[00:00:00] Speaker 01: Our next case is Immunogen versus the Undersecretary of Commerce, 2023-1762. [00:00:07] Speaker 01: Good morning, Your Honors. [00:00:10] Speaker 03: Good morning. [00:00:11] Speaker 01: It's the morning when you're ready. [00:00:16] Speaker 03: Good morning, Your Honors. [00:00:17] Speaker 03: Good morning. [00:00:18] Speaker 03: May it please the Court. [00:00:20] Speaker 03: I'd like to focus on three points this morning, the first having to do with the issue of indefiniteness and the other two on the issue of obviousness. [00:00:29] Speaker 03: Starting with indefiniteness, the intrinsic evidence, including the claims, the specification, and the file history, make clear that the claim formula for AIBW is the one and only formula recited in the specification, both in the definitions and example four. [00:00:46] Speaker 01: Let's go to obviousness, because if you lose on either, you lose. [00:00:53] Speaker 01: The difference between what's in the claims and what's in the prior art is six versus seven milligrams per kilogram and the definition of body weight. [00:01:07] Speaker 01: It's within the scale of the art to vary doses to obtain the best dose and the concept of AIBW was in the prior art, so why wasn't the obviousness determination correct? [00:01:23] Speaker 03: It was incorrect for two different reasons, Your Honor. [00:01:26] Speaker 03: The first having to do with the motivation and the second having to do with the reasonable expectation of success. [00:01:32] Speaker 03: Starting with the motivation, when you say, Your Honor, respectfully, that AIBW, that method of dosing, was in the prior art, it was in the prior art on totally different things. [00:01:43] Speaker 03: It was in the prior art in nutrition, in small molecule drugs, in different ones. [00:01:48] Speaker 03: But there are two salient key points. [00:01:51] Speaker 03: that are undisputed and part of the court's factual findings. [00:01:54] Speaker 03: One, that an AIBW dosing regimen had never been used with an ADC, with an antibody drug conjugate, which is a completely different type of drug with different pharmacokinetic properties. [00:02:07] Speaker 03: And number two, and we probably should have highlighted this even more in the brief, [00:02:11] Speaker 03: that AIBW had never been suggested in any drug, in any area, to address the issue of ocular toxicity. [00:02:20] Speaker 03: Not for any drug. [00:02:21] Speaker 04: I'm not going to say that, but the PTL expert said that someone skilled in the art would have looked to AIBW [00:02:32] Speaker 04: as a matter of course. [00:02:33] Speaker 04: And the district court credited that testimony. [00:02:37] Speaker 04: And so why is that conclusion clearly erroneous? [00:02:42] Speaker 03: Your Honor, I would say the following, that that conclusion in view of those factual findings should be reviewed here under a de novo standard, because the ultimate conclusion of obviousness, just having an expert say it, is an issue of law. [00:02:56] Speaker 03: The underlying factual findings that are not in dispute [00:02:59] Speaker 03: and that the district court found were that, number one, it wasn't recognized that A53 had an ocular toxicity problem, but even if you got there, the court found that AIBW had never, ever been used with this category of drug. [00:03:13] Speaker 04: Wait a second. [00:03:14] Speaker 04: You're saying that's a legal issue? [00:03:16] Speaker 04: Why isn't that a fact issue as to whether someone's skilled in the art? [00:03:22] Speaker 04: would be motivated to look to AIBW in this connection. [00:03:27] Speaker 04: I mean, that's quite an essential fact-finding. [00:03:31] Speaker 03: Your Honor, I would respectfully disagree. [00:03:33] Speaker 03: If the issue of obviousness is ultimately a question of law with underlying factual determinations, the facts are the ones that oversight it, that it's never been used in this category before, that it's never been used in this way before. [00:03:46] Speaker 03: As a matter of fact, Your Honor, in the indefiniteness section, the court went out of its way to say you'd be wandering the woods not knowing what AIBW formula to use, then you get the obviousness and with the specification out of hand, he says you'd focus right in on it. [00:04:02] Speaker 03: Those are ultimately legal conclusions based off the facts of record. [00:04:06] Speaker 03: And there's a green review on that, do you lose? [00:04:09] Speaker 03: No, Your Honor, because there's one other fundamental problem, Your Honor, with the whole thing that, again, underlies the entirety of the obviousness issue, which is the following. [00:04:19] Speaker 03: As this Court is well aware, and as Your Honors have been authors on, opinions on, of course you must always show reasonable expectation of success to show obviousness. [00:04:29] Speaker 03: An example of this is, of course, the Teva Corsep case, where even if it would have been obvious, [00:04:34] Speaker 03: in terms of a motivation to combine different references, you fail without a reasonable expectation of success. [00:04:41] Speaker 03: In this case, neither the district court nor the government ever really even contend that someone who was wandering around and trying all these different things and trying A by BW and trying different formulae and trying to solve it this way would have expected success in the end of the day. [00:05:00] Speaker 03: What they do remarkably, and I point your honors to the red brief at page 52, [00:05:04] Speaker 03: is they say that if expectation of success in the result is required then this court's precedents are wrong. [00:05:12] Speaker 03: At page 52 they identify six cases from this court and they say that these cases are wrongly decided in that they require expectation of success in the outcome. [00:05:23] Speaker 03: They effectively admit or acknowledge that if the test is, as this court has said six different times and many more times than that, [00:05:32] Speaker 03: that there has to be reasonable expectation of success in the outcome that they can't satisfy that. [00:05:37] Speaker 03: We thought that was striking in page 52 of the rubric. [00:05:41] Speaker 04: We have a situation where the district court did make a finding of reasonable expectation of success, correct? [00:05:48] Speaker 03: This court has a section entitled reasonable expectation of success. [00:05:52] Speaker 03: And if you read that section, it basically repeats what he said previously in terms of it would have been reasonable for someone to experiment in the way that they said the inventors experimented. [00:06:04] Speaker 03: And as a matter of fact, they point to the inventor's old testimony, Judge Ellis did, to try to support that it would have been reasonable to experiment in that way. [00:06:13] Speaker 03: Nowhere in the reasonable expectation of success analysis [00:06:16] Speaker 03: Does it carry through and say that a person skilled in the art carried by the same motivation that he identifies? [00:06:23] Speaker 03: The motivation to try to solve ocular toxicity would have expected to solve the problem. [00:06:29] Speaker 03: So there's a mismatch there. [00:06:30] Speaker 03: It's not unlike this court's decision in Institut Pasteur. [00:06:34] Speaker 03: where the party challenging obviousness there used one motivation and said they would have wanted to come up with a viable cell and then unreasonable expectation of success said it didn't matter what was viable. [00:06:47] Speaker 03: Their entire motivation case is based on the proposition that someone would have used AIBW to try to solve ocular toxicity and nowhere, nowhere in their briefs and nowhere in the district court's decision is there any analysis [00:07:00] Speaker 03: where it even tries to say that that person's skill in the art reasonably would have expected to succeed in tearing out that method. [00:07:09] Speaker 03: So that is ultimately a fatal error irrespective, Your Honor, of whether we disagree on the ultimate conclusion of obviousness on the motivation side being an issue of law or fact. [00:07:21] Speaker 01: Of course, this is claimed as a method of treating a patient having an FRLR1-expressive ovarian cancer. [00:07:29] Speaker 01: And the prior oft deals with discloses treating ovarian cancer with this compound. [00:07:37] Speaker 01: We're not talking about a big difference. [00:07:40] Speaker 03: We're talking about we fundamentally think it's a patentable and significant difference between the two. [00:07:46] Speaker 03: Your Honor, they are giving the same drug. [00:07:47] Speaker 03: I will acknowledge this, as I should, I think. [00:07:50] Speaker 03: In the prior art, they were talked about giving the same drug to treat the same disease. [00:07:55] Speaker 03: That is true. [00:07:56] Speaker 03: But that ended up having terrible toxicity issues. [00:08:00] Speaker 03: You had grade three ocular toxicity, which means you couldn't function. [00:08:03] Speaker 03: You could go blind from the prior treatment. [00:08:06] Speaker 03: The fundamental difference here was a paradigm shift, not a simple dosing shift going from one to five milligrams or something like that. [00:08:13] Speaker 03: paradigm shift to use a different method, a different regimen that not only had never been used with an ADC, but had never been used in any drug. [00:08:22] Speaker 04: What does reasonable expectation of success mean with respect to these claims? [00:08:28] Speaker 04: The claims don't require an effective treatment, right? [00:08:34] Speaker 03: The claims, I would say, are the following in two respects. [00:08:37] Speaker 03: Is my statement correct? [00:08:39] Speaker 03: I would say the claims don't say effective treatment, but this court's precedent makes clear, for example, in Teva v. Corecept, it was required to be a safe and effective treatment in that case, even though the claim didn't recite that. [00:08:52] Speaker 03: Anyone looking at a method of treating these ovarian and peritoneal cancers would understand that you would have to be successful in having both a safe and effective treatment in the end of the day. [00:09:04] Speaker 04: So your whole argument about reasonable expectation of success [00:09:08] Speaker 04: depends on reading the claims that require a safe and effective treatment? [00:09:13] Speaker 03: I disagree, Your Honor, but it's one of the two arguments. [00:09:15] Speaker 03: I have two arguments with respect to reasonable expectation of success, respectfully, Your Honor. [00:09:21] Speaker 03: The first is, just like in other precedents of the court, like Teva versus Corsept and many other cases, [00:09:28] Speaker 03: the claim to treating a patient with the disease carries with it the idea that it has to be safe and effective. [00:09:35] Speaker 03: In that case, expressly said that. [00:09:37] Speaker 03: The claim didn't say, in that case, it was methesprosome. [00:09:41] Speaker 03: In that case, it didn't say it has to be safe. [00:09:44] Speaker 03: It said a method of treating a patient. [00:09:46] Speaker 03: And it was found to be non-obvious by this court because it didn't show the prior log didn't suggest it would be [00:09:52] Speaker 03: Safe and effective to give that dose, 600 milligrams. [00:09:56] Speaker 01: If it weren't safe and effective, it would be inoperative. [00:10:00] Speaker 03: They could make that argument. [00:10:02] Speaker 03: There's not an enablement or a utility argument here. [00:10:05] Speaker 01: Do you want to quickly address indefinite tests? [00:10:08] Speaker 03: Sure, Your Honor, but may I just, I would like to do whatever the court would like, but may make my second point in response to Judge Dyke. [00:10:15] Speaker 03: The second reason it doesn't turn on safe and effectiveness is Institute Pasteur is really telling. [00:10:21] Speaker 03: If you're going to rely on a certain goal for your motivation, their goal, the government's goal is, we're going to solve ocular toxicity, then it makes no sense to decouple what the reasonable expectation of success is going to be from what motivated you. [00:10:36] Speaker 03: When you're saying, is it obvious? [00:10:38] Speaker 03: Would you have been motivated? [00:10:39] Speaker 03: They say yes by ocular toxicity. [00:10:41] Speaker 03: The success, the reasonable expectation of success for it to have been obvious must match that goal, and this court found exactly that in Institute Pasteur. [00:10:50] Speaker 03: That case, the claim did not require a viable cell in the end of the day that would work in some intended function. [00:10:56] Speaker 03: It was simply a product claim. [00:10:58] Speaker 03: And in the end of the day, it was a method claim, but it didn't require a viability, the court found. [00:11:04] Speaker 03: But in the end of the day, the court said specifically, and I'll quote it, [00:11:07] Speaker 03: that expectation of success analysis must match the highly desired goal, the thing that created the motivation. [00:11:15] Speaker 03: With respect to indefiniteness, Your Honor, I'm sorry to digress there, but with respect to indefiniteness, to answer your question, it's the claims, the specification, and the file history all compelled a finding that the definition in the claims, to be used in the claims, is the only definition in the specification. [00:11:33] Speaker 03: The claims themselves, it is true, do not spell forth the definition. [00:11:38] Speaker 03: But the claims say two very important things. [00:11:41] Speaker 03: They say both, what drug you're going to use, A54, and that's a finding of the court at finding a fact 37. [00:11:48] Speaker 04: And they also say the dosage... So it wouldn't infringe if we didn't use example four? [00:11:53] Speaker 03: That's correct. [00:11:55] Speaker 03: Absolutely true. [00:11:55] Speaker 03: If you do not use the formula in example four, you would not infringe. [00:12:00] Speaker 03: And this is an interesting case, Judge Dyke. [00:12:02] Speaker 00: You don't think there would be a DOE argument made by you? [00:12:05] Speaker 03: There will not be, and I'll represent that to the court here, but there would not be if you don't use the formula set forth in the claim. [00:12:13] Speaker 03: The formula set forth in the claim is the only formula set forth in the specification [00:12:18] Speaker 03: is the only formula anywhere in the intrinsic evidence. [00:12:22] Speaker 00: Why is that not a fair read by the district court that the preface, for example, [00:12:28] Speaker 00: means that this is only one example of a number of potentials. [00:12:31] Speaker 03: It's not a fair read, Your Honor. [00:12:32] Speaker 03: And may I just briefly digress for one second? [00:12:37] Speaker 03: Teva, Sandoz, and VASF both say that those are issues of law that are de novo, what the intrinsic evidence teaches. [00:12:43] Speaker 03: And the intrinsic evidence says AIBW is a certain way of looking at things. [00:12:48] Speaker 03: And for example, that formula, if you were to talk about my height, height would be how you measure someone. [00:12:53] Speaker 03: For example, six foot three, that's what I am. [00:12:56] Speaker 03: Maybe I'm six two now, whatever the case is. [00:12:59] Speaker 03: But more importantly, this claim sets forth not only what the drug is, 854, which this court previously found was important when it sent it back down the first time, [00:13:10] Speaker 03: It also tells you it's six milligrams per kilogram. [00:13:13] Speaker 03: The only place you'll find that anywhere in the specification, those things, are in example four, which set forth the AIBW. [00:13:20] Speaker 03: There'd be no support for those claims without it. [00:13:22] Speaker 03: And the other very interesting thing, Your Honors, is [00:13:25] Speaker 03: that this is an interesting case. [00:13:27] Speaker 03: It's a 145 case. [00:13:29] Speaker 03: The patent hasn't yet issued. [00:13:30] Speaker 03: As friends acknowledged at the last oral argument, it means the 145 is part of the intrinsic record. [00:13:37] Speaker 03: What we're saying here is actually part of the intrinsic record of this case. [00:13:41] Speaker 03: It's very unusual because the patent hasn't issued. [00:13:43] Speaker 04: If you want to make it clear, file a continuation application. [00:13:47] Speaker 04: What's the problem with that? [00:13:49] Speaker 03: Your Honor, we think, first of all, that there is absolutely no lack of clarity as to what AIBW would be used once you look at the specification and the prosecution history. [00:13:57] Speaker 03: It's been 10 years since we filed this application. [00:14:00] Speaker 03: It should not have to linger on further. [00:14:02] Speaker 03: The claims are perfectly definite as they are, and we shouldn't be put in a position where we have to go back and maybe have new rejections by the Patent Office at this point in time. [00:14:11] Speaker 03: The 145 action is to get a thumbs up or a thumbs down [00:14:14] Speaker 03: on the validity of these claims, and we think that they're clearly valid both on the indefiniteness front and on the obviousness front. [00:14:21] Speaker 03: And I see I only have a minute left. [00:14:23] Speaker 03: Unless the court has questions, I'll reserve. [00:14:25] Speaker 01: We'll save it. [00:14:26] Speaker 01: Thank you. [00:14:27] Speaker 01: Thank you, Your Honor. [00:14:29] Speaker 01: Dr. Kasdan. [00:14:33] Speaker 02: May it please the court, Daniel Kasdan, on behalf of the USPTO. [00:14:38] Speaker 02: I'll start with obviousness, because I think that was where most of the focus was. [00:14:42] Speaker 02: So just one of the points that I think Judge Dyck mentioned, or maybe Judge Lloyd, that this drug had been used to treat this type of cancer in very similar doses. [00:14:53] Speaker 02: The prior loss references focuses on doses of six milligrams per kilogram total body weight. [00:14:59] Speaker 02: And what they're doing is they're saying, we use a new dosing methodology, adjusted ideal body weight. [00:15:05] Speaker 02: And the expert testified that it would have been obvious to use this because, and I think they undersold how widespread adjusted ideal body weight had been, it had been used for smaller molecules, larger molecules contemporaneously, it had been used for a different immunoconjugate. [00:15:22] Speaker 02: It was the expert. [00:15:24] Speaker 02: and the district court found that as a factual matter, this is what people would look at. [00:15:28] Speaker 02: And this court has said that motivation to combine is a factual issue, and so I think that that should be reviewed for clear error. [00:15:36] Speaker 04: So what about the reasonable expectation of success? [00:15:39] Speaker 02: So the district court found, and I'm reading from page 52, both Dr. Figg, that was the PTO's expert who wasn't paid, and Dr. Tulture testified that a skilled artisan understood that dose was relevant to toxicity, and a skilled artisan would therefore have had a reasonable expectation that changing the dose would impact the resulting ocular toxicity. [00:16:01] Speaker 02: That's a finding that you know that toxicity is often correlated to dose. [00:16:07] Speaker 02: There's testimony from both experts that that's true. [00:16:10] Speaker 02: And so you'd reasonably expect that if you start moving the dosing methodology around, you'll likely affect toxicity in one direction or another. [00:16:20] Speaker 02: That seems like a reasonable expectation of success, I think. [00:16:25] Speaker 04: What about efficacy? [00:16:28] Speaker 04: Is efficacy and safety part of the claim here? [00:16:32] Speaker 02: It's not part of the claim, so I don't know what specific amount is required. [00:16:36] Speaker 02: And remember, this is important. [00:16:38] Speaker 02: And I think that this gets... What they say in the patent is that when they were giving five milligrams per kilogram total body weight, that's the prior approach, one in 11 patients had grade three ocular toxicity. [00:16:52] Speaker 02: So this came up in the secondary considerations findings, and this is on appendix page 58. [00:17:00] Speaker 02: Ultimately, they had 11% grade 3 ocular toxicity the way they dose it, under 6 milligrams per kilogram. [00:17:06] Speaker 02: They've changed the dosing methodology, but there's no evidence that this change has actually improved toxicity or efficacy. [00:17:14] Speaker 02: So whatever the prior art has, that's what we know then to have still. [00:17:18] Speaker 02: This was hotly litigated at trial, but not appealed. [00:17:22] Speaker 02: that there's no evidence that they've improved by changing to adjusted ideal body weight, that they've improved safety or efficacy in any way. [00:17:29] Speaker 01: Safety and efficacy is a 101 issue, awkwardness, and that's not raised, right? [00:17:36] Speaker 02: Right. [00:17:37] Speaker 02: That's not raised. [00:17:38] Speaker 02: I just mean to say that they're not – this change hasn't settled – it's not like they now have changed it and unexpectedly have great efficacy or safety that they didn't have before. [00:17:47] Speaker 02: It's the same efficacy and safety they had. [00:17:49] Speaker 02: So they've changed the dosing, and they haven't actually changed anything in the result, as far as we can tell. [00:17:58] Speaker 02: If there are no other questions – oh, I wanted to – on ocular toxicity, it's important to note that while nobody had – there's no reference that we showed that ocular – that people changed the adjusted ideal body weight successfully to combat ocular toxicity. [00:18:13] Speaker 02: There is the alpha now reference that people tried that. [00:18:16] Speaker 02: So that means this is also with – at least the district court's finding that people who space ocular toxicity would test out adjusted ideal body weight. [00:18:24] Speaker 02: That's supported, and so I think that's not clearly eroding. [00:18:28] Speaker 02: If there's nothing else on obviousness, I'm happy to take more questions. [00:18:33] Speaker 00: Can I ask you, this is probably a very stupid question, so you can disabuse me of my notion that I have. [00:18:39] Speaker 00: But I felt a little tension between the argument you were making with respect to indefiniteness and obviousness, mainly because in indefiniteness you kept repeatedly saying, we don't know [00:18:50] Speaker 00: what this AIBW means. [00:18:54] Speaker 00: We have no idea. [00:18:55] Speaker 00: But with respect to obviousness, your real hook is everybody knew what it was. [00:19:00] Speaker 00: It was used all the time in the prior art. [00:19:02] Speaker 00: Isn't there a tension? [00:19:04] Speaker 00: I mean, for you suggesting [00:19:05] Speaker 00: that nobody knows what it is because it's an incommensurate formula, and then saying we all know what it is because it's in the prior arc. [00:19:13] Speaker 00: Different arguments made to make different points. [00:19:15] Speaker 00: But why am I – what am I missing? [00:19:18] Speaker 02: So I see the tension. [00:19:18] Speaker 02: But to me, let's say there were – maybe let's go back to the Taber case. [00:19:22] Speaker 02: So there are three ways to use molecular weight. [00:19:25] Speaker 02: It could be obvious to use any of the three tests for molecular weight, but it's still important that there be one that the patent is claiming. [00:19:32] Speaker 02: So adjust that ideal body weight. [00:19:34] Speaker 02: Let's just focus on the correction factor. [00:19:35] Speaker 02: It could be 0.4 or 0.5. [00:19:38] Speaker 02: Those are, let's say, both known correction factors. [00:19:41] Speaker 02: It's indefinite if you say, my claim would apply either one of them, because I don't know if I'm infringing or not, because I have to choose which of the correction factors to use. [00:19:50] Speaker 02: But it would still be obvious to try them both. [00:19:52] Speaker 02: So if there are multiple options, all the options could be obvious, but you still, as a matter of definiteness, need to tell me which of those you're trying to claim so that I know what the limits of the claim are. [00:20:04] Speaker 02: Does that make sense? [00:20:05] Speaker 04: Well, both. [00:20:06] Speaker 02: Well, both. [00:20:07] Speaker 02: You can say both, but they're not saying that they mean both. [00:20:09] Speaker 02: They're actually saying they mean one specific one. [00:20:12] Speaker 00: Well, under obviousness, multiple depends on what you're talking about. [00:20:16] Speaker 00: If you're talking about a finite group that you would pick them against, as opposed to [00:20:22] Speaker 00: thousands or millions or whatever, and I don't know what that number is associated with AIBW. [00:20:27] Speaker 02: It's a range. [00:20:28] Speaker 02: I mean, it's just basically a correction factor. [00:20:32] Speaker 02: Depending, it could be .2 or .5 or .8 or .9. [00:20:36] Speaker 02: So you're picking within that range, and we feel that the claim is indefinite as to which of those you're picking. [00:20:43] Speaker 02: That specific choice is just routine optimization, which you would find anyway. [00:20:48] Speaker 02: So it's sort of both obvious, but you haven't specified which one you mean. [00:20:54] Speaker 02: In terms of indefiniteness, I just want to focus on one point here, which is there is a definition section, and I feel like an applicant reading a claim has a right to look to the definitions and say, whatever you said in the definitions, that's what I'm going to understand the terms to mean. [00:21:11] Speaker 02: And the term, let's say, ideal body weight, which is part of the definition, says that optionally you can include frame size. [00:21:18] Speaker 02: But the formula they're proposing doesn't include frame size. [00:21:21] Speaker 02: So that means that they're saying that the definition, they're not putting it straight, and they're limiting it narrower than the definition. [00:21:27] Speaker 02: So again, paragraph 69, this is on page APBX 157, they say it optionally includes frame size. [00:21:35] Speaker 02: They're saying that isn't an option, even though that's in the definitions. [00:21:38] Speaker 02: So it seems to me that, given that we're still in prosecution, and 145 is still prosecution, they should file a continuation [00:21:46] Speaker 02: and then file cleaner claims, which they did. [00:21:49] Speaker 02: I think they recently abandoned it, but they could have just gone through with those claims, and then we would have cleaner claims, which is a benefit of prosecution. [00:21:59] Speaker 02: I know I have some time left, and I'm obviously happy to answer any questions, but if there's nothing else, I'm happy to cede my time. [00:22:04] Speaker 01: We don't lose any points by not using up all your time. [00:22:08] Speaker 01: Thank you. [00:22:09] Speaker 01: Thank you. [00:22:10] Speaker 01: Dr. Kasdan, Mr. Mohran, we'll give you two minutes for a vowel. [00:22:14] Speaker 03: Thank you, your honor. [00:22:16] Speaker 03: Very quickly, on a couple of issues, my friend said that AIBW had been used on immunoconjugates before. [00:22:23] Speaker 03: That's incorrect. [00:22:25] Speaker 03: Rosenblatt, which is a reference I think he was referring to for simultaneous invention, was a radio immunoconjugate, which has a radioactive piece. [00:22:36] Speaker 03: And it's not relevant, therefore. [00:22:37] Speaker 03: It's not prior art. [00:22:39] Speaker 03: For simultaneous invention, [00:22:40] Speaker 03: As this court has held multiple times, it has to actually be the invention, not something that they argue is similar. [00:22:46] Speaker 03: Radioactive materials have very different properties than chemotherapy drugs. [00:22:55] Speaker 03: Most importantly, on the reasonable expectation of success point, the best that my friend could come up with is that varying dosing could affect toxicity. [00:23:03] Speaker 03: Of course, varying dosing in general could affect toxicity. [00:23:06] Speaker 03: There is still no contention [00:23:08] Speaker 03: that someone skilled in the art at the time would have looked to AIBW and thought that that was, had a reasonable expectation of success of solving this problem, despite it never having been used with the same category of drug, and never having been used at all, ever on ocular toxicity. [00:23:26] Speaker 03: My friend came up with only one example, the alkanar, [00:23:28] Speaker 03: In the entirety of this three-day trial and the massive appendix that we have here, the Alphenol reference references AIBW in passing and then concludes that you should use a different method. [00:23:42] Speaker 03: It is a finding of the court below that, indeed, AIBW has never been suggested, and that's a finding of fact that we are willing to live with and we embrace, that it's never been suggested for AIBW. [00:23:56] Speaker 03: That is a finding of this court that is at paragraph 72 of the court's decision. [00:24:03] Speaker 03: And Your Honor, I want to be a little more precise on a question that you raised, Judge Dyke. [00:24:08] Speaker 03: You asked me earlier, well, if the standard of review on the [00:24:13] Speaker 03: motivation combined is clear error rather than de novo. [00:24:17] Speaker 03: Do we lose? [00:24:18] Speaker 03: And the answer is no, Your Honor. [00:24:20] Speaker 03: While we think it's a de novo standard of review, when you take all the things that we talked about, that had never been recognized to be a problem similar to a forced lab situation, [00:24:29] Speaker 03: that AIBW had never been used to address ocular toxicity. [00:24:33] Speaker 03: When you get to the point that Judge Prost made that when in the decision, when the court wanted to emphasize indefiniteness, it said there's all sorts of different ways to do it, then in obviousness they zero in on the only one. [00:24:45] Speaker 03: When you layer hindsight on top of hindsight on top of hindsight, it is clear error to find these claims obvious. [00:24:52] Speaker 03: And finally, I'll close with this. [00:24:54] Speaker 03: Again, the court and our friends' lack of response despite more time on this point is telling. [00:25:00] Speaker 03: At page 52, they essentially acknowledge that if the test is as this court has said in six different cases, that you need a reasonable expectation of success [00:25:09] Speaker 03: on the outcome, then they cannot win this case. [00:25:13] Speaker 03: And I heard him say nothing in response to that. [00:25:15] Speaker 03: On page 52 of their brief, they advocate effectively an en banc type of an argument that this court should disregard the prior precedents of this court. [00:25:23] Speaker 03: This court's prior precedents are both right and they're binding. [00:25:26] Speaker 03: Unless the court has additional questions, I thank the court for its time. [00:25:30] Speaker 01: Thank you, counsel. [00:25:31] Speaker 01: The case is submitted.