[00:00:40] Speaker 02: The next case is Warner-Chilcott v. Weber Pharmacy, the case 2015-1588. [00:00:46] Speaker 02: Mr. Alton, when you're ready. [00:00:53] Speaker 04: May I proceed? [00:01:02] Speaker 02: Yes. [00:01:03] Speaker 04: May it please the Court, very rarely do you come across a case [00:01:08] Speaker 04: where the defendant itself says it is hard to believe, hard to believe the patentee was able to achieve the claimed invention. [00:01:17] Speaker 04: But that's what we have here. [00:01:19] Speaker 04: Teva tried and failed to create a bisphosphonate formulation that could be taken either with or without food. [00:01:27] Speaker 04: Teva said it could not ethically proceed with a formulation containing more than five milligrams EDTA, even after it had the Atelvia patents [00:01:38] Speaker 02: Wasn't it conceded that the Brazilian patent disclosed this invention, except possibly for the addition of the language, pharmaceutically effective absorption? [00:01:50] Speaker 04: No, Your Honor. [00:01:51] Speaker 04: All that was conceded is that one could hunt there and find the coding agent, the chelating agent, and the bisphosphonate listed somewhere in a laundry list of ingredients. [00:02:04] Speaker 04: And this is clear at A1109. [00:02:07] Speaker 04: And then in the 717 AM transcript, 64, line 19 through 65, line 7. [00:02:16] Speaker 02: So was the bisphosphonate disclosed with EDTA, 100 milligram dosage? [00:02:23] Speaker 04: No, Your Honor. [00:02:24] Speaker 04: What we have in BR601 is a long laundry list. [00:02:28] Speaker 04: It gives a list of, it says you can use any bisphosphonate and provides examples. [00:02:35] Speaker 03: One of those many. [00:02:37] Speaker 03: that's being used here was a common one that was used, right? [00:02:41] Speaker 03: It was a common one that was used. [00:02:43] Speaker 03: 35 milligrams dose was a common dose, right? [00:02:46] Speaker 04: 35 milligrams was in the Actinel dose, and BR601 said lower the dose. [00:02:52] Speaker 04: It's absolutely crystal clear when you look at both the... But it's true that that was a common dose, right? [00:02:58] Speaker 04: Certainly, and if one follows BR601, you have to lower that dose. [00:03:03] Speaker 04: As far as EDTA goes, [00:03:05] Speaker 04: What it says is in a particular embodiment, a preferred but not exclusively preferred embodiment, EDTA should not exceed 175 milligrams. [00:03:18] Speaker 04: Right above that, it gives a formula for a proportion, a ratio. [00:03:22] Speaker 04: And putting those two together, if 35 milligrams against the teachings of BR601 to lower dose is nevertheless chosen, you end up with 20 to 175 milligrams. [00:03:33] Speaker 04: Which BR601 promises [00:03:36] Speaker 04: will increase intestinal permeability, which everyone concedes was undesirable. [00:03:42] Speaker 04: BR-601 teaches against the claimed invention. [00:03:45] Speaker 04: And I think the evidence that the district court disregarded or dismissed the objective considerations of non-obviousness have much to say here. [00:03:57] Speaker 04: The Teva scientists expressed skepticism about the invention over and over again. [00:04:03] Speaker 03: How did the Brazilian application teach away? [00:04:06] Speaker 04: The BR601 teaches away from the invention in two distinct ways. [00:04:11] Speaker 04: First, it tells you to pick a dose and then lower it. [00:04:17] Speaker 04: It talks on page 1623 about the aim being to enhance absorption so that you don't have to give so much bisphosphonate. [00:04:27] Speaker 04: 1625 in the reference, and I'm referring to the appendix site, it speaks of accomplishing that invention, enhancing absorption by [00:04:36] Speaker 04: and thereby allowing the dose to be diminished, to be dropped. [00:04:43] Speaker 04: So if you started with 35 milligrams, you're going to go down. [00:04:47] Speaker 03: BR-601 also teaches... So you're arguing that it teaches away from using 35 milligrams? [00:04:52] Speaker 04: Yes. [00:04:54] Speaker 04: Clearly, and the district court erred in saying it did not suggest that. [00:04:58] Speaker 04: It doesn't only suggest that, it instructs that. [00:05:03] Speaker 04: And this is... [00:05:06] Speaker 04: at page A16 of the opinion, the district court said that BR601 did not suggest using less than the known effective quantity of the bisphosphonate. [00:05:18] Speaker 04: BR601 states that the problem is having to give too much bisphosphonate, that's on A1623, and then says that with its compositions, and I'm quoting from A1625, we obtain an effective treatment with a small quantity of bisphosphonate [00:05:35] Speaker 04: compared to the current treatment by its association with the chelating agent. [00:05:41] Speaker 04: And then BR601 speaks in both places about one of the ways that it accomplishes that is by increasing intestinal permeability. [00:05:50] Speaker 04: That means opening up those tight junctions that the rest of the prior art said oughtn't to be opened. [00:05:57] Speaker 04: And the rest of the prior art is universal in saying that those tight junctions should not be altered. [00:06:04] Speaker 04: BR601 says, [00:06:05] Speaker 04: You're going to get that if you use 20 to 175 milligrams of EDTA. [00:06:13] Speaker 04: It's crystal clear on 1623 through 1625 of the appendix. [00:06:22] Speaker 04: I think they go hand in hand because BR601 is describing a formulation containing both. [00:06:32] Speaker 04: And it says, if you use a chelating agent and in smaller quantities than was used in a prior art reference, deliver it to the small intestine, chelate and alter intestinal permeability, then you will be able [00:06:47] Speaker 04: to enhance absorption and reduce the bisphosphonate dumps. [00:06:51] Speaker 04: So those passages speak to both of these issues. [00:06:54] Speaker 02: The district court said the parties agree that, quote, somewhere in the Brazilian application are all the elements of the assertive claim to have chemically effective absorption. [00:07:06] Speaker 02: And your argument is that there are a number of bisphosphonates. [00:07:11] Speaker 02: But that's really an anticipation argument. [00:07:13] Speaker 02: In terms of obviousness, the disproportionate is there. [00:07:17] Speaker 02: The EDTA within the range is there. [00:07:22] Speaker 02: And the only addition is pharmaceutical effective absorption. [00:07:27] Speaker 02: And that's a functional. [00:07:29] Speaker 02: That's a result. [00:07:30] Speaker 02: That's result language. [00:07:32] Speaker 02: There's nothing in the claim to necessarily bring about that result compared with what's in the resilient application. [00:07:40] Speaker 02: We're dealing with obviousness here, not anticipation. [00:07:42] Speaker 04: Correct, Your Honor, and in obviousness as well, if all that you have in the principal prior art is a laundry list of ingredients, there still has to be a reason why the person of ordinary skill in the art would have selected those ingredients at those doses. [00:07:58] Speaker 04: We're dealing with claims that are very particular. [00:08:03] Speaker 02: Well, the claims here recite quite a large range of EDTA dosages. [00:08:13] Speaker 02: Not particular at all. [00:08:15] Speaker 04: Not in the asserted claims, Your Honor. [00:08:18] Speaker 04: The asserted claims are very specific. [00:08:21] Speaker 04: They name the EDTA. [00:08:22] Speaker 02: Is claim eight an asserted claim? [00:08:26] Speaker 04: Your Honor, the asserted claims in the 459 patent is claim 16. [00:08:33] Speaker 04: And by that point, the dosages for both the chelating agent and the bisphosphonate had been narrowed. [00:08:43] Speaker 03: Down to 100 milligrams. [00:08:45] Speaker 04: Of the EDTA, down to 35 milligrams of resedrinate. [00:08:49] Speaker 04: And there's a particular coding agent. [00:08:52] Speaker 03: 35 milligrams is the common dosage. [00:08:53] Speaker 03: And the 100 milligram you could compute using a well-known formula, right? [00:08:59] Speaker 04: The 100 milligrams certainly could not be computed. [00:09:02] Speaker 04: using a well-known formula. [00:09:05] Speaker 03: Well, didn't the district court find that that was the case? [00:09:08] Speaker 03: What the district court found... Isn't that the case? [00:09:11] Speaker 03: That that's something the district court found? [00:09:14] Speaker 04: The district court... I'm trying to answer your question as best I can. [00:09:17] Speaker 04: This is on A59 through 60 of the appendix. [00:09:22] Speaker 04: She cites to Dr. Yates saying that you can apply [00:09:27] Speaker 04: Two other references, Mitchell and Mahe, combine them, do a calculation, and according to Dr. Yates, you would end up at slightly above 100 milligrams EDTA. [00:09:40] Speaker 04: On cross-examination, it was 75 to 150. [00:09:43] Speaker 04: And the prior art, the prior art that... Well, first of all, she disregarded the fact that Dr. Yates said [00:09:54] Speaker 04: that 75 to 150 would be the range. [00:09:58] Speaker 04: It's also the case that the district court did not rely on that combination to support its obviousness decision in its entirety. [00:10:07] Speaker 04: That's in a special section about reasonable expectation of success. [00:10:11] Speaker 04: Her obviousness opinion is founded and rests on BR 601, which is the reference talking about the key leading agent in the bisphosphonate. [00:10:21] Speaker 04: MAHE is simply about measuring [00:10:24] Speaker 04: calcium in the small intestine at different places. [00:10:28] Speaker 04: Mahe specifically says different results were reached in a different study. [00:10:33] Speaker 04: There was no attempt on the district court's case. [00:10:36] Speaker 04: That's the Fairweather-Tate reference that's mentioned. [00:10:41] Speaker 04: There was no attempt by the district court to reconcile the different teachings in these art. [00:10:47] Speaker 04: All of this smacks of hindsight. [00:10:50] Speaker 04: And this court said time and again, [00:10:53] Speaker 04: What guards against hindsight? [00:10:55] Speaker 04: It's the objective considerations of non-obviousness. [00:10:59] Speaker 04: Skepticism. [00:11:00] Speaker 04: Those statements by the Teva scientists warning against using EDTA at the doses. [00:11:07] Speaker 04: This is after they have the Atelvia patents in hand. [00:11:10] Speaker 04: Example one is Atelvia. [00:11:12] Speaker 04: And they say it would not be ethical to proceed. [00:11:16] Speaker 04: They said as well that they couldn't find support for the 100 milligrams in the literature. [00:11:24] Speaker 04: They believed at the time that it was not safe. [00:11:28] Speaker 01: Only in litigation. [00:11:35] Speaker 01: asserting the narrowness of claim 16 here. [00:11:38] Speaker 01: But your claim does the same thing. [00:11:40] Speaker 01: It starts with claim 8, which has these huge, broad ranges of both things, are ones that you now say the prior art taught away from. [00:11:49] Speaker 01: I mean, it kind of baffles me that you're saying that the earlier stuff didn't teach this, and your patent claims the same thing. [00:11:57] Speaker 04: I think, Your Honor, that's the essence of hindsight. [00:12:00] Speaker 04: It's looking at our patents, using them as a blueprint. [00:12:03] Speaker 04: The specification of RPATS also talks about the dependence of the chelator dose and the bisphosphonate dose. [00:12:12] Speaker 04: It then goes on and provides examples. [00:12:14] Speaker 04: And I think that it's in the pharmaceutical arts, having prophetic examples, having broad claims, and then choosing to assert the narrow ones, that's a sensible strategy that's time-honored. [00:12:29] Speaker 04: But it's the essence of hindsight to look at [00:12:31] Speaker 04: the patents and use them as a blueprint going backwards. [00:12:34] Speaker 03: And one of the things... So what was the invention here, figuring out that 100 milligrams was the right amount of EDTA? [00:12:41] Speaker 04: The invention here is the combination of using... The 30-milligram dose of this phosphate was well known. [00:12:50] Speaker 03: And it was well known that if you used something like EDTA, you would solve the problem, the calcium problem. [00:13:01] Speaker 04: Right? [00:13:01] Speaker 04: EDTA was thought to be unsafe, and BR-601. [00:13:05] Speaker 03: No, no, I understand. [00:13:06] Speaker 03: Yes. [00:13:07] Speaker 03: What you're basically saying is the invention here was figuring out that 100 milligrams was safe. [00:13:13] Speaker 04: Much more than that, Your Honor, because the other thing is pharmaceutical effective absorption. [00:13:19] Speaker 04: BR-601 and some of the other references that the court relied on are about boosting [00:13:26] Speaker 04: enhancing absorption both in fasted and fed states. [00:13:30] Speaker 04: Remember, this is an ingredient, the bisphosphonate, that has a very low bioavailability. [00:13:36] Speaker 04: By some counts, less than 1%. [00:13:38] Speaker 04: With food, it approaches zero. [00:13:41] Speaker 04: So most of the references in the prior art were seeking to boost absorption across the board. [00:13:48] Speaker 04: The inventors here wanted to achieve pharmaceutically effective absorption, similar absorption of fasted and fed states. [00:13:55] Speaker 04: That's not what BR601 was addressing. [00:13:58] Speaker 04: That's not what W0111 was addressing, which the district court clearly misread. [00:14:05] Speaker 04: So if one looks at Poiger, and we pointed this out in the brief, that's the reference, is from 1978, there is no comparison there of, and I see that I'm in my rebuttal time, there is no comparison there of the same EDTA [00:14:24] Speaker 04: and food dose fasted and fed, or EDTA and bisphosphonate dose, both fasted and fed. [00:14:32] Speaker 04: And Dr. Yates admitted in his testimony that there may well have been pre-calation of the food and the EDTA. [00:14:43] Speaker 04: And I think that explains also why in 1978 reference of record in the prosecution, like every other bit of prior art, why there was such a gap between that [00:14:54] Speaker 04: and the time of the invention here. [00:14:56] Speaker 04: At the end of the day, the objective evidence of non-obviousness was systematically disregarded or ignored. [00:15:02] Speaker 04: It answers these questions. [00:15:04] Speaker 03: Why did Teva choose? [00:15:12] Speaker 03: Yes, Your Honor. [00:15:17] Speaker 04: That's clearly erroneous. [00:15:19] Speaker 04: The district court elsewhere relied on those same scientists. [00:15:23] Speaker 03: The same scientists who relied on me? [00:15:24] Speaker 04: Dr. Shake. [00:15:26] Speaker 03: Where did she rely on the same scientists? [00:15:27] Speaker 04: I believe it's A60, the last line in that footnote that we were discussing. [00:15:34] Speaker 04: If you look up that transcript site, that's Dr. Shake. [00:15:37] Speaker 04: Dilberger, who the court relied on, also a toxicologist. [00:15:41] Speaker 04: One of these scientists is a toxicologist. [00:15:44] Speaker 04: It's not like these people were working in the mail room. [00:15:46] Speaker 04: It's simply incredible that this highly probative evidence of non-obviousness was systematically disregarded. [00:15:53] Speaker 04: And I've got only a few seconds left. [00:15:55] Speaker 04: I'm going to reserve whatever time I have there. [00:15:58] Speaker 02: Well, there isn't much, but we'll give you two minutes of rebuttal time. [00:16:01] Speaker 02: Thank you, Your Honor. [00:16:02] Speaker 02: Ms. [00:16:03] Speaker 02: Holland. [00:16:04] Speaker 00: Thank you, Your Honor. [00:16:05] Speaker 00: May it please the court, Elizabeth Holland of Goodwin Proctor for Teva. [00:16:09] Speaker 00: Every single issue that Mr. Alican raised this morning in his argument was factual in nature, and it was addressed in a specific finding made by the district court in this case. [00:16:20] Speaker 00: The district court heard five days of testimony from expert formulators, toxicologists, physicians, and from fact witnesses, was able to assess their credibility, and at the end of the day, issued a 68-page, careful, extensive opinion [00:16:39] Speaker 00: with that addressed all of the evidence at trial? [00:16:43] Speaker 02: Was there something unexpected compared with the broader prior art disclosure in the 100 milligram EDTA composition? [00:16:54] Speaker 00: No, Your Honor. [00:16:55] Speaker 00: There was nothing unexpected. [00:16:57] Speaker 00: As the district court found, BR-601 taught a range that went from 20 to 175 milligrams. [00:17:04] Speaker 00: The district court found that BR-601 in particular [00:17:07] Speaker 00: addressed the issue head on that had been raised in the prior art that Mr. Ellican alluded to. [00:17:13] Speaker 00: Mr. Ellican said there was a safety issue with high amounts of EDTA. [00:17:16] Speaker 00: BR-601, as the district court found, said, look, I'm acknowledging that issue in the prior art and I'm teaching you how to solve it. [00:17:25] Speaker 00: Use a lower amount of EDTA and you can do that by administering to the small intestine instead of the stomach. [00:17:30] Speaker 00: It takes care of any safety concerns. [00:17:33] Speaker 00: Poyger, also pointed to by the district court, said, [00:17:37] Speaker 00: I used 250 milligrams of EDTA on an empty stomach in the fasted state. [00:17:43] Speaker 00: No harm, no excess absorption. [00:17:46] Speaker 00: So there was nothing unexpected about the 100 milligrams here. [00:17:54] Speaker 00: And it was Warner Chilcott's burden in this case. [00:17:58] Speaker 00: Once it was shown that the 100 milligrams of EDTA was encompassed within the range of BR601, [00:18:03] Speaker 00: Warner-Chilcott had to rebut the presumption that that range was obvious, either by showing a teachaway or by showing criticality. [00:18:11] Speaker 00: And as the district court found, it was able to establish neither one of those. [00:18:18] Speaker 00: The references, as I mentioned earlier, that Mr. Ellicott points to and as Warner-Chilcott pointed to in its briefs, all used very high doses of EDTA on the order of 7,000 milligrams or so, none of them that allegedly [00:18:32] Speaker 00: teach this safety issue had anything near 100 milligrams of EDTA. [00:18:40] Speaker 00: The Poyger reference addressed 250 milligrams. [00:18:43] Speaker 00: Importantly here, there was no expert testimony at trial rebutting Dr. Yates' testimony on Poyger. [00:18:50] Speaker 00: The district court properly found based on unrebutted testimony that Poyger taught that 100 milligrams would be safe. [00:19:00] Speaker 00: Also importantly, the district court found that the experts had agreed that even in the fasted state, there's always a calcium buffer in the intestines. [00:19:08] Speaker 00: So you can give EDTA on completely fasted state and there would be no harm at all to the tight junctions unless all the calcium reserve in the intestines have been depleted and that simply wouldn't happen. [00:19:26] Speaker 00: with 100 milligrams of EDTA as the district court found and as the experts testified. [00:19:33] Speaker 00: And this was not the first time that Warner Chilcot had characterized those references, the Lynn, Jenner's, the college references that it now claims teach safety concerns and teach away from the 100 milligrams. [00:19:50] Speaker 00: In fact, Warner Chilcot had used those very same references [00:19:54] Speaker 00: to convince the FDA that 100 milligrams was safe and could be used in its product, using the opposite arguments that it did at trial to show that the district court, to try to convince the district court there was a teachaway. [00:20:08] Speaker 00: Same thing at the patent office. [00:20:12] Speaker 00: Warner-Chilcot has repeatedly said in its briefing that all these references were before the examiner. [00:20:18] Speaker 00: What the examiner didn't know is about the Warner-Chilcot's statements to the FDA characterizing [00:20:24] Speaker 00: those references as teaching no problem with 100 milligrams. [00:20:33] Speaker 00: I'll address briefly the secondary considerations points. [00:20:36] Speaker 00: It's hard to understand Mr. Ellicott's argument that the district court overlooked something. [00:20:40] Speaker 00: If you look at the court's opinion, there's a careful analysis of every single one of the secondary considerations that Warner Chilcot had tried to convince the court existed in this case. [00:20:50] Speaker 00: Warren and Chilcott doesn't like the result of that analysis, but there's no way to look at the opinion and say the district court didn't consider all the evidence. [00:20:58] Speaker 02: Are only claims 16 and 20 of the two patents at issue? [00:21:07] Speaker 00: Yes, those were the only two claims at issue in this case. [00:21:10] Speaker 00: But what's important, and as I think all of the court noted earlier, [00:21:16] Speaker 00: Warner Chilcott says in its claims that 10 to 500 milligrams of EDTA will give you pharmaceutically effective absorption. [00:21:24] Speaker 00: Those claims had to have been enabled or Warner Chilcott could not have gotten them out of the patent office. [00:21:30] Speaker 00: So there's no way now for Warner Chilcott to come back and say any amount of EDTA in that range would not work. [00:21:37] Speaker 00: They simply could not have patented it if it wouldn't work. [00:21:40] Speaker 00: It's kind of beside the point that the particular claims at issue here only have the 100 milligrams of EDTA. [00:21:46] Speaker 02: So did the court only decide the claims 16 and 20 are invalid, not the rest of the claims? [00:21:54] Speaker 00: Correct. [00:21:58] Speaker 00: I think I'll sit down unless there are other questions from the bench. [00:22:01] Speaker 02: Thank you. [00:22:05] Speaker 00: I didn't think so, Your Honor. [00:22:08] Speaker 02: Mr. Ellington, we'll give you two minutes. [00:22:10] Speaker 04: Thank you, Your Honor. [00:22:12] Speaker 04: The 20 to 175 milligram range, there was a failure in there, 40 milligrams. [00:22:19] Speaker 04: The court disregarded that. [00:22:21] Speaker 04: That was Teva's own failure with its own attempt to make a bisphosphonate formulation to anticipate Atelvia. [00:22:29] Speaker 04: It fits within the range. [00:22:30] Speaker 04: It shows that it matters what dosage is picked. [00:22:34] Speaker 04: The district court said that there was no evidence as to why it failed. [00:22:39] Speaker 04: A3785, which is the document the district court cited to, says there were no measurable residrinate concentrations in the fed state. [00:22:48] Speaker 04: Clear error. [00:22:49] Speaker 04: Copying. [00:22:50] Speaker 04: There is no contention here that the district court, as I understand it, the district court simply disregarded the issue of copying. [00:22:59] Speaker 04: There's a section in the memorandum of opinion titled Failure of Others in Copying. [00:23:04] Speaker 04: It doesn't address copying. [00:23:06] Speaker 04: If it didn't matter what dose was chosen, [00:23:08] Speaker 04: Why was Teva picking the same chelator at the exact same dosage? [00:23:14] Speaker 04: It didn't need to do so to comply with FDA requirements. [00:23:17] Speaker 04: There was simply no explanation. [00:23:21] Speaker 04: That the experts agreed to the safety of these low doses? [00:23:25] Speaker 04: Not true. [00:23:28] Speaker 04: I'd like to point to the undisputed evidence that the prior art said that segments... Why do they have to agree? [00:23:35] Speaker 04: I'm sorry? [00:23:35] Speaker 03: Why do they have to agree? [00:23:37] Speaker 04: I believe that was the statement I heard, Your Honor. [00:23:40] Speaker 04: But in any event, Dr. Dillberger, this was in their brace, said the intestines are often empty based on his experiments with animals. [00:23:48] Speaker 04: The prior art said that in humans, he said, I'm sorry, I'm not sure if I said that correctly, that they're never empty in animals. [00:23:56] Speaker 04: The prior art, and this is Dr. Yates, Teva's other expert, admitting that the prior art taught that segments are often empty. [00:24:03] Speaker 04: That's A577 to 79. [00:24:06] Speaker 04: DTX-264 at 1458. [00:24:09] Speaker 04: Backup argument, according to Dr. Dillberger, the digested food flies through the intestine so quickly that there can be no concern. [00:24:19] Speaker 04: But the prior art again, of record, DTX-234, penultimate page in that reference 615, paragraph 10 said, the transport through the intestines is slow and allows absorption. [00:24:32] Speaker 04: So Dr. Dillberger is a lone [00:24:35] Speaker 04: and unsupported, that's who the district court relied on in each and every instance. [00:24:40] Speaker 04: What he said was at odds with Parliament. [00:24:44] Speaker 04: Thank you, Your Honor. [00:24:45] Speaker 04: Thank you for your time. [00:24:45] Speaker 04: Good morning.