[00:00:00] Speaker 03: case number 20-1933. [00:00:02] Speaker 03: It is an appeal from the district court in the northern district of West Virginia. [00:00:10] Speaker 03: Mr. Lee, I understand you want three minutes for rebuttal? [00:00:14] Speaker 04: That's correct, Your Honor. [00:00:15] Speaker 04: Thank you. [00:00:16] Speaker 03: Okay. [00:00:17] Speaker 03: You may proceed. [00:00:19] Speaker 04: May it please the court? [00:00:20] Speaker 04: This is Bill Lee again on behalf of Biogen. [00:00:24] Speaker 04: As the panel knows, [00:00:25] Speaker 04: The only issue in this appeal is whether the asserted claims of the 514 patent are invalid for lack of written description. [00:00:33] Speaker 04: As this court said in ALCON, written description is about whether the skilled reader of the patent disclosure can recognize what is claimed and what is described. [00:00:44] Speaker 04: What is claimed is a method for treating MS by administering 480 milligrams per day of DMF. [00:00:56] Speaker 04: Hempel claim is disclosed expressly in the specification, and I'd like to turn to that specification if I could, and then turn to the legal errors we believe this court made that led it to the incorrect result. [00:01:12] Speaker 03: Well, Mr. Lee, I understand that your argument is that the court improperly applied our blazemarks type of cases with respect to method four. [00:01:25] Speaker 03: Is that correct? [00:01:26] Speaker 04: Yes, Your Honor. [00:01:28] Speaker 03: Does the blazemark analysis apply to the portion of the spec that shows up in column 18? [00:01:38] Speaker 04: Yeah, Your Honor. [00:01:39] Speaker 04: Actually, I don't think this is a blazemark case. [00:01:43] Speaker 04: I think this is an express disclosure case. [00:01:46] Speaker 04: And if you take the claim, which is a method, method four is a method, of treating MS [00:01:54] Speaker 04: the specification specifically describes method four as a method of treating MS with a compound, DMF, by administering a therapeutically effective amount, then when you get to column 18, if you read the specification from the beginning at column one through claim column 18, which your honor has just identified, the range, one of the ranges for a therapeutically effective amount [00:02:24] Speaker 04: includes 480 milligrams per day. [00:02:27] Speaker 04: So this is actually not a place-marked case like a new-assigned case where you have this extensive, overwhelming genus and you're trying to identify a point within the genus. [00:02:40] Speaker 04: This is a specification where the focus from the very first sentence of specification is on MS. [00:02:49] Speaker 04: This is a specification that says you can treat MS [00:02:53] Speaker 04: and you can treat the hallmark characteristics of MS with DMF. [00:02:59] Speaker 04: This is the specification that says you can treat MS with DMF in a therapeutically effective amount. [00:03:07] Speaker 04: And then you get to column 18. [00:03:10] Speaker 04: And that's where the range, the nested range and the narrowest nested range of 480 milligrams per day to 720 milligrams per day is specifically identified. [00:03:22] Speaker 04: And if you look [00:03:24] Speaker 04: in column 18, your honor, at portions that were not cited by the district court, not considered by the expert, Dr. Greenberg, at all, you will see that in the portions of column 18 immediately above the nested ranges, the reference is specifically to a therapeutically effective amount. [00:03:44] Speaker 04: Now, that's important, as the panel knows, because therapeutically effective amount is a limitation of the claims. [00:03:52] Speaker 04: With the exception of one independent claim, there's no real argument, I do not believe, that that claim should be dealt with differently. [00:04:00] Speaker 04: Therapeutically effective mount is a limitation to claims. [00:04:04] Speaker 04: In column five, it is a concept that is specifically defined. [00:04:11] Speaker 04: It is specifically defined as treating the hallmark characteristics of MS. [00:04:17] Speaker 04: It is specifically what ultimately culminates in the 480 to 720 milligrams per day dose in column 18. [00:04:27] Speaker 04: And the person of ordinary skill and the art, with all of that, Your Honor, reading from the beginning... Mr. Lee, this is Judge Hughes. [00:04:34] Speaker 02: Can I just interrupt you here? [00:04:36] Speaker 02: Sure. [00:04:36] Speaker 02: I get this. [00:04:37] Speaker 02: I've read this passage. [00:04:38] Speaker 02: I get your argument, but at the end of the day, isn't this an actual conclusion by the district court? [00:04:45] Speaker 02: And we have to determine whether [00:04:47] Speaker 02: You know, our reading of this passage makes the district court's decision clear air. [00:04:51] Speaker 02: And if it was just a, can I just, let me just finish. [00:04:55] Speaker 02: I know this is really hard to do by phone and without the visual signals. [00:04:58] Speaker 02: I wish we were doing video. [00:05:01] Speaker 02: If this were just a passage about 480 to 720, I would be there with you. [00:05:04] Speaker 02: That would be easy. [00:05:05] Speaker 02: But it has a bunch of different ranges. [00:05:08] Speaker 02: And at the time, everybody knew that 720 worked and 360 didn't work, right? [00:05:14] Speaker 02: Some of these ranges have things that work and don't work, and then turns out that one of them has things that all work. [00:05:20] Speaker 02: How do we know that it was specifically understood that 480 would work when we have overlapping ranges where things don't work? [00:05:31] Speaker 04: So, Your Honor, and I apologize. [00:05:33] Speaker 04: I thought you were done your question when I started to wade in, and you're right. [00:05:36] Speaker 04: It's the problem with that without being able to see visual cues. [00:05:40] Speaker 04: So let me say the following. [00:05:43] Speaker 04: I think, again, I would make these three points. [00:05:46] Speaker 04: One is you have to read that portion of column 18 as the culmination of a progression that starts in column one, line one. [00:05:55] Speaker 04: If it's read that way, you understand then that you're talking about a therapeutically effective dose. [00:06:03] Speaker 04: And the therapeutically effective dose is claimed in the limitation and is described in column five. [00:06:09] Speaker 04: So that's a critical portion of the analysis. [00:06:12] Speaker 04: You then have these nested ranges and the narrowest nested range is 480 to 720. [00:06:20] Speaker 04: And one of ordinary skill there would know that the 720 is effective and they would know that the pattern is saying that 480 to 720 is effective. [00:06:30] Speaker 04: And the reason that's important, my second point is this, your honor. [00:06:35] Speaker 02: The 480... Can I just, before you move on to that second point, but let me follow up. [00:06:40] Speaker 02: on that. [00:06:41] Speaker 02: This is where I have the problem, though. [00:06:42] Speaker 02: Again, I agree with you. [00:06:43] Speaker 02: If that was the only range, then that would be okay. [00:06:47] Speaker 02: But by the logic you just said, if a skilled artisan would know 720 is effective, that range would be effective. [00:06:54] Speaker 02: Well, why wouldn't that same logic apply to the 240 to 720 milligrams per day? [00:07:00] Speaker 02: And a skilled artisan would then, by that logic, assume that all of that would be effective, which we know is not correct. [00:07:07] Speaker 04: And your honor, this is why, to go back to where I started, this is why the fact that this is the narrow issue of written description is so important. [00:07:17] Speaker 04: Because this court, the predecessor court and this court have addressed this issue of whether inoperative embodiments can somehow affect the question or the issue of whether an operative embodiment is in fact disclosed. [00:07:34] Speaker 04: And the Snitzer case, which we have cited, which remains good law says, look, the fact that there are inoperative embodiments that are identified in specification does not mean that an operative embodiment is not disclosed. [00:07:48] Speaker 04: And in fact, the inoperative may go through. [00:07:51] Speaker 03: So is it your position then that the 240 is an express disclosure? [00:07:55] Speaker 03: It just doesn't happen to be operative? [00:07:58] Speaker 04: Yeah, Your Honor, I think if it were the 240 that were an issue, I think that there would be an express disclosure of 240, but it would not be enabled. [00:08:06] Speaker 04: And that's why I think it's critically important that the issue here is just written description. [00:08:14] Speaker 04: And one of the errors, as the panel knows, that we believe the district court made is it collapsed concepts of obviousness, written description, and enablement. [00:08:25] Speaker 04: If the patent said expressly that 240 was a therapeutically effective dose for the treatment of MS, it would be disclosed, but it would not be enabled. [00:08:40] Speaker 04: There is no question here that this 480 milligram per day dose is enabled. [00:08:47] Speaker 04: And there's a reason, and the reason's in the district court's opinion, [00:08:51] Speaker 04: The 480 milligram per day dose was actually conceived by Dr. O'Neill, conceived and documented before the filing of the provisional application. [00:09:00] Speaker 04: And I think as the panel knows from the opinion of the district court, this range of 480 to 720 that Judge Shoes has asked me about was not a coincidence. [00:09:11] Speaker 04: These were the phase two, phase three numbers, the doses that were going to be tested in phase three, as the district court says, and in fact, [00:09:20] Speaker 03: within a month after filing of the application that had this range of 480 to 720, the phase three started without the... What about the fact, I mean, does it matter that Dr. O'Neill said that he conceived of it, but he wasn't positive it would work at the time of the application? [00:09:42] Speaker 04: Not for written description purposes, Your Honor. [00:09:44] Speaker 04: And the question is, again, for written description purposes is disclosure. [00:09:49] Speaker 04: Is there a disclosure of what is claimed? [00:09:53] Speaker 04: And there is a disclosure of the monotherapy treatment method four at 480 milligrams per day, and that's sufficient. [00:10:02] Speaker 04: And to go back to Judge Hughes' question, the third point I would make is this. [00:10:07] Speaker 04: There are a series of nested ranges in column 18, all of which follow three independent references to therapeutically effective mount [00:10:16] Speaker 04: There is an effective dose in every single one of those ranges. [00:10:21] Speaker 04: And when you get down to 480 to 720, it is saying expressly that that is effective ranges and those endpoints are effective. [00:10:32] Speaker 04: So if we ask ourselves, and I think if you go back. [00:10:36] Speaker 02: Sorry, Mr. Lee, can I follow up on that? [00:10:39] Speaker 02: Then are you saying in these other ranges, the low end point is effective for something? [00:10:45] Speaker 04: Your Honor, the fact of the matter is specification describes other disease conditions and it's not part of the record and I'm not representing to you now that those other ranges might be or might not be effective for those other disease conditions. [00:11:04] Speaker 04: You're not going to get an argument from us that when it talks about 240 to 720, we're not claiming that 240 was effective. [00:11:12] Speaker 04: We're saying that [00:11:13] Speaker 04: as a legal matter, the fact that there were inoperative feces or inoperative doses under Smither? [00:11:21] Speaker 02: No, no, I get that, but I just thought what you were just saying right before I asked the question was that these ranges all corresponded to effective ranges for something. [00:11:32] Speaker 02: You know, I just didn't see that explicitly tied anywhere in. [00:11:39] Speaker 04: If that's what I communicated, that's not what I intended to communicate, Your Honor. [00:11:43] Speaker 04: What I intended to communicate is each of those ranges had a dose, 720, that was known to be effective to a person of ORGase scale in the arts as a result of the phase two trial. [00:11:56] Speaker 03: And if you... What is the point of the distinction between therapeutically effective, which I understand is an actual time limitation, [00:12:08] Speaker 03: and a defined term, and clinically effective? [00:12:14] Speaker 04: It's a great question, Your Honor. [00:12:16] Speaker 04: The therapeutically effective is defined, and it's specifically defined as treating one... You can finish that. [00:12:28] Speaker 04: It's specifically defined as treating one or more of the characteristics [00:12:35] Speaker 04: that are hallmark characteristics of MS, but also could be characteristics of other neurological diseases. [00:12:42] Speaker 04: That is a threshold level of efficacy. [00:12:45] Speaker 04: And I think as the panel knows from your consideration of other life sciences patents, it is often true that the patent, the invention is discovered, a compound, a method of treatment. [00:12:58] Speaker 04: It's known to have a threshold level of efficacy. [00:13:02] Speaker 04: But then when it goes into phase three, when it goes into the clinic, what turns out to be true is it has much greater clinical efficacy than the threshold level of therapeutic efficacy. [00:13:17] Speaker 04: So that pattern requires, as you would think as a matter of logic, that there be a threshold level of efficacy. [00:13:25] Speaker 04: And in fact, there was and is. [00:13:27] Speaker 04: But then when it went into phase three and there were tests of the 480 and 720 across a whole series of not only radiological endpoints and clinical endpoints, the unexpected results or the surprising results were that that dose, which had demonstrated, which had and was represented to have a threshold level of efficacy, in fact had this surprising [00:13:56] Speaker 04: clinical efficacy across all of the radiological endpoints, across all of the clinical endpoints. [00:14:04] Speaker 04: And it was as effective across all of those endpoints as the 720-milligram-per-day dose. [00:14:13] Speaker 04: And that's precisely what the experts said. [00:14:17] Speaker 04: And the last thing I'll say in answering part of this question, but also a question that Joe Grimelli asked about the experts, [00:14:24] Speaker 04: This isn't just a question of what the expert says, because the predicate of Dr. Greenberg's testimony, which was the predicate of Mylan's attack on the patent and the predicate of the district court's opinion, the fundamental proposition that he offered did not consider the key claim limitation of therapeutic efficacy at all. [00:14:46] Speaker 04: And as a consequence, it's just legal insufficient to satisfy their burden. [00:14:51] Speaker 00: Thank you. [00:14:53] Speaker 00: Dr. Jomeli, may I ask a question? [00:14:54] Speaker 00: Yes, yes, of course. [00:14:56] Speaker 00: Yes. [00:14:57] Speaker 00: Counselor, where in the pan do we see anything regarding the efficacy of the 480 dose? [00:15:06] Speaker 00: I look and I do see significant reference with this, very specific references as to what was an effective dose in the February 2007 priority date for the 720 dose. [00:15:23] Speaker 00: that does have specific references to efficacy, but I don't see that with respect to 480. [00:15:29] Speaker 00: And it seems to me you're using this anchoring argument. [00:15:33] Speaker 00: You're saying since it's in the same range, it doesn't have to have, the specification doesn't have to have any specific references as to efficacy. [00:15:42] Speaker 00: But then if that's the case, how do we evaluate that with respect to the February 2007 priority date? [00:15:49] Speaker 04: Your Honor, I think that the answer is in column 18, and I'll be brief. [00:15:55] Speaker 04: At column 18, line 3, you'll see a reference to a therapeutically effective dose. [00:16:02] Speaker 04: You'll see it repeated in the same column at line 16, and you'll see it again repeated at line 39. [00:16:11] Speaker 04: With that as the backdrop, because what column 17 and column 18 are talking about are [00:16:18] Speaker 04: the mechanisms for determining a therapeutically effective dose. [00:16:23] Speaker 04: And then when you get to column 18, the culmination of that is, for DMF, which is the compound we're considering, an effective amount can range from, and then the narrowest range is 480 to 720 milligrams per day. [00:16:40] Speaker 00: That expressed... Was a 480 dose subject to clinical testing in 2007? [00:16:48] Speaker 04: No, Your Honor, it was part of the phase three. [00:16:50] Speaker 04: And that's why the Alcon case, and I'll end on this because this is where I began. [00:16:56] Speaker 04: In the sentence that follows the portion of Alcon that I quoted at the outset of the argument, the very next sentence says, it is not about whether the patentee has proven to the skilled reader that the invention works or how to make it work. [00:17:12] Speaker 04: And that's because that's the enablement question that Judge O'Malley was asking me about. [00:17:19] Speaker 04: Thank you, Your Honor. [00:17:21] Speaker 03: Okay. [00:17:21] Speaker 03: Mr. Lee, we'll restore your three minutes for rebuttal, and Mr. Anstead, if he needs another three minutes, we'll give it to him as well. [00:17:30] Speaker 01: Thank you. [00:17:31] Speaker 01: Thank you, Judge O'Malley, and good morning, Your Honors, and may it please the Court. [00:17:34] Speaker 01: This is David Anstead representing Mylan. [00:17:37] Speaker 01: Because Biogen is on the wrong side of the District Court's factual findings and credibility determinations, its appeal presents what Biogen [00:17:45] Speaker 01: Contends are a handful of legal arguments, but in reality, and I think it's been borne out by the discussion this morning, Biogen is simply trying to re-argue the facts. [00:17:56] Speaker 01: All the asserted claims narrowly require the use of a 480-milligram dose of DMF to treat MS, but that 480-milligram dose of DMF is mentioned precisely once. [00:18:08] Speaker 01: in the entire 30-column patent specification in column 18, and it's not connected to the treatment of MS or any of the dozens of other neurological diseases that the specification deals with. [00:18:21] Speaker 01: So the issue at trial was whether a skilled artisan reading the specification in light of her background knowledge of the prior art would make the connection between the precise 480-milligram dose mentioned once in column 18 and an effective MS treatment as claimed. [00:18:39] Speaker 03: Well, counsel, let me ask you something that I started with Mr. Lee with, because I understand the court's consideration of BlaseMark's analysis for purposes of seeing if method four is tied to MS. [00:18:56] Speaker 03: And frankly, it doesn't seem like a difficult leap to conclude that it is. [00:19:01] Speaker 03: So the question is, once you believe that that is [00:19:07] Speaker 03: that there is a connection between method four and the treatment of MS. [00:19:13] Speaker 03: Why doesn't the question of column 18 just simply devolve to an expressed disclosure? [00:19:22] Speaker 01: A few answers to that, Judge O'Malley. [00:19:24] Speaker 01: First of all, even if you accept the proposition that method four mentions MS, it doesn't explicitly mention MS. [00:19:32] Speaker 01: That never happens in the specification. [00:19:34] Speaker 01: What they argue is that it mentions [00:19:36] Speaker 01: demyelination, axonal loss, and neuronal death, which are kind of what they characterize as the hallmarks of MS. [00:19:44] Speaker 01: But even if you accept that method four mentions MS, the problem is method four mentions all of the neurological diseases that are treated or that are dealt with by the specification. [00:19:57] Speaker 01: And there are three dozen of them. [00:20:00] Speaker 01: And that's equally true of the definition of therapeutically effective dose. [00:20:05] Speaker 01: Biogen likes to kind of treat that as if it starts with the words demyelination, but it doesn't. [00:20:11] Speaker 01: They have to excise the vast majority of that definition, which plainly deals with all the neurological conditions. [00:20:18] Speaker 03: And then, so then they have to get... But the fact that it deals with more conditions doesn't change the fact that it deals with this particular condition, does it? [00:20:30] Speaker 01: Here at the issue, I think, Judge O'Malley, is when you get to column 18, [00:20:34] Speaker 01: If we accept the fact that method four and the definition of therapeutically effective dose deal with dozens of diseases, and MS is one of them, that's absolutely right, then comes the question, we get to column 15, which is the only places that the dose ranges are disclosed. [00:20:51] Speaker 01: And this was a... In column 18. [00:20:54] Speaker 01: In column 18, yes, in column 18. [00:20:57] Speaker 01: And this was a hotly disputed issue at trial because [00:21:02] Speaker 01: If you look at that sentence in column 18, it says the following doses, quote, can be effective. [00:21:10] Speaker 01: It doesn't specify any of the neurological diseases. [00:21:13] Speaker 01: And then it goes on to list four ranges, 100 to 1,000 milligrams, 200 to 800, 240 to 720, and then 480 to 720. [00:21:22] Speaker 01: Now, Dr. Nguyen, who was Biogen's expert, was examined about this, was cross-examined about this. [00:21:30] Speaker 01: And he said, under cross-examination, well, the skilled artisan, with their background knowledge of the prior art, reading the specification, when they come to this passage at column 18, lines 58 to 62, they would not regard 100 to 1,000 milligrams to be a range for MS. [00:21:52] Speaker 01: they would not regard 200 to 800 to be a range for MS. [00:21:57] Speaker 01: They would not regard 240 to 720 milligrams to be a range for MS. [00:22:03] Speaker 01: He testified that that was the skilled artisan's belief, reading the specification. [00:22:08] Speaker 03: And so the issue then became... Well, I don't... Is that exactly what he said? [00:22:11] Speaker 03: I thought what he said was he wouldn't know what is the preferred clinical efficacy [00:22:22] Speaker 03: As it relates to those ranges. [00:22:30] Speaker 01: I think that's respectfully incorrect, Judge O'Malley. [00:22:33] Speaker 01: If we look, starting at appendix page 1542, and this is Dr. Winn's examination, and so he's asked at starting at 19, line 19 on appendix 1542, [00:22:46] Speaker 01: Doctor, when reading this patent specification in view of the prior art at the priority date, you would not have expected a dose range of 100 milligrams to 1,000 milligrams of BMS to be effective in treating MS. [00:22:57] Speaker 01: Is that right? [00:22:58] Speaker 01: His answer, that's correct. [00:23:00] Speaker 01: Then we go on to Appendix 1543, and he's asked essentially the same question about 200 to 800 milligrams, and he says, correct. [00:23:07] Speaker 01: The only dose that I would know prior to reading the patent would be the dose of 720. [00:23:12] Speaker 01: And then he goes on to 240. [00:23:15] Speaker 01: Prior to reading the patent. [00:23:17] Speaker 01: Prior to reading the patent. [00:23:19] Speaker 01: But then he says, and then he's asked, in reading the patent specification at the priority date in view of the prior art, this is the 240 to 720 we've moved on to now. [00:23:31] Speaker 01: You would not have expected a dose range of 240 to 720 milligrams of DMF per day to be effective in treating MS, correct? [00:23:37] Speaker 01: And he would say, I would not expect the lower estimate of the range to be effective. [00:23:41] Speaker 01: That's correct. [00:23:42] Speaker 01: And then on the next page, it's 1544, and this is the issue that Judge Hughes was raising. [00:23:48] Speaker 01: He's asked now, and this is at line nine, now in one of these three ineffective dose ranges, a 240 milligram dose is to a 720 milligram dose, right? [00:24:02] Speaker 01: But you don't think a skilled artisan reading the patent application would believe a 240 milligram dose would be effective to treat despite that linkage. [00:24:11] Speaker 01: Isn't that right? [00:24:13] Speaker 01: Answer, that's correct. [00:24:15] Speaker 01: Now, what you're referring to, Dr. Malley, comes a little bit later when Dr. Nguyen kind of backtracks. [00:24:23] Speaker 01: And he says, well, actually, I don't know that these three dose ranges that he had just said would be regarded as ineffective [00:24:31] Speaker 01: Maybe they would have some effect of MS. [00:24:35] Speaker 01: I just don't know if they would be ideal or preferred. [00:24:39] Speaker 01: And that was a complete reversal of what he had just testified to. [00:24:43] Speaker 01: And the district court watched all this unfold live and understandably, in her opinion, decided not to credit Dr. Wynn's testimony. [00:24:53] Speaker 03: But what do we make of the fact that just in terms of what the law requires, [00:24:58] Speaker 03: we have to keep in mind that there are distinctions between written description enablement and distinctions between obviousness and written description. [00:25:11] Speaker 03: So in other words, you don't have to show efficacy to prove written description if you actually contain the language calling it out, right? [00:25:21] Speaker 01: I would slightly disagree with that. [00:25:26] Speaker 01: Judge O'Malley, and here's why. [00:25:28] Speaker 01: First of all, the question is, the question throughout all of this court's written description precedence is, does the skilled artisan reading the patent specification understand with reasonable clarity that the inventors actually possessed the claimed invention? [00:25:48] Speaker 01: And that was the question of fact that was presented to the district court. [00:25:51] Speaker 01: And so the claims require a therapeutically effective amount [00:25:56] Speaker 01: of VMF of 480 milligrams. [00:26:00] Speaker 01: And so the question is, is the skilled artisan who comes to this specification, do they understand based on it that the inventors actually possess that? [00:26:08] Speaker 01: And that was the factual question that the district court decided in Mylan's favor. [00:26:14] Speaker 03: And a second- So in other words, if there's skepticism with respect to what it is you're claiming, then you haven't described it? [00:26:23] Speaker 01: No, no. [00:26:24] Speaker 01: It's not that principle at all, Judge O'Malley, and we are certainly not advocating for that kind of principle. [00:26:30] Speaker 01: The issue is, and it was undisputed between the parties, that for written description purposes, the patent specification is read in light of the knowledge of the skilled artisan. [00:26:39] Speaker 01: And it was undisputed. [00:26:42] Speaker 01: This was Biogen's own testimony. [00:26:43] Speaker 01: It's in their blue brief at page 57. [00:26:47] Speaker 01: that the skilled artisan coming to this patent specification would expect that 480 milligrams would not be an effective dose, effective period at any level of efficacy in MS. [00:26:59] Speaker 01: And at the blue brief, at page 57, Biogen acknowledges that. [00:27:04] Speaker 01: They say the skilled artisan picking up this specification wouldn't expect 480 to be effective as efficacy is defined in the patent specification. [00:27:13] Speaker 01: Dr. Nguyen, in his cross-examination, admitted the same thing multiple times. [00:27:17] Speaker 01: That's an appendix 1523, 1524, 1527. [00:27:23] Speaker 01: And he even went so far as to say even the 720 milligram dose would have been viewed by the skilled artisan at the priority date as lackluster. [00:27:32] Speaker 01: That was his word. [00:27:33] Speaker 01: That's an appendix 1551. [00:27:36] Speaker 01: And that the skilled artisan would have been interested in looking at higher doses than 720 milligrams. [00:27:43] Speaker 02: Council, this is Judge Hughes. [00:27:44] Speaker 02: I have a couple hypotheticals, if I might. [00:27:47] Speaker 02: If instead of the ranges we have in the specification, we had instead, you know, dosage of 720 to 1,000, 480 to 720, and just 720. [00:28:00] Speaker 02: So every single range is either 480 and above or at 720. [00:28:08] Speaker 02: Would that change the result? [00:28:09] Speaker 02: Because it seems like then every range [00:28:12] Speaker 02: And everything else is the same. [00:28:14] Speaker 02: There's no direct connection to NFs, all that kind of stuff. [00:28:17] Speaker 02: At least then it would seem that everything was in a range that skilled artisans might have known would work, or eventually found would work. [00:28:28] Speaker 01: Judge Hughes, I would agree with you if the range started at 720 milligrams and went up. [00:28:34] Speaker 01: Okay. [00:28:36] Speaker 02: Yeah, address the 480 to 720 range, if that's in there, because I think that's really what [00:28:41] Speaker 02: What Mr. Lee is talking about is that, you know, that is an effective range, as we all now know, and why isn't that enough? [00:28:48] Speaker 01: Well, and I think I see that we all now know that. [00:28:52] Speaker 01: And we now know that range, including 480, is effective because of the Phase III trials that were released in 2011. [00:28:59] Speaker 01: And this goes back to Judge Raina's question, which was, was there any evidence in 2007 at the priority date [00:29:06] Speaker 01: that 480 milligrams would be effective. [00:29:09] Speaker 01: And I think my friend on the other side answered candidly, no, there wouldn't have been. [00:29:13] Speaker 01: So, but taking your hypothetical, Judge Hughes, if we were to exercise... Yes? [00:29:20] Speaker 02: Sorry, I just wanted to stop, though, because this is where I'm a little confused about whether we're really still talking about written description or we're going into enablement. [00:29:31] Speaker 02: the ranges disclosed are things that are written descriptions of precisely the amount claimed, then why isn't that now an enablement problem that it wasn't enabled at the time rather than a written description problem? [00:29:45] Speaker 01: It's a written description problem, Judge Hughes, because this court's cases just only hold that to have adequate written description [00:29:57] Speaker 01: the four corners of the specification, you know, read by the skilled artisan have to convey with reasonable clarity, actual possession of the invention. [00:30:07] Speaker 01: And so I'll take this two ways, one as the specifications written and one with your hypothetical. [00:30:13] Speaker 01: And as the specifications written, I think as you pointed out, we have this problem that in this single sentence where the 480 to 720 ranges, we've got three dose ranges as the district court found, [00:30:26] Speaker 01: that the skilled artisan and the biogen admits that the skilled artisan would regard as ineffective in MS. [00:30:32] Speaker 01: And so then the question became, why would you say first one, second one, third one, these can't be about MS. [00:30:37] Speaker 01: Oh, but this fourth one is. [00:30:39] Speaker 01: And as I believe Judge Raina pointed out, the biogen theory was this anchoring theory. [00:30:45] Speaker 01: Well, 480 is anchored to the known 720 milligram effective dose. [00:30:49] Speaker 01: Of course, that was completely undercut when Dr. Nguyen admitted that so was 240 milligrams, but the skilled artisan wouldn't regard that as effective. [00:30:57] Speaker 01: Now, in your hypothetical, if we were to say cut out the first three dose ranges from column 18, and so we don't say 100 to 1000, [00:31:06] Speaker 01: 200 to 800, 240 to 720, and we start with 480 to 720 and then maybe go higher. [00:31:12] Speaker 01: It's counterfactual, of course, but I think there would still be a problem. [00:31:16] Speaker 01: That was effectively the situation in NUVO. [00:31:20] Speaker 01: In NUVO, there's no dispute that there was an expressed disclosure of the claims invention, an un-coded PPI that was effective to raise gastric pH. [00:31:31] Speaker 01: But as the NUVO court recognized, this court's precedents say that an in-ipsis verbis recitation of the claim language in the specification isn't necessarily enough. [00:31:41] Speaker 03: Right, but in NUVO there was a very important distinction, wasn't there? [00:31:45] Speaker 03: And that is that the patent itself said that the un-coded wouldn't work. [00:31:51] Speaker 03: It went on to claim it, but it expressly stated that it didn't work. [00:31:57] Speaker 01: I would respectfully, Judge Umali, say that that is a distinction without a difference. [00:32:01] Speaker 01: There's no dispute that for written description purposes, the patent specification is read from the perspective and with the background knowledge of the skilled artisan. [00:32:12] Speaker 01: So whether the knowledge that a dosing regimen or dose is not going to be effective is stated in the specification or whether the skilled artisan brings that knowledge with them to the specification [00:32:28] Speaker 01: It's the same. [00:32:30] Speaker 01: It would be quite odd to suggest that the skilled artisan's belief doesn't matter for written description purposes unless it's memorialized in the patent specification. [00:32:40] Speaker 01: And what this court said in Nouveau was that based on the specific facts of certain cases, it's unnecessary to prove that a claimed pharmaceutical compound actually achieves a certain result. [00:32:52] Speaker 01: But when the inventor expressly claims that result, [00:32:56] Speaker 01: our case law provides that that result must be supported by adequate disclosure and specification. [00:33:03] Speaker 01: And just as a nouveau, here the skilled artisan comes to the specification thinking 480 milligrams is not effective. [00:33:10] Speaker 01: And the factual question, again, for the district court who watched the party's two experts, who watched the two inventors testify was, is that sole reference to 480 in column 18, not linked to MS, [00:33:24] Speaker 01: in a sentence with three other dose ranges that the skilled artist in reading the specification would believe would be ineffective in MS, is that enough of a blaze mark to convey actual possession? [00:33:39] Speaker 01: And she found that the answer to that was no, and that is not a clearly erroneous fact-finding we submit. [00:33:45] Speaker 02: Counsel, this is Judge Hughes again. [00:33:47] Speaker 02: I want to just ask you one more hypothetical. [00:33:49] Speaker 02: Sure. [00:33:50] Speaker 02: And just changing just two key facts. [00:33:54] Speaker 02: Instead of a patent directed to a bunch of different diseases, this one is solely directed at MS. [00:34:01] Speaker 02: And then in the ranges, instead of all these different ranges, the only range is the 240 to 720 range. [00:34:09] Speaker 02: Everything else is the same. [00:34:10] Speaker 02: We know that 720 doesn't work, that skilled artisans know that 360 doesn't work, [00:34:17] Speaker 02: when the only range includes both some that work and some don't work, and there's a limitation on, I guess, therapeutical efficacy, does that, would that have disclosed a 480 dosage? [00:34:32] Speaker 01: I don't think it would. [00:34:34] Speaker 01: I don't think it would, Judge Hughes, and here's why. [00:34:37] Speaker 01: So the hypothetical is we get rid of all the three dozen other diseases, we get rid of all the dose ranges, so we just have 240 to 720. [00:34:46] Speaker 01: But we still have the skilled artisan's background knowledge coming to the specification that that 240 milligram dose doesn't work, that another dose within that range, 360 milligrams, doesn't work in MS. [00:35:00] Speaker 01: And so the question then becomes the specification has to somehow convey, notwithstanding that background knowledge to the skilled artisan, that 480, another dose picked out of this range, works. [00:35:13] Speaker 01: They could have done that. [00:35:14] Speaker 01: They certainly could have put in the specification information that would show that, yeah, in fact, we think that 480 milligrams would work, but they didn't. [00:35:23] Speaker 02: Well, can I ask you about that, then? [00:35:26] Speaker 02: Because I'm a little confused about the kind of dividing line between when you're allowed to claim a range that has both workable and non-workable dosages and when it's a sufficient written description, when that range is in effect. [00:35:41] Speaker 02: and what you have to do to have blaze marks. [00:35:43] Speaker 02: Because, you know, under the hypothetical, it seems pretty pinned down. [00:35:47] Speaker 02: This is only for MS. [00:35:49] Speaker 02: Here's a fairly limited range, even though some of it ultimately doesn't work. [00:35:53] Speaker 02: You know, we're claiming everything in a range that does work. [00:35:56] Speaker 02: And, you know, the way you're answering this seems to suggest that the only way you're going to have written description is if you actually call out the specific dosage amount. [00:36:06] Speaker 02: And it doesn't seem to me that that's our law. [00:36:09] Speaker 01: Well, and I think, and if I could, if I may just answer that question. [00:36:13] Speaker 03: Yes, you may, of course. [00:36:15] Speaker 01: Okay. [00:36:16] Speaker 01: Thank you. [00:36:17] Speaker 01: And I think this gets to the argument that my friend Mr. Lee was making about inoperative embodiments and citing the Snitzer, the Edsel case. [00:36:25] Speaker 01: And I want to be clear that Mylan's argument is not that the disclosure of inoperative embodiments negates the disclosure of operative embodiments for written description purposes. [00:36:36] Speaker 01: Myelin's argument is that there are no blaze marks at all to an effective method of treating MS with 480 milligrams of DMF. [00:36:44] Speaker 01: There is no adequate disclosure in the patent specification of an operative embodiment period full stop. [00:36:51] Speaker 01: And Biogen's reliance on SNITZR is completely off point if you look at the facts of that case. [00:36:57] Speaker 01: In SNITZR, the specification described 14 specific ions for a single specific use, activating a laser. [00:37:05] Speaker 01: It was undisputed in Snitzer that the claimed ion was described for that precise purpose and it worked for that purpose. [00:37:14] Speaker 01: But several of the other ions were eventually found not to work and that didn't result in a lack of written description. [00:37:20] Speaker 01: The facts here are entirely different. [00:37:22] Speaker 01: Snitzer was not a blaze marks case. [00:37:25] Speaker 01: It was undisputed that the claimed embodiment worked and that it was described. [00:37:30] Speaker 01: the use of the claimed ion was expressly disclosed for the specific claimed purpose. [00:37:34] Speaker 01: And unlike Snitzer's express disclosure of the claimed ion for a single specific purpose, the specification here discloses the possible use of DMF or a host of other drugs in dozens of different neurological diseases [00:37:48] Speaker 01: And the specifications loan reference to 480 milligrams is not tied to any of those specific diseases. [00:37:54] Speaker 01: And again, the dismissor debate here is kind of, again, a fact question. [00:37:59] Speaker 01: A fact question about whether there were sufficient blaze marks. [00:38:03] Speaker 01: And again, the district court, who sat through four days of trial, watched both of the party's experts, heard from both of the inventors, made the factual finding that it doesn't. [00:38:14] Speaker 01: And it's our position that that certainly cannot be [00:38:17] Speaker 01: on this record found to be clearly erroneous. [00:38:24] Speaker 01: And unless there are any other questions, I believe that's all I have. [00:38:27] Speaker 03: We'll hear from Mr. Lee. [00:38:29] Speaker 04: Thank you, Your Honor. [00:38:30] Speaker 04: Let me make four points. [00:38:32] Speaker 04: The first is this. [00:38:34] Speaker 04: The suggestion that method four is not tied to MS, which is actually a foundation of the argument that Mylan made below, and at 829, a foundation that just supports opinion, [00:38:45] Speaker 04: is simply wrong on the express language of the patent. [00:38:51] Speaker 04: At column three, lines one to four, and 14 to 16, column 16, lines 19, 26, the methods described are specifically identified one through five as applying to MS. [00:39:06] Speaker 04: And the only monotherapy in the five methods is method four. [00:39:10] Speaker 04: So this is not a question of blaze marks tying method four to MS. [00:39:15] Speaker 04: There's an explicit disclosure. [00:39:18] Speaker 04: Point two, NUVO is a different case and a distinction where the difference is significant. [00:39:25] Speaker 04: In NUVO, the specifications suggest that un-coded PPIs would not work. [00:39:31] Speaker 04: And the knowledge of one of the organizations on the art was affirmatively that un-coded PPIs would not work. [00:39:39] Speaker 04: That is not what's at issue here. [00:39:41] Speaker 00: And in fact, when jobs... This is Judge Raina. [00:39:45] Speaker 00: I think what is an issue here is whether the specification contains any evidence of the efficacy of the 480 dose. [00:39:54] Speaker 00: Can you point where in the specification I have specific evidence regarding the efficacy of the 480 dose at the time of the filing in February 2007? [00:40:07] Speaker 04: So, Your Honor, I think the answer to that question is in two parts. [00:40:13] Speaker 00: And I'm not referring to your anchoring argument. [00:40:18] Speaker 00: I want to get to your attorney argument, and I want to get to specific evidence in the specification. [00:40:24] Speaker 04: Yeah, no, I understand your argument. [00:40:26] Speaker 04: Your Honor, if I'm misstating it, just tell me. [00:40:28] Speaker 04: Column 18 says expressly that 480 is effective. [00:40:32] Speaker 04: That's all that's required for written description. [00:40:34] Speaker 04: There's no requirement that there be any evidence that is, in fact, effective. [00:40:39] Speaker 04: And that's what ALCON says. [00:40:42] Speaker 04: For sure, Your Honor, if there was an enablement challenge, then that would be important. [00:40:47] Speaker 00: Doesn't that column say that 480, it includes it in a range, but within that range, there's also other doses that are not effective. [00:40:55] Speaker 04: There's nothing in the record that indicates that there are doses between 480 and 720 that are not effective, Your Honor. [00:41:01] Speaker 04: And in fact, what counsel just said to you is in distinguishing snitzer, the claimed convention worked in snitzer. [00:41:10] Speaker 04: Well, Your Honor, the claimed [00:41:12] Speaker 04: invention of 480 here worked. [00:41:14] Speaker 04: It was known to work before the application was filed. [00:41:18] Speaker 04: It went into phase 3s one month after the application was filed. [00:41:23] Speaker 04: It resulted in extraordinary results in the phase 3s. [00:41:29] Speaker 04: I think the answer to your question is in three parts. [00:41:32] Speaker 04: The word that 480 is effective, and it's not in a range. [00:41:37] Speaker 04: 480 specifically identified is there. [00:41:39] Speaker 04: There is not the information [00:41:42] Speaker 04: I think that Your Honor is asking about that here's the proof that it was effective, but the argument we're making is for written description that that is not necessary. [00:41:51] Speaker 04: And at the end of the day, that's the distinction from nouveau. [00:41:58] Speaker 04: Could I just make one last point, Your Honor? [00:42:00] Speaker 04: Yes. [00:42:01] Speaker 04: Okay. [00:42:02] Speaker 04: To take counsel's last argument about the importance of the experts, this is not just a battle of experts. [00:42:09] Speaker 04: There are legal issues here. [00:42:12] Speaker 04: And the legal issue is, can a opinion from an expert that doesn't have the most critical claim limitation be legally effective? [00:42:21] Speaker 04: The answer is it cannot be. [00:42:22] Speaker 04: If there was an opinion on infringement that didn't consider the key limitation, it wouldn't be. [00:42:29] Speaker 04: It can't be because it's based upon a judicial estoppel argument that isn't articulated by the court or correct. [00:42:37] Speaker 04: And then lastly, this idea that Dr. Nguyen [00:42:40] Speaker 04: gave away the keys to the kingdom. [00:42:43] Speaker 04: If Your Honor just consider, if the panel just considers what the court said at page 31 of the appendix, it dismisses Dr. Nguyen only because he could not say that these doses were the most effective or preferred. [00:42:57] Speaker 04: And again, that might be relevant to another issue, but it's not relevant to written description. [00:43:01] Speaker 04: Thank you, Your Honor. [00:43:02] Speaker 03: Okay, thank you. [00:43:03] Speaker 03: All right, the cases will be submitted. [00:43:07] Speaker 03: This court is adjourned.