[00:00:00] Speaker 03: Our next case is Mylan Pharmaceuticals versus Merck Shopping Dome 2021-21-21. [00:00:06] Speaker 03: Mr. Whirlingham. [00:00:10] Speaker 00: May I please the court? [00:00:14] Speaker 00: The 708 patent is both anticipated and obvious because it does little more than give instructions on how to make acidic lictin salt using phosphoric acid that is encompassed within the prior art. [00:00:27] Speaker 00: The board's decision to the contrary is marred by legal error. [00:00:30] Speaker 03: Well, these aren't process claims. [00:00:34] Speaker 00: For anticipation specifically, no. [00:00:36] Speaker 00: We're talking about the compound claims themselves. [00:00:39] Speaker 00: That is correct. [00:00:42] Speaker 00: And the fundamental flaw with the board's anticipation analysis is that it applied the standard too narrowly. [00:00:48] Speaker 00: It seemed that it was only looking for an express single disclosure of a one-to-one Cytigliptin DHP salt combined as it appears in the 708 patent. [00:00:58] Speaker 00: Nothing else would seemingly do. [00:01:00] Speaker 00: But that's not the law. [00:01:02] Speaker 00: The anticipating reference does not have to expressly spell out all the limitations arranged or combined as they are in the claim. [00:01:10] Speaker 00: That's KineMetal. [00:01:11] Speaker 00: Nor do all the limitations have to be gleaned from a single reference. [00:01:15] Speaker 00: That's Glaxco Group. [00:01:17] Speaker 00: So long as the skilled artisan can read the reference, apply their knowledge of the art, and arrive at the invention without undue experimentation, it's anticipated. [00:01:27] Speaker 03: That sounds like obviousness. [00:01:30] Speaker 00: I don't think so, Your Honor. [00:01:31] Speaker 00: I think what distinguishes this from obviousness is that we are looking specifically at a single reference, and we're asking, what is the skilled artisan going to [00:01:40] Speaker 00: going to read based on that reference and that reference alone. [00:01:43] Speaker 00: We're not looking outside the four corners. [00:01:44] Speaker 03: Are you talking about claims one and two or three and four? [00:01:48] Speaker 00: We're talking about claim one. [00:01:50] Speaker 00: I'm using claim one at this particular point, because we're talking about the one-to-one sitagliptin DHP. [00:01:55] Speaker 02: And you're relying on that at once in vids of that line of cases, right? [00:01:59] Speaker 02: Just to make sure I'm following you. [00:02:02] Speaker 00: For the stoichiometry, yes, we are relying upon the envisaging doctrine, because I think the reference gives you the salt. [00:02:10] Speaker 00: It gives you sitagliptin. [00:02:11] Speaker 00: It claims pharmaceutical acceptable salts. [00:02:15] Speaker 00: And it says, make the salts using phosphoric acid. [00:02:19] Speaker 00: The only thing that is not explicitly black and white on the paper is the stoichiometry of that salt. [00:02:26] Speaker 03: But claims 1 and 2, the reference was overcome with respect to 1 and 2, because they showed a reduction of practice of as much as is in the reference prior to its effective date. [00:02:44] Speaker 00: So Your Honor, that goes to the antidation argument. [00:02:47] Speaker 00: And that applies to 103. [00:02:49] Speaker 00: I'm speaking at the moment about 102. [00:02:53] Speaker 00: And I do not believe that antidation impacts that argument. [00:02:56] Speaker 00: I'm happy to talk about antidation. [00:02:58] Speaker 00: But at the moment, we're speaking of antidation. [00:03:01] Speaker 03: But if the reference is overcome, it's overcome for all purposes. [00:03:05] Speaker 03: It's not a reference. [00:03:08] Speaker 00: I don't know if that's entirely accurate, Your Honor. [00:03:10] Speaker 00: And certainly, I don't think that's anything that Merck argued. [00:03:12] Speaker 00: And that's not what the board held. [00:03:15] Speaker 00: For the antedation argument didn't come in as the antedation argument only came in as a defense to our 103 argument as it relates to these claims. [00:03:25] Speaker 02: So is it 102E prior? [00:03:28] Speaker 00: Beg your pardon? [00:03:29] Speaker 02: Is the reference prior under 102E? [00:03:33] Speaker 00: I believe that is accurate. [00:03:35] Speaker 00: Yes, Your Honor. [00:03:39] Speaker 00: OK, thank you. [00:03:40] Speaker 00: So turning to the envisaging doctrine, [00:03:44] Speaker 00: Every salt has stoichiometry. [00:03:46] Speaker 00: We're not dealing with a boundless universe here. [00:03:48] Speaker 00: We have a known salt. [00:03:50] Speaker 00: We have a known compound. [00:03:52] Speaker 00: And those two are going to interact in finite ways. [00:03:55] Speaker 00: And you can envisage what those are. [00:03:56] Speaker 03: Well, hydrogen, phosphoric acid has three hydrogens. [00:04:00] Speaker 03: And there are several basic nitrogens. [00:04:04] Speaker 03: And so there are a lot of possibilities here. [00:04:07] Speaker 00: There are possibilities, Your Honor, but I believe the parties agree that, at most, the citiglyptin compound is going to accept a proton at two sites. [00:04:18] Speaker 00: And phosphoric acid is triprotic. [00:04:21] Speaker 00: It only has three protons to donate, so six possible combinations. [00:04:25] Speaker 00: And realistically, we're only talking about four. [00:04:29] Speaker 00: Only four have been found by the parties. [00:04:38] Speaker 02: and the board seems to have credited that there could be at least 264 possible assaults. [00:04:45] Speaker 02: I think there was a number of 900 and something different combinations. [00:04:50] Speaker 02: Why is that not substantial evidence to support the board's ultimate conclusion here? [00:04:56] Speaker 00: Your Honor anticipates where I'm going. [00:04:59] Speaker 00: That's not substantial. [00:05:00] Speaker 00: That's legal error because the framing is wrong. [00:05:05] Speaker 00: We have on the paper, we have citiglyptin, we have phosphoric acid, and that should be your starting point. [00:05:13] Speaker 00: By trying to broaden the scope out to all of the compounds that are in claim 15 of the prior art, [00:05:19] Speaker 00: You're basically grafting onto that some kind of motivation to select analysis by not looking specifically at city lipids. [00:05:26] Speaker 00: They're on the paper. [00:05:27] Speaker 00: And the court in Paracone rejected the notion that a teaching in the prior art cannot anticipate because it appears without special emphasis in a longer list. [00:05:39] Speaker 00: And I think you had a similar issue in the impacts case, which I think is very illustrative of what's going on here. [00:05:45] Speaker 00: There you had two patents. [00:05:47] Speaker 00: One of them recited the formula. [00:05:48] Speaker 00: plus the compound. [00:05:50] Speaker 00: This court reversed, saying that patent can potentially anticipate, because it identifies the compound. [00:05:57] Speaker 00: You had a second patent that only had the formula. [00:06:01] Speaker 00: This court affirmed, saying no, that cannot anticipate, because all it has is the formula. [00:06:07] Speaker 00: And there are no preferences expressed in the art that would allow you to envisage or get to the specific compound that was at issue. [00:06:23] Speaker 00: So the one-to-one stoichiometry is the most basic arrangement and the first that would come to the mind of the skilled artisan. [00:06:29] Speaker 00: And there's three areas that I point the court to. [00:06:31] Speaker 00: The first is the examples in the prior art. [00:06:35] Speaker 00: If you look at example seven, you have a one-to-one citaglyptan salt made in 1,000-fold excess of hydrochloric acid, which is much stronger than phosphoric acid, one-to-one. [00:06:47] Speaker 00: Contrast that with examples one through five. [00:06:50] Speaker 00: These examples concern citiglyptin analogs. [00:06:54] Speaker 00: Those are Merck's words. [00:06:55] Speaker 00: Made using hydrochloric acid. [00:06:58] Speaker 00: They are in 1 to 2 ratios. [00:07:00] Speaker 00: Based upon this, you can draw the inference that citiglyptin is going to form a 1 to 1 ratio with phosphoric acid. [00:07:10] Speaker 00: Reason being, phosphoric acid is weaker than hydrochloric acid. [00:07:14] Speaker 02: It feels like what you're talking about. [00:07:17] Speaker 02: It feels like the obviousness. [00:07:19] Speaker 02: But I'm having a little bit of a hard time with your talking about the picking and choosing of different parts of the reference. [00:07:27] Speaker 02: It sounds like you're talking about obviousness. [00:07:30] Speaker 02: You want to make sure you are entertaining my concern. [00:07:33] Speaker 00: No, I am entertaining your concern, Your Honor. [00:07:36] Speaker 00: I understand that at the margins 102 and 103, the margin would be a little gray. [00:07:43] Speaker 00: But here, I think we are within the boundaries of what 102 allows us to do, because we are looking at a single reference. [00:07:49] Speaker 00: All of these are contained in a single prior art reference. [00:07:52] Speaker 03: Are you talking about the old Petering case, that one can look at a generic formula and envisage all the species within that genus? [00:08:05] Speaker 03: Is that your point? [00:08:06] Speaker 00: So Petering certainly is one of the cases that we are relying upon. [00:08:08] Speaker 03: But Petering involved about 20 compounds. [00:08:12] Speaker 03: But here, even with preferred salts, the court found 957 possibilities, a very different situation. [00:08:24] Speaker 00: That's right, Your Honor. [00:08:25] Speaker 00: But again, I think this goes back to the problem with the way that the board framed up the issue. [00:08:31] Speaker 00: They were unwilling to consider the fact that City Libden is illustrated right there on the paper, and that that should be the starting point. [00:08:40] Speaker 03: On which paper? [00:08:40] Speaker 00: It is claim 15 of W-O-4-9-8. [00:08:45] Speaker 00: And that appears on appendix page 420. [00:08:52] Speaker 03: But you're saying it is anticipated by which reference? [00:08:56] Speaker 03: The W-O reference? [00:09:00] Speaker 00: So there are two references that are identical to each other. [00:09:05] Speaker 00: And the parties and the board refer to them interchangeably. [00:09:08] Speaker 00: So you have W-O-4-9-8. [00:09:09] Speaker 00: That's the international patent. [00:09:11] Speaker 00: And then you have the 871 patent. [00:09:14] Speaker 00: It is identical in all material respects to W0498. [00:09:19] Speaker 00: So we refer to W0498, but honestly, you could use either of them, and you can rely exclusively upon one or the other. [00:09:27] Speaker 00: So the citation that I just gave you to page 422 of the record, that is to W0498. [00:09:33] Speaker 00: There is an analogous disclosure, claim 15, on the 871 patent. [00:09:39] Speaker 00: And once again, the problem that I have with the board and Mark's framing of this is that citiglyptin is illustrated right there on the paper. [00:09:47] Speaker 00: The pharmaceutical acceptable salt is claimed as part of claim 15. [00:09:51] Speaker 00: And in defining what a pharmaceutical acceptable salt is, the specification says particularly preferred is phosphoric acid. [00:09:58] Speaker 00: That should be the starting point. [00:10:00] Speaker 00: Not all of the 33 compounds in claim 15 and certainly not formula 1 from which those compounds derive. [00:10:08] Speaker 00: So turning back to the one-to-one. [00:10:11] Speaker 00: I think the examples themselves are illustrious, but I want to point out two other areas from which you could envisage the one-to-one. [00:10:19] Speaker 00: The first is the testing that is in the record to verify the stoichiometry. [00:10:24] Speaker 00: Merck created one-to-one sitagliptin DHP by running an automated salt screen that was conducted by a relatively novice chemist with a bachelor's degree, far below the skill of the skilled artisan. [00:10:39] Speaker 00: An automated salt screen is not undue experimentation, and I think it therefore falls within the ambit of 102. [00:10:47] Speaker 00: Relatedly, there is evidence in the record from Dr. Shial of tests he ran in a related proceeding in Israel. [00:10:54] Speaker 00: He ran 12 different experiments deliberately trying to create something of the one-to-one sitagliptin DHP salt, but he got one-to-one every time. [00:11:04] Speaker 00: The third area is Dr. Matzger. [00:11:06] Speaker 00: He doesn't deny that you could envisage a one-to-one. [00:11:09] Speaker 00: He doesn't even deny that it would be the first that you envisage. [00:11:11] Speaker 00: His point, Your Honors, is that other stoichiometries exist. [00:11:16] Speaker 00: And I'll address that in a moment. [00:11:18] Speaker 00: The fact that you can see the one-to-one should be enough for the envisaging analysis. [00:11:22] Speaker 00: We're dealing with a limited universe of options, which is what is required by Petery. [00:11:27] Speaker 00: And you can envisage the claims arrangement, which is what is required under Kinemeta. [00:11:33] Speaker 00: Even if we do have to envisage those other stoichiometries, you can. [00:11:36] Speaker 00: And my basic point here is that the tests that Merck ran were, in the words of the board, conventional. [00:11:43] Speaker 00: If it's conventional testing, that's not undue experimentation. [00:11:50] Speaker 00: The court has no further questions. [00:11:51] Speaker 00: I'll use the remainder of my time to address the annotation. [00:11:56] Speaker 00: I'm going to focus specifically on the claims that are subject to antidation. [00:11:59] Speaker 00: These are claims that should have been pretty easy calls under 103, but we didn't even get to the obviousness analysis because the board accepted Merck's bid to disqualify the prior art on annotation grounds. [00:12:09] Speaker 00: This is Merck's argument, Your Honor. [00:12:11] Speaker 00: It's their burden to prove it up, and we believe that the flaw in the board's analysis is that they did not hold them to their burden. [00:12:18] Speaker 00: The at-issue claims from the 708 patent broadly recite hydrates of sitagliptin. [00:12:23] Speaker 00: And the prior ART definition of a pharmaceutically acceptable salt encompasses hydrates. [00:12:29] Speaker 00: The problem for Merck is that they admit that they did not reduce hydrates to practice before the effective date of the prior ART. [00:12:35] Speaker 00: So what they do is they try to remove that element from the equation by saying that the prior ART does not enable hydrates. [00:12:43] Speaker 00: The prior ART is presumptively enabling. [00:12:45] Speaker 00: And to overcome the presumption of enablement, Merck needed to offer a WANDS analysis. [00:12:50] Speaker 00: And if you look at the record, your honor, [00:12:52] Speaker 00: It's not a wands analysis there. [00:12:54] Speaker 00: There's nothing that even looks like a wands analysis in the record. [00:12:58] Speaker 00: Put simply, Merck could not have overcome the presumption of enablement, excuse me, the presumption of enablement, if it did not even engage the controlling law. [00:13:08] Speaker 03: Counsel, you're into your rebuttal time. [00:13:10] Speaker 03: You can continue or save it. [00:13:12] Speaker 00: I will save it, Your Honor. [00:13:13] Speaker 01: Thank you. [00:13:14] Speaker 03: Mr. Lampton. [00:13:16] Speaker 01: Good morning, and may it please the court. [00:13:18] Speaker 01: We've gone from Peloton to Fitbit to diabetes medication. [00:13:23] Speaker 01: Seems like the signs of aging. [00:13:25] Speaker 01: PTAP's 76-page opinion carefully considered and rejected each of Mylan's arguments on multiple grounds based meticulously on the record. [00:13:37] Speaker 01: Mylan does not come close to showing an absence of substantial evidence for the PTAP's decisions. [00:13:42] Speaker 01: Starting with anticipation. [00:13:45] Speaker 01: Ordinarily, anticipation requires disclosure of all the limitations as arranged in the claim. [00:13:51] Speaker 01: The idea of at once envisaging is sort of an exception to that as arranged in the claim requirement, where you can sort of take things from different lists and combine them to provide the limitations as arranged. [00:14:05] Speaker 01: If it results in a small enough class that it would immediately come to mind to the skilled artisan [00:14:11] Speaker 03: That's Petering. [00:14:13] Speaker 01: Yes, exactly. [00:14:13] Speaker 01: That's exactly Petering. [00:14:15] Speaker 01: Because the lists just bring it to mind. [00:14:16] Speaker 01: It's each class and its limitations as if it were just written out, as if they had listed them expressly. [00:14:21] Speaker 01: But the PTAB here gave four reasons why the at once envisaged exception to sort of, you know, [00:14:27] Speaker 01: As a range requirement doesn't apply why one skilled artist and looking at w 0 4 9 8 wouldn't Just look at the 33 compounds in claim 15 I should mention the claim 15 is 33 compounds including see the clipped and freebase not one-to-one city clipped in DHP One thing I'm puzzling about [00:14:49] Speaker 02: is how do you respond to opposing counsel's argument that you have to start with Cetagliptin, not all 33 compounds in 2015? [00:14:58] Speaker 01: So the first is, when you're combining those lists, what's in 2015? [00:15:03] Speaker 01: It's Cetagliptin along with 33 other compounds as the board. [00:15:06] Speaker 01: There's nothing that points to Cetagliptin in particular. [00:15:09] Speaker 01: As a matter of fact, [00:15:10] Speaker 01: their own expert, if you look at page 2347 of the record, page 189, line one, he admits that W49 did not give any reason to pick Cetaglifton and put it into a composition as it compared to any other compound in that record. [00:15:23] Speaker 01: So there's nothing that narrows you in. [00:15:24] Speaker 02: What was that site again? [00:15:26] Speaker 01: I'm sorry. [00:15:26] Speaker 01: It would be 2347 of the record, and then 2374. [00:15:29] Speaker 01: We're going to flip the last two digits. [00:15:33] Speaker 01: And he responds to a question, yes, that is correct, yes. [00:15:36] Speaker 01: They would not be able to choose between the many compounds. [00:15:39] Speaker 01: Appendix 2341, page 60, line 9. [00:15:43] Speaker 01: He admits that there's nothing in W-498 that emphasizes cetyglyptin over any other 32 compounds in the claim. [00:15:49] Speaker 01: So we're going to start with claim 1533, which is where [00:15:53] Speaker 01: their experts started and our experts started and the board started and then we assume just for the sake of argument that you're going to use the eight preferred acids. [00:16:01] Speaker 01: That's going to come up with, once you add all the potential stoichiometries, approximately 957. [00:16:07] Speaker 01: But it's not just that you have 957 different compounds you're supposed to have once in visiting. [00:16:12] Speaker 01: There's four reasons the board gave why you wouldn't at once envisage them, wholly apart from just that number. [00:16:18] Speaker 01: The first is you're just plain missing one of the limitations. [00:16:22] Speaker 01: One of the requirements of the at once envisage doctrine is you have to get all the limitations from the reference. [00:16:28] Speaker 01: You can't pull it from a different reference because then you're, as you pointed out Judge Dole, you're outside the zone of anticipation and something that [00:16:34] Speaker 01: is obviousness, but without the requirements and limitations of obviousness. [00:16:38] Speaker 01: And in this case, the board pointed out that the stoichiometries, the potential stoichiometries, aren't actually there. [00:16:43] Speaker 02: But would one ordinary scale in the art know that there's only so many stoichiometries available? [00:16:49] Speaker 01: Yeah, so it's possible that there's, you know that there might be a range of stoichiometries, but you don't know which ones are actually going to occur here because this is an unpredictable art. [00:17:00] Speaker 01: As their expert and ours and the board found on, I think it's page 33 and 34, said this is something you will only decide by trial and error. [00:17:08] Speaker 02: Did they say there's three different stoichiometries? [00:17:10] Speaker 01: There's actually, I think, four and a potential one hypothesized. [00:17:13] Speaker 01: The four are the one to one, let me flip that page, one to one, two to one, [00:17:18] Speaker 01: 3 to 2, 1 to 2, and then on page 2658, one of our experts explained that there might also be a 6 to 5 out there, but unless you actually do the science, unless you do the experiments, you just don't know. [00:17:30] Speaker 01: And so if you're looking to provide the stoichiometries, it's just not in there. [00:17:34] Speaker 01: There's no stoichiometry for the phosphates. [00:17:36] Speaker 01: There's not even a disclosure of any phosphate salt at all in there other than trying to combine [00:17:42] Speaker 01: one list from 40 pages earlier with the list of 33 compounds in claim 15. [00:17:47] Speaker 01: So that fails because you can't pull in your stoichiometry to someplace else. [00:17:52] Speaker 01: But another requirement is you have to at once envisage each member of the class. [00:17:57] Speaker 01: And here the board had overwhelming proof that skilled artisans wouldn't at once envisage each member of the class. [00:18:04] Speaker 01: Because Mylan's own expert for months envisaged only one. [00:18:09] Speaker 01: of the four or more potential stoichiometries. [00:18:12] Speaker 01: He insisted that there was only a one-to-one stoichiometry. [00:18:16] Speaker 01: And as the board pointed out, look, it's just not plausible when his own envisaging theory is that he said for months there's only a one-to-one solid. [00:18:26] Speaker 01: You can't say skilled artisans would at once envisage every stoichiometry when Mylan's own expert for months envisaged only one out of a larger number of potential stoichiometries. [00:18:38] Speaker 01: There's a third reason as well, and that is this salt formation is unpredictable. [00:18:44] Speaker 01: So when you have these 957 hypothetically existing salts, you don't actually know which ones will exist until you do the experiments, trial and error experiments. [00:18:55] Speaker 01: And so when you're asking the skilled artisan, once a visage, all the members of the class, [00:19:01] Speaker 01: Skilled artisan isn't going to look at these two lists and say, I once envisage all the members of the class. [00:19:06] Speaker 01: Skilled artisan looks and says, I don't know what that class consists of because these reactions are unpredictable. [00:19:11] Speaker 01: I don't know what salts I will get. [00:19:13] Speaker 01: I might get a smaller number. [00:19:15] Speaker 01: I might get a majority. [00:19:16] Speaker 01: I have no idea what I'm going to get. [00:19:18] Speaker 01: And even that [00:19:19] Speaker 01: Even that underestimates the degree of unpredictability because the skilled artisan knows not only that he can't tell which are going to form salts because they're unpredictable, he also knows that he doesn't know what the techniques necessary for salt formation will be for any one of those salts. [00:19:35] Speaker 01: There's just a vast array of techniques available and some of them will produce nothing and some might work. [00:19:42] Speaker 01: And so, for example, you have questions of what are your solvents? [00:19:46] Speaker 01: Sometimes you use solvent mixtures, which increases the number of parameters astronomically. [00:19:51] Speaker 01: How do you get things to fall out of solution? [00:19:52] Speaker 01: Are you going to drop the temperature? [00:19:54] Speaker 01: Are you going to change the pH? [00:19:55] Speaker 01: Are you going to have evaporation? [00:19:57] Speaker 01: All these things affect whether you get a salt at all. [00:20:00] Speaker 01: And so this means in the end that you just have no idea either whether you're going to get a salt or how to get there. [00:20:12] Speaker 03: particular salt was, I guess, obvious because it was in a small list? [00:20:19] Speaker 01: So in Pfizer, the court pointed out that the prior art heavily suggested that the particular anion would cure the problem. [00:20:28] Speaker 01: And it spoke of the witness there who admitted that he had a reasonable, although not guaranteed, and that's the quotation, expectation of getting a phosphate or getting the salt in that case. [00:20:41] Speaker 01: So when they went and did it, that simply confirmed the expectation based on the art. [00:20:45] Speaker 01: Here, there's nothing in the art that tells you, I am going to get a phosphate salt. [00:20:50] Speaker 01: It's unpredictable as a result. [00:20:52] Speaker 01: It doesn't tell you this is how you go about and get a phosphate salt, much less a phosphate salt of cetyglyptin, much less one-to-one cetyglyptin DHP. [00:21:01] Speaker 01: That's just simply nowhere in the prior art. [00:21:04] Speaker 01: One-to-one cetyglyptin DHP was discovered by Merck apart from that reference. [00:21:10] Speaker 01: In the case where you actually don't have that type of evidence, where you don't have the expert saying, I have a reasonable expectation of getting this, maybe not guaranteed, where you don't have the record heavily suggesting a particular solution. [00:21:25] Speaker 01: And we're in the land of obvious now, right? [00:21:26] Speaker 01: Because we're looking at multiple records. [00:21:28] Speaker 01: This Sanofi Synthelout case, you ended up with the opposite result because you just didn't have that record. [00:21:35] Speaker 01: So the unpredictability means that you're very unlikely to have somebody who's a skilled artist and who looks at it and says, I will once and visit every member. [00:21:43] Speaker 01: Because he doesn't know what the members are. [00:21:45] Speaker 01: And he doesn't know even how he would necessarily make them. [00:21:49] Speaker 01: And then finally, the fourth rationale the board gave is that the board just thought that Milan's case was weaker than Merck's. [00:21:56] Speaker 01: The PTAB explained, and this is on page 31, that Dr. Chorghadeh, Mylan's expert, never testified that artisans would immediately envision all the conceivable salts. [00:22:07] Speaker 01: And the quote from Dr. Chorghadeh does not opine that a posa would at once envisage the 1 to 1 C to go to the DHB salt. [00:22:12] Speaker 01: Instead, the PTAB credited [00:22:15] Speaker 01: our expert, Dr. Mansker, who gave, I'm quoting, unequivocal and repeated testimony that Oppoza would not and could not at once envisage all the possible salts or the claimed one-to-one cedical consults. [00:22:26] Speaker 01: So Meinle's theory in the end just simply fell for lack of persuasive force when it came to the once envisaging, of course. [00:22:32] Speaker 01: And in the end, it really isn't an at once envisaging theory at all. [00:22:37] Speaker 01: Say they want to take one list from claim 15, 33 compounds, another list from 40 pages earlier, the preferred salts, combine them, and they say, once the Xylodarsin combines Cetagliptin, from the one list, and phosphoric acid to make a salt from the second, then [00:22:54] Speaker 01: they will inquire about stoichiometry. [00:22:55] Speaker 01: But when you're going through all those steps, and I think the word used inferred or assume or think, that's not in one's envisage. [00:23:03] Speaker 01: That's just a calculation of possibilities. [00:23:05] Speaker 01: That's potentially in the land of obviousness argument. [00:23:08] Speaker 01: But once you go to obviousness, they confront the problem of anticipation. [00:23:13] Speaker 01: They come up with the findings of no motivation and no expectation excess that foreclose it. [00:23:20] Speaker 01: So if I should turn to obviousness just for a moment. [00:23:23] Speaker 01: W of 498 can't render the 708 obvious given that Merck previously reduced whatever the 498 discloses to practice. [00:23:35] Speaker 01: There's no real dispute that Merck reduced a practice, at least one embodiment, of claim one of the 708. [00:23:41] Speaker 01: And that would be one-to-one sedagliptin-DHP before the 498 published. [00:23:46] Speaker 02: And just to make sure I understand, everybody agrees that the proper law is that only one of the claimed embodiments has to be reduced to practice to end to date. [00:23:54] Speaker 02: Is that right? [00:23:55] Speaker 01: So you have to do that. [00:23:56] Speaker 01: There's one further step. [00:23:58] Speaker 01: And once you do that, [00:24:00] Speaker 01: Why would you take away Merck's entitlement to a patent when it got there first, right? [00:24:04] Speaker 01: So we got to one-to-one see the glitch in DHP before. [00:24:07] Speaker 01: The disclosure prior right, W0498, even published. [00:24:11] Speaker 01: So we get there first. [00:24:12] Speaker 01: But Clark provides another requirement. [00:24:14] Speaker 01: But that requirement is also in here. [00:24:16] Speaker 01: And Clark says, look, you have to reduce to practice so much of the claimed invention as the reference here, W0498, discloses. [00:24:26] Speaker 01: And I would say discloses enables, because you can't render something obvious if you're not an enabling reference. [00:24:32] Speaker 01: And here, the PTAD ruled that W0498 doesn't either. [00:24:35] Speaker 01: It doesn't disclose anything that wasn't reduced to practice. [00:24:39] Speaker 01: And it doesn't show the hydrate forms. [00:24:42] Speaker 01: And it doesn't enable the hydrate forms. [00:24:44] Speaker 01: And I should back up for a minute, because I just got ahead of myself. [00:24:48] Speaker 01: Mylan's argument is what we didn't end Antidote on was hydrates. [00:24:53] Speaker 01: Concededly, we did not have hydrates reduced to practice before the W0498 came out. [00:24:59] Speaker 01: But then the question is, OK, does the 498 disclose hydrates? [00:25:03] Speaker 01: Does it enable hydrates? [00:25:05] Speaker 01: And the board made extensive findings that the 498 neither discloses nor enables the hydrate forms. [00:25:12] Speaker 01: For example, on disclosure, on appendix 48, Petitia's declarant concedes, none of the W498 compounds are disclosed as being synthesized as hydrates. [00:25:21] Speaker 01: There's just no identification of a hydrate, much less a hydrate of cediglyptin, much less one-to-one cediglyptin DHP hydrates. [00:25:30] Speaker 01: It doesn't disclose a phosphate salt of any of the 33 compounds. [00:25:35] Speaker 01: The sole mention of hydrates comes in a definition where it says salts in the solid form may exist in more than one crystal structure and may also be in the form of hydrates. [00:25:46] Speaker 01: And that's at PENIX 48 is where they quote it. [00:25:49] Speaker 01: But that's a statement that isn't connected to c-de-glyptin. [00:25:52] Speaker 01: It's not connected to phosphates at all. [00:25:55] Speaker 01: And saying that some salts may exist in hydrate form is a bit like saying there may be extraterrestrial life out there in a galaxy. [00:26:02] Speaker 01: It may exist. [00:26:03] Speaker 01: We all know it's a possibility. [00:26:05] Speaker 01: But it doesn't disclose it so as to make it obvious for someone who actually comes up and discovers and makes it. [00:26:11] Speaker 01: And the PTAB-credited Merck expert who explained that skilled artisans would understand that reference, that statement, to mean [00:26:17] Speaker 01: In general knowledge, we know that some of these will actually have salts. [00:26:21] Speaker 01: Some of them might be hydrates. [00:26:22] Speaker 01: But it doesn't disclose any particular hydrate salt. [00:26:25] Speaker 01: And that makes sense because Formula 1 has millions and millions of possible compounds out there. [00:26:30] Speaker 01: You wouldn't read that phrase to mean each and every one of them has a hydrate, and we are now disclosing the hydrate, and we're enabling the hydrate. [00:26:37] Speaker 01: And that gets the alternative ground that the board gave, which is that there's no enablement. [00:26:42] Speaker 01: And the board acknowledged that possibly there is a presumption of enablement here, but it held that that presumption was overcome. [00:26:48] Speaker 01: And I wanted to mention very specifically about Wann's factors. [00:26:54] Speaker 01: There was nothing in the opening brief that complained that the Wanns factors weren't addressed. [00:26:58] Speaker 01: So the argument is waived. [00:26:59] Speaker 01: If we had seen that, we would have pointed out there's a case called Amgen versus Chugai Pharmaceuticals that says you don't have to walk through the Wanns factors. [00:27:07] Speaker 01: But here, the board actually did walk through the Wanns factors without calling the Wanns factors. [00:27:13] Speaker 01: So if I go to page, we talked about the first quantity of experimentation, appendix 51. [00:27:19] Speaker 01: says, discovery unforeseen and arose only after substantial work with other salt forms. [00:27:24] Speaker 01: In that case, it was more than a year. [00:27:26] Speaker 01: Second, what factor? [00:27:27] Speaker 01: Amount of guidance presented. [00:27:29] Speaker 01: Appendix 49. [00:27:30] Speaker 01: No guidance in W498 for making hydrates. [00:27:34] Speaker 01: Presence of working examples. [00:27:35] Speaker 01: Appendix 49 again. [00:27:37] Speaker 01: W498 does not show that any such hydrates do exist. [00:27:41] Speaker 01: Nature of invention. [00:27:42] Speaker 01: Appendix 51 to 52, and note 32. [00:27:45] Speaker 01: It's an unpredictable nature of salt formation. [00:27:48] Speaker 01: State of the prior art. [00:27:50] Speaker 01: Appendix 50 talks about the literature, says the literature or record firmly supports Merck and its expert. [00:27:54] Speaker 01: Relative skill of those in the arts. [00:27:56] Speaker 01: Appendix 51. [00:27:58] Speaker 01: Skilled artists would not have arrived at the particular experimental conditions necessary. [00:28:02] Speaker 01: Predictability of the art. [00:28:04] Speaker 01: Whether any salt is even capable of forming as a hydrate is highly unpredictable. [00:28:08] Speaker 01: That's Appendix 49. [00:28:09] Speaker 01: Finally, breadth of the claims. [00:28:11] Speaker 01: There are at least thousands, likely millions of salts embraced by hypothetical combinations of DP4 compounds and potential counter arms in W0498. [00:28:18] Speaker 01: That's Appendix 48. [00:28:19] Speaker 01: So the board actually went through all of those things. [00:28:22] Speaker 01: And if it had been in the opening brief, we would have pointed that out. [00:28:25] Speaker 01: I see that my time is virtually up. [00:28:26] Speaker 01: Oh, now it's up. [00:28:28] Speaker 01: Thank you. [00:28:28] Speaker 01: If the court has no questions, I will take my seat. [00:28:31] Speaker 03: Thank you, Mr. Lampton. [00:28:32] Speaker 03: Thank you. [00:28:35] Speaker 03: Mr. Worley has just two minutes. [00:28:39] Speaker 00: Thank you, Your Honor. [00:28:42] Speaker 00: The comments by Mr. Lampkin confirm that Merck's anticipation defense is built entirely upon looking at those 33 compounds and using that as your starting point. [00:28:54] Speaker 02: What is your best case for saying that that shouldn't be the starting point? [00:28:57] Speaker 02: And how do you respond to the point about your expert admission? [00:29:01] Speaker 00: So my best cases, I have two, are going to be paraconid impacts, because those involve cases where you had a formula that was narrowed down [00:29:08] Speaker 00: by expressly pointing to the compound that was at issue. [00:29:11] Speaker 00: And that's where the court started, with the compound, not with the formula. [00:29:15] Speaker 00: As to what our experts said, I don't think those questions that were elicited are relevant, because they only matter if there is indeed a lead compound analysis that is grafted onto anticipation. [00:29:28] Speaker 00: And for the reasons that you have an impericonate impact, that's not accurate. [00:29:33] Speaker 00: So regardless of what he says, it's not legally relevant. [00:29:38] Speaker 00: Mr. Lampkin also made a number of points about the unpredictability of the art. [00:29:44] Speaker 00: And Judge Lurie, I think you were accurate in pointing out that this is in tension with Pfizer. [00:29:48] Speaker 00: I think the proposition of law that their case runs into is that if they're right, you run the risk of establishing a rule that, quote, any new salt would be separately patentable simply because the formation and properties of each salt must be verified through testing. [00:30:04] Speaker 00: I don't see any way you can get around that if you credit their point. [00:30:12] Speaker 00: Briefly on antidation, regarding the disclosures, the definition of pharmaceutically acceptable salts encompasses hydrates. [00:30:20] Speaker 00: And that definition applies to acidic lipid. [00:30:23] Speaker 00: Go back to claim 15. [00:30:25] Speaker 03: You're saying a salt encompasses a hydrate? [00:30:28] Speaker 00: I'm saying the definition that is provided in the prior art says that pharmaceutically acceptable salts may include hydrates. [00:30:36] Speaker 00: That's what the prior art says on page 376 of the record, and that definition applies to acidic Lipton by a claim 15. [00:30:45] Speaker 00: Lastly, Your Honors, if I may, I see my time is... One last thought. [00:30:50] Speaker 00: One last thought. [00:30:51] Speaker 00: The evidence that was cited by Mr. Lampkin, all of that comes reclaimed for, which is not even at issue for Antidation. [00:30:57] Speaker 00: If the families have any questions, I will... Thank you, Counsel. [00:31:02] Speaker 03: We'll take the case on the submission.