[00:00:00] Speaker 04:
Good morning again, ladies and gentlemen.

[00:00:04] Speaker 04:
We now have Teva Pharmaceuticals versus Eli Lilly, 2020, 1747, 48, 49, 50, 51, and 52.

[00:00:16] Speaker 04:
Mr. Jay, please proceed.

[00:00:18] Speaker 00:
Thank you, Your Honor.

[00:00:19] Speaker 00:
May it please the court?

[00:00:21] Speaker 00:
These patents claim the first humanized antibodies to target the ligand CGRP

[00:00:25] Speaker 00:
And the board thought that the asserted combination of references would teach a skilled artisan to study or use such a humanized NICGRP antibody.

[00:00:34] Speaker 00:
That study or use motivation was procedurally improper, but it also is not borne out by the substance.

[00:00:40] Speaker 00:
The board focused so narrowly on whether the references used the words study or explore, that it failed to consider the references as a whole, and that changed how it weighed three things in particular.

[00:00:51] Speaker 04:
Differences between... Council, the claim is...

[00:00:55] Speaker 04:
almost anticipated by CAN, except for the humanized limitation, and that is provided by Queen.

[00:01:08] Speaker 04:
So why wasn't the board correct?

[00:01:13] Speaker 00:
The board wasn't correct, Your Honor, because in order for there to be a motivation to make a humanized

[00:01:20] Speaker 00:
anti-CGRP ligand targeting antibody, you would need more motivation than TAN can possibly provide.

[00:01:29] Speaker 04:
And so what are antibodies to be used for?

[00:01:32] Speaker 04:
Not for wraps.

[00:01:35] Speaker 04:
It's fairly obvious to humanize an antibody that is related to human disease.

[00:01:46] Speaker 00:
Perhaps eventually, Your Honor, but I think as the collection of art in this case indicates, there was substantial uncertainty both about the role of CGRP and about the appropriate mechanism to take advantage of the role that CGRP plays in disorders such as migraine.

[00:02:06] Speaker 00:
So, for example, the superiority of targeting the receptor

[00:02:12] Speaker 00:
based on, among other things, safety concerns, that's something that's taught by Wimalalansa.

[00:02:17] Speaker 00:
And if there's a broader point that I can make about this collection of art, just to respond directly to your question, you have several aspects of both TAN and Wimalalansa that are urging further animal studies before proceeding to human trials.

[00:02:37] Speaker 00:
So I think that while a

[00:02:41] Speaker 00:
The ultimate goal of researching antibodies may well be to develop a human therapy.

[00:02:50] Speaker 00:
The teachings of TAN alone, which remember is 10 years before the priority date, don't give the skilled artisan a basis to pursue a humanized antibody that would target the ligand.

[00:03:03] Speaker 04:
Why wasn't it obvious to try?

[00:03:06] Speaker 00:
I don't think it was obvious to try, Your Honor, most significantly because of the failed result in TAN itself.

[00:03:14] Speaker 00:
The full-size antibody in TAN did not achieve immunoblocade, and on that point, the board agreed with us and made a finding to that effect at Appendix 43.

[00:03:27] Speaker 04:
Lily is attempting to derive... Weren't there suggestions to improve the effectiveness of the pull sequence?

[00:03:39] Speaker 00:
So this is the 16% point that our friends on the other side refer to and what the board referred to as optimism.

[00:03:48] Speaker 00:
What TAN says is that there

[00:03:52] Speaker 00:
There may be prospects if you change the dosage and the time of getting the full-size antibody into the interstitial space.

[00:04:05] Speaker 00:
But even that expression of optimism doesn't, doesn't suggest that there'd be a positive result, even in an animal study.

[00:04:13] Speaker 00:
That's just about getting the full-length antibody on site in a sufficient concentration.

[00:04:19] Speaker 00:
There's no finding that it would work, that it would actually achieve immunoblocade.

[00:04:24] Speaker 00:
And we would submit that given that this optimism is expressed 10 years before the priority date, it was not a routine matter to go forward and develop a humanized antibody at the full length that would be efficacious.

[00:04:45] Speaker 02:
Isn't that exactly the problem, that last word that you're saying, efficacious?

[00:04:50] Speaker 02:
I mean, you talk about humanized

[00:04:53] Speaker 02:
antibody, but I think the board's concern was the breadth of the claims in these patents, which don't really require that they be efficacious for any real purpose.

[00:05:06] Speaker 00:
I take that point, Your Honor, but I do think that even if we're looking just at motivation to make a humanized antibody, antibodies can be studied in rat trials.

[00:05:16] Speaker 00:
TGRP can be studied in animal trials.

[00:05:19] Speaker 00:
I think it's

[00:05:19] Speaker 00:
I think it's the ground here that the only reason to humanize this antibody is to use it in human patients.

[00:05:28] Speaker 00:
And if the art taught that there would not be a successful result from using the full length antibody to antagonize the ligand as opposed to the receptor, then that is certainly relevant to motivation.

[00:05:44] Speaker 00:
But if you look at what the board did,

[00:05:45] Speaker 00:
Take, for example, the way it treated the studies of the small molecule receptor antagonist BIBN, or BIBN.

[00:05:54] Speaker 00:
And this is at pages 54 and 55 of the decision in the appendix.

[00:06:02] Speaker 00:
The board just declined to reach the question whether someone would believe that based on the success of BIBN that an anti-CGRP

[00:06:11] Speaker 00:
ligand targeting antibody would be effective, says that a skill origin would just be motivated to study antagonism generally.

[00:06:19] Speaker 00:
And our submission is that that's not a sufficient basis to make a humanized antibody, especially not one that, as the dependent claim indicates, is to be in a pharmaceutical opposition.

[00:06:31] Speaker 03:
It seems to me, this is just, Bryson, that what your argument is is that the ultimate goal, as I think you described it, of treating humans

[00:06:40] Speaker 03:
has to be satisfied even though the claims are not directed to that ultimate goal.

[00:06:47] Speaker 03:
And the claims are explicitly directed to the generation of humanized anti-CGRP antagonist antibodies.

[00:06:56] Speaker 03:
And medicine often proceeds by stages where the ultimate goal is treatment, but that doesn't mean that you have to have an expectation

[00:07:10] Speaker 03:
that in the prior art that the treatment will be successful if your intermediate stage is more modest.

[00:07:22] Speaker 00:
I understand that point, Your Honor, and I certainly agree as a general matter.

[00:07:26] Speaker 00:
But on the facts of this case, where you have, for example, the board putting together the TAN experiment from 10 years before the priority date,

[00:07:38] Speaker 00:
with Wimolawansa, which is primarily a literature review, but that focuses heavily on antagonizing the receptor and not the ligand.

[00:07:49] Speaker 00:
And Wimolawansa's warning of potential deleterious side effects of targeting the ligand rather than the receptor.

[00:07:56] Speaker 00:
That's why it advocates for extremely specific receptor antagonists.

[00:08:02] Speaker 00:
So when you have right there in the references in the obviousness combination,

[00:08:06] Speaker 00:
urging taking a different path because of safety considerations.

[00:08:11] Speaker 00:
I think that's certainly relevant to the asserted motivation to combine what are, you know, fairly disparate references.

[00:08:18] Speaker 03:
But both Wimlalenta and Pan do refer to the possibility of

[00:08:25] Speaker 03:
creating humanized antibodies, full length anti-CRGP, CGHRM-P antagonist antibodies, right?

[00:08:34] Speaker 03:
I mean, Wimlolynsa certainly does, not at great length, but they do make a reference to that possibility.

[00:08:39] Speaker 03:
So it's not as if they were saying, this isn't workable.

[00:08:43] Speaker 00:
So I don't agree with that reading of Wimolawansa, Your Honor, although I don't think that you necessarily need to agree with what I'm about to say in order to agree with the thrust of our point about Wimolawansa, which is the focus on the safety concerns and the recommendation to pursue the receptor antagonist.

[00:09:01] Speaker 00:
But if you look at

[00:09:02] Speaker 00:
The sentence on which the board relies is literally the last sentence of Wimla-Lawrence in the conclusion, and it is summarizing what has come before.

[00:09:11] Speaker 00:
And if you look at what has come before, you see specifically that for all of the conditions where the reference is discussing the use of anti-CGRP antibodies,

[00:09:26] Speaker 00:
They're all receptor-specific, or they aren't antibodies at all.

[00:09:30] Speaker 00:
So diabetes, receptor-specific.

[00:09:32] Speaker 00:
Sepsis, blocking the receptor, and specifically calling for further studies in an animal model.

[00:09:38] Speaker 04:
Migraine, extremely... I'm sorry.

[00:09:41] Speaker 04:
You mentioned the conclusion of Rimmel-Wanzer, which states the role of CGRP antagonists in humanized monoclonal antibodies should be explored.

[00:09:55] Speaker 04:
And these are antagonists of the ligands, not the receptors.

[00:10:01] Speaker 00:
No, that's my point, Your Honor, is that if you look, for example, at the discussion of septic shock, you will see that an anti-CGRP antibody, as Wimalawansa uses that term, can be a receptor antagonist.

[00:10:12] Speaker 00:
An antibody can antagonize the receptor and not the ligand.

[00:10:15] Speaker 00:
And that's our submission, that that is what Wimola-Lawrence is talking about.

[00:10:20] Speaker 02:
Consistent with- Can I ask you a hypothetical question?

[00:10:24] Speaker 02:
You know, assuming, what if there were, for instance, a transgenic mouse that expresses human TGRP protein?

[00:10:35] Speaker 02:
Couldn't use humanized monoclonal antibodies to study in that

[00:10:42] Speaker 02:
methodology without worrying about all the safety concerns that you point out?

[00:10:50] Speaker 00:
So, in your hypothetical, the CGRP in the mouse's body is, so the mouse has both its own CGRP and there's also human CGRP in the mouse's body?

[00:11:01] Speaker 02:
Yeah, in a transgenic mouse.

[00:11:05] Speaker 02:
I guess that might be something.

[00:11:08] Speaker 02:
In other words, isn't there a way to use

[00:11:11] Speaker 02:
humanized monoclonal antibodies to study without having to put it into a person?

[00:11:20] Speaker 00:
Yeah, I understand the question.

[00:11:23] Speaker 00:
I'm not aware of anything in the record from the time of the priority date that suggests anything other than human trials for humanized antibodies.

[00:11:34] Speaker 00:
I don't want to say that it's impossible, but I'm not aware of any suggestion in the record supporting the motivation.

[00:11:41] Speaker 00:
on a theory like that.

[00:11:44] Speaker 00:
I take it to be agreed upon in the record in this case that the purpose of making a humanized antibody is to avoid the immunogenicity that would be caused by using it in a human that is subject to the human immune system and that would react negatively to a non-human antibody.

[00:12:11] Speaker 03:
I'm sorry, Mr. Jay, just to go back to Wimalawansa and accepting, as you say, that Wimalawansa does not discuss at great length, much length at all, the possibility of a non-receptor-based CGRP antagonist

[00:12:35] Speaker 03:
Nonetheless, both the last sentence but also an earlier sentence that I think Appendix 6586 says much the same thing about saying that the CGRP antagonist or humanized anti-CGRP monoclonal antibodies or both seems to me to suggest at least that they're talking not just about receptor-based

[00:13:04] Speaker 03:
antagonist, isn't that right?

[00:13:07] Speaker 00:
I don't think so.

[00:13:08] Speaker 03:
I'll put it this way, isn't that a fair reading of Wimah Lawansa that would be within the board's discretion to read the reference in that way?

[00:13:19] Speaker 00:
I don't think so and not even in isolation on that sentence and let me give you two answers, one based on that sentence and one based on something that comes after.

[00:13:28] Speaker 00:
So the first is that the sentence begins

[00:13:30] Speaker 00:
Clearly, more data from carefully designed studies are necessary before any definitive conclusions can be reached and before, this is where we get to the part that your honor just read from, CGRP antagonists, humanized NICGRP monoclonal antibodies, or both, can be evaluated as therapeutic agents in humans.

[00:13:46] Speaker 00:
So it's advocating for more study before there's even evaluation in humans.

[00:13:50] Speaker 00:
But then the second point is something I alluded to before.

[00:13:53] Speaker 00:
At the top of 6587, so this is the next page, at the very end of the septic shock discussion,

[00:14:00] Speaker 00:
you see expressly blocking CGRP receptors with specific antagonists or monoclonal antibodies.

[00:14:08] Speaker 00:
I think that makes very clear that monoclonal antibodies as women are launching using it is in the receptor context consistent with the overall focus of the reference.

[00:14:19] Speaker 00:
And I understand the point about the fact finders authority to resolve ambiguities.

[00:14:24] Speaker 00:
I think once you look at this reference as a whole and it's focused throughout on

[00:14:28] Speaker 00:
receptor therapy that there's not any ambiguity left for the fact finder to resolve.

[00:14:34] Speaker 04:
But if you have a peptide playing a role in disease, would it seem clear that there were two possible ways to deal with it, to deal with how it reacts on a receptor and to block it itself as a ligand?

[00:14:54] Speaker 04:
Aren't there just two clear ways to do it?

[00:14:57] Speaker 04:
And when you've got to establish the role of CGRP, and particularly when you've got TAN too, then what you're claiming is not far off.

[00:15:16] Speaker 00:
So a couple of responses to that, Judge Laurie.

[00:15:19] Speaker 00:
First, there are at least three ways because there's also the tryptans which suppress the release of the peptide to begin with.

[00:15:28] Speaker 00:
And second, what would you antagonize the ligand with?

[00:15:32] Speaker 00:
There are other possibilities in the art.

[00:15:35] Speaker 00:
But third and most fundamentally, CGRP does more than just

[00:15:40] Speaker 00:
uh... activate this one receptor that is the focus of the uh... of the migraine science and that is why when the law wants it for for a migraine treatment

[00:15:51] Speaker 00:
the antagonist must be extremely specific to the CGRP receptors located in cerebral arteries to avoid potential deleterious side effects caused by blocking other vascular and nonvascular CGRP receptors.

[00:16:03] Speaker 00:
In other words, this is a peptide that does a number of things in the body.

[00:16:06] Speaker 00:
If the focus is on shutting off its ability to activate one receptor, then targeting the ligand itself potentially has significant downstream implications, and that has consequences for safety.

[00:16:19] Speaker 00:
And especially given that this is the body's natural rescue mechanism for ischemic shock.

[00:16:27] Speaker 00:
I'm just going to finish this sentence if I may.

[00:16:30] Speaker 04:
You can finish your thought and use a little more if you want to.

[00:16:34] Speaker 00:
Thank you.

[00:16:34] Speaker 00:
I appreciate that, Your Honor.

[00:16:37] Speaker 00:
The, if this is the body's natural rescue mechanism, and this has a much longer half-life, certainly than the small molecule antagonists, but also,

[00:16:46] Speaker 00:
even then the aptamers, which are another comparator that the board referred to, aptamers have a half-life of hours to days, appendix 10309, whereas the full-length antibody has a much, much longer half-life, and that has significant consequences for safety.

[00:17:05] Speaker 00:
The skilled artisan would take into account in deciding what path to explore, lumping together the entire quote-unquote CGRP pathway

[00:17:14] Speaker 00:
is an oversimplification, and the board, looking at these disparate references, didn't identify substantial evidence to justify the obviousness combination.

[00:17:25] Speaker 00:
I've not said anything about objective indicia, but unless the court has questions about our submission on that, I'm prepared to rest on our briefs on that subject.

[00:17:37] Speaker 04:
We will save the remainder of your time, Mr. Jay.

[00:17:41] Speaker 04:
Mr. Raich?

[00:17:44] Speaker 01:
Thank you, Your Honor.

[00:17:45] Speaker 01:
The board's judgment should be affirmed.

[00:17:47] Speaker 01:
The board found it's a fact that a person of ordinary scale would have been motivated to apply the technique of antibody humanization developed in the 1980s to anti-CGRP antibodies, which were known in the literature and even commercially available by 2005.

[00:18:02] Speaker 01:
The board's finding was supported by substantial evidence

[00:18:06] Speaker 01:
Reflecting the routine nature of this combination, TEVA does not dispute reasonable expectation of success or disclosure of all elements in the claim in the prior art.

[00:18:15] Speaker 01:
And I'd like to turn specifically to Wimala Lawntz and Tan.

[00:18:20] Speaker 01:
So TEVA's factual arguments fail to demonstrate a lack of substantial evidence support because they run squarely into the board's detailed analysis of each of these references.

[00:18:31] Speaker 02:
Council, before you get into that, can I ask a question about

[00:18:34] Speaker 02:
the hypothetical that I posed to your friend on the other side.

[00:18:37] Speaker 02:
Do you agree with him that on this record there's no dispute that what we are talking about is the use of these antibodies in a human?

[00:18:52] Speaker 01:
No, Your Honor.

[00:18:53] Speaker 01:
And so Teva's experts testified that antibody humanization would have been needed before the antibodies could be administered to patients.

[00:19:02] Speaker 01:
And so, for example, while the motivation ultimately is therapeutic, humanized antibodies would have needed to have been made, they would have been needed to have been tested in vitro, and they would have needed to be tested in animals before ultimately satisfying the treatment goal.

[00:19:17] Speaker 01:
The board addresses this at Appendix 17, Note 20.

[00:19:23] Speaker 01:
So turning then to Wimalawansa,

[00:19:27] Speaker 01:
There's a heading in Wimolawansa, Therapeutic Potentials of CGRP Antagonists.

[00:19:33] Speaker 01:
And under that heading, Wimolawansa expressly discloses humanized anti-CGRP monoclonal antibodies, the subject matter of TEVA's claims.

[00:19:41] Speaker 01:
Wimolawansa also identifies CGRP as a potential causative factor in migraine and other diseases.

[00:19:48] Speaker 01:
The board's finding that Wimolawansa supported motivation to humanize

[00:19:53] Speaker 01:
anti-CGRP antibodies for diseases such as migraine was thus robustly supported.

[00:19:57] Speaker 01:
So there are three important fact findings that I think outweigh Teva's arguments with an attempt, their attempts to limit Wimowalansa.

[00:20:09] Speaker 03:
What do you say in response to Mr. Jay's reliance on the Senate at the end of the carryover paragraph at Appendix 6587 of Wimowalansa?

[00:20:22] Speaker 03:
This is the sentence that says these data warrant further studies in an animal model of sepsis to determine whether blocking CGRP receptors with specific antagonists, i.e., his argument being that that indicates that the earlier references to CGRP antagonists was limited to receptors.

[00:20:43] Speaker 01:
I mean, I just think there's substantial evidence from the board to indicate that that's not the case.

[00:20:48] Speaker 01:
And first of all, sepsis isn't the only... Well, maybe if you can explain why.

[00:20:53] Speaker 01:
Sure.

[00:20:53] Speaker 01:
So first of all, Lilly's experts in reviewing Wimolawansa agreed with the interpretation of the board that Wimolawansa encouraged antibodies generally and not just receptor-limited antibodies.

[00:21:08] Speaker 01:
And then I think another important point is that the board's findings were consistent with other contemporaneous prior art in the migraine field, which likewise cited Wimolawansa

[00:21:18] Speaker 01:
for its teaching regarding antagonizing the CGRP ligand.

[00:21:23] Speaker 01:
And so, at Appendix 6429, and this is in the 1749 records, Your Honor, there's a reference called Bader.

[00:21:31] Speaker 01:
And it states that the CGRP ligand has recently attracted attention as a novel target in acute migraine treatment.

[00:21:38] Speaker 01:
And to support that statement, it cites the Wimla-Lawrence record.

[00:21:42] Speaker 01:
And this is reflected in the board's opinion at page 81, note 65.

[00:21:51] Speaker 01:
So we have both expert support and contemporaneous art interpreting wimolawansa consistent the way that Lily interpreted it before the board.

[00:21:59] Speaker 01:
So Tev's argument that wimolawansa would have discouraged humanized anti-CGRP antibodies simply because more data remained to be generated just can't be squared with wimolawansa's statement.

[00:22:09] Speaker 01:
the humanized monoclonal antibodies should be explored.

[00:22:14] Speaker 01:
So the board appropriately credited this express statement of encouragement and again heard supporting testimony from Lilly's clinical expert.

[00:22:22] Speaker 01:
I'd like to turn now to the TAN reference.

[00:22:26] Speaker 01:
So Teva's factual challenges to the TAN reference similarly lack merit.

[00:22:31] Speaker 01:
Teva argued in its opening brief that TAN failed to show immunoblocade with anti-CGRP antibodies

[00:22:37] Speaker 01:
in a particular assay based on just a subset of TAN's experimental results, but have failed to dispute three factual findings providing substantial evidence for the board's motivation findings.

[00:22:49] Speaker 01:
First, the board found that TAN disclosed achieving a 16% response with a longer two-hour incubation time and a higher dose.

[00:22:58] Speaker 01:
The board found that this was a positive trend in results, that's a quote, showing that TAN's anti-CGRP antibody has activity in vivo

[00:23:07] Speaker 01:
The board heard testimony on this point from all three of Willy's experts, a clinician, an antibody engineer, and an antibody pharmacologist.

[00:23:15] Speaker 01:
Second, the board credited TAN's disclosure of specific recommendations to use higher doses and longer incubation times to further improve antibody activity.

[00:23:25] Speaker 01:
Again, the board heard testimony about TAN's recommendations from all of Willy's experts.

[00:23:30] Speaker 01:
As the board concluded, TAN expressed optimism that higher concentrations or longer incubation times would achieve the desired results for anti-CGRP activity.

[00:23:41] Speaker 01:
That's at A57.

[00:23:43] Speaker 01:
And third, the board found a lack of deterrence in the prior art after TAN as researchers continued to propose anti-CGRP antibodies for treating diseases such as migraine, psoriasis, neurogenic inflammatory pain, and eye pain

[00:23:59] Speaker 01:
This is objective evidence that TAN did not have the effect, as Teva argues, of discouraging or teaching away in the prior art.

[00:24:09] Speaker 01:
And I guess the final point that I would make on this is that Teva does not dispute that it itself used higher doses and longer incubation times just as TAN recommended.

[00:24:21] Speaker 01:
Teva even cited TAN in the specific example where it used higher doses and longer incubation times.

[00:24:27] Speaker 01:
doing exactly what the prior art says to do is not inventive, it is obvious.

[00:24:34] Speaker 03:
What response do you have to the argument that your opposing counsel makes that TAN was 10 years prior to the invention in this case, suggesting that if TAN had really been as revelatory as your argument is, that surely it wouldn't have taken 10 years for someone to come up with the idea?

[00:24:57] Speaker 01:
I think, Your Honor, there are sort of two fundamental responses to that.

[00:25:01] Speaker 01:
The first is more factual in nature, is that people continue to explore CGRP and the intervening period after TAN.

[00:25:09] Speaker 01:
And in particular, there were studies that showed that the safety concerns that have emphasized

[00:25:19] Speaker 01:
were potential concerns and not actual concerns.

[00:25:22] Speaker 01:
So I think in terms of balancing safety and efficacy, there was just a finding that the safety concerns were not perhaps at all significant.

[00:25:37] Speaker 01:
And I think the second thing I think that's important is just, you know, legally there is case law that says, for example, that

[00:25:48] Speaker 01:
It's not, you know, it's not so much time that's not necessarily just positive.

[00:25:52] Speaker 01:
I think this comes up in Graham versus John Deere.

[00:25:55] Speaker 01:
And I think that the, you know, to my point in terms of an important finding with the Olson study, and that actually involved a clinical success by blocking the CDRP pathway.

[00:26:06] Speaker 01:
And so I think with all of those things, all signed in 2005.

[00:26:13] Speaker 01:
That's right, Your Honor.

[00:26:16] Speaker 01:
The Olsen study itself involved antagonizing the receptor, but I think there were quite a few statements in the prior art that antagonizing the receptor and antagonizing the ligand were viewed as alternatives.

[00:26:31] Speaker 04:
Counsel, what about commercial success?

[00:26:33] Speaker 04:
There are a couple of products on the market that are dominated by this claim, isn't that correct?

[00:26:42] Speaker 01:
That's right, Your Honor.

[00:26:44] Speaker 01:
And so I think there's a couple of responses to that.

[00:26:47] Speaker 01:
First of all, the claims are incredibly broad.

[00:26:51] Speaker 01:
These are exceedingly broad claims.

[00:26:54] Speaker 01:
And so there is a nexus problem between these commercial antibodies that have very specific properties, very specific amino acid sequences that confer particular results.

[00:27:07] Speaker 01:
And the board agrees that these were material properties.

[00:27:10] Speaker 01:
And I will point out that Teva has separately claimed and separately patented antibodies limited by sequence.

[00:27:17] Speaker 01:
So these are not the claims that we're talking about here.

[00:27:21] Speaker 04:
What if this were a generic compound claim with a nucleus and a recitation of substituents and fraud, but the marketed products were

[00:27:37] Speaker 04:
come within the scope of that claim.

[00:27:41] Speaker 04:
Would you say that a broad generic compound claim, structurally claimed, and that's important, structurally claimed, the compounds being within the scope of the claim, would you say that the bread would disqualify commercial success from being effective?

[00:28:02] Speaker 01:
I think that that is a reasonable interpretation of the case law in terms of the presumption of nexus.

[00:28:09] Speaker 01:
I think that one could make a showing in terms of a specific correlation between elements that were new and novel in the claim and the specific property that was leading to the commercial success.

[00:28:22] Speaker 01:
That's simply just not the case here.

[00:28:24] Speaker 01:
And just to echo the point,

[00:28:28] Speaker 01:
Teva's claims are entirely functional.

[00:28:30] Speaker 01:
These are not structural claims, so I just want to draw a divide between our facts and even the facts of your hypothetical.

[00:28:38] Speaker 01:
I think the other point on commercial success is that even beyond NECTF considerations, the board here found that Teva's secondary considerations evidence was weak on the merits and entitled to little or no weight for independent reasons.

[00:28:53] Speaker 02:
Council, do you agree, though, that the board seemed to

[00:28:56] Speaker 02:
to overstate the holding of Fox Factory?

[00:29:01] Speaker 01:
I don't think that the board overstated the holding of Fox Factory.

[00:29:07] Speaker 01:
I think it applied it in determining that there were really material characteristics, critically material characteristics, that were elements of the commercial antibodies that are not reflected in the claims, and that that should appropriately

[00:29:26] Speaker 01:
to eliminate any presumption.

[00:29:30] Speaker 01:
And I think it is important.

[00:29:31] Speaker 04:
Fox Factory didn't involve chemical or biological materials, which is where you've got the question of a generic claim, as you and I just discussed.

[00:29:45] Speaker 04:
Fox Factory dealt with a mechanical gadget where another aspect of the commercial product

[00:29:55] Speaker 04:
was not covered by the claim.

[00:29:59] Speaker 01:
I agree, Your Honor, that is factually correct.

[00:30:04] Speaker 01:
But I think in terms of thinking about the material elements that are representative of these antibodies, in addition to sequence that I mentioned, there are also antibody fragments, which Tebazone experts testify would be useless as therapeutics.

[00:30:25] Speaker 01:
There's antibody class, where the claims encompass antibodies from several classes that had never been used in any FDA-approved therapeutics.

[00:30:34] Speaker 01:
And there's an antibody affinity, where even the narrowest claims encompass antibodies with 5,000 times weaker binding affinity than a Joby, which is Tevis commercial antibody.

[00:30:47] Speaker 04:
In other words, as you point out, these are functional claims.

[00:30:51] Speaker 01:
Yeah, these are absolutely functional claims.

[00:30:53] Speaker 01:
I mean, these claims are not limited in any way by structure.

[00:30:57] Speaker 01:
These claims are directed to the idea of any antibody that would antagonize CGRP.

[00:31:06] Speaker 01:
These are functional claims.

[00:31:16] Speaker 01:
Are there any other further questions around or otherwise?

[00:31:19] Speaker 01:
we respectfully request.

[00:31:21] Speaker 02:
I have one question about the licensing issue.

[00:31:25] Speaker 02:
You know, I understand that where you've got very broad licenses and you don't have anything that would sort of steer you to the licensing agreement having been entered into because of the particular patented issue, then obviously we can't say that the licenses have that much meaning.

[00:31:46] Speaker 02:
But here,

[00:31:48] Speaker 02:
the particular patents at issue were the ones that prompted the licensing discussions and agreement in the first place.

[00:31:56] Speaker 02:
Isn't that right?

[00:31:59] Speaker 01:
Well, I think in this instance it was actually a European patent because there was a European opposition proceeding.

[00:32:07] Speaker 02:
Right, but it related to the exact same invention, correct?

[00:32:13] Speaker 01:
I think it was a related patent application.

[00:32:17] Speaker 01:
But I think here, again, the appropriate test was whether there was a nexus between the patent and the licensing activity itself.

[00:32:26] Speaker 01:
Here, none of the six patents at issue, there was no showing made that those patents had a nexus with a specific licensing activity.

[00:32:38] Speaker 01:
And moreover, the evidence here showed, and the board found, that

[00:32:43] Speaker 01:
Even if all six of the challenged patents were invalidated, all of the licensees' payment obligations would continue unabated on the other 182 patents that were involved.

[00:32:54] Speaker 02:
Right, but if, you know, what you've got is that there's litigation relating to particular patents.

[00:33:01] Speaker 02:
And then you, so you say, let's settle that, let's enter into a licensing agreement.

[00:33:05] Speaker 02:
And the normal common practice is to say, well, we want something that covers the whole landscape.

[00:33:12] Speaker 02:
So we cover the landscape regardless of whether the other patents are any good or meaningful.

[00:33:17] Speaker 02:
And so what my problem is is that the board seemed to simply say, just because there's a lot of patents in the ultimate settlement, in the ultimate license, that therefore you can't have a nexus to the very patents that prompted the discussions in the first place.

[00:33:36] Speaker 01:
Well, again, I think

[00:33:38] Speaker 01:
First of all, I mean, the Board had several lines of reasoning to its analysis, and one of which ultimately is just even if you accept that there is some kind of nexus here, the evidence was still weak as compared to the evidence of obviousness that was, that we've been discussing and that the Board found with respect to the prior art.

[00:34:03] Speaker 01:
So that's the first thing.

[00:34:04] Speaker 01:
And second of all,

[00:34:08] Speaker 01:
I mean, Teba made no effort, no showing that the license was the result specifically of these challenge claims, which are these incredibly broad claims.

[00:34:20] Speaker 01:
And so while there may be some kind of formal relationship between the patent that was the subject of the European opposition, they didn't actually make a showing that these claims, the challenge claims, were important to the licensing activity.

[00:34:36] Speaker 01:
Ultimately, the license included a number of different patent families, not just this particular patent family.

[00:34:44] Speaker 01:
And so some sort of showing should have been made, and it was not, Your Honor.

[00:34:53] Speaker 04:
Thank you, Mr. Rach.

[00:34:56] Speaker 04:
We will hear from you in a few moments.

[00:34:58] Speaker 04:
In the meantime, Mr. Jay has some rebuttal time.

[00:35:03] Speaker 00:
Thank you, Your Honor.

[00:35:04] Speaker 00:
Just a few quick points.

[00:35:07] Speaker 00:
On Wimla 1st, the sentence at the end of the reference that we've discussed a couple of times, I just want to point out that in that sentence,

[00:35:16] Speaker 00:
If you read to the end of the sentence, you'll see that the role of these antibodies should be explored, and then the reference says, with respect to, and refers back to the several medical conditions that it has discussed above, including such as septic shock syndrome, and as the colloquy with Judge Bryson brought out, that's specifically referring to receptor antagonists.

[00:35:39] Speaker 00:
It couldn't be plainer.

[00:35:42] Speaker 00:
the positive trend in results of finding that my friend referred to.

[00:35:47] Speaker 00:
Lily's expert admits at 21018 of the appendix that that's not a significant finding.

[00:35:55] Speaker 00:
It's based on data in two wraps and that he would have, he admitted that he would have to repeat that in order for, repeat that study in order to draw any conclusions from it.

[00:36:06] Speaker 03:
The board- Oh, I'm sorry.

[00:36:07] Speaker 03:
Mr. Jay, what was that appendix reference?

[00:36:09] Speaker 03:
I missed it.

[00:36:10] Speaker 00:
I'm sorry, Your Honor, it's 21018.

[00:36:11] Speaker 00:
Okay, good.

[00:36:14] Speaker 00:
And the board kind of brushes past this at pages 43 to 44, so it refers to it but doesn't explain why that admission isn't damaging.

[00:36:24] Speaker 00:
Just to respond to another thing my friend said, we do dispute the point and we did dispute in our reply brief the notion that TEVA relied on TAN's path.

[00:36:33] Speaker 00:
The citation to example three

[00:36:38] Speaker 00:
shows only that TEVA used the same control, a receptor antagonist called CGRP837, as in the TAN experiment.

[00:36:46] Speaker 00:
That's not at all the same thing as following the TAN path.

[00:36:49] Speaker 00:
On VATER, I just want to point out quickly that the board at note 54 said the same thing that it said about the IBN, that it was not considering whether the success with aptamers would motivate someone to believe that an anti-CGRP ligand antagonist would be effective, just motivated to study antagonism.

[00:37:10] Speaker 00:
Turning to the secondary considerations,

[00:37:13] Speaker 00:
The test has always been, you know, reasonably commensurate.

[00:37:17] Speaker 00:
As Fox Factory said, it's a spectrum.

[00:37:19] Speaker 00:
It's not perfect correspondence.

[00:37:21] Speaker 00:
And here, the points that my friend tried to bring up saying that aspects that are unclaimed are responsible for the commercial success.

[00:37:30] Speaker 00:
This is not correct.

[00:37:31] Speaker 00:
I just want to make two quick points about that.

[00:37:34] Speaker 00:
One is that the commercial products have different sequences from each other.

[00:37:37] Speaker 00:
So it's difficult to claim that the sequence is what's driving the success.

[00:37:42] Speaker 00:
The second about affinity is to just note that in the definition of anti-CGRP antagonist antibody at column 14, starting at note 9, sorry, at line 19, binding affinity is actually built into the definition in the claim term.

[00:38:03] Speaker 00:
Thank you.

[00:38:05] Speaker 04:
We appreciate the arguments of both counsel.

[00:38:08] Speaker 04:
The case is submitted.