[00:00:41] Speaker 04: All right. [00:00:42] Speaker 04: The next case before the court, Roche Molecular Systems versus CEPHEDE. [00:00:46] Speaker 04: Did I pronounce that correctly? [00:00:49] Speaker 04: CEPHEDE. [00:00:51] Speaker 04: Case number 171690. [00:00:55] Speaker 04: Mr. Rabinowitz, do you want five minutes for rebuttal? [00:00:58] Speaker 02: Yes, please, Your Honor. [00:01:00] Speaker 02: OK. [00:01:03] Speaker 04: We'll see if we give it to you. [00:01:18] Speaker 02: Okay. [00:01:19] Speaker 02: May it please the court. [00:01:21] Speaker 02: The claims of the Pershing Patent are directed to novel materials and methods for detecting tuberculosis infection and detecting drug-resistant tuberculosis weeks or months earlier than could be accomplished in the prior art. [00:01:36] Speaker 02: This case presents the issue that this court did not resolve in Rebricker 1 with respect to claim 21 of myriad [00:01:47] Speaker 02: 441 patent, which was directed to detecting 10 particular mutations in the BRCA1 gene sequence. [00:01:55] Speaker 04: But with respect to the primers themselves, there's really broad language in the BRCA1 and 2 case that basically just says primers are not patent-eligible. [00:02:08] Speaker 04: I mean, it's that broad. [00:02:11] Speaker 04: How do we get around that if you want us to say, [00:02:16] Speaker 04: Well, some primers are pathological. [00:02:19] Speaker 02: So I would identify three points of distinction from the holding and from the statement in NREBRECA 1. [00:02:26] Speaker 02: And let me just enumerate them, and then I'll deal with them in some greater length. [00:02:29] Speaker 02: First, these primer claims are specific, not generic as in NREBRECA 1. [00:02:35] Speaker 02: Secondly, because MTB has a circular chromosome, faithfully applying the principles stated in NREBRECA 1 to the facts of this case produces a different result. [00:02:47] Speaker 02: And third, the import of the three prime hydroxyl structural difference was not argued to or addressed by the court in entry breaker one. [00:02:57] Speaker 04: Well, it clearly wasn't addressed the last point. [00:03:02] Speaker 04: I concede the court didn't address it. [00:03:04] Speaker 04: But wasn't it argued in the briefing at least? [00:03:07] Speaker 02: No, Your Honor, it was not. [00:03:09] Speaker 02: And the district court heard when it suggested that it was. [00:03:13] Speaker 02: And I'd like to quote to you. [00:03:15] Speaker 02: the portions that the district court focused on when it made what is really an erroneous factual finding that the distinction was argued. [00:03:23] Speaker 02: And I'll also show you that, in fact, the patent owner, Henry Bracco, made a factual concession that doomed the particular defense that we're relying on. [00:03:35] Speaker 04: OK, what page are you on? [00:03:37] Speaker 02: So this is in the Lexus version, which the district court [00:03:43] Speaker 02: cited to star 12, which is in the facts section. [00:03:51] Speaker 04: So where do I find that in your actual appendix? [00:04:17] Speaker 02: So this is on page, the first statement is on page eight of the brief, of the opening brief that's submitted to the court. [00:04:27] Speaker 02: In the carry on page eight. [00:04:28] Speaker 01: Of your brief? [00:04:29] Speaker 02: Of your brief, or of the? [00:04:32] Speaker 02: Of the brief submitted in Enri Brecker 1. [00:04:33] Speaker 02: The district court cited to the appellant brief in Enri Brecker 1 for the proposition that the issue had been argued to the panel in Enri Brecker 1. [00:04:45] Speaker 02: OK. [00:04:45] Speaker 01: Do you have a citation to the record that we can look at? [00:04:49] Speaker 01: To where the court cited to that. [00:04:52] Speaker 02: Yes, Your Honor. [00:04:57] Speaker 02: In appendix 23 to 24, beginning on line 28 of the appendix of the district court's opinion on page 23, [00:05:10] Speaker 02: district court states, indeed, Rocha's argument relating to this distinction was raised in an opening brief in Inry Brecker 1. [00:05:18] Speaker 02: And then the district court cites two portions of the appellant's opening brief. [00:05:24] Speaker 04: All right. [00:05:24] Speaker 04: And you say those citations by the district court are not correct? [00:05:28] Speaker 02: Well, let me identify what the appellant actually said in Inry Brecker 1. [00:05:34] Speaker 02: The appellant said, at star 12, [00:05:37] Speaker 02: The appellant said, there are no short single strands of DNA with a free three prime hydroxyl group that can serve as primers. [00:05:44] Speaker 02: And the appellant made, identified multiple features. [00:05:50] Speaker 02: Short single strands free three prime hydroxyl group. [00:05:57] Speaker 02: And then in the second quotation, they argued the import of this. [00:06:04] Speaker 02: And this is at star page 65. [00:06:08] Speaker 02: and then said claims to them the isolated fragments only cover use of the claimed material in PCR, an entirely separate man-made utility, as demonstrated below. [00:06:22] Speaker 02: In short, while a DNA fragment might be capable of being utilized by a scientist as a single primer, which is a fact we dispute, unless it's been changed to add a 3-prime hydroxyl, [00:06:33] Speaker 02: A claim to a pair of primers functioning together for use in PCR does not claim an unpatentable DNA fragment alone divorced from the pairs application in PCR. [00:06:44] Speaker 02: And so as we pointed out in our brief, the appellant in Rebricka 1 relied on two arguments. [00:06:50] Speaker 02: One was single strandedness and the other is that a pair of primers appropriately chosen had a utility together which a single DNA segment did not. [00:07:01] Speaker 02: Neither of those arguments relied on the chemical structural difference that we're relying on here between an isolated segment of DNA and one that has been changed by chemically adding a hydroxyl to the 3-primer. [00:07:16] Speaker 01: What's been changed? [00:07:17] Speaker 01: You get a primer because of that change? [00:07:20] Speaker 01: Yes, Your Honor. [00:07:21] Speaker 02: Merely isolating a segment of DNA does not produce a primer. [00:07:25] Speaker 02: A mere isolated segment of DNA, you need to actually chemically add [00:07:31] Speaker 02: a three prime hydroxyl. [00:07:33] Speaker 04: Right, because the three prime hydroxyl on a regular strand only ends up at the end, only appears at the end. [00:07:38] Speaker 02: If it's a linear strand, then it will have, as in humans, as in BRCA1, it will have a hydroxyl at the three prime end of the chromosome. [00:07:47] Speaker 02: In a bacterium like MTB, which has a circular chromosome, a circle has no end, there is no three prime hydroxyl. [00:07:53] Speaker 02: But certainly the segment that you've isolated does not, by virtue of its isolation, [00:07:59] Speaker 02: acquire a three-prime hydroxyl. [00:08:01] Speaker 04: So is that what you claim differentiates these primers, the three-prime hydroxyl, from what occurs in nature? [00:08:11] Speaker 02: From what may be isolated from nature, yes. [00:08:14] Speaker 02: And that was the issue that the Supreme Court addressed in the Myriad case. [00:08:19] Speaker 02: It said, it considered, it entertained the argument that in isolating you make a chemical change, but it said, well, for these claims, they don't depend. [00:08:28] Speaker 02: on any particular chemical change. [00:08:30] Speaker 01: The primers in BRCA1, they also had a three-prime hydroxyl group. [00:08:38] Speaker 02: They had a three-prime hydroxyl group at the end of the chromosome, not at the position of the prime, well, not within the BRCA1 gene. [00:08:50] Speaker 01: So they did have a three-prime hydroxyl group, it's just not, it's at a different [00:08:56] Speaker 01: location than what you have in this case. [00:08:59] Speaker 01: Yes, Your Honor. [00:08:59] Speaker 01: Well, how does that still make the primers in this case eligible for patenting? [00:09:09] Speaker 01: It seems to me you still have a problem that this is a naturally occurring substance. [00:09:15] Speaker 02: Your Honor, our argument is the primers claimed here do not occur in nature. [00:09:21] Speaker 02: There is no DNA strand [00:09:24] Speaker 02: with the required sequence that has a 3-prime hydroxyl on it. [00:09:28] Speaker 02: In order to create such a primer, you have to either synthesize or isolate a piece of DNA and put a 3-prime hydroxyl on it. [00:09:38] Speaker 04: And what is the benefit of doing that? [00:09:43] Speaker 02: isolate a strand of DNA that has a sequence but not the 3-prime hydroxyl, it will hybridize, it will stick to the DNA in the right portion, but it cannot prime a DNA amplification reaction. [00:09:56] Speaker 02: It cannot function in the PCR methods, which require actually a pair of primers, but it certainly requires these methods require a primer of a particular structure that was based on the discovery the inventors had made. [00:10:11] Speaker 02: But it is not a naturally occurring isolated segment of DNA. [00:10:15] Speaker 02: Because if you simply isolate without chemically changing, then you end up with a DNA that will hybridize but will not be a primer. [00:10:23] Speaker 04: So even if we were to agree, based on your reading of what was actually argued in the BRCA1 and BRCA2 cases, that this argument about the primers having a 3-prime hydroxyl was not [00:10:40] Speaker 04: actually presented to the court, so we shouldn't say they impliedly decided it. [00:10:44] Speaker 04: The language that was used in Bracket 1 and Bracket 2 is about as broad as you can imagine. [00:10:51] Speaker 02: It is, Your Honor. [00:10:52] Speaker 02: Let me address that. [00:10:53] Speaker 04: How do we get around that? [00:10:55] Speaker 02: The answer is McCutcheon. [00:10:57] Speaker 02: The Supreme Court addressed this issue with McCutcheon. [00:11:00] Speaker 02: And in McCutcheon, there are a total of three sentences in the Bracket 1 case, exactly three sentences that deal with this. [00:11:08] Speaker 02: In McCutcheon, the Supreme Court- Pretty deadly sentences for you. [00:11:13] Speaker 02: If they bind this law, then it would be constrained in the decision it could reach here. [00:11:20] Speaker 02: I suggest they do not. [00:11:22] Speaker 02: For the reason that it was said in McCutcheon, because in McCutcheon, the Supreme Court had decided an issue in Buckley v. Vallejo, actually, the aggregate contribution limits. [00:11:35] Speaker 02: It reached exactly the opposite conclusion in McCutcheon. [00:11:38] Speaker 02: And it said it was free to do so for the following reason. [00:11:41] Speaker 02: They said, this case cannot be resolved by merely pointing to three sentences in Buckley that were written without the benefit of full briefing or argument. [00:11:51] Speaker 02: In other words, the parties in McCutcheon directed their focus to this particular issue, which had been stated clearly in the contribution, the aggregate contribution limit had been upheld in [00:12:07] Speaker 02: Buckley v. Vallejo as incidental to the individual contribution limits and a means of avoiding evasion, the Supreme Court held it was not constrained by stare decisis, because it had not considered the particular arguments being advanced in McCutcheon, which weren't in McCutcheon. [00:12:24] Speaker 02: Because three sentences written without the benefit of briefing and argument were not enough to please the court. [00:12:31] Speaker 01: And Mariette, it's emphasized that genetic information encoded is not penitent. [00:12:37] Speaker 02: That's correct, Your Honor, and we embrace that. [00:12:40] Speaker 01: Now, it seems to me, just from what I can gather, that these primers are exactly that. [00:12:47] Speaker 01: You're still left with genetic information that's encoded. [00:12:51] Speaker 02: With respect, Your Honor, I disagree with that and let me explain why. [00:12:56] Speaker 01: As the Supreme Court points out in... But just the primers are not, they're not genetic information encoded? [00:13:05] Speaker 02: They have a sequence which actually... Yeah, and that's genetic encoded... That is part of the structure of the primer, but not all of it. [00:13:14] Speaker 04: But the nucleotide sequence itself is found in nature, right? [00:13:19] Speaker 02: That's correct. [00:13:20] Speaker 02: So if you look at the claims in Myriad and the... All genetic information encoded is found in nature. [00:13:29] Speaker 02: Your Honor, you can claim a piece of DNA for what it encodes, which happened in Myriad, or you can change it and use it as a tool and claim it as a tool, which is what's happening in these primer claims. [00:13:43] Speaker 01: In Myriad... OK, so now I think we're getting, at least in my view, the point here. [00:13:49] Speaker 01: What is it about these primers that are different than what we saw in BRCA1? [00:13:56] Speaker 02: So in BRCA1, [00:13:59] Speaker 02: The first thing that's specific, unlike the claims in BRCA1 were any pair of primers that hybridizes to any part of the BRCA1 gene at all. [00:14:10] Speaker 02: So these are very specific. [00:14:12] Speaker 02: They must hybridize to one or more of the 11 identified signature nucleotides. [00:14:17] Speaker 01: But if the standard is all genetic code, and now you've taken us to just part of it, it seems to me you're still included in that more general [00:14:29] Speaker 01: group. [00:14:30] Speaker 02: No, Your Honor, I think specificity, which the underlying concern of these judicial exceptions is preemption, and this is very narrow and specific, coupled with the fact that it requires a physical change. [00:14:43] Speaker 02: The Supreme Court said in myriad that cDNA is patent eligible because it does not occur like that in nature. [00:14:50] Speaker 01: Yes, but this is not cDNA. [00:14:52] Speaker 02: But the Supreme Court did that recognizing two things. [00:14:55] Speaker 01: Okay, well that's fine, but [00:14:57] Speaker 01: This is not cDNA we have here. [00:15:00] Speaker 02: That's correct, Your Honor. [00:15:03] Speaker 02: cDNA is patent eligible if it has been altered in the structure of its sequence. [00:15:08] Speaker 02: We say these primers are patent eligible because they have been altered in the structure at the ends. [00:15:16] Speaker 02: They are claimed and used as tools that can accomplish something, in other words, priming a copying reaction. [00:15:23] Speaker 02: They are not being used for the information content, which was the claim in Myriad. [00:15:27] Speaker 02: They must do two things simultaneously. [00:15:31] Speaker 02: Number one, they must have the correct sequence that allows them to hybridize. [00:15:35] Speaker 02: And it's not really the gene coding content, because this happens whether it's a coding or a non-coding element of the interface. [00:15:43] Speaker 02: And secondly, they must have this free-prime hydroxyl, because otherwise they cannot perform the priming function. [00:15:51] Speaker 04: OK, your time's about up. [00:15:52] Speaker 04: I'll give you back some time for rebuttal. [00:15:54] Speaker 04: But do you want to say something about the other claims [00:15:57] Speaker 04: first in the Mayo issue? [00:16:00] Speaker 02: Yes, Your Honor. [00:16:03] Speaker 02: So on the method claims, we would say they're patent eligible on two separate bases. [00:16:10] Speaker 02: First, if the court upholds the prime offender's patent eligible and under this court's decision in association for molecular pathology, a method of using a patent eligible material is itself patent eligible. [00:16:22] Speaker 02: But even if [00:16:23] Speaker 02: uh... the uh... uh... uh... uh... uh... uh... uh... uh... uh... uh... uh... uh... uh... uh... uh... uh... uh... [00:16:43] Speaker 02: in PCR which comprises the use of a primer with recited structure, which was the undisputed evidence shows this was unprecedented to do in PCR. [00:16:54] Speaker 02: When you perform, so the process step, the amplification step, has been changed from what was conventional. [00:17:02] Speaker 02: Are you saying these claim a new PCR process? [00:17:05] Speaker 02: It is a process, a process using such a primer is an advance in PCR [00:17:13] Speaker 03: But the PCR process is the same. [00:17:15] Speaker 02: The general process for PCR is the same, but when you focus the claims on a particular way of performing PCR that gives you a completely new... But do these claims then have to rise and fall together? [00:17:28] Speaker 04: In other words, we have to agree with you that the primers are patent eligible? [00:17:31] Speaker 02: No, Your Honor, you do not. [00:17:33] Speaker 02: If the primary claims are patent eligible, then so are the method claims, but the reverse is not true. [00:17:38] Speaker 02: If the primary claims are not patent eligible, the method claims are separately. [00:17:42] Speaker 02: patent eligible because they represent an improvement in a PCR test which comprises integrating the inventor's discovery into a general PCR method in the same way that the Arrhenius equation was integrated into a general old method for curing rubber. [00:18:00] Speaker 03: Isn't that just Arioso though? [00:18:04] Speaker 03: They made a discovery about how you could detect fetal DNA in the bloodstream [00:18:11] Speaker 03: and extract it and amplify it and do sequencing to discover certain defined genetic conditions. [00:18:19] Speaker 03: You've made the discovery that this particular sequence identifies this bacteria as tuberculosis, and you then use PCR in a routine way to identify it as tuberculosis. [00:18:33] Speaker 02: No, Your Honor. [00:18:34] Speaker 02: If our claims said, as the claims in Ariosa said, performing [00:18:41] Speaker 02: PCR using any primer you like and detecting the presence of these signature nucleotides, which you can do by performing PCR and then doing a sequencing reaction or using a probe, that would be appending conventional methods stated at a high level of generality to the recitation of a natural phenomenon. [00:19:06] Speaker 03: But you're still just using one specific natural phenomenon [00:19:10] Speaker 03: to detect and identify a certain type of bacteria. [00:19:13] Speaker 02: There are many ways of detecting these particular signature nucleotides that are not embraced by these very specific claims. [00:19:22] Speaker 02: You can amplify using primers directed to other portions of the gene, in other words, ones that don't hit at signature nucleotide, and amplify a region including the signature nucleotide, and then sequence it, or use a... How do you get around the language in our cases and in the Supreme Court that say, [00:19:40] Speaker 04: that there's a difference between just identifying something and providing for a more practical use? [00:19:47] Speaker 02: The answer is in CellsDirect. [00:19:50] Speaker 02: In CellsDirect, there was an old method of preserving hepatocytes which included a single free store step. [00:19:56] Speaker 02: The inventors discovered that hepatocytes could survive not only one, but two rounds, multiple rounds, and so they [00:20:06] Speaker 02: applied this, they integrated this discovery into a method by doing something which was perfectly obvious once you identified the multiple freeze-thaw viability, they did freezing and thawing twice. [00:20:19] Speaker 02: And that actually produced an improvement which solved problems in the prior arms. [00:20:24] Speaker 02: Here, the inventors discovered particular 11 specific signature nucleotides [00:20:30] Speaker 02: And they didn't claim a method of amplifying and then comparing to detect. [00:20:34] Speaker 02: That would have been the equivalent of the claim in BRCA1. [00:20:38] Speaker 02: And they didn't claim general methods of amplifying, as was the case in Ariosa. [00:20:46] Speaker 02: They specified that you cannot do the amplification step in the way it was conventionally done in PCR, but you had to use a novel primer that they were able to design based on their discovery. [00:20:58] Speaker 03: Well, that sounds like to me you're basing that part of the argument on the notion that the primer itself is patent eligible. [00:21:04] Speaker 03: Let's assume it's not. [00:21:05] Speaker 02: No, Your Honor, it's not. [00:21:07] Speaker 03: Well, let's assume it's not, because that's where I want to talk about Ariosa. [00:21:11] Speaker 03: I mean, I think you're running into the same problem on this point with the broad language in Ariosa that you are in BRCA1. [00:21:18] Speaker 03: I mean, Ariosa said when it starts with a natural phenomenon, like a gene sequence, and it ends with identifying that gene sequence, which is what you do, [00:21:28] Speaker 03: to say, this is tuberculosis, that that's not patent-eligible. [00:21:32] Speaker 02: Not if you specify a particular improved way of detecting the natural phenomenon that the inventors have discovered. [00:21:40] Speaker 02: I think we're getting a little bit circular here, but... John, may I just point out that the Supreme Court in there has emphasized that new ways of using an existing drug are patent-eligible. [00:21:52] Speaker 04: Okay, but you're way past your time. [00:21:54] Speaker 04: So I'll give you three minutes for rebuttal. [00:21:57] Speaker 04: will allow you to go overall, try to even out the time. [00:22:00] Speaker 02: May I have my five minutes? [00:22:02] Speaker 04: No, three. [00:22:05] Speaker 04: We're way over. [00:22:06] Speaker 00: Thank you, Your Honor. [00:22:14] Speaker 00: May it please the Court. [00:22:18] Speaker 00: To rely on Mayo, the patent here just tells the relevant audience, biologists, about the natural law that the inventors discovered. [00:22:26] Speaker 00: that the signature nucleotides can be used to identify MTB? [00:22:31] Speaker 04: Well, I want to start with the primers. [00:22:33] Speaker 00: OK. [00:22:33] Speaker 04: All right. [00:22:33] Speaker 04: So if we conclude that the argument really wasn't made about the three-prime hydroxyl at the end of these primers, that that argument really wasn't made in bracket 1 and bracket 2, are we bound by the language in bracket 1 and bracket 2? [00:22:52] Speaker 00: You are, because first of all, [00:22:55] Speaker 00: But Rocha's counsel tries to dismiss the holding of Brocka 1, that the primers are not eligible in that case, as three offhand sentences citing the Kutchum case. [00:23:08] Speaker 00: Those three sentences are the culmination of a pretty thorough analysis of the primers in the context of the Myriad case. [00:23:17] Speaker 04: But never was there any discussion of the three-prime hydroxyl at the end. [00:23:22] Speaker 00: Well, there was. [00:23:23] Speaker 00: And I have actual quotes from the brief. [00:23:25] Speaker 00: He missed a couple of quotes. [00:23:27] Speaker 04: No, I'm talking about in the opinion itself. [00:23:29] Speaker 00: In the opinion itself, there's not. [00:23:30] Speaker 00: But let me go through and talk about why it doesn't make a difference, because the 3-prime hydroxyl exists on the BRCA primers, just as it exists on the primers here. [00:23:46] Speaker 00: The three prime hydroxyl has to exist on every primer that's ever existed, whether it's natural or whether it was made in the lab. [00:23:53] Speaker 01: And we said something a little bit different in BRCA, and that was, I guess, dicto or not essential to the holding. [00:24:01] Speaker 01: Am I correct on that? [00:24:03] Speaker 00: No. [00:24:04] Speaker 00: No, there's nothing that's inconsistent with what I just said in BRCA. [00:24:09] Speaker 00: In fact, when you look at BRCA's statement, [00:24:13] Speaker 00: that says primers do not perform a significantly new function that's equally true for the priming function here because primers in nature perform the priming function and in fact primers as they've ever been used every primer ever made performs the priming function because every primer has to have a three prime hydroxyl which gets us to the myriad analysis because it's not enough [00:24:40] Speaker 01: So for Claim 21 in BRCA, we said we expressed no view on primaries reciting certain sequences. [00:24:47] Speaker 00: Correct. [00:24:49] Speaker 01: And remember, in BRCA for the method claims... So there was... We did recognize that there's something there that we're not addressing in BRCA. [00:24:59] Speaker 00: Correct. [00:25:00] Speaker 00: The preemption argument that Roche's counsel brought up. [00:25:03] Speaker 00: But remember, in BRCA, [00:25:06] Speaker 00: The claims are being analyzed in the abstract idea context of Alice, not in the natural phenomena, natural law context of Mayo. [00:25:16] Speaker 00: And as the court said in Ariosa, that when you're talking about a natural law, it doesn't matter whether you're talking about a broad natural law or a narrow natural law. [00:25:25] Speaker 00: It's a natural law, and it's ineligible, regardless of its scope. [00:25:28] Speaker 00: And in fact, when you're considering preemption. [00:25:31] Speaker 04: But if you look at Funkin, [00:25:34] Speaker 04: Chakrabarti, the question is, is there a marked difference from what occurs in nature? [00:25:38] Speaker 00: Correct. [00:25:40] Speaker 04: And so is there anything about these primers that is not different from what occurs in nature? [00:25:47] Speaker 00: There's nothing. [00:25:48] Speaker 00: And that's what I was getting to with the discussion of Myriad. [00:25:50] Speaker 00: Remember, in Myriad, the Supreme Court recognized that the isolated claims in front of it were different. [00:25:56] Speaker 00: from that sequence in nature. [00:25:58] Speaker 00: They were different because the bonds were severed. [00:26:00] Speaker 00: And so they refer, the Supreme Court refers to those claims as a non-naturally occurring molecule. [00:26:06] Speaker 00: They're different than what occurs to nature. [00:26:08] Speaker 00: But the court doesn't stop there. [00:26:10] Speaker 00: It says, OK, let's look at the differences, and let's decide whether those differences are the result of an inventive concept. [00:26:18] Speaker 00: It's the language used in Alice. [00:26:21] Speaker 00: Myriad uses the language, they're not the result of invention. [00:26:25] Speaker 00: So the question that Rocha's council needs to answer is whether these three prime hydroxyls at the ends of these primers are invention. [00:26:32] Speaker 00: Are they an inventive concept? [00:26:34] Speaker 04: But do these particular primers occur in nature? [00:26:38] Speaker 00: They're a little different. [00:26:41] Speaker 04: Right. [00:26:41] Speaker 00: They're different. [00:26:42] Speaker 00: That's the point, right? [00:26:42] Speaker 00: The isolated, the sequence that's claimed as it exists in the MTB chromosome doesn't have a three prime hydroxyl because it's surrounded [00:26:51] Speaker 00: by other nucleotides. [00:26:52] Speaker 00: Exactly. [00:26:53] Speaker 04: So you'd have to be all the way at the end of the strand to get to the hydroxyl. [00:26:57] Speaker 00: Well, there's no hydroxyl at all in the circular MTB chromosome. [00:27:03] Speaker 00: But in the BRCA case, the BRCA gene had no three prime hydroxyl either. [00:27:10] Speaker 00: The gene that was at issue in the three prime hydroxyl, there's a three prime hydroxyl on the chromosome. [00:27:15] Speaker 00: But that's millions of miles, millions of miles. [00:27:18] Speaker 04: And so isn't that a distinction between the BRCA case and this case? [00:27:21] Speaker 00: It's not a valid distinction. [00:27:22] Speaker 00: It's not a valid distinction because, well, their own experts said that whether you're talking about a linear chromosome or a circular chromosome, the process of making a primer is going to be the same. [00:27:35] Speaker 00: That's within the ordinary skill. [00:27:36] Speaker 04: All you have to know, as soon as you know... Well, that goes to obviousness, not to... No, no, no. [00:27:41] Speaker 00: It goes to conventional methods. [00:27:43] Speaker 00: It goes to the primer, which is an essential part of PCR. [00:27:47] Speaker 00: Everybody who's ever done PCR [00:27:50] Speaker 00: needs to make a primer. [00:27:51] Speaker 00: And so making the primer is a conventional step as part of the conventional process of PCR. [00:27:57] Speaker 00: All you have to know is the sequence. [00:28:00] Speaker 00: So the natural law is the sequence. [00:28:02] Speaker 00: This sequence helps identify MTB. [00:28:04] Speaker 00: Once you've identified that to the relevant audience, to biologists, the rest is easy. [00:28:09] Speaker 00: The rest is just standard PCR. [00:28:11] Speaker 00: Their own expert admits it. [00:28:13] Speaker 00: The patent admits it. [00:28:14] Speaker 00: It talks about primer manufacture is just conventional. [00:28:18] Speaker 00: They use standard processes. [00:28:20] Speaker 00: The amplification step using that primer is just a standard process. [00:28:24] Speaker 04: That wasn't the basis for the Brackett decision. [00:28:26] Speaker 04: The basis for the Brackett decision was that there was no identification of anything about these primers that wasn't exactly the same as what occurs in nature. [00:28:37] Speaker 04: And here, you're conceding that these primers don't occur in nature. [00:28:41] Speaker 00: So I disagree that the court based its premise on it's exactly the same as it is in nature. [00:28:47] Speaker 00: It recognized the overarching concern [00:28:50] Speaker 00: with the primers in BRCA is the same as the overarching concern with the primers here. [00:28:55] Speaker 00: And that is the genetic sequence that you need to amplify. [00:29:00] Speaker 00: So the primer needs to mimic the complementary sequence that you're trying to amplify. [00:29:05] Speaker 00: That's the overriding concern. [00:29:07] Speaker 00: Now, this idea of the three prime hydroxyl, if you want an indication of the relative importance between the importance of the sequence [00:29:15] Speaker 00: and the importance of a three prime hydroxyl, all you have to do is look at the patent. [00:29:18] Speaker 00: There's not a single mention anywhere in the patent of a three prime hydroxyl. [00:29:22] Speaker 00: It is an unremarkable feature of every primer that's ever existed. [00:29:28] Speaker 00: And so it doesn't even merit mentioning it in the 723 patent. [00:29:33] Speaker 01: Does it make a difference? [00:29:34] Speaker 01: What if it did mention it? [00:29:36] Speaker 00: If it did mention it, it would mention it in the context of [00:29:39] Speaker 00: Other than the sequence, this primer is identical to all the other primers that have ever been made in a lab. [00:29:44] Speaker 00: It's made out of DNA. [00:29:45] Speaker 00: It's going to have the three prime hydroxyl on it because it needs to mimic primers that exist in nature. [00:29:55] Speaker 00: I can go to the method claims. [00:29:57] Speaker 04: Yeah, I mean, it seems to me like you've already done. [00:29:59] Speaker 04: In other words, you seem to be conflating Mayo and Myriad. [00:30:03] Speaker 04: We have two different types of analyses going on here, right? [00:30:06] Speaker 00: The underlying principle is the same. [00:30:09] Speaker 00: Mayo makes the two-step analysis explicit. [00:30:14] Speaker 00: Remember, Myriad recognizes that, yeah, there are going to be some differences between the claim and the natural corollary to the claim, the analog in nature. [00:30:27] Speaker 00: But then the court goes on and says, mimicking the language of Mayo, where it says, [00:30:35] Speaker 00: In that case, isolating DNA from its surrounding genetic material is not an active invention. [00:30:41] Speaker 00: That's the inventive concept of step two of NAO. [00:30:45] Speaker 00: And what we're saying is putting this three prime hydroxyl at the end of a primer is not an active invention. [00:30:51] Speaker 00: It's not an inventive concept. [00:30:52] Speaker 00: Because as soon as you tell biologists, here's the sequence you need to amplify. [00:30:58] Speaker 00: They're going to get the complementary sequence, and they're going to put a 3-prime hydroxyl on it, because that's the only way primers will work. [00:31:04] Speaker 00: And that's the way everybody knows primers are going to work. [00:31:07] Speaker 00: So it's just a conventional step that's taken in the claims. [00:31:11] Speaker 00: And so I don't think I'm conflating the two. [00:31:13] Speaker 00: I think the two are actually pretty close analyses, although I will admit that myriad doesn't make the two-step analysis explicit. [00:31:20] Speaker 01: What if the claim is for concentrations that are above that, of primers that are above that, what you find in nature? [00:31:29] Speaker 01: If, let's say like two million times more than what you find in nature, is that pannable? [00:31:35] Speaker 00: That could be. [00:31:37] Speaker 00: I don't know enough about PCR to know whether something like that would be routine to a person in the lab. [00:31:43] Speaker 00: But certainly the three prime hydroxyl is routine. [00:31:46] Speaker 00: It's not just routine. [00:31:47] Speaker 00: It's necessary. [00:31:49] Speaker 00: And biologists recognize it is necessary. [00:31:51] Speaker 00: It's just part of the routine, part of PCR. [00:31:53] Speaker 00: But that's the kind of thing that might be eligible under step two of MEA. [00:31:59] Speaker 00: which is, yeah, you know, standard PCR is conventional, but this is a modification of PCR, like the modification to the lab technique in cells direct, where all of a sudden you're not doing it. [00:32:11] Speaker 04: What if someone created a triple-stranded DNA, but it had the same sequence? [00:32:20] Speaker 00: I'd say, off the top of my head, triple-stranded DNA doesn't exist in nature. [00:32:26] Speaker 00: That sounds to me more like cDNA. [00:32:28] Speaker 00: than the kind of primers that are involved here. [00:32:30] Speaker 00: I think that sounds to me like it would pass muster under the Supreme Court's tests. [00:32:39] Speaker 00: So I'll go to the method claims. [00:32:41] Speaker 00: And there really is no real distinction here between the method claims in Ariosa, the method claims in genetic technologies, and the method claims here. [00:32:52] Speaker 00: Roche takes the position that nobody has ever [00:32:55] Speaker 00: amplified this sequence of DNA with primers to detect MTB before. [00:33:00] Speaker 00: Well, the patent owner in Ariosa said nobody had ever amplified SIF DNA with primers out of maternal blood before. [00:33:10] Speaker 00: The patentee in genetic technologies, nobody had ever used a primer to amplify non-coding sequences to detect coding sequences. [00:33:18] Speaker 00: The question is not whether anybody's ever done that before. [00:33:21] Speaker 00: The question is, first look at the claims. [00:33:23] Speaker 00: Are they directed to? [00:33:25] Speaker 00: ineligible subject matter. [00:33:27] Speaker 00: Here, the claims are directed to the correlation between these signature nucleotides and the presence of MTB. [00:33:36] Speaker 00: Just like Mayo correlation, genetic technologies, the correlation between coding and non-coding, the Cleveland Clinic case. [00:33:48] Speaker 03: I mean, I understand it. [00:33:49] Speaker 03: I find Arioso. [00:33:52] Speaker 03: hard to get around to, but the implications of this to me are really troubling. [00:33:57] Speaker 03: What's the difference between saying we have this naturally occurring piece of DNA that we can then use to do a specific test and predict a specific result, and we have this natural occurring product of nature that we have discovered will treat a certain condition? [00:34:21] Speaker 03: It's because there's no alteration of the natural product. [00:34:29] Speaker 03: There's nothing. [00:34:29] Speaker 03: It's either you take a pill or even something. [00:34:33] Speaker 03: The example I was thinking about was aloe. [00:34:39] Speaker 03: If somebody was the first person to discover if you take an aloe plant and slice it open and put it on a burn, can they patent that? [00:34:48] Speaker 00: I think the analysis would have to go to the second step of Mayo, which is this is a routine conventional step to take aloe, take something from a plant and rub it on your skin. [00:34:59] Speaker 04: I think that the Mayo case addresses that kind of concern, which is a new use of an existing... But isn't there a difference between just identifying something and then putting it to a non-conventional use? [00:35:15] Speaker 00: There is. [00:35:16] Speaker 00: There is a difference. [00:35:17] Speaker 00: And the method claims here are identifying the MTB, identifying the natural phenomenon, that if you see these nucleotides, then MTB exists. [00:35:35] Speaker 00: That's exactly the kind of claim that CellsDirect distinguished, which is CellsDirect [00:35:43] Speaker 00: used a natural law, but it used the natural law, used the insight gained from the natural law in order to create something, in order to create a collection of cells that had improved viability. [00:35:54] Speaker 00: And so that's an example of integration. [00:35:57] Speaker 00: But the Cells Direct case itself pointed to ARIOSA, pointed to genetic technologies and said [00:36:03] Speaker 03: But you have to create a new product in order for it to be patent eligible, or can it just be a new application of an existing product? [00:36:11] Speaker 00: It can be a new application as long as that application is not conventional. [00:36:15] Speaker 00: Here, the application of their discovery is PCR. [00:36:21] Speaker 03: In the words of... Well, that's the way you want to describe it. [00:36:24] Speaker 03: I mean, you could describe it as the application of their product is a new way to identify tuberculosis. [00:36:34] Speaker 00: Well, and Ariosa, you'd have a long line of patentees behind them saying that, because the Ariosa... I get it. [00:36:42] Speaker 03: I think Ariosa has language that forecloses that argument. [00:36:45] Speaker 03: It's just that the scope of that is kind of breathtakingly broad. [00:36:51] Speaker 03: I totally understand the concern, but I... Can you tell me, can you give me an example of a diagnostic method based upon [00:37:00] Speaker 03: discovery of a gene sequence that is now patent eligible in any way you stated? [00:37:06] Speaker 00: If such a thing exists, I think it would be patent eligible under the second step of MAYA. [00:37:14] Speaker 00: And what would you have to put into it to get it eligible under the second step? [00:37:18] Speaker 00: You'd have to use something other than off-the-shelf PCR. [00:37:21] Speaker 03: But then it's not the gene sequence, it's the actual process itself that's [00:37:26] Speaker 00: Well, and I think that's the gist of Mayo. [00:37:29] Speaker 03: So your answer really is there is no genetic testing patent that, if it's using conventional methods, is patent eligible? [00:37:35] Speaker 03: I think that's the necessary implication of Mayo. [00:37:38] Speaker 04: Do you agree that if the primers, if we find the primers to be patent eligible, if we distinguish this case from BRCA1 and we found the primers to be patent eligible, that the method claims would necessarily be patent eligible? [00:37:53] Speaker 00: If you were to find the primers eligible, you'd have to go so far as to say that the creation of the primers, notwithstanding the statement in the patent that we're just using conventional processes to make the primers. [00:38:06] Speaker 00: If you're going to make that finding, I think you're right. [00:38:11] Speaker 00: I don't see how we could also say that the method claims are ineligible if you make that finding. [00:38:17] Speaker 00: But I just don't think the record and the law can support that finding. [00:38:20] Speaker 01: But if we find penability under step one, then we don't go to step two. [00:38:25] Speaker 00: That's correct. [00:38:26] Speaker 00: If you find eligibility under step one, then the answer to step two doesn't really matter. [00:38:32] Speaker 01: And that's normally where the PCR-type application falls into place in these cases? [00:38:39] Speaker 00: On the step one? [00:38:40] Speaker 01: On the step two. [00:38:41] Speaker 00: On step two, yes. [00:38:42] Speaker 00: I think that's right, that they have to show something other than just standard off-the-shelf PCR. [00:38:48] Speaker 00: Thank you. [00:38:49] Speaker 04: OK. [00:38:50] Speaker 04: Thank you. [00:39:03] Speaker 02: Your Honour, if I may very briefly address just a couple of points. [00:39:07] Speaker 02: First, in the Bricklewine case, counsel for the patentee made a concession opposite to the one the counsel here has made. [00:39:17] Speaker 02: And this is pointed out twice on pages 27 and 37 of the appellee's brief, where they cite to a finding of fact that the district court made, which appears at page 1266 of the district court's opinion. [00:39:33] Speaker 02: at 1266, where the district court said, utility depends on the fact that a DNA segment used as a primer is structurally and functionally the same as a native genomic DNA segment with the same sequence and length. [00:39:51] Speaker 02: That is an untrue fact. [00:39:53] Speaker 02: It was conceded to be true in the Prickle One case. [00:39:58] Speaker 02: is we have created a report that refutes that proposition. [00:40:02] Speaker 04: What's your response to your friend's argument that the patent doesn't even emphasize the three prime hydroxyl? [00:40:10] Speaker 02: It does, Your Honor, because it uses the word primer. [00:40:13] Speaker 02: And there is no need to tell a molecular biologist that a primer has a three prime hydroxyl anymore than you need to tell a carpenter that a nail has a sharp point at one end. [00:40:22] Speaker 04: So then why doesn't that make it just a conventional response to [00:40:28] Speaker 04: analyzing these things that occur in nature. [00:40:31] Speaker 02: It makes it structurally different from what occurs in nature. [00:40:34] Speaker 02: And the Supreme Court in Myriad said, CBNA is patent eligible, even though it acknowledged that methods for making CBNA were well known in genetics at the time, and that the sequence of the CBNA is determined by the naturally occurring mRNA. [00:40:52] Speaker 02: It doesn't require an innovative method if it is structurally different. [00:40:56] Speaker 02: That's what the Supreme Court held in May. [00:40:58] Speaker 02: And for the same reasons that cDNAs produced by conventional method with sequences determined by the mirror image natural sequence of mRNA were patent eligible because they were not found in nature. [00:41:13] Speaker 02: So these claim primers are not found in nature and are likewise patent eligible. [00:41:18] Speaker 02: Primers found in nature are RNA, they're not DNA. [00:41:21] Speaker 02: They don't have a length of 15 or 14 to 15 nucleotides as these claimed [00:41:26] Speaker 02: primers have, and they're never single-stranded. [00:41:30] Speaker 02: That's undisputed in the record. [00:41:31] Speaker 02: They are different. [00:41:33] Speaker 02: And the fact that an untrue fact was conceded in an argument we rely on here was not made in the Brecker 1 case, or not to bind this panel in the decision it reaches on this record. [00:41:46] Speaker 01: But the primer series genetic information encoded. [00:41:49] Speaker 02: Yes, part of it. [00:41:51] Speaker 01: And that is what's not pannable. [00:41:53] Speaker 02: But we're not trying to patent the genetic information. [00:41:56] Speaker 02: We're trying to patent... But your primers end up being that. [00:41:59] Speaker 02: No, Your Honor, it doesn't. [00:42:00] Speaker 02: If all the primer contains its genetic information, it will not function as a primer because it doesn't have a 3-prime hydroxyl. [00:42:08] Speaker 02: The primer has been fashioned into a tool by taking a segment of DNA that cannot support priming and changing it chemically so that it can. [00:42:18] Speaker 02: And even though it's an addition of a single chemical group at a particular point, that all that distinguishes naturally occurring penicillin, which cannot be patented because it's isolated from a fungus that it goes in nature, and ampicillin, where you've attached a single chemical group and created a non-naturally occurring synthetic penicillin with new properties, new broad spectrum results, [00:42:44] Speaker 02: There's a vast array of pharmaceutical patents which depend on changing naturally occurring compounds by adding a single chemical group, or perhaps more than one. [00:42:53] Speaker 02: The Supreme Court in Mayo said the typical pharmaceutical patent for a new compound, even if you create it by the obvious step of adding a hydroxyl, is not patented and ineligible. [00:43:07] Speaker 02: And then to go to the point you raised, Judge Hughes, about- No, your time is up. [00:43:11] Speaker 04: Your time is up. [00:43:12] Speaker 04: I'd let you even go past your three minutes. [00:43:14] Speaker 04: Thank you, Your Honor. [00:43:16] Speaker 04: We have to stop at some point.