[00:00:00] Speaker 03: Team 1485, ARCH development versus OSI pharmaceutical. [00:01:00] Speaker 03: We're ready, Mr. Sullivan, whenever you are. [00:01:12] Speaker 01: Good morning. [00:01:13] Speaker 01: It may please the court, Peter Sullivan for Dana-Farber Cancer Institute and Arch Development. [00:01:18] Speaker 01: There are three points on appeal. [00:01:20] Speaker 01: I'm going to start with the Aganaka grounds. [00:01:24] Speaker 01: below found that the combination of Akanaga, Taneyev, Friedman, and Tan, in light of the knowledge of a person of ordinary skill in the art, rendered claims one, two, three, and five of the 512 patent obvious. [00:01:38] Speaker 01: And as part of that determination, there was an issue that I want to focus on. [00:01:46] Speaker 01: The board held that a person of ordinary skill in the art knew that UCN01 was an inhibitor, a tyrosine kinase inhibitor in humans and animals. [00:01:57] Speaker 01: And that's with respect to CSARC, but also with respect to other tyrosine kinase inhibitors. [00:02:03] Speaker 01: We submit that that was a decision without substantial evidence in the record. [00:02:09] Speaker 01: Now there are three inferential jumps that the board makes [00:02:14] Speaker 01: in connection with finding that UCN01 is a tyrosine kinase inhibitor. [00:02:20] Speaker 01: It starts with Okanaga. [00:02:22] Speaker 01: The Okanaga reference reports that there is inhibition of something called B, viral sarc. [00:02:30] Speaker 01: Vsarc is mutant kinase that is found in the rouse sarcoma chicken virus. [00:02:39] Speaker 01: It's found in chickens. [00:02:40] Speaker 01: It's not found in humans. [00:02:42] Speaker 01: And Okanaga reported [00:02:44] Speaker 01: that in a test of the actual substrate of VSARC, not in cells, but like an in vitro test of the substrate, that there was inhibition by UCN01. [00:02:57] Speaker 01: The rest of the art that's used in order to come to the conclusion that UCN01 is a tyrosine kinase inhibitor in humans and animals [00:03:08] Speaker 01: comes largely from expert testimony and storosporine. [00:03:13] Speaker 01: And storosporine is another drug, another treatment drug, that has a structural similarity to UCNL-1. [00:03:23] Speaker 01: But they're not the same. [00:03:24] Speaker 02: Close structural similarity. [00:03:26] Speaker 01: Yes. [00:03:27] Speaker 02: And you sort of semi-disparaged the testimony, but the testimony counts and was believed. [00:03:36] Speaker 01: It was believed that there's structural similarity. [00:03:39] Speaker 01: And that may lead someone to look at that drug. [00:03:42] Speaker 01: But the conclusion that was made, Your Honor, is that that drug would act the same way as UCN01. [00:03:51] Speaker 01: And that's a leap too far. [00:03:53] Speaker 01: And what we pointed out below to the board was that there's actually record evidence in another Okanagan reference. [00:04:01] Speaker 01: It's Okanagan, 1991. [00:04:04] Speaker 01: And that reference actually compared [00:04:06] Speaker 01: UCN01 to staurosporine. [00:04:09] Speaker 01: It showed there was a host of differences having to do with specificity, potency, and activity, the kinds of things that you worry about when you're trying to figure out whether something inhibits tyrosine kinases. [00:04:22] Speaker 01: So staurosporine was shown to not be similar in its function to UCN01. [00:04:32] Speaker 01: The other piece of evidence that was used to [00:04:38] Speaker 01: support a conclusion that UCN01 was a styrosine kinase inhibitor was reference to Robinson. [00:04:49] Speaker 01: Robinson is also a storosporin reference. [00:04:53] Speaker 01: It's actually the the goal of the investigators in Robinson. [00:04:58] Speaker 02: What about the C-naive reference, if I've not mispronounced it? [00:05:03] Speaker 01: We're all just guessing about that, Judge. [00:05:05] Speaker 01: SNAVE is a UCN01 reference. [00:05:09] Speaker 01: That reference talks about four unknown proteins, and it finds in one of its tests that there's phosphorylation. [00:05:20] Speaker 01: What phosphorylation will tell you is that that may be an indication that there is tyrosine kinase inhibition taking place. [00:05:27] Speaker 01: But it can also be increased phosphatase activity. [00:05:31] Speaker 01: And both experts agreed [00:05:33] Speaker 01: that you need to understand whether there was increased phosphatase activity before you can conclude that this was tyrosine kinase inhibition. [00:05:45] Speaker 02: This pattern is expired, correct? [00:05:47] Speaker 01: It is. [00:05:50] Speaker 01: Dr. Alan Eastman's testimony on that point is found at appendix 2135, lines 9 to 15. [00:06:00] Speaker 01: And Sinev and Okanagan are the only two UCN01 references. [00:06:04] Speaker 01: The rest of them are starosporin references. [00:06:09] Speaker 02: And starosporin differs from UCN only by a hydroxyl group. [00:06:15] Speaker 02: It's pretty close. [00:06:16] Speaker 01: Right. [00:06:19] Speaker 01: Exactly. [00:06:20] Speaker 01: Let me get the actual statement about the difference. [00:06:25] Speaker 01: Because it notes that the difference actually, in Okanagan 91, [00:06:31] Speaker 01: The investigators note that that actual difference in hydroxyl may be the precise reason why there's a difference in function. [00:06:38] Speaker 01: So insofar as it's different, that difference was being ascribed as the reason why store of scoring doesn't act the same way that UCNL-1 does. [00:06:47] Speaker 04: Since it's the only difference between the two, it would have to be inferentially the basis for a difference in function, right? [00:06:56] Speaker 04: That's what the investigator said. [00:06:59] Speaker 01: And I would agree with that presumption. [00:07:12] Speaker 01: There are two other grounds. [00:07:14] Speaker 01: One is an alternative ground for relief based on the Hamna art. [00:07:18] Speaker 01: And then there's a constitutional argument that we've raised. [00:07:22] Speaker 01: So going to the Hamna grounds. [00:07:26] Speaker 01: The person of ordinary skill in the art, the grounds for Hanma were a person of ordinary skill in the art plus Hanma plus McGann would render the claims that asserted the 512 patent invalid. [00:07:38] Speaker 01: And the board correctly noted that the term cell death and apoptosis should be equated to cell killing. [00:07:50] Speaker 01: And it should not be broadened to include induction of a differentiation pathway. [00:07:56] Speaker 01: And in that case, as Judge Lori mentioned, this is an expired patent. [00:08:01] Speaker 01: The claim construction was on the basis of Phillips. [00:08:04] Speaker 01: And in this case, the court construed, the board construed that cell death was not to include differentiation. [00:08:16] Speaker 01: And the reason why that's important is Hahn-Mazart talks about converting [00:08:24] Speaker 01: benzidine negative cells to benzidine positive cells, taking cancerous cells and converting them to non-cancerous cells. [00:08:30] Speaker 01: It doesn't talk of cell killing. [00:08:33] Speaker 01: So because the court, the board, construed the claims to exclude differentiation, that was the basis for concluding that the Hamna art would not be relevant and that it would not be [00:08:52] Speaker 01: The board would not reject or find unpatentable the claims on the basis of the harm or art. [00:08:59] Speaker 02: You mentioned a constitutional argument. [00:09:01] Speaker 02: We've already held that re-examining a granted patent is not taking or is not unlawful. [00:09:15] Speaker 01: Right. [00:09:15] Speaker 01: That's in the Patlix decision, Your Honor. [00:09:18] Speaker 01: Yes. [00:09:19] Speaker 01: As we mentioned in our reply brief, [00:09:23] Speaker 01: The Patlic's decision relied in part on Supreme Court precedent that included a substantially advances aspect of the Takings Clause. [00:09:32] Speaker 01: Subsequent Supreme Court cases, including the Lingel case, L-I-N-G-L versus Chevron, held that in a Takings Clause, we presume that the Congress was provided an adequate basis and has a law that's appropriate, whereas in the due process, [00:09:51] Speaker 01: A due process case, you look at both the government's interest and whether it was a rational basis to achieve that interest. [00:09:59] Speaker 01: So to the extent Patlix is relying on cases involving substantial advances and the policy behind the legislation, it can be reexamined because that law is no longer right. [00:10:16] Speaker 01: And the Supreme Court took pains to correct that law. [00:10:20] Speaker 01: in the Lingo case. [00:10:22] Speaker 01: So our position is that Patlix can be re-examined in light of the Supreme Court case, and the Takings Clause case can be decided. [00:10:32] Speaker 01: As I said, the constitutional law issue involves both a due process and Takings Clause. [00:10:40] Speaker 01: Both of those. [00:10:41] Speaker 02: Well, certainly due process in the extensive re-examination or review process. [00:10:48] Speaker 01: I'm sorry? [00:10:48] Speaker 02: It's certainly due process in the IPR process. [00:10:56] Speaker 01: We're arguing substantive due process, which is rarely granted. [00:11:01] Speaker 01: We understand that. [00:11:03] Speaker 01: The basis is whether there is a legitimate government interest and a rational basis to go forward. [00:11:09] Speaker 01: The government's interest, as expressed through this Court and through Congress, looking at the statute, has been [00:11:17] Speaker 01: That there is both dubious patents out there, and that we want to strengthen the patent community. [00:11:23] Speaker 01: And we submit that IPRs do not have a rational basis for that second part. [00:11:31] Speaker 01: There is nothing in the IPR statute that strengthens already valid patents. [00:11:35] Speaker 01: We can be examined. [00:11:37] Speaker 01: This patent's expired, but you can take a patent. [00:11:39] Speaker 01: You can have it examined by an IPR by a party, and then you can come through that. [00:11:44] Speaker 01: And then another party can come right back [00:11:47] Speaker 01: There's no super presumption of validity. [00:11:50] Speaker 01: There's nothing that says, OK, we went through this process. [00:11:53] Speaker 01: Now it's stronger. [00:11:54] Speaker 01: No, it's just subject to more and more challenges. [00:12:00] Speaker 01: We submit that that means that that second part that Congress talked about wasn't met in the IPR challenge. [00:12:07] Speaker 01: And for those who had applied for patents under the prior regime, [00:12:15] Speaker 01: It's unfair for them to be subjected to this new process. [00:12:19] Speaker 01: I see I'm in my... OK, let's hear it from the other side. [00:12:21] Speaker 01: Thank you. [00:12:31] Speaker 03: So you are splitting time with the government? [00:12:34] Speaker 03: That's correct, Your Honor. [00:12:35] Speaker 03: And they are arguing just the constitutionality question? [00:12:38] Speaker 00: That's correct, Your Honor. [00:12:40] Speaker 00: May it please the court, Ryan Matsui, and I am presenting argument for both appellees here. [00:12:46] Speaker 00: And I'm going to address the patentability issues. [00:12:49] Speaker 00: This is a straightforward, substantial evidence appeal. [00:12:52] Speaker 00: Even though the board made numerous factual findings based upon the prior art, adopted our claim charts in full, credited our expert in his 114-page declaration, and found Arch's expert in his seven-page declaration not persuasive, [00:13:11] Speaker 00: Arch raises no legal challenges to patentability. [00:13:15] Speaker 00: Instead, it raises two narrow, substantial evidence issues. [00:13:20] Speaker 00: There's substantial evidence to support both of the findings that Arch challenges, but the court only needs to address one to affirm on the patentability issues, and that's that UCN01 is a tyrosine kinase inhibitor. [00:13:33] Speaker 00: And we know that UCN01 is a tyrosine kinase inhibitor because of the board found Akanaga says so. [00:13:40] Speaker 00: It says that at Appendix 32 and Appendix 29, that Table 1 in Akanaga expressly states that UCN01 inhibits VSRC. [00:13:52] Speaker 04: But that's VSRC, not CSRC. [00:13:54] Speaker 04: That's correct, Your Honor. [00:13:55] Speaker 04: And their argument is predicated entirely on the distinction. [00:13:58] Speaker 00: That's true, but Akanaga says that VSRC is a tyrosine kinase. [00:14:03] Speaker 00: And the 512 patent itself. [00:14:05] Speaker 00: says that VSRC is a tyrosine kinase. [00:14:09] Speaker 04: So you don't think that the inference needs to be made that CSRC is the same as VSRC? [00:14:22] Speaker 00: Not when at column 19, line 28. [00:14:24] Speaker 00: It operates equivalently. [00:14:25] Speaker 00: Not when at column 19, line 28. [00:14:28] Speaker 00: The patent discloses that genistein, a compound, is a tyrosine kinase inhibitor. [00:14:33] Speaker 00: because it inhibits VSRC. [00:14:36] Speaker 00: So the patent itself is treating VSRC as a tyrosine kinase inhibitor, as a tyrosine kinase. [00:14:42] Speaker 00: But more importantly, this is a factual finding here. [00:14:45] Speaker 00: The board found, as a matter of fact, at appendix 33, that a person of ordinary skill in the art would understand that a compound that inhibits VSRC would inhibit CSRC. [00:14:57] Speaker 00: It found Dr. Keefe's testimony not persuasive, and it credited and quoted [00:15:03] Speaker 00: are experts' testimony saying there are similarities between VSRC and CSRC such that a skilled artisan would understand that the compound that inhibits VSRC also inhibits CSRC. [00:15:17] Speaker 00: That's one reason, in addition to the fact that Okanaga says VSRC is a tyrosine kinase, that [00:15:24] Speaker 00: their argument fails. [00:15:25] Speaker 00: But another reason why their argument fails is because of the signage reference. [00:15:29] Speaker 00: The signage reference says that UCN01, and the board made findings about this at appendix 29 and at appendix 29 and at 33, that the signage, sorry, 35, where the board said that signage discloses [00:15:53] Speaker 00: that UCN01 inhibits multiple tyrosine, seronine, threonine kinases. [00:16:00] Speaker 00: And it did experiment testing on human breast cancer cells to determine that it led to decreased tyrosine phosphorylation of at least four proteins when UCN01 is applied to human breast cancer cells. [00:16:15] Speaker 00: And the board found, as a matter of fact, based upon this reference and based upon our expert's testimony, [00:16:22] Speaker 00: that a person of ordinary skill in the art would understand that UCN01 is a tyrosine kinase inhibitor. [00:16:28] Speaker 00: And that's being applied to cells right there. [00:16:32] Speaker 00: So that's additional substantial evidence that supports the board's decision here in this case, where they found Archer's expert's testimony not persuasive. [00:16:44] Speaker 00: That should resolve the appeal, because there is no need then to look to any other art when you have [00:16:50] Speaker 00: References that explain that you see no one is a tyrosine kinase inhibitor And it doesn't and I think that it's important also to look to take a step back and look at the what the board Did here in this case the board's rehearing decision which arch really wholly ignores? [00:17:08] Speaker 00: Rejected the very premise of arches argument that it depends upon its ruling depends upon any difference between VSRC [00:17:20] Speaker 00: in CSRC. [00:17:21] Speaker 02: I noticed some references to protein kinase inhibitor as opposed to tyrosine kinase. [00:17:28] Speaker 02: Tyrosine, of course, is not a protein. [00:17:30] Speaker 02: It's an amino acid, which is a component of a protein. [00:17:33] Speaker 02: Is that difference of any significance to us here? [00:17:36] Speaker 00: No, because the fact that UCN01 is also a protein kinase inhibitor doesn't mean that it's not a tyrosine kinase inhibitor as well. [00:17:46] Speaker 00: A lot of this art is showing that these compounds [00:17:48] Speaker 00: inhibit multiple different enzymes or proteins. [00:17:54] Speaker 00: And that's all that's being shown here. [00:17:56] Speaker 00: The board here had the evidence before it and made a determination on the facts based upon the significant evidence in the prior art and in our expert's testimony that UCN01 is a tyrosine kinase inhibitor. [00:18:10] Speaker 00: There's nothing in the 512 patent that requires a particular tyrosine kinase inhibitor. [00:18:16] Speaker 00: It just lists a number of examples. [00:18:18] Speaker 00: It doesn't say that it needs to inhibit tyrosine kinases with any sort of degree. [00:18:24] Speaker 00: It just says, any tyrosine kinase inhibitor, any low molecular weight tyrosine kinase inhibitor. [00:18:30] Speaker 00: Now, I just would also like to briefly touch upon the motivation argument that Arch raises, because again, that's another issue that the [00:18:39] Speaker 00: Court does not need to reach, because as Arch has said, you needed to look at the store sporing art in order to determine whether or not UCN01 is a tyrosine kinase inhibitor. [00:18:52] Speaker 00: But you don't need to do that, because, again, Okanaga and Sinai have explained that UCN01 is a tyrosine kinase inhibitor. [00:18:59] Speaker 00: And the board made a finding of that on its rehearing decision at 43 and 44, where it says its decision doesn't depend [00:19:07] Speaker 00: upon any of the storage boring art. [00:19:10] Speaker 00: So given that, that's enough right there to affirm the board's decision. [00:19:15] Speaker 02: Now, the link between the VSRC and C is based on the testimony which the board accepted and believed. [00:19:26] Speaker 00: That's correct, Your Honor. [00:19:27] Speaker 00: And it's the same thing for the motivation argument. [00:19:30] Speaker 00: If the court needed to reach the motivation to combine argument, that's another factual finding that's supported by substantial evidence where the board found [00:19:38] Speaker 00: ARCH's evidence, not persuasive, it looked at the fact that our expert testified that UCN01 and storage sporing have a similar mechanism of action. [00:19:47] Speaker 00: They both inhibit kinases by interfering with ATP binding. [00:19:52] Speaker 00: They both have similar effects on the cell cycle, and they are structurally similar. [00:19:57] Speaker 00: The board was perfectly well within its rights to weigh that evidence and make a factual finding and determine that [00:20:05] Speaker 00: a person of ordinary skill in the art that has this Okanaga reference, which basically discloses, it does disclose everything, adding a DNA agent to a taryzin kinase inhibitor to enhance cell death, a person of ordinary skill in the art that wanted to learn more about UCN01 would look at the Storus boring art. [00:20:25] Speaker 00: If there are no further questions, we would ask the court to affirm. [00:20:30] Speaker 03: Thank you. [00:20:44] Speaker 05: Thank you, Your Honor. [00:20:45] Speaker 05: May it please the court. [00:20:46] Speaker 05: Katherine Allen on behalf of the United States. [00:20:48] Speaker 05: We intervene to address the constitutional issues. [00:20:51] Speaker 05: And I would just like to start out by responding to a couple of points that the other side made. [00:20:55] Speaker 05: First is that the due process question here is whether there is any rational basis for Congress's decision to apply inner party's review to patents that issue prior to the AIA. [00:21:06] Speaker 05: They agree that it serves the purpose of weeding out erroneously granted patents. [00:21:12] Speaker 05: That ends the due process question. [00:21:14] Speaker 05: Also, they dispute Pat Lex's citation of cases that look to congressional purpose. [00:21:19] Speaker 05: And I just want to point out that those citations are in the due process portion of the opinion. [00:21:25] Speaker 05: And there's no dispute that the due process question is whether Congress had a rational basis for this application of the statute. [00:21:35] Speaker 05: So Pat Lex is still good law on that issue. [00:21:38] Speaker 05: And we think it forecloses the due process question here. [00:21:42] Speaker 05: In addition, we think that there is no takings problem because the cancellation of a patent through IPR rests on a determination by the agency that the patent holder never had a valid property interest. [00:21:57] Speaker 05: And the patent wouldn't actually be canceled until this court affirms that determination. [00:22:03] Speaker 05: And in that sense, it's really no different than when a district court determines that a patent is invalid. [00:22:11] Speaker 04: What do you say as to the failure to raise this issue before the board? [00:22:19] Speaker 04: Had the issue been raised before the board, what would the board have been empowered to do about it? [00:22:25] Speaker 05: Yes, Your Honor. [00:22:27] Speaker 05: If the issue had been raised before the board and the board agreed with the constitutional challenge, it could have declined to institute inter-parties review in this case. [00:22:39] Speaker 04: And so you think that this is something that needs to be raised prior to the institution of the IPR? [00:22:47] Speaker 05: Well, that would be the best time to raise it. [00:22:49] Speaker 05: But in addition, the board could terminate the proceedings and, in effect, reconsidering the institution decision if it was raised later. [00:22:56] Speaker 05: in the proceedings. [00:22:57] Speaker 04: But I think the fundamental point is that they think that the board, in effect, has the power to entertain a constitutional argument of this sort. [00:23:06] Speaker 04: It was a constitutional challenge to the statute that the board is charged with enforcing. [00:23:12] Speaker 05: Yes, Your Honor. [00:23:12] Speaker 05: I do think it does. [00:23:13] Speaker 05: Section 314A does not require the agency to institute in our party's review in any case. [00:23:19] Speaker 05: So it's clear that the agency does have discretion, as the Supreme Court recognized in Cuozo, to decline to institute. [00:23:26] Speaker 05: that that decision is committed to the agency's discretion. [00:23:30] Speaker 05: And I would point out that the Supreme Court in Thunder Basin and more recently in 2012 in Elgin made clear that the sometimes quoted statement that agencies don't have jurisdiction to consider constitutional issues is not mandatory. [00:23:45] Speaker 05: And we think here, just as in Ray DBC, it would not have been futile for the party to raise it. [00:23:51] Speaker 05: And therefore, the issue should be considered forfeited. [00:23:56] Speaker 04: But just to finish the point, then, are you saying that the board does have the authority, quite independent of its right to decline, to institute, but it does have authority to rule on a constitutional challenge to the statute? [00:24:17] Speaker 04: Or are you saying that, well, it can always decline and thereby avoid the problem altogether? [00:24:26] Speaker 05: William, I think it's clear that Congress authorized the agency to make institution decisions. [00:24:33] Speaker 04: My question really goes to whether the board, if the board wants to be perfectly [00:24:39] Speaker 04: transparent about this and say, we would institute this, but for the fact that we think that statute is unconstitutional, and we think it's unconstitutional, therefore we decline to institute. [00:24:51] Speaker 04: Is that a lawful act in your view, in the view of the Department of Justice, for the board to take? [00:24:58] Speaker 05: Yes, Your Honor. [00:24:59] Speaker 04: It is. [00:24:59] Speaker 05: We think the board could issue a decision when it declines to institute. [00:25:04] Speaker 05: Sorry, if the board agreed with the constitutional challenge, [00:25:07] Speaker 05: it could decline to institute and issue a decision explaining that the reason it was declining to institute is because it- And that would be unreviewable under QoSo by us? [00:25:17] Speaker 05: Yes, Your Honor. [00:25:17] Speaker 05: I do think that because that's committed to the agency discretion, that if the agency found that there was a constitutional problem, that would be unreviewable. [00:25:26] Speaker 05: But of course, the agency has addressed this issue in a different case that is also pending before this court. [00:25:32] Speaker 05: And there, the agency rejected the retroactivity challenge. [00:25:35] Speaker 05: And the issue is now properly presented [00:25:37] Speaker 05: to this court in that case. [00:25:39] Speaker 05: And that obviously is reputable. [00:25:42] Speaker 05: If there are no further questions, thank you. [00:25:50] Speaker 01: I'll start with the constitutional issues. [00:25:53] Speaker 01: The court obviously can see this here, the case in the interest of justice, if it believes it's important and proper to do so. [00:26:02] Speaker 01: The property interest here is broader than [00:26:05] Speaker 01: The government is professing. [00:26:07] Speaker 01: It's not just those who have invalid patents. [00:26:10] Speaker 01: It's all patent holders are under the same regulatory disability of having to deal with a quasi-judicial additional judicial administrative process. [00:26:19] Speaker 01: A process that has a lower bar to institution than the substantial new question of patentability line that was drawn for re-examination and that also has the additional disability of [00:26:30] Speaker 01: Having institution be granted when there's competing testimony under 42 CFR 108 when when the board is confronted with conflicting expert testimony on an issue It is instructed to weigh that in favor of institution so the bar is lower so suppose that the Congress decided that the clear and convincing evidence test in district court was really to [00:26:57] Speaker 04: onerous for patent challengers and decided to convert the test into 1-4 by a preponderance, do you think that would be constitutionally invalid? [00:27:07] Speaker 01: If retroactively applied? [00:27:09] Speaker 01: Yes. [00:27:10] Speaker 01: On the basis of retroactivity, I would. [00:27:12] Speaker 01: I would also believe that that's the case. [00:27:15] Speaker 01: At some point, the process drives the results. [00:27:17] Speaker 01: The fact that this IPR has been so popular should tell us all that maybe something's different than it was with the old re-examination regime. [00:27:26] Speaker 01: And patent holders certainly feel that way. [00:27:28] Speaker 01: It changes the calculus for licensing negotiations. [00:27:31] Speaker 01: I represent two cancer institutes. [00:27:34] Speaker 01: They have to every day. [00:27:35] Speaker 01: They're on the lines with licensing decisions. [00:27:38] Speaker 01: And those decisions are affected by the fact that a large pharmaceutical company could just throw you into re-exam or IPR, excuse me. [00:27:44] Speaker 01: and have to go through a mid-six-figure challenge before you get to enforce, like we have here. [00:27:50] Speaker 01: I'd like to turn just for a couple more points on a couple things about CINEF. [00:27:56] Speaker 01: Judge Laurie, of course, it's critical that there's a difference between proteins and tyrosine kinases. [00:28:01] Speaker 01: CINEF does not identify what tyrosine kinases have been inhibited. [00:28:07] Speaker 01: How could someone of ordinary skill in the art know that it's a tyrosine kinase inhibitor without knowing what the tyrosine kinases that are being inhibited? [00:28:15] Speaker 01: That's the point. [00:28:16] Speaker 01: This evidence doesn't get us far enough to make the leap. [00:28:20] Speaker 01: There's inferences upon inferences upon inferences. [00:28:23] Speaker 01: And I want to close with the cell cycle. [00:28:26] Speaker 01: I've got a minute. [00:28:26] Speaker 01: The irony of this case is that this is a classic hindsight reconstruction. [00:28:31] Speaker 01: If you look at Akanaga, Akanaga talks about cell cycle and says that Akanaga says that the fact that compound A [00:28:42] Speaker 01: MMC and compound B, UCN01 act on two different parts of the cell cycle is a good thing because Perhaps it's a one-two punch the fact that one's not interfering with the other is a good thing whatever Akanaga thought that's what it said that was the state of the art the inventors here believed that tyrosine kinase inhibition [00:29:08] Speaker 01: was a counteracting move. [00:29:09] Speaker 01: They saw the cell cycle arrest in G2 to be a negative, not a positive. [00:29:15] Speaker 01: And they went looking for a drug that would counteract that negative aspect. [00:29:21] Speaker 01: That's contrary to what Akinaga was looking at. [00:29:24] Speaker 01: When we talk about the problem to be solved, Akinaga was looking at it way different than the inventors of the 512 path. [00:29:33] Speaker 01: Time. [00:29:34] Speaker 01: Thank you. [00:29:35] Speaker 01: Thank you. [00:29:35] Speaker 01: We thank both sides, and the case is submitted.