[00:00:00] Speaker 02: Our first case is from the PTAB, Pfizer versus Sanofi Pasteur SK Chemicals, 2019, 18, 71, 73, 75, 76, and 22, 24. [00:00:11] Speaker 02: Mr. Scheibeler? [00:00:16] Speaker 02: Yes, sir. [00:00:19] Speaker 02: Please proceed. [00:00:21] Speaker 01: May it please the court. [00:00:23] Speaker 01: My name is John Scheibeler. [00:00:24] Speaker 01: I represent Pfizer, the appellant here. [00:00:27] Speaker 01: The appeal concerns five IPR decisions that found the claims of the Pfizer's 559 patent invalid for obviousness. [00:00:37] Speaker 01: And I'd like first to address why this court should reverse the board's decision finding claims three and four, the dependent claims, obvious. [00:00:47] Speaker 01: And that's discussed in detail at page 39 of our opening brief and beginning at page 19 of our reply brief. [00:00:58] Speaker 01: In essence, the decision is not supported on claims three and four by the board, is not supported by substantial evidence. [00:01:05] Speaker 01: Claim three recites a three-valent pneumococcal serotype multivalent conjugate composition. [00:01:15] Speaker 01: It requires the 22F serotype glyco conjugate from claim one, plus two additional conjugates of serotypes 15B and 33F. [00:01:25] Speaker 01: Claim four depends from claim three and adds conjugates of four additional serotypes, namely serotypes 12F, 11A, 10A, and eight for a total of seven conjugates. [00:01:40] Speaker 01: Now, the board in the final written decision determined that the term immunogenic in the claims requires immunogenicity across all the serotypes in the composition. [00:01:51] Speaker 01: So the board also determined that the term immunogenic [00:01:55] Speaker 01: is construed as eliciting functional antibody. [00:01:59] Speaker 01: And this is at APPX280 of the Sanofi decision, and it's in the other decisions as well. [00:02:05] Speaker 01: I should mention that the decisions here for these purposes track one another very closely. [00:02:11] Speaker 01: That is to say, the decisions in IPR2131, 2132, and 187. [00:02:18] Speaker 01: I'll be referring mostly to the appendix in the decision of the 187 proceeding. [00:02:27] Speaker 01: What's new here? [00:02:29] Speaker 01: 22F is old, isn't it? [00:02:31] Speaker 01: 22F was known at least since 1983 in the free polysaccharide vaccine, Mimivax. [00:02:40] Speaker 01: But that 22F stereotype was not conjugated until the Merck reference came along in 2011. [00:02:51] Speaker 01: And I can walk through that a little bit in a moment, Your Honor, but the point there is that this area, this field is unpredictable. [00:03:00] Speaker 01: It's unpredictable to generate these conjugates and have them elicit functional antibody. [00:03:06] Speaker 01: It's even more unpredictable to put them together in a multivalent composition and have them all in that multivalent composition elicit functional antibody across all the serotypes. [00:03:17] Speaker 05: But the petitioner's experts said exactly the opposite of that, and the board evaluated both sides' evidence and came out on the other side. [00:03:26] Speaker 01: Don't we have to affirm that? [00:03:29] Speaker 01: I think the board overlooked the unpredictability in the field and overlooked the fact that [00:03:35] Speaker 01: Without a conjugate being produced in the prior art, there's no evidence of reasonable expectation of success that it would be immunogenic, that is to say that it would elicit functional antibody, which is a requirement of the claims. [00:03:52] Speaker 01: In fact, none of the petitioners, none of the board in the final written decision even addressed whether these multivalent compositions elicit functional antibody. [00:04:02] Speaker 05: The board accepted your construction of immunogenic, didn't it? [00:04:06] Speaker 01: Yes, they did. [00:04:07] Speaker 01: And what they did, Your Honor, is in the decision, I'll get the site for you, in the decision they said, just as immunogenic means, immunogenic across all the serotypes, the fact that the GSK references, the word uses the term immunogenic, necessarily means that all the conjugates in the GSK reference would [00:04:29] Speaker 01: be immunogenic. [00:04:31] Speaker 01: That's not proven in the evidence. [00:04:33] Speaker 03: Moreover, the judge in the... Why isn't that a reasonable inference from the JSK 711? [00:04:42] Speaker 01: Because when we look at the data in the GSK 711 reference, there's no data on eliciting functional antibody. [00:04:52] Speaker 01: There's an IgG serum data across all the serotypes, which admittedly elicits some immune response. [00:05:00] Speaker 01: But the only OPA assay data which is required to demonstrate functional antibody is with respect to serotypes 19A and 22F. [00:05:09] Speaker 01: There's no OPA data showing functional antibody across all these serotypes. [00:05:17] Speaker 03: If we disagree with you on that point and conclude that the GSK 711 reference does demonstrate immunogenicity, [00:05:29] Speaker 03: Is it true that the only difference between the GSK 711 and claims 3 and 4, 4 in particular, is the absence of 15A? [00:05:43] Speaker 01: The GSK reference lists [00:05:46] Speaker 01: Well, the GSK 711 reference lists serotype 15B, which is in claim 3. [00:05:55] Speaker 01: It also lists the serotypes that are provided in claim 4. [00:06:00] Speaker 01: But it provides them in a laundry list of serotypes. [00:06:03] Speaker 01: It never exemplifies those serotypes in conjugates in the examples. [00:06:08] Speaker 01: It simply says, well, it'll be immunogenic. [00:06:10] Speaker 01: But it provides no data for that. [00:06:11] Speaker 01: And this field is unpredictable. [00:06:13] Speaker 01: I'd like to, if you don't mind, Your Honor, I'd like to, if I could direct the court to the table [00:06:20] Speaker 01: and paragraph 159 of Sunopi's expert. [00:06:24] Speaker 01: Sorry. [00:06:25] Speaker 03: Just to make sure. [00:06:26] Speaker 01: Sure. [00:06:26] Speaker 03: I think I said 15A. [00:06:28] Speaker 03: You're talking about 15B. [00:06:29] Speaker 01: Correct. [00:06:30] Speaker 03: OK. [00:06:30] Speaker 01: Correct, Your Honor. [00:06:31] Speaker 01: Yes. [00:06:31] Speaker 01: Yes, it's 15B. [00:06:33] Speaker 01: It's 15B. [00:06:35] Speaker 01: But to come back to it, the point is that this is not a predictable field. [00:06:39] Speaker 01: Knowing that, having knowledge of [00:06:42] Speaker 01: prevalent serotype does not automatically get you to the conjugate. [00:06:47] Speaker 01: Certainly not the conjugate that elicits functional antibody. [00:06:50] Speaker 01: It's even more unpredictable to take that conjugate and combine it with other conjugates in a multivalent composition that elicits functional antibody across all the serotypes. [00:07:01] Speaker 01: And I direct the court to the table and paragraph [00:07:05] Speaker 01: in Sanofi's expert, Dr. Lee's, at APPX24960. [00:07:09] Speaker 01: And if you have a look at that, you'll see that at the top of them, the top rows list the serotypes that we're discussing here, 15B, 10A, sorry, 15B, 12F, 11A, 10A, and 8. [00:07:24] Speaker 01: And that table in the far right shows those serotypes who are known in Mimivax. [00:07:29] Speaker 01: That's the free polysaccharide vaccine that was approved in 1983, not conjugate. [00:07:35] Speaker 01: The first Nucleococcal conjugate vaccine that was approved that included conjugates, Prednar, had seven serotypes. [00:07:43] Speaker 01: None of those were the serotypes that I've mentioned. [00:07:46] Speaker 01: That was approved in 2000. [00:07:48] Speaker 01: That's 17 years after Mimivax was approved. [00:07:51] Speaker 01: The next serotype vaccine that Pfizer got, Prednar-13, took another 10 years to get approved. [00:07:59] Speaker 01: And Merck's vaccine, which added 22F and 33F in the Merck 2011 reference, so the Merck 086 reference, came along after the Pfizer reference. [00:08:10] Speaker 01: the GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GSK, GS [00:08:35] Speaker 01: On functional antibody, I'd like to draw the court also to the attention of the testimony that we took of Dr. Casper. [00:08:47] Speaker 01: on this issue, and this is at the appendix 4145 to 4146. [00:08:52] Speaker 01: Now I asked Dr. Casper in his deposition about Claim 3, and I said, would it be routine to make a claim, a multivalent conjugate with serotypes 33F, 15B, and 22F? [00:09:06] Speaker 01: And he said, to get it immune, yes. [00:09:10] Speaker 01: To get an immune response, sure. [00:09:12] Speaker 01: But I define immunogenic as functional antibody in the questioning. [00:09:16] Speaker 01: And he said, functional antibody? [00:09:18] Speaker 01: I can't predict that. [00:09:20] Speaker 01: That, to me, directly contradicts what the board found in these cases. [00:09:26] Speaker 05: What about Dr. Lees? [00:09:28] Speaker 05: Do you have the same deficiency in your view in terms of applying the immunogenicity construction? [00:09:35] Speaker 01: In Dr. Lee's deposition, we ask, and this is at appendix 31, 359 to 360, [00:09:43] Speaker 01: We're asked a similar question. [00:09:45] Speaker 01: Would it be routine optimization to make a multivalent composition that's immunogenic? [00:09:53] Speaker 01: Would that require routine optimization? [00:09:57] Speaker 01: Here is the response. [00:09:58] Speaker 01: I was called as an expert in the synthesis of conjugates, not in immunology. [00:10:04] Speaker 01: I'm not in a position to answer that question. [00:10:06] Speaker 05: OK, but you don't contend that Dr. Lees failed to apply the construction properly, do you? [00:10:12] Speaker 01: Well, that's a great question, Your Honor. [00:10:14] Speaker 01: In the opening declaration, Dr. Lees glosses over the term immunogenic. [00:10:23] Speaker 01: He doesn't define it. [00:10:24] Speaker 01: He doesn't define it in his opening declaration. [00:10:26] Speaker 01: The petitioner did. [00:10:28] Speaker 01: Dr. Lees, in his opening declaration, just points to various evidence and never says whether [00:10:34] Speaker 01: never directly says whether it's functional antibody. [00:10:37] Speaker 01: In his deposition, I asked him, do you agree immunogenic meets functional antibody? [00:10:42] Speaker 01: And he said, yes, in his deposition. [00:10:44] Speaker 01: His reply declaration doesn't address the issue so far as I can see. [00:10:48] Speaker 05: If just one of the experts in one of these five IPRs we're reviewing applied the correct construction, do we have substantial evidence to uphold the board? [00:11:00] Speaker 01: I don't believe so, Your Honor, because I think the evidence unequivocally shows the unpredictability here that when you have a serotype alone, that's not enough to get a conjugate. [00:11:15] Speaker 01: Conjugate development is not easy. [00:11:17] Speaker 01: We have testimony from our experts. [00:11:21] Speaker 01: This one's at [00:11:26] Speaker 01: Our expert Dr. Boones, APPX 5456, no single conjugation chemistry generates conjugates uniformly suitable across serotypes for a vaccine. [00:11:37] Speaker 01: Our expert Dr. Wang, no single at APPX 29437, no single protocol applies for generating conjugates for all serotypes. [00:11:47] Speaker 02: Counsel, you're into your rebuttal time. [00:11:49] Speaker 02: You can continue or save it as you like. [00:11:51] Speaker 01: OK. [00:11:52] Speaker 01: Yeah, thank you. [00:11:52] Speaker 01: Thank you. [00:11:53] Speaker 01: Let me move on very quickly here as time flies. [00:11:58] Speaker 01: I just want to say one thing about a few quick comments about the motion to amend. [00:12:03] Speaker 01: The motion to amend, we think, is an abuse of discretion in finding the claims obvious in the motion to amend. [00:12:11] Speaker 01: It's an abusive discretion because it found the claims obvious over Hausdorff in view of the secondary reference, Merck, in the face of evidence in the Merck reference that there was no reasonable expectation of success. [00:12:27] Speaker 01: Claim 46 requires [00:12:30] Speaker 01: a fourteen-valent composition, and it requires that it elicits a two-log increase across all fourteen serotypes. [00:12:37] Speaker 01: That's exactly what the Merck reference did. [00:12:40] Speaker 01: It took the thirteen-valent composition of Hausdorff, it tried to increase it, and [00:12:46] Speaker 01: And when it did, table four of that reference shows that there was no two-log increase across all the stereotypes. [00:12:53] Speaker 01: We think that's directly contrary to the judge's finding and the evidence. [00:12:58] Speaker 01: Now, I'll try to have a little time left, but I want to also say, claim 48 and claim 49, they require all 14 stereotypes elicit a two-log increase. [00:13:11] Speaker 01: Nobody, the board or the petitioners below, has addressed whether the serotypes of those claims elicit a two-log increase across all serotypes in the competition. [00:13:23] Speaker 01: So with that, I'll reserve the rest of my time. [00:13:25] Speaker 01: Thank you. [00:13:27] Speaker 02: Mr. Goffman. [00:13:50] Speaker 04: Good morning, Your Honors. [00:13:51] Speaker 04: May it please the court? [00:13:53] Speaker 04: The board's decision is supported by substantial evidence and should be affirmed. [00:13:58] Speaker 04: There's nothing inventive about the claims of the 559 patent and the proposed substitute claims that were proposed by Pfizer in its motion to amend. [00:14:13] Speaker 04: Those claims are directed to [00:14:15] Speaker 04: known immunogenic compositions comprising known conjugates made from known immunogenic polysaccharides that are conjugated with methods that are routine and optimizable. [00:14:33] Speaker 05: Could you talk about 48 and 49 and that two-log limitation? [00:14:38] Speaker 05: I don't see where the board ever addressed where that limitation was disclosed in the prior article. [00:14:44] Speaker 04: Yes, Your Honor. [00:14:46] Speaker 04: What the board did with claims 48 and 49, there's no heading in the final written decision that says, here's our analysis relating to claims 48 and 49. [00:14:58] Speaker 04: But the analysis that supports the judgment by the P tab that claims 48 and 49 are obvious is throughout the final written decision. [00:15:10] Speaker 04: For example, the board undisputedly analyzed the obviousness of claim 46. [00:15:20] Speaker 04: And even Pfizer doesn't argue that there's no analysis. [00:15:23] Speaker 05: Specifically, the two log increase [00:15:26] Speaker 05: for the serotypes that are added in 48 and 49 that are not in 3 or 4 or in 46. [00:15:32] Speaker 05: Where is that analysis? [00:15:33] Speaker 04: Yes. [00:15:33] Speaker 04: So for example, if you go to the final written decision at appendix 350, so this is a portion [00:15:55] Speaker 04: Give me another second to get there. [00:16:04] Speaker 02: But 350 doesn't talk about 48 and 49. [00:16:07] Speaker 02: And if you go to 355, we conclude that claim 46 would have been obvious over Hausdorff and the others. [00:16:18] Speaker 02: It can deal with 48 and 49. [00:16:19] Speaker 04: Yes, Your Honor. [00:16:20] Speaker 04: On appendix 350 in the final written decision, [00:16:24] Speaker 04: The board is addressing whether the two-log increase in immunogenicity, as broadly applied across all the serotypes, not serotype-specific, can be optimized in order to achieve a two-log increase. [00:16:44] Speaker 03: What language on 350 are you specifically referencing? [00:16:47] Speaker 03: Is this the first paragraph after the? [00:16:52] Speaker 04: Yes. [00:16:53] Speaker 04: The board in the first paragraph is referring to the testimony by Sanofi's expert, Dr. Van Alfen, regarding the fact that a two log increase across all serotypes by routine optimization. [00:17:11] Speaker 04: Specifically, Hausdorff reported several studies [00:17:14] Speaker 04: examining the immune response to the 13 V PNPC composition in New Zealand white rabbits. [00:17:22] Speaker 04: And so what the board is saying there is that the two log increase, which is not serotype specific, can be achieved through routine optimization. [00:17:33] Speaker 04: It doesn't matter whether it's a serotype that is disclosed or recited in claims 48 and 49. [00:17:44] Speaker 04: or a serotype recited in claim 46, they are using Dr. Van Elfen's expert testimony to conclude that it is a matter of routine optimization to achieve a two-log increase in immunogenicity by, for example, picking rabbits that have a low baseline or [00:18:04] Speaker 04: optimizing the amount of adjuvant that is used in the study. [00:18:10] Speaker 02: You're saying what applies to 46 also applies to 48 and 49? [00:18:14] Speaker 04: Yes, because the board's conclusion regarding the optimizability of the two-log increase is not predicated on a specific serotype. [00:18:26] Speaker 04: They are finding as a matter of fact that [00:18:29] Speaker 04: a two-log increase can be achieved regardless of what specific serotype is at issue. [00:18:37] Speaker 04: And in fact, there was no evidence in the record that any of the serotypes that were specifically addressed in Claim 46 had [00:18:48] Speaker 04: unique properties that made them routinely optimizable that would not be achieved with other serotypes. [00:18:56] Speaker 04: And Pfizer didn't put any evidence in the record on that. [00:19:00] Speaker 02: What about the unpredictability in the field that your opposing counsel talked about? [00:19:07] Speaker 04: So Pfizer made the argument, that precise argument that is in their opening brief, [00:19:15] Speaker 04: in the reply brief, and that my good friend made here earlier, that the immunogenic composition development field, multivalent PCV compositions, is unpredictable. [00:19:32] Speaker 04: That argument was made by the board. [00:19:34] Speaker 04: It was considered by the board. [00:19:36] Speaker 04: It was found to be unpersuasive by the board. [00:19:39] Speaker 04: And the board credited [00:19:40] Speaker 04: the evidence of record, the substantial evidence of record, that supports their conclusion that molecular weight, for example, is routinely optimizable. [00:19:55] Speaker 04: So the board considered Pfizer's argument that it was unpredictable and rejected it. [00:20:01] Speaker 04: And I don't think it's proper [00:20:03] Speaker 04: for Pfizer to be asking this court to reweigh the evidence and relitigate factual disputes that were squarely put in front of the board and considered by the board. [00:20:16] Speaker 05: You say consider, your friend says they overlooked the unpredictability. [00:20:20] Speaker 05: Can you give us an example of where we can see that the board did consider the unpredictability of the art? [00:20:27] Speaker 04: Well, I think I would start with the fact that the board concluded that molecular weight was routinely optimizable. [00:20:35] Speaker 04: I think the fact that they found that it was optimizable, there was considerable substantial evidence in the record to support that, for example, in GSK 711. [00:20:45] Speaker 05: So it's implicit in the finding of routine optimizable. [00:20:50] Speaker 05: Do they explicitly say, and it's [00:20:54] Speaker 05: you know, predictable or at least not unpredictable or do we just find it implied in the finding? [00:21:01] Speaker 04: It's at least implied. [00:21:04] Speaker 04: I don't have a site to give you standing here where the board specifically mentions unpredictability and rejects it. [00:21:15] Speaker 04: But I think when you look at the final written decision and you consider the substantial evidence of record, that supports their conclusion that molecular weight is a routine, optimizable, results-effective variable that [00:21:31] Speaker 04: It's undisputed that Pfizer made the unpredictability argument during the PTAP proceedings. [00:21:40] Speaker 04: And the fact that the board found that molecular weight was a routine, optimizable, results-effective variable, I think, acknowledges and confirms that the board considered the argument and rejected it. [00:21:54] Speaker 04: And there is substantial evidence in the record, regardless of any argument, that it is unpredictable. [00:22:01] Speaker 04: I mean, let's assume for a moment that Pfizer made an unpredictability argument, but it wasn't specifically addressed by the board. [00:22:13] Speaker 04: I'm not saying that that's what happened, but let's assume that's what happened. [00:22:18] Speaker 04: Under the substantial evidence standard, there's still record evidence that [00:22:24] Speaker 04: That is substantial evidence that supports the conclusions by the board that molecular weight is a routinely optimizable results-effective variable. [00:22:37] Speaker 04: And there's no dispute that there's overwhelming evidence, not just substantial evidence, to support that finding. [00:22:52] Speaker 04: You know, Pfizer's argument, my colleague's argument earlier, that there is no exemplification of the serotypes in claims three and four in GSK 711. [00:23:07] Speaker 04: The board, again, specifically addressed that argument and found that exemplification is not necessary and that [00:23:17] Speaker 04: that the record evidence did support the fact that the immunogenicity of the serotypes in claims three and four supported the fact that those claims are obvious. [00:23:36] Speaker 03: Just a second. [00:23:40] Speaker 03: Could you return to 48 and 49? [00:23:42] Speaker 03: Yes, Your Honor. [00:23:43] Speaker 03: The language that you relied on earlier, [00:23:46] Speaker 03: At A350, as a quote from Dr. Alfond, I don't see that the board expressly adopts that quote. [00:23:54] Speaker 03: Is there language in which the board expressly states what you assert they implicitly at least made, a finding that would extend the logic of 46 over to 48 and 49? [00:24:14] Speaker 04: Well, I think in the middle of this page on 350, the board states, Dr. Van Elfen states that the dad and house are- But they're just quoting him there. [00:24:25] Speaker 03: They're not specifically adopting his statement. [00:24:30] Speaker 03: I'm looking for something more concrete suggesting or stating that [00:24:36] Speaker 03: They specifically endorse the view that what was good for 46 was also good for 48 and 49. [00:24:45] Speaker 04: I don't think they tie it specifically into claims 48 and 49. [00:24:53] Speaker 04: Is that a problem? [00:24:55] Speaker 04: I don't think so, Your Honor, because the question is whether there's substantial evidence in the record to support the judgment by the board. [00:25:03] Speaker 03: But the judgment by the board, there has to be substantial evidence to support a finding on which the judgment can be predicated. [00:25:11] Speaker 03: And I'm not seeing a finding with respect to 48 and 49. [00:25:14] Speaker 03: That's my problem. [00:25:16] Speaker 03: We can't make that finding, obviously, under Chenery. [00:25:19] Speaker 04: Well, the board made findings that would support the obviousness of claims 48 and 49, even though they didn't specifically relate those findings to claims 48 and 49. [00:25:38] Speaker 04: And I think those findings, still under the substantial evidence standard, support the judgment by the board that claims 48 and 49 are obvious. [00:25:49] Speaker 05: But what I think you're saying is you think a finding that all serotypes will predictably or routinely have the 2 log increase would necessarily encompass the serotypes that are added in 48 and 49. [00:26:05] Speaker 05: That logically makes sense. [00:26:06] Speaker 05: but I don't see where the board made that finding that all serotypes will have this two log increase. [00:26:13] Speaker 05: Is the place where the board made that finding A350 or is it somewhere else? [00:26:16] Speaker 04: Well, the board found that a two log increase is routinely optimizable and the board does have a discussion [00:26:27] Speaker 04: in the final written decision regarding all of the different variables in measuring the immunogenicity of the serotype that could be optimized in order to achieve a 2 log increase. [00:26:42] Speaker 04: So for example, they say [00:26:44] Speaker 04: they made findings that the baseline could be reduced and they made findings regarding the fact that... I think I understand all that. [00:26:53] Speaker 05: I'm just not seeing where the board says this applies to all serotypes or less than that, which would also be fine for you, this applies to all serotypes that are added in 48 and 49. [00:27:06] Speaker 05: I don't see where either of those findings exist. [00:27:09] Speaker 04: I don't think they said that [00:27:11] Speaker 04: explicitly it applies to all serotypes. [00:27:15] Speaker 04: But they didn't say it applies only to specific serotypes. [00:27:20] Speaker 04: And I think a reasonable inference from that [00:27:24] Speaker 04: is that it does apply to all serotypes. [00:27:26] Speaker 04: And again, there's no evidence in the record that the serotypes in claim 46 are somehow unique from the serotypes in claims 48 and 49. [00:27:40] Speaker 02: Thank you, counsel. [00:27:41] Speaker 02: I think we have your answer. [00:27:43] Speaker 02: And you're into the Patent Office's time. [00:27:46] Speaker 02: But we'll give her five minutes. [00:27:49] Speaker 04: Thank you, Your Honor. [00:27:50] Speaker 02: Ms. [00:27:50] Speaker 02: Kelly. [00:28:08] Speaker 00: Good morning, Your Honors. [00:28:08] Speaker 00: May it please the Court, as stated in our 28 January letter, since the Carousel decision effectively renders Pfizer's APA claims moot, I'd like to address some of the questions Your Honor pose to Sanofi. [00:28:28] Speaker 00: The first is that, at least in the Merck challenges, [00:28:36] Speaker 00: The board did make express findings about claims 48 and 49, and you can find those in the appendix at ABBX 154 to 155. [00:28:46] Speaker 00: And the court realized in those cases the expert testimony of Dr. Casper and the fact that, as the board found, [00:29:05] Speaker 00: at appendix page 155, the patent owner provided no evidence to rebut the petitioner's assertions or Dr. Casper's expert testimony that serotype 15B would also be included in the mention and in Dr. Casper's testimony [00:29:33] Speaker 00: that that would produce an immunogen-specific response, immunogenic, sorry, serotype-specific response. [00:29:43] Speaker 05: Where on 154 or 155 does the board talk about the two-log increase? [00:29:48] Speaker 00: Okay, the two-log increase, if you look at the appendix at 143 and 145, I mean 143 to 145, if you look at [00:30:02] Speaker 00: Page 143, you'll see Merck's Table 2. [00:30:08] Speaker 05: Table 4. [00:30:09] Speaker 00: I'm sorry, Table 4. [00:30:10] Speaker 00: I apologize. [00:30:13] Speaker 00: And Table 4 includes the non-prevnar serotypes. [00:30:17] Speaker 00: If you look at Table 4, you can see the board's binding just underneath it. [00:30:23] Speaker 00: I'll read it here. [00:30:25] Speaker 00: In Table 4, Merck 2011 teaches the fold rise in antibody levels [00:30:32] Speaker 00: to the non-prevener serotypes from day 0 to day 28. [00:30:36] Speaker 00: That's meaning that matches the expressed terms of supplemental claim 46. [00:30:46] Speaker 00: And then if you look to the following paragraph, they specifically point to the results that are greater than 100, 100 being two log or twofold. [00:31:01] Speaker 00: They say that [00:31:02] Speaker 00: these things, that these serotypes, at least in these sets of rabbits, produce more than a two-log or two-fold increase in immunogenicity, and you can see that in the table itself. [00:31:16] Speaker 05: Right, but are these the serotypes that are added in 48 and 49? [00:31:22] Speaker 00: With respect to 48 and 49, we're talking about primarily the 15 serotypes. [00:31:29] Speaker 00: And then that's why I would say going back to the board's decision at APPX 154 and 155. [00:31:36] Speaker 00: And the board relies on Dr. Casper's testimony that at least the polysaccharide for that serotype, not the conjugate, admittedly not the glycoconjugate, had been used in the past and had been shown to be immunogenic. [00:31:58] Speaker 00: and that the board found that this at least meant, based again on expert testimony, that this was on everyone's mind, that this was a routine optimization, and that this would have been reasonably predictable as to that specific serotype. [00:32:21] Speaker 00: And so those are the points I wanted to address. [00:32:25] Speaker 05: I asked about Dr. Casper. [00:32:27] Speaker 05: There's a contention that he failed to apply the correct construction of immunogenicity. [00:32:35] Speaker 05: Are you familiar with that argument? [00:32:42] Speaker 00: It certainly wasn't something that I recall being raised in the Merck [00:32:55] Speaker 00: decisions, an argument being raised there. [00:32:58] Speaker 00: However, I would say that that is mooted by the board's finding with respect to Merck's tables three and four. [00:33:11] Speaker 00: You see this immunogenicity across all manner of serotypes. [00:33:18] Speaker 00: And the board's general finding that everyone in skill in the art knew [00:33:25] Speaker 00: that molecular weight affected immunogenicity. [00:33:29] Speaker 00: They knew that molecular weight range just had to be determined for each individual serotype to maximize immune response. [00:33:40] Speaker 00: They knew how to create, isolate, and identify [00:33:47] Speaker 00: glycoconjugates of a variety of molecular weights. [00:33:52] Speaker 00: And they knew how to test for their immunogenicity. [00:33:54] Speaker 02: And they had done. [00:33:55] Speaker 02: Counsel, you've exceeded your time. [00:33:57] Speaker 02: Do you want to finish your thought? [00:34:00] Speaker 00: Yes. [00:34:01] Speaker 00: I would say that substantial evidence supports the board's determination that this molecular weight ranges were results effective activity. [00:34:11] Speaker 00: And that they were routinely optimizable. [00:34:17] Speaker 00: And while I may have been not doing so, it may have been not obvious in the past that time has long since passed and that this court should affirm the court decision. [00:34:29] Speaker 02: Thank you, counsel. [00:34:31] Speaker 02: Mr. Shiabella, I'm going to take three minutes. [00:34:35] Speaker 01: Yes. [00:34:35] Speaker 01: Thank you, your honor. [00:34:41] Speaker 01: So for claims three and four, just to quickly note that the evidence that the board glossed over this decision is further shown that in the decision, you'll see that the board doesn't even mention stereotypes 12F or eight from claim four. [00:34:54] Speaker 01: It mentions those stereotypes in connection with the discussion of the prior law. [00:35:00] Speaker 01: But in the analysis, zero. [00:35:01] Speaker 01: In the subheadings, nothing. [00:35:03] Speaker 01: That's just another thing. [00:35:04] Speaker 01: On the motion to amend in Claim 46, we think this case lines up factually and legally with the Strathclyde case that we've cited at page 25 and 27 of our reply brief. [00:35:17] Speaker 01: In that case, the board found the claim obvious. [00:35:20] Speaker 01: over two references. [00:35:22] Speaker 01: The secondary reference, the NITSAN reference, explicitly had data where it tried to achieve the claimed invention, and it failed. [00:35:33] Speaker 01: And we think that lines up with the facts here. [00:35:36] Speaker 01: Because as Dr. Paradiso showed in the excerpt of the table four of the Merck reference, which is at APPX 31021, and at the excerpt of table three, APPX 31027, [00:35:48] Speaker 01: He highlighted in those tables, in table four, he highlighted instances in all four study arms where the Merck vaccine failed to elicit the two log increase across all the serotypes in the composition. [00:36:04] Speaker 01: Now, that study in Table 4 reports on eight serotypes. [00:36:07] Speaker 01: It doesn't even report on all the serotypes that are listed in Claim 46. [00:36:11] Speaker 01: So the Merck reference is silent as to whether the two log inquiries can be achieved in the other serotypes. [00:36:18] Speaker 01: The challengers say, oh, well, that's all shown in the Hausdorff, the lead reference, the Hausdorff reference. [00:36:24] Speaker 01: But that's ridiculous, Your Honor. [00:36:26] Speaker 01: What Merck did in Merck 2011 is try to extend the Hausdorff teaching, which the Hausdorff teaching was a 13-valent conjugate. [00:36:35] Speaker 01: The Merck reference tried to increase that, tried to add 22f and 33f. [00:36:40] Speaker 01: the data in Table 4 shows that when Merck tried to increase that, that valency of that multivalent composition, it was unable to achieve two log increments across all the serotypes. [00:36:53] Speaker 01: The data in Table 3, our expert Dr. Paradiso also reported on that, and that's a comparison of the Merck vaccine [00:37:02] Speaker 01: to Prevnar, the 7-valent vaccine, our expert Dr. Paradiso showed that there were instances there where the Merck PCV7 vaccine, and he highlights this at 31.027, he highlights several instances where the Merck vaccine had a poorer immunogenic response than Prevnar, and some of those, which you'll see, he's got a red box around entries that Merck considered statistically significant. [00:37:28] Speaker 01: The PTL mentioned APP, excuse me, the Sanofi's Council mentioned APPX350. [00:37:37] Speaker 01: That's Sanofi's expert saying to get to the two log increase, just optimize the test conditions. [00:37:43] Speaker 01: That it's easily done and that the references show one log and two log mixed results, skilled artisan could allow you to optimize test conditions. [00:37:52] Speaker 01: That's hindsight. [00:37:53] Speaker 01: It's also addressed in the Strathclyde decision that I mentioned earlier. [00:37:56] Speaker 01: In Strathclyde, the board said, oh, the primary reference says you can optimize test conditions, light, dose, illumination, time, and culture to eradicate the MRSA bacteria. [00:38:07] Speaker 01: That's in the claim with that. [00:38:09] Speaker 01: And the board said, well, even in the absence of a photosensitizer, you could still get the primary reference shows that you could optimize test conditions. [00:38:19] Speaker 02: That's not the case. [00:38:21] Speaker 02: Your time has expired. [00:38:23] Speaker 02: Thank you. [00:38:24] Speaker 02: The case is submitted.