[00:00:00] Speaker 00: Our last appeal of the day is appeal number 21-2270. [00:00:05] Speaker 00: Pharmacyplex versus Alvigin. [00:00:09] Speaker 00: Mr. Gutman? [00:00:11] Speaker 00: Yes, Your Honor. [00:00:11] Speaker 00: You've reserved five minutes. [00:00:13] Speaker 00: Yes. [00:00:13] Speaker 02: Thank you. [00:00:15] Speaker 02: Good afternoon, Your Honors. [00:00:16] Speaker 02: May it please the court. [00:00:18] Speaker 02: My name is Zygmunt Gutman. [00:00:19] Speaker 02: I represent Appellants. [00:00:20] Speaker 02: And with me is John Roberts, my colleague. [00:00:23] Speaker 02: And also from Alvigin is Andrea Sweet, the Vice President of Legal Affairs. [00:00:30] Speaker 00: Just curious, if we affirm on any one of these patents, do you still want us to go forward and consider the validity of the other patents? [00:00:41] Speaker 00: Yes, Your Honor. [00:00:44] Speaker 01: Assuming the patent that we affirmed on was the 857, which I think has the latest expiration date, is there any practical consequence of if we were not to address the other three patents? [00:00:56] Speaker 02: There is, Your Honor. [00:00:57] Speaker 02: I think it's important to address the validity of all of the patents. [00:01:01] Speaker 02: Because? [00:01:02] Speaker 02: Well, not just because of Alvigen, but because of the importance that other generic pharmaceutical companies may, armed with that information, still be able to enter the market early, as Alvigen may be able to as well. [00:01:20] Speaker 02: So given the amount of time that I have, I'll address [00:01:25] Speaker 02: But four issues, specifically written description and obviousness with respect to the 090 method of treatment patent and inherent anticipation and obviousness with respect to the 455 crystal form patent. [00:01:43] Speaker 02: And I'll start with claim two of the 090 patent written description. [00:01:48] Speaker 02: Claim two is invalid for lack of written description. [00:01:51] Speaker 02: Court error because the court erroneously failed to consider and properly apply the blaze marks law. [00:01:59] Speaker 02: which required that the court objectively identify within the four corners of the specification of the 090 patent, blaze marks that would allow Opposa to visualize claim to from the scattered and disjointed claim elements that are strewn across the specification and the vast genus of methods of treatment that are discussed in the specification. [00:02:25] Speaker 02: The court erred because it used hindsight by using claim to as a guide to walk through the specification and indiscriminately pick out various claim elements. [00:02:37] Speaker 00: What's wrong with the passage in the summary of the invention at columns four to five for the 090? [00:02:43] Speaker 02: Thank you, Your Honor. [00:02:44] Speaker 02: I was just about to address that. [00:02:46] Speaker 02: So that passage does not expressly disclose claim to. [00:02:52] Speaker 02: What that passage discloses, and by the way, both the court and the appellees in their citation were even unable to identify fully all of the elements of claim two in their cited passages. [00:03:05] Speaker 02: And I think that emphasizes the scattered nature of the disclosure. [00:03:10] Speaker 02: But putting that aside, that passage really is talking about a vast genus of methods of treatment. [00:03:20] Speaker 02: Um, it, within that passage is, uh, a disclosure of individual non-claim elements as well as claim elements that are included in specific embodiments, um, for which the embodiments are never actually identified. [00:03:41] Speaker 00: Um, it calls out, um, using ibrutinib at about 560 milligrams a day, doesn't it? [00:03:47] Speaker 02: It does, Your Honor, but the claim is not merely directed to using abrutinib at about 560 milligrams a day. [00:03:54] Speaker 02: The claim is a combination claim that combines many different elements. [00:03:58] Speaker 02: And what claim two is directed to is a method of treating our MCL using about 560 milligrams per day orally administered. [00:04:10] Speaker 02: And that claim, as a combination, [00:04:13] Speaker 02: is nowhere actually described in the summary of invention. [00:04:16] Speaker 00: The oral dose form that's missing from this one passage at column four to five? [00:04:21] Speaker 02: Well, the court actually missed two elements. [00:04:23] Speaker 02: The court missed the route of administration, oral, as well as the frequency of administration. [00:04:29] Speaker 02: The appellees actually did a little bit better at page 17 of their responsive brief. [00:04:36] Speaker 02: And they were able to identify the oral [00:04:39] Speaker 02: route of administration, but still failed to identify the frequency of administration. [00:04:44] Speaker 01: The frequency of the number of milligrams per day? [00:04:47] Speaker 02: Correct, Your Honor. [00:04:48] Speaker 00: But doesn't Tome 5 say about 560 milligrams per day? [00:04:52] Speaker 00: I mean, what else does that communicate to us other than using 560 milligrams a day, per day? [00:04:59] Speaker 02: Well, the frequency of administration, Your Honor. [00:05:02] Speaker 01: Oh, in other words, there's no suggestion that it has to be done every day? [00:05:07] Speaker 01: Is that the argument? [00:05:08] Speaker 02: Well, that it has to be done every day or how many times a day. [00:05:12] Speaker 00: Oh, you could break it up, maybe divide 560 by 4, and then you could get four separate doses. [00:05:20] Speaker 02: That's right. [00:05:21] Speaker 02: And when you go down in the passage, you'll actually see that the summary of invention discusses that it could be a single dose or a divided dose. [00:05:32] Speaker 02: And so the passage in total is really [00:05:38] Speaker 02: discussing a vast genus of methods of treatment and different permutations where these claim elements are being mixed and matched to define the genus. [00:05:47] Speaker 02: And when you read through it, there is no disclosure actually of the claim to combination that is the method of treatment. [00:05:59] Speaker 02: The court never addressed in its decision [00:06:03] Speaker 02: the language used in the patent at the summary of invention regarding that these disparate claim elements are used in specific embodiments without mentioning what those embodiments are. [00:06:16] Speaker 02: In other words, where is claim two within this forest of possible methods of treatment? [00:06:23] Speaker 02: So the court turned to example 13 in order to try to find written description support for claim two. [00:06:32] Speaker 02: And example 13 is also a vast genus of methods of treatment. [00:06:37] Speaker 02: It talks about using a broad genus of BTK inhibitors. [00:06:42] Speaker 02: And the patent tells us what those BTK inhibitors are. [00:06:46] Speaker 02: I'll direct the court's attention to columns 45 through 46 of the 090 patent, where it discusses what a BTK inhibitor is. [00:06:55] Speaker 02: And notably, the discussion about what a BTK inhibitor is [00:07:00] Speaker 02: also employs this in some embodiments language without telling. [00:07:05] Speaker 02: Opposa or anyone else for that matter, what embodiments are being specifically addressed. [00:07:12] Speaker 00: But Ibrutinib is at least highlighted in the summary of invention, which maybe there could be arguments as to one of the other possible BTK inhibitors disclosed at column 45, and we could quibble about which one of those are actually part of example 13. [00:07:29] Speaker 00: But Ibrutinib is at least spotlighted in the summary, which gives us some [00:07:35] Speaker 00: I mean, I guess to use your word blazemark to understand that perhaps we should think of example 13 in the context of what is described in the summary. [00:07:45] Speaker 02: So your honor, the test is that the specification must objectively identify what the blazemarks are that would lead Opposa to visualize the claimed invention. [00:07:58] Speaker 02: I think your honor is referring to the court's conclusion that a brutinib is somehow a preferred BTK inhibitor and therefore can be plugged into example 13. [00:08:11] Speaker 02: I don't believe that that is an appropriate objective inquiry. [00:08:16] Speaker 02: I think the court committed error in characterizing a brutinib as a preferred BTK inhibitor. [00:08:22] Speaker 02: In fact, the specification [00:08:25] Speaker 02: in a different portion of the summary of invention at column three, lines one through 30, talks about this vast genus of BTK inhibitors using the same language in some embodiments, exactly in the same way that the passage focused on by the court is talking about a brutinib in talking about the various methods of treatment. [00:08:52] Speaker 02: And additionally, [00:08:54] Speaker 02: The specification, and this goes to whether Abrutinib as a preferred BTK inhibitor can objectively be found within the specification. [00:09:07] Speaker 02: The patentee in this case knew how to signal what was preferred. [00:09:12] Speaker 02: When you look through the specification, there are different areas of the specification [00:09:17] Speaker 02: where the patentee indicated what was preferred or what was preferable. [00:09:21] Speaker 00: Mr. Gutman, just to let you know, I'm going to do my best to hold you to your time. [00:09:25] Speaker 00: So if you want to get to anything else, I just want you to know that. [00:09:30] Speaker 02: OK. [00:09:30] Speaker 02: Thank you, Your Honor. [00:09:33] Speaker 02: But I'll move away from the preferred issue. [00:09:38] Speaker 02: But the one thing that I'll say about it also is that even if a Brutinib is a preferred BTK inhibitor, [00:09:46] Speaker 02: The court never found, and again, there's no objective indication within the four corners of the specification, that abrutinib is a preferred BTK inhibitor for use in a method of treating RRMCL. [00:10:00] Speaker 02: So at best, the only thing that the court found was that abrutinib was a BTK inhibitor, a preferred BTK inhibitor, excuse me. [00:10:10] Speaker 02: I'll move on to obviousness now. [00:10:13] Speaker 02: Claim two is obvious. [00:10:15] Speaker 02: The court erred by failing to conclude that claim, too, was obvious in view of the presumption of obviousness, as well as admissions and other undisputed evidence of record. [00:10:30] Speaker 00: There's an argument that the presumption of obviousness issue here was forfeited in the sense that you presented it below only in the context of an obviousness-type double patenting theory and not in a classic 103 theory. [00:10:45] Speaker 02: Yes, Your Honor. [00:10:45] Speaker 02: I understand that's an argument made by Apolize. [00:10:49] Speaker 00: We can put that to the side. [00:10:50] Speaker 00: Go ahead with your argument. [00:10:51] Speaker 00: OK. [00:10:51] Speaker 02: Thank you, Your Honor. [00:10:53] Speaker 02: Apolize prior art 015 patent, including Claim 2, when combined with any one of the Apolize prior art clinical trial references, discloses all the elements of Claim 2. [00:11:10] Speaker 02: The only allegedly novel aspect of Claim 2 [00:11:14] Speaker 02: is using about 560 milligrams of abrutinib to treat or MCL. [00:11:22] Speaker 02: But that amount, that dose, falls squarely within a disclosed range of doses in the 015 patent, and therefore is presumptively obvious. [00:11:33] Speaker 00: Is the claim directed to treating relapsed MCL? [00:11:37] Speaker 02: RR is relapsed and refractory. [00:11:40] Speaker 00: RR MCL? [00:11:42] Speaker 00: Yeah. [00:11:42] Speaker 00: I'm sorry? [00:11:43] Speaker 00: The claim in the 090 patent is directed to treating RR MCL. [00:11:47] Speaker 02: It doesn't specifically call that out, but we've never made the argument that it's not directed. [00:11:52] Speaker 00: And the 015 patent disclosure and claim is not directed to RR MCL. [00:11:58] Speaker 02: Claim 20 mentions MCL, which is a genus that would include our MCL, as we argued in our briefing. [00:12:08] Speaker 02: It's a two-species genus. [00:12:10] Speaker 00: The district court found differently, if I recall, correct? [00:12:14] Speaker 02: The district court found, I think in error, that the MCL to which the claim 20 was directed would not have included [00:12:27] Speaker 02: our MCL, and more importantly, and this is really important, that the disclosure in the 015 patent, as well as the disclosure in the 090 patent, there is an admission within these patents that the amount of the dose, regardless of whether the presumption of obviousness applies, and regardless of the severity of the disease, [00:12:56] Speaker 02: excuse me, Your Honors, can be determined through routine experimentation. [00:13:03] Speaker 02: The 090 patent and the 015 patent are very clear on those points, that the severity of the disease. [00:13:09] Speaker 02: And the appellees have conceded that, and the court agrees, that our MCL is merely a more severe form of MCL. [00:13:22] Speaker 02: So the district court erred. [00:13:24] Speaker 02: by not applying the presumption of obviousness. [00:13:29] Speaker 02: And if your honors determine that the presumption of obviousness applies, then claim two is obvious for that sole reason. [00:13:38] Speaker 02: But even without the presumption, claim two is still obvious in view of Appellee's binding admissions in both the 090 patent as well as the 015 patent that [00:13:49] Speaker 02: Therapeutically effective amounts of Abrutinib can be determined through routine experimentation, not just routine experimentation, but the disclosures add on the fact, including the types of studies that were disclosed [00:14:06] Speaker 02: in the prior art clinical trial studies that were relying on to demonstrate obviousness. [00:14:12] Speaker 00: The friend on the other side is going to get up and say, well, what happened here to discover the 560 milligram amount was a critical, unexpected discovery that was located and found through using non-routine techniques, not what a person of ordinary skill of art would have actually done, which would have been the routine types of experimentation. [00:14:34] Speaker 02: Yes, Your Honor. [00:14:35] Speaker 00: So even though you're out of time, can you quickly respond to that? [00:14:38] Speaker 02: Yes. [00:14:39] Speaker 02: So first of all, this method is not directed to a method of discovering a dose. [00:14:44] Speaker 00: This method is directed to... But the point is that through routine experimentation, you wouldn't have arrived at 560. [00:14:52] Speaker 00: You would have arrived at something else. [00:14:53] Speaker 00: You probably would have arrived at something much higher than 560. [00:14:57] Speaker 02: So Your Honor, first of all, the way that the inventors arrived at the claim [00:15:03] Speaker 02: is not relevant to how a POSA could have arrived at the claim. [00:15:08] Speaker 01: So the fact that the inventors here decided to take some path to identify about 560 milligrams as... But it has something to do with the characterization of the dosage as being a product of routine experimentation, if in fact the method that was used was not routine at all. [00:15:31] Speaker 02: Well, to be clear, the method that the inventors used may not have been routine, but that doesn't foreclose that there are other methods that are routine. [00:15:41] Speaker 01: But didn't the district judge specifically find that the other methods would not have produced 560 as a factual matter? [00:15:50] Speaker 02: The district court found that usually, the district court did not say that always the MTD [00:15:58] Speaker 02: of this kind of phase one study must be used as the therapeutically effective dose. [00:16:05] Speaker 02: Even the district court acknowledged in the decision that it usually is, but doesn't have to be. [00:16:11] Speaker 02: And so the first point is that is not inconsistent with the patentees admissions in the patented issue as well as the prior art that therapeutically effective amounts could be determined through routine experimentation, particularly in view of the additional guidance that those doses would typically fall within the range of one to 1500 milligrams per day. [00:16:36] Speaker 00: Okay, you're out of your time, so we will give you back your rebuttal. [00:16:41] Speaker 03: Thank you, Your Honor. [00:16:42] Speaker 00: Mr. Sipes. [00:16:44] Speaker 03: Thank you, Your Honor. [00:16:45] Speaker 03: I'm Christopher Sipes. [00:16:46] Speaker 03: On behalf of the plaintiffs with me at Council Tables, my colleague Erica Anderson, Linda Fridley of Farber Cyclets and Abbey is here, as is Clara Jimenez of Janssen. [00:16:56] Speaker 03: Let me start first just to address the question that was said last, in which Mr. Goodman suggested that the court didn't find that routine dose escalation would not result in 560. [00:17:08] Speaker 03: In fact, at appendix 45, the court found specifically, and this is a factual finding, had an artisan of ordinary skill conducted a routine dose escalation study for a brute nib before the priority date, [00:17:21] Speaker 03: she would have escalated the dose amount to a dose far greater than 560 milligrams. [00:17:27] Speaker 03: So there is no question, and Algen has not shown clear error in that finding. [00:17:31] Speaker 00: I guess the skilled artisan would have located 560 milligrams a day, right? [00:17:37] Speaker 00: I guess the point is that she, the proceder, would have just kept on going. [00:17:43] Speaker 03: actually it's not clear that a post would even have ever landed on five six or anything about that the way the three-by-three dose escalation study works there's constant increases so that you don't check every number you go to a certain number you jump so that there is no there is no testimony let alone clear convincing evidence that a post would ever have even tested five sixty but the the larger point is what the post would have been looking for is is the dose tolerable not [00:18:12] Speaker 03: Is it effective, or more importantly, is it a pharmacokinetic study that's saying, is the BTK kinase fully occupied? [00:18:21] Speaker 03: So there's no testimony that 560 would ever have been tried. [00:18:24] Speaker 03: But there is clear testimony that the POSA ends up with a dose well above 560. [00:18:30] Speaker 03: In fact, the MTD for Brutinib has never been found. [00:18:35] Speaker 03: But it's been tested up to 840. [00:18:38] Speaker 03: So it's above 840. [00:18:41] Speaker 03: So what is clear is a routine dose escalation study, as the district were found, would end up with a dose far above. [00:18:48] Speaker 03: Whether 560 would ever have been tried, we have no idea. [00:18:51] Speaker 03: There's no evidence in the record as to that. [00:18:53] Speaker 00: So is the unexpected advantage that you don't need as much of the Igrutinib to be effective? [00:18:59] Speaker 03: It's more than that, Your Honor, because what distinguishes, the claim requires about 560. [00:19:05] Speaker 03: So the claim is directed to that dose. [00:19:08] Speaker 03: As the court found, this met a long-felt need. [00:19:11] Speaker 03: for a treatment that was both effective and safe and tolerable because the patient population we're talking about here are incredibly, they're elderly and vulnerable. [00:19:22] Speaker 03: Prior to Brutinib, relapsed refractory MCL was in the course of a dismal outcome. [00:19:30] Speaker 03: The patients were not put to a death's door. [00:19:34] Speaker 00: The 015 patent already disclosed the range. [00:19:37] Speaker 03: that it disclosed a range. [00:19:39] Speaker 00: That this 560 is inside it. [00:19:41] Speaker 03: It is inside it, but it disclosed several things. [00:19:44] Speaker 03: It disclosed the range for MCL. [00:19:46] Speaker 03: And as I believe, Judge Chen, you pointed out, the district court found, which is true, that MCL and relapse for factory MCL are different diseases treated in different ways. [00:19:56] Speaker 03: That's, I think, in footnote eight of the court's opinion. [00:19:59] Speaker 03: And so one, it's a different disease. [00:20:01] Speaker 03: But two, if you look at the disclosure there, it's one, disclosing that a therapeutic effect could be found. [00:20:10] Speaker 03: It doesn't even suggest that it's a fixed amount. [00:20:13] Speaker 03: And the range is 1 to 1,500. [00:20:15] Speaker 03: And it may well be with routine dose escalation, you could find a therapeutic dose, say 900 or 840. [00:20:22] Speaker 03: But would it be as safe? [00:20:24] Speaker 03: Would it be as effective, as tolerable, as the dose that was found? [00:20:29] Speaker 03: We don't know, because it's never been tested clinically. [00:20:32] Speaker 03: What the 015 does not say is you can find the clinically optimal dose, the best dose, that way. [00:20:40] Speaker 03: And the district court made a number of findings. [00:20:42] Speaker 03: This was all presented. [00:20:43] Speaker 03: This argument was waived. [00:20:44] Speaker 03: It was never presented in obviousness. [00:20:46] Speaker 03: It was presented in the context of obviousness type double patenting. [00:20:49] Speaker 03: And the court went on to consider it there and found specifically in that case that the 015 patent has a lot of differences, but more to the point that the range is so great that you would post it would never from that range ever have hit upon 560. [00:21:07] Speaker 03: And that's consistent with this court's case law. [00:21:09] Speaker 03: In Genetics Institute, it rejected an argued presumption because the facts here present a case where the disclosed range is so broad as to encompass a very large number of possible distinct compositions. [00:21:21] Speaker 03: In Allegan v. Sandoz, the disclosed ranges are so broad as to encompass a very large number of possible distinct compositions. [00:21:28] Speaker 03: So now we have a range. [00:21:30] Speaker 03: It's not even for RMCL. [00:21:31] Speaker 03: It's not even fixed daily dosing. [00:21:35] Speaker 03: It could be weight-based dosing, something very different, of 1 to 1,500. [00:21:40] Speaker 03: That broader range for a different disease for a particularly different dosing region will not lead a POSA to the about 560 milliliter a day. [00:21:51] Speaker 00: And the record shows that conclusion that there's been a rebuttal of the presumption of obviousness. [00:21:55] Speaker 00: Is that a question of law or a question of fact? [00:21:59] Speaker 03: So that was not teased out because of the odd way it was presented here. [00:22:04] Speaker 03: i believe at the end of the day the question whether there is a presumption of remains the same in the bird remains the same they have the burden to show offices by clear convincing evidence and that's the subsidiary factual findings are factual that would include actual questions about whether or not [00:22:20] Speaker 03: even if there's a presumption, a POSA would hit upon from the disclosed range the claim to about 560. [00:22:28] Speaker 03: We believe that's a factual question. [00:22:29] Speaker 03: So you can view that as either it's rebutted based on all the differences between the disclosure and the claim, or the presumption should have applied in the first place. [00:22:41] Speaker 03: You end up in the same place, which is you cannot take a teaching that says for a wide range of conditions, [00:22:46] Speaker 03: a therapeutic dose of 1 to 1,500 milligrams may be used. [00:22:52] Speaker 03: Could be fixed, could be daily, it's first line MCL, and arrive at treating relapsed refractory MCL with a fixed daily dose of 560 milligrams per day. [00:23:06] Speaker 03: Now let me make it if I could. [00:23:09] Speaker 03: I don't want to move on if there's still questions, but I do want to address the written description argument, because I [00:23:14] Speaker 03: substantial misstatements, both about what the district court found and what's in the written description that are important. [00:23:21] Speaker 03: First of all, the district court found, and this is important, that example 13, when read in light of the remainder of the written description, enables and describes claim two of the 090 patent. [00:23:33] Speaker 03: And that is correct. [00:23:35] Speaker 03: Example 13 describes a protocol for treating relapsed refractory MCL with the fixed daily dose of 560 milligrams with capsules, which is an oral administration. [00:23:46] Speaker 03: The court found that that is everything about claim to accept which BTK. [00:23:51] Speaker 03: It just says a BTK inhibitor. [00:23:53] Speaker 03: Which BTK inhibitor? [00:23:55] Speaker 03: And either supporting evidence, for example, from Dr. Ruhl that the court credited at appendix 15065, [00:24:04] Speaker 03: that says following example 13 with a Brutinib is the same as the method of claim 2. [00:24:09] Speaker 03: It has the 560 milligrams. [00:24:11] Speaker 03: Now, it's 560 not about, but of course, in carrying something out, you get variation. [00:24:15] Speaker 03: It's fixed daily dosing, so you get the once a day, 560 milligrams per day. [00:24:20] Speaker 03: The only challenge in Alvagen's brief to the connection here, and it says it's opening at 15 and replied 4, what they challenge is the conclusion that a person with a skill level reading this would recognize the inventors [00:24:34] Speaker 03: in possession of carrying out Example 13 with Ibrutinib. [00:24:38] Speaker 03: But here's the problem they have. [00:24:39] Speaker 03: And the court made extensive fact findings on this. [00:24:42] Speaker 03: As it found in Appendix 46, there's one and only one BTK inhibitor identified by name for the treatment of relapsed and refractory MCF. [00:24:55] Speaker 03: And that's Ibrutinib. [00:24:57] Speaker 03: That's its finding. [00:24:59] Speaker 03: So it is the only BTK inhibitor identified by name in the summary of the invention, and is the only BTK identified for the treatment of RRMCL. [00:25:11] Speaker 03: So this is a pretty clear blaze mark. [00:25:12] Speaker 03: The court's word was preferred, but the patent singles out by name only one BTK inhibitor for the treatment of RRMCL, which immediately [00:25:25] Speaker 03: connects it to example 13, the treatment of RRMCL. [00:25:29] Speaker 03: This is a blaze mark where you have only one trail. [00:25:33] Speaker 03: If you want to get to the land of treating RRMCL, and example 13 tells you how to treat RRMCL, the written description describes a single trail by name. [00:25:43] Speaker 03: And that single trail is ibrutinib. [00:25:46] Speaker 03: It's hard to imagine clearer connection. [00:25:49] Speaker 03: It's not scattered between the patent. [00:25:50] Speaker 03: There's two places in the patent that repeat the fact that ibrutinib is the BTK inhibitor that's called out by name for the treatment of RxM. [00:25:57] Speaker 00: Can you review that in example 13 when it talks about BTK inhibitor, quote unquote, that equals ibrutinib? [00:26:05] Speaker 03: no what i would say it is written support for any other btk inhibitor but i haven't seen other ones if a claim was to using a btk inhibitor generally for the treatment of our mcl perhaps example thirteen would give support for such a broad i don't know i haven't thought about that i'm not there's no other btk is i'm aware of it's not is not a truck spent a lot of the but but the court found that we've it's corrected his own video called out for r m c l so i believe it called out a different [00:26:35] Speaker 03: BTK inhibitor, not a Brutinib, but some other BTK inhibitor, there would be no support for that. [00:26:40] Speaker 03: Because as far as the court found of my reading, as Dr. Ruhl's testimony says, he too testified, there's one and only one BTK inhibitor called out in the patent expressly for the treatment of RRMCL. [00:26:55] Speaker 03: And that's a Brutinib. [00:26:56] Speaker 03: And that's clear. [00:26:57] Speaker 03: Example four, in column four, rather, this is Appendix 18269, that chemical name is a Brutinib. [00:27:05] Speaker 03: And then it says specifically, in identifying, it says it's useful for non-Hodgkin's lymphoma is relapsed or refractory diffused B-cell, relapsed or refractory mantle cell lymphoma. [00:27:15] Speaker 03: So it's calling out by name. [00:27:17] Speaker 03: In example five, you can find also the idea that you can use about 560 milligrams a day orally once a day. [00:27:24] Speaker 03: Then if you go to column 29, this is in appendix 18282. [00:27:30] Speaker 01: Where's the orally once a day? [00:27:32] Speaker 03: OK, so orally, so the appendix 18270, that's column 5, at line 19 is administered orally. [00:27:42] Speaker 03: Right. [00:27:43] Speaker 03: It's also about one a day. [00:27:44] Speaker 03: OK, yeah. [00:27:45] Speaker 01: And then two lines lower. [00:27:47] Speaker 03: Yeah. [00:27:47] Speaker 03: But also, and Dr. Ruhl's testimony shows this, example 13, by saying the fixed, I'm sorry, example 13 says, [00:27:56] Speaker 03: a fixed daily dosing regimen, a BTK inhibitor capsules, the capsules is oral. [00:28:00] Speaker 03: And the fixed daily dosing, that's once a day. [00:28:03] Speaker 03: It doesn't say twice a day, three times a day divided dose. [00:28:06] Speaker 03: So you have all of everything of claim to. [00:28:08] Speaker 01: Meaning a fixed to daily dose is once. [00:28:12] Speaker 03: I'm just going by the trial testimony. [00:28:14] Speaker 03: I don't want to claim any expertise I don't have. [00:28:16] Speaker 03: As I understand it, this is a phase two protocol. [00:28:19] Speaker 03: And I'm just going by what Dr. Ruhl testified on what the court found is a POSA reading, example 13, would understand it to disclose everything in claim two, except the identity of a Brutinib. [00:28:33] Speaker 03: And I believe the fixed daily dosing refers to the fact that you give it once. [00:28:38] Speaker 03: It doesn't say divide a dose. [00:28:39] Speaker 03: And fixed means it's not by weight. [00:28:42] Speaker 03: It's the same dose for every patient. [00:28:43] Speaker 03: By weight of patient. [00:28:44] Speaker 03: It's not by weight of patient. [00:28:45] Speaker 03: Yeah, that's what I'm saying. [00:28:46] Speaker 03: Correct. [00:28:47] Speaker 03: In fact, there are other phase one trials. [00:28:50] Speaker 03: If you look at example seven, which is the phase one trial, that's by weight. [00:28:55] Speaker 03: One of the challenges they have for the L15 is the L15 pattern actually describes altering the dose, therapeutic dose, by weight. [00:29:03] Speaker 03: So it's calling out that it's a fixed dose. [00:29:07] Speaker 03: You give 560 to everyone. [00:29:09] Speaker 03: And because it's a daily dose, it's not a divided dose. [00:29:12] Speaker 03: In the context of this example 13, it's once a day. [00:29:17] Speaker 03: So it's disclosing everything but choosing Ibrutinib. [00:29:21] Speaker 03: And both in column 4 and column 29, Ibrutinib is singled out, and there's no other call out of another BTK inhibitor for use of RRMCL. [00:29:33] Speaker 03: It's hard to imagine anything that's more of a blaze mark, if you will. [00:29:37] Speaker 03: As I respect this court's statement in Starbucks, that you review judgments, not opinions. [00:29:42] Speaker 03: I'm not trying to rewrite the court's opinion. [00:29:44] Speaker 03: The court found that a POSA would connect BTK to example 13, because in the court's words, it's preferred. [00:29:51] Speaker 03: I think what that means is, when you look at the patent, you come to the conclusion that it's telling you, if you're going to treat RMCL, pick out Ibrutinib. [00:30:01] Speaker 03: And one thing that is clear is, it's not a laundry list. [00:30:05] Speaker 03: It's in a passage that refers only to a brutinib for treating RRMCL. [00:30:09] Speaker 03: And it repeats that in column 29. [00:30:12] Speaker 03: that Ibrutinib is for use in treating RRMCL. [00:30:16] Speaker 03: That's pretty clear linkage to carry out the protocol for treating RRMCL in example 13 with Ibrutinib. [00:30:25] Speaker 03: Now, it goes beyond that, because in column five, each of the elements, each of the elements that are in example 13 in income claim two are also called out as something that Ibrutinib is suitable for. [00:30:37] Speaker 03: But the real point here is you have a protocol that tells you how to treat RRMCL. [00:30:42] Speaker 03: And then you have the single with a BTK inhibitor. [00:30:44] Speaker 03: And then you have the description that the one BTK inhibitor that's called out in the court's words for treating RMCL is a brutnit. [00:30:53] Speaker 03: A post is going to understand to connect those two and recognize that the inventors are at least in possession of carrying out example 13 with a Brutinib. [00:31:03] Speaker 03: That is, applying a Brutinib to treat RRMCL with a fixed daily dose of 560 milligrams per day orally, you know, as capsules. [00:31:11] Speaker 03: And so that is the written description here. [00:31:18] Speaker 03: There was an amendment that suggested he wanted to talk about inherent disclosure. [00:31:21] Speaker 03: I don't think he got injured there, so I'm happy to rest on our briefs unless the court has any questions about inherent anticipation in the crystalline form. [00:31:30] Speaker 02: Thank you, Your Honor. [00:31:33] Speaker 02: So my friend on the other side spent quite a bit of time mentioning that abrutinib is the only named compound associated with treating RRMCL. [00:31:45] Speaker 02: That's incorrect. [00:31:46] Speaker 02: Let's take a look at. [00:31:48] Speaker 02: column four and column five of the 090 patent, which is the beginning of the summary of invention. [00:31:56] Speaker 02: That is the focus of this discussion. [00:32:03] Speaker 02: So first of all, I want to reiterate that even plaintiffs couldn't identify all the claim elements in the summary of invention that make up [00:32:14] Speaker 02: claim to. [00:32:15] Speaker 02: And I think that speaks volumes about the difficulty that someone, Opposa, would find in identifying objectively blaze marks within the four corners of the specification to arrive and to be able to visualize claim to. [00:32:32] Speaker 02: If the appellees who have every incentive to do it couldn't do it, how could Opposa do it? [00:32:39] Speaker 02: Now, turning to column four, what column four says [00:32:44] Speaker 02: And actually, before I get to that, one of the things here is, why didn't the inventors here disclose in the specification, claim too clearly? [00:32:57] Speaker 02: How difficult would it have been for the inventors to say, in one embodiment of a method of treatment, [00:33:08] Speaker 02: is using approximately 560 milligrams of Ibrutinib per day to treat RR MCL. [00:33:13] Speaker 02: Why wasn't that done? [00:33:14] Speaker 02: And the reason why it wasn't done, this is a classic example of a failure to properly identify blaze marks. [00:33:23] Speaker 02: Because what was happening was the inventors wanted to try to disclose many different permutations in a vast genus. [00:33:33] Speaker 02: of method of treatments that it could then claim later on. [00:33:39] Speaker 02: And in fact, example 13 is a prophetic example. [00:33:44] Speaker 02: It's not a working example. [00:33:45] Speaker 02: That protocol was never done. [00:33:48] Speaker 02: And it's only referred to in connection with using the broad genus of BTK inhibitors. [00:33:55] Speaker 02: But going back to column four, what column four says is at lines [00:34:04] Speaker 02: 62 is starting with line 59. [00:34:12] Speaker 02: In certain embodiments, is the method for treating relapsed or refractory non-Hodgkin's lymphoma, not RRMCL, a genus of non-Hodgkin's lymphoma, in an individual in need thereof, comprising, administering to the individual, a therapeutically effective amount of abruptness. [00:34:32] Speaker 02: OK, so it's saying you can use a Brutinib to treat a genus of non-Hodgkin's lymphoma. [00:34:39] Speaker 02: Now let's go to the next line. [00:34:41] Speaker 02: The next line says, in some embodiments, but it doesn't tell you what those embodiments are. [00:34:48] Speaker 02: All it says is, in some embodiments, the non-Hodgkin's lymphoma is relapse or refractory diffuse large B cell lymphoma, or [00:35:02] Speaker 02: relapsed or refractory mantle cell lymphoma, or relapsed or refractory follicular lymphoma. [00:35:08] Speaker 02: All that sentence says, and by the way, abrutinib is not mentioned in that sentence. [00:35:15] Speaker 02: And all that sentence says is that in some embodiments, and we don't know what they are, and we don't know whether they pertain to using abrutinib, include those species of non-Hodgkin's lymphoma. [00:35:29] Speaker 02: So that is hardly a clear statement [00:35:32] Speaker 02: that the specification is expressly disclosing the use of abrutinib to treat RRMCL, let alone using about 560 milligrams of abrutinib to treat RRMCL. [00:35:47] Speaker 00: And then as you go- You call that RRMCL right there, right? [00:35:51] Speaker 02: I'm sorry, excuse me, Your Honor? [00:35:52] Speaker 00: It does call out RRMCL when it says relapsed or refractory menthol silica and plomo. [00:35:58] Speaker 02: It does, but it says in some embodiments [00:36:01] Speaker 02: the non-Hodgkin's lymphoma could be RRMCL. [00:36:06] Speaker 02: But it doesn't tell you what embodiments. [00:36:09] Speaker 02: It doesn't tell you that the embodiment that could be used to treat RRMCL is an embodiment that includes a Brutonib. [00:36:19] Speaker 02: Or does it include something else, like one of the other many BTK inhibitors that are identified in the specification? [00:36:30] Speaker 02: This sentence, all this sentence says, is that in some embodiments, the non-Hodgkin's lymphoma can include RRMCl. [00:36:38] Speaker 02: But it doesn't tell you that the in some embodiments that are being referred to there are embodiments in which abrutinib is used to treat RRMCl. [00:36:49] Speaker 02: And that's a defect all throughout the specification. [00:36:53] Speaker 02: And it emphasizes the classic nature of the blaze marks problem here, where [00:37:00] Speaker 02: Here, the inventors are seeking a claim for which they were not in possession based on an objective inquiry into the four corners of specification. [00:37:11] Speaker 02: Because what happened here was that the inventors were trying to claim different permutations. [00:37:17] Speaker 02: And I'll again direct the court's attention to column 3, lines 1 through 30, where [00:37:28] Speaker 02: It uses the same language. [00:37:32] Speaker 02: It says, in some embodiments, the hematological malignancy is relapsed or refractory, DLBCL, relapsed or refractory mantle cell lymphoma, relapsed or refractory follicular lymphoma. [00:37:46] Speaker 02: And then it says, in some embodiments, the BTK inhibitor forms a covalent bond. [00:37:51] Speaker 02: So the point is, if you read the summary of invention at column three, [00:37:56] Speaker 02: It tracks the language that was used in columns four and five regarding insulin embodiments. [00:38:02] Speaker 02: But instead of a Brutinib, it's talking about BTK inhibitors. [00:38:06] Speaker 00: OK. [00:38:06] Speaker 00: I think we have your argument. [00:38:08] Speaker 00: Your time has expired a few minutes ago. [00:38:11] Speaker 00: Thank you, Ron. [00:38:11] Speaker 00: Thank you very much. [00:38:12] Speaker 00: The case is submitted.