That's the 284 compounds. [00:39:11] Speaker 01: We had a jury trial. [00:39:13] Speaker 01: The jury heard a lot of conflicting evidence in this case. [00:39:17] Speaker 01: If you just looked at nothing more than the testimony of our two experts, Dr. DeFranchesco and Dr. Meyer, you'll walk away thinking, how could this judge have taken away this jury verdict? [00:39:27] Speaker 01: He shouldn't have. [00:39:29] Speaker 01: What we heard from my friend on the other side was largely summarized at page 38 of his brief. [00:39:36] Speaker 01: And this, by the way, Judge Prost, goes to confirming the point you asked me about Dr. Goslin, the same person who authored that chart, saying you don't know whether a nucleoside will have activity against HCV until you make it and test it. [00:39:52] Speaker 01: That was not a statement in any way tied to our patent. [00:39:55] Speaker 01: That was a, by the way, a non-native English speaker put that aside. [00:39:59] Speaker 01: And that was actually simply a question posed to him by Gilead's counsel, but it wasn't tied to the teachings of the patent here. [00:40:07] Speaker 01: We heard my friend talk about the numbers. [00:40:12] Speaker 01: If you look again at page 38 of their brief, the DeFranchesco testimony about screening is, again, also not tied to the patent. [00:40:20] Speaker 01: It's about screening generally. [00:40:22] Speaker 01: It doesn't have anything to do with the class of two prime methyl up ribonucleosides. [00:40:26] Speaker 01: And in fact, that set the [00:40:29] Speaker 01: Dr. Meyer's testimony about the unpredictability of a nucleoside's effectiveness was also not tied to our invention. [00:40:37] Speaker 01: In fact, that same page of the transcript points to the novel aspect and says, quote, there were surprisingly high number of two prime methyl up compounds that were active. [00:40:48] Speaker 01: This goes to the point, Judge Newman, that you were making with regard to my friend here during his argument. [00:40:53] Speaker 01: We made a major contribution here. [00:40:55] Speaker 01: Our patent enabled commensurate with the scope of our claims. [00:40:58] Speaker 01: Our contribution was chief prime methyl up ribonucleosides. [00:41:02] Speaker 01: And most of them worked. [00:41:04] Speaker 01: And Chief Judge Prost, this goes to one of the questions that really permeates the court's decisions, like the recent one in ENSO, which has been the subject of letter writing earlier this week, predictability. [00:41:18] Speaker 01: What could a person of ordinary skill in the art predict in light of our patent disclosure? [00:41:23] Speaker 01: A person of ordinary skill in the art, based on this record, based on the testimony of witnesses, would predict that all, or at worst for my case, most, two prime methyl-up ribonucleosides would work. [00:41:36] Speaker 01: If we're in the world of most, that takes us into wands and Atlas powder, where routine, ordinary screening doesn't constitute undue experimentation for enablement. [00:41:48] Speaker 01: With regard to written description, there's a lot of overlap. [00:41:52] Speaker 01: The judge heard that, said there were factual issues galore on that. [00:41:56] Speaker 01: But with regard to written description, I just want to point this board out one sentence from the in-bank area decision. [00:42:03] Speaker 01: The written description requirement, and here I quote, never created a heightened requirement to provide a nucleotide by nucleotide recitation of the entire genus of claimed genetic material. [00:42:14] Speaker 01: It has always permitted the disclosure of structural features common to the members of the genus. [00:42:21] Speaker 01: We disclosed two prime methyl up ribonucleosides. [00:42:24] Speaker 01: That's the important structure. [00:42:26] Speaker 01: That's what we claimed. [00:42:27] Speaker 01: That's what we enabled. [00:42:29] Speaker 01: We are entitled to our verdict back. [00:42:31] Speaker 01: Thank you very much. [00:42:32] Speaker 02: Thank both sides and the case is submitted. [00:42:46] Speaker 02: The next case for argument is 18.