[00:00:00] Speaker 04: The final case for argument this morning is 25-1228 Janssen Pharmaceuticals v. Teba. [00:00:10] Speaker 04: We're ready whenever you are, Mr. Quinn. [00:00:12] Speaker 03: Thank you, Judge Prost. [00:00:13] Speaker 03: May I please the court, John O'Quinn, on behalf of the appellants? [00:00:16] Speaker 03: This case returns to this court following a decision that provided extensive guidance and direction, but on remand, the district court repeated many of its prior legal errors and committed new ones to avoid the conclusion of obviousness. [00:00:28] Speaker 04: Can I ask you a housekeeping question first? [00:00:32] Speaker 03: Yes. [00:00:32] Speaker 04: Which is, if any of the claims at issue, and I think there are five of them, six of them, is upheld as non-obvious, are you barred from entering the market until the expiration of the 906 patent? [00:00:42] Speaker 03: I believe that's correct, Judge Post. [00:00:44] Speaker 03: I think actually all the claims are at issue. [00:00:45] Speaker 03: It's just five of the claims are representative. [00:00:48] Speaker 03: Claims 2, 10, 13, 20, and 21. [00:00:51] Speaker 03: or representative. [00:00:53] Speaker 03: But respectfully, I submit that all of the claims here are obvious. [00:00:58] Speaker 01: As this court previously observed, the safety of Palo Verde and- I'm sorry, can I just- So just hypothetically, suppose we thought that the opening claim- Claim two. [00:01:11] Speaker 01: Claim two was valid. [00:01:14] Speaker 01: Do we need to get to the other, to the renal insufficiency patients or the particle size one, because they wouldn't make any difference to your getting a FDA approval? [00:01:31] Speaker 01: Or do we not need to get to them, or what? [00:01:33] Speaker 03: So Judge Taranto, I think that if you look at the way that the renal impairment claims are written, many of the same arguments apply to them as they do claims one and two. [00:01:46] Speaker 03: And so I don't think that there would be a separate basis to get to them. [00:01:51] Speaker 03: And in addition- And vice versa? [00:01:55] Speaker 03: I mean, again, I think if any of the claims survive, then you couldn't get approval for an handout. [00:02:02] Speaker 01: And that's the only thing that's at stake. [00:02:04] Speaker 03: And that's what's at stake here. [00:02:05] Speaker 01: Even claim 13, right? [00:02:09] Speaker 03: Even claim, well, yes, because I think the label requires that you have that range. [00:02:14] Speaker 03: And there's no possibility of modifying labels or whatever in the interim, that sort of thing. [00:02:18] Speaker 03: I'm not aware of any, for purposes of giving an and a, with respect to, given that the labor requires that you have a range that covers, that recovers all of these. [00:02:33] Speaker 03: But Judge Post, I actually, on whether or not claim 13 versus claim 10 and whether the labor could be adopted as [00:02:40] Speaker 03: adapted as to that I'm actually not sure that might there is perhaps a possibility there that that could be done so I don't want to speak categorically but I think as a general matter [00:02:49] Speaker 03: We've stipulated an infringement as to all of them. [00:02:52] Speaker 03: The question would then be, is there a way to adjust the label based on those differences? [00:02:57] Speaker 04: Can we start with claim two? [00:02:59] Speaker 03: Yes. [00:03:00] Speaker 04: It's not your typical range case in at least one major respect, which is you've got range arguably laterally, but not horizontally. [00:03:12] Speaker 04: And so I'm looking for a case or something that extends our analysis, our presumption analysis, that applies, at least in certain circumstances, to this case. [00:03:26] Speaker 03: Yes. [00:03:26] Speaker 03: So Judge Crouse, to take a step back, what you have here in terms of the range is something that differs from the prior error by a single dose on a single day. [00:03:37] Speaker 03: And everything else. [00:03:39] Speaker 03: related to that is obvious. [00:03:41] Speaker 00: There's other differences, right? [00:03:43] Speaker 00: Other than just a dose. [00:03:46] Speaker 03: So the other difference, Judge Raina, the only difference other than a numerical difference is the injection into the deltoid. [00:03:53] Speaker 03: as opposed to the gluteal. [00:03:55] Speaker 00: The 548 protocol was certainly directed to the gluteal, but the other... The cytone injection is one difference, and I think that that's a major difference. [00:04:06] Speaker 00: But let's start with the notion here that CLAIM-2 is a methods claim. [00:04:12] Speaker 00: Sure. [00:04:13] Speaker 00: And to take a step back... It's not a composition claim, and it's not a claim that goes to a specific dosage. [00:04:20] Speaker 00: It's a method, a steps, a schedule. [00:04:23] Speaker 03: Right. [00:04:24] Speaker 03: And Judge Raina, if you look, for example, and coming back, I think this is responsive to your question, Judge Post, as well. [00:04:31] Speaker 03: If you look at this court's decision in Peterson, I think Peterson rejected exactly the same kind of argument that there's something about being, quote, unequal and decreasing that then takes you out of the [00:04:42] Speaker 03: the overlapping ranges case law. [00:04:45] Speaker 01: And in that case, I'd like to kind of complete Judge Prost's question. [00:04:52] Speaker 01: We do not have a classic range case where there's an earlier piece of prior art that says, you may use from n to m. And the new patent comes along, and you have something that actually falls within that range. [00:05:10] Speaker 01: We don't have that. [00:05:12] Speaker 03: Well, respectfully, Judge Toronto, I mean, this court's range cases recognize that you can take a range from various data points that are disclosed in the prior error. [00:05:21] Speaker 03: This court recognized that page 926 of its prior opinion that the, quote, loading dose amounts were undisputably disclosed in the prior error, both as a particular dose and as a point within a disclosed range, in a quote. [00:05:34] Speaker 01: And what is that here? [00:05:36] Speaker 03: So the disclosed range is at least 50 to 150 milligram equivalents. [00:05:41] Speaker 03: That's disclosed by the 548 protocol, which was doing 150, 150, 150, 100, 100, 100, and 50, 50, 50. [00:05:48] Speaker 01: It's also disclosed. [00:05:49] Speaker 01: I'm telling you, that protocol did not say, let's do everything between 50 and 150. [00:05:55] Speaker 03: No, but the recognition is, right? [00:05:58] Speaker 01: In separate ranges. [00:06:01] Speaker 01: This is not insignificant. [00:06:03] Speaker 01: range law involved. [00:06:06] Speaker 01: And the question I think Judge Prost was asking is, do all the cases fit into this, or are there some that go beyond that? [00:06:15] Speaker 01: The ordinary range case, maybe all of them, is where what's now claimed [00:06:21] Speaker 01: is actually claimed inside the prior art. [00:06:25] Speaker 01: And it's sort of surprising, if you don't know anything else, that you wouldn't just stop there and say, anticipate it. [00:06:33] Speaker 01: Or maybe there's some other things, but that at least is another range. [00:06:36] Speaker 01: We don't have that. [00:06:37] Speaker 01: And hence you have all of this all of this law about We're gonna still give you a chance to show that is nevertheless not obvious something unexpected results or Criticality or something like that, but I'm not sure we even get into the door of the range cases here Well coming back to my reference to Peterson in Peterson what you had is different [00:07:01] Speaker 03: components, different compositions that were all within different ranges. [00:07:07] Speaker 03: And Almerell itself recognized that the different ranges that different components can come from can be in different pieces of prior art. [00:07:16] Speaker 03: And in Peterson, the court was faced with the argument that, well, yes, it's true that chromium was disclosed in a particular range in the prior art, and rhenium was disclosed in a range in the prior art. [00:07:32] Speaker 03: But what was not disclosed was that you needed rhenium to basically be in a certain relationship with chromium. [00:07:39] Speaker 03: This court in Peterson nonetheless applied [00:07:42] Speaker 03: the overlapping ranges presumption and address the issue of the difference between the rhenium and the chromium and the purported relationship in the claim versus what was in the prior area. [00:07:53] Speaker 01: Is that Peterson you're talking about? [00:07:54] Speaker 03: That is Peterson. [00:07:55] Speaker 03: And I point you to pages 1328 to 1331 of the Peterson decision. [00:08:01] Speaker 03: I thought that Peterson actually disclosed ranges. [00:08:04] Speaker 03: Peterson disclosed ranges for each component separately. [00:08:12] Speaker 03: And then you had the claim that said, ah, but I need a particular short range of rhenium and then a particular point of chromium. [00:08:22] Speaker 03: And the argument was, sort of like the argument here about unequal decreasing, was to say, but no one would have known you needed this ratio between [00:08:30] Speaker 03: And the court said, no, the overlapping range is presumption applied, and the argument you're making goes to criticality. [00:08:38] Speaker 03: Is there something about that that creates a synergy? [00:08:40] Speaker 04: Well, let me say where we are. [00:08:41] Speaker 04: It seems to me there's a range here, an arguable range, and that range is if you take the first loading dose, and you say, okay, the range in the prior art is first is 150, then it's 100, and then there's 50. [00:08:54] Speaker 04: This comes between that. [00:08:55] Speaker 04: Second loading dose. [00:08:57] Speaker 04: Is there a range there? [00:08:58] Speaker 04: So there are arguably two ranges, but that doesn't account for the unequal part. [00:09:06] Speaker 04: And there's no range there. [00:09:08] Speaker 04: Tell me where the range is that would cover the unequal portion of the body. [00:09:14] Speaker 03: I mean, to take one step back, Judge Kroos, our basic proposition here is that any dosing regimen [00:09:19] Speaker 03: in the range where any of the doses on base 1, 8, 30, 60, et cetera, would be obvious if those doses are in the range of 50 to 150. [00:09:30] Speaker 03: But any of them would be obvious. [00:09:32] Speaker 03: And it would be obvious that to [00:09:34] Speaker 03: for the particular needs of a patient to use doses that fare within that range. [00:09:40] Speaker 03: I mean, it's telling the original claims here were claims where both loading doses were in the range of 100 to 150. [00:09:47] Speaker 03: And then they went in and they picked 150 and 100. [00:09:49] Speaker 03: Not because 150, 100 is special and works better than 150, 150. [00:09:54] Speaker 04: That's not true. [00:09:57] Speaker 04: Well, I'm at least not disputing that it wouldn't necessarily satisfy the criticality. [00:10:03] Speaker 04: The question is how you get to that inquiry unless you have the presumption, and the presumption needs a range. [00:10:10] Speaker 04: Now, let me ask you about another case in ray titanium, which you cite in gray, but I don't think you make a detail. [00:10:17] Speaker 04: But in that case, they were dealing with two different priorite alloys. [00:10:25] Speaker 04: And so they had two variables. [00:10:28] Speaker 04: And Judge Rich, in that case, sort of did the two variables. [00:10:32] Speaker 04: That was the closest I could come to what we're talking about here. [00:10:35] Speaker 03: I think Judge Laurie's opinion in Peterson is exactly the same. [00:10:39] Speaker 03: I mean, the exact same argument was potentially an issue in Almerell as well, page 269 of that decision. [00:10:49] Speaker 03: Both of those involve not just two components, but actually multiple compositions. [00:10:54] Speaker 03: where, you know, there were prior ranges. [00:10:56] Speaker 03: And again, in Almorall, you know, in Peterson, I think you could point to a single prior art that disclosed all of the various ranges that applied to the various compositions. [00:11:07] Speaker 03: In Almorall, we actually had to go to different pieces of prior art to point to the ranges that applied to the different compositions. [00:11:13] Speaker 00: Are those composition patterns? [00:11:16] Speaker 03: I don't recall off the top of my head, Judge Raina, whether they involve just in both compositions or they involve both compositions as well. [00:11:23] Speaker 00: Well, but it doesn't matter, doesn't it? [00:11:24] Speaker 00: The presumption obviously supplies whether we have the pen as a method, your pen in the method, that maybe ties in the quantity of the dosage, but on a specific, very specific schedule, which itself is tied into the injection site. [00:11:45] Speaker 03: Well, so a lot built into that. [00:11:47] Speaker 03: Let me try to unpack that. [00:11:49] Speaker 03: So first, the injection schedule is specifically disclosed by the 548 protocol. [00:11:55] Speaker 03: And so what you have. [00:11:57] Speaker 03: Just the timing. [00:11:58] Speaker 03: What do you mean by the schedule? [00:12:00] Speaker 03: Well, the schedule, yes, the timing. [00:12:02] Speaker 03: That's what I mean. [00:12:03] Speaker 03: And so what you have, the claims cover doing 150, 100, 100, 100, 100. [00:12:09] Speaker 03: What that means is one difference on one day. [00:12:12] Speaker 03: That is the very first day of doing 150 instead of 100. [00:12:15] Speaker 03: Otherwise, the 548 would [00:12:18] Speaker 03: It still would be an obviousness argument rather than an anticipation because the injection in the 5-4-8 was to the gluteal. [00:12:23] Speaker 03: The 5-4-4, the W-0-3-8-4-0 disclose intramuscular injection generally. [00:12:30] Speaker 03: They also disclose their range as a range. [00:12:33] Speaker 03: The W-0-3-8-4-0, for example, specifically teaches injections ranging from 25 milliliters to 150 milliliter and anything in between those, except I think they're regimented in either 25 or 50 milliliter increments. [00:12:46] Speaker 03: The 5404 itself teaches from 65 to 230 milligrams, that's the converting based on body weight, and teaches that it results from investigations into development of an efficient, well tolerated depot formulation. [00:13:02] Speaker 03: So what you have is a difference that is known in the prior art. [00:13:05] Speaker 03: They're all expected to be safe and effective. [00:13:07] Speaker 03: Indeed, the district court [00:13:09] Speaker 03: said in appendix 29 that a scared artisan quote would credit Janssen's hypothesis that the doses tested are likely to be safe and effective. [00:13:18] Speaker 03: And you're just changing either the first dose from 100 to 150 compared to what's in the 548 protocol, or you're changing the second dose from 150 to 100 compared to a different dosing regimen in the 548 protocol. [00:13:33] Speaker 03: And with respect to [00:13:34] Speaker 03: Glutero versus deltoid, number one, the district court did find on remand, had not previously, but did find, I think, correctly that that is an obvious distinction. [00:13:50] Speaker 00: It's another obvious factor that must be considered in an obvious analysis. [00:13:55] Speaker 00: Sure. [00:13:56] Speaker 00: But here, we're just not looking at obviousness through the lens of range. [00:14:02] Speaker 00: I mean, there's other issues involved in this case as well. [00:14:06] Speaker 00: And the judge's side is one of them. [00:14:08] Speaker 03: Just one of them. [00:14:10] Speaker 03: So I would point you to Judge Laurie's opinion in Valiant. [00:14:12] Speaker 03: This court specifically addressed the question of, quote, whether overlapping ranges may only establish a prima facie case of obviousness when the only difference between the prior is the range or value of a particular variant. [00:14:25] Speaker 03: And the court rejected the idea that the overlapping ranges presumption can only apply if there's only a single difference. [00:14:34] Speaker 03: In that case, there were multiple differences, more significant differences. [00:14:37] Speaker 03: Deltoid and gluteo well established what the differences were in the prior textbook differences, as you can see in appendix 14.134 and 14.183. [00:14:47] Speaker 03: In that case, it involved an entirely different compound [00:14:50] Speaker 03: And the clerk still applied the overlapping ranges framework. [00:14:54] Speaker 03: Now, I realize that we've spent most of my time, and then some, on overlapping ranges. [00:15:00] Speaker 03: We also explained why the district clerk was wrong on motivation, wrong on expectation of success, legally wrong as to those. [00:15:07] Speaker 04: OK, we're really out of time, but we've got to spend more time than allotted. [00:15:13] Speaker 04: But can you move to moving to the reno impairment claims? [00:15:16] Speaker 04: I think we're left with mild, but I think that's the case you put on. [00:15:22] Speaker 04: So if I – let me just – Oh, I'm sorry. [00:15:25] Speaker 04: I'll give you a chance to respond. [00:15:26] Speaker 04: If I think the district court was wrong about the teaching away in Cleeton, however you – it's on mild impairment, at least with respect to teaching away, and that you showed enough motivation for Invega ER to reduce the dosages by half, [00:15:44] Speaker 04: Does it really matter that the district court viewed your theory as a mild renal impairment? [00:15:50] Speaker 04: I think you should embrace it. [00:15:51] Speaker 03: It does not, Judge Post. [00:15:52] Speaker 03: I mean, the district court's warning himself, and you can see the appendix 10331, relied on the Clinton 2007 reference, which they were saying [00:16:02] Speaker 03: you know, teaches array. [00:16:04] Speaker 03: So if he's relying on it, then that just shows that it wasn't limited to mild. [00:16:10] Speaker 03: But regardless, the only significance of limiting it to mild would be then for their teaching array argument, which I think is wrong for the reasons that this quote previously found. [00:16:20] Speaker 03: And then with respect to Claim 13, [00:16:22] Speaker 03: I mean, they're treating the scale of the Edison like an automaton to say, oh, well, you're only going to divide by half, as opposed to just recognizing there's a general proposition you would reduce. [00:16:32] Speaker 03: And I think, again, you're within ranges that are disclosed by the prior error. [00:16:38] Speaker 00: Can I ask? [00:16:38] Speaker 00: Sure. [00:16:39] Speaker 00: Could you address briefly secondary considerations or objective addition, rather? [00:16:44] Speaker 03: Sure. [00:16:45] Speaker 03: I'd be happy to. [00:16:46] Speaker 03: I think, first of all, and perhaps most principally, [00:16:49] Speaker 03: You know, the fact that the majority of practitioners, physicians, do not use the claim method, you can see this is an appendix 17,903, majority do not use the regimen. [00:17:04] Speaker 03: I think is kind of fatal to their secondary considerations theory in and of itself. [00:17:13] Speaker 03: So you don't have the necessary nexus. [00:17:17] Speaker 03: Second, I think the district court kind of repeated its prior mistake of relying on the safe harbor alone. [00:17:23] Speaker 03: And then third, even if you think there is some evidence of secondary considerations, [00:17:28] Speaker 03: Well, as this court made clear in Alcon v. Apotex, then you, in making the ultimate de novo determination vis-a-vis obviousness, would weigh those against what I think are plainly obvious claims. [00:17:41] Speaker 03: And as the Supreme Court said in the Ag Pro case, Longfield needing commercial success without a mention will not make patentability. [00:17:48] Speaker 03: So I think their secondary considerations argument also depends on really relying on compound claims and composition claims. [00:17:58] Speaker 00: You argue no nexus, essentially, right? [00:18:00] Speaker 03: I'm arguing no nexus. [00:18:02] Speaker 03: I'm arguing a diminished value of any commercial success. [00:18:08] Speaker 03: You know, for the same reasons that this court recognized in cases like Accordia versus Roxanne, that you do have a situation, whatever rate you put on it, you do have a situation where they're plainly blocking patents. [00:18:20] Speaker 03: It kept the field, you know, from being able to be entered for decades. [00:18:24] Speaker 03: Judge Trotter, I think, yes. [00:18:26] Speaker 03: You had a question. [00:18:27] Speaker 01: Oh, this is really trivial. [00:18:30] Speaker 01: And I'm sorry, but you know. [00:18:32] Speaker 01: On page 77 of your brief, where you have your blocking the fortress diagram. [00:18:40] Speaker 01: Yes. [00:18:42] Speaker 01: Two questions. [00:18:42] Speaker 01: Sentence above, he said, then added esters, including palimperidone, palmitate. [00:18:48] Speaker 01: And you cite the 556 patent. [00:18:51] Speaker 01: Yes. [00:18:52] Speaker 01: Is that? [00:18:53] Speaker 01: Esters. [00:18:58] Speaker 01: And then second, what is the 459 patent from October 1994 underneath that? [00:19:09] Speaker 03: I don't know off the top of my head. [00:19:10] Speaker 03: I mean, they are different patents. [00:19:11] Speaker 03: That's not a typo. [00:19:13] Speaker 03: They do go to other – they go to – I think the 556 claimed a broad category that included palatone – palmitate, and I think that's why they were pointing to it. [00:19:27] Speaker 03: And then, you know, the – I'm sorry, the 459 patent, I think, went to particular technology that was used in the production. [00:19:37] Speaker 01: Okay, one more kind of doctrinal question. [00:19:45] Speaker 01: When somebody makes out a prima facie case, then a burden of production is cast on the patent owner to put in certain evidence. [00:19:57] Speaker 00: Correct. [00:19:58] Speaker 01: We've said, I think, that once that evidence comes in, the burden of persuasion remains on the challenger. [00:20:05] Speaker 01: Does that scheme, which is a very standard scheme, apply even [00:20:12] Speaker 01: in the range cases? [00:20:14] Speaker 01: Or are you suggesting that there's a shift in the burden of persuasion when you meet the preconditions for the range cases? [00:20:25] Speaker 03: No, Judge Toronto. [00:20:26] Speaker 03: I think it's the same regime, same scheme that you just described. [00:20:31] Speaker 03: Our position is that, number one, they don't make out the case for criticality here. [00:20:37] Speaker 03: Their evidence [00:20:38] Speaker 03: And second, their own evidence actually rebuts the case for criticality, because what it shows you is that there is nothing special about 150-100. [00:20:47] Speaker 03: It's not like this is some synergy and 150-100 is miraculously better than 150-150. [00:20:52] Speaker 03: It's not. [00:20:52] Speaker 03: In fact, the patent itself discloses that 150-150 and 150-25 did better than 150-100. [00:20:59] Speaker 03: in various clinical trials. [00:21:02] Speaker 03: And that goes. [00:21:03] Speaker 00: This case really, when I hear that argument, really brings to the thought, if that's a case, why didn't they think about this before? [00:21:11] Speaker 00: But just a deep view at that. [00:21:14] Speaker 04: Just a couple minutes, a minute on the particle size claims. [00:21:19] Speaker 04: Let's assume hypothetically that we or I disagree that there was teaching away from formulation B in the 5-4-4. [00:21:29] Speaker 04: I don't know how we get to a reversal in that case, rather than a remand, because I don't know whether you carried your burden of motivation to select formulation B in combination. [00:21:40] Speaker 03: Well, I think, Judge Post, we're actually in the world of a slightly different presumption, because our argument is that we are in the world of a results-effective variable. [00:21:56] Speaker 03: And so I think this case would be controlled by cases like applied materials. [00:22:01] Speaker 03: And so you don't need a separate motivation. [00:22:03] Speaker 03: And in fact, motivation is in many ways conceited. [00:22:07] Speaker 03: If you look at Appendix 23, the district court observed, quote, both sides experts agreed that a skilled Edison seeking to achieve rapid therapeutic effects would be motivated to modify the political size, end quote. [00:22:19] Speaker 03: Their expert essentially conceded the same thing at appendix 11,777. [00:22:22] Speaker 03: There can be no dispute that it's a result-effective variable. [00:22:29] Speaker 03: That's clearly disclosed in the 5404 patent that teaches, quote, the pharmacokinetic properties depend on portable size. [00:22:35] Speaker 03: That's appendix 13,239. [00:22:37] Speaker 03: And their own expert effectively conceded. [00:22:40] Speaker 04: But does the district court address the result-effective variable there? [00:22:44] Speaker 03: So the district court purports to punt on that, and that's Appendix 47, footnote 34. [00:22:52] Speaker 03: But again, I think the district court's recognition at Appendix 23 that both sides' experts agree that Skilled Edison would be motivated to modify the political size and the fact that there is [00:23:03] Speaker 03: No evidence whatsoever, none on the other side, to show that it is anything but a result-effective variable means there is only one conclusion that can follow from the undisputed facts as a matter of law. [00:23:16] Speaker 03: And I don't think that a remand would be fruitful in this case. [00:23:20] Speaker 03: I think this court can decide all of this because, again, there is no evidence that it's not a result-effective variable. [00:23:26] Speaker 03: That's the reason that they rest so hard on an erroneous teaching away argument. [00:23:33] Speaker 01: I think you said, and I may have misheard, that the 906 patent itself shows that if you have two loading doses, 150 and I think you said 25, that that's better than 150 and 100? [00:23:50] Speaker 03: Yes. [00:23:51] Speaker 01: Where's that? [00:23:51] Speaker 03: Yeah, I'd point you to a couple of places, Judge Taranto. [00:23:54] Speaker 03: First, the first optimized loading doses at column 23, lines 15 to 25. [00:24:01] Speaker 03: And then with respect to performance compared to, I'm sorry, lines what? [00:24:06] Speaker 03: 15 to 25. [00:24:07] Speaker 01: And so where does that? [00:24:11] Speaker 03: So that goes to the optimized loading doses point. [00:24:15] Speaker 03: And then with respect to your particular question, if you look at [00:24:21] Speaker 03: Which ones achieved eight-day efficacy? [00:24:25] Speaker 03: In clinical trials, it's column 28, lines 3 to 8. [00:24:30] Speaker 03: And it identifies 150, 150, 150, 25 as achieving eight-day efficacy. [00:24:38] Speaker 03: Again, this is column 28, lines 3 through 8. [00:24:41] Speaker 03: 150, 100 only, I think, achieved eight to day 22 in these experiments. [00:24:49] Speaker 03: And for the idea that all of this is just a difference in degree, none of this is a difference in kind, I would just also point you to appendix 41907, 54693. [00:24:58] Speaker 03: But both of those go just more generally to how whether you were using [00:25:07] Speaker 03: 75, 75, 100, 100, 150, 110. [00:25:11] Speaker 03: It's just a difference in degree, not a difference in time. [00:25:15] Speaker 03: But as I said, the patent itself, I think, concedes that array, both in terms of identifying that all of these were optimized loading doses, that all of these were better than placebo. [00:25:26] Speaker 03: That's column 28, lines 3 through 7, and then the thing that I referred you to specifically at column 28, lines 3 through 8. [00:25:37] Speaker 03: Thank you. [00:25:39] Speaker 03: Thank you, Judge Crosley. [00:25:41] Speaker 03: Thank you very much. [00:25:52] Speaker 02: Well, good morning, Your Honors. [00:25:53] Speaker 02: Are you ready? [00:25:54] Speaker 02: Yes. [00:25:55] Speaker 02: May it please the court, Barbara Mullen for Janssen. [00:25:58] Speaker 02: So let's start from the premise that TEVA had the burden of proving obviousness by clear and convincing evidence for every represented claim. [00:26:05] Speaker 02: OK, can we start? [00:26:05] Speaker 04: But you sat here for all of this, so can we just dive into? [00:26:08] Speaker 04: I'm struggling with the question of whether a presumption applies, and that really affects what you're going to be talking about. [00:26:14] Speaker 04: So if the claim loading dose was 149 to 149, first and second, would you say that the presumption of obviousness applies? [00:26:30] Speaker 02: I still don't think it applies, Your Honor. [00:26:33] Speaker 02: So first let's step back and say that from the perspective of the 548 protocol and what it discloses, I think it's important to remember not only does it disclose all equal-dose dosing regimens, but that Dr. Wermeling admitted that that does not motivate any unequal dosing. [00:26:48] Speaker 04: But I guess here's – I'm surprised to hear you say that, because I thought the whole difference of what anybody thought was the decrease [00:26:58] Speaker 04: in the claimed, and if you have a situation where there's no decrease, I'm really having a hard time seeing why that wouldn't come within the range protocol. [00:27:09] Speaker 02: Would 149-149 come within the range of 150-150 or 150-150? [00:27:14] Speaker 04: The range that we already have in the prior art, 150-150 to 150, 100 to 100, 25 to 25. [00:27:21] Speaker 02: I suppose if you're saying we're just going to look at the range and ignore that there's other differences, perhaps it does. [00:27:28] Speaker 02: But the difference here, obviously, is not that. [00:27:30] Speaker 02: We have a difference because not only is the difference in the specific sequence of dosing and claim to, which is 150 then 100, but also in the fact that that is so far removed than what's suggested by the 548 protocol that Dr. Wermeling said the 548 doesn't even suggest or motivate, opposed to use any unequal doses. [00:27:49] Speaker 02: And that's at appendix 10479. [00:27:53] Speaker 04: But I'm talking about a claim that doesn't have unequal doses, that has 149 and 149. [00:27:59] Speaker 04: So if there are no unequal doses in the claim, wouldn't a range apply? [00:28:07] Speaker 02: Potentially. [00:28:08] Speaker 04: OK. [00:28:09] Speaker 04: So then if we have, let's say the claim was 149 first dose, 148 the second. [00:28:16] Speaker 04: Is that really avoid? [00:28:19] Speaker 04: So the 150 to 100, wouldn't 150 to 100 be presumptively obvious? [00:28:26] Speaker 02: No. [00:28:27] Speaker 02: The answer is no, right? [00:28:29] Speaker 04: And that's because, just because it's one different, 149 going down to 148, that avoids the end? [00:28:36] Speaker 02: No. [00:28:37] Speaker 02: It really is because the presumption of obviousness cases apply. [00:28:40] Speaker 02: First of all, as you've already discussed, [00:28:42] Speaker 02: primarily in cases where it's only a range that's different. [00:28:45] Speaker 02: Now, I know that my friends was talking about certain cases, such as Valiant, Amaral, Titanium, perhaps, where this quarter has extended that to say, okay, if it's not just an overlapping range, if there's another difference, for example, here, the Deltoid difference. [00:29:00] Speaker 02: But in those cases, they've said if it's not just an overlapping range, if there's another difference, maybe, maybe we apply a prima facie case to this where the facts establish [00:29:11] Speaker 02: that the two things that you're applying to are interchangeable. [00:29:15] Speaker 02: So let's go back to Valiant. [00:29:17] Speaker 02: Valiant was talking about chemical compounds. [00:29:19] Speaker 02: It was two different chemical compounds. [00:29:21] Speaker 02: The prior art disclosed a pH range for one of them. [00:29:24] Speaker 02: And they said that creates a prima facie obviousness case for the pH range for the other one. [00:29:29] Speaker 02: Why? [00:29:30] Speaker 02: Because the factual evidence was that they were structurally and functionally similar so that it would be expected to apply. [00:29:36] Speaker 02: Same thing in Almaral. [00:29:38] Speaker 02: Right? [00:29:39] Speaker 02: The two agents were found to be interchangeable. [00:29:41] Speaker 02: And that's why the range was applied to both. [00:29:43] Speaker 02: That's not the case we have here. [00:29:45] Speaker 02: One of the distinctions we have here is the deltoid. [00:29:48] Speaker 02: And the district court, what the district court found was that the deltoid, a post-it, would have expected to be interchangeable. [00:29:54] Speaker 04: OK, so hypothetically, let's assume that we take deltoid off the table. [00:29:57] Speaker 02: OK. [00:29:58] Speaker 04: That we don't think our cases necessarily preclude that. [00:30:01] Speaker 04: So then we're left with the ranges. [00:30:02] Speaker 04: So can we talk about the ranges? [00:30:04] Speaker 04: Your friends seem to rely heavily on inmate Peterson. [00:30:08] Speaker 04: in rate titanium as a secondary thing. [00:30:10] Speaker 04: Do you have any view on Peterson? [00:30:13] Speaker 02: Well, I think that you're taking out a key part of obviousness, which is with respect to the claim as a whole. [00:30:18] Speaker 02: So if you're saying can we ignore everything in the claim except potentially numbers, I still don't think it's a range case. [00:30:23] Speaker 02: Because I think that the concept of an equal dose dosing regimen is much different [00:30:28] Speaker 02: then the concept is to claim two regimens. [00:30:30] Speaker 02: I don't think that it's just a simple presumption can apply here, right? [00:30:33] Speaker 02: Because you have a difference not only between the start with 150 and then 100, but you have the very difference that, conceptually, if you have a patient that can be maintained on 25-mig equivalents or 50-mig equivalents as a maintenance dose, okay, that's going to be their monthly dose, they still get 150 [00:30:54] Speaker 02: and then 100 to start with. [00:30:56] Speaker 02: That's not only a conceptual difference, it's an actual difference. [00:31:00] Speaker 02: Because what we know when you compare the 548 protocol to what actually happens is that when the 548 protocol is used, you don't get rapid efficacy. [00:31:09] Speaker 02: whereas with the claimed dosing regimen, you do. [00:31:12] Speaker 04: Is there anything in the spec that calls out the criticality or the need of this? [00:31:17] Speaker 04: Because your friend did call out the provisions in the spec, as he did. [00:31:21] Speaker 04: It suggests that there's this isn't. [00:31:25] Speaker 04: I mean, the only optimal language I could find in the spec was the fact that these three are all optimal. [00:31:33] Speaker 04: And in fact, there's that other provision he cited to say that the other two were even better. [00:31:38] Speaker 02: Sure. [00:31:38] Speaker 02: Well, actually, if you look at the appendix page 171 and 172, this is example 8, at the bottom of column 26 and continuing into example for column 27. [00:31:50] Speaker 02: What my friend is pointing to is not what's in the prior art, because the prior art doesn't involve deltoid injections at all. [00:31:57] Speaker 02: So what he's pointing to is not in the prior art. [00:32:00] Speaker 02: What he's pointing to here is a study where every single patient got 150 mig equivalents in the deltoid on day one. [00:32:08] Speaker 02: So that whatever efficacy they saw by day eight, that was from the 150 mig deltoid dose. [00:32:15] Speaker 02: What it goes on to say in column 27 is what happens after that when you change the dose at day eight, where some patients got 25, some got 100, and some got 150. [00:32:26] Speaker 02: And what happened was on that day eight, if you gave them 150, those levels continued to rise. [00:32:32] Speaker 02: If you gave them 25, they completely dropped. [00:32:34] Speaker 02: But if you just gave them that 100, not only did you reach the threshold, but you maintained that steady. [00:32:40] Speaker 02: And that is what the patent is explaining to you, and that is the regimen explained. [00:32:46] Speaker 04: All right, but does any of this call out that there was some criticality more optimized than others for this 150-100 that's claimed? [00:33:00] Speaker 02: I think that calls out that that's the combination that gives you not just rapid, but sustained efficacy, which is what is achieved by the claim. [00:33:06] Speaker 02: It's not just the loading doses achieve the rapid efficacy, but then the maintenance doses maintain the sustained efficacy. [00:33:12] Speaker 02: without, for example, the 150 dose taking you to an area of potentially very dangerous, very severe side effects or the 25 risking relapse. [00:33:21] Speaker 02: So I do think it shows that that is critical. [00:33:23] Speaker 02: I think the other thing to think about with the presumption cases is that in all these cases where presumption applied, routine optimization was a theme, right? [00:33:33] Speaker 02: You have cases saying that [00:33:39] Speaker 02: It is not invented to discover optimum ranges by routine optimization. [00:33:44] Speaker 02: Where the general conditions of a claim are disclosed in the prior art, it is not invented to discover the optimum or workable ranges by routine experimentation. [00:33:52] Speaker 02: That's the premise. [00:33:53] Speaker 02: That's why you're changing things a little bit. [00:33:58] Speaker 02: Because the premise of all of the presumption cases are that routine optimization is involved. [00:34:07] Speaker 02: In this case, [00:34:08] Speaker 02: It's not very well suited to that, because we don't have anything to optimize. [00:34:13] Speaker 02: The 548 protocol is a protocol without any data, so there's no data to optimize. [00:34:19] Speaker 02: And when I asked Dr. Wermeling-Jurton trial, is routine optimization part of your theory, that was the only time those words came up at trial, and he said no. [00:34:28] Speaker 00: Did you find any cases where the presumption applies? [00:34:32] Speaker 00: And we're dealing with a method pattern [00:34:39] Speaker 02: I don't recall one off the top of my head. [00:34:45] Speaker 02: But I do recall many where you're talking about a composition and whether or not you get ranges from one reference or two references or three references. [00:34:56] Speaker 02: That may not make a difference, but I'm actually not aware of one standing reference. [00:35:00] Speaker 02: OK. [00:35:00] Speaker 04: What about Inmate Peterson? [00:35:02] Speaker 02: Inmate Peterson was about alloys. [00:35:07] Speaker 02: And I think it was actually just applying a range to the alloys. [00:35:12] Speaker 04: Did it involve different variables? [00:35:14] Speaker 02: It involved different references that provided the ranges. [00:35:20] Speaker 02: One reference that provided multiple, sorry, one reference that applied multiple ranges. [00:35:27] Speaker 04: And I know in-ray titanium was only cited in gray. [00:35:31] Speaker 04: But to you, that seemed to me it's not a range case, but it was referred to in Peterson discussing ranges. [00:35:39] Speaker 04: And it feels like it was an obviousness case. [00:35:43] Speaker 04: And that involved two different variables. [00:35:46] Speaker 04: So you analyzed each separately and said, is this within the range for variable one? [00:35:50] Speaker 04: Is this within the range for variable two? [00:35:52] Speaker 04: That seems closer to our case than some of the others I've seen. [00:35:56] Speaker 02: Maybe, but you're still just applying ranges, right? [00:35:59] Speaker 02: And I guess we get back to the premise of does the 540 protocol disclose a range at all? [00:36:03] Speaker 04: Well, actually, it was a little different than ranges. [00:36:05] Speaker 04: I mean, it had numbers. [00:36:06] Speaker 04: Like the prior art had 30 and 50, and then this had three. [00:36:10] Speaker 02: Right, but that was said to establish a range, right? [00:36:13] Speaker 02: Effectively establish a range, right? [00:36:15] Speaker 02: Right. [00:36:17] Speaker 02: Yes, but again, it was a range, not the distinction between a regimen [00:36:24] Speaker 02: that had all equal doses versus a regimen where you have a maintenance regimen that is completely separate from the loading dose regimen and a loading dose regimen that is specific. [00:36:34] Speaker 02: You give 150 in deltoid on day one and 100 on day eight. [00:36:38] Speaker 02: And if you do that, and only if you do that, do you get most of the patients into the therapeutic window within one week and keep them [00:36:48] Speaker 02: I think in addition to the issue of whether or not the presumption applies, should even apply here, if it did, it would be rebutted. [00:36:58] Speaker 02: As Teva said in its reply brief at 7, the presumption is rebutted with evidence that the claimed values are critical or special. [00:37:06] Speaker 02: or otherwise not from routine optimization. [00:37:09] Speaker 04: So what you're saying is, if the 548 had 150 and 140, then that would establish a range that would be applicable to the claimed? [00:37:22] Speaker 02: I think it's a different concept. [00:37:25] Speaker 02: I see it conceptually different, because you're talking about an equal dose regimen where you have a patient who needs 150 make equivalents to be stable. [00:37:31] Speaker 02: So that's what you give them. [00:37:33] Speaker 02: Or they need only 50. [00:37:34] Speaker 02: So that's what you give them. [00:37:35] Speaker 04: No, but that's why I said the hypothetical is 150 to 140. [00:37:38] Speaker 04: So it's a variation in the first and the second loading doses. [00:37:43] Speaker 02: It would be a variation. [00:37:44] Speaker 02: It would not suggest a specific combination here. [00:37:47] Speaker 02: And I would not characterize it still as a range if it's on specific doses, right? [00:37:55] Speaker 04: Do you want to comment on the renal claims? [00:37:58] Speaker 04: We had a little discussion there. [00:38:00] Speaker 04: Yes. [00:38:01] Speaker 04: In terms of renal teaching away. [00:38:04] Speaker 04: Let's assume that we're talking about mild renal impairment. [00:38:10] Speaker 02: Yeah. [00:38:11] Speaker 02: I don't think that the district court was actually had a finding of teaching away for the renal impairment claims. [00:38:16] Speaker 02: That was only for claims 20 and 21. [00:38:20] Speaker 02: But Clayton 2007, I guess the issue is that [00:38:25] Speaker 02: TEVA had to establish not just the general proposition that because these drugs are cleared renally, that you have to reduce them in a renally impaired patient, but how you'd get to the actual regimens of claims 10 and 13. [00:38:38] Speaker 02: And the prior art was kind of all over the place, right? [00:38:41] Speaker 02: So. [00:38:42] Speaker 04: Well, what about Invega ER? [00:38:44] Speaker 02: Invega ER says a 75% dose reduction for moderate or severe renal impairment. [00:38:54] Speaker 02: That's appendix page 16233, but it's not talking about mild renal impairment. [00:38:59] Speaker 02: Clayton 2007 said, no reduction for mild and renal impairment, only consider it for moderate to severe. [00:39:05] Speaker 02: And if you apply that 75% reduction from Envega ER, and I think that's actually between the maximum allowable dose and the renal dose, [00:39:19] Speaker 02: But if you apply that 75% reduction, you don't get to claim 10 or 13. [00:39:24] Speaker 04: I'm sorry. [00:39:24] Speaker 04: I made me wrong on this. [00:39:26] Speaker 04: I understood it should be a 50% reduction. [00:39:28] Speaker 02: Well, that was a theory. [00:39:29] Speaker 02: The question is, where did that come from, right? [00:39:32] Speaker 04: Well, the argument is it came from Invega ER, which represented a 50% reduction. [00:39:40] Speaker 02: Well, Invega ER actually says that there's a 75% reduction. [00:39:47] Speaker 02: Can you grab that 16? [00:39:49] Speaker 02: 233. [00:39:49] Speaker 04: Okay, I mean, you know the record obviously better than I do, so I'll maybe be right about that. [00:39:55] Speaker 02: Yeah, at appendix 16233, the NVEGA ER label says that there's a 75 percent dose reduction for moderate or severe renal impairment. [00:40:09] Speaker 02: So, but the bottom line is the prior didn't have anything consistent about how you would reduce the doses in order to [00:40:19] Speaker 02: to address renal insufficiency in not to address renal insufficiency. [00:40:26] Speaker 02: And in addition to that, it's not just that you have to reduce them, but how much you have to reduce them, right? [00:40:47] Speaker 02: I don't know if you have another question on that, if you'd like me to. [00:40:49] Speaker 04: Yeah, I'm just trying to look, because I thought, but I don't mean to quibble with you, as I said. [00:40:55] Speaker 04: It's your record. [00:40:56] Speaker 04: It's just I thought that the in-vega ER went from 12 to 6, which was a 50% reduction. [00:41:02] Speaker 04: But maybe I'm mistaken about that. [00:41:03] Speaker 04: Anyway, just one quick question, then, on the particle size. [00:41:08] Speaker 04: Do you want to, just any comment? [00:41:11] Speaker 04: on the touching away formulation. [00:41:15] Speaker 04: Yes. [00:41:16] Speaker 02: So the question was, as this court instructed the district court to do, to determine whether or not the D50 value in the 544 patent was criticized, discredited, or otherwise discouraged. [00:41:28] Speaker 02: And the 544 patent says that a formulation having a D90 of less than 2,000 nanometers is necessary to be acceptable for intended patients. [00:41:38] Speaker 02: That is the characteristic of formulation C and D, which were the only formulations against its stability. [00:41:46] Speaker 02: Our expert, Dr. Sinka, testified that when you read all of this together, that a post-it would have eliminated formulation B from further testing. [00:41:55] Speaker 02: And Applied Materials says that when a post-it would be led in a direction divergent when the path of the inventors followed, that that constitutes teaching away. [00:42:06] Speaker 02: My friends talked about the idea that everybody knew that particle size impacts the pharmacokinetics. [00:42:11] Speaker 02: That's true. [00:42:12] Speaker 02: But it's not enough that the posts are moved. [00:42:15] Speaker 02: We could do something here to change things. [00:42:16] Speaker 02: The question is, what would they have done? [00:42:18] Speaker 02: And if you actually look at the four examples in the 544 pattern, formulations A, B, C, and D, the record evidence shows that the 544 pattern is about a formulation that's being given every three weeks or months. [00:42:31] Speaker 02: So that's a long-acting formulation from the rapid efficacy. [00:42:34] Speaker 02: If you wanted to make it more rapidly effective, then all that's in the record is that you would make the particle sizes smaller. [00:42:41] Speaker 02: Well, C and D actually already have the smallest particle sizes. [00:42:44] Speaker 02: And they were the ones that were tested for stability. [00:42:47] Speaker 01: The smaller the particle size, the higher the ratio of surface area to volume. [00:42:51] Speaker 01: The faster it's exposed. [00:42:52] Speaker 01: So you get more exposure. [00:42:54] Speaker 02: But the thing is, it doesn't actually happen. [00:42:57] Speaker 01: What's the best setness if there is one in 544 that says, [00:43:04] Speaker 01: this D-90 cap is essential to what we're up to here, obviously, in different words. [00:43:14] Speaker 02: Yeah, it's Appendix Page 1-3-2-3-8, at Column 2, Lines 60-64. [00:43:21] Speaker 02: Column 2, Lines 60-64, and Appendix 1-3-2-3-9, at Columns 3, Lines 11-45. [00:43:30] Speaker 02: And then you have [00:43:34] Speaker 02: At 13242, at column 9, lines 33 to 44, only formulations C and D with advanced stability tests. [00:43:43] Speaker 01: And the other side made a point about how I think that the D50 figure is, or what's in the claim here, is covered by claim 7 of the 544. [00:43:58] Speaker 01: I'm not sure I really understood the point, but. [00:44:02] Speaker 02: So. [00:44:04] Speaker 02: Claim seven at the 544 patent. [00:44:07] Speaker 02: Let's grab it so I don't mis-port it. [00:44:16] Speaker 02: Is a method for treating schizophrenia and other diseases. [00:44:19] Speaker 01: With the composition of claim one. [00:44:21] Speaker 02: The composition of claim one. [00:44:22] Speaker 02: The composition of claim one is talking about, if you see, [00:44:29] Speaker 02: The description of CLAIM-1, and particularly with respect to the particle size, it is talking about a surface area greater than 4 meters squared per gram, corresponding to an effective average particle size of less than 2,000 nanometers. [00:44:45] Speaker 02: And this patent defines effective average particle size as V90. [00:44:52] Speaker 01: OK, one other small question about the objective indicia, in particular the industry praise. [00:45:02] Speaker 01: The label, this is at, what, 13118 to 120, seems to allow initial doses significantly larger than the claim [00:45:20] Speaker 01: than the doses in the claimed here. [00:45:23] Speaker 01: And if that's right and people were praising the dosing regimen from the label, why would that indicate praise for the claimed dosing regimen? [00:45:33] Speaker 02: The label dosing regimen is 150 on day one and 100 on day eight. [00:45:38] Speaker 01: So OK, just show that to me. [00:45:41] Speaker 01: I'm just looking. [00:45:42] Speaker 01: I figured I was misreading this. [00:45:45] Speaker 01: I'm showing a box that says 234 and 156. [00:45:49] Speaker 02: Oh, I'm sorry. [00:45:50] Speaker 02: So that's the difference between milligrams and milligrams equivalent. [00:45:53] Speaker 01: I see. [00:45:54] Speaker 02: OK, so the milligram equivalent is 150 milligrams equivalent. [00:46:00] Speaker 01: Oh, you're telling me those translate? [00:46:02] Speaker 02: Yes, I am. [00:46:04] Speaker 02: Don't make me do the math in my head. [00:46:09] Speaker 04: Thank you. [00:46:10] Speaker 02: Can I? [00:46:11] Speaker 02: Sure. [00:46:11] Speaker 02: If I can just, I want to make just one or two more comments because I feel like I need to based on what's already been said here today, okay? [00:46:18] Speaker 02: The 544 patent teaches administration of a single dose of palperidone permatate that's effective for three weeks to a month. [00:46:24] Speaker 02: It doesn't teach loading doses. [00:46:27] Speaker 02: W0384 does not disclose anything about a dosing regimen, much less give a motivation to select the claimed loading doses. [00:46:33] Speaker 02: They were admissions by Dr. Wermeling at appendix pages 105 [00:46:38] Speaker 02: 06 to 7, and 105, 11 to 12. [00:46:42] Speaker 02: So the district court was not erroneous in its findings that these do not teach loading doses to initiate treatment, discuss a multi-dose regimen, or address the complexities that present themselves when administering multiple doses of varying amounts at different times. [00:46:59] Speaker 02: The other comment I would make is about the blocking pattern. [00:47:01] Speaker 02: If you look at the graph, it includes things that, by the way, aren't even Janssen. [00:47:05] Speaker 02: It's got Elon technology on there. [00:47:08] Speaker 02: But in addition to that, the question on blocking patents is a fact-specific inquiry. [00:47:15] Speaker 02: The question is, would competitors have been deterred from investing resources needed to make the invention at the priority date? [00:47:21] Speaker 02: And the district court here went through a several-page analysis in concluding that there was no deterrence in fact. [00:47:30] Speaker 02: And in fact, Teda itself, [00:47:33] Speaker 02: filed an application, a patent application, to Palo Peridot and Palmitate about the same time as the priority date. [00:47:39] Speaker 02: And since we know that drug development takes at least 10 years, [00:47:44] Speaker 02: We also now have on the market Rizofri, which the first clinical trials were done in November of 2018. [00:47:51] Speaker 02: So Rizofri had to be being developed at the same time. [00:47:55] Speaker 02: Now, that is a drug that uses palperidone palmitate in a different dosing measurement. [00:47:59] Speaker 02: It was approved by the 505b2 pesticide in the Hatch-Waxman Act. [00:48:05] Speaker 02: So it's not that the world is precluded from using this drug. [00:48:10] Speaker 02: for many years. [00:48:11] Speaker 02: They're just for the limited period of time that we have our patent. [00:48:16] Speaker 02: They're precluded from copying our very specific dosing regimen. [00:48:19] Speaker 04: Thank you. [00:48:20] Speaker 02: Thank you. [00:48:22] Speaker 04: Will we store four minutes, everybody? [00:48:33] Speaker 03: Thank you, Judge Prost. [00:48:35] Speaker 03: Judge Taranto, on your questions about D90 and D50 and such, there's no inconsistency between having the claim D90 in the 544 and the claim D50 in the 906 patent. [00:48:47] Speaker 03: Their whole theory of teaching away comes from basically them looking at formulations A, B, and C and saying, well, these two that fit the D90 that they had experimented with [00:48:58] Speaker 03: wouldn't fit our D50, but there's no inherent inconsistency between having a D90 of 2000 and having a [00:49:04] Speaker 03: a D50 in the 900 to 1600 range. [00:49:09] Speaker 03: It's only that the D90 has got to be 2000 or lower. [00:49:12] Speaker 03: It's just a different way of measuring things. [00:49:13] Speaker 01: But the formula B had a D50 that was within the range, but the D90 was through the roof. [00:49:20] Speaker 03: The D90, well, I think it's actually the D. That's right. [00:49:25] Speaker 03: That's exactly right. [00:49:26] Speaker 03: Whereas C was DC. [00:49:28] Speaker 03: Excuse me. [00:49:28] Speaker 03: The formulation C was very close on both. [00:49:30] Speaker 03: And the idea that you would, based on those [00:49:34] Speaker 03: Relatively arbitrary formulations would say, ah, this now teaches away. [00:49:38] Speaker 03: It's just bootstrapping upon bootstrapping, because there's nothing that specifically teaches away from the D50 that is claimed. [00:49:44] Speaker 03: Now turn to the real impairment claims. [00:49:46] Speaker 03: Now that is one where the labor is different from the claims. [00:49:52] Speaker 03: The labor actually teaches, starting with 100-milligram equivalents [00:49:56] Speaker 03: As opposed to 75 milligram equivalents, which is what the focus of the patent is, although I do agree with the fact that the things that you were asking about just go to a mathematical conversion. [00:50:08] Speaker 03: But with respect to the renal impairment claims, the district court did, in fact, rely on teaching rate. [00:50:13] Speaker 03: That was at appendix 41. [00:50:14] Speaker 03: And Judge Prost, you're absolutely right. [00:50:16] Speaker 03: VEG and ER teaches a 50% reduction for mild [00:50:19] Speaker 03: It does teach a 75% reduction for moderate to severe. [00:50:23] Speaker 03: You can see that in appendix 16233, which all again goes to why not just claim 10, which is directly half, but also claim 13. [00:50:33] Speaker 03: you know, on a scale of Anderson's non-automaton. [00:50:35] Speaker 03: And we'll understand that for different patients, maybe you're on the border between mild and moderate, you might want to do something even better for those so-called maintenance doses. [00:50:44] Speaker 03: Judge Adrena, you were asking about what are examples in this court's precedents that involve method claims? [00:50:52] Speaker 03: Alma-El was a method claim. [00:50:54] Speaker 03: Both claimed one. [00:50:55] Speaker 03: and CLAIM-6 in ALMORAL, or methods for treating a dermatological condition. [00:51:02] Speaker 03: And each one of those, you know, it's not just titanium. [00:51:06] Speaker 03: Each one of those involves multiple different compositions. [00:51:10] Speaker 03: It was having a certain rate of DASPOM, another with respect to diethylene glycol, another with respect to a polymeric viscosity barrier. [00:51:21] Speaker 00: That was a composition case? [00:51:23] Speaker 03: No, it's a method for treating a dermatological condition. [00:51:27] Speaker 03: You can see Claims 1, Claims 6 of the Alvaro case, which is 28F43. [00:51:33] Speaker 03: And I'm pointing to pages 268 to 269. [00:51:37] Speaker 03: But the key point that ALBERAL stands for and that Peterson stands for is that you can have various things that are being modified, each one of which falls within a range. [00:51:48] Speaker 03: And you are still in the presumption that's created by the range cases. [00:51:53] Speaker 03: And that's exactly what you have here. [00:51:55] Speaker 03: Each day that is on a known schedule, by which I mean the date, [00:51:59] Speaker 03: each day it falls within a disclosed range. [00:52:02] Speaker 03: It falls, in fact, squarely between either 150 or 100. [00:52:08] Speaker 03: And as our expert explained, it's 10,322. [00:52:15] Speaker 03: the fact that you knew that 150, 150, 150 was safe, was thought to be safe and effective, and 100, 100, 100 was thought to be safe and effective, that ergo, anything in between them, mixing and matching on any day, would be safe and effective. [00:52:30] Speaker 03: It's literally taking the two for the living doses, taking the two, 150 and 100, adding them together, you get 250, and then splitting it out and saying, okay, I'm going to do 150 on the first day and 100 on the next. [00:52:43] Speaker 03: And prior, our life [00:52:45] Speaker 03: Eroshevsky and the Harbaugh labor at appendix 16,651 teach that that is a way that you would do that. [00:52:53] Speaker 03: The other thing, too, her argument about trying to distinguish the 548 protocol saying, oh, it's a fixed amount every day. [00:53:00] Speaker 03: A skilled artisan knew at the time it was very, very common to vary the dosing. [00:53:05] Speaker 03: You might titrate up. [00:53:06] Speaker 03: You might titrate down. [00:53:09] Speaker 03: I point you to appendix 12,379. [00:53:12] Speaker 03: with the testimony that it was not at all unusual to start patients with the highest approved and tapered down. [00:53:18] Speaker 04: OK, I think we're running out of time. [00:53:19] Speaker 04: One final thought, one sentence. [00:53:21] Speaker 03: Yeah, so my final thought is that trying to distinguish array the 5-4-8 protocol, which doesn't stand alone. [00:53:29] Speaker 03: It stands with the 5-4-4 pattern, the W-8-1-8-4, on the basis that it was fixed-dosing. [00:53:35] Speaker 03: It is not supported by the priority, and it is certainly not supported by this court's cases like Almerell and Peterson, among others. [00:53:46] Speaker 03: I'm happy to answer any additional questions the court might have. [00:53:48] Speaker 04: Time up. [00:53:48] Speaker 04: Thank you. [00:53:49] Speaker 03: Thank you, Judge Frost.