[00:00:40] Speaker 03: The next case is Sanofi Aventis versus Dr. Reddy's. [00:00:46] Speaker 03: Presenting is Kabi Akhtavis Elizabeth Apotex Mylan, 2018, 1804, 08, and 09. [00:00:53] Speaker 03: Mr. Solander. [00:00:55] Speaker 03: Thank you, Your Honor. [00:00:57] Speaker 05: Good morning, Your Honors, and may it please the court. [00:01:00] Speaker 05: At the time that the district court entered its decision and its judgment with respects to claims 7, 11, [00:01:08] Speaker 05: 14 to 16 and 26, those claims had been canceled. [00:01:14] Speaker 05: Those claims could not block any defendant from launching a product, nor would deciding them have any effect on a party's ability to do anything at the time that the judgment and decision were entered. [00:01:28] Speaker 01: Is cancellation irreversible in law? [00:01:30] Speaker 05: Yes. [00:01:32] Speaker 05: It cannot be brought back by re-examination or any other way, as far as I know. [00:01:37] Speaker 05: Yes, it's irreversible. [00:01:39] Speaker 05: As such, the district court lacks subject matter's jurisdiction over those disclaimed claims, and the judgment and opinion applying those claims should be vacated. [00:01:49] Speaker 02: Though this doesn't go to subject matter jurisdiction, per se, because either you have it or you don't, whether you know about it or not, why didn't your client notify the district court of the cancellation in a timely fashion? [00:02:01] Speaker 05: Your Honor, I believe we did do it in a timely fashion. [00:02:04] Speaker 05: It was shortly after the cancellation that we notified the court. [00:02:07] Speaker 05: And then there was briefing on that matter prior to the court's decision. [00:02:11] Speaker 02: And we- Well, I remember there was a point in time in this record in which you told the court you weren't intending to proceed on certain of the claims. [00:02:18] Speaker 02: That's correct. [00:02:18] Speaker 02: But I don't remember that that document containing any notice or reference to the cancellation. [00:02:24] Speaker 02: Are you referring to your simple notice to the court that you intend not to proceed on certain claims and then the fact that you didn't offer expert testimony on them? [00:02:31] Speaker 02: Or are you talking about actually submitting a copy of the cancellation? [00:02:35] Speaker 05: So I'm talking about both, Your Honor. [00:02:37] Speaker 05: So at trial, after the PTAB decision came down in the middle of trial, we decided to focus our case on only two claims and to drop all of the other claims. [00:02:46] Speaker 05: We told the defendants that. [00:02:47] Speaker 05: We told the court that. [00:02:48] Speaker 03: So did you file a statutory disclaimer in the PTO? [00:02:52] Speaker 05: We did, yes, but not at that time. [00:02:54] Speaker 05: So at that time, we then proceeded to finish the trial. [00:02:58] Speaker 05: Afterwards, we did not appeal the PTAP's decision with respect to those claims. [00:03:02] Speaker 05: And so they automatically will have been canceled. [00:03:04] Speaker 05: We then had a discussion with the district court via letter. [00:03:08] Speaker 05: The district court [00:03:09] Speaker 05: The defendants were advocating to the district court that despite that fact that we had not appealed Those claims were still not canceled and still existed so then just to button that up we filed a Cancellation with the PTO which we don't think was necessary because they would have been canceled at the time. [00:03:25] Speaker 03: What do you mean cancellation? [00:03:27] Speaker 03: There's a statutory disclaimer, right? [00:03:28] Speaker 05: Yes, Your Honor, statutory disclaimer of the claims at that time. [00:03:31] Speaker 01: But you have a kind of built-in [00:03:34] Speaker 01: that the statutory cancellation is one reason they were dead and the second one was that official cancellation under 318, is it 318, would in some [00:03:46] Speaker 01: amount of time have automatically followed once you decided not to appeal the unpatentability rulings on those claims from the final written decision. [00:03:57] Speaker 01: That's correct, Your Honor. [00:03:58] Speaker 05: I also think there's a second set of suspenders when you drop claims at trial ordinarily. [00:04:02] Speaker 05: Two pairs of suspenders. [00:04:03] Speaker 05: Two pairs of suspenders when you drop claims at trial ordinarily that deprives the court of subject. [00:04:09] Speaker 01: Can I ask you a question? [00:04:11] Speaker 01: And I think it's a simple factual question, but you tell me. [00:04:16] Speaker 01: Do you dispute the dosages of cabezitaxel greater than 20 were known in the prior art and used to treat dositaxel-resistant prostate cancer? [00:04:30] Speaker 05: Your Honor, there was an ongoing clinical trial at the time. [00:04:34] Speaker 05: And the prior art that was available to the court [00:04:38] Speaker 05: was a description of that clinical trial ongoing at the time. [00:04:42] Speaker 05: So there was a description in the art of a use of 25 milligrams. [00:04:49] Speaker 01: Greater than. [00:04:49] Speaker 01: Greater than. [00:04:50] Speaker 01: Greater than 25? [00:04:51] Speaker 01: Yes. [00:04:52] Speaker 05: Not that I'm aware of, Your Honor. [00:04:55] Speaker 01: So you do dispute that proposition. [00:04:57] Speaker 05: That greater than 25. [00:04:59] Speaker 01: Here's what I'm getting at. [00:04:59] Speaker 01: Yes. [00:05:00] Speaker 01: So the other side, as I understand it, and they'll correct me if I'm wrong, [00:05:04] Speaker 01: say that there are two ways in which they have a stake. [00:05:09] Speaker 01: in including the six disclaimed claims in the judgment here. [00:05:14] Speaker 01: One has to do with claim preclusion. [00:05:16] Speaker 01: That's not what I'm interested in at the moment for this question. [00:05:20] Speaker 01: The other is they have a little paragraph about issue preclusion. [00:05:24] Speaker 01: Their paragraph about issue preclusion says, with respect to claim 11, which is one of the six disclaimed claims, that they think that keeping claim 11 in the judgment [00:05:37] Speaker 01: would provide issue preclusion as to the proposition that, and now I'm just going to repeat what I asked you about, dosages of cabezitaxel greater than 20 milligrams, is that meters squared? [00:05:51] Speaker 05: Yeah, milligrams per meter squared. [00:05:52] Speaker 01: Per meter squared. [00:05:53] Speaker 01: Were known in the prior art and used to treat dositaxel resistant prostate cancer. [00:05:59] Speaker 01: One way that you could [00:06:02] Speaker 01: Maybe not the only way. [00:06:03] Speaker 01: But one way that you could answer that little bit of issue conclusion is to say, on that factual proposition, we don't dispute it. [00:06:13] Speaker 05: I think the better answer to that is the one we've pressed in our briefs. [00:06:18] Speaker 05: And that is, as I understand what they're saying, is if you combine 11 [00:06:23] Speaker 05: claim 11 and its dependency all the way up to claim 1, that is an issue preclusion on our later claims. [00:06:32] Speaker 05: And what we're saying is, as those later claims survive, they're so materially different than that combination of claims and that they are not dependent on, that the findings with respect to claim 1, for example, do not apply to those claims because of their different construction and their different limitations. [00:06:51] Speaker 05: I think that's the assertion we'll make. [00:06:54] Speaker 05: We are not abandoning claims to 25 milligrams. [00:07:00] Speaker 01: Just to be clear, there are other possible answers, but I just want to be sure. [00:07:05] Speaker 01: You are not prepared to say, and I'm again just reading their sentence, that dosages of cabezitaxel greater than 20 milligrams per meter squared were known in the prior art and used to treat dositaxel-resistant prostate cancer. [00:07:22] Speaker 05: I agree with that factual finding, not used to treat, used in a clinical trial. [00:07:26] Speaker 05: I don't agree that they were used to treat, that the dosage was known and in a clinical trial. [00:07:33] Speaker 05: That fact was known. [00:07:39] Speaker 05: And our claims do cover 25 milligrams per meter squared as well as 20. [00:07:43] Speaker 05: So we are pressing those, the amended claims that we are pressing in the [00:07:48] Speaker 01: I don't remember whether you said the following explicitly or not but the reason you care about this you want to get rid of these claims has something or other to do with trying to reduce the chances of your not being able successfully to assert the [00:08:09] Speaker 01: amended claims should they emerge from the PTO? [00:08:12] Speaker 05: Right. [00:08:12] Speaker 05: That's the threat by the other side, that if this judgment survives and will be used later as some sort of collateral estoppel or claim preclusion or something with respect to claims that we might get in the future. [00:08:28] Speaker 05: Yes. [00:08:29] Speaker 05: That's the problem. [00:08:31] Speaker 05: So the issue, though, Your Honor, is that that contingent [00:08:37] Speaker 05: Possibility the possibility that the PTAB will issue claims and at the time that the court Decided this case that the federal circuit would reverse the PTAB in the first instance that since happened But we have to focus on when this when the district has that happened a while ago has the board acted on remand yet? [00:08:55] Speaker 05: The board has just set a briefing schedule. [00:08:56] Speaker 05: We've one brief has been filed the other one is due Friday, so but the focus of this court's [00:09:05] Speaker 05: Analysis should be at the time that the district court entered its opinion and entered its judgment. [00:09:11] Speaker 05: Did the district court at that time have subject matter jurisdiction? [00:09:14] Speaker 05: The fact that the claims no longer existed, the fact that they could not be asserted against any party, the fact that they did not need a decision of infringement on those claims in order to launch their products distinguishes them from the Daiichi case and the 3M case. [00:09:33] Speaker 05: The fact that they would not affect another proceeding that was being stayed distinguishes them from the ITC versus Microsoft case. [00:09:41] Speaker 05: And the fact that those claims did not exist at the time distinguishes them from the Teva versus Novartis case. [00:09:52] Speaker 05: If I could turn to the 170 patent? [00:09:54] Speaker 05: Yes. [00:09:55] Speaker 05: Yes, OK. [00:09:55] Speaker 05: So Your Honor, that decision should be upheld. [00:09:58] Speaker 05: here because the court's finding that a person of ordinary skill in the art would not have been motivated by the prior art to simultaneously modify the C7 and the C10 carbons of dositaxel by adding methoxy substituents was supported by substantial evidence and is not clear error. [00:10:16] Speaker 05: Moreover, the court found compelling evidence of non-obviousness with respect to failure of others and commercial success. [00:10:24] Speaker 05: Those findings are unchallenged on appeal. [00:10:27] Speaker 05: The defendants allege that the court made essentially three errors below. [00:10:33] Speaker 05: The first, that the court did not consider the hate reference. [00:10:38] Speaker 05: Turning to the hate reference, the court made a number of findings showing that the court clearly understood the hate reference and clearly understood the testimony about the hate reference. [00:10:49] Speaker 05: It found that the hate reference itself does not discuss tax aides. [00:10:53] Speaker 05: I understand that's not dispositive, but it is [00:10:56] Speaker 05: a factor in this analysis. [00:10:58] Speaker 05: It found that it was not cited in any of the many articles of prior art in the taxane field by any taxane researcher at the time, including not just persons of ordinary skill in the art, but all of the experts doing taxane research at the time. [00:11:15] Speaker 05: It discusses the hate reference, discusses a completely different class of compounds that have substantially different chemistry than taxanes, including [00:11:25] Speaker 05: having a charge on the molecule. [00:11:28] Speaker 05: The compounds in hate were tested for a completely different purpose. [00:11:31] Speaker 05: They were trying to block the action of hate, not trying to avoid it. [00:11:36] Speaker 01: Right, but do I understand that the other side's theory is that hate, and you're going to have to fix maybe more than one thing to this, hate shows that stuff that binds closely to the molecule that goes from the inside to the outside will block its, let's call it its pumping action. [00:11:55] Speaker 01: That suggests that we really want to keep a structure that isn't going to attach to the molecule that crosses the cell membrane. [00:12:11] Speaker 01: I realize there's a gap, because that has nothing to do with preventing, essentially tying it up to prevent the blocking, but it tells you something about the action of this cross-membrane. [00:12:24] Speaker 01: Is it protein? [00:12:27] Speaker 01: I guess it's a protein. [00:12:28] Speaker 05: It's a transmembrane protein. [00:12:29] Speaker 05: That's right. [00:12:30] Speaker 01: And therefore, we would like a molecule that doesn't actually attach to it at all, because then that won't be moved. [00:12:38] Speaker 05: Right, Your Honor, so it's a question of interacting with the protein in a way that diminishes its function. [00:12:46] Speaker 05: So that can be done a number of different ways. [00:12:48] Speaker 05: As Your Honor mentioned, you could attach something to it which physically blocks it. [00:12:51] Speaker 03: Doesn't Hape disclose phenothyozines? [00:12:54] Speaker 05: That's correct, Your Honor. [00:12:55] Speaker 03: It's an entirely different class of compound. [00:12:57] Speaker 05: Absolutely. [00:12:58] Speaker 05: And there's lots of testimony in the record that the court observed about how they are different. [00:13:02] Speaker 05: They're planar, not conformed like taxanes. [00:13:06] Speaker 05: They're charged. [00:13:08] Speaker 05: They have aromatic rings. [00:13:09] Speaker 05: That's right. [00:13:09] Speaker 05: The aromatic rings are planar and unlike the rings in taxanes. [00:13:12] Speaker 03: You are well into your rebuttal time. [00:13:14] Speaker 03: Do you wish to continue or save it? [00:13:16] Speaker 05: I'll save it, Your Honor. [00:13:23] Speaker 03: Mr. [00:13:23] Speaker 03: LL, you're going to take nine minutes and leave six for Ms. [00:13:29] Speaker 03: Rapalino, of which she will want to save one. [00:13:33] Speaker 03: So please proceed. [00:13:35] Speaker 04: That is correct. [00:13:35] Speaker 04: May it please the court, Andy Llewellyn for Apotex, on behalf of all defendants, cross appellants, with respect to Sanofi's appeal. [00:13:42] Speaker 04: Your Honor, I'd just like to focus preliminary matter, correct something that Mr. Solander said in response to Judge Moore's question. [00:13:50] Speaker 04: Actually, Sanofi never at any point during trial said, either formally or informally, or just simply said, we drop assertion of claims 7, 11, 14, through 16, and 26. [00:14:03] Speaker 04: They never said it in their post-trial briefing. [00:14:06] Speaker 04: They didn't do it until I believe we could. [00:14:08] Speaker 02: Subject matter jurisdiction is not waivable, right? [00:14:11] Speaker 04: That is correct, Your Honor. [00:14:12] Speaker 02: And if they had, in fact, divested themselves of that property right as though it never existed by having filed a statutory disclaimer prior to the conclusion of that trial, it divested the Court of Subject Matter jurisdiction, did it not? [00:14:27] Speaker 04: It did not, Your Honor. [00:14:28] Speaker 02: Do you think the fact that they didn't give notice of it [00:14:32] Speaker 02: means it can't divest a court of subject matter jurisdiction? [00:14:35] Speaker 04: It can't, Your Honor, because there are some rights at issue here. [00:14:38] Speaker 04: And those rights, first and foremost, are patent certainty and the ability to enter the market [00:14:44] Speaker 04: in the face of patents that we don't infringe. [00:14:48] Speaker 01: It's OK. [00:14:48] Speaker 01: Can I ask you this question? [00:14:49] Speaker 01: Yes, you are. [00:14:50] Speaker 01: Let me just tell you what's on my mind about this issue. [00:14:54] Speaker 01: It seems to me that you have said two things about why there is some stake, some concrete stake, in your keeping the disclaimed claims within the judgment. [00:15:06] Speaker 01: The first is a claim [00:15:08] Speaker 01: preclusion point, which is kind of your overwhelming point, and then you have this little issue preclusion point that I was talking about with your opposite number. [00:15:17] Speaker 01: But on claim preclusion, here's what I guess I'm stuck on. [00:15:21] Speaker 01: Your claim preclusion point is that as you read the Senju case, the amended claims would have been encompassed within claims that Sanofi could have asserted, and indeed, in at least one respect, did assert in this case. [00:15:39] Speaker 01: And therefore, there's going to be claim preclusion. [00:15:42] Speaker 01: I will assume for purposes of this question that that's correct. [00:15:46] Speaker 01: That seems to be completely unaffected by whether the disclaimed claims are within the judgment. [00:15:53] Speaker 01: And that is correct, Your Honor. [00:15:54] Speaker 01: Because there remains a final judgment on these claims. [00:15:58] Speaker 01: Not on these claims, I'm sorry. [00:15:59] Speaker 01: In the case, because 21 and 30 remain, and there's no question about removing them. [00:16:08] Speaker 04: That's correct, Your Honor. [00:16:09] Speaker 01: So what does this claim preclusion argument have to do with whether the disclaimed claims are in the judgment or not? [00:16:15] Speaker 04: It's only if Senju is read narrowly, Your Honor. [00:16:18] Speaker 04: It's only if Senju is read narrowly to require an actually adjudicated claim. [00:16:23] Speaker 01: But you can litigate that if and when the amended claims issue and they are asserted. [00:16:29] Speaker 01: You can say, claim preclusion, Senju says it's not just no material difference, it's also [00:16:36] Speaker 01: being a subset of the claims that you could have asserted. [00:16:41] Speaker 01: And indeed, you did assert one of them by 1 or 27 or something. [00:16:46] Speaker 01: And you'll either win or you'll lose about that. [00:16:48] Speaker 01: But has that argument you will never mention or need to mention in the course of that argument whether the disclaim claims are in this judgment? [00:16:57] Speaker 04: Your Honor, if this Court vacates on the disclaim claims and we make that argument that Sanofi is precluded from asserting [00:17:06] Speaker 04: the amended claims against us by virtue of the fact that it could have in fact did assert claims 1 and 27, and we have the judgment on 2130. [00:17:14] Speaker 04: But Sanofi argues that Senji should be read narrowly, such that [00:17:18] Speaker 04: Well, claims 1 and 27 were never taken at trial. [00:17:21] Speaker 04: And the only ones that were taken at trial and judgment was entered on were 21 and 30. [00:17:26] Speaker 04: And those claims are directed to the 20 milligram per meter squared dosage, not the up to 25. [00:17:34] Speaker 04: Then we're out of luck here. [00:17:36] Speaker 04: So it really depends on the court's reading. [00:17:41] Speaker 04: And so that's why we essentially have two positions with respect to justice, the ability over the disclaimed claims in this case. [00:17:48] Speaker 04: In assessing justiciability, of course, this court is going to have to apply the Supreme Court's all the circumstances test. [00:17:55] Speaker 04: As part of that, this court is going to have to determine whether Santa Fe on the one hand and defendants on the other hand had adverse legal interests at the time the district court entered judgment over the disclaimed claims. [00:18:04] Speaker 04: And our position is if Santa Fe was already precluded at the time the district court entered judgment from suing us a second time on the 592 patent by virtue of claims 1 and 27, [00:18:17] Speaker 04: Then, and only then, will we agree that there was no justiciable controversy of the disclaim claims at the time of district court action. [00:18:23] Speaker 01: Right. [00:18:23] Speaker 01: So I'm not actually focusing on the conditions under which you will agree or not, but rather putting aside your agreement or let's assume that you resist this. [00:18:36] Speaker 01: And then you say, here are the reasons we're resisting it. [00:18:40] Speaker 01: We think we had a stake because of claim preclusion. [00:18:46] Speaker 01: And if the claim preclusion argument that you make is independent of whether the disclaimed claims are in the judgment, I don't see how that can give you a stake in inclusion or exclusion of the disclaimed claims. [00:18:59] Speaker 01: And then you do make this one little point, basically a single carryover sentence on some page or other, [00:19:07] Speaker 01: in which you cite, you say, claim 11, keeping claim 11 helps us [00:19:16] Speaker 01: invoke issue preclusion about the district court's finding. [00:19:19] Speaker 01: And it's the one that I read about four times before. [00:19:22] Speaker 01: And you cite appendix 91 and 96 through 97. [00:19:25] Speaker 01: And 91 is about claims 21 and 30, which are in the judgment. [00:19:34] Speaker 01: And then 96 and 97 don't discuss the 20 milligram point at all. [00:19:39] Speaker 01: So again, I don't see what that issue preclusion point has to do with keeping the disclaimed claims in the judgment. [00:19:50] Speaker 01: You have that argument based on a part of the judgment that's not being asked to be altered, which is the discussion of 21 and 30. [00:20:00] Speaker 04: That's correct, Your Honor. [00:20:02] Speaker 04: We are focusing on the disclaimed claims. [00:20:05] Speaker 04: We're asking for judgment to be maintained on there, if this court doesn't agree with us that Santa Fe was already precluded based on 127, because we believe the judgment over the disclaimed claims sets up a claim preclusion and issue preclusion as to dosages above the 20 milligrams per meter squared, which were the subject of 21 and 30. [00:20:24] Speaker 01: Which, again, is independent of the disclaimed claims being in the judgment or not. [00:20:29] Speaker 04: That's only for 20, because 21 and 30 were directed to the 20 milligram per meter squared dosage. [00:20:36] Speaker 04: But they don't cover the higher dosages that the substitute claims are directed to. [00:20:40] Speaker 03: Do you want to address your cross appeal? [00:20:44] Speaker 04: Yes, I believe. [00:20:45] Speaker 04: I believe I still have time remaining. [00:20:48] Speaker 03: You have less than two minutes. [00:20:49] Speaker 04: OK. [00:20:50] Speaker 04: My colleague's going to be addressing the cross appeal. [00:20:52] Speaker 04: All right, fine. [00:20:53] Speaker 04: So just short of this court. [00:20:57] Speaker 04: agreeing with us that Sanofi was already precluded from suing a second time, we believe there was a justiciable controversy over the disclaim claims at the time the district court entered judgment because we need all the Teva v. Novartis factors for justiciability. [00:21:09] Speaker 04: Sanofi's only response is, well, there in Teva v. Novartis, the four unasserted fan v. patents were live and presently assertable. [00:21:17] Speaker 04: Well, that should not drive this court's analysis because [00:21:22] Speaker 04: We have the Carrico and Daiichi line of cases, which hold that claims do not need to be live and presently assertable for there to be a justiciable controversy over those claims. [00:21:31] Speaker 04: And so to the extent this court feels that we're not 100% on all fours with Tavavino Vardis, one way to look at this is that we are essentially a hybrid between Tavavino Vardis on the one hand and this court's Carrico and Daiichi line of cases on the other hand. [00:21:45] Speaker 04: The patent uncertainty is posing a barrier to market entry. [00:21:49] Speaker 04: If this court reverses on the 170, some of us may not go to market by virtue of the uncertainty on the 592 patent. [00:21:56] Speaker 04: If this court affirms and the IPR is resolved in sanity's favor before September of 2021, [00:22:02] Speaker 04: Sanity is likely going to be suing us for preliminary and permanent injunctive relief to keep us off the market. [00:22:07] Speaker 04: We respectfully submit that that's the antithesis. [00:22:09] Speaker 02: Why are you saying some of us would not go to market if the amended claims haven't even issued yet? [00:22:15] Speaker 02: Why would you not go to market? [00:22:16] Speaker 04: Because of the uncertainty, Your Honor. [00:22:18] Speaker 02: And Congress and then... That's the quintessential definition of an advisory opinion. [00:22:24] Speaker 02: What you just said is the textbook definition of an advisory opinion. [00:22:27] Speaker 04: In this case, Your Honor, Congress amended the Hatch-Waxman to specify that when Hatch-Waxman litigation is properly instituted, an antifiler is guaranteed certainty as to that patent, good or bad. [00:22:38] Speaker 04: And so that's why we respectfully maintain that there continues to be a just as well controversy of the disclaim claims if Sanofi was not already precluded. [00:22:45] Speaker 04: I will yield the rest of my time to my colleague for the cross-appeal. [00:22:47] Speaker 03: Thank you. [00:22:48] Speaker 03: Let me say we have no objection to an associate coming up and giving you [00:22:53] Speaker 03: Note, but he was about to come up four times which is disruptive what my apologies are my apologies Ms. [00:23:00] Speaker 00: Rapelino Good morning, may it please the court. [00:23:08] Speaker 00: I'm going to address defendant's cross-appeal on the 170 patent the district court here made one significant legal error not the three errors that Mr. Solander talked about and if this court corrects that single legal error [00:23:22] Speaker 00: then the district court's own fact findings compel a conclusion of obviousness. [00:23:28] Speaker 00: That legal error, it's not the legal error that Mr. Solander pointed out of not considering the Haight and Lampedus references. [00:23:37] Speaker 00: Instead, that legal error is the district court's limiting its analysis of those two key prior art references, Haight and Lampedus, exclusively to the explicit teachings of those references. [00:23:49] Speaker 00: By doing that, [00:23:50] Speaker 00: The district court found that those two references were not, the teachings of those references were not relevant to taxanes because they didn't explicitly address taxanes. [00:23:59] Speaker 03: Even though... You're talking about hate? [00:24:01] Speaker 00: I'm talking about both the hate and Lampadis prior art references. [00:24:04] Speaker 03: If hate didn't fail to explicitly address taxanes, it was an entirely different chemical field. [00:24:10] Speaker 00: So it is true that the hate reference, that the compounds discussed in hate were phenothiazines, but the subject of the hate reference was the PGP protein, [00:24:19] Speaker 00: And there was evidence. [00:24:21] Speaker 00: And the district court, in dismissing the relevance of hate, didn't dismiss hate because it was a different class of compounds. [00:24:27] Speaker 00: When you look at the district court's opinion, this is at Appendix 52, the district court said that it afforded- This is a claim to a chemical compound. [00:24:35] Speaker 03: And one skilled in the art. [00:24:38] Speaker 03: starting with doxine, would not have looked to the phenothiazine art for determining whether to put a methoxy on the 7 and the 10 groups. [00:24:51] Speaker 00: Well, the evidence at trial was to the contrary. [00:24:54] Speaker 00: So the district court didn't address, didn't even mention the evidence at trial, the real world evidence from plaintiff's own expert, Dr. Ojima, himself a taxing expert, their only expert who actually worked in the taxing field at the relevant time. [00:25:07] Speaker 00: Dr. Ojima's testimony was that he took account of hate in designing taxanes, that he was aware of hate, and he took account of it in designing his own taxanes. [00:25:15] Speaker 00: And this was at Appendix 24286. [00:25:17] Speaker 00: In addition, plaintiff's own other expert, Dr. Ludwania, offered testimony that despite the structural differences between phenothiazines and taxanes, [00:25:30] Speaker 00: There was another prior art reference, the Greenberger prior art reference. [00:25:33] Speaker 00: So this is Greenberger and Safa. [00:25:35] Speaker 00: These are two references not addressed by the district court. [00:25:37] Speaker 00: And Dr. Ludwania's testimony also was not addressed by the district court. [00:25:41] Speaker 00: Dr. Ludwania clearly testified that the Greenberger reference showed that there was common ground between phenothiazines and taxanes in their interaction with PGP, and specifically that they shared a common binding site on PGP. [00:25:54] Speaker 00: And this was at appendix 24249. [00:25:56] Speaker 00: None of that testimony was addressed by the district court. [00:25:59] Speaker 00: which leads to the conclusion that the district court in dismissing Haight and Lampedus wasn't relying on actual factual distinctions between an expert testimony distinguishing phenothiazines from taxanes, but rather on the lack of an explicit disclosure in Haight and Lampedus of taxanes. [00:26:16] Speaker 00: Where the district court got the legal standard right, the district court's factual findings actually support obviousness. [00:26:23] Speaker 00: So if we turn to some of those factual findings, [00:26:26] Speaker 00: First, the district court properly found that the person of skill in the art would have identified dositaxel along with paclitaxel as a lead compound at the relevant time. [00:26:34] Speaker 00: Second, the district court also properly found that the person of skill in the art would have identified multi-drug resistance as the problem with dositaxel and would have been motivated to modify dositaxel to overcome that. [00:26:45] Speaker 00: And importantly, the district court found that in addressing that problem, the person of skill in the art would be focused on P-glycoprotein or PGP. [00:26:53] Speaker 00: Third, the district court made findings about Hayden-Lampadis. [00:26:56] Speaker 00: The district court found that those references taught strategies for overcoming or disrupting binding to PGP based on the physical properties of the compounds studied in those references, specifically based on improving the lipophilicity of those compounds. [00:27:10] Speaker 00: And finally, the district court also properly found that cabazitaxel's properties were not entirely unexpected. [00:27:16] Speaker 00: The POZA would have expected cabazitaxel to have improved potency over dositaxel. [00:27:21] Speaker 00: In other words, the district court made findings that support the person of skill in the arts reasonable expectation of success. [00:27:27] Speaker 00: Really, the only element that the district court found missing in the obviousness analysis was the motivation to make simultaneous modifications at C7 and C10 of dositaxel. [00:27:37] Speaker 00: But that finding was based on its erroneous finding that the person of skill in the art would not have looked at Haidt and Lampedus to solve the PGP problem, the very problem that the person of skill in the art would have been concerned with, [00:27:49] Speaker 00: just because those references were not explicitly about taxanes, but rather about other classes of compounds. [00:27:56] Speaker 00: That was legal error under this court's precedent in Alza versus Milan. [00:28:00] Speaker 00: The court must take into account not only the explicit. [00:28:02] Speaker 01: You say that was an underlying error infecting the determination that proof was not adequate, that among the many, many, many possible choices for modifying at different places and different ways, that this one would have been selected. [00:28:23] Speaker 01: Why does that actually? [00:28:26] Speaker 01: harmfully infect that conclusion when there are so many other choices. [00:28:31] Speaker 01: And others were choosing a lot of different locations to make modifications. [00:28:36] Speaker 00: So I would make two points in response to that. [00:28:39] Speaker 00: First, the court's dismissal of the relevance of hate and lampidus to taxing means that the court didn't take account of the fact that hate and lampidus [00:28:48] Speaker 00: directly point the person of skill in the art to the northern hemisphere, to the hydrophilic substituents in the northern hemisphere, which are the C7 and C10 positions. [00:28:57] Speaker 00: So that legal error of dismissing Hayden Lampadis infects the motivation to modify those two positions. [00:29:04] Speaker 00: The second point I would make is that, to the extent the district court talked about the modifications being made all over the taxing core, [00:29:10] Speaker 00: The evidence was that those modifications simply weren't relevant to the obviousness analysis, because those didn't happen at the relevant time. [00:29:17] Speaker 00: The relevant time under Alagan versus Apotex for assessing the state of the art is at the priority date, not before. [00:29:23] Speaker 00: And the evidence at trial from plaintiff's inventor, Dr. Bouchard, was that those modifications that had been made all around the taxing core had already been published as of the priority date in the Commerson reference. [00:29:35] Speaker 00: And so the modifications that had been made mostly by Sanofi's own predecessor, RPR, prior to the priority date, simply aren't relevant to what was known to the person of ordinary skill in the art as of the priority date. [00:29:48] Speaker 00: If there are no further questions, I would like to reserve my remaining time. [00:29:50] Speaker 03: We will give you a minute to respond as you requested. [00:29:56] Speaker 03: Mr. Solon. [00:30:03] Speaker 03: Tell us why the fact that Haight discusses phenothiazines isn't the point, that the interaction with the PGP protein is what counts. [00:30:18] Speaker 05: Your Honor, the question is, would a person of ordinary skill in the art in the taxane field have taken into account that model in designing changes to the taxane molecule? [00:30:27] Speaker 05: The answer is nobody ever did. [00:30:29] Speaker 05: And nobody ever would, because that model, first of all, it's totally hypothetical based on a different protein, chalumidin. [00:30:36] Speaker 05: They don't know what the structure of PGP is. [00:30:39] Speaker 05: He's hypothesizing that it might look like this other protein, chalumidin. [00:30:44] Speaker 05: It says it right in the hate reference. [00:30:46] Speaker 05: And he's hypothesizing that that's how it interacts with the phenothiazines. [00:30:52] Speaker 05: noted, the taxane molecule is completely different. [00:30:55] Speaker 05: There's no teaching that the taxane molecule interacts with that binding model in the same way that the phenothiazine molecule does. [00:31:04] Speaker 05: They rely on the Greenberger and Safa references, but all those say is that within a relatively large domain of the PGP molecule, [00:31:15] Speaker 05: photoaffinity label experiments show that chemotherapy drugs and these chemosynthesizers interact. [00:31:24] Speaker 05: They don't say how they interact, which is critically important. [00:31:27] Speaker 05: And the testimony from Dr. Valduena was crystal clear on this point. [00:31:31] Speaker 05: I have no idea how those interact. [00:31:33] Speaker 05: And therefore, if you don't know how they interact, how can you change a molecule? [00:31:37] Speaker 05: to better that interaction without doing experiments and SAR. [00:31:41] Speaker 05: And second, when Dr. LaDueña saw the Greenberger reference, he said, this completely undercuts hate. [00:31:49] Speaker 05: There's no way what Greenberger says is true, that all these molecules of very different shapes, of very different sizes, interact with the hate molecule, I'm sorry, the PGP molecule, [00:32:03] Speaker 05: at roughly the same domain, he said, then it's impossible that the hate model is right. [00:32:09] Speaker 05: It completely contradicts the hate model. [00:32:12] Speaker 05: And as to Dr. Ojima, this notion that Dr. Ojima was looking at hate as a person of ordinary skill in the art, well, first of all, he's an expert. [00:32:19] Speaker 05: And second of all, he was asked the question, I'm just focusing on what was going on in March 1995, the relevant date. [00:32:26] Speaker 05: And clearly, it shows that you were at least considering the binding model, the hate binding model, for tax aims. [00:32:33] Speaker 05: Is that correct? [00:32:34] Speaker 05: No. [00:32:35] Speaker 05: I said that is no. [00:32:36] Speaker 05: The testimony they quote in their brief, where he says he took that into account, was later research on chemosensitizers. [00:32:45] Speaker 05: Those are the type of compounds that were being studied in hate. [00:32:50] Speaker 05: Not phenothiazines, but compounds that block the action of PGP. [00:32:55] Speaker 01: Of the things that you've said in the last three or four minutes, how much is reflected in district court findings? [00:33:02] Speaker 05: The district court findings, a lot of what I said is not reflected in district court findings, except that the district court was right to find that hate was not applicable. [00:33:12] Speaker 05: It's supported by substantial evidence in the record, including [00:33:16] Speaker 05: all of the points beyond just the notion that it doesn't cite taxing, that the district court explicitly said, including that the compounds were different, different chemistry, used for a different purpose, has no information about the actual binding site of PGP, a hypothetical model based on totally different protein that's in A50 of the court's findings. [00:33:37] Speaker 05: And again, our testimony is clear that he could believe, and that is that Drs. [00:33:43] Speaker 05: Rausch and LaDwayne said, [00:33:46] Speaker 05: that a poster would not have considered hate helpful in designing molecules. [00:33:52] Speaker 03: Thank you, counsel. [00:33:53] Speaker 03: Your time has concluded. [00:33:54] Speaker 03: Thank you. [00:33:55] Speaker 03: Ms. [00:33:55] Speaker 03: Rapalino has a minute for response. [00:34:01] Speaker 00: Judge Toronto, I think your question is a critical point here, that the district court simply didn't take into account, and there's no evidence that the district court considered any of the contrary evidence that the [00:34:12] Speaker 00: any structural differences between the hate compounds, phenythiazines, and taxanes made any difference to the person of skill in the art in terms of its applicability to taxanes. [00:34:21] Speaker 00: That suggests, again, that the district court's standard that it applied here in determining that hate and lampidus weren't relevant to taxanes was based on legal error. [00:34:29] Speaker 00: It was based on a lack of an explicit teaching rather than an analysis. [00:34:33] Speaker 03: The district court said hate was not cited in any prior op taxane references, including those discussed by defendant's experts, [00:34:41] Speaker 03: that only provides a hypothetical binding molecule for calmodulin, which is different from and unrelated to PGP. [00:34:50] Speaker 00: Right. [00:34:50] Speaker 00: So the district court cited that but did not take into account or address or mention the testimony, the evidence, or the prior art that suggested otherwise. [00:34:59] Speaker 00: In other words, the district court, there's no evidence that the district court weighed that expert testimony and those fact findings in determining that the reason that [00:35:10] Speaker 00: hate was inapplicable to taxanes had to do with any of the structural differences rather than just a lack of an explicit teaching. [00:35:17] Speaker 03: Do you have a final thought? [00:35:20] Speaker 00: Well, my final thought is that if this court does reverse the legal error and applies the teachings of hate and lampidus to taxanes, finds that a person of skill in the art would have applied those teachings to taxanes, then the obvious thing for the person of skill in the art to do would be to make those C7 and C10 positions more lipophilic [00:35:38] Speaker 00: using the very substitutions that are found in cabazitaxel rendering cabazitaxel obvious. [00:35:43] Speaker 03: Thank you. [00:35:43] Speaker 03: We will take the case under five minutes.