[00:00:00] Speaker 02: The next case for argument is 24-2058, Regeneron versus Myron. [00:00:45] Speaker 02: Okay, see, I guess you can guess the first thing we're going to ask you is why we didn't get a 28-J letter. [00:00:51] Speaker 04: Of course. [00:00:52] Speaker 04: May it please the court, Jonathan Ellis, on behalf of Celter Young. [00:00:56] Speaker 04: So I think I will, I think, came to the same conclusion as my friends did on the 28-J, and I apologize if it was a wrong conclusion. [00:01:04] Speaker 04: uh... this court would be aware of the decisions and of the consulate wants for companion and solid appeals here i'd take your point judge pros uh... another point you might make in twenty eight j letter of the distinctions and the differences here [00:01:20] Speaker 04: But I took the rules of 2088 and not asked for excessive argument. [00:01:26] Speaker 04: I assume that our discussion this morning would focus in large part around those differences, and I am prepared to address them here. [00:01:32] Speaker 03: Well, let's focus on the things that it's saying. [00:01:34] Speaker 03: Which items do you now stand down on, if anything? [00:01:39] Speaker 03: Sure. [00:01:39] Speaker 04: So we are not withdrawing our personal jurisdiction or our causal nexus arguments from the case. [00:01:45] Speaker 04: But we do understand and accept that Samsung controls those issues in this appeal. [00:01:50] Speaker 04: And so I'm not depressing this more. [00:01:57] Speaker 04: OK. [00:01:58] Speaker 02: So we're left with what? [00:02:00] Speaker 04: So we're left with ODP, your honor. [00:02:02] Speaker 04: I think the question on that is whether Zeltrian has presented a substantial question that the asserted claims of the 865 patent are invalid under the doctrine of an obviousness type double patent. [00:02:15] Speaker 02: And there are a number of different grounds that we talk about. [00:02:18] Speaker 02: So there's stability, and there's LICO. [00:02:24] Speaker 02: Dicostalization. [00:02:26] Speaker 02: need to affirm on one. [00:02:28] Speaker 02: We're at the PI stage, and this is just so. [00:02:31] Speaker 02: You would have to prevail on all of those. [00:02:34] Speaker 04: I think we have to show a substantial question that none of the three asserted patentable distinctions are, in fact, patentable distinctions. [00:02:44] Speaker 04: I think the Samsung and Formicon decisions did both address glycosylation and the stability limitations. [00:02:51] Speaker 01: I think importantly, though... Well, regarding the stability limitations, let me drill down a little bit. [00:02:56] Speaker 01: Which of the following issues from SB that the SB decision noted were not appealed or challenged? [00:03:07] Speaker 01: Has Celty not appealed, and where is it in the briefing? [00:03:11] Speaker 01: And I have a long list. [00:03:14] Speaker 01: SB has not challenged that. [00:03:16] Speaker 01: district courts finding that the genus of stable VEGF trap formulations is not so small that it anticipates. [00:03:26] Speaker 01: SB has not appealed the district court's construction of stable. [00:03:30] Speaker 01: SB doesn't challenge the district court's factual findings that this requirement was not inherent in the 594 patents claim, that a relevant artisan would not have had the motivation to obtain such a high level of native court confirmation. [00:03:46] Speaker 01: that a relevant artisan would not have reasonably expected to succeed in doing so. [00:03:50] Speaker 01: That's all from SB. [00:03:54] Speaker 01: Yes. [00:03:54] Speaker 04: So we actually, I think, if I got all this correct, have challenged every one of those in this case. [00:04:00] Speaker 04: So we have, in fact, challenged the claim construction of the stable after four months in claim five of the five-man court patent. [00:04:11] Speaker 01: But we have a presidential opinion, which says you didn't do it there. [00:04:15] Speaker 04: no i'm sorry we are not seltzer on advance different argument right then samsung did right we've advanced it here and we advanced uh... challenge the the construction of stable after four months in your position is that because it wasn't covered here because the party didn't raise it you're free to raise it here absolutely not i think the court went out its way to identify that we've also challenged uh... the construction of the stability limitation in the eight six five that is to say that [00:04:43] Speaker 04: what, 98% of the VEGF trap considered. [00:04:47] Speaker 01: So you appeal to all of those? [00:04:48] Speaker 01: Yes, Your Honor. [00:04:49] Speaker ?: Okay. [00:04:50] Speaker 04: I think the easiest way to sort of cut through on the stability limitation are those two points that I've just identified. [00:04:55] Speaker 04: And I think they're independent, that you can either construe the 595 of the 594 patent stable after four months to require, at least with regard to aggregation, the same 98% native confirmation after two months. [00:05:10] Speaker 04: Or alternatively, you can construe the stability limitation, the 98% native confirmation, to speak to aggregation over time instead of a sort [00:05:19] Speaker 04: absolute purity, as LeGeneron asserts here. [00:05:24] Speaker 04: Beginning with the first, I think we start with the plain language of the claim, stable after four months. [00:05:29] Speaker 04: I think that tells you immediately that we're talking about stability over time. [00:05:33] Speaker 04: Unfortunately, it doesn't tell you exactly what kind of stability you're talking about. [00:05:36] Speaker 04: And so you have to look to the specification, a postal would look to the specification, to understand what that is. [00:05:41] Speaker 04: I think if you do, you see that stability does at least include aggregation. [00:05:46] Speaker 04: That should be no surprise to someone who is skilled in the pharmaceutical arts that aggregation is a measure of stability. [00:05:53] Speaker 04: You see that the SEC, measured by SEC, is how is included there. [00:05:59] Speaker 04: And then I think the question is, does it include also the 98% [00:06:02] Speaker 04: after two months requirement. [00:06:06] Speaker 04: And I think it does. [00:06:07] Speaker 04: I think the only place that the post-up could look in the specification of the 594 patent, the shared specification, to find what sort of native confirmation we're looking at are examples three and four and the tables there. [00:06:20] Speaker 04: And what you see is that they all satisfy that 98% native confirmation. [00:06:25] Speaker 03: Now my friends say that... Is there anything in the specification that you would see and show us that looks like lexicography for the word stable? [00:06:33] Speaker 04: So we're not making a lexicography argument. [00:06:35] Speaker 04: I do think that's what a post-it would understand to be required. [00:06:39] Speaker 04: I think it really turns on two facts. [00:06:41] Speaker 03: I mean, are there discussions of stable or stability that are not tied to the 98% value? [00:06:49] Speaker 03: I'm sorry? [00:06:50] Speaker 03: Aren't there other references to stable or stability in the patent that are not constrained to the 98% value? [00:06:59] Speaker 04: So there aren't ones that say you don't have to meet 98-98%. [00:07:03] Speaker 04: There are discussions of stability that include aggregation and that are measured by SEC. [00:07:09] Speaker 04: I think you might be referring to the discussion in column six that says that, preferably, you would start with a fusion protein that's substantially free of aggregates. [00:07:19] Speaker 04: Are we talking about? [00:07:20] Speaker 02: I'm having a hard time recalling all the details, particularly since this is the last case of the week. [00:07:26] Speaker 02: But I thought the district court rejected your argument because you were trying to show inherency from examples three and four. [00:07:33] Speaker 04: So there's two pieces here. [00:07:35] Speaker 04: The district court rejected our construction of stable after four months. [00:07:39] Speaker 04: It actually just said stable. [00:07:40] Speaker 04: But it rejected that argument. [00:07:42] Speaker 04: And then it separately rejected our independent argument that even if the 594 is not construed to require 98% native confirmation after two months, that it was inherent in the 594. [00:07:55] Speaker 04: That argument turns on a construction of the 865 stability limitation. [00:08:01] Speaker 04: Indeed, the only reason that the district court or Regeneron here has offered for why the 98% native confirmation limitation is not inherent is because they have a different reading of that limitation in the 865 patent. [00:08:15] Speaker 04: And we just think we have the better of that view. [00:08:17] Speaker 04: This is, again, an issue that wasn't presented in Samsung or Informacon. [00:08:23] Speaker 04: Indeed, Informacon went out of its way to identify it as not presented. [00:08:27] Speaker 02: And I think, Ellen? [00:08:29] Speaker 02: I want to see if anybody else, I'm ready to move to, I'll call it G, the other point. [00:08:35] Speaker 02: Black constellation. [00:08:35] Speaker 02: Yeah, yeah. [00:08:36] Speaker 02: Because I think this is, in that with regard to that, I think the evidence here is somewhat different. [00:08:43] Speaker 02: The evidence is different. [00:08:45] Speaker 04: I think also the construction is different as well. [00:08:49] Speaker 04: Samsung identified the fact that the Samsung decision identified the fact that Samsung had not challenged the construction of the VEGF antagonist limitation. [00:09:00] Speaker 02: But what about the understanding that all five sites are covered? [00:09:07] Speaker 02: Isn't that kind of different here? [00:09:11] Speaker 02: the five sites resulting in the 30 possible forms? [00:09:15] Speaker 02: Sure. [00:09:16] Speaker 04: Yeah. [00:09:17] Speaker 04: So that goes to the anticipation argument. [00:09:19] Speaker 04: So first, we've got an argument that the VEGF limitation, antagonist limitation, in the 5-9-4 patent by itself is construed, would be understood by the POSA, to refer only to a fliversept with its glycans intact. [00:09:33] Speaker 04: That is, glycosylated fliversept at all five sites. [00:09:36] Speaker 04: I think we have a strong argument on that ground. [00:09:40] Speaker 04: We have, again, an alternative argument here that says even if the VEGF antagonist limitation includes a genus, claims a genus of both non-glycosylated and glycosylated afliprocept, [00:09:52] Speaker 04: that that genus is sufficiently small that the species that's claimed in the 865 patent, the asserted claims, would be anticipated and would be immediately envisioned by the POSA. [00:10:04] Speaker 04: I'm happy to address either one, but absent questions else. [00:10:07] Speaker 03: What did we say in the Samsung opinion about that very question? [00:10:11] Speaker 04: In the Samsung opinion, I don't think the court said anything. [00:10:13] Speaker 04: In the Formicon decision, [00:10:15] Speaker 04: What the court said was that the former had argued it was a genus of two. [00:10:20] Speaker 04: That's wrong. [00:10:21] Speaker 04: It's a genus of 30. [00:10:22] Speaker 04: And therefore, it would not be anticipated. [00:10:25] Speaker 04: I think importantly, of course, that decision is non-precedential. [00:10:28] Speaker 03: But at the same time, the import of the reasoning there is that the genus must have been too big to say that the genus anticipated. [00:10:38] Speaker 04: So I think that's a fair reading of the reasoning there. [00:10:41] Speaker 04: I think there's a couple of reasons why I don't think you should follow that reasoning here. [00:10:45] Speaker 04: The first is, as I said, Formicon is non-presidential. [00:10:49] Speaker 04: It doesn't bind you. [00:10:49] Speaker 04: And second, Formicon didn't actually argue that it was sufficiently small. [00:10:53] Speaker 04: All Formicon argued was that the district court was wrong to see it as a genus of 30 at all. [00:10:59] Speaker 04: And I do think if you get to the merits of that, that is sufficiently small, sufficiently simple, that a post a would envision immediately at least a flipper step with all five sites glycosylated. [00:11:11] Speaker 04: I think you just step away from the science for a moment and think about a car with five seats. [00:11:15] Speaker 04: There may be 30 possibilities for where the different seats could be filled, but anyone who knows anything about cars could immediately envision all five being filled. [00:11:24] Speaker 04: I think that's true here even more in spades, because the only protein in the prior art that's known that has this sequence ID number four, the truncated porson, is a flipper step with all five. [00:11:37] Speaker 04: sites glycosylated. [00:11:39] Speaker 04: That's discussed in daily. [00:11:41] Speaker 03: If any one of the five locations is glycosylated, does that make it a glycosylated flibbersome? [00:11:50] Speaker 04: I think that is the understanding of the party is how we're treating that, yes. [00:11:54] Speaker 03: So then out of the 30 possible iterations, does that mean there's 29 of them are glycosylated? [00:12:01] Speaker 04: Yes. [00:12:03] Speaker 03: Because there's only one that would be non-glycosylated. [00:12:05] Speaker 04: That's right. [00:12:06] Speaker 04: And I think a POSA would immediately envision, if you have even a 30-member genus of non-glycosylated one and 29-glycosylated, would it imagine, envision a glycosylated version? [00:12:18] Speaker 04: And indeed, I think further, would envision a glycosylated version at all five sites. [00:12:25] Speaker 04: So that is the argument on anticipation for the glycosylated limitation. [00:12:29] Speaker 04: The argument on construction is that, in fact, you don't need to get there at all, because the claim 5 of the 5-9-4 patent is properly construed to only teach a glycosylated afloborecept. [00:12:42] Speaker 01: uh... we think that's where to claim five the reference uh... claim throughout your uh... your brief for farm selfie on lost at the district court regarding them the five nine four patent is a proper reference for o t p purposes yes sir and samson from the district court on the same question how do you justify calling claim five uh... [00:13:11] Speaker 01: what you want it to be instead of referring to it by what it is, which is what you argue it should be. [00:13:19] Speaker 04: So we do argue that claim five is a proper reference patent and the 594 patent. [00:13:27] Speaker 04: I think I might have understood you to say that Samsung decided against this. [00:13:31] Speaker 04: I don't think that's correct, Your Honor. [00:13:33] Speaker 04: The Samsung decision expressly said it didn't need to decide. [00:13:36] Speaker 04: It didn't need to address the arguments about whether 594 was a proper reference patent, because even if it were, it went on to then reject it found to potentially patentable and distinct limitations. [00:13:49] Speaker 04: I don't think it's really a very good case that the 594 patent is not a proper reference patent. [00:13:56] Speaker 04: I think what this court's cases teach and reselect and have be an allergan is that the question is whether the reference patent is earlier filed. [00:14:05] Speaker 03: Just a quick hypothetical. [00:14:07] Speaker 03: If an applicant is prosecuting an application and there are 20 claims and the examiner allows [00:14:18] Speaker 03: claims 1 through 5, but finally rejects claims 6 through 20. [00:14:24] Speaker 03: And then the applicant decides, well, I'm just going to take claims 1 through 5 right now and pay the issue fee on that and cancel claims 6 through 20. [00:14:35] Speaker 03: And then I'll try to find another day and file a continuation application to continue to try to work with the examiner on claims 16 through 20. [00:14:47] Speaker 03: Africans barred from doing that because it should have just kept on fighting for those points in the first application. [00:14:55] Speaker 04: So I don't think the inventor would necessarily be barred from doing that. [00:15:00] Speaker 04: I think if they came in and they found another continuation patent with the same priority date and the same expiration date, I don't think we'd get to an ODP analysis at all. [00:15:11] Speaker 04: I think the problem here is that what the inventor did was to say, in order to get the 594 out of the patent office, [00:15:17] Speaker 04: I'm not going to just give up on some subset of claims. [00:15:20] Speaker 04: I'm going to terminally disclaim the patent term. [00:15:23] Speaker 04: And I think when they do that, what Yamasaki teaches or says and holds, is that changes the statutory term of that patent protection and can't be undone. [00:15:32] Speaker 03: I need to ask another question after your time is up. [00:15:36] Speaker 03: The 594 patents term got tied to a different patent, right? [00:15:42] Speaker 04: A different, yes. [00:15:43] Speaker 03: What's the number of that patent? [00:15:44] Speaker 04: I don't have the number. [00:15:45] Speaker 04: I can get it to you on the fly. [00:15:47] Speaker 03: Yeah, let's call it the 123. [00:15:49] Speaker 03: OK. [00:15:50] Speaker 03: Is there a reason why you didn't try to make an ODP attack using the 123 as the reference patent? [00:16:01] Speaker 03: In that way, then maybe we would have a more [00:16:06] Speaker 03: fair comparison, because the 594 got tied to the 123. [00:16:11] Speaker 03: And now what we're really trying to figure out, perhaps, is whether the 865 likewise ought to be tied to the 123. [00:16:17] Speaker 04: So that could have been an argument we made. [00:16:20] Speaker 04: I think it's fair to present the one we did. [00:16:22] Speaker 04: And I think that because the terminal disclaimer is a meaningful event. [00:16:26] Speaker 04: What it does is cannot be undone. [00:16:28] Speaker 04: And what it does is make a bargain with the public. [00:16:30] Speaker 04: That when the invention in this patent has expired, the patent, the public can practice it in its obvious variance. [00:16:37] Speaker 04: That's the very premise and the purpose of ODP. [00:16:40] Speaker 04: So whether or not we could have challenged that, I think we are perfectly within our rights to challenge it here. [00:16:45] Speaker 04: And I think the 594 patent should be considered a proper reference patent, in which case we need to ask, have they identified or have we identified substantial question of unpatentability and validity based on the differences that they've identified. [00:17:02] Speaker 02: OK. [00:17:02] Speaker 02: Thank you. [00:17:03] Speaker 02: We'll restore some later. [00:17:04] Speaker 02: Thank you. [00:17:14] Speaker 00: Good morning. [00:17:15] Speaker 00: I think it's still good morning, maybe. [00:17:16] Speaker 00: No, it's not. [00:17:17] Speaker 00: Good afternoon. [00:17:18] Speaker 02: So let me cut to this. [00:17:22] Speaker 02: You had the luxury of the 28J that you didn't take advantage of. [00:17:26] Speaker 02: Is it fair to say the other side already conceded two issues are off the table? [00:17:29] Speaker 02: So we're left with the one issue. [00:17:33] Speaker 02: And with respect to that one issue, I think we've recognized that with respect to stability, there is a little bit of a door open left by the other case because of the claim construction otherwise. [00:17:45] Speaker 02: Why don't you address what your friend addressed with respect to why the result should be different based on this new argument? [00:17:50] Speaker 00: Sure. [00:17:51] Speaker 00: Respectfully, I think the door is much less open than it was presented a few moments ago. [00:17:55] Speaker 00: I think if one looks at pages 12 and 13 of the Formicon opinion, [00:17:59] Speaker 00: Acclaimed construction issue about what 98 percent means is addressed the court found that it was waived But then wrote on pages 12 through 13 [00:18:10] Speaker 00: We see no basis for accusing the forfeiture, as a substantial argument would be needed to overcome the apparent meaning of the claimed language on its face, which requires that at least 98% of the VEGF antagonist is present in native confirmation following storage for two months, a reference simply to a property at that time without calling for a comparison to an earlier time. [00:18:35] Speaker 00: So you've covered it. [00:18:36] Speaker 02: In fairness to my colleagues, would we consider that dicta? [00:18:38] Speaker 00: Think one could consider dicta because your colleague said that it had been forfeited But nevertheless it was addressed and I think I appreciate that so whether it's dicta or holding I think it's right to be honest And it's not only I who thought it was right their expert thought it was right if you look at a 10 741 [00:18:59] Speaker 00: That's their expert, Dr. Tessier's chart, where he's calculating the percent native confirmation after two months. [00:19:06] Speaker 00: And he's using our construction, and the construction that everyone in the two years of this litigation, from Mylon to all the other defendants have used. [00:19:13] Speaker 00: There's no subtraction, where you sort of make times zero a hundred, and then subtract. [00:19:18] Speaker 00: He didn't do that at 10-7-41. [00:19:20] Speaker 00: And look at their own preliminary injunction opposition brief below. [00:19:24] Speaker 00: That's at A-10-601 through 602. [00:19:28] Speaker 00: Celtrian does the same thing. [00:19:30] Speaker 00: No subtraction over time. [00:19:32] Speaker 00: They used our construction, the other defendant's construction, the court's construction, and we called them out on this in the opposition, and they said nothing in response in reply. [00:19:42] Speaker 00: Their expert agrees with us. [00:19:43] Speaker 00: He never put in another declaration saying, mea culpa. [00:19:46] Speaker 03: So when did this construction first come up? [00:19:49] Speaker 00: It came up in the surreply below. [00:19:53] Speaker 00: And, you know, the court there said, [00:19:55] Speaker 00: I'll let you offer a surreply. [00:19:58] Speaker 00: He then said it was waived, of course, because you can't now advance a new construction at a surreply. [00:20:03] Speaker 00: But nevertheless, the district court proceeded to analyze it and concluded correctly, I think, that it was wrong. [00:20:09] Speaker 00: There's no basis in the specification to say that there's some difference that is required, some subtraction that's required in order to determine what percent native confirmation there is, because the claim says [00:20:23] Speaker 00: It's the percent that is present after two months, as this court said nine days ago. [00:20:28] Speaker 00: It's a reference to a property at that time, not called for comparison to an earlier time. [00:20:35] Speaker 00: We think that construction resolves their first claim, which is 98% somehow means some difference. [00:20:42] Speaker 00: Now, they have another claim constructed earlier. [00:20:44] Speaker 00: This is not construing our 865 claims, but rather construing the words stable for four months in what they call the reference claim, claim five of the 594 patent. [00:20:53] Speaker 00: That was waived to. [00:20:55] Speaker 00: Below, that's found at A77 and 78. [00:20:59] Speaker 00: They don't respond in any way to the waiver argument, other than to say, somehow it was a new argument by us, and they had to respond in surrequired. [00:21:07] Speaker 00: I don't think that's correct. [00:21:09] Speaker 00: This is the exact thing. [00:21:10] Speaker 02: We want to briefly deal with the merits of that. [00:21:13] Speaker 00: Sure. [00:21:14] Speaker 00: Take your waiver point. [00:21:15] Speaker 00: I'm happy to deal with the merits, because I think it's exactly what Judge Chen said, which is that the patent at column six and column seven makes clear that the concept of stability is far broader [00:21:27] Speaker 00: than what they're construing it to mean, which is 98% by SEC. [00:21:31] Speaker 00: Column 6 shows that stability goes well below 98%, down to 90% and less. [00:21:37] Speaker 00: And then Column 7 explains that stability is a far broader concept than just aggregation measured by size exclusion chromatography and encompasses all sorts of other sorts of stability [00:21:48] Speaker 00: Chemical stability and otherwise measured in different ways in fact this court again do you quit equate? [00:21:55] Speaker 03: Substantially free of aggregates as being staple Yes, and I think that's how it was understood that that's a desirable component of stability right But I'm just in terms of the the document itself the patent the patent itself doesn't say that [00:22:10] Speaker 03: When we're talking about substantially free of aggregates, we should be thinking the same thing as stability. [00:22:15] Speaker 00: It does not use the exact word stability. [00:22:17] Speaker 00: I agree with you, Judge Chen. [00:22:18] Speaker 00: But if the patent is clear and the personal ordinary skill would have been clear that stability was an important, sorry, aggregation was an important component of stability. [00:22:26] Speaker 00: That's one of the most important parts. [00:22:28] Speaker 00: We don't want these. [00:22:29] Speaker 03: Particles to agglomerate because then you get particles and that's a disaster when you shoot in the eye and so and when the 98% number in your claim That's referring to the same thing substantially free of aggregates. [00:22:42] Speaker 00: That's 98% free right? [00:22:45] Speaker 00: Yes [00:22:45] Speaker 00: Yes. [00:22:46] Speaker 00: So that's right. [00:22:47] Speaker 00: So it's talking about the same sorts of stability there. [00:22:49] Speaker 00: And it says, this is desirable. [00:22:51] Speaker 00: You'd like to have at least 90% free of aggregates or less at the time that you formulate it. [00:22:56] Speaker 00: And then our claim, of course, goes further and says, you want 98%. [00:23:01] Speaker 00: as measured by SEC after two months. [00:23:03] Speaker 00: And so it's a narrower concept of stability than what you see in column six with respect to the number that we have to meet, and then much narrower than what you see in column seven of the patent with respect to the sorts of stability that are issued. [00:23:16] Speaker 00: So I think what they're trying to do in their claim construction is import [00:23:20] Speaker 00: certain data from examples three and four of the patent into the claims. [00:23:26] Speaker 00: So that when it says stable in the 594 claim five, they're saying, well, you take the 98% from example three, and you somehow read it into claim five of the 594. [00:23:35] Speaker 00: That's, of course, contrary to the most basic principles of claim construction. [00:23:39] Speaker 00: And the court therefore rejected it. [00:23:41] Speaker 03: And don't recall if we reject both claim construction arguments by the other side or find them to have been waived. [00:23:49] Speaker 03: Does that end the matter on stability, or do they still have yet other arguments? [00:23:54] Speaker 00: They raised, as I understand it, one additional argument that they also forfeited below, which is an argument that 98% would have been obvious somehow, that the personal ordinary still would have gotten there, even if there was a difference. [00:24:06] Speaker 00: That's addressed by the district court at A112, where he explains that was also forfeited, raised for the first time in a sub-reply brief. [00:24:14] Speaker 00: But also, it's incorrect, and they have no evidence to support it. [00:24:19] Speaker 00: The district court found at A112 that there's no motivation at 98%, and there's no reasonable expectation of success, citing what's now found at A5238, which is Dr. Trout's testimony, explaining that a person of ordinary skill, in view of the prior art, would not have expected to get 98% free of native confirmation, because the prior art showed no native confirmation data for a flavor step. [00:24:44] Speaker 00: And the relevant prior art, this is the ranibizumab prior art that you discussed with my colleague before, showed less stability and more aggregation when you use 40 milligrams per milliliter. [00:24:55] Speaker 00: And the district court found, and this is an important finding I think at A112-113, [00:25:00] Speaker 00: as it relates to ranibizumab compared to aflibrosep. [00:25:05] Speaker 00: Aflibrosep is a fusion protein. [00:25:07] Speaker 00: The court called it a Frankenstein kind of molecule, not natural like antibodies. [00:25:11] Speaker 00: And so what the district court explained at A112-113 is, [00:25:16] Speaker 00: The person of ordinary skill in New York would have expected a flibber step to be worse than ranivizumab. [00:25:22] Speaker 00: So that when ranivizumab shows a certain stability, and it showed bad stability in Goudreau when he used it at 40 milligrams per million. [00:25:30] Speaker 03: I guess we can't look at Dix, which shows 98%. [00:25:33] Speaker 00: It wasn't used for this purpose because that would again be combining dicts with other prior art. [00:25:40] Speaker 00: That was never done. [00:25:42] Speaker 00: That was excluded by the district court as an evidentiary matter because it wasn't preserved in the [00:25:49] Speaker 00: expert reports below. [00:25:50] Speaker 00: That was, again, another case. [00:25:51] Speaker 00: But Dix was not relied on by the preliminary injunction defendants. [00:25:54] Speaker 00: I'm now mixing cases. [00:25:56] Speaker 00: I don't mean to confuse you. [00:25:57] Speaker 00: We're both mixing them. [00:25:59] Speaker 00: But suffice it to say, it was not relied on here by the preliminary injunction defendants. [00:26:05] Speaker 00: And with respect to Milam, they tried to rely on it below in a combination. [00:26:09] Speaker 00: And that was excluded evidentially, not preserved by the expert reports. [00:26:15] Speaker 00: So I think that's their other argument though It's the 98% and I would submit that they have no response at all to the district court's finding on reasonable expectation of success Especially their only response is on pages 63 of their first brief and page 30 of their reply brief and what they do is [00:26:34] Speaker 00: They go back and they say, well, there would have been a reasonable expectation of success to get to 98% at the time of formulation, citing no evidence, by the way. [00:26:43] Speaker 00: But they say the patent assumes that. [00:26:46] Speaker 00: That's not the claim, of course. [00:26:47] Speaker 00: The claim requires 98% after three months. [00:26:50] Speaker 00: And the district court found, again, A112 relying on copias. [00:26:55] Speaker 00: evidence in the record that there was no expectation of success to meet 98% after two months and so that's why their obviousness argument even if not forfeited is unsuccessful on appeal. [00:27:09] Speaker 03: If we were to affirm on the stability limitation, that ends the case. [00:27:13] Speaker 00: That ends the case. [00:27:15] Speaker 00: I can sit down if you want. [00:27:16] Speaker 00: I can talk about glycosylation if you want. [00:27:18] Speaker 02: Well, glycosylation is a little different. [00:27:20] Speaker 02: So why don't you just spend? [00:27:21] Speaker 02: We're not going over time. [00:27:22] Speaker 02: There's no time. [00:27:24] Speaker 02: I have no desire to do that either, Your Honor. [00:27:27] Speaker 03: There's daylight between the glycosylation [00:27:30] Speaker 03: arguments here and the glycosylation arguments that were decided in the earlier case. [00:27:36] Speaker 00: I think that's right. [00:27:37] Speaker 00: I think it's fair to say that this court did not squarely address the same glycosylation issues. [00:27:42] Speaker 00: I think the assumption and [00:27:46] Speaker 00: explicit statements even by the court nine days ago reflect that there is a difference in breadth between the 594 patent on the one hand and the 865 patent claims on the other hand with respect to glycosylation necessarily there has to be otherwise there wouldn't have been the sort of analysis that this court undertook about what the differences are and whether or not they were obvious and so [00:28:12] Speaker 00: But this court did not undertake a claim construction analysis. [00:28:16] Speaker 03: Is it a genus species issue we're dealing with on the glycosylation? [00:28:20] Speaker 00: I think that's one way to conceive of it, yes, is that it is a genus of different sorts of proteins in the 594 claims. [00:28:27] Speaker 00: A genus of 30? [00:28:29] Speaker 00: It's actually 32. [00:28:30] Speaker 00: 32? [00:28:30] Speaker 03: How many of them would be glycosylated? [00:28:34] Speaker 00: 31 would be glycosylated in response to your questions earlier. [00:28:37] Speaker 00: I would note, though, that claim 14 [00:28:39] Speaker 00: of the 865 patent, one of the asserted claims here, requires all five sites to be glycosylated. [00:28:46] Speaker 00: And though my friend at the bar analogized it to five seats in a car, that was, of course, nowhere in the record. [00:28:53] Speaker 00: And the district court said that there was no showing by any of the preliminary injunction defendants that the genus was small, as is required to invoke the sort of petering analysis of anticipation by a small genus. [00:29:06] Speaker 00: And this court said the same thing nine days ago. [00:29:11] Speaker 03: If 31 isn't small, what in your view is small? [00:29:14] Speaker 00: I think Petering had eight, if I recall. [00:29:17] Speaker 00: Some of the other cases that have applied Petering have applied it up to numbers like 10 or 12, but never 32 in my knowledge of the law. [00:29:26] Speaker 00: And they never cited any case that would support deeming such a genus small for purposes of the immediately envisaged anticipation line of cases. [00:29:34] Speaker 03: I guess even we're just at the preliminary injunctions stage, right? [00:29:37] Speaker 03: So the other side would still have an opportunity to further develop this question on the size of the genus? [00:29:43] Speaker 03: Indeed, they would. [00:29:44] Speaker 00: Absolutely, they could. [00:29:46] Speaker 00: Absolutely, they could. [00:29:49] Speaker 02: Thank you. [00:29:50] Speaker 00: Thank you. [00:29:52] Speaker 02: Were we still two minutes early? [00:29:54] Speaker 01: Yeah, and I want to ask a question. [00:29:57] Speaker 04: I'm happy to, of course, answer your question, John. [00:29:59] Speaker 01: I practiced law for 20 years in federal courts. [00:30:04] Speaker 01: And it was routine for the district judge to ask for proposed findings and factual conclusions of law. [00:30:10] Speaker 01: And once in a while, I'd blanch when I'd get it back and the word proposed was crossed off and it was signed, thinking, jeez, did I get it all right? [00:30:20] Speaker 01: That's not what this judge did. [00:30:22] Speaker 01: You attacked him. [00:30:23] Speaker 01: for nakedly signing the proposed findings and conclusions from the other side with just a few changes. [00:30:35] Speaker 01: So I had my clerk very kindly did a red line of the proposed findings and the judge's actual opinion. [00:30:45] Speaker 01: There are a lot of changes in there. [00:30:48] Speaker 01: Some of them are small, some of them are [00:30:50] Speaker 01: substantial full pages, but it indicates to me that the judge very carefully reviewed those proposed findings and used them as he would. [00:31:03] Speaker 01: How on earth? [00:31:04] Speaker 01: You cited to some authority which says judges shouldn't just sign off without checking things. [00:31:10] Speaker 01: Very clearly, the judge checked all of this. [00:31:13] Speaker 04: So let me just say, first, if you read that as an attack, it certainly wasn't intended. [00:31:16] Speaker 04: We did cite this court's case law that says when the order is very, very close to the proposed order, that it doesn't change the standard review, but it warrants close scrutiny. [00:31:27] Speaker 04: I have a red line too. [00:31:29] Speaker 04: I did close review. [00:31:31] Speaker 04: And I think the changes are small in my view. [00:31:33] Speaker 04: And we thought that was relevant. [00:31:34] Speaker 04: It came within that precedent of this court. [00:31:37] Speaker 04: That's why we cited it. [00:31:39] Speaker 04: I would like to address the stability limitation. [00:31:43] Speaker 04: I have three points on the 865 stability limitation. [00:31:47] Speaker 04: The first is my friend said that we forfeited that construction by raising an innocent reply, and the district court held as much. [00:31:54] Speaker 04: It did not. [00:31:54] Speaker 04: A112 is where there was a waiver finding. [00:31:57] Speaker 04: It's all about our obviousness argument, not about our claim construction. [00:32:00] Speaker 04: There's no finding of forfeiture here. [00:32:02] Speaker 04: And I don't even take the red brief to actually come out and say we forfeited it. [00:32:06] Speaker 04: He also said that our argument is inconsistent with the written description argument below. [00:32:10] Speaker 04: The written description argument we made there, but not here, was that they didn't describe the full range from 98% to 100%. [00:32:16] Speaker 04: I don't think there's any consistent with that argument. [00:32:19] Speaker 04: and the argument that we're making here about how you should construe that limitation. [00:32:25] Speaker 04: My friend pointed to the Formicon decision and the tentative construction that the court gave there of the stability limitation. [00:32:33] Speaker 04: I think it was in the course of finding that argument forfeited, it would be sort of strange to then take that as a construction, a definite construction, and of course it is non-presidential. [00:32:44] Speaker 04: And so that leaves the merits of the claim construction there, and I'd love to address why [00:32:48] Speaker 04: I think that it is a comparator, that it has to be aggregation over time. [00:32:54] Speaker 04: What it says right from the get-go is 98% of the VEGF trap, of the VEGF antagonist. [00:33:00] Speaker 04: A percentage itself is a comparison. [00:33:02] Speaker 04: It has a numerator and a denominator. [00:33:04] Speaker 04: It must be a comparison. [00:33:06] Speaker 04: So then you ask, what is it a comparison of? [00:33:09] Speaker 04: Well, it's 98% of the VEGF trap. [00:33:11] Speaker 04: The VEGF trap is the un-aggregated, the flippercept. [00:33:15] Speaker 04: aggregated of liver sep is an impurity. [00:33:17] Speaker 04: It's not a VEGF trap. [00:33:18] Speaker 04: It's not a VEGF antagonist. [00:33:20] Speaker 04: So now we ask, well, what point in time do we compare the reading at two months to the VEGF antagonist? [00:33:28] Speaker 04: And I think it only makes sense in the course of this claim to look at what VEGF antagonist was present before you put it into storage. [00:33:35] Speaker 04: After all, it's a limitation about stability during storage over two months. [00:33:42] Speaker 02: One more quick thought. [00:33:44] Speaker 02: Sure. [00:33:45] Speaker 04: One more quick thought. [00:33:46] Speaker 04: My friend points to the 90%, preferably 90% free of aggregates when you start. [00:33:51] Speaker 04: Purity is not stability. [00:33:52] Speaker 04: You could start with 70% pure flibbersept, unaggregated flibbersept. [00:33:57] Speaker 04: After two months, if you still have 70% unaggregated flibbersept, that's a very stable formulation, even if it was not highly pure. [00:34:06] Speaker 02: Thank you. [00:34:07] Speaker 02: We thank both sides. [00:34:08] Speaker 02: The case is submitted. [00:34:09] Speaker 02: The concludes our proceeding.