[00:00:56] Speaker 01: Okay, the next case is, case is combined. [00:01:00] Speaker 01: Number 14, 1778, South Alabama Medical Science against Noosis. [00:01:06] Speaker 01: And 14, 1779, American Company against Noosis. [00:01:12] Speaker 01: Mr. Parter. [00:01:27] Speaker 04: Good morning, Your Honors, may it please the court. [00:01:29] Speaker 04: My name is Thomas Parker, and I represent the Appellant, South Alabama Medical Science Foundation, also referred to as SAMHSAF in our briefs. [00:01:38] Speaker 04: The patents at issue include, there are three patents, the 778, 915, and 381 patent. [00:01:45] Speaker 04: Your Honors, this morning we respectfully ask that the board's obvious determination be overturned because the board committed at least three legal errors. [00:01:54] Speaker 04: First, it failed to expressly articulate [00:01:56] Speaker 04: whether a person of ordinary skill in the art, at the time of the invention, would have had a reasonable expectation of success in combining surf and seam, excuse me, and maraza. [00:02:05] Speaker 04: Second, the board in finding that the prior art did not teach against surf between the maraza. [00:02:11] Speaker 04: And the board compounded this error by ignoring data in certain of these prior art references. [00:02:16] Speaker 04: And third, the board applied an erroneous legal standard in rejecting SAMHSA's objective evidence. [00:02:23] Speaker 03: Your Honor, with respect to... I'll ask you the same question I asked the earlier Council. [00:02:27] Speaker 03: If you had to pick your strongest argument, what would you pick? [00:02:31] Speaker 04: That the Board failed to articulate a reasonable expectation of success analysis in support of their obviousness determination. [00:02:42] Speaker 04: Your Honor, even if all the limitations were met by the prior art in which the Board combined, and even under those circumstances, [00:02:53] Speaker 04: KSR, as well as this court's precedent, requires that in an obviousness determination that a reasonable expectation of success analysis be conveyed, especially in connection with cases that are complex or where the technology is unpredictable. [00:03:09] Speaker 04: There's no dispute with respect to the complexity and unpredictability of the subject matter of this case. [00:03:15] Speaker 04: In fact, both experts have agreed and testified that they were complex. [00:03:21] Speaker 04: And in those circumstances, [00:03:22] Speaker 04: there is no analysis that is provided. [00:03:26] Speaker 04: And even if it's somehow implicit or indirect in the board's opinion, which we say it is not, which Nosas agrees that there's no explicit analysis provided, that that still is not enough. [00:03:39] Speaker 04: Because this court's precedent also makes clear, as well as KSR, that the obviousness analysis must be explicit. [00:03:47] Speaker 04: It must set forth those particular grounds and reasons for finding the claims [00:03:52] Speaker 04: obvious. [00:03:53] Speaker 04: So if the board were to conduct a reasonable expectation of a successful analysis, the question would have been, would a person of ordinary skill and the art, in combining serpentine and miraza, would they have a reasonable expectation, for example, to be able to treat vascular disease, which is a claim element in the 7th and 8th patent, by lowering that individual's homocysteine level? [00:04:19] Speaker 04: And the reason why I include homocysteine levels is because serpentine, the reference, the main reference by the board relied on, requires that the serpentine reference is strictly directed to lowering homocysteine. [00:04:34] Speaker 04: And there's nothing in serpentine which expresses treating any other condition independently of lowering homocysteine. [00:04:42] Speaker 04: And so the board was not or is not enabled to, when they were combining it, they mentioned there was a common purpose with respect to folate deficiency. [00:04:50] Speaker 04: But that's not what serpentine is. [00:04:52] Speaker 04: It is a reference that teaches lowering homocysteine and requires it. [00:04:57] Speaker 04: It's a requirement of serpentine. [00:04:59] Speaker 04: So that would have to be built into the RES analysis, reasonable expectation of success. [00:05:06] Speaker 04: And that wasn't done with respect to [00:05:10] Speaker 04: So to the extent that that was not done until the board, so to your honor, Judge Plager's comment, that would be the one defense that we would choose to be, we would most likely went on. [00:05:21] Speaker 04: Now, I just want to just touch on other aspects of the case teaching away. [00:05:26] Speaker 04: There are a series of references, Harpy 1 and Harpy 2, for example, which contained live data showing that if one were to administer what I would refer to the 5MTHF [00:05:39] Speaker 04: This is a racemic version of 5-methyltetrahydrochloric acid, and its natural isomer, which I would refer to as L5, actually shows when you administer L5 to a patient who is unable to make L5, homocysteine levels are not decreased. [00:05:57] Speaker 04: They're actually increased. [00:06:00] Speaker 04: They actually go up, which is contrary to serpentine, which serpentine requires it to go down. [00:06:07] Speaker 04: And that data was ignored by the board in this situation. [00:06:13] Speaker 04: The board acknowledges the existence of HP1 and HP2 references with respect to stability, but did not take any consideration, or at least does not appear to incorporate that or take it into account in its analysis. [00:06:27] Speaker 04: And then there's another series of references, which we refer to as HORN, sometimes referred to Wagner. [00:06:33] Speaker 04: And we apply the HORN reference [00:06:36] Speaker 04: together with what's referred to as the Eulin reference. [00:06:39] Speaker 04: These two references are very significant because they also teach a way, they teach against, I mean, Harpy 1 and Harpy 2 would teach against combining Serpentine and Marazzo, as would Harpy, I'm sorry, as would Horne and Wagner. [00:06:50] Speaker 04: For the reasons discussed in our papers, but just briefly, in order for the natural isomer L5 to be biologically active and to be retained in the cells for purposes of metabolism, it has to be polyglutamated. [00:07:05] Speaker 04: And what HORN shows is that when L5 is administered, it is not polyglutamated. [00:07:11] Speaker 04: And how do we know that? [00:07:12] Speaker 04: Because it's not metabolized. [00:07:13] Speaker 04: Because HORN shows that it stays in the reference that it's not significantly metabolized. [00:07:21] Speaker 04: Now, where the board went wrong with respect to the HORN reference is that it relied on a particular aspect. [00:07:28] Speaker 04: Because in our papers, we were saying that L5 is a poor substrate for polyglutamation. [00:07:34] Speaker 04: And as a result, it's poorly retained, and it's not able to function. [00:07:42] Speaker 04: But the board now, when the board looked at the horn reference, it said, well, look, it says here on A2073 in the second column, it says that 5-methyl is concentrated by the hepatocytes, the cells in the case. [00:07:57] Speaker 04: Thus, there are two mechanisms by which liver may retain folates. [00:08:01] Speaker 04: But the problem there is that the board wrongly assumed [00:08:05] Speaker 04: that what was being concentrated there was functional L5, a functional folate. [00:08:13] Speaker 04: The reference horn makes clear that it is not significantly metabolized. [00:08:17] Speaker 04: In fact, they're expert, no such an expert, even testified to the effect that he acknowledged that five MTHFs were substrate for polyglutamation. [00:08:26] Speaker 04: And as a result, there is a decrease or there is no formation of functional folate. [00:08:32] Speaker 04: So the cells actually become deficient [00:08:34] Speaker 04: functional folate. [00:08:36] Speaker 04: So it's unable to metabolize. [00:08:37] Speaker 04: If it's not being metabolized, then the whole process of converting homocysteine to methionine is not going to take place. [00:08:46] Speaker 01: But they did agree it was a metabolite, L5. [00:08:52] Speaker 04: L5 in its form, when you ingest folic acid and you go through all the cycles, there's going to be a formation naturally in the cells of L5. [00:09:02] Speaker 04: And that'll be polyglutamated through the whole process. [00:09:04] Speaker 04: And then it'll be converted into, it'll help, it'll donate the methyl group to convert homocysteine to methionine. [00:09:10] Speaker 04: Correct. [00:09:11] Speaker 04: But what the board, where the board didn't appreciate was the fact that Horne did not contradict Dr. Gregory's testimony or his opinions. [00:09:20] Speaker 04: In fact, Horne supported it. [00:09:21] Speaker 04: So it was a misinterpretation of the reference because there's nothing in this reference suggesting that any of the material that was concentrated [00:09:31] Speaker 04: in the cells was actually a functional form of folate. [00:09:35] Speaker 04: And it actually supported the opinions of Dr. Gregory that directly administered 5L5 and 5MTHF are poor substrates for polyglutamation. [00:09:46] Speaker 04: And therefore, without that, they're not biologically active. [00:09:50] Speaker 04: And without that, they're not retained in the cell. [00:09:52] Speaker 04: So all the while, when we're referring to accumulated L5 in the cells, [00:09:59] Speaker 04: we're referring to functional L5 because it would not make any sense to be relying on HORN for a proposition that we were looking to HORN to show the accumulation of non-functional folate. [00:10:10] Speaker 04: So that's where the board erred in that respect. [00:10:15] Speaker 04: And then we have also the board rejected Dr. Miller's testimony when he described and he conceded this whole notion about directly administered 5MTHF in this particular case would not [00:10:29] Speaker 04: be a poor substrate for polyglutamation and therefore would not be able to form functional folate. [00:10:34] Speaker 04: The board rejected that testimony on the grounds that the deposition testimony itself was really directed to his statement as of the day the deposition was taking place, which was May 6, 2013. [00:10:46] Speaker 04: But that was incorrect because if you look at the transcript, the predicate, the foundation of the time frame was clearly set out from the time period of 1995 to 1996 [00:10:58] Speaker 04: He was handed an exhibit, the exhibit in the line of question and dealt with folic acid, and it continued. [00:11:05] Speaker 04: So it's clear that the time frame was established, and that he was testifying not as of May 6, 2013, but of one of ordinary skill in the art prior to the 95, 96 time frame. [00:11:19] Speaker 04: So the board, I think, the board aired there as well, and then as such, with respect to the proposition that Horne [00:11:28] Speaker 04: together with Ewing, taught against combining surf and genome metabolism. [00:11:32] Speaker 04: The board either ignored or the board misapprehended the evidence that was submitted. [00:11:46] Speaker 04: Okay. [00:11:47] Speaker 04: Now, with respect to secondary considerations, the board rejected all of SAMHSA's objective evidence. [00:11:54] Speaker 04: And for [00:11:58] Speaker 04: various reasons. [00:12:00] Speaker 04: First, the Board took the position that we failed to tie the, in this particular case, the secondary considerations, for example, commercial success, was based upon the sales of products that were sold by a company called PM1. [00:12:14] Speaker 04: The Board took the position that we did not tie the products, the components of the products, to any particular claimed elements to tie into the commercial success. [00:12:26] Speaker 01: What was their reason for [00:12:29] Speaker 01: saying there was no tie. [00:12:30] Speaker 01: They were not willing to accept what you proffered, I assume, that it is the product itself that is sold. [00:12:40] Speaker 04: The problem was the board used the word novel element in the claim. [00:12:45] Speaker 04: We failed to tie the evidence to a novel element in the claim. [00:12:49] Speaker 04: There is no individual novel element. [00:12:51] Speaker 04: What we have is a novel combination of elements that were known in the prior art. [00:12:57] Speaker 04: And so that was the problem with the board's rationale. [00:13:01] Speaker 04: We in fact tied the evidence, which is, you see the products are a combination of vitamins, and we tied the elements, which the claim is directed to, it's directed to reduce folate in one or more vitamins, and we tied all that together in the form of six declarations by six experts. [00:13:22] Speaker 04: And so the notion of tying it to a novel element just doesn't work when you have [00:13:26] Speaker 04: a combination, a novel combination of prior elements. [00:13:29] Speaker 04: So that was one of the reasons and one of the grounds. [00:13:30] Speaker 04: And that was a mistake on the part of the board. [00:13:35] Speaker 04: Also, the board seemed to be requiring that we, that the claims have to explicitly recite the specific vitamins, the vitamin combinations or the specific ingredients exactly as they appear in the product. [00:13:49] Speaker 04: When in fact, that is not a requirement. [00:13:50] Speaker 04: I mean, the claims are certainly broader than the products and that's fine. [00:13:54] Speaker 04: In fact, under this course precedent, [00:13:56] Speaker 04: that seems to be the case when you're introducing objective evidence. [00:13:59] Speaker 04: You don't have to show objective evidence for every conceivable embodiment under the scope of the claim. [00:14:04] Speaker 04: In another aspect as well, the board rejected the evidence requiring SAMSF to show evidence that other embodiments within the scope of the claim would have behaved the same as the PAM lab products. [00:14:18] Speaker 04: That we had to provide evidence showing that they would have other [00:14:22] Speaker 04: undefined embodiments would have behaved the same as each of the five PAM lab products that we were working with. [00:14:28] Speaker 04: And that is not a requirement under any of the case law, at least that I'm aware of. [00:14:35] Speaker 04: And what the board did to put it all together is there were references to the word unique with respect to some of our witnesses' statements in the declarations. [00:14:46] Speaker 04: But this word unique was, and then the board took the word unique to say, well, you are implying [00:14:51] Speaker 04: that the combinations of the specific vitamins used in the PamLab products are so unique that no other embodiment within the scope of the claim would behave the same as these products. [00:15:03] Speaker 04: Well, that's just not a reasonable interpretation of the testimony. [00:15:06] Speaker 04: And I think it speaks for itself. [00:15:08] Speaker 04: And for example, he cites to Mr. Ladner, who was senior vice president of PamLab. [00:15:15] Speaker 04: And when he was referring to the word unique, he was just making a comparison to the market in terms of conventional drugs [00:15:22] Speaker 04: which are usually chemical entities, versus what we have here is what's referred to as medical foods, vitamins, which are exempt from the Hatch-Waxman Act. [00:15:30] Speaker 04: So the word unique does not at all justify the sweeping conclusion by the board that somehow these statements by themselves would stand for a proposition that every conceivable embodiment under the scope of the claims would not behave the same as the Pamela products. [00:15:49] Speaker 04: So in that particular, in that regard, [00:15:51] Speaker 04: The board rejected all of SAMHSA's objective evidence. [00:15:54] Speaker 04: And we believe that that was error. [00:15:56] Speaker 04: That does not follow this court's precedent. [00:16:01] Speaker 04: In fact, it just required way much too stringent. [00:16:06] Speaker 04: It imposed a much too rigorous requirement for establishing the nexus with respect to the commercial success, the licensing, the copying, the industry praise, the long felt need. [00:16:20] Speaker 04: I mean, there's an abundance amount of objective evidence that we submitted to each of these five products. [00:16:24] Speaker 04: I mean, this case is a little bit atypical. [00:16:26] Speaker 04: We have five different products. [00:16:28] Speaker 03: What's our standard of review for all of those underlying facts coming from the board? [00:16:33] Speaker 04: So the standard review will be substantial evidence for the factual findings. [00:16:37] Speaker 04: Obviously, the legal conclusion of obviousness would be undeniable. [00:16:41] Speaker 03: This whole case is based on an accumulation of a variety of factual determinations, is it not? [00:16:49] Speaker 03: no i mean the underlying case surely but the gist of which we have to give deference under the most deferential standard that exists which is if there's substantial evidence in that record we're bound you agree with that i agree that that is the you're absolutely correct that is the standard but what we're saying here is the board applied the wrong legal standard to the facts [00:17:18] Speaker 03: We were just talking about factual issues. [00:17:20] Speaker 03: What's the wrong legal standard? [00:17:21] Speaker 04: The wrong legal standard. [00:17:23] Speaker 04: Requiring that a claim has to recite the specific embodiment exactly. [00:17:27] Speaker 04: That is not the requirement for establishing nexus. [00:17:30] Speaker 04: That the products have to behave the same across the board of the range of the claim. [00:17:35] Speaker 04: That is not a legal, that is not a requirement on this court's precedent. [00:17:38] Speaker 03: You're getting all this from your interpretation of the board's explanation of what it did. [00:17:43] Speaker 04: Yes. [00:17:44] Speaker 03: Okay. [00:17:45] Speaker 04: Yes. [00:17:45] Speaker 04: And that's quite apparent from the board. [00:17:47] Speaker 04: Because they also cite the case of Henry Coe, and they focused on the section of Henry Coe dealing with unexpected results. [00:17:54] Speaker 04: Now, unexpected results has a little bit of somewhat of an obligation to show that you have to show the unexpected results across the range of the claim. [00:18:01] Speaker 04: But that's not so, for example, for commercial success. [00:18:04] Speaker 04: And there are a number of cases from this court which says that you don't have to show commercial success featuring every embodiment under the scope of the claim. [00:18:12] Speaker 04: So that's what we're essentially saying, Your Honor, is that it was a wrong... [00:18:17] Speaker 04: It was an improper legal, they did not properly apply the precedent of this court as we laid out in our papers. [00:18:24] Speaker 03: So if they were a little more careful on how they'd written it, we wouldn't, you wouldn't be up here. [00:18:28] Speaker 03: That's correct, Your Honor. [00:18:30] Speaker 03: That's absolutely correct. [00:18:33] Speaker 03: If they were to follow, if they were to follow this court's precedent. [00:18:36] Speaker 03: Even with the same result, since it's all fact based. [00:18:41] Speaker 03: Excuse me, one more. [00:18:41] Speaker 03: Even if they reach the same result, which is [00:18:45] Speaker 03: all fact-based, had they written it more carefully, you wouldn't be up here. [00:18:51] Speaker 04: I would like to think not. [00:18:53] Speaker 04: I mean, if they apply the case law correctly, I would like to think they would have come to the conclusion that the claims were not obvious, or that they would have given due weight, significant weight, to the evidence, to the objective evidence. [00:19:04] Speaker 01: Well, they're required to consider the objective evidence, the secondary considerations, as a matter of law. [00:19:11] Speaker 01: That is correct. [00:19:12] Speaker 04: That's correct, Your Honor. [00:19:14] Speaker 04: That's correct. [00:19:14] Speaker 04: And just another example as well is we provided evidence of industry praise. [00:19:20] Speaker 04: And it was rejected because the court found that it was not tied, that it was tied to just the L5 and not the combination and said, well, the L5 is a prior element. [00:19:32] Speaker 04: I mean, that is a situation where perhaps maybe a factual issue. [00:19:37] Speaker 04: But when you read the declarations, as we cite in our papers, it's just not the case. [00:19:43] Speaker 04: They clearly, the experts clearly associate the industry praise with the invention, claimed invention as a whole, not with respect to one vitamin. [00:19:58] Speaker 04: Now I reserve three minutes of time. [00:20:00] Speaker 01: Well, are the issues any different between the university and Merck? [00:20:06] Speaker 01: Perhaps it would make more sense to continue with your argument in chief and with your rebuttal. [00:20:12] Speaker 01: Yes, Your Honor, there are overlapping... Are all issues different? [00:20:16] Speaker 04: There are. [00:20:17] Speaker 04: There are some issues that are different. [00:20:18] Speaker 04: For example, anticipation, claim construction, and the way in which the board handled the objective evidence. [00:20:23] Speaker 04: Otherwise, the priority is essentially the same. [00:20:25] Speaker 01: Well, in that case, let's hear from the other side on the first appeal. [00:20:45] Speaker 01: Mr. Swick. [00:20:46] Speaker 00: Good morning, Your Honors. [00:20:48] Speaker 00: My name is Joe Swick. [00:20:49] Speaker 00: I'm here on behalf of the Appellee's Gnosis in this case. [00:20:52] Speaker 00: I'd like to address some of the comments that my opposite counsel just made to the Court. [00:21:00] Speaker 00: First point he talked about was the fact that this idea of the reasonable expectation of success. [00:21:06] Speaker 00: And I will concede that in the final written decision, there is no specific express language talking about [00:21:13] Speaker 00: the reasonable expectation of success. [00:21:15] Speaker 00: Those words are not an opinion. [00:21:17] Speaker 00: However, it's clear to us that the Board did engage in that analysis and that is evidence in the actual opinion itself. [00:21:27] Speaker 00: The way the Board expressed its belief that there would be a reasonable expectation of success is that it talked about, and this is on page 837 of the record, that [00:21:38] Speaker 00: The serpentine reference calls for a suitable active metabolite of folate in an oral preparation. [00:21:44] Speaker 00: It uses those words. [00:21:45] Speaker 00: And then after looking at those words of what serpentine calls for, which is a suitable active metabolite, the board takes the next step and looks at the Marazza reference, which I also relied upon and said, that's it. [00:21:59] Speaker 00: Marazza is raising its hand. [00:22:01] Speaker 00: Marazza is saying, I am the suitable active metabolite. [00:22:05] Speaker 00: I am the 6S5MTHF. [00:22:08] Speaker 01: But it isn't just that the L5 might be a suitable metabolite. [00:22:13] Speaker 01: As far as the reasonable expectation success, doesn't there also have to be a reason for selecting L5 to start with? [00:22:22] Speaker 00: There does have to be a reason for selecting the L5 as well. [00:22:26] Speaker 00: And the Meraz reference absolutely did talk about that. [00:22:29] Speaker 00: And the board recognized the reason that one would pick the L5 MTHF among the suitable active metabolites. [00:22:36] Speaker 00: The Meraz reference talks about [00:22:38] Speaker 00: how the L5 is going to be useful for vitamin therapy as an active metabolite of folate. [00:22:47] Speaker 00: It then talks about the distinction between the L5, the 6S isomer, and how that is different than the 6R isomer. [00:22:56] Speaker 01: I'll tell you what troubles me in this what looks like a hindsight. [00:23:01] Speaker 01: Here we have years, decades of an appreciation of the role [00:23:07] Speaker 01: role in metabolism of this vitamin. [00:23:12] Speaker 01: And without this step, this selection, until these scientists came along? [00:23:21] Speaker 00: Well, Your Honor, I think it's clear that the 6S L5 isomer was seen as the most promising isomer of the eight reduced folates that are in the metabolite [00:23:37] Speaker 00: cycle that happens with folic acid. [00:23:40] Speaker 01: Well, the idea of selecting an isomer or selecting a metabolite seems to be something that was not particularly present other than perhaps as a scientific curiosity. [00:23:53] Speaker 00: Well, Your Honor, I think Meraza really did solve the problem of figuring out which of the eight isomers would be believed to be the most useful. [00:24:02] Speaker 00: And Meraza is the one who says, you know, after he comes after Serpentine, raises his hand and says, here it is, the 6S5M. [00:24:09] Speaker 02: But how do you get from Serpentine to Meraza? [00:24:13] Speaker 02: Even assuming Meraza discloses that, where's the board's analysis on the motivation to combine those two? [00:24:20] Speaker 00: The motivation to combine the, and that was an argument that was not in the [00:24:28] Speaker 00: They did not raise that argument in this appeal, but they did raise that argument in the other appeal. [00:24:33] Speaker 00: And the motivation to combine, the board did find it in page 823 in the 1779 Merck appeal. [00:24:44] Speaker 00: And the board found that the close similarity of purpose and disclosure between these references, talking about circunstance and marazza, provides sufficient rationale for one or no or near skill in the art to have combined them. [00:24:57] Speaker 00: And it cites KSR. [00:24:59] Speaker 00: And before it gives that statement of law, it talks about how serpentine was there to correct folate deficiency and treat diseases associated with elevated levels of homocysteine. [00:25:12] Speaker 00: And then it recognizes that Marazza is disclosing the same purpose and disclosure by stating that Marazza specifically identifies a carly pure [00:25:24] Speaker 00: L5MTHS has an active metabolite of folate suitable for use as a therapeutic agent in folate deficient states. [00:25:33] Speaker 00: And that's a quote from the board, and that's on page 823 in the 1779 appeal when it's expressly addressing the motivation to combine. [00:25:43] Speaker 00: So that's for the motivation. [00:25:45] Speaker 02: But this used to be the board's own reasoning about why it would combine. [00:25:48] Speaker 02: I mean, instead of actual evidence that some person of ordinary skill would have combined. [00:25:55] Speaker 02: Isn't there a distinction there? [00:25:58] Speaker 00: Your Honor, I think the actual evidence is in the references themselves. [00:26:03] Speaker 00: I mean, is there a reference that says, you know, explicitly, did Morad just say okay? [00:26:10] Speaker 02: So is this more in your line, you think this is the Board's conclusion that a person of ordinary skill looking at these two references would have found enough that they would have combined serpentine and morassage just based upon the closeness of the references? [00:26:24] Speaker 00: And based on the similarity of the purposes of which they were both, you know, designated for and the actual disclosures within the references themselves. [00:26:38] Speaker 00: Council raised the issue of the Harpe references. [00:26:43] Speaker 00: And the primary argument they made with respect to the Harpe references is he talked about the effectiveness, but down below what we were really talking about was whether [00:26:54] Speaker 00: Harvey disclosed whether the L5MTHF or the 5MTHF would be thought to be stable enough. [00:27:00] Speaker 00: And what the board correctly recognizes that, well, Harvey did express some concerns about stability in that time period. [00:27:08] Speaker 00: But then the board recognized that after Harvey came the Godfrey reference, came the Reggie reference, came the Patini reference, which all found that the 5MTHF was suitable and stateable enough to therapeutically treat [00:27:23] Speaker 00: So the Board correctly recognized that whatever concerns Harvey had in the beginning, those concerns had been overcome in the arts prior to the invention through those three references. [00:27:35] Speaker 00: With respect to the Horne and Wagner-Ewellen argument that Council made, you know, that argument, you know, had a long factual basis. [00:27:45] Speaker 00: They first started their argument by saying, well, those references teach away because the L5MTHF is a poor [00:27:53] Speaker 00: substrate for polyglutamation. [00:27:55] Speaker 00: Then we did the depositions and the both experts said, well, actually, folic acid is just as bad for the substrate activity for polyglutamation. [00:28:06] Speaker 00: Then we presented them with the Chick-Wets reference, which showed folic acid was actually a worse substrate than the 6S5MTHF. [00:28:14] Speaker 00: Therefore, we thought Wagner and Yolen could not be a teaching away. [00:28:18] Speaker 00: Then the argument morphed into [00:28:21] Speaker 00: They said, well, what we're really seeing is it's the amount of the L5MTHF that's retained in the cells. [00:28:27] Speaker 00: That's what's important. [00:28:29] Speaker 00: And the Wagner shows that there was really no accumulation of the L5MTHF in the cells themselves. [00:28:37] Speaker 00: An oral argument at the board, the board confirmed this and said, well, actually, Wagner does say that some L5MTHF is within the cells. [00:28:44] Speaker 00: Isn't that correct? [00:28:45] Speaker 00: And that's what the board found. [00:28:46] Speaker 00: In fact, that's what Horne and Wagner do show. [00:28:50] Speaker 00: So then their argument really morphed into, well, okay, L5MTHF is just as bad of a poor substrate. [00:28:57] Speaker 00: It is retained in the cells, but it's the amount of L5MTHF in the cells that can be metabolized. [00:29:06] Speaker 00: And that's what Wagner shows. [00:29:08] Speaker 00: Well, and the board, you know, addressed that and said, no, that's not a sign on a factual basis. [00:29:12] Speaker 00: We find what Wagner's teaching is that some of the L5MTHF is being metabolized. [00:29:18] Speaker 00: And Wagner is being conducted in a in vitro experimental type condition. [00:29:23] Speaker 00: There's no evidence in the record that that experimental result would translate into a similar result in vivo in the humans. [00:29:30] Speaker 00: So we're not going to accept that evidence as persuasive teaching away. [00:29:35] Speaker 00: And also they recognize that to the extent that Wagner and Horn say that the L5MTHF is not significantly metabolized, [00:29:47] Speaker 00: in the cells metabolized was never defined by the Merck experts or the SAMSF experts, so it's really just unpersuasive. [00:29:57] Speaker 01: The metabolite was never defined. [00:29:59] Speaker 01: What do you mean? [00:30:01] Speaker 01: The word metabolite? [00:30:02] Speaker 00: Right, right. [00:30:03] Speaker 01: The... The word's in the dictionary, isn't it? [00:30:07] Speaker 00: The word is in the dictionary, right, but the word, you know, has probably a very scientific meaning and the problem is there was no scientific basis [00:30:16] Speaker 00: or expert opinion of what metabolized means in the context of what Horne and Wagner were talking about in an experimental condition. [00:30:25] Speaker 01: Maybe I misread the record, but the whole thing is about metabolites and selection of metabolites and how many metabolites and how many variations. [00:30:36] Speaker 00: Right, right. [00:30:38] Speaker 00: And that's our contention, that it is one of the... So where was the lack of definition? [00:30:45] Speaker 01: Will you define it? [00:30:47] Speaker 01: Can you define it? [00:30:50] Speaker 00: I cannot, and that's the problem. [00:30:51] Speaker 00: There was not expert testimony of what metabolization means in the context of that experimental test. [00:30:57] Speaker 01: You're saying that in this case, the word has a different meaning from the ordinary common meaning of metabolite? [00:31:05] Speaker 01: Is there any doubt when they say that there are eight primary metabolites, what they're talking about? [00:31:10] Speaker 00: There's no doubt as to what those eight metabolites are in the folate cycle that is moving around. [00:31:17] Speaker 00: Unquestionably, there's not. [00:31:18] Speaker 01: I just want to understand your argument. [00:31:21] Speaker 00: I'm sorry, can you say that? [00:31:22] Speaker 01: I want to understand the argument that you're making about metabolite not being defined. [00:31:28] Speaker 00: Right, right. [00:31:29] Speaker 00: Well, I'm just recognizing that the board had struggled trying to define itself what metabolization meant [00:31:37] Speaker 00: in the context of one sentence that was cherry-picked out of the Horn and Wagner reference. [00:31:43] Speaker 00: And it asked counsel, I believe, at oral argument, that's my recollection, what does that mean? [00:31:49] Speaker 00: And no one was able to define it at the board's hearing. [00:31:52] Speaker 00: So if they're going to use this as a teaching away, they need to come forward and explain what it means. [00:31:58] Speaker 00: I don't think it's my duty to prove what their teaching away reference means and what the experimental result meant in a teaching away. [00:32:07] Speaker 03: Council, I take it you handled this before the board? [00:32:11] Speaker 00: Yes, co-counsel and actually split it. [00:32:13] Speaker 00: Correct. [00:32:16] Speaker 00: All four of the cases? [00:32:19] Speaker 00: Correct, Your Honor. [00:32:20] Speaker 00: It was, they were split into two, we, similar to this one, we had three daily patents and one oral argument and then we had the Merck patent, a separate oral argument on the same day, consecutive order two. [00:32:35] Speaker 01: You never objected to the absence of definition of metabolite until now? [00:32:44] Speaker 00: I don't recall, Your Honor. [00:32:45] Speaker 00: I really don't recall if I objected to that or not. [00:32:50] Speaker 03: Your case doesn't turn on that issue, is that right? [00:32:53] Speaker 00: It really does not turn on that issue at all. [00:32:55] Speaker 00: I mean, because this is one teaching away that they're saying, well, this would have dissuaded a person with an ordinary skill in the art from [00:33:03] Speaker 00: ever using an L5 MTHF because of this experimental result. [00:33:06] Speaker 00: This is one experimental result. [00:33:09] Speaker 00: Contrast that to, we have serpentine saying, use a suitable active metabolite to lower homocysteine. [00:33:15] Speaker 00: We have marazza saying, here I am. [00:33:16] Speaker 00: I am the suitable active metabolite. [00:33:18] Speaker 00: It's the best one out there. [00:33:20] Speaker 00: This is the one you want to use. [00:33:21] Speaker 00: We have Godfrey actually using 5 MTHF in experimental conditions and getting good results in treating depression. [00:33:28] Speaker 00: We have Regis [00:33:29] Speaker 00: who's using an actual 5MTHF product that's made by BioResearch in Milan, Italy, and he's using that. [00:33:36] Speaker 00: We have Patini who's using it to treat bicyclists in the Alps Mountains who have insufficient folate and is giving them iron and the 5MTHF. [00:33:47] Speaker 00: So if in fact this one experimental result about there's a question as how well the L5MTHF is retained in the cells and metabolized, [00:33:57] Speaker 00: Why do we have this avalanche of evidence of all these other people actually using 5-MCHF? [00:34:03] Speaker 00: And we have Serpentine and Marazza all suggesting that this is the way to go. [00:34:06] Speaker 01: So it is one teaching. [00:34:08] Speaker 01: Excuse me. [00:34:09] Speaker 01: Are you saying they provided too much evidence or not enough evidence? [00:34:14] Speaker 00: Not enough. [00:34:15] Speaker 00: I mean, on this teaching away reference, I think this is an anomaly and it's undefined, it's inconclusive, it's unpersuasive. [00:34:23] Speaker 00: The board actually looked at this and they came up with their substantial [00:34:27] Speaker 00: evidence in their mind of why this reference was simply just not a persuasive reference. [00:34:38] Speaker 00: Regarding the secondary factors, first of all, counsel suggested that the Board took a strict test and said that, well, we're looking for what the novel element is in the claim. [00:34:56] Speaker 00: and it's a single novel element and unless the commercial success or the secondary evidence is tied to that novel element, then we're going to reject it. [00:35:08] Speaker 00: First of all, they didn't ever reject any of the secondary evidence. [00:35:11] Speaker 00: What they said, the secondary evidence was tenuous at best. [00:35:14] Speaker 00: So it wasn't a wholesale rejection as counsel has implied. [00:35:17] Speaker 00: But also, it's clear to me that the board did not limit its analysis to looking for only a single [00:35:26] Speaker 00: element as opposed to the claim as a whole. [00:35:30] Speaker 00: Because what we see on page A40 of the record, which is the page 40, the final written decision for the 915, Pat says, the particular combination of active ingredients in any of the PAM lab products is not recited as an element or combination of elements of any claim under review. [00:35:51] Speaker 00: As such, the objective evidence for each product lacks a clear nexus with the claims. [00:35:56] Speaker 00: Here, it's clear to me that by saying that any element or combination of elements, the Board is correctly considering the claimed invention as whole. [00:36:05] Speaker 00: It's looking if indeed there is any novel element, it's not finding any. [00:36:11] Speaker 00: Council just told us that there are no specific novel elements. [00:36:15] Speaker 00: They say the claim is novel because its claim as a whole is what's novel, but here we see the Board actually did consider the combination of elements as well and expressly said that it was looking at that. [00:36:26] Speaker 00: as well. [00:36:30] Speaker 00: Council makes the point over and over again that, well, they don't have to prove that every single embodiment within this very broad scope of claims is tied to the secondary evidence. [00:36:43] Speaker 00: It's never been our position, and it was not the board's position that 100% of the embodiments within a specific claim needs to be attributed to the commercial success. [00:36:54] Speaker 00: But there has to be [00:36:55] Speaker 00: a nexus. [00:36:56] Speaker 00: There has to be a reasonable tie to the amount of products that fall within the claim and how they relate to the claims as a whole. [00:37:09] Speaker 00: Because here in this case, in the Bailey patents, we have very broad claims covering the 6S 5MCHF and any combination of any vitamin, any mineral. [00:37:21] Speaker 00: So in my mind, the claims are as broad as a swimming pool where [00:37:26] Speaker 00: every one of these embodiments is a specific marble within this swimming pool. [00:37:30] Speaker 00: What SAMHSA did is says, all right, we've got five or six SAMHSA products, and these are our five, six marbles. [00:37:37] Speaker 00: We've made them. [00:37:38] Speaker 00: They have specific uses. [00:37:40] Speaker 00: They have specific vitamin combinations. [00:37:43] Speaker 00: Our five or six marbles, we're going to throw them into the swimming pool. [00:37:47] Speaker 00: That's the claim as a whole. [00:37:49] Speaker 00: The fact that we can show five or six of these marbles within the entire swimming pool, we're [00:37:56] Speaker 00: Therefore, that means the entire swimming pool is successful. [00:38:00] Speaker 00: And the objective evidence should be tied to this entire swimming pool full of marbles. [00:38:04] Speaker 00: And that's just illogical. [00:38:05] Speaker 00: It doesn't make sense. [00:38:06] Speaker 00: In this case, the boar town, it was a very, very small subset of embodiments that they presented on evidence as it relates to the claim as a whole. [00:38:15] Speaker 00: So for them to find that the secondary evidence was tenuous, I think there's substantial evidence in the record to support their finding on that. [00:38:26] Speaker 01: Okay, I think that as far as, let's hear the rebuttal on the university's appeal, and then we'll proceed with the other case, the remaining issues. [00:38:37] Speaker 04: All right, thank you, Your Honor. [00:38:41] Speaker 04: Thank you, Your Honors. [00:38:44] Speaker 04: With respect to the requirement that the Board make a finding of reasonable expectation of success, let me just cite, just for the Court's benefit, I'm sure I know I understand the Court's aware of this case, [00:38:56] Speaker 04: Perfect Web 587 of 1324-1329, where they're citing to KSR, the court said, with respect to obviousness, to facilitate review, this analysis should be made explicit. [00:39:11] Speaker 04: So to the extent that Pelley was arguing that it was indirect, that the word suitable, which by the way is a claim limitation, I'm sorry, it's part of an entire phrase, suitable act of metabolite [00:39:25] Speaker 04: that there was somehow a built-in reasonable expectation of success analysis into the term suitable, even then I don't think that that would be considered to be an explicit analysis of reasonable expectation of success. [00:39:39] Speaker 04: In fact, the word suitable wasn't even really defined in this case. [00:39:43] Speaker 04: I mean, the board did not adopt any particular definition of the word suitable. [00:39:46] Speaker 03: But our view was that it should be made explicit to facilitate review. [00:39:53] Speaker 03: Correct. [00:39:54] Speaker 03: Assuming we can review a matter without it being explicit, there's no error on that issue, is there? [00:40:02] Speaker 04: To the extent that it was either an indirect or implicit, I'm not aware of a situation where that would be so, especially in a situation where you have a subject matter which is so complex. [00:40:14] Speaker 04: I mean, we were not on notice, I would say, in terms of what the basis was and what would be our recourse to that extent if we weren't even able to discern [00:40:23] Speaker 04: what the RES analysis was done if it was done indirectly or implicitly. [00:40:28] Speaker 04: And you're going back and forth different pages. [00:40:30] Speaker 04: A couple of things. [00:40:32] Speaker 04: Now with respect to with the Harpy references, Gnosis was the, they were the ones that raised Harpy to establish that it taught. [00:40:43] Speaker 02: But the problem with Harpy is even if we agree with you that they teach away, there's a whole bunch of other references that the board relies on to say they don't. [00:40:50] Speaker 02: So in this very deferential substantial evidence review, [00:40:53] Speaker 02: It doesn't matter what Harvey says, it matters what the other one says, doesn't it? [00:40:58] Speaker 04: But there's two classes of references. [00:41:02] Speaker 04: The ones that they were just referring to, there's a whole slew of them, that were not even addressed in the board's decision. [00:41:08] Speaker 04: No factual findings were made, for example, Godfrey. [00:41:11] Speaker 04: I'm sorry, not Godfrey. [00:41:13] Speaker 04: There are other references, I can't think of right now, but there's a series of references that were not relied upon in the board's decision. [00:41:21] Speaker 04: So it's tough to announce. [00:41:23] Speaker 04: come forward and say, well, this reference teaches toward the invention. [00:41:29] Speaker 04: For example, Godfrey, at the very end of Godfrey, he concludes. [00:41:33] Speaker 04: He has no idea why this works. [00:41:35] Speaker 04: He doesn't understand the mechanism of action. [00:41:37] Speaker 04: He doesn't understand if correct and fully deficiency. [00:41:39] Speaker 02: But we're not the fact-fighters. [00:41:41] Speaker 02: No, no, actually not. [00:41:42] Speaker 02: We're looking at whether there's substantial evidence. [00:41:44] Speaker 02: As long as we find one of those references, [00:41:46] Speaker 02: that doesn't teach away isn't that substantial evidence to support the board's conclusion. [00:41:50] Speaker 04: Well, but then again, if we go back to Harpy though, I mean, Harpy is live. [00:41:54] Speaker 04: But that's the problem. [00:41:55] Speaker 04: We don't have to go back to Harpy. [00:41:57] Speaker 02: It doesn't matter what Harpy says as long as there's enough evidence to support the other conclusion. [00:42:03] Speaker 04: Agreed. [00:42:03] Speaker 04: But now Harpy, in addition to the horn and everything else that we've laid out, would suggest that these other references do not say anything about lowering homocysteine. [00:42:13] Speaker 04: They don't tell you anything about the uptake [00:42:16] Speaker 04: of what's going on. [00:42:16] Speaker 04: We know that there's the uptake, but there's substantial evidence. [00:42:20] Speaker 04: But where is the reference that's teaching that if you administer L5 specifically, you're going to lower homocysteine? [00:42:27] Speaker 04: That is not in the record. [00:42:29] Speaker 04: There's no prior art teaching that. [00:42:32] Speaker 04: The references he cited do not teach that. [00:42:35] Speaker 04: And that would not be substantial evidence at all. [00:42:38] Speaker 04: And by the way, they don't offer a single expert, a single expert to discuss those references. [00:42:44] Speaker 04: which also makes it a little bit more difficult because now it's just attorney argument that's being substituted in the place of evidence. [00:42:53] Speaker 04: With respect to the metabolism, that was not ever in dispute, the word metabolism. [00:43:00] Speaker 04: It was clear. [00:43:01] Speaker 04: I mean, the references, the horn references shows metabolism is the L5, it's radio labeled. [00:43:07] Speaker 04: There was, I'm not sure where that came from, but that was not something that we were [00:43:12] Speaker 04: had a problem with or anyone had a problem with during the oral argument. [00:43:16] Speaker 04: And with respect to the secondary evidence, although not required, noses do not provide or put forth an expert to rebut any of the experts in that respect. [00:43:32] Speaker 04: All they provided with, in essence, is an attorney argument. [00:43:35] Speaker 04: They didn't address the market. [00:43:37] Speaker 04: They didn't have an expert addressing the market, an expert addressing [00:43:41] Speaker 04: the long felt need for an expert addressing the commercial sales and putting it in perspective. [00:43:48] Speaker 04: This is not in a sense a case of substantial evidence. [00:43:55] Speaker 04: It really is primarily an application of the law by the board that was incorrect with respect to secondary considerations. [00:44:03] Speaker 04: That is the heart of what we're saying versus the facts itself. [00:44:10] Speaker 01: Okay, can we proceed to the second case or are there anything else you need to tell us in rebuttal in a sentence or two? [00:44:20] Speaker 04: Yes, there is just one more point. [00:44:23] Speaker 03: Okay, we have it. [00:44:36] Speaker 03: Okay, we will.