[00:00:25] Speaker 03: argument is 15-1-2-0-0, industrial technology research versus specific biosciences. [00:00:36] Speaker 01: Thank you your honor, may it please the court. [00:00:38] Speaker 01: The count in this case requires that you locate modified bases in a circular molecule by comparing the sequences of the forward and the reverse strand and then looking for mismatches in those sequences. [00:00:52] Speaker 01: The board here [00:00:53] Speaker 01: awarded PACBIO priority based on an application that didn't even mention, didn't even disclose mismatches, let alone use them to locate modified bases. [00:01:04] Speaker 01: And PACBIO doesn't defend the board's reasoning on two of the three grounds of obviousness and the third ground of obviousness improperly used eTree's own disclosure in the 630 patent against it. [00:01:18] Speaker 01: Before getting to priority and obviousness, I feel I need to address claim construction first. [00:01:23] Speaker 01: There's been a question raised whether the board adopted E-Tree's claim construction of the count. [00:01:30] Speaker 01: And at A10, the board construed the count. [00:01:33] Speaker 01: It wasn't just simply repeating the party's positions. [00:01:36] Speaker 01: It construed the count to require, quote, comparing. [00:01:40] Speaker 01: One compares the sequences of the forward and reverse strands and determines that a modified base is present at positions where there is a disagreement. [00:01:48] Speaker 01: That's E-Tree's construction. [00:01:50] Speaker 01: That's the construction where pushing on appeal. [00:01:53] Speaker 01: The board applied only that construction. [00:01:56] Speaker 01: It applied that construction to the layered reference at A40. [00:02:00] Speaker 01: It applied that construction to the 551 application at A53 and 54. [00:02:08] Speaker 01: And that's the correct construction. [00:02:11] Speaker 01: It's the correct construction because it makes no sense to ignore the mismatch that's recited in the determining by comparing step. [00:02:19] Speaker 01: In fact, PacBio's own expert, Dr. Zahn, [00:02:22] Speaker 01: admitted that not only is the mismatch rendered irrelevant under PAC BIOS construction, but the entire comparing step is irrelevant under PAC BIOS construction. [00:02:34] Speaker 01: And then finally, the count, because it comes from eTree's specification, needs to be construed. [00:02:40] Speaker 01: In light of that specification, there is a section in the 630 patent talking about how you determine the position of modified bases. [00:02:49] Speaker 01: That's the title of the section. [00:02:50] Speaker 01: And every time a mismatch is mentioned in that section, it's actually used to determine the modified base. [00:02:57] Speaker 03: Before your time, you've got a limited amount of time. [00:03:00] Speaker 03: Speaking only for myself, of course, I'd appreciate your turning to Claim 23 and Claim 27 and 28. [00:03:08] Speaker 03: Of course. [00:03:09] Speaker 01: Well, those are the rejections I talked about earlier that PacBio abandons the board's reasoning. [00:03:15] Speaker 01: And Claim 23 requires that you use known inserts. [00:03:20] Speaker 01: And then you compare, you check the results of your sample sequence based on how accurate your known sequence was. [00:03:29] Speaker 01: The board found that that was taught by the 375 patent and Laird. [00:03:33] Speaker 01: And nowhere in either reference is that discussed. [00:03:39] Speaker 01: And so PacBio takes a different tack on appeal. [00:03:43] Speaker 01: And it decides that the advance of using known sequences [00:03:49] Speaker 01: in the inserts is just not too modest of an advance over the prior art to be given patentability. [00:03:57] Speaker 03: Well, they cite a section, a disclosure in 375 patent, which they say supports that this was already known. [00:04:04] Speaker 01: It doesn't support confirming the sequence of your sample by looking at scores of the insert. [00:04:13] Speaker 01: It talks about scoring, but it only talks about scoring the sample sequence. [00:04:18] Speaker 01: and then rejecting or accepting the sample sequence based on the score that you derive from the sample sequence. [00:04:24] Speaker 01: There is no disclosure of using the inserts. [00:04:26] Speaker 01: There are a lot of useful things that the 375 patent talks about the inserts being used for, but it doesn't talk about scoring the inserts and then using that score to accept or reject the samples. [00:04:39] Speaker 03: But we're not talking about anticipation here. [00:04:41] Speaker 03: We're talking about obviousness. [00:04:42] Speaker 01: We are talking about obviousness. [00:04:45] Speaker 01: There are two responses to PacBio's position. [00:04:47] Speaker 01: The first is this isn't the position they raised in front of the PTO, so it's waived. [00:04:51] Speaker 01: But even if this court were inclined to perform that factual determination here, the board didn't make that factual determination that the differences are significant. [00:05:01] Speaker 01: They found that they were actually disclosed in the prior arc. [00:05:06] Speaker 01: But if this panel were to do that kind of fact finding, there's simply no evidence in the record. [00:05:13] Speaker 01: their expert did not provide any testimony on obviousness of claim 23. [00:05:18] Speaker 01: And so there's nothing in the record that would support PacBio's attorney argument that claim 3 is just an insignificant difference. [00:05:25] Speaker 01: And in fact, PacBio ignores the significant advantage that claim 23 provides in that you can confirm a sample sequence without having to do the kind of redundant consensus sequencing that the 375 patent provides. [00:05:43] Speaker 03: What about claims? [00:05:44] Speaker 01: Claims 27 and 28? [00:05:45] Speaker 01: Yeah. [00:05:48] Speaker 01: Those claims require the use of a base-linked analog in order to discriminate between modified and unmodified bases. [00:05:57] Speaker 01: The board found that because Laird simply discriminates between modified and unmodified bases, that's met. [00:06:03] Speaker 01: But there's no disclosure in Laird of using a base-discriminating analog to do that. [00:06:07] Speaker 01: PAC-FIO must recognize that. [00:06:10] Speaker 01: because they push a different rejection in front of this board. [00:06:13] Speaker 01: And that is combining the 375 patent with the 614 patent. [00:06:18] Speaker 01: Again, there's no evidence showing why that combination would have been made. [00:06:24] Speaker 02: If we agree with you that claims would not have been obvious, do you also have to win on the issue of an intact buyer's entitlement to its [00:06:34] Speaker 02: earlier provisional date? [00:06:36] Speaker 01: I do, and I'd like to get to that if we're done talking about claims 27 and 28. [00:06:42] Speaker 01: The board first applied the wrong legal standard in granting priority. [00:06:49] Speaker 01: The test isn't whether the 551 application requires only looking for matches. [00:06:55] Speaker 01: And the correct standard is not whether one skilled in the art might be able to reconstruct the count based on the disclosure of the 551 application. [00:07:04] Speaker 01: The 551 application necessarily needs to disclose an embodiment of the count. [00:07:10] Speaker 01: Now, all of PacBio's arguments, all of the board's reasoning is based on the assumption that the 551 application teaches subjecting a circular molecule to bisulfite treatment and then comparing the forward and reverse strands. [00:07:28] Speaker 01: And there's no disclosure in the 551 application of doing that. [00:07:32] Speaker 01: They point to paragraph 17. [00:07:34] Speaker 01: The board pointed to paragraph 17, and PacBio mostly points to paragraph 17. [00:07:40] Speaker 01: And to be sure, there is reference to a circular molecule. [00:07:45] Speaker 01: There is reference to comparing the forward and reverse strands. [00:07:48] Speaker 01: And then at the bottom of the paragraph, in the context of a different method for determining uracil, the statistics-based methods that are described in the 551 application, that's the only time bisulfite treatment is mentioned. [00:08:02] Speaker 01: And so even though it's in the paragraph, the bisulfite treatment is not mentioned in the context of this circular molecule where you compare the forward and reverse strands. [00:08:12] Speaker 01: In fact, bisulfite treatment is mentioned only four times in the 551 application, at the bottom of paragraph 17 in the context of the statistics-based method, in paragraph 21, in paragraph 28, and in paragraph 23, where the authors of the 551 application tell us [00:08:32] Speaker 01: that the methods of the 551 application do not require or do not use the similarities of uracil to thymine. [00:08:43] Speaker 01: Well, in the context of bisulfite treatment, the relevant similarity between uracil and thymine is its propensity to bind with adenine. [00:08:54] Speaker 01: And so in the count, if you're going to subject the count to bisulfite treatment and use that embodiment of the count, [00:09:02] Speaker 01: The only way the count works is if you rely on uracil's propensity to bind with adenine, which paragraph 23 explicitly disclaims. [00:09:15] Speaker 01: Now in the time I have left, I'd like to touch on the other obviousness rejection, which is the obviousness rejection of claims 1 to 26. [00:09:22] Speaker 01: 23 is a different issue. [00:09:26] Speaker 01: And that is the count needs you [00:09:31] Speaker 01: to find the position of a modified base by comparing the forward and reverse strands to each other. [00:09:38] Speaker 01: The board said Laird explicitly looks for mismatches as evidence of the modified base, but it doesn't. [00:09:45] Speaker 01: Figure two is where everybody focused all their attention. [00:09:50] Speaker 01: And figure two has this nice comparison of the molecule with the forward and reverse strands on top of each other and certain [00:10:00] Speaker 01: pairs are highlighted. [00:10:03] Speaker 01: Rare determines where the modified bases are before figure two is created. [00:10:09] Speaker 01: So before he matches up the forward and reverse strands, he compares the bisulfite-treated strand, the top strand, to this top strand of the untreated reference strand. [00:10:19] Speaker 01: And the untreated reference strands are shown in 2A and 2C. [00:10:24] Speaker 01: And then for the reverse strands, he compares the reverse strand of the bisulfite-treated molecule [00:10:29] Speaker 01: to the reverse strand of the untreated reference. [00:10:33] Speaker 01: Now, PacBio makes a lot of the highlighting that's in Figure 2. [00:10:37] Speaker 03: Can I ask you? [00:10:38] Speaker 03: This is very difficult for me to understand. [00:10:41] Speaker 03: So it would be at least helpful for me. [00:10:43] Speaker 03: I mean, you're talking now about the board's analysis, which is at A39 and A40. [00:10:48] Speaker 03: Correct. [00:10:48] Speaker 03: So maybe you could point not to what PacBio is saying, but what the board said that was [00:10:56] Speaker 03: wrong here and missing. [00:10:58] Speaker 03: I guess it's mainly, it's an A40, they say, we disagree with your argument. [00:11:03] Speaker 03: And that's, and their analysis follows. [00:11:05] Speaker 03: So can you point me to where they went stray in their analysis? [00:11:10] Speaker 03: Cause it's pretty detailed and compelling to me. [00:11:15] Speaker 01: It is distilled in this sentence at A40 16 to 18. [00:11:20] Speaker 01: Laird explicitly teaches looking for Guanyin [00:11:24] Speaker 01: thymine mismatches as evidence of non-methylated cytosine in a forward or reverse strand locus. [00:11:31] Speaker 01: And there's no support for that. [00:11:33] Speaker 01: The only evidence about how the mismatched modified bases were located and layered is from Dr. Levy, who, pointing to the description at A724, finds indications that the top strands are compared to the top strands, the reverse strands are compared to the reverse strands, [00:11:52] Speaker 01: But nowhere in order to locate the position of the modified bases are the top strands compared to the reverse strands. [00:12:00] Speaker 01: That that layup is only done after the modified bases have been located in order to study whether the methylation pattern, because this is what Laird is concerned about, whether the methylation pattern carries from one generation of cell to the next after they're divided. [00:12:18] Speaker 01: But the key to the count is how you locate those bases in the first instance. [00:12:23] Speaker 01: And Laird just uses the prior art method of doing that. [00:12:29] Speaker 01: I see I'm about to get into my rebuttal time. [00:12:31] Speaker 03: Why don't we hear from Mr. Reinus and I'm going to save you the rebuttal time. [00:12:34] Speaker 00: Thank you. [00:12:41] Speaker 00: Good morning and may it please the court, Edward Reinus for PacBio. [00:12:44] Speaker 03: Sorry, could you start off, and this is not on one side or the other, but just, there's several issues floating around, and Judge Lurie touched on this in terms of if we find one thing, if the case is over, and how that works. [00:12:57] Speaker 00: Right, as my good friend pointed out, there's two independent grounds. [00:13:02] Speaker 00: There's the priority issue of benefit, and then there's obviousness. [00:13:06] Speaker 00: And if you resolve in our favor, that is Pacquiao's favor, on priority that ends the interference [00:13:14] Speaker 00: and that's all you need to do. [00:13:16] Speaker 00: If you address obviousness and find their claims invalid, then that would resolve the obviousness question against them. [00:13:25] Speaker 00: So the judgment can be held on either ground. [00:13:27] Speaker 03: And there are alternatives? [00:13:29] Speaker 00: Yes, and that was acknowledged, I think, under questioning. [00:13:33] Speaker 00: And they acknowledge that [00:13:37] Speaker 00: We stated that priority is an independent barrier to relief, and they didn't object to that, and they acknowledged all claims corresponding to the calendar, page seven of their brief. [00:13:49] Speaker 00: On the benefit question, which I think is the easier of the two, because it's just one question rather than more than one, the easiest way to think about this. [00:14:01] Speaker 03: I'm sorry, which question are you dealing with? [00:14:02] Speaker 00: On the benefit priority. [00:14:05] Speaker 00: The easiest way to think about it is this is at A19 of paragraph 17 disclosure of using what's called the circular sequencing platform for modified base detection. [00:14:18] Speaker 00: In the key sentence, it says sequence reads from the sense or forward strand can be compared to sequence reads from the anti-sense or reverse strand. [00:14:29] Speaker 03: I'm sorry, you're on A19? [00:14:31] Speaker 00: A918. [00:14:33] Speaker 00: Sorry, A918. [00:14:36] Speaker 00: This is the 551 application. [00:14:38] Speaker 00: And we're establishing that we disclosed modified nucleotide identification through mismatch. [00:14:49] Speaker 00: OK? [00:14:51] Speaker 00: And it's actually a two or three step argument. [00:14:53] Speaker 00: So it's not that complex, in a very complex sea of information. [00:14:59] Speaker 00: It says the sequence reads from the forward strand are compared to sequence reads from the reverse strand, which is exactly what the claim says. [00:15:05] Speaker 00: And it says to further validate the existence of one or more modified bases. [00:15:10] Speaker 00: This is modified base detection. [00:15:12] Speaker 00: The easiest way for me to think about that is if you go to paragraph 21, which is on A919, the next page, it provides a very small genus, a very small group of [00:15:29] Speaker 00: modified bases that fall within the scope of the invention. [00:15:33] Speaker 00: And it includes bisulfite converted bases as the second, and frankly, methylated bases, which is the meth C as the first. [00:15:42] Speaker 00: So it tells you that the modified base that's being detected by the comparison of one to the other is bisulfate. [00:15:49] Speaker 00: The only other real fact you need to know is the admitted fact that A2236 and other places [00:15:58] Speaker 00: that bisulfite treatment in the priority is typically harnessed to detect five math or meth C, which are not mismatched. [00:16:08] Speaker 00: So the purpose for bisulfite treatment is that this is the key to the whole thing that you need in the modified base point. [00:16:16] Speaker 00: The key to the bisulfite treatment is you have Cs and you have meth Cs. [00:16:22] Speaker 00: So C is the standard base and METC is the special modified base that you want to learn about because it affects life and genetics in humans. [00:16:30] Speaker 00: And if you treat the DNA with bisulfate, the regular C becomes a U. And the METC is not changed. [00:16:40] Speaker 00: So it stays a METC. [00:16:42] Speaker 00: The result of that is that when you run your sequencing reaction, however you do it, you can do it a gazillion ways, but when you fill in the complement, [00:16:51] Speaker 00: The U is complemented by an A, which is a mismatch because the U is really a C, not an A, and for some reason U simulates a T. So what you do is you basically filter out the Cs by converting them to Us with bisulfate. [00:17:07] Speaker 00: You keep the C pluses so you know when you have a complement of a G, G, you've got your modified base. [00:17:14] Speaker 00: So you just look at the complementary strand that you create where you have Gs, you know you have your C met. [00:17:21] Speaker 00: That's the only reason in the record that they used bisulfate. [00:17:26] Speaker 00: No other reason for this modified base detection. [00:17:29] Speaker 00: They didn't invent this. [00:17:30] Speaker 00: They don't claim to have invented it. [00:17:31] Speaker 00: They're very candid about that. [00:17:33] Speaker 00: That's the only reason you use it. [00:17:35] Speaker 00: It says bisulfite modified nucleotides are what you use to identify the modified bases. [00:17:43] Speaker 00: There's really not an argument that's very good on the other side in this situation. [00:17:47] Speaker 00: I'm always happy to address [00:17:49] Speaker 00: He made the point that there are several references to bisulfate. [00:17:54] Speaker 00: It's defined as one of the modified bases. [00:17:58] Speaker 00: That's all you need to know. [00:17:59] Speaker 00: Now the debate about claim construction, let me just debunk that, is our position is that the mismatch enables detection of the modified base, but the position of ITRI is that the mismatch modified base, that the modified base has to be the mismatch. [00:18:17] Speaker 00: In the case of this bisulfide treatment, which is what everyone's using and what everyone really cares about in general, is that the meth C is not mismatched because it still matches the G. You're filtering out the U's. [00:18:31] Speaker 02: Mr. Reinus, why didn't the board, with respect to claims 27 and 28, with respect to the disclosure of Laird, which didn't disclose the use of discriminating analog? [00:18:47] Speaker 00: Yeah, I think I can shed some light there. [00:18:49] Speaker 00: So the issue that ITRI itchery made below was a motivation to combine. [00:18:56] Speaker 00: So there's another way that modified bases are detected. [00:19:00] Speaker 00: Forget bisulfite. [00:19:02] Speaker 00: And this is you just have a special discriminating nucleotide analog that identifies them. [00:19:08] Speaker 00: It's just got a big flag on it, and that serves that special function. [00:19:13] Speaker 00: That's priority. [00:19:14] Speaker 00: that's disclosed in their own patent application. [00:19:16] Speaker 00: In the 630 patent application, they disclose that and they refer to the 614 patent. [00:19:22] Speaker 00: And they just admit that that's prior art. [00:19:25] Speaker 00: I mean, it's not a debated item whatsoever. [00:19:27] Speaker 00: They admit it at A357 paragraph 76. [00:19:32] Speaker 00: They admit it at column 24, line 42, 46. [00:19:35] Speaker 00: So the idea of using a discriminating analog to find your modified base is old as the hills. [00:19:40] Speaker 00: Like their other claims, what they're basically doing is they're saying this circular sequencing platform that we invented can be used with a couple of bells and whistles. [00:19:48] Speaker 00: One is identifying modified bases with bisulfite. [00:19:52] Speaker 00: They admit bisulfite's old. [00:19:54] Speaker 00: There's no reason you wouldn't combine the two. [00:19:56] Speaker 00: They admit that these discriminating nucleotide analogs are old. [00:20:01] Speaker 00: It's just identified as part. [00:20:03] Speaker 00: They attempt on that one to argue why that shouldn't be combined. [00:20:09] Speaker 00: And their argument is that the discriminating nucleotide analogs that they refer to in their patent are base labeled. [00:20:19] Speaker 00: The label is on the base of the nucleotide. [00:20:23] Speaker 00: And their argument is that in RRs, being packed bios, version of a circular sequencing platform, that the preferred embodiment [00:20:33] Speaker 00: is a system that doesn't work very well with a base label. [00:20:36] Speaker 00: So it's only a motivation argument. [00:20:38] Speaker 00: The fact that they didn't invent discriminating nucleotide analogs, and my friend here will not come up and tell you that they did. [00:20:45] Speaker 00: It's acknowledged prior art. [00:20:47] Speaker 00: It's the idea of using the two together. [00:20:49] Speaker 00: What this misapprehends is that there are numerous other alternatives, such as Sanger sequencing and sequencing by synthesis, disclosed in R375 patents. [00:21:00] Speaker 00: disclosed at column five, line 10 through 35. [00:21:05] Speaker 00: Yes, we describe a special kind of circular sequencing platform that may not work so great with base labeled nucleotide analogs. [00:21:17] Speaker 00: The other point is that there's no claim requirement, and maybe this cuts to it easier, there's no claim requirement that the discriminating nucleotide analog be base labeled. [00:21:29] Speaker 03: Am I missing something or is, I mean, accepting your analysis is persuasive that none of this is in the board opinion? [00:21:36] Speaker 03: On which point? [00:21:37] Speaker 03: On the point you were making on claims 27-28. [00:21:40] Speaker 00: On 27-28? [00:21:40] Speaker 03: On 27-28... Can I refer to the reference you just talked about, I think? [00:21:46] Speaker 03: I couldn't find an analysis by the board in its opinion on those points. [00:21:51] Speaker 00: I think the analysis that they adopted was [00:21:55] Speaker 00: Why wouldn't you want, what they focused on and why they identified Laird, I think this got a little lost in the, you know, maybe we could have done a better job on our end, is that you would want to use, you've got this new circular platform that's wonderful, that's our company. [00:22:12] Speaker 00: There are all kinds of things you'd want to do with it. [00:22:14] Speaker 00: Identifying NetSea, I think you're going to hear about that in the future. [00:22:18] Speaker 00: It's important. [00:22:19] Speaker 00: So they took an old way of putting that. [00:22:21] Speaker 00: They thought they actually invented this circular platform, right? [00:22:25] Speaker 00: The analysis of the board is dead on because it's not whether discriminating analogs are in the prior art. [00:22:31] Speaker 00: They're old as the hills in the patent itself is known. [00:22:34] Speaker 00: It's whether you would combine them with the circular platform, whether that would be obvious. [00:22:39] Speaker 00: What the board did state is that Laird and the 375 and the sophisticated skill of those skilled in the art would want to use discriminating nucleotide analogs with this great new circular platform. [00:22:56] Speaker 00: And so the question is, well, why wouldn't you want to use something? [00:22:59] Speaker 00: It's just a sequencing platform. [00:23:01] Speaker 00: Why wouldn't you want to use something people use with other sequencing platforms with this sequencing platform? [00:23:05] Speaker 00: You ask yourself the question. [00:23:07] Speaker 00: They have an answer. [00:23:08] Speaker 00: Let's respect that. [00:23:10] Speaker 00: Their answer is, well, you don't like base labeled nucleotide analogs. [00:23:15] Speaker 00: The board's point was you would be highly motivated [00:23:22] Speaker 00: to use a really good way of identifying modified bases on this circular platform. [00:23:27] Speaker 00: And the substantial evidence in the record to support it is that you're not limited to base labeled nucleotide analogs by the claim. [00:23:37] Speaker 00: So why is that a problem, first of all? [00:23:39] Speaker 00: And second of all, you don't have to use the particular sequencing preferred embodiment we have where it doesn't work. [00:23:45] Speaker 00: There's Sanger sequencing, which [00:23:47] Speaker 00: Base labels have been used forever on those, of course, and sequencing by synthesis, where base labels are common. [00:23:53] Speaker 00: So, and there's other cases that have been up in the score talking about base labeling. [00:23:57] Speaker 00: So, base labeling is not unusual. [00:23:59] Speaker 00: It's used routinely in sequencing. [00:24:01] Speaker 00: Why wouldn't you just use a different one than the preferred embodiment if you have this great new discriminating nucleotide analog? [00:24:07] Speaker 00: I think there's at least substantial evidence to support the board on this. [00:24:11] Speaker 00: Not to mention the strength of the benefit position, which I started with. [00:24:16] Speaker 00: So if there's other questions, I know it's complicated subject matter. [00:24:20] Speaker 00: OK. [00:24:21] Speaker 00: Well, thank you very much. [00:24:21] Speaker 00: I appreciate it. [00:24:28] Speaker 01: Thank you, Your Honor. [00:24:29] Speaker 01: Just a few brief points in rebuttal. [00:24:33] Speaker 01: Mr. Reinus's two to three step argument analysis for why they're entitled to the priority, that's an obviousness analysis. [00:24:42] Speaker 01: What he did in his presentation was he took a disclosure from one part of the 551 application, took a disclosure from another part of the 551 application, and then put them together in a way that does not satisfy the written description requirement of this court's case law and its predecessor's case law, which requires some sort of blaze marks or something in the record that shows that the inventors had in their possession the count. [00:25:11] Speaker 01: He talked about two things in particular. [00:25:14] Speaker 01: One is the description of modified bases and that it includes both bisulfite modified bases. [00:25:23] Speaker 01: It does, but there are 12 other categories of modified bases that are listed in that very same paragraph. [00:25:28] Speaker 01: And there's nothing in paragraph 17 that would say use that particular modified base in combination with the circular molecule. [00:25:36] Speaker 01: He also said something else that I thought was revealing. [00:25:39] Speaker 01: He used the phrase U, the uracil, simulates a T. And it does. [00:25:44] Speaker 01: But paragraph 23 tells you that's not their invention. [00:25:48] Speaker 01: Paragraph 23 says, we do not use methods where a U simulates a T. Now turning to claims 27 and 28, the point is not whether the claims require base-labeled nucleotides. [00:26:02] Speaker 01: The point is that the 614 patent, the Zahn patent, teaches base-labeled nucleotides. [00:26:09] Speaker 01: And the 102A Prior Art Pacific Bioscience presentation at the Cold Springs Harbor meeting tells you that base-linked nucleotides cause enzyme inhibition. [00:26:20] Speaker 01: Our expert looked at that, and he didn't say it was limited just to the smart bell molecule, which is the preferred embodiment of the 375 patent. [00:26:29] Speaker 01: He said one skilled in the art would interpret that as a general problem and be led away from combining the Zon patent with the 375 patent. [00:26:38] Speaker 01: Zahn was their expert. [00:26:40] Speaker 01: He didn't provide any evidence, any testimony, rebutting Dr. Levy on that point. [00:26:44] Speaker 01: And my last point is there was a lot of discussion about Sanger sequencing. [00:26:51] Speaker 01: Sanger sequencing is not single molecule sequencing, and the 630 patent expressly distinguishes the two at A92, column 15, lines 13 to 19. [00:27:05] Speaker 01: The basic point is that both the board and PACBIO relied on the SMART-L embodiment in order to argue obviousness of all the claims. [00:27:14] Speaker 01: And you can find that at A259 to 60, which is PACBIO's arguments, and A28 to 29, where the board relies on that specific embodiment in its obviousness analysis. [00:27:24] Speaker 01: Unless there are any other questions, see you the rest of my time. [00:27:28] Speaker 03: Thank you. [00:27:29] Speaker 03: Thank you. [00:27:29] Speaker 03: We thank both parties in the case to signal.