[00:00:00] Speaker 01: We have three cases on the calendar this morning. [00:00:04] Speaker 01: One from the PTAB and two from district courts. [00:00:08] Speaker 01: One of the district court cases is submitted on the briefs and will not be argued. [00:00:14] Speaker 01: And so the first case [00:00:18] Speaker 01: consolidated. [00:00:19] Speaker 01: So here is or are Carus MPI versus Foundation Medicine, 2018-86, 2020 that is, 2020-1887. [00:00:32] Speaker 01: Mr. Singer, and will you begin with the [00:00:43] Speaker 01: There will be three patents and then get to 660 with one. [00:00:51] Speaker 04: It's made please the Court, and it's really nice to be back here in person. [00:00:56] Speaker 04: I have to say, the last time I was here was arguing for the PTAB on this very case, the Friday before the world changed. [00:01:03] Speaker 01: Nice to have you here. [00:01:05] Speaker 04: In both of these appeals, the Board, and particularly Judge Lurie, beginning with the foundational patents, the Board made essentially the same error in applying the BRI standard, essentially, as it were, emphasizing the B at the expense of the R. [00:01:18] Speaker 04: to yield a claim construction in the foundational patents that swept in the prior art that was criticized in the specification and in the CIP patent that was improved upon. [00:01:30] Speaker 04: With respect to the foundational patents, the board's ultimate construction did not take into account step B2 of the claims. [00:01:41] Speaker 04: And the step B2 of the claims, each of the three patents, links the drugs [00:01:47] Speaker 04: that the system is looking at to the markers, the genetic markers. [00:01:53] Speaker 04: And those genetic markers, as was not disputed below and as the board ultimately found, are lineage independent. [00:02:01] Speaker 04: And by linking the drugs to the markers, you end up with a lineage independent list of drugs. [00:02:08] Speaker 01: Mr. Singer, I'd like to ask you [00:02:12] Speaker 01: Generally, generating a report is not very inventive. [00:02:20] Speaker 01: Comparing data is not very inventive. [00:02:23] Speaker 01: The inventiveness here would seem to be clinical. [00:02:28] Speaker 01: Notice there's one of these patents. [00:02:31] Speaker 01: There are eight inventors, which seems very strange for an invention of this sort. [00:02:36] Speaker 01: But the invention would seem to be a recognition that a drug would be effective [00:02:43] Speaker 01: against a tumor, and that that was determined by the genetics, by the marker, not by the location of the tumor. [00:02:56] Speaker 01: And that would seem to be something determined by clinicians. [00:03:00] Speaker 01: Are all of you inventors, doctors, clinicians, working in the laboratory? [00:03:05] Speaker 04: So on that, Judge Lloyd, the eight inventors is on the continuation in part. [00:03:10] Speaker 04: First, the foundational patents are [00:03:13] Speaker 04: invented by physicians. [00:03:14] Speaker 04: And the physicians, you have it correct, that what they did was realize that, or determined through experimentation and also conceived, that it was improper, improper is not the right word, it was limiting to look only at the, or to continue 50 years of the same practice of looking at the quote unquote lineage [00:03:37] Speaker 04: the site of origin of the cancer. [00:03:39] Speaker 01: So why do these claims read generating a report rather than a method of treatment? [00:03:46] Speaker 01: If they discovered that a certain drug is beneficial against a certain tumor unexpectedly, I mean, that's really patentable. [00:03:55] Speaker 04: So the approach wasn't for a specific drug, Your Honor. [00:04:00] Speaker 04: It's for a treatment of cancer. [00:04:03] Speaker 04: Generating the report, if you want, it's not reflected in the record. [00:04:07] Speaker 04: That was a 101 issue in the prosecution. [00:04:10] Speaker 01: Not surprising. [00:04:12] Speaker 04: That's where that came from. [00:04:13] Speaker 04: But with respect to the inventiveness aspect, you have to remember the claims are directed to any patient with any type of cancer. [00:04:22] Speaker 04: And so what the claims are regarding is looking at that we don't really care anymore. [00:04:27] Speaker 04: We the inventors, Drs. [00:04:29] Speaker 04: Von Hoff and Dr. Penney, we don't really care anymore what type of cancer that patient has, where the origin is. [00:04:35] Speaker 04: You just give me the tumor. [00:04:37] Speaker 04: I will look at the markers. [00:04:39] Speaker 04: We will run the markers. [00:04:40] Speaker 04: We will link those markers to drugs. [00:04:43] Speaker 04: Those drugs may be on-label, they may be off-label, but we will link those drugs to the markers, and from there we will select for the patient. [00:04:51] Speaker 04: And that was an absolute paradigm change from what was done priorly as [00:04:56] Speaker 04: the director of the National Cancer Institute. [00:04:58] Speaker 02: Isn't that the discovery, though, linking the therapeutic drugs to markers? [00:05:03] Speaker 02: I'm sorry. [00:05:03] Speaker 02: Isn't that the actual inventive moment, the linkage of the therapeutic drugs to the markers? [00:05:12] Speaker 04: It is in respect to without the high bound, if you will, prior paradigm of using the lineage of the cancer. [00:05:23] Speaker 02: But wasn't it known to already optimize treatments by looking at the molecular profile of a patient and based on the genotype considering various therapeutic agents? [00:05:38] Speaker 04: Only within the lineage. [00:05:39] Speaker 04: So that's the prior art. [00:05:40] Speaker 04: So the prior art is [00:05:42] Speaker 04: OK, so that was known. [00:05:44] Speaker 02: But it was known in combination with considering cancer lineage. [00:05:47] Speaker 02: And then this claim doesn't say anything about don't consider cancer lineage. [00:05:53] Speaker 04: It absolutely does, in effect of its language. [00:05:56] Speaker 04: It doesn't use the words that the board was looking for. [00:05:59] Speaker 04: The board was looking for some proxy of that. [00:06:02] Speaker 04: But they didn't apply the actual language as written, Your Honor. [00:06:06] Speaker 00: Putting aside whether you can [00:06:08] Speaker 00: put a limitation into this otherwise very broad claim language. [00:06:11] Speaker 00: And we'll get to that in a second. [00:06:13] Speaker 00: What do you do about the whole list of things in the red brief where they explain that the septum and herbotoxin, all of those other products, did exactly what you're saying that prior art didn't know how to do? [00:06:28] Speaker 04: Your Honor, those were also looking within the lineage. [00:06:31] Speaker 04: If you look at those articles, you'll see. [00:06:33] Speaker 00: No, each one of them says, but not just for that particular cancer. [00:06:36] Speaker 00: They could also apply to other cancers. [00:06:38] Speaker 04: It applies to other cancers in the lineage. [00:06:40] Speaker 04: So if you look at those prior articles, Your Honor, which were not, I'll make the point, they're not part of a ground here. [00:06:46] Speaker 04: But if you look at them, you'll see they're sorted by disease. [00:06:49] Speaker 04: And so what they're still looking at, if this were lineage independent, they wouldn't be looking at the disease. [00:06:55] Speaker 04: They wouldn't care. [00:06:56] Speaker 04: about the type of cancer that the patient had. [00:06:59] Speaker 04: They would simply be looking at the molecular markers. [00:07:01] Speaker 00: Well, the mere fact that they might have started by realizing it works well for breast cancer doesn't mean that they didn't also appreciate before the priority date that it worked well for other cancers. [00:07:10] Speaker 04: Well, I guess I disagree with that, Your Honor. [00:07:14] Speaker 04: What the articles are talking about in terms of the other uses of these drugs is, in fact, in the lineage. [00:07:21] Speaker 04: So if we will investigate Herceptin in another cancer, and maybe it'll work in another cancer in that lineage, not we will investigate Herceptin based on the HER2 marker in any cancer, in all cancers. [00:07:38] Speaker 04: I mean, I would ask the court to think about, in terms of paradigm shifts, it's a significant and important shift here, where the prior art looked at lineage, and yes, looked at lineage with markers, and then shifted from, we don't care about the lineage at all. [00:07:59] Speaker 04: We're going to just simply look at the markers, [00:08:02] Speaker 04: And we're going to test it. [00:08:03] Speaker 04: We don't care if the cancer comes from breast, pancreas, et cetera. [00:08:06] Speaker 04: We only want that information. [00:08:08] Speaker 04: And then we're going to go and find whether or not the markers match up to the drugs. [00:08:15] Speaker 04: And that's the invention. [00:08:17] Speaker 04: That was the conception here. [00:08:18] Speaker 01: But you're concerned with whether lineage independence is in the claims. [00:08:26] Speaker 01: the claims of a parent application and delete it, right? [00:08:31] Speaker 04: There was a, I think, yes. [00:08:32] Speaker 04: The phrase, I think, was single disease restricted that was deleted. [00:08:38] Speaker 04: And that's neither. [00:08:41] Speaker 01: And so why doesn't that carry through here? [00:08:44] Speaker 04: Because again, the board. [00:08:46] Speaker 01: Indicating what the inventors thought all that language meant. [00:08:49] Speaker 04: Well, the language is in the specification. [00:08:52] Speaker 04: And the court's authorities say we have to look at the invention of specification. [00:08:56] Speaker 04: But if you simply apply the language in the claims. [00:08:58] Speaker 00: You can't ignore the claims. [00:08:59] Speaker 00: You can't ignore the claims. [00:09:00] Speaker 00: And you actually amended the language in the claims to take out what would have made it clear, or at least more clear. [00:09:07] Speaker 04: And I'm not asking at all to ignore the claims. [00:09:09] Speaker 04: And if you look, it's right in our brief. [00:09:11] Speaker 04: If you follow the language of the claims, [00:09:14] Speaker 04: whether you want to put the word lineage independent in there or not. [00:09:17] Speaker 04: If you follow the language of the claims, the drugs are linked to the markers. [00:09:22] Speaker 04: The markers are lineage independent. [00:09:25] Speaker 04: Therefore, you get a lineage independent list of drugs. [00:09:27] Speaker 04: Just find the words of the claim. [00:09:30] Speaker 04: And the board did not do that, manifestly did not do that. [00:09:34] Speaker 04: At page A27, for example, of the 350. [00:09:37] Speaker 00: What language in the claim itself? [00:09:40] Speaker 00: So start with the claim. [00:09:41] Speaker 00: What language in the claim do you say specifically makes it clear that lineage independence is within the claim? [00:09:48] Speaker 04: Let me get the precise language. [00:09:49] Speaker 04: So it's step B2, Your Honor. [00:09:54] Speaker 04: In each of the patents, I'll just go to the 193 patents. [00:09:57] Speaker 04: I have it handy. [00:09:59] Speaker 04: Appendix 239. [00:10:01] Speaker 04: Right? [00:10:02] Speaker 04: So step B2 is at least one computer day-to-day is comprising. [00:10:05] Speaker 04: And then as you go to B2, a listing of available therapeutic agents for each of the plurality of the molecular targets. [00:10:13] Speaker 04: Right? [00:10:14] Speaker 04: And those molecular targets are lineage independent. [00:10:17] Speaker 04: They're not associated with any particular type of cancer or one cancer. [00:10:22] Speaker 04: And so therefore, you get a list by necessity. [00:10:25] Speaker 04: that is lineage independent. [00:10:27] Speaker 04: And that's what the board didn't do. [00:10:29] Speaker 04: They didn't take that step. [00:10:30] Speaker 04: They were looking for language. [00:10:32] Speaker 04: I understand that. [00:10:33] Speaker 04: And we deleted language in the file history. [00:10:35] Speaker 04: And gosh, I wish we had. [00:10:36] Speaker 04: It would have been a lot clearer, I suppose. [00:10:38] Speaker 04: But at the end of the day, the job of the courts is to apply the language as written. [00:10:43] Speaker 04: And that's all we're asking for. [00:10:45] Speaker 04: And when the board got to step B2, it didn't apply it. [00:10:48] Speaker 04: If you look at their opinion, the board went right to the result. [00:10:52] Speaker 02: I guess what I'm wondering is, [00:10:54] Speaker 02: Because this is an open-ended comprising claim, why can't there be a consideration of cancer lineage of a patient also considered and be within the scope of this open-ended comprising claim? [00:11:14] Speaker 04: Because the drugs, Your Honor? [00:11:17] Speaker 04: have to be tied to this lineage-independent list of markers. [00:11:21] Speaker 04: You could do that too, but you still have to do that first thing. [00:11:25] Speaker 04: So if you were appending lineage dependence onto it, you'd still have to do the lineage-independent analysis to generate the recommended therapy. [00:11:36] Speaker 04: So the fact that it's comprising shouldn't change the analysis. [00:11:38] Speaker 00: But the list is not limiting because you have the comprising language. [00:11:44] Speaker 04: The list is required, though, to be for each of the molecular targets. [00:11:49] Speaker 04: Those molecular targets right there, at a minimum, have to have the seven listed in the claims. [00:11:55] Speaker 04: And those seven, as the board found and as wasn't disputed below, are lineage independent. [00:12:01] Speaker 04: So if you link drugs to a lineage independent list, you get lineage independent drugs. [00:12:07] Speaker 00: So you're saying that even if you put something, an input that's lineage independent, you could never have an output that's not? [00:12:18] Speaker 04: Let me see if I understand your question. [00:12:20] Speaker 04: If I use the system of the claim, could I get an output that was lineage dependent? [00:12:25] Speaker 04: No. [00:12:26] Speaker 04: You might get a result, Your Honor, that's unlabeled. [00:12:31] Speaker 04: Right. [00:12:32] Speaker 04: So you might get a result that's on label, but you wouldn't be selecting the drugs in an on-label, off-label paradigm. [00:12:39] Speaker 04: You'd be selecting the drug. [00:12:41] Speaker 00: Your answer is actually yes. [00:12:42] Speaker 04: Right. [00:12:43] Speaker 04: But. [00:12:44] Speaker 04: No, I don't think so. [00:12:46] Speaker 04: I think to conflate the result of the claim. [00:12:51] Speaker 02: Would you say an on-label drug is lineage dependent? [00:12:55] Speaker 04: It depends how you got there, your honor. [00:12:58] Speaker 04: If you end up, and I think that was in the Bisgrove study, if you look at the Bisgrove study, looking at things in a lineage-independent way, choosing the drugs, I choose to treat this tumor based on the markers, and I use markers that are lineage-independent, I might end up treating that tumor [00:13:20] Speaker 04: Let's just make it easy. [00:13:21] Speaker 04: Let's make it breast cancer. [00:13:23] Speaker 04: I may end up treating that tumor. [00:13:25] Speaker 04: The markers may say, use a breast cancer drug. [00:13:28] Speaker 04: The markers may say something as well. [00:13:29] Speaker 04: But that's very different. [00:13:30] Speaker 04: Looking at the output is very different than looking at the inputs that go in. [00:13:35] Speaker 00: And this is all about the inputs that go in. [00:13:37] Speaker 00: Did FASGRO even use the claimed system? [00:13:39] Speaker 04: Fisgrove used the, that was a point of dispute below, the board found that Fisgrove didn't use the particular computer that it hadn't demonstrated, that particular computer, but it absolutely used the lineage independent selection of drugs by looking at the tumors. [00:13:55] Speaker 00: Well, the particular computer is a particular limitation, right? [00:13:59] Speaker 04: It is, but the court's authorities, in terms of secondary and issue, regard it about the inventive aspect of the invention. [00:14:06] Speaker 04: And the specification makes clear that the computer aspects are not the inventive aspect here. [00:14:11] Speaker 04: It's what we talked about at the beginning, the selection of drugs. [00:14:14] Speaker 01: Now, the claim must include lineage-independent situations. [00:14:22] Speaker 01: But you wanted to preclude lineage-dependent. [00:14:27] Speaker 01: You want it to be lineage independent only. [00:14:34] Speaker 01: Because otherwise we're in trouble with a prior op. [00:14:36] Speaker 04: Sure, sure. [00:14:38] Speaker 04: I think by operation of the words and the claim, it is lineage independent. [00:14:43] Speaker 04: If I have a lineage independent set of markers, [00:14:47] Speaker 04: And then I utilize and link the drugs to those markers so that I get a lineage-independent set of drugs. [00:14:53] Speaker 04: And that's step B2 in each of the patents. [00:14:56] Speaker 04: I have a lineage-independent system. [00:14:57] Speaker 00: But the board said, yes, it could be lineage-independent, but it also could be lineage-dependent. [00:15:03] Speaker 04: And that's the error that the board made. [00:15:05] Speaker 04: The board, if you look at, Your Honor, at page, for example, A27 of the 350, they said that they looked at the output. [00:15:15] Speaker 04: It doesn't require the identification of all available therapeutic agents, including off label. [00:15:23] Speaker 04: So the board equated the result. [00:15:26] Speaker 04: I get to the result of an off label drug as lineage independent. [00:15:32] Speaker 01: Those are two different things. [00:15:34] Speaker 01: Why don't you get to 660? [00:15:36] Speaker 04: OK, let me move on to the 660. [00:15:38] Speaker 01: And then we'll want to get to Claim 12. [00:15:40] Speaker 04: Yes. [00:15:41] Speaker 04: So with respect to the 660, I think I described at the beginning that the error was a similar nature in emphasizing the broadest aspect and not the more reasonable aspect. [00:15:56] Speaker 04: And again, the board was fixated on finding particular words in the claim and didn't focus on the claim language that was actually there. [00:16:05] Speaker 04: And with respect to the point you're smiling, you're going to ask me a question. [00:16:08] Speaker 04: That's fine. [00:16:09] Speaker 01: The board focused on particular words but didn't look to the language. [00:16:13] Speaker 04: The absence of language. [00:16:15] Speaker 04: That's a little bit circular. [00:16:15] Speaker 04: They focused on the absence of words, as opposed to the language that was actually there. [00:16:20] Speaker 00: Why is the language likely lack of benefit limitation in Claim 12 even meaningful if you say it's already in Claim 1? [00:16:28] Speaker 04: Because Claim 12 is about the report, Your Honor. [00:16:32] Speaker 04: If you look at the language of Claim 12, it's about generating a report. [00:16:36] Speaker 04: Both of them are about generating a report. [00:16:38] Speaker 04: And the report of Claim 12 is different than the report of Claim 1. [00:16:41] Speaker 04: The report of Claim 1 only requires you report drugs that have likely benefit, if there are any. [00:16:47] Speaker 04: The report of claim 12 requires the additional reporting of a contraindication marker and the contraindicated drug. [00:16:56] Speaker 04: So there's just two different reports. [00:16:57] Speaker 04: That's all. [00:16:58] Speaker 04: So that's why it matters. [00:17:00] Speaker 00: But you argue that claim one actually has a contraindication limitation. [00:17:04] Speaker 04: It has a requirement that you look at the information that is in the claim. [00:17:10] Speaker 04: So the claim has multiple markers in the claim that only served a purpose at the time of the invention for contraindication, BRAF and PIC3CA. [00:17:19] Speaker 04: And the board's construction to construe likely benefit [00:17:22] Speaker 04: to encompass identifying drugs that wouldn't be of likely benefit because they were contraindicated is erroneous. [00:17:30] Speaker 04: That's the phraseology the board didn't apply with respect to claim one. [00:17:37] Speaker 02: The board questioned whether a mutational analysis for some of these markers is absolutely required by this claim. [00:17:43] Speaker 02: because this claim, it just very broadly says compare molecular profile test values with a corresponding reference value. [00:17:53] Speaker 02: And the way you would like us to read the claim is, OK, for some of these listed markers, you do one kind of analysis, a mutational analysis. [00:18:03] Speaker 02: For other markers recited in this claim, you're going to do a completely different kind of analysis. [00:18:09] Speaker 02: Is that fair to say? [00:18:11] Speaker 04: No, I don't think that's what we're asking. [00:18:12] Speaker 04: We're asking that the claims be construed at the time of the invention. [00:18:16] Speaker 04: and the understanding of the person of skill in the art. [00:18:18] Speaker 04: And the person of skill in the art. [00:18:19] Speaker 02: But the comparison test for some of these markers is going to be of a different nature than the comparison test being done for other markers. [00:18:28] Speaker 04: The comparison test is going to embrace the mutational analysis for BRAF, for sure. [00:18:32] Speaker 02: Well, you want, for a couple of these markers, the comparison to be a mutational analysis, right? [00:18:40] Speaker 02: I would say it would include the BRAF. [00:18:41] Speaker 02: For BRAF, it would include mutational analysis. [00:18:43] Speaker 02: All right, and then for other markers, [00:18:45] Speaker 02: You wouldn't be doing mutation analysis. [00:18:47] Speaker 04: No, you'd do a mutational analysis if that was available at the time of the invention. [00:18:51] Speaker 04: We're talking about in 2000, at the time of the invention. [00:18:54] Speaker 02: But I guess the relevant information you want to extract from these comparisons for these different markers is one is you're looking at different levels of biological activity. [00:19:07] Speaker 02: And another one, you're looking for a mutation. [00:19:09] Speaker 02: And then if there is a mutation, then that would suggest some contraindication. [00:19:15] Speaker 02: For BREP, I agree with you on that. [00:19:16] Speaker 02: So then that's why I'm saying you're asking us to understand this comparison step to be undertaking two different kinds of comparisons for these different markers that you've listed. [00:19:31] Speaker 04: I guess I don't agree, Judge Chen. [00:19:33] Speaker 04: I think that the comparison step is asking to compare... We're talking about the testing of the markers. [00:19:40] Speaker 04: BRAF only had utility at the time of the invention to communicate contraindication. [00:19:45] Speaker 04: And the comparison step simply is... [00:19:48] Speaker 04: Is the marker, excuse me, is the drug indicated by, if you will, an overexpression or underexpression of the marker or mutation or not lacking mutation by the marker? [00:19:59] Speaker 04: Is the drug indicated? [00:20:00] Speaker 04: And then is it contraindicated by a different marker? [00:20:03] Speaker 04: I.e. [00:20:03] Speaker 04: does it have likely benefit altogether? [00:20:05] Speaker 04: I see that in my rebuttal time. [00:20:08] Speaker 04: I'm happy to keep answering questions. [00:20:12] Speaker 01: We will save it for you. [00:20:14] Speaker 01: OK, thank you. [00:20:14] Speaker 01: Thank you so much. [00:20:32] Speaker 00: Would you mind going backwards for just a second in terms of the way your friend on the other side went? [00:20:37] Speaker 00: And I want you to address that last point with respect to Claim 12. [00:20:42] Speaker 00: Which last point specifically? [00:20:44] Speaker 00: About the contraindications. [00:20:46] Speaker 03: Yes, Your Honor. [00:20:47] Speaker 03: So on the BRAF point specifically, I agree with His Honor about the different testing, but there's even a shorter route to the same result at A17, 22, 14, to 20. [00:21:00] Speaker 03: And this is throughout the patent, but I'm going to pick one quote. [00:21:03] Speaker 03: The patentee said, quote, one may find additional targets or molecular findings that can be exploited, end quote. [00:21:11] Speaker 03: And the board picked up on this and the similar quotes and said, and this is at A18, the 660 patent contemplates that the therapeutic agent database would be continuously updated as new agents and new associations are discovered, end quote. [00:21:24] Speaker 03: So they suggest to us that we must know that you are doing contraindication, as they put it. [00:21:30] Speaker 03: We would say likely lack of benefit. [00:21:33] Speaker 03: interrogation because of the presence of BRAF in the claim, when in the very patent they say, we may find new indications. [00:21:42] Speaker 03: We may find new likely benefits. [00:21:45] Speaker 03: Don't hold us to what exists now. [00:21:48] Speaker 03: We're going to find in the future that BRAF may be helpful, not just not helpful. [00:21:52] Speaker 03: And so this was important to the board. [00:21:56] Speaker 03: Correctly, if you're going to say in your patent, don't hold us to the state of the art now, well then you're not held to the state of the art for all purposes. [00:22:04] Speaker 03: So I agree with his honor, but I think it's kind of more fundamental than that. [00:22:08] Speaker 03: You can't draw the assumption that, you know, kind of prune or [00:22:13] Speaker 03: died deep to say, oh, obviously they meant looking for likely lack of benefit. [00:22:17] Speaker 03: When they've told us in the patent, we're going to keep looking for benefits for all these different markers. [00:22:23] Speaker 03: So I think that's maybe the simpler route to the same point, Your Honor. [00:22:28] Speaker 03: Would Your Honor prefer I start with the 1887 or the 1886 appeal? [00:22:32] Speaker 01: 1887, fine. [00:22:35] Speaker 03: Your Honor, and Judge O'Malley, you asked a very important question, and I'm going to use Herceptin as the example. [00:22:43] Speaker 03: In 1998, Herceptin was approved for breast cancer based on HER2 overexpression. [00:22:50] Speaker 03: That was the insight. [00:22:52] Speaker 03: And at A6396 and elsewhere in the record, we see scientists, physicians saying, aha, [00:22:59] Speaker 03: if overexpression of HER2 is important in this context, it might be important in other contexts. [00:23:04] Speaker 03: And so we see investigations, for example, of bladder and ovarian cancer. [00:23:09] Speaker 03: Now, what counsel just did, and this has been a little bit of a frustration for us throughout the litigation, throughout the PTAP proceeding, the meaning of lineage independent seems to change from brief to brief, sometimes even from page to page. [00:23:22] Speaker 03: And even today, we heard a different meaning. [00:23:24] Speaker 03: Because what counsel suggested is that that bladder or ovarian cancer that was reached because of not the breast cancer link, but the HER2 link at the genotyping link, that that is now, and I wrote this down, in that lineage. [00:23:42] Speaker 03: How is bladder and ovarian cancer in the lineage of breast cancer? [00:23:46] Speaker 03: I think he's saying they're all can be female-related things, I guess. [00:23:51] Speaker 03: I hope that wasn't what he was suggesting. [00:23:53] Speaker 03: I think it's just that this is an amorphous concept that if scientists knew it well enough, then we're going to kind of push it to the side and try to exclude it as a matter of prior. [00:24:04] Speaker 03: And if they didn't know it well enough, well, we're going to say we get credit for it. [00:24:10] Speaker 03: But fundamentally, Your Honor's point was absolutely right, and both of Your Honor's points about the underlying insight that we should be looking to the genotyping, the genetic markers, not necessarily to the cancer, the one original cancer. [00:24:26] Speaker 03: That was well known, and we laid out five examples with Herceptin and Herbatux and Iressa and Gleevec. [00:24:33] Speaker 03: And then more generally, Dr. Spellman talked about [00:24:36] Speaker 03: Let me get this right, the Sawyer 2004 article that went into this in great detail, why you want to look at the markers. [00:24:43] Speaker 01: But why isn't there part of the prior art cited here, and maybe I've missed it, showing the activity of cancer agents against a particular genotype, aside from location of the tumor? [00:25:03] Speaker 01: I mean, if that was old, not very old, but an effective prior art discovered by others than these inventors, why isn't that the issue here? [00:25:18] Speaker 03: Your Honor, we have Lew explicitly, and I hate to quote long quotes in court, but I think it's an important one, to predict this is from A6878. [00:25:28] Speaker 03: So this is the lead prior art reference. [00:25:30] Speaker 03: The system of Lou, which otherwise is identical, the same steps, the same computer, the same database, the same interrogation, the system can be used to predict or identify the optimum drug for treating cancers other than breast cancer and can be used to identify optimum drug for treating virtually any disease for which there exists an established correlation between a patient genotype and the efficacy and toxicity of each group of drugs developed to treat the general condition. [00:25:59] Speaker 01: And what was the date of that? [00:26:01] Speaker 03: Lou was three years before the critical date, I believe. [00:26:05] Speaker 03: And critically, that's the magic language there, the patient genotype, not the patient's cancer type, the genotype. [00:26:13] Speaker 03: And then of course we get to Illumina, which is nothing but an assay of all of the relevant genotypes at the time, I believe 512, that number's off the top of my head. [00:26:23] Speaker 03: And so all the board did is it said you take Lew and then pre-critical date, you take the assay that is most contemporary at the time, [00:26:32] Speaker 03: And you cover every single one of the markers in every single one of the claims. [00:26:38] Speaker 03: So it's whether or not you agree with the board's decision to eliminate cancer lineage independence or rather not to incorporate, I don't want to say eliminate, to not incorporate cancer lineage independence, even if you understand what that term means. [00:26:50] Speaker 03: And just to suggest the mischief of the term or the concept or the amorphousness or the fuzziness or whatever word you want to use, [00:26:59] Speaker 03: If you look at column 14A237, in back-to-back sentences, there is a different definition of what this concept is supposed to mean. [00:27:09] Speaker 03: On the one hand, it says, it's not previously associated with a specific disease. [00:27:14] Speaker 03: And then immediately above the table, it says, based on a cancer that has a known target, that has an associated known drug. [00:27:21] Speaker 03: Isn't that the definition of something being previously associated with the disease? [00:27:25] Speaker 03: So again, I'm not sure where the line is drawn. [00:27:28] Speaker 03: With that, if there are no further questions, I'd like to move on to the 1886 appeal, if I may, Your Honor. [00:27:38] Speaker 03: I'd like to point out that, and particularly on claim 12, we're not exactly sure what the board thought likely lack of benefit meant. [00:27:52] Speaker 03: But we are sure why the board rejected the invalidity challenge to claim 12. [00:27:58] Speaker 03: And this is from May 21. [00:28:00] Speaker 03: Quote, the dispute over claim 12 focuses on whether the requirement that the report indicate a, quote, likely lack of benefit, end quote, is satisfied with the prior arts disclosure indicating only that the value for markers fall within a normal range. [00:28:15] Speaker 03: That's the dispute. [00:28:16] Speaker 03: That is the sum total of the dispute. [00:28:18] Speaker 03: What the board did, I think, and again, it's a little bit ambiguous. [00:28:22] Speaker 03: is that we're going to equate likely lack of benefit with contraindication, and then we're going to find that contraindication, which isn't in the claim, so we're going to construe a construction, we're going to find that contraindication excludes normal readings and requires negative predictive biomarkers. [00:28:44] Speaker 03: Now, let me use a simple analogy to explain why we disagree with this respectfully. [00:28:50] Speaker 03: And this is an oversimplification, but I take Advil far too frequently, given how much damage I've done to my knees through the years. [00:28:58] Speaker 03: Advil works by reducing inflammation. [00:29:01] Speaker 03: And again, it may have others, but let's simplify it by analogy. [00:29:04] Speaker 03: Advil works by reducing inflammation. [00:29:07] Speaker 03: If I run a report that says my inflammation levels are normal, I now know that Advil is not likely to help that pain in my knee, that there's another source [00:29:19] Speaker 03: There's another problem. [00:29:21] Speaker 03: There needs to be another solution. [00:29:23] Speaker 03: So depending on the context, it is perfectly reasonable to say that a normal reading gives me important information. [00:29:31] Speaker 03: And that's exactly the case with Herceptin and HER2. [00:29:35] Speaker 03: Herceptin works if the reason the patient has breast cancer is because of an overexpression of HER2. [00:29:44] Speaker 02: Now, we understand your point. [00:29:46] Speaker 02: Yes, Your Honor. [00:29:47] Speaker 02: Likely, lack of benefit. [00:29:49] Speaker 02: in the most ordinary sense, could include normal readings. [00:29:53] Speaker 02: Yes, Your Honor. [00:29:54] Speaker 02: But the board appears to be understanding this term, likely lack of benefit, in the context of this patent, in the context of this disclosure, and the fact that claim 12 talks about identifying yet another marker, identifying yet another agent. [00:30:12] Speaker 02: And in the context of this patent, it talks about repeatedly how you would do that when you [00:30:19] Speaker 02: discover some kind of contraindication. [00:30:21] Speaker 02: And then when it says contraindication, what it means by that is determining that a given therapeutic agent that you would expect to work actually wouldn't work, because perhaps there's some kind of resistance to it based on a mutational analysis. [00:30:40] Speaker 02: And so therefore, in the context of this patent, [00:30:42] Speaker 02: likely lack of a benefit means something particular and not so general. [00:30:48] Speaker 02: So that's the hurdle you've got to get over. [00:30:50] Speaker 02: I mean, your Advil hypothetical, I understand it, but that hypothetical is divorced in the context of this patent. [00:30:59] Speaker 02: We have to read this claim inside the context of this integrated legal instrument. [00:31:05] Speaker 03: Understood, Your Honor. [00:31:07] Speaker 03: But here's where I would push back and say, let's start from first principles. [00:31:11] Speaker 03: The term says likely lack of benefit. [00:31:14] Speaker 03: And I think we all know what that means in a vacuum. [00:31:17] Speaker 03: It means it's less likely to work or unlikely to work, whatever particular modifier you want to use. [00:31:24] Speaker 03: All right. [00:31:25] Speaker 03: Is there anything in the claim language itself, any surrounding language, that narrows that, that would exclude a normal indication as evidence that something is unlikely to work? [00:31:37] Speaker 03: I don't think the board or CARES has pointed to any claim language that would accomplish that result. [00:31:44] Speaker 03: That would result in that. [00:31:45] Speaker 00: You begin with the plain language and sort of the [00:31:50] Speaker 00: dictionary definition of contraindication, which means that it's not just not going to benefit, but it's actually going to hurt. [00:31:56] Speaker 00: Indeed. [00:31:57] Speaker 03: And it's interesting, Your Honor, because, of course, contraindication is not in the claim language. [00:32:01] Speaker 03: And it's odd that the P tab kept swapping in that word. [00:32:06] Speaker 03: I mean, intuitively, I think contraindication means something different than likely lack of benefit. [00:32:11] Speaker 03: I think it means that it's affirmatively going to hurt you. [00:32:13] Speaker 03: That's my intuition. [00:32:15] Speaker 03: I'm not sure that's the board's intuition, but that's mine. [00:32:18] Speaker 03: But I think there is no reason to do this kind of two-step that the board does, likely lack of benefit, contraindication. [00:32:25] Speaker 03: OK, why does contraindication mean? [00:32:28] Speaker 03: When contraindication doesn't appear in the claim. [00:32:32] Speaker 03: Contraindication isn't something we're being asked to interpret. [00:32:35] Speaker 03: So let's go back to likely lack of benefit and say, what does the spec, what do the claims, what does the wrapper tell us about likely lack of benefit? [00:32:44] Speaker 03: And I don't think we see any evidence in either of any of those three sources, the three things that we all grew up looking at. [00:32:52] Speaker 03: That says likely lack of benefit shouldn't mean anything different. [00:32:57] Speaker 03: And I'd like to, if I could go to the actual reference and look at figure 3B. [00:33:08] Speaker 03: And this is at 2777. [00:33:14] Speaker 02: This is the figure that's reporting normal values? [00:33:17] Speaker 03: Right. [00:33:17] Speaker 03: Well, and not just. [00:33:18] Speaker 03: I want to put this in the language of the claim. [00:33:27] Speaker 03: So this is what the patentee is saying. [00:33:28] Speaker 03: This is an example of my invention. [00:33:31] Speaker 03: If I have GI cancer, gastric cancer, and this report is wrong, this report tells me that [00:33:42] Speaker 03: Herceptin is unlikely to work, but Gleevec is likely to work. [00:33:48] Speaker 03: Exactly what counsel just told us, claim 12 requires the claimed. [00:33:52] Speaker 03: And let me just walk you through it. [00:33:54] Speaker 03: C-Kit we see as positive specific. [00:33:56] Speaker 03: So I think they would acknowledge that this indicates a likely benefit, that that's the prototypical [00:34:04] Speaker 03: case of their likely benefit as called for by the claims. [00:34:09] Speaker 03: There's a positive, there's an overexpression, and so Gleevec would work there. [00:34:17] Speaker 03: We see up above, Herceptin, which we now know also treats gastric cancer through the same mechanism it treats breast cancer, if there's an overexpression of HER2. [00:34:27] Speaker 03: We know that Herceptin would be a bad idea, or at least not likely to work idea, for gastric cancer based on this same report. [00:34:35] Speaker 03: And just to gild the lily here, not to make too much of it, but we see just below C-Kit one of the other markers that's in the claims, EGFR, which is also negative. [00:34:46] Speaker 03: So what we're being told by this report is there are two normal readings that tell us don't use Herceptin and don't use Herbatux, but do use Gleevec. [00:35:01] Speaker 03: in the prior item, in one page, all in one place. [00:35:06] Speaker 03: No combination necessary. [00:35:07] Speaker 02: Based on normal values, right? [00:35:10] Speaker 03: Well, right. [00:35:11] Speaker 03: Exactly. [00:35:13] Speaker 02: And this patent, I know it says contraindication, and I know there's a general understanding of what that means. [00:35:22] Speaker 02: The way this patent uses the term contraindicate is a shorthand, basically, to mean indication of a resistance to a particular drug. [00:35:34] Speaker 02: So if that's how they're using it and that's how they are describing what a lack of a benefit or a lack of clinical benefit means in the context of this patent, [00:35:49] Speaker 02: And why can't we understand the claim terminology of likely lack of a benefit to mean basically a resistance to a particular therapeutic drug? [00:36:00] Speaker 03: That's an excellent point, Your Honor. [00:36:02] Speaker 03: If the term contraindicate had appeared in the claim, then I think we could look to the specification and we could see that the gloss or the nuance or the connotation, whatever you want to call it, [00:36:12] Speaker 03: contraindication, not just that something doesn't work because there's no inflammation, but because it doesn't work because there's actually some conflict, as it were. [00:36:21] Speaker 03: Again, that's not a technical medical term, but I think Your Honor understands my point. [00:36:26] Speaker 03: If contraindication were the term in the claim [00:36:31] Speaker 03: We might have a closer fight, and we'd have more of a textual analysis. [00:36:35] Speaker 03: And then we'd be pointing you to suggestions, like in column 51, where contraindicate seems to be used as a verb, not a noun. [00:36:43] Speaker 03: And we could have gotten into a much different discussion. [00:36:46] Speaker 03: But they didn't choose to use the word contraindicate in the claim. [00:36:49] Speaker 03: They chose to use the phrase less likely to benefit. [00:36:55] Speaker 03: And that's a phrase that we all understand. [00:36:58] Speaker 03: And there's no suggestion. [00:36:59] Speaker 03: There's no IE. [00:37:01] Speaker 03: There's no by that we mean anywhere that should change that common meaning. [00:37:09] Speaker 02: What do you think figure 40B is illustrating and describing? [00:37:14] Speaker 02: Figure 40B, the one that's identifying some therapeutic agents and then indicates at the top of the column lack of clinical benefit. [00:37:25] Speaker 03: And importantly about Figure 40B, of course, Your Honor, none of the identified markers are in Figure 40B in that context. [00:37:40] Speaker 03: Your Honor, if I could find it. [00:37:42] Speaker 03: I'm sorry, there's too many pages here. [00:37:55] Speaker 01: You're having a common problem. [00:37:58] Speaker 03: Yes, Your Honor. [00:38:02] Speaker 03: So, figure 40B. [00:38:08] Speaker 03: is one of the set of reports that are exemplars from the patent. [00:38:15] Speaker 03: If we look at 40B, there is not a single, and we see the heading, lack of clinical benefit, which is still a third term, but close to likely lack of benefit. [00:38:28] Speaker 03: There is not a single reference to any of the markers at issue here. [00:38:33] Speaker 03: So there's nothing to be gleaned one way or the other. [00:38:37] Speaker 02: Second thing I'd say about figure 40B is of course... Sorry, before you go on, you're saying the biomarker column, those identified markers are different from the decided markers in the claim? [00:38:47] Speaker 02: Yes, Your Honor. [00:38:48] Speaker 03: Okay. [00:38:51] Speaker 03: I believe there's one overlap in the previous with clinical benefit, the C-Kit. [00:38:55] Speaker 03: 40A? [00:38:56] Speaker 03: 40A. [00:38:57] Speaker 03: I believe C-Kit is the only overlap. [00:39:00] Speaker 03: and counsel will correct me if I'm wrong, but I believe that none of those starting with MGMT down in figure 40B, I believe none of those are in the claim. [00:39:08] Speaker 03: The other thing I'd note is many of these reports are not called for in the claims. [00:39:16] Speaker 03: So the reference is exemplary. [00:39:19] Speaker 03: They're not called for in the claims. [00:39:20] Speaker 03: But most fundamentally, the specific examples they give show that there is an increase in expression, an overexpression. [00:39:32] Speaker 03: But you know, Your Honor, there's no dispute that an underexpression [00:39:35] Speaker 03: The patent office wouldn't suggest that an under-expression can satisfy the claims, and there's no under-expression in this either. [00:39:43] Speaker 03: So we're at risk of over-reading, to use the phrase again, over-reading the import of figure 40B if we say anything can be made from the fact that all of the exemplars are indicating likely lack of benefit because of over-expression. [00:39:59] Speaker 03: Did my answer not satisfy your honor? [00:40:03] Speaker 03: So your honor, I think what you're suggesting is that there's something that may be read, or at least questioning whether something could be read in the fact that all of the exemplars in 40B have likely lack of benefit. [00:40:12] Speaker 03: The result is an overexpression of the given gene or protein, whichever the case may be. [00:40:18] Speaker 03: Is that understanding roughly what you're asking? [00:40:21] Speaker 02: Well, yeah. [00:40:22] Speaker 02: I'm trying to figure out if 40B is [00:40:27] Speaker 02: enough to suggest lack of benefit should be understood to be resistance to a drug. [00:40:37] Speaker 03: Your Honor, I don't think it is, and for the reasons I gave. [00:40:41] Speaker 03: One, it doesn't have anything to do with the particular markers at issue. [00:40:44] Speaker 02: So the fact that these markers are resistant because... I understand the specifics of the individual markers, but I'm talking more about the concept of how this patent understands lack of benefit. [00:40:55] Speaker 03: Your Honor, I think that this patent understands likely lack of benefit to mean the drug won't work or is less likely to work or is unlikely to work. [00:41:04] Speaker 03: The reason why it's unlikely... Where would that be in the specification? [00:41:09] Speaker 03: That's tricky because it doesn't actually use that phrase, but if you look at column 51, I believe it's 51. [00:41:26] Speaker 03: The candidate treatment selected can depend on the... I'm sorry, what line are you on? [00:41:29] Speaker 03: Yes, sorry. [00:41:33] Speaker 03: starting at 40, well it started at 46. [00:41:36] Speaker 03: As a non-limiting example, molecular profiling might reveal that the EGFR gene is amplified or overexpressed, thus indicating selection of a treatment that can block EGFR activity, et cetera. [00:41:49] Speaker 03: It goes on to simply say, the question is, does it block, does it succeed in solving the problem? [00:41:56] Speaker 03: There's no suggestion in that paragraph. [00:41:58] Speaker 02: I mean, the bottom of that same paragraph, [00:42:04] Speaker 02: starts talking about like around line 59 molecular profiling may also reveal that some or all of these treatments are likely [00:42:13] Speaker 02: to be less effective. [00:42:14] Speaker 02: For example, patients taking G or E eventually develop drug resistance mutations in EGFR. [00:42:23] Speaker 02: Accordingly, the presence of a drug resistance mutation would contraindicate selection of the small molecule kinase inhibitors. [00:42:31] Speaker 02: So this right here is [00:42:35] Speaker 02: Right in line with my working understanding of what this patent is describing. [00:42:40] Speaker 03: Your honor, that is an example of how a drug might fail. [00:42:44] Speaker 03: But there's no suggestion that that is the only example of how a drug might fail. [00:42:49] Speaker 03: Again, there's no the invention is. [00:42:52] Speaker 03: There's no lexicography. [00:42:54] Speaker 03: There's no disclaimer. [00:42:56] Speaker 03: And so the fact that there are exemplars that would support it doesn't mean that we should exclude it. [00:43:04] Speaker 03: With that, Your Honor, I move to further questions. [00:43:06] Speaker 03: I'm deep in my rebuttal time. [00:43:11] Speaker 02: Just a last question. [00:43:12] Speaker 02: How should claim 12 have been written to capture the actual thought that they invented and disclosed? [00:43:21] Speaker 03: I think it was written to capture, I don't think there's anything in this patent that suggests, so let's take a step back. [00:43:29] Speaker 03: What counsel suggested the invention was is look at the particular biomarker and based on that biomarker the comparison of [00:43:41] Speaker 03: the normal to the patient and based on what you know about the drug, the available therapeutic, should you or should you not use it? [00:43:49] Speaker 03: Is it likely to be effective or likely not to be effective? [00:43:53] Speaker 03: And there are lots of different reasons why a drug might not be effective. [00:43:56] Speaker 03: And I don't think they wrote this. [00:43:58] Speaker 03: I mean, think about the other way. [00:44:00] Speaker 03: Imagine if we were in court arguing non-infringement [00:44:03] Speaker 03: Because although our system spits out a report that does exactly what the claim says and says, don't use Herceptin, it is not likely to be effective. [00:44:12] Speaker 02: Is the answer that they should have written in once you identify a resistance to a drug? [00:44:19] Speaker 02: Something like that, Your Honor. [00:44:21] Speaker 02: OK. [00:44:21] Speaker 02: Thank you, Your Honor. [00:44:24] Speaker 01: Mr. Wolfe, we will save four minutes for rebuttal. [00:44:28] Speaker 01: Thank you. [00:44:28] Speaker 01: If it turns out you have something to rebut, understand 12. [00:44:33] Speaker 01: Dr. Sanger, you have five minutes plus, close to six minutes. [00:44:39] Speaker 00: I want you to start there, too. [00:44:40] Speaker 00: Yes, of course. [00:44:41] Speaker 00: Because, I mean, everyone in America knows that whether you're hurt too negative or hurt too positive, the question is, does Herceptin help you? [00:44:50] Speaker 00: Not, is it going to hurt you? [00:44:51] Speaker 00: The question is, is it going to help you? [00:44:53] Speaker 00: So that's why I don't understand how you can say that likely lack of benefit means the same thing as the contraindication. [00:45:00] Speaker 04: So I was going to pick up right where counsel left off. [00:45:04] Speaker 04: And we looked at 40B and 40A, but we didn't look at 40E, figure 40E, Your Honor. [00:45:11] Speaker 04: That actually does have one of the markers in the claim that's easy to spot. [00:45:15] Speaker 04: And we all apologize for the blurriness of this. [00:45:19] Speaker 04: But if you look at A166, [00:45:22] Speaker 04: It answers the question here with respect to, for example, P10. [00:45:26] Speaker 04: In the middle column about the 10th line down, you'll see P10, which is one of the claimed markers. [00:45:32] Speaker 04: And it describes it as no change. [00:45:34] Speaker 04: Now, counsel's argument was that no change tells you information about whether something is likely to benefit or not likely to benefit. [00:45:42] Speaker 04: And yet P10, which no change, the normal result or whatever it is, [00:45:48] Speaker 04: is not listed, if you will, on figure 40B as a likely lack of clinical benefit. [00:45:54] Speaker 04: That is the concept that the claims require. [00:45:57] Speaker 04: Something is, in fact, resistant. [00:45:59] Speaker 04: Something that was indicated or might be indicated for the patient based on one marker is then contraindicated by the resistance of another. [00:46:08] Speaker 04: That's what the board construed. [00:46:10] Speaker 00: So why was the word contraindicated used? [00:46:13] Speaker 04: Pardon me? [00:46:14] Speaker 00: The word contraindication does not appear in the claims. [00:46:16] Speaker 04: It does not appear in the claims, but it's using the phraseology of these reports, right? [00:46:22] Speaker 04: The 40A and 40B, clinical benefit, likely lack of clinical benefit. [00:46:27] Speaker 04: And 40E tells you what was tested, as does 40D, I believe, as well. [00:46:32] Speaker 04: And it tells you when there's no change, which is what the board found. [00:46:35] Speaker 04: It doesn't list it. [00:46:37] Speaker 04: as likely lack of clinical benefit, because you're looking for that resistance to something that was already indicated. [00:46:43] Speaker 02: Everything you just said might be consistent with how you want us to translate likely lack of benefit, but it doesn't tell us why we must think of likely lack of benefit in that way. [00:46:54] Speaker 02: What is it about this patent that demands us to [00:46:58] Speaker 02: construe this rather broad, vague language to be about resistance to drug mutation, contraindication, whatever you want to use to swap in for likely lack of benefit? [00:47:12] Speaker 04: The concepts in the specification that we've gone through, the specification repeatedly describes the invention as using that concept of contraindication in the comparison step. [00:47:21] Speaker 04: It doesn't use the word. [00:47:22] Speaker 04: And then it has exemplar reports which use phraseology that's very, very close to what is in the claims instead of the word likely it uses clinical. [00:47:31] Speaker 04: And so the phraseology in the figures is very nearly the same phraseology in the claims. [00:47:38] Speaker 04: And so the phraseology in the figures should govern the phraseology in the claims where there is support and specification otherwise, which the board also found. [00:47:46] Speaker 04: The discussion about, I think, column 51, Your Honor, with respect to actually equating the word contraindicate to something where it's a resistance. [00:48:00] Speaker 04: Does that answer your question? [00:48:01] Speaker 00: I hope. [00:48:03] Speaker 00: What column is that where you equate? [00:48:05] Speaker 04: So if you look at column 51, Judge O'Malley, if you go to the bottom there, I think counsel went through that with Judge Chan describing, if you look at line 58, continue with the exemplary embodiment. [00:48:19] Speaker 04: Profiling may also reveal that some or all these students are elected. [00:48:22] Speaker 00: Right. [00:48:23] Speaker 00: But again, this goes back to the whole notion of that's using contraindicate as a verb there. [00:48:28] Speaker 04: Right. [00:48:28] Speaker 04: The word contraindicate, you were asking whether it's equated to resistance. [00:48:32] Speaker 04: That's what I understood your question to be. [00:48:34] Speaker 00: Right. [00:48:34] Speaker 00: But here, they're talking about contraindicate the selection. [00:48:37] Speaker 00: So that's using contraindicate as a verb. [00:48:41] Speaker 04: Right, to contraindicate something that already has been indicated. [00:48:44] Speaker 00: Contraindicate the selection, meaning don't go there. [00:48:48] Speaker 00: Don't bother to go there. [00:48:50] Speaker 04: That's right. [00:48:50] Speaker 00: That's very different from what the common understanding, meaning of contraindication with respect to medications. [00:48:58] Speaker 04: It is different, right? [00:49:00] Speaker 04: And so the patent is using, to the extent we're arguing about what the board, the construction within the construction. [00:49:05] Speaker 04: The board construed likely less of a lack of benefit to [00:49:09] Speaker 04: require this contraindication concept as used in the patents, not the medical use of the terminology. [00:49:17] Speaker 04: That's not what the board was talking about. [00:49:18] Speaker 02: This patent basically hijacks the word contraindicate and uses it in a different way. [00:49:23] Speaker 04: It does. [00:49:23] Speaker 04: I mean, that's what it does. [00:49:24] Speaker 04: And I don't think there's anything wrong with that under this court's authorities to use a word in a different way than what someone might use it. [00:49:33] Speaker 04: That is different than don't use this, right? [00:49:36] Speaker 04: It's contraindicated for a medical reason. [00:49:41] Speaker 04: OK. [00:49:44] Speaker 04: Finally, with respect to the, I just want to say one last word about the prior use that was raised in the von Hoff, the charts, the negative and the no change. [00:50:01] Speaker 04: I couldn't quite tell if there was an argument in the briefs that this wasn't considered by the board. [00:50:06] Speaker 04: It absolutely was considered by the board. [00:50:09] Speaker 04: The petition for IPR equated figures 3B and 3C. [00:50:18] Speaker 04: The board quoted the petition equating the two as no change to the extent that that was an issue. [00:50:24] Speaker 04: I wasn't quite sure from the argument. [00:50:26] Speaker 04: where there was a distinction being made between no change and negative that was equated before the board in the petition. [00:50:33] Speaker 04: And the board cited it as having considered both of those figures in the prior art. [00:50:37] Speaker 02: Does CARES have any patents or continuations off of these specifications that used words like contraindicate or resistance to a drug or without considering cancer lineage or any of that? [00:50:57] Speaker 02: I'm talking about both appeals. [00:50:59] Speaker 04: No, no. [00:51:01] Speaker 04: There's a patent that relates to off-label, Your Honor. [00:51:05] Speaker 04: The non-disease specific agent is a little better, but there is not something that talks about [00:51:11] Speaker 04: with that non-disease lineage or outside the lineage, those kinds of concepts, or phrase contraindication. [00:51:18] Speaker 04: This is how CARES claimed it. [00:51:19] Speaker 02: But you have something that says non-disease specific. [00:51:22] Speaker 02: Pardon me? [00:51:23] Speaker 02: You have a claim that says something like non-disease specific. [00:51:26] Speaker 02: Agent. [00:51:26] Speaker 02: Agent. [00:51:27] Speaker 02: Which is defined as an off-label agent. [00:51:31] Speaker 02: OK. [00:51:31] Speaker 02: OK, so any other questions? [00:51:32] Speaker 02: Thank you. [00:51:33] Speaker 02: And is claim 12 is asserted in the litigation somewhere? [00:51:35] Speaker 02: It is. [00:51:36] Speaker 02: OK. [00:51:37] Speaker 01: Thank you, counsel. [00:51:39] Speaker 01: Mr. Wolf has some rebuttals on. [00:51:41] Speaker 03: Yes, sir, two brief points. [00:51:48] Speaker 03: Very briefly, Your Honor. [00:51:50] Speaker 03: At the opening brief in the 1886 appeal at footnote two, page eight, Harris said, there was much debate before the board as to the meaning of the word contraindicated as used by doctors. [00:52:02] Speaker 03: As the record reflects, the word can mean something far more serious to doctors than its use in the 660 patent specification as meaning lack of efficacy. [00:52:11] Speaker 03: That is how they told us in the brief that contraindication should be understood, essentially synonymous with likely lack of benefit, without all of the gloss that they have tried to import about resistance or the battle I was describing earlier. [00:52:27] Speaker 03: Emphasizing that point, if we were talking about column 51, if we go to, this is at A197, 51, roughly line 31, [00:52:38] Speaker 03: There are a series of exemplars of how this can work. [00:52:42] Speaker 03: And they say, quote, the best evidence can be used as the basis for a rule. [00:52:46] Speaker 03: The simplest rules are constructed in the format of, quote, if biomarker positive in the treatment option one, else treatment option two. [00:52:54] Speaker 03: A neutral, natural, normal result that gives treatment option two, specifically called out in specification, consistent with the plain meaning of claim 12, [00:53:07] Speaker 03: Respectfully, the PTAB did everything right here except over-reading the meaning of likely lack of benefit in Claim 12. [00:53:15] Speaker 01: Thank you for your time, Your Honors, and it's wonderful to be back live.