[00:00:00] Speaker 00: Start the clock again on case 14-1779, Merkin Company against Noseph. [00:00:06] Speaker 00: And Mr. Parker. [00:00:08] Speaker 03: Thank you, Your Honor. [00:00:08] Speaker 03: And for the record, my name is Tom Parker, representing the appellant, Merkin C. Your Honor, the situation here in terms of the teaching away, in terms of the issues with respect to the references in the board [00:00:28] Speaker 03: the board's handling of those references are essentially the same with respect to Horne and also with respect to Harper. [00:00:37] Speaker 03: What's different about this case? [00:00:39] Speaker 01: I think we have your argument on those issues. [00:00:45] Speaker 01: What's different that we have to decide about this case that isn't resolved by the arguments in that case? [00:00:50] Speaker 03: Anticipation, the issue of anticipation. [00:00:52] Speaker 03: Let me just get to that. [00:00:55] Speaker 01: Can I ask you this, because you also have a claim construction argument here too. [00:00:58] Speaker 03: Yes, that's correct. [00:01:02] Speaker 01: Does a claim construction argument matter if we disagree with you on obviousness? [00:01:14] Speaker 01: It didn't seem to me like you argued that in your brief here. [00:01:18] Speaker 03: No, no. [00:01:20] Speaker 01: Even if we agree that the claim construction may be [00:01:23] Speaker 01: faulty for including both forms, and that might affect the anticipation question. [00:01:29] Speaker 01: Could we conclude that the Board's obviousness determination that serpentine and mirage are sufficient, does the claim construction affect that combination? [00:01:41] Speaker 03: The answer is no, Your Honor, and this is the reasons why. [00:01:45] Speaker 03: Because it's still out of position, despite the construction of the claim, whether you affirm or overturn the Board's construction. [00:01:53] Speaker 03: The position with respect to obviousness is still the same, that the prior art teaches against combining surf and chain. [00:02:01] Speaker 04: But that's not true of the anticipation issue, is it? [00:02:05] Speaker 03: With respect to the anticipation issue, that is correct. [00:02:07] Speaker 03: The board's construction... No, no, no, let me back up, because I want to just lay this out. [00:02:14] Speaker 03: One of the main arguments we have is that the surf and chain reference, just standing alone, is not a proper anticipatory reference. [00:02:24] Speaker 03: So if you were to read Serpentine the way in which the board interpreted Serpentine and adopt- It's a question of fact. [00:02:32] Speaker 03: On Serpentine? [00:02:35] Speaker 03: Yeah. [00:02:35] Speaker 03: It might, there's no- The patient is a question of fact. [00:02:39] Speaker 03: Right, right. [00:02:40] Speaker 03: On factual findings, exactly. [00:02:41] Speaker 03: Substantial evidence. [00:02:42] Speaker 04: And what the prior art means is a question of fact. [00:02:45] Speaker 04: That's right. [00:02:46] Speaker 04: Okay. [00:02:46] Speaker 04: Okay. [00:02:47] Speaker 04: So if you adopt the board's reading of Serpentine- In which case the claim construction [00:02:53] Speaker 04: doesn't matter to the anticipation outcome, does it? [00:02:57] Speaker 03: If you adopt our interpretation of serpentine, if you agree with our interpretation of serpentine, then the board's claim construction would not matter. [00:03:08] Speaker 03: And if I can, I can explain. [00:03:11] Speaker 03: Okay, serpentine, the whole thing boiled down to the phrase suitable active metabolite folate, SMOF. [00:03:20] Speaker 03: Now, the board explained, in its opinion, why it felt that SMAF was limited to a series of eight individual compounds, or at least that's what one of the ordinary skilling out would have thought of, based upon a declaration submitted by their expert, Dr. Miller. [00:03:38] Speaker 03: But on his deposition, at his deposition, he testified, in essence, that the term SMAF did not include those eight single individual compounds [00:03:50] Speaker 03: which were in the free acid form, he testified quite clearly that it covers all variations, all the salt forms, perhaps crystalline forms, polyglutamated forms, whatever. [00:04:04] Speaker 03: But it did not, it included so much, the class was so large, thousands of compounds. [00:04:11] Speaker 03: In fact, he testified that you'd have to conduct experimentation to determine which ones would be proper for any particular route of administration. [00:04:18] Speaker 03: Because he also testified [00:04:20] Speaker 03: that surfantene, this is the word smart, encompasses an appropriate compound, for example, for use in a suppository, for use in a lotion, or a transdermal patch. [00:04:32] Speaker 03: So this is how broad surfantene is. [00:04:34] Speaker 03: And I think it's not a question of there is no substantial evidence supporting the board's interpretation that on the one hand, you have Dr. Miller testifying that the reference covers thousands of compounds. [00:04:47] Speaker 03: And in fact, in the companion case we laid out in our brief, [00:04:50] Speaker 03: where the board summarized Dr. Miller's testimony, which would show the size, the breadth of what's being included in that term. [00:05:00] Speaker 03: It's not defined at all in the specification. [00:05:03] Speaker 03: This is not an in-rate petering situation. [00:05:06] Speaker 03: This is one term, insurfantine, not defined at all. [00:05:10] Speaker 03: There are no preferences at all explained or identified. [00:05:15] Speaker 03: In fact, the only identifiable compound by name is folic acid. [00:05:20] Speaker 03: So we would say that the reference by itself is too broad to be an anticipatory reference, because one ordinary skill in the eye could not envisage immediately all these compounds at once, especially when you have to do experimentation, especially when they require all these routes of administration. [00:05:40] Speaker 03: And the problem is, when you have an expert who provides contradicting testimony versus his declaration, that can't be substantial evidence. [00:05:50] Speaker 03: So our expert agreed in terms of the scope, and our expert's testimony is consistent with the scope of serpentine as Dr. Miller testified under oath during his deposition. [00:06:01] Speaker 03: They don't challenge his deposition in terms of what he said. [00:06:04] Speaker 03: They don't. [00:06:05] Speaker 03: And the board though just stuck with that declaration and ignored the deposition testimony. [00:06:13] Speaker 03: So in that respect, your honors, then surfanchine would not be an anticipatory reference, because it's more like a Eli Lilly case or an IMPACT case, as opposed to N-ray Petering, where you actually have specific compounds identified as their preferences in this N-ray Schwab as well. [00:06:31] Speaker 03: So the claim construction. [00:06:32] Speaker 03: Now, on the issue of claim construction, [00:06:43] Speaker 03: The board construed the phrase, it's 5-methyl-6-S tetrahydropolic acid, which is cited in the claim. [00:06:52] Speaker 03: And if I may I like to refer to it as L5, it's just a lot easier. [00:06:56] Speaker 03: They construed that claim. [00:06:58] Speaker 03: We took the position that a proper construction of that claim term would be just the isomer itself. [00:07:04] Speaker 03: And that's it. [00:07:05] Speaker 03: And they agree that that claim term, on its own, is directed to the natural isomer, not the unnatural isomer, where [00:07:13] Speaker 03: the disagreement comes is with the word comprising. [00:07:16] Speaker 03: Does the word comprising open up the claim so much so that the amount of unnatural isomer can be within the scope of the claim to the point where you could have a 99% of the unnatural isomer and 1% of the natural isomer when in fact the claim limitation specifically recites the natural isomer? [00:07:39] Speaker 03: And our position is no, I think this is more of a legal question because claim construction [00:07:43] Speaker 03: The board didn't adopt, the board basically premised it on their review of the claim language and the specification. [00:07:50] Speaker 03: They rejected Dr. Gregory's opinions with the claim construction. [00:07:54] Speaker 03: I mean, if that were to be reviewed, it would be reviewed for clear error. [00:07:56] Speaker 03: But in this particular case, the board did its own, you know, it's relied on, it may not underline factual findings or subsidiary findings in fact. [00:08:05] Speaker 03: And then we mentioned a fair amount of case law, and there are really two things with the word comprising. [00:08:10] Speaker 03: I think you have to ask two questions. [00:08:12] Speaker 03: Does it negate a particular limitation if you use the word comprising and you make it so open-ended? [00:08:18] Speaker 03: Okay, does it negate it? [00:08:19] Speaker 03: And then, does that construction reasonably reflect what's actually being disclosed and being described in the specification? [00:08:29] Speaker 03: And if you look at the board's construction, the answer is going to be no. [00:08:33] Speaker 03: Because if you adopt the board's construction, you can get two types of situations. [00:08:37] Speaker 03: One where you can have equal amounts of the natural and unnatural iceberg. [00:08:43] Speaker 03: considered to be a totally different compound. [00:08:45] Speaker 03: That's the racemic. [00:08:47] Speaker 03: And you would essentially vitiate the element reciting the actual isomer itself individually. [00:08:56] Speaker 03: And another situation you can have is where you have so much of the unnatural isomer and a very little amount of natural isomer, 0.1%, then the unnatural isomer is doing all the work, if it's doing any work at all. [00:09:12] Speaker 01: Why is that a claim construction issue? [00:09:14] Speaker 01: Why isn't that better left to an infringement question? [00:09:19] Speaker 01: It may be that the claim comprises, because you use the word comprises, includes both, but that if it really is 99% of the unnatural one, it doesn't infringe, because the claim really is about the natural one. [00:09:32] Speaker 03: That's a great question, and in so many respects, I would agree. [00:09:38] Speaker 03: But I think since the way the board wrote their decision, now we're stuck with this comprising almost as if it's a legal conclusion that the comprising is open-ended and it just opens up the floodgates to the natural isomer. [00:09:50] Speaker 03: And just let me reflect a little bit on the specification itself. [00:09:54] Speaker 01: The whole invention is about utilizing natural... Is it your... I mean, this stuff I have a hard time with, but is it your view, I think, that if the board uses comprising in this sense with particularly [00:10:08] Speaker 01: kind of drug patents or pharmaceutical whatever is here, that it doesn't limit it to anything. [00:10:15] Speaker 01: Like, every kind of possible ingredient could be included if the board's interpretation of comprising samples. [00:10:22] Speaker 03: No, no. [00:10:23] Speaker 03: I mean, in this particular case, the word comprising would be, if I'm answering your question correctly, would be just with respect to the unnatural isomer. [00:10:33] Speaker 03: Other components, of course, can be added. [00:10:36] Speaker 03: Did I? [00:10:37] Speaker 03: That's okay. [00:10:37] Speaker 03: Okay, did I go ahead? [00:10:39] Speaker 03: No. [00:10:40] Speaker 03: I mean, just to reflect on the specification, that the issue, I mean, the description there to use a natural isomer to influence levels of homocysteine. [00:10:49] Speaker 03: Each and every embodiment, there are 10 examples, for example, each and every one utilizes a very specific natural isomer. [00:10:56] Speaker 03: And they call it out by name, by name, by structure, not its three dimensional structure, but they call it out. [00:11:02] Speaker 03: And there, and also in the patent in column one, they also describe [00:11:07] Speaker 03: racemic five-methyl. [00:11:09] Speaker 03: So it would indicate that certainly the inventors knew how to describe, if they wanted their claim to include five-methyl, what to say and how to do it. [00:11:18] Speaker 03: So the cases that we cite that I think are instructive are in our briefs, and which really exemplify situations where the word comprising is in place. [00:11:32] Speaker 03: And then when the word comprising was construed to be open-ended, it ended up [00:11:38] Speaker 03: being overturned because it negated a limitation or did not reasonably reflect the plain language and disclosure of the patent. [00:11:46] Speaker 03: So that's the basis on the claim construction issue. [00:11:51] Speaker 03: One other item that's not common to the other case is this whole notion that we have a set of claims in the O4O patent that are directed to levels of homocysteine rising due to genetic deficiency. [00:12:07] Speaker 03: which is the methyl tetrahydrofolate reductase deficiency. [00:12:11] Speaker 03: And there, the board rejected those claims, as obvious in light of surfantine, marazza, and the reference, eubank. [00:12:20] Speaker 03: Now, they never even challenged our position in their reply brief. [00:12:24] Speaker 03: And they didn't provide any expert testimony to about our expert who described exactly why one of one of their skill in the eye. [00:12:31] Speaker 03: I think it's important here, too, because I mentioned the experts, because it is how else are you going to be able to get [00:12:37] Speaker 03: situations like this to be able to perceive the prior art as a whole from the vantage point from one of ordinary skill. [00:12:44] Speaker 03: It certainly can't come from the attorneys. [00:12:45] Speaker 03: I understand sometimes references say what they say, but the expert will have that body of knowledge in his mind when he's reviewing the references and certainly can apply what one of ordinary skill would have thought of when reviewing the particular reference. [00:12:58] Speaker 03: And in Eubanks, for example, Eubank talks about, Eubank associates the genetic deficiencies in the claims. [00:13:08] Speaker 03: in the claims in the O4O patent. [00:13:11] Speaker 03: But it does so, and it teaches that you can use folic acid to lower the homocysteine. [00:13:18] Speaker 04: I didn't follow your argument about the expert. [00:13:22] Speaker 04: What were you trying to say about the expert, the significance of the expert? [00:13:28] Speaker 03: Well, in this case, this is a complex technology. [00:13:32] Speaker 03: We put forth a fair amount of expert testimony in various respects. [00:13:38] Speaker 03: None of it was rebutted by any counter-expert testimony on the paradoxes. [00:13:42] Speaker 03: And I think in a situation like that, what you miss out is what you have as attorney argument, as opposed to something based upon an expert opinion. [00:13:51] Speaker 04: But the finder of fact is always free to just count the weight. [00:13:56] Speaker 04: It's a matter of weight, isn't it? [00:13:57] Speaker 03: That's right. [00:13:58] Speaker 03: How much weight to give. [00:14:00] Speaker 03: But what the board cannot do is substitute, for evidence, simply attorney argument. [00:14:07] Speaker 03: or its own expertise, but that's the particular case here that we have in situations here. [00:14:12] Speaker 03: Let me give you an example of UBINC. [00:14:15] Speaker 03: UBINC basically teaches the use of folic acid to lower the homocysteine. [00:14:24] Speaker 03: And serpentine also teaches the use of folic acid as well to lower homocysteine. [00:14:29] Speaker 03: But nowhere in the board's decision, I mean, there's nothing in the board's decision [00:14:34] Speaker 03: to motivate or suggest to the portion of ordinary skill in the art, as our experts describe, why someone would make the substitution from folic acid to the reduced folate. [00:14:44] Speaker 03: Folic acid was working fine in eubank, and it's also even disclosed in serpentine. [00:14:49] Speaker 03: So what's the reason to make the switch? [00:14:51] Speaker 03: There's no problem to be solved in that particular case. [00:14:55] Speaker 03: And so we would submit that the claims were not obvious in light of these three particular references. [00:15:03] Speaker 03: And so that's one of the differences between the two cases. [00:15:05] Speaker 03: Again, we provided a substantial amount of evidence in response to that. [00:15:14] Speaker 03: Your Honor, I may stop here. [00:15:16] Speaker 00: Okay, we'll save you some rebuttal time. [00:15:18] Speaker 00: Let's hear from Mr. Swain. [00:15:31] Speaker 02: For the record, good morning, Your Honors. [00:15:32] Speaker 02: Joe Swick on behalf of the appellees. [00:15:38] Speaker 02: Regarding claim construction, I think as Your Honors correctly noted that if this Court finds that the obviousness analysis was correct with respect to this patent as well, then we need not go into the anticipation issues or even the claim construction issues. [00:15:55] Speaker 02: That being said, I do want to address the claim construction issues because I think they were correctly decided. [00:16:00] Speaker 02: The first point I want to make is that the board did recognize that the claims in the 04 patent were a comprising patent claim. [00:16:09] Speaker 02: And this court in Dipping Dots versus Mosey said that when the word comprising is used, that raises a presumption that the list of elements is non-exclusive. [00:16:20] Speaker 02: So is it a bright line 100% test? [00:16:24] Speaker 02: No, I'm not going to say that it is, but it does give us the presumption that [00:16:28] Speaker 02: the claims are not limited to only the elements that are stated right there. [00:16:34] Speaker 02: The second point I want to make is if you look at the specification for the old thorough patent or the claims of the old thorough patent, you won't see any of the words that they're asking be imported into claims, which is substantially free of the non-natural isomer. [00:16:51] Speaker 02: So there's no express language supporting their claim construction. [00:16:57] Speaker 02: And another point I want to make is that we've got to consider the standard that the Board was using that Council did not talk about. [00:17:05] Speaker 02: The Board, of course, has a standard that is looking for the broadest reasonable construction of the claims. [00:17:13] Speaker 02: And I submit that what Merck is talking about here is the narrowest possible construction of the claims. [00:17:19] Speaker 02: To the extent there's any ambiguity, whether the non-natural isomer should be included or not, that should tip in our favor given the construction [00:17:27] Speaker 02: standard that the board was required to apply. [00:17:31] Speaker 02: To the extent they've raised these issues of, well, the board's construction means that you can only have 1% of the success by the MTHF. [00:17:45] Speaker 02: Well, they never made those arguments. [00:17:48] Speaker 02: That's not the construction they asked for the board to make. [00:17:51] Speaker 02: They asked for the board to completely exclude the amount of the non-natural isomer. [00:17:56] Speaker 02: So for them to be arguing in the briefs here that, well, the board is making a finding that the claim encompasses administering any amount of 0 to 99% of the unnatural isomer, I think it's a straw man argument because they're saying, well, the board ruled this way. [00:18:13] Speaker 02: Well, the board was never asked to rule on what 0%, 1%, 2%, what would be appropriate in this case. [00:18:19] Speaker 02: The board was given a specific question. [00:18:21] Speaker 02: Does it exclude the non-natural isomer? [00:18:23] Speaker 02: And they made that decision. [00:18:25] Speaker 02: The fact that a non-natural isomer example is not in the specification, in my mind, is not persuasive. [00:18:32] Speaker 02: If we look at the InnoVe pure... But isn't it true? [00:18:36] Speaker 00: The record says the unnatural isomer is inactive, so that to interpret a claim to be ineffective, is that reasonable? [00:18:50] Speaker 02: It is, Your Honor, because there were, at that period of time, racemic mixtures. [00:18:54] Speaker 02: There was the five MTHF racemic mixture that included the natural ice. [00:19:01] Speaker 00: Racemic is different. [00:19:02] Speaker 00: That's 50-50. [00:19:04] Speaker 02: Correct. [00:19:04] Speaker 02: Correct. [00:19:06] Speaker 00: That's not the 1%. [00:19:08] Speaker 02: That's not 1%. [00:19:09] Speaker 02: Correct. [00:19:11] Speaker 02: So, you know, in my mind, there was, you know, yes, I mean, there was an understanding that [00:19:19] Speaker 02: mixtures were possible and we saw that Mirage was trying to separate the good 6S isomer from the bad 6R isomer. [00:19:28] Speaker 02: So there was the prevalent knowledge that there were mixtures out there and that what was important was getting the 6S5MTHF. [00:19:40] Speaker 02: into the claims. [00:19:41] Speaker 02: But the fact that other ingredients such as the non-natural isomer may come in was understood at the time based on the racemic mixtures being out there. [00:19:50] Speaker 02: That was understood as a possibility. [00:19:56] Speaker 02: Another thing I think is important on this substantially curly pure or the fact that the claims should not be read to include the non-natural isomer is that if we look at the Bailey patents, they do have that link. [00:20:10] Speaker 02: they do have the language that the claims are limited to the substantially entirely pure 6S5MTHF. [00:20:17] Speaker 02: So that shows that Merck could have claimed it that way, but chose not to do so. [00:20:26] Speaker 02: Regarding the anticipation arguments where they said that the suitable act of metabolite [00:20:33] Speaker 02: an unlimited number of compounds. [00:20:36] Speaker 02: I mean, I disagree that our expert conceded that. [00:20:39] Speaker 02: What our expert did say in his declaration is that the natural reduced folates are limited to eight compounds. [00:20:47] Speaker 02: He didn't say that by himself. [00:20:49] Speaker 02: He cited to the Modern Nutrition textbook. [00:20:53] Speaker 02: He also cited to the IUPAC nomenclature materials, which supported his opinion that the [00:21:00] Speaker 02: reduced folates in the metabolite cycle are limited to eight. [00:21:06] Speaker 02: And we went through this issue at oral argument at the board. [00:21:10] Speaker 02: And I understood counsel at the board to concede that it was limited to these eight natural reduced folates. [00:21:19] Speaker 02: Because here we have on page A1175 of the record, this is the oral argument. [00:21:28] Speaker 02: Judge Camholtz at the board said, is L5 an active metabolite of folate? [00:21:32] Speaker 02: Mr. Parker said, L5 methyl polyglutamate is biologically active in the system. [00:21:37] Speaker 02: It's an active metabolite of folate, yes. [00:21:39] Speaker 02: Judge Camholtz said, what else is? [00:21:41] Speaker 02: Mr. Parker said, what else is? [00:21:43] Speaker 02: Yes, can you list them? [00:21:45] Speaker 02: All the various metabolites of folic acid when it's going through the cycle? [00:21:49] Speaker 02: Judge Camholtz, yes. [00:21:51] Speaker 02: Well, they're the ones that were listed in the reference that petitioners identified. [00:21:55] Speaker 02: They are part of the cycle. [00:21:57] Speaker 02: Judge Kamholtz, if you had a diagram of the cycle in front of you, could you read off to me the act of metabolites? [00:22:04] Speaker 02: Mr. Parker, yes. [00:22:05] Speaker 02: They would be showing the metabolite, yes. [00:22:08] Speaker 02: Judge Kamholtz says, about how many? [00:22:10] Speaker 02: Mr. Parker says, well, there's at least eight or nine. [00:22:14] Speaker 02: Judge Bonilla says, are there any more than what's listed by the petitioner? [00:22:18] Speaker 02: Mr. Parker, are there any additional ones? [00:22:21] Speaker 02: Not that I am aware of, no. [00:22:23] Speaker 02: There may be THF, maybe one. [00:22:25] Speaker 02: I'm not sure if that's included. [00:22:27] Speaker 02: I don't know. [00:22:28] Speaker 02: So for, you know, if we're looking at serpentine and the board's reading of the meaning of serpentine, we see that they have concluded and there's substantial evidence to support their conclusion that the... Where was the substantial evidence leading to the selection of the L5 from those eight or nine? [00:22:50] Speaker 02: The substantial evidence is that the language in MARAZA is calling out as [00:22:57] Speaker 02: L5MTHF as a promising, suitable active metabolite to be used as an active metabolite in vitamin therapy. [00:23:08] Speaker 02: We have Marazza saying that. [00:23:10] Speaker 02: We have other references. [00:23:13] Speaker 02: You know, we saw McGoffrey, the Reggie, the Patini, all these other references are using 5MTHF. [00:23:20] Speaker 02: There's universal recognition that the [00:23:23] Speaker 02: 6S isomer within the 5MTH. [00:23:27] Speaker 00: And how about the references leading away? [00:23:29] Speaker 00: Your position is we ignore those? [00:23:32] Speaker 02: No. [00:23:33] Speaker 02: I would never ask the court to ignore anything. [00:23:36] Speaker 02: My position is that the teaching away references are very weak. [00:23:41] Speaker 02: They're inconclusive. [00:23:42] Speaker 02: They're unsupported in the context of all the other references. [00:23:46] Speaker 02: If you look at the totality of the circumstances and all the other references and [00:23:52] Speaker 02: pointing towards the use of this as a vitamin, as an active metabolite to lower homocysteine that it's a balancing. [00:24:00] Speaker 02: And the board was faced with that same issue. [00:24:03] Speaker 02: They looked at the teaching away references and they looked at all the references we presented as showing it's not taught away. [00:24:10] Speaker 02: If it was really taught away, why do we have people actually using this in real life experimental trials? [00:24:15] Speaker 02: Why are they giving this to bicycle riders in the Alps to see and address their colate deficiencies? [00:24:20] Speaker 02: If everybody believed that this was a teaching away, why do we have so many people? [00:24:24] Speaker 02: We don't have to guess whether people would think conceptually, would this work or would this not work or should I use this or should I not use this? [00:24:31] Speaker 02: We don't have to go to that conception question. [00:24:33] Speaker 02: People were actually using it. [00:24:35] Speaker 02: So for them to say a teaching away and everybody else was wrong, well, they may have been using it, but they were wrong. [00:24:40] Speaker 02: Well, they were using it. [00:24:42] Speaker 00: But if the other metabolites or some of them are just as effective? [00:24:45] Speaker 00: Why wouldn't your client just use something other than L5? [00:24:53] Speaker 02: What the priority also says, and Marazza says this too, is the L5 MTHF was known as to be the predominant folate in the folate metabolite cycle. [00:25:04] Speaker 02: So it was recognized scientifically as the predominant reduced folate in the folate cycle. [00:25:11] Speaker 02: So if I'm looking for a [00:25:14] Speaker 02: which are the folates, which are the aids to use. [00:25:17] Speaker 02: I mean, I read Morazz and I say, wow, he's saying it's the predominant one. [00:25:20] Speaker 00: But until these scientists found a particular benefit and combination, people were just using folic acid. [00:25:32] Speaker 02: People were using folic acid. [00:25:33] Speaker 02: And I think the record is clear that the folic acid was a much cheaper alternative. [00:25:41] Speaker 02: What the prior also talked about is folic acid had its limitations. [00:25:45] Speaker 02: Folic acid is a chemically made product. [00:25:48] Speaker 02: Not everybody can absorb the folic acid, and the patent specification talks about this itself. [00:25:55] Speaker 02: Not everybody can absorb the folic acid equally. [00:25:59] Speaker 02: It has to be broken down into the reduced folates. [00:26:02] Speaker 02: So the idea was, well, why don't we use the natural reduced [00:26:07] Speaker 02: folate, the 5-MTHF, which, by the way, exists in leafy greens like spinach and things like that. [00:26:13] Speaker 02: Why don't, you know, why are we making the body go through the metabolization process of folic acid? [00:26:18] Speaker 02: The idea was, and it was understood. [00:26:20] Speaker 00: Yeah, that's exactly what I'm thinking about. [00:26:25] Speaker 00: If it was so clear after all of these decades, particularly in pregnancy and the serious consequences of folate deficiency, until these scientists [00:26:37] Speaker 00: came along with this formulation and this focus, there were extremely serious consequences of deficiencies. [00:26:47] Speaker 02: Right, right. [00:26:49] Speaker 00: And the challenge that people were facing... So if it was so obvious, what took so long? [00:26:53] Speaker 00: I mean, this is really what I wonder about. [00:26:56] Speaker 02: Right, right. [00:26:56] Speaker 02: Great question. [00:26:57] Speaker 02: And what we saw and what they recognized in HARPE is the stability of the L5NTHF [00:27:04] Speaker 02: had not been optimized. [00:27:06] Speaker 02: There were concerns about the stability of L5 MTHF, and that's part of their teaching. [00:27:11] Speaker 02: Now, we do know through the Godfrey and the Reggie that they had found a product that was therapeutically stable enough to treat. [00:27:19] Speaker 02: Had it become commercially successful? [00:27:21] Speaker 02: No. [00:27:22] Speaker 02: They had not figured out the optimization of the stability until after these patents issued. [00:27:27] Speaker 02: I had a diagram in my briefs, and what we saw in the Bailey patents, the 915 was issued in 1999. [00:27:34] Speaker 02: And then in 2002, Merck itself gets the 168 patent, where they claim in the 168 patent, aha, we have now optimally stabilized the L5M PHS. [00:27:47] Speaker 02: And that's in 2002. [00:27:48] Speaker 02: And then two years later, the Pam Lab products come on, and then the products they claim take off. [00:27:54] Speaker 02: So what we see is we see a point where, well, there were some concerns about stability. [00:28:00] Speaker 02: Is it really the [00:28:01] Speaker 02: You know, folic acid is just, is stabler absolutely than L5MTHF, but the L5MTHF was figured and was shown to be stable enough to treat, and that's the standard. [00:28:12] Speaker 02: The standard should not be, was the L5MTHF stable enough for widespread commercial success in order to be obvious? [00:28:20] Speaker 02: It only has to be shown that it was therapeutically effective and obvious to be therapeutically effective. [00:28:25] Speaker 04: Mr. Quick, let me take you back to a question that Judge Newman asked, which I thought was a [00:28:31] Speaker 04: perceptive one. [00:28:34] Speaker 04: Let's assume we have two prior art references that teach away from the proposition that we're interested in. [00:28:43] Speaker 04: And we have two prior art references that teach toward the proposition we're interested in. [00:28:51] Speaker 04: And the question we have to address is, is there substantial evidence in the record to support the proposition? [00:29:02] Speaker 04: How do you understand an appellate court's determination of what is substantial evidence in the record? [00:29:10] Speaker 04: My understanding of the standard, at least, is substantial evidence is evidence that a reasonable person could believe to arrive at that conclusion. [00:29:23] Speaker 04: Would we subtract prior arts one and two from prior arts three and four and say, [00:29:31] Speaker 04: Zero, no evidence. [00:29:34] Speaker 04: Or would we be able to say, well, there's prior art going this way, and there's prior art going that way, and a reasonable person could believe one or the other. [00:29:48] Speaker 04: How do we do that? [00:29:50] Speaker 04: That was the question she put to you. [00:29:52] Speaker 04: I'm not sure I fully understood your answer. [00:29:56] Speaker 02: Okay. [00:29:56] Speaker 02: Okay. [00:29:56] Speaker 02: Thank you. [00:30:00] Speaker 02: We did have some language in our briefs talking what the reasonable, the substantial evidence standard means. [00:30:06] Speaker 02: But my understanding is essentially, yes, if a reasonable mind could have come to our conclusion that the Board, then that should be upheld. [00:30:14] Speaker 02: If the Board, you know, if it's also a reasonable conclusion, the positions that they're making, well then that's for the Board to weigh. [00:30:21] Speaker 02: That's the job of the fact finder to weigh references one and two against references three and four. [00:30:28] Speaker 02: They make their decision. [00:30:29] Speaker 02: I understand the job of this court is to look at that and say, well, was that a reasonable decision based on the record that we've seen so far that they picked references one and two as being stronger, more persuasive than the RAD references in three and four? [00:30:48] Speaker 04: But- How about if we disagree with them? [00:30:51] Speaker 02: If you disagree that they're- We would have picked the other two. [00:30:55] Speaker 02: Then I think, again, the- [00:30:59] Speaker 02: If you disagree that it was unreasonable... No, I didn't say that. [00:31:02] Speaker 04: We just would have picked the other two. [00:31:04] Speaker 02: Then I think you have to affirm the board's decision. [00:31:06] Speaker 02: My understanding is as long as the board's decision is a reasonable decision to make, regardless of whether you sitting in their chair would have decided the same way, the decision has to be affirmed. [00:31:17] Speaker 02: That's a fact-finding question and that's really the standard of review that we're talking about here. [00:31:23] Speaker 00: Substantial evidence is what a reasonable mind would accept. [00:31:28] Speaker 00: in view of the entirety of the evidence. [00:31:30] Speaker 02: What a reasonable mind could accept. [00:31:32] Speaker 02: What a reasonable mind could accept. [00:31:34] Speaker 02: I mean, a reasonable, because then we're taking our, yeah. [00:31:37] Speaker 00: Well, or I don't want to, but you have raised the question, perhaps it's a diversion, but on the substantial evidence standard, which certainly is not a clear and convincing standard, Merck can then go back and sue in the district court on the [00:31:56] Speaker 00: established standard of infringement and the result on the premise of an exact wash between the evidence on each side can't be therefore clear and convincing evidence on one side or the other. [00:32:13] Speaker 00: So where are we after all this? [00:32:17] Speaker 02: Where we are, Your Honor, is, I mean, I understand today we're only looking at what the standards are that the Board applied and what deference we have to give that. [00:32:28] Speaker 02: Where we're going in the future, I'm not sure where we're going in the future. [00:32:30] Speaker 02: I mean, the Texas case that they filed is still stayed. [00:32:36] Speaker 02: So we'll see what happens to that. [00:32:38] Speaker 02: I got to believe that the Board's decisions are going to be very persuasive to the extent there's two other patents in this Bailey family that are still out there. [00:32:46] Speaker 02: that in my mind are the same if not, you know, substantively identical to what we're talking about. [00:32:53] Speaker 02: Where are we going? [00:32:54] Speaker 02: I mean, that's going to be fleshed out. [00:32:56] Speaker 02: I can't force and tell where we're going. [00:32:58] Speaker 02: I think a lot of it depends on what they want to do with it. [00:33:00] Speaker 02: So... Okay. [00:33:04] Speaker 00: Anything else you need to tell us? [00:33:05] Speaker 00: I think that's it, Your Honor. [00:33:06] Speaker 00: Thank you. [00:33:08] Speaker 00: Okay. [00:33:09] Speaker 00: Mr. Parker, you have a bit of time. [00:33:12] Speaker 03: Thank you, Your Honor. [00:33:15] Speaker 03: With respect to this whole issue of stability, I just want to point out that on the one hand, NOSIS has taken two positions. [00:33:27] Speaker 03: They were saying that as far as the reduced folate, whether it be 5-methyl or L5, it was sufficiently stable for obvious purposes, but it was not stable when it came time to looking at the evidence with respect to secondary considerations. [00:33:44] Speaker 03: Their contradiction, I could just cite in their own briefs, are located at pages 43 to 45. [00:33:52] Speaker 03: This is where they say that the stability concerns were not resolved until 2002. [00:33:58] Speaker 03: And then in their briefs at pages 28 to 27, they made clear that their stability issues were resolved in 1991. [00:34:06] Speaker 03: And the board adopted these conflicting positions. [00:34:10] Speaker 03: And also, with respect to the BRI standard, [00:34:17] Speaker 03: This court's clarification at BRI does apply to IPRs would not have an impact on our position with respect to claim construction because BRI does not change the principles of construing claims to negate limitations or construing claims that just don't reasonably reflect the invention that is described and disclosed in the patent specification. [00:34:39] Speaker 03: As far as the issue of claim construction, we offered a [00:34:45] Speaker 03: construction before the board, but the board went ahead and came up with its own construction for its own reasons, and that's what we responded to. [00:34:53] Speaker 03: So there is a difference of what was said down below in terms of what was going on here because they adopted something on their own, and so we had to respond appropriately. [00:35:04] Speaker 03: And then with respect to these SLUR references that are used in five-methyl that council keeps indicating, the main issue here is [00:35:14] Speaker 03: Would a person of ordinary skill in the art have a reasonable expectation that when you administer L5 for purposes of treating, let's say for example, vascular disease, will that person have an expectation of lowering that person's level of homocysteine as a result treating their vascular disease? [00:35:34] Speaker 03: And the reason why I raise that because these papers that he's talking about don't deal with that issue. [00:35:38] Speaker 03: They talk about depression. [00:35:39] Speaker 03: They talk about schizophrenia. [00:35:41] Speaker 03: They talk about other psychological conditions. [00:35:44] Speaker 03: But that issue is not resolved in those papers. [00:35:48] Speaker 04: Well, you're touching on a very interesting underlying problem that's been troubling me and that you and I talked about and that Judge Newman has now talked about with Mr. Quick. [00:36:02] Speaker 04: You don't disagree, or do you? [00:36:03] Speaker 04: Do you disagree with Mr. Quick's explanation of how we should go about figuring out whether there's substantial evidence in the record? [00:36:13] Speaker 04: That is, if we had two prior arts going this way and two prior arts going that way, we wouldn't necessarily say they neutralize each other. [00:36:23] Speaker 04: We would look at them and then we would ask the question, could a reasonable person have arrived at the conclusion that the board arrived at, even if we thought a equally reasonable conclusion would have been the opposite. [00:36:40] Speaker 04: had we been doing it in the first place. [00:36:43] Speaker 04: That seemed to be his view. [00:36:45] Speaker 04: Do you go along with that? [00:36:47] Speaker 03: No, I think you would have to look at the strength of the suggestion that's made in the references individually. [00:36:54] Speaker 03: In other words, if it's a strong... We would reweigh the evidence. [00:37:00] Speaker 03: Well, what we're saying is you would look at a reference. [00:37:05] Speaker 03: For example, in Institute of Pasteur, the board's decision was reversed. [00:37:09] Speaker 03: for a couple of other reasons, but one of them included for ignoring or misapprehending a prior art reference. [00:37:18] Speaker 04: Well, ignoring or misapprehending a prior art reference is a different thing. [00:37:22] Speaker 04: I don't want to push this too far, but you harped on Harpy. [00:37:27] Speaker 04: So let me harp back on the issue of Harpy. [00:37:30] Speaker 04: There was a time, back in time, you probably don't go back that far, but I do, when our view of factual [00:37:39] Speaker 04: evidence coming out of the USPTO was whether there was clear error or not. [00:37:47] Speaker 04: So back in the good old days, we might have looked at Harvey and said, you guys got that wrong. [00:37:54] Speaker 04: That's clear error. [00:37:57] Speaker 04: And so we're going to reverse the whole thing and send it back and now start over. [00:38:01] Speaker 04: Along in 1999, I think it was, the Supreme Court stuck its finger in our eye in the Zirco case and said, that's not the way it works. [00:38:13] Speaker 04: That's okay court to court, but that's not okay agency to court. [00:38:19] Speaker 04: And now you guys gotta shape up and follow section 706 of the APA. [00:38:25] Speaker 04: Even those of us who are old administrative lawyers, [00:38:29] Speaker 04: sitting on the court thought clear error was okay. [00:38:33] Speaker 04: We were wrong. [00:38:34] Speaker 04: We now can't do clear error on facts coming out of the USPTO. [00:38:39] Speaker 04: The only thing we can do now is is there substantial evidence in the record. [00:38:44] Speaker 04: What troubles me about this whole discussion today was there are four patents involved. [00:38:54] Speaker 04: Each one of those went through a determination by a three-judge board to determine whether to institute a review. [00:39:04] Speaker 04: And in each case, a board of the PTO, PTAB, determined it was more likely than not that they were invalid. [00:39:13] Speaker 04: It then went before four panel discussions and reviews in which you all put in all this [00:39:22] Speaker 04: testimony and all this fact and everything else. [00:39:25] Speaker 04: And there's multiple prior art. [00:39:30] Speaker 04: And as has become clear, there's also multiple complications in this. [00:39:36] Speaker 04: You're now coming up here and asking us to determine that there's no substantial evidence in the record to support any of this. [00:39:43] Speaker 04: But you then want to make a legal issue out of it, which is sort of hard to do when you're really talking about basically factual questions of what the prior art meant, what it interpreted, what it stood for, and how to weigh it. [00:39:59] Speaker 04: And I'm having a lot of problem. [00:40:02] Speaker 04: We're in a whole new world. [00:40:04] Speaker 04: The AIA is not simply more of the old days. [00:40:08] Speaker 04: The AIA as [00:40:09] Speaker 04: Judge Newman pointed out, where are we? [00:40:11] Speaker 04: That's a very good question. [00:40:13] Speaker 04: We don't know where we are. [00:40:15] Speaker 04: And we're first getting into, this is among the early AIA cases and we really don't know what to do with these. [00:40:22] Speaker 04: And I'm puzzled as to how I'm supposed to go about deciding what you want us to decide when I think what we need to decide is, is there substantial evidence in this enormous record to support what these four [00:40:39] Speaker 04: merits panels decided and three institute panels all agreed on by all these administrative judges. [00:40:50] Speaker 04: What are we to do? [00:40:51] Speaker 03: Well, I mean, I share your pain because we're all going through this process, in some respects, this new IPR process. [00:40:57] Speaker 03: And so we're getting, we're slugging through it. [00:41:00] Speaker 03: But with respect to the references, I think there are situations where the panel can look at a reference [00:41:07] Speaker 03: and see what the board said or characterized and say, well, no, this is not what the reference says. [00:41:13] Speaker 03: In fact, it says the opposite. [00:41:16] Speaker 03: And I think that would be a situation where you could find there's no substantial evidence supporting the board's reading or interpretation of the particular reference. [00:41:24] Speaker 03: And that would be in view of the evidence. [00:41:25] Speaker 04: But any one reference isn't going to decide. [00:41:28] Speaker 04: In the old days, a bad reference might have sent the whole thing back. [00:41:31] Speaker 04: But we can't do that anymore, Ken. [00:41:35] Speaker 03: I mean, I know. [00:41:36] Speaker 04: And the misunderstood reference doesn't get a reversal anymore because there may be some, as Judge Hughes pointed out, even if your favorite Harvey case is wrong, doesn't matter if there are other prior art references that provide the board with substantial evidence. [00:41:58] Speaker 00: We're going to have to figure it out, but I'm not sure we can solve it this morning. [00:42:05] Speaker 03: I mean, but there are the checks and balances, and that's the whole point of the appellate process, just to ensure that we're getting consistency in terms of the obligations of the board or whether it could be at a court. [00:42:18] Speaker 03: Just quickly, with respect to the claim construction, the BRI doesn't apply. [00:42:27] Speaker 03: And as far as referring to me as conceding, [00:42:33] Speaker 03: Pseudoactive metabolite folate that phrase used in serpentine that it only was directed to eight single compounds That was not the nature of the discussion. [00:42:41] Speaker 03: It was simply it has been known in biochemistry when you ingest folic acid It's going to be metabolized. [00:42:47] Speaker 03: It's going to form a certain level of number of metabolites And that's all depicted in the diagrams we provided to the board. [00:42:54] Speaker 03: That's what I was referring to to those compounds [00:43:05] Speaker 03: And the last point on the plant construction, we're offering or procuring a construction that says freer, substantially freer than natural isomer. [00:43:16] Speaker 03: And the reason being is it's known in the art, and it hasn't been challenged, at least by notice, is that you can never make a compound 100% pure, especially when it comes, I'm sorry, with isomers. [00:43:27] Speaker 03: It's really, really tough to get them 100%. [00:43:30] Speaker 03: And that was something that's well recognized in the art. [00:43:33] Speaker 03: And we have an expert to support that, expert testimony from a person of ordinary skill and the art perspective. [00:43:38] Speaker 03: And that aspect wasn't challenged by notice. [00:43:40] Speaker 03: Your Honor, thank you very much for your time this morning. [00:43:42] Speaker 03: I appreciate it. [00:43:43] Speaker 00: Thank you. [00:43:43] Speaker 00: Thank you both. [00:43:45] Speaker 00: The case is well presented.