[00:00:00] Speaker 00:
I have two argued cases today, but before we get to the arguments, we have a motion from Judge Taranta.

[00:00:10] Speaker 03:
I want to move the admission of Stephen Michael Siegel, who is a member of the bar and is in good standing with the highest court of Maryland.

[00:00:21] Speaker 03:
He is also currently my law clerk.

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And I will attest to what a fine lawyer, advisors,

[00:00:29] Speaker 03:
scholar, colleague he has been.

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And I welcome him to the bar and know that everybody who will deal with him throughout his career will be honored to do so.

[00:00:44] Speaker 00:
I think we'll grant the motion.

[00:00:48] Speaker 00:
And I've heard from my own law clerks

[00:00:53] Speaker 00:
Uh, the same things about you that, uh, Judge Taranto mentioned.

[00:00:57] Speaker 00:
I haven't had the privilege of working with you personally, but I'm glad to have you as a member of the bar of this court and motion to admit it's granted and, uh, you may take the oath.

[00:01:11] Speaker 05:
Thank you for your guidance.

[00:01:15] Speaker 05:
Do you follow, swear, or affirm that you will comport yourself as an attorney and counsel of this court?

[00:01:18] Speaker 05:
I've written an authority to all, and he will support the Constitution of the United States of America.

[00:01:25] Speaker 05:
I do.

[00:01:25] Speaker 05:
Welcome to the bar of the United States Court of Appeals for the Federal Circuit.

[00:01:32] Speaker 00:
All right, that brings us to our first argued case, which is number 141634, Prometheus Laboratories versus Roxanne Laboratories Inc., Mr. Cocktail.

[00:01:45] Speaker 01:
Thank you, Judge Dyke.

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It may please the court.

[00:01:48] Speaker 01:
The 770 patented issue is called, quote, medicaments for the treatment of non-concipated female irritable bowel syndrome.

[00:01:55] Speaker 01:
The PTO found it valid and non-obvious, but the district court disagreed by cobbling together pieces of several different studies.

[00:02:03] Speaker 01:
That was wrong.

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Section 282 requires

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that a patent issued by the PTO, quote, shall be presumed valid.

[00:02:10] Speaker 01:
And Microsoft versus I4I makes clear that invalidity must be proven by clear and convincing evidence.

[00:02:16] Speaker 00:
What is the test here?

[00:02:18] Speaker 00:
I mean, this seems to me to be a kind of a genus species situation in which the 800 patent at the genus also, it was used in treatment of a broad

[00:02:33] Speaker 00:
class before the priority date here.

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And we have various cases involving geni or genuses, whatever it is, of chemical compounds, of ranges.

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We have ABV which dealt with a situation similar to this.

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Do you agree that we're dealing with a genus species situation?

[00:03:00] Speaker 01:
We do.

[00:03:00] Speaker 01:
We think that is one of the key mistakes that the district court made, a legal error in this case, disregarding essentially the teaching of your opinion for the court in AbbVie.

[00:03:09] Speaker 01:
Because what AbbVie says is that it is very clear that just because a genus is patented doesn't mean that a species of that genus isn't also

[00:03:17] Speaker 01:
patentable, and non-obvious.

[00:03:20] Speaker 00:
Well, that's one of the few things that everybody would seem to agree on, that it's not automatic invalidation.

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But the question is, what is the test for non-obviousness in that context?

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The way I would read every is that you've got to show that there's an inability to envision the smaller species and also that there are unexpected results.

[00:03:46] Speaker 00:
It seems to be, you know, you go to Peeling and these other cases, it seems to be a bit of a different test than you ordinarily have in the obviousness context.

[00:03:56] Speaker 01:
We agree that that is the test in ABVI and that that should be applied here.

[00:04:01] Speaker 01:
We don't think that's what the district court said, by the way.

[00:04:02] Speaker 01:
The district court, we think, read, didn't anticipate ABVI and instead said that subset claims essentially aren't patentable.

[00:04:10] Speaker 01:
But if we took the ABVI test, which is essentially, you know, could we envisage this claim

[00:04:16] Speaker 01:
We think it's different than an Appian, which it was just literally sicker patients or not sicker patients.

[00:04:21] Speaker 01:
Here the question is not sicker versus non-sicker.

[00:04:24] Speaker 01:
The innovation in the 770 patent is four different limitations.

[00:04:28] Speaker 01:
The first is it excluded IBSC, that is IBS constipated patients.

[00:04:32] Speaker 01:
The second is it limited it to women.

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The third is that it limited treatment to only those who had symptoms of six months.

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And the fourth is that it limited those to moderate abdominal pain or more.

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Now the question then is,

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Either, could you anticipate that?

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Was that something that was understood at the time?

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And did this yield unexpected results?

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And here, Judge Steick, we think the PTO is very clear.

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This is the Joint Dependix, page 674.

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Once these limitations were introduced, there were unexpected results that happened.

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The cost-benefit, the risk-benefit ratio changed unexpectedly and markedly.

[00:05:08] Speaker 00:
And that... That may be true.

[00:05:11] Speaker 00:
with respect to women, if we can just put that aside for a moment, the other three criteria here, you're using it to treat diarrhea as opposed to constipation, the six-month timeframe and the moderate pain, those limitations don't show unexpected results, do they?

[00:05:32] Speaker 01:
Well, they do, Judge Steichen.

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This is joint effects phase 6-74.

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This is what the PTO found.

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Quote, the evidence now with record shows that selecting a patient population of women

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suffering from IBSD for at least six months increases the benefit-risk ratio for elistron.

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The popular demand of patients for elistron showed the invention meets a need that was long felt in the art.

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Unexpectedly favorable results have been obtained.

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And so it's not just one thing, it's all.

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And we think that's one of the other legal errors that the district court made in this case by not thinking through that these limitations all work together and asking the KSR question, which is what would a reasonable person in the art have done

[00:06:11] Speaker 01:
taken all of the different studies at the time where they've been motivated to combine them in this way.

[00:06:16] Speaker 01:
The best evidence to show that the district court was wrong about its conclusion is what happened in 2000, because the drug was introduced without these four restrictions, and we have massive side effects, horrible deaths ensuing, and it took the innovation of the 770 patents issued in 2001 to bring the drug back on the market in 2002.

[00:06:37] Speaker 01:
That's the innovation.

[00:06:38] Speaker 03:
There was some testimony

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I think from Dr. Howden, that there is a disparity between the claim requirements of the 770 and the indications, the full set of indications in the label upon the introduction.

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How do we know that the markedly more beneficial benefit cost or benefit risk ratio is attributable to

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New York claims as opposed to the additional items in the list of indications.

[00:07:17] Speaker 01:
I'd say two things, one on the facts and one on the law.

[00:07:19] Speaker 01:
On the law, we think the district court got it flatly wrong by thinking that for commercial success or the reintroduction of the drug, that the patent had to be the sole cause of the success.

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This court's decision in the Colichem and other decisions is very clear that as long as it's a contributing factor, that alone is enough.

[00:07:39] Speaker 01:
We think that was a reversible error.

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And second, on the facts of your question, Judge Toronto, we do think that the 770 patent, for all practical purposes, is incorporated into the REMS.

[00:07:49] Speaker 01:
That's what the district court found in the Markman hearing at Joint Appendix, page 400,

[00:07:54] Speaker 01:
clear as day that the reintroduction of the drug followed the contours of the 770 patent.

[00:08:00] Speaker 01:
And if you just look at the label and you look at the 770 patent, you see the same thing.

[00:08:05] Speaker 01:
So the 770 patent, which is a joint appendix, page 71, excludes IVFC, that is, IVF constipated patients, and it excludes men.

[00:08:15] Speaker 01:
The label, which is a joint appendix, page 888, does the same thing.

[00:08:20] Speaker 01:
The six months language is really very similar.

[00:08:22] Speaker 01:
The label says,

[00:08:24] Speaker 01:
that it is for IBSD patients, quote, generally lasting six months or longer.

[00:08:28] Speaker 01:
That's a Joint Appendix 888.

[00:08:29] Speaker 03:
What about the ones that I think that Dr. Howden focused on, what I think in his testimony he described as in the black box, and I think was referring to what's at 789 in Joint Appendix, PTX123.

[00:08:44] Speaker 03:
I take it the black box is this thing there.

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And there are other indications there about if you,

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Physicians should instruct patients to immediately report constipation or symptoms of one thing or another.

[00:08:58] Speaker 03:
Aren't those meaningful distinctions?

[00:09:00] Speaker 01:
Look, our claim is not at all that the patent alone allowed the drug, that that is solely responsible for the commercial success.

[00:09:08] Speaker 01:
But their burden is to show by clear and convincing evidence that this wasn't a contributing cause to the drug being reintroduced.

[00:09:18] Speaker 03:
Can I ask a change subject?

[00:09:21] Speaker 03:
And this is a question I perhaps should ask the other side, but I want your take on it first.

[00:09:26] Speaker 03:
In the red brief at page 17, the other side says, at the bottom of the page, patients having all of the characteristics identified in the claimed method were treated with Elocitron before October 1997.

[00:09:44] Speaker 03:
There's no citation there.

[00:09:48] Speaker 03:
true, supported by the evidence?

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If it is, why is there not an anticipation?

[00:09:52] Speaker 03:
I'm trying to understand what to make of this declaration.

[00:09:56] Speaker 01:
I'm not sure whether there's any evidence in the record of whether that's true or not, but I certainly think even if it were true that that happened, that that wouldn't bear on the question here, which is whether or not there was some innovation that by selecting this patient population, this subset, you narrowed the risk-benefit ratio

[00:10:18] Speaker 01:
substantially, to the point where for the first time in its history, to our knowledge, the FDA allowed reintroduction of this drug.

[00:10:25] Speaker 03:
Right, but I mean, suppose it were true that there were patients, women, six months, moderate pain, predominantly diarrhea, who were in fact being given this drug beforehand.

[00:10:41] Speaker 03:
And nevertheless, you think that this can be

[00:10:47] Speaker 03:
non-obvious to say, give this drug to women only, the diarrhea predominant ones, and then the other conditions which don't come for whatever the significance or non-significance would be with only kinds of limitations.

[00:11:04] Speaker 01:
I do, and I think that follows straightforwardly from Judge Dyke's opinion in ABDI on the unexpected results prompt.

[00:11:10] Speaker 00:
So what you're saying is that you're agreeing that there was a genus

[00:11:15] Speaker 00:
that included this species in the prior art.

[00:11:19] Speaker 00:
And you're saying that nonetheless, the species is patentable over the prior art.

[00:11:23] Speaker 01:
That is correct.

[00:11:23] Speaker 01:
There's a very large genus in the 800 patent.

[00:11:26] Speaker 01:
The 800 patent is found at joint mechanics pages like 775 to 800.

[00:11:30] Speaker 01:
It is tens of thousands of words long.

[00:11:33] Speaker 01:
It includes using elicitron, not just for IBS, which is mentioned in literally just those three words, but things like anxiety, schizophrenia, substance abuse, flatulence, nausea,

[00:11:44] Speaker 01:
100 different ailments.

[00:11:46] Speaker 01:
And our point is that it was the innovation of the 770 patent by limiting the subset to this group of people that allowed the drug to be brought back on the market.

[00:11:57] Speaker 00:
When you're saying the unexpected results was the ability to bring it back on the market, is that essential?

[00:12:04] Speaker 01:
I think it's a good way of trying to understand what would a POSA, here a person, a gastroenterologist in 1997 would have thought.

[00:12:12] Speaker 01:
Would they have thought it'd be obvious

[00:12:14] Speaker 01:
to have these four limitations.

[00:12:16] Speaker 01:
We think both the 2000 introduction of the drug without those limitations, as well as the... I'm not sure that's the test.

[00:12:27] Speaker 00:
I would have thought that the test would be whether there were unexpected results, that it was a dual test that said you have to be able to say that you couldn't envision the species.

[00:12:39] Speaker 00:
You've got a problem with that because I think that there's a fairly

[00:12:44] Speaker 00:
fairly obvious to look at the earlier group being treated and single out the women.

[00:12:52] Speaker 00:
But put aside that for a moment.

[00:12:54] Speaker 00:
But turn to the unexpected results that you'd have to show that there were unexpected results from imposing these limitations.

[00:13:02] Speaker 00:
And I guess what you're saying is the unexpected results here are the ability to get this approved when the broader

[00:13:10] Speaker 00:
treatment regimen was disapproved.

[00:13:14] Speaker 01:
We're not saying it was the ability to get it approved, Judge Doug.

[00:13:16] Speaker 00:
No.

[00:13:16] Speaker 01:
What we're saying is that that's one barometer to show unexpected results.

[00:13:21] Speaker 01:
Probably the best barometer, those with the PTO itself found, and they have to disprove that barometer.

[00:13:25] Speaker 03:
The barometer of the benefit-risk calculation is being quite different.

[00:13:28] Speaker 01:
Exactly.

[00:13:28] Speaker 03:
That's the underlying fact and the FDA approval is the evidence of that.

[00:13:33] Speaker 01:
That is the underlying evidence of what

[00:13:36] Speaker 01:
of the unexpected result.

[00:13:37] Speaker 01:
Exactly.

[00:13:38] Speaker 01:
And that's what the PTO found.

[00:13:40] Speaker 01:
And we think that shows that on the first part of your question, which is it was obvious to anticipate this.

[00:13:46] Speaker 01:
No, not at all.

[00:13:46] Speaker 00:
Envision.

[00:13:47] Speaker 01:
Envision this.

[00:13:49] Speaker 01:
Envision this.

[00:13:49] Speaker 01:
We think not at all.

[00:13:50] Speaker 01:
And we think once you go through the district court's prior studies, it's just like this court's decision of cycle benzoprene.

[00:13:57] Speaker 01:
It doesn't actually hold up what they're saying.

[00:13:59] Speaker 01:
So the district court's cobbling together not one or two things, but 15 different studies

[00:14:04] Speaker 01:
to try and say, for example, the IBSC limitation was anticipated, and there's really very little support for that.

[00:14:12] Speaker 01:
Really, the district court has two baskets of studies.

[00:14:15] Speaker 01:
One is a basket of studies about 5-HT3 receptor antagonists in general.

[00:14:20] Speaker 01:
That's a large class.

[00:14:22] Speaker 01:
The district court's preferred study on this tally adjoined to 5852 says there's at least nine of these, including cocaine.

[00:14:29] Speaker 01:
I don't think that says anything about the effect of this particular receptor antagonist, and that's indeed what Talley himself says.

[00:14:38] Speaker 03:
Can I ask you about this?

[00:14:42] Speaker 03:
What difference does it make whether one reads the claim, in particular with its reference to a female population, as having or not having implicitly the kind of

[00:14:58] Speaker 03:
excluding men the way there is this excluding the constipation predominant.

[00:15:07] Speaker 03:
Why would it make any difference if it said excluding men as opposed to we've identified a subclass for whom

[00:15:15] Speaker 03:
We know that the benefit-risk calculus is really good.

[00:15:18] Speaker 03:
We don't know about the rest of the world.

[00:15:20] Speaker 03:
So meanwhile, do these.

[00:15:22] Speaker 01:
We think we would win either way, Judge Toronto.

[00:15:24] Speaker 01:
That is, it's common ground between all of us that it excludes IVFC patients.

[00:15:30] Speaker 01:
That alone is enough of an innovation.

[00:15:32] Speaker 01:
It's a huge innovation in allowing the drug to be safe and effective.

[00:15:37] Speaker 01:
So even whether it's men or women, we don't think that alone is enough of an innovation.

[00:15:42] Speaker 01:
Now with respect to the exclusion, we think the district court's absolutely right in joint appendix page 404 when it said this patent, by limiting it to women, means to exclude women.

[00:15:53] Speaker 01:
Now whether or not you could read it one way or the other, we think doesn't matter.

[00:15:58] Speaker 01:
At the end of the day, it's still a limitation.

[00:16:00] Speaker 01:
It's still an innovation in the patent.

[00:16:03] Speaker 01:
Beforehand, in 2000, the drug was prescribed

[00:16:06] Speaker 01:
to men and women under that 800 broad genus patent, and it took the innovation of the 770 patent to say, no, that's a mistake.

[00:16:13] Speaker 01:
Limit it to this subset of people.

[00:16:16] Speaker 01:
That's what allows the risk-benefit ratio to be at its best.

[00:16:20] Speaker 01:
And if you look at, for example, the 2000 label, when the drug was introduced, it said that it could be used for constipated patients.

[00:16:29] Speaker 01:
It's joint appendix 876.

[00:16:30] Speaker 01:
It said you can manage that constipation

[00:16:33] Speaker 01:
through things like laxatives and so on.

[00:16:36] Speaker 01:
The innovation of this patent is to say, no, you have to blanketly exclude these people because if you give it to them, that risk-benefit ratio doesn't work.

[00:16:46] Speaker 01:
That's the innovation.

[00:16:47] Speaker 01:
That's what, when you're asking, did the prior, was that something that would have been envisioned in 1997 by a POSA judge, the answer is no.

[00:16:56] Speaker 01:
The best evidence of that is it didn't happen three years later in 2000.

[00:17:01] Speaker 01:
Rather, the drug was introduced

[00:17:03] Speaker 01:
wholesale to everyone.

[00:17:05] Speaker 01:
And indeed, when it was yanked off the market, it was also blankly withdrawn.

[00:17:08] Speaker 01:
It wasn't left on the market with these four limitations.

[00:17:12] Speaker 01:
We think that's a pretty good test, pretty good evidence to indicate that that was something that wasn't envisioned at the time.

[00:17:20] Speaker 00:
Okay.

[00:17:22] Speaker 00:
Well, you're out of time.

[00:17:22] Speaker 00:
We'll give you two minutes for rebuttal.

[00:17:32] Speaker 04:
May I please the court?

[00:17:35] Speaker 04:
We agree that this case presents fundamentally a genus species issue.

[00:17:43] Speaker 04:
And we agree with the test as set forth in ADVI.

[00:17:47] Speaker 04:
But I think it is clear that that test has not been satisfied.

[00:17:52] Speaker 04:
It is absolutely, it is trivial to imagine the subset, the women, the IVF patients

[00:18:02] Speaker 04:
that are diarrhea predominant, that are women, and that had suffered moderately severe pain and symptoms for at least six months.

[00:18:11] Speaker 04:
Those constituted the bulk of IBS patients in the prior art.

[00:18:16] Speaker 04:
It is also there is nothing.

[00:18:18] Speaker 02:
I understand that the bulk of the patients are women.

[00:18:21] Speaker 02:
Do you have any numbers on which are more IBSD predominant versus IBSC predominant?

[00:18:28] Speaker 04:
Nothing specific.

[00:18:29] Speaker 04:
My understanding is that IBSD is more predominant.

[00:18:35] Speaker 03:
Can I ask you this question, which I asked Mr. Katyal?

[00:18:40] Speaker 03:
You say on page 17, patients having all of the characteristics, not each one separately, but all together identified in the claim method were treated with elositron before October 1997.

[00:18:52] Speaker 04:
There were two studies in the record, the Foster study and the Bardham study.

[00:18:58] Speaker 04:
They are found at Foster's at 868 of the appendix, and Bardem is at 866 of the appendix.

[00:19:09] Speaker 04:
We should have tried those, and I apologize for not.

[00:19:12] Speaker 04:
There were clinical studies done on Olosetron, obviously, before the FDA.

[00:19:16] Speaker 04:
Before the priority date.

[00:19:17] Speaker 03:
And those all included?

[00:19:18] Speaker 03:
And testimony.

[00:19:21] Speaker 03:
And did those all establish that there were six months worth of symptoms?

[00:19:26] Speaker 03:
I didn't think so.

[00:19:28] Speaker 04:
I believe so.

[00:19:30] Speaker 04:
The record sites that I gave you just, Toronto, are the testimony of Roxanne's witnesses.

[00:19:43] Speaker 04:
And the testimony was that these studies would have included persons with at least six months of symptoms.

[00:19:51] Speaker 00:
Was there any evidence of unexpected results?

[00:19:55] Speaker 00:
Put aside the female.

[00:19:57] Speaker 00:
population, unexpected results of limiting it to these other three, that is, limiting it to the diarrhea patients, the moderate pain, and the six months of symptoms.

[00:20:10] Speaker 04:
I mean, first of all, it's our position that the patent doesn't limit it to those patients, that the only exclusion in the patent is the exclusion for IBSC, the constipation patients.

[00:20:21] Speaker 00:
I understand that, but let's assume there are arguments that it is limited to those.

[00:20:28] Speaker 00:
Is there anything in the record about unexpected results with respect to those three criteria?

[00:20:35] Speaker 04:
There is nothing unexpected about elocitron treating any member of that subclass.

[00:20:43] Speaker 04:
The Prior Art 800 patent taught that elocitron would treat the symptoms of IBS.

[00:20:49] Speaker 03:
But I take it, and it almost has to be the case in this context, that the results that we're interested in here are a comparison of benefits and risks.

[00:20:59] Speaker 03:
So is it not unexpected, as indicated by what happened to the drug in 2000, that without some narrowing of the patient pool,

[00:21:10] Speaker 03:
The benefit-risk calculus was a very unfortunate one.

[00:21:14] Speaker 04:
The benefit-risk calculus, I mean, this patent did nothing to solve the problem of these side effects.

[00:21:22] Speaker 03:
The incidents of side effects, how is it that the FDA allowed this back on the market with a set of indications that if not identical is awfully close to what's claimed here?

[00:21:33] Speaker 04:
There's no evidence in the record why the FDA took the action it did, but it is at least as plausible, if not more plausible,

[00:21:41] Speaker 04:
that the reason the FDA proved it was precisely the black boxes.

[00:21:46] Speaker 03:
What are the elements of that that are different from the claim requirement?

[00:21:51] Speaker 04:
It requires specific instructions and education both to physicians and to patients.

[00:21:58] Speaker 04:
On what?

[00:21:59] Speaker 04:
On the severe side effects.

[00:22:02] Speaker 04:
I mean, what was critical.

[00:22:04] Speaker 04:
And indeed, what the district judge found resulted in a diminishment of the severity of side effects.

[00:22:10] Speaker 04:
Not the incidents.

[00:22:11] Speaker 04:
Nobody knows what causes these things.

[00:22:13] Speaker 04:
And they have occurred at the same rate as they did before the product was withdrawn.

[00:22:19] Speaker 04:
But if they're less severe, that changes the benefit?

[00:22:22] Speaker 04:
But the district judge's finding was, and there are articles that explain this, the reduction in the severity resulted from doctors being more alert to the risks and monitoring their patients.

[00:22:37] Speaker 04:
I mean, there's a paper in the record which identifies that as the reason why the severity, not the incidence, but the severity of these adverse events has diminished.

[00:22:47] Speaker 04:
And those precautions, those monitoring precautions, the education precautions are in the label, but they are not in the patent.

[00:22:56] Speaker 00:
Could we back up a moment so I could better understand how this product came back on the market and what the FDA process is for that?

[00:23:05] Speaker 00:
I mean, it was taken off the market because people died because there were adverse effects.

[00:23:11] Speaker 00:
How does it work with the FDA that the thing comes back on the market?

[00:23:15] Speaker 04:
I think the proponent requested the FDA approve it under a new label.

[00:23:23] Speaker 04:
And there was some process of negotiation with the FDA over the label.

[00:23:28] Speaker 04:
And it included indications.

[00:23:31] Speaker 04:
The only contraindication in the label, by the way,

[00:23:35] Speaker 04:
I mean, as far as the patent is concerned, there's nothing in the label that says don't give it to men.

[00:23:41] Speaker 04:
There's nothing in the, in the label that says don't give it to people who haven't had six months of symptoms or who have not had at least moderate pain.

[00:23:50] Speaker 04:
I mean, the Prometheus is one of the principal expert witnesses, the gastroenterologist.

[00:23:57] Speaker 04:
She testifies, but she does prescribe.

[00:24:00] Speaker 04:
for male patients suffering from IBSD.

[00:24:04] Speaker 03:
Can I ask you the same question which I asked Mr. Cattil?

[00:24:08] Speaker 03:
I'm a little bit puzzled about this.

[00:24:11] Speaker 03:
Suppose somebody has a drug and they haven't defined the patient pool and without defining the patient pool, very bad idea, this drug.

[00:24:22] Speaker 03:
Then they say, okay, we've got some subclass of potential patients.

[00:24:26] Speaker 03:
For them, we've just established this is a good,

[00:24:30] Speaker 03:
benefit-risk calculus.

[00:24:32] Speaker 03:
We don't know about the rest of the world now.

[00:24:34] Speaker 03:
We'll do that later.

[00:24:35] Speaker 03:
But for now, I will claim a method of giving this drug to the patient pool subclass that we know presents a good benefit-risk calculus.

[00:24:47] Speaker 03:
I'm not excluding the rest, but we don't know.

[00:24:50] Speaker 03:
Is that not a significant advance?

[00:24:55] Speaker 04:
I'm not sure it is a significant advance.

[00:24:57] Speaker 03:
I mean, suddenly the drug can be made available

[00:24:59] Speaker 03:
in the market, whereas before it couldn't.

[00:25:02] Speaker 03:
I'm not sure what this whole limitation business is, what function it's playing in the analysis.

[00:25:12] Speaker 04:
Again, I go back to the point, the only limitation is IBSC.

[00:25:16] Speaker 04:
The others are not limitations.

[00:25:18] Speaker 04:
They are assessment stages and they are not... Can I ask you this?

[00:25:22] Speaker 02:
I know you have a lot of prior art for why the IBSC limitation was already known.

[00:25:28] Speaker 02:
Assuming none of that was there, and people had no idea why this was causing certain people to die or have serious side effects, and the patentee discovered it's because this drug works badly for C patients, but works well for the D patients.

[00:25:45] Speaker 02:
Would that be a patentable idea?

[00:25:51] Speaker 04:
It depends, I think, on how, in part, on how the claim is- Why isn't that an unexpected result?

[00:25:57] Speaker 02:
You know, you create this drug, you say it can be used for this whole universe of things.

[00:26:01] Speaker 02:
As you know, it wasn't just for IVF.

[00:26:05] Speaker 02:
It was indicated for other things.

[00:26:07] Speaker 02:
But it turns out that it works very badly for certain people.

[00:26:11] Speaker 02:
And you do some more research, and you identify here is why it's working badly.

[00:26:16] Speaker 02:
Isn't that an unexpected result?

[00:26:19] Speaker 04:
There is no evidence that Elocitron works badly for anybody.

[00:26:25] Speaker 04:
any IBS patients other than IBS constipation.

[00:26:28] Speaker 04:
Well, that's what I'm asking about, though.

[00:26:30] Speaker 00:
I think he's asking a hypothetical, that there is a drug on the market and it has very bad effects on people.

[00:26:38] Speaker 00:
And researchers discovered the unexpected fact that this works effectively without side effects for teenagers.

[00:26:51] Speaker 00:
and it doesn't work for other categories of people.

[00:26:54] Speaker 00:
Is that potentially patentable?

[00:26:58] Speaker 04:
If the patent went on and, responsive to Judge Toronto's question, affirmatively excluded them the way this patent does to IBSC patients, then maybe there's an argument.

[00:27:10] Speaker 04:
But that's not what these claims do.

[00:27:12] Speaker 04:
They do not exclude other than IBSC patients.

[00:27:15] Speaker 00:
But would there be in that situation also a requirement

[00:27:20] Speaker 00:
in not being able to envision the limitation.

[00:27:25] Speaker 00:
Frankly, our cases are not always easy to follow.

[00:27:34] Speaker 00:
Just hold on a second.

[00:27:35] Speaker 00:
In terms of the chemical genus species, those are cases where the genus includes hundreds of thousands or millions of compounds and we couldn't envision singling out the one.

[00:27:49] Speaker 00:
Whereas in this situation, even putting aside unexpected results, there's an ability to envision a subset of patients which is smaller than the whole.

[00:28:00] Speaker 00:
I don't know whether, should that make a difference?

[00:28:02] Speaker 00:
It seems to under the cases.

[00:28:04] Speaker 00:
I think it does.

[00:28:05] Speaker 04:
I mean, it was, the patient population defined in these claims, women with IBSD,

[00:28:17] Speaker 04:
symptoms of certain severity and duration are commonplace.

[00:28:23] Speaker 04:
They are typical of many, many IBS patients.

[00:28:29] Speaker 04:
It was certainly possible to imagine Elositron as a treatment for them given the prior art.

[00:28:39] Speaker 04:
And there is nothing unexpected given the teachings of the prior art that Elositron would be effective for that subset.

[00:28:47] Speaker 04:
Now whether you can patent in addition, you can get a patent based on the idea that there's an unfavorable cost benefit analysis for other patients or you don't know, I don't think you can get a patent on that.

[00:29:02] Speaker 04:
I think that is, you know, give it to women but don't give it to men, that's non-functional.

[00:29:06] Speaker 02:
This is what I was trying to get at with my hypothetical.

[00:29:09] Speaker 02:
I'm not sure I still understand your answer, but it sounds like you're saying you can't patent an exclusion.

[00:29:16] Speaker 02:
If you have a drug,

[00:29:17] Speaker 02:
that is already indicated to treat a certain condition, if it turns out that a certain segment of that population it works badly for, and you exclude them, that that's not a patentable idea.

[00:29:31] Speaker 04:
I think that's right.

[00:29:32] Speaker 04:
How do you infringe a patent which says a method for avoiding illness by not treating persons in a particular category?

[00:29:43] Speaker 04:
I don't think that's a method of treatment.

[00:29:45] Speaker 04:
This patent claims a method of treating a certain class of patients.

[00:29:51] Speaker 03:
Let me just elaborate a little bit on maybe it's too high a level of concern.

[00:29:56] Speaker 03:
But the fact is a drug works in an individual patient or it doesn't.

[00:30:04] Speaker 03:
Everything that goes under the heading of now personalized medicine, but even before that heading came to be subclass medicine,

[00:30:13] Speaker 03:
Um, has to do with figuring out what human bodies measured in some way will match up well with a particular drug.

[00:30:24] Speaker 03:
It really is now not going to be a, an area of patentable invention to figure out which either individuals or subclasses match up well with, with the drug and say,

[00:30:40] Speaker 03:
For this drug, these individuals match up.

[00:30:43] Speaker 03:
We haven't studied a lot of the others.

[00:30:45] Speaker 03:
Put those aside for now.

[00:30:47] Speaker 03:
Maybe some others will.

[00:30:48] Speaker 03:
But for now, we suddenly have a good match.

[00:30:54] Speaker 04:
If it is otherwise patentable, a method for treating a particular class of patients, sure, can be patented.

[00:31:01] Speaker 04:
Isn't that what this is?

[00:31:02] Speaker 04:
No, I don't think so, because I think prior art taught the use of this drug to treat.

[00:31:09] Speaker 04:
a class that included these people.

[00:31:11] Speaker 00:
Well, it can be patented, but what's the test for whether it can be patented?

[00:31:16] Speaker 00:
Unexpected results.

[00:31:17] Speaker 00:
Unexpected results.

[00:31:19] Speaker 00:
And what about envisioning?

[00:31:21] Speaker 04:
I mean, both.

[00:31:22] Speaker 04:
I think both are satisfied here.

[00:31:24] Speaker 04:
I mean, that's what Judge Nike wrote in the ADVI case.

[00:31:30] Speaker 04:
It was, you know, if a method of treating a genus

[00:31:36] Speaker 04:
makes obvious the method of treating a species.

[00:31:41] Speaker 04:
If a person of ordinary skill in the art has clearly in mind, unlike the many chemical patents which claim a formula that encompasses millions of compounds, I mean, here we have, it's not a class of molecules, it is a class of patients, of human beings suffering from a disease.

[00:32:02] Speaker 04:
And there aren't thousands and thousands of parameters

[00:32:05] Speaker 04:
This patent deals with the most common characteristics that gastroenterologists look at in order to diagnose whether the disease is present at all.

[00:32:18] Speaker 04:
And persons of skill and the art understood the mechanism by which this class of drugs worked.

[00:32:23] Speaker 04:
It slowed colonic transit.

[00:32:26] Speaker 04:
And as the judge found, and there's no claim of clear error, a person of skill and the art would understand that a drug in this category

[00:32:34] Speaker 04:
with slow colonic transit, and that's good for diarrhea patients, and it's not good for constipation patients.

[00:32:41] Speaker 04:
So that exclusion was obvious, and there are no other exclusions.

[00:32:46] Speaker 03:
Why is that exclusion obvious, since it's possible that the adverse effect on the constipation patients might be, while real, sufficiently minor relative to at least one well-recognized benefit, which is the

[00:33:02] Speaker 03:
I guess the analgesic effect, the pain reduction that in fact, you might not want to exclude those patients, even though there was an increase or potential increase in the constipation.

[00:33:15] Speaker 04:
The district judge found that the prior art taught persons of ordinary skill in the art, that it was imprudent.

[00:33:22] Speaker 04:
And many of the prior art references on which the district judge revived discouraged the tally reference in particular.

[00:33:28] Speaker 04:
suggested that administering a 5-HT3 receptor antagonist would be contraindicated, would not be a good idea, but giving it to a diarrhea patient would be a good thing.

[00:33:43] Speaker 04:
So there was a finding that, I mean, which is not to say that individual doctors might not disagree, they're free to prescribe off label, but the finding here, and it's not been challenged, is clearly erroneous.

[00:33:55] Speaker 04:
that a person of ordinary skill in the art in 1997 would conclude that it was appropriate to prescribe Elocitron and other 5-HT3 receptor antagonists to diarrhea patients and not to constipation patients.

[00:34:16] Speaker 00:
OK.

[00:34:16] Speaker 00:
Thank you, Mr. Dean.

[00:34:18] Speaker 00:
Mr. Crottyell, you've got two minutes now.

[00:34:22] Speaker 01:
Thank you.

[00:34:22] Speaker 01:
If I could, I'd like to start with Judge Hu's question to my friend on the other side, which was, would it be patentable if we had an unexpected result for a subset of the population?

[00:34:31] Speaker 01:
My friend's answer was yes, as long as the patent affirmatively excluded that population.

[00:34:37] Speaker 01:
That's exactly what this patent does.

[00:34:38] Speaker 01:
It's common ground with respect to at least IDSC, but that's what it does.

[00:34:43] Speaker 01:
That's enough to make it patentable.

[00:34:44] Speaker 01:
As I said before, the PTO found unexpected results for this in terms of the risk benefit ratio being markedly different.

[00:34:52] Speaker 01:
And they have to disprove that by clear and convincing evidence.

[00:34:56] Speaker 01:
There's a huge impact if you don't allow unexpected results claims like the ones here with respect to the IBFC limitation on personalized medicine and all the things that Judge Toronto is talking about.

[00:35:08] Speaker 00:
Well, don't you run into the findings that the district court made here about

[00:35:13] Speaker 00:
they were not expected, right?

[00:35:16] Speaker 01:
We do think that you have to review those in the same way as this court did in Cyclobenzapine for clear and convincing error.

[00:35:21] Speaker 01:
We think they are.

[00:35:22] Speaker 01:
That is, they fall into two baskets.

[00:35:24] Speaker 01:
One is a basket of generic 5-HT3 studies, which don't teach anything about elosteron, and indeed some of them say that it has no effect on colonic transit, like the Stedman case.

[00:35:35] Speaker 01:
The other is studies done on healthy volunteers.

[00:35:37] Speaker 01:
And the district court's own studies say you can't look to those.

[00:35:41] Speaker 01:
So the analysis by the district court essentially swallowed itself.

[00:35:44] Speaker 01:
It used different studies to try and cobble this obviousness claim together.

[00:35:49] Speaker 01:
But when you actually look at the studies, they don't add up.

[00:35:51] Speaker 01:
It's zero plus zero plus zero plus zero.

[00:35:54] Speaker 01:
So I don't think the studies get to where the district court wanted to go.

[00:35:58] Speaker 01:
So then I think they're left with what they say at page 17, Judge Toronto, that this population.

[00:36:04] Speaker 03:
Well, but they also have Dr. Howden's.

[00:36:07] Speaker 03:
testimony that builds on the studies, which perhaps all by themselves don't have examples of this particular antagonist with this particular patient class, but a lot of stuff pointing in that direction.

[00:36:24] Speaker 01:
Why doesn't he add enough?

[00:36:27] Speaker 01:
He doesn't explain anywhere in there why the generic class is enough for a listron, and indeed he himself says,

[00:36:34] Speaker 01:
that these antagonists have very different effects.

[00:36:37] Speaker 01:
Things like cocaine have different effects.

[00:36:38] Speaker 01:
In fact, the district court's preferred study studies on donestron and finds no effects on colonic transit.

[00:36:45] Speaker 01:
But be that as may, you can fight about colonic transit or not.

[00:36:48] Speaker 01:
The fact is the drug was introduced in this way, blanketly, and all of these devastating effects occurred.

[00:36:55] Speaker 01:
And sure, there's maybe 12 people in the Foster study that followed some of the limitations in the 770 patent, which is all the Foster study is.

[00:37:04] Speaker 01:
Our point is it was introduced to more people and it took the innovation of the 770 patent to winnow it down to the right cost-benefit ratio allowing the drug to be prescribed in a safe and efficacious way and indeed brought back to the market.

[00:37:18] Speaker 00:
Is that winnowing down for safety and efficacy reflected in the 770 patent itself?

[00:37:25] Speaker 00:
We do think it is, yes.

[00:37:27] Speaker 00:
Well, in terms of the discussion.

[00:37:30] Speaker 01:
Yes, I think that's a...

[00:37:31] Speaker 01:
I do.

[00:37:32] Speaker 01:
I think that the specifications explain that this is the right population.

[00:37:36] Speaker 01:
That is, of course, exactly what the PTO found, that when you have these four limitations and when you take them all together, and I think that was another legal problem that the district court did, is they looked at each limitation in isolation instead of thinking, as KSR did, what would the motivation be to combine?

[00:37:52] Speaker 01:
And so Houghton, I don't think, gets them to where they want.

[00:37:55] Speaker 01:
At most, it says, yeah, there's a worry about constipation.

[00:37:59] Speaker 01:
We know from 2000 that the FDA said the way to deal with that is by giving laxatives and other things, not to exclude IVF patients entirely.

[00:38:09] Speaker 01:
That's what the 770 patent did.

[00:38:11] Speaker 01:
That's the innovation.

[00:38:12] Speaker 01:
And if you allow this to be declared as obvious, I really do think you're driving the stake into these subset patent claims and agreed that they're not all going to be patentable, which is your decision in that thesis.

[00:38:24] Speaker 01:
But when you have something like this with a bunch of different parameters,

[00:38:28] Speaker 01:
And really no evidence except for an academic study of 12 people that says, oh, it was limited in this way.

[00:38:35] Speaker 01:
It turns out that doesn't even say that it wasn't limited to women and so on.

[00:38:39] Speaker 01:
I don't think that you can get to affirming the district court on a 103 claim.

[00:38:44] Speaker 00:
OK.

[00:38:44] Speaker 00:
Well, thank you, Mr. Conchal.

[00:38:45] Speaker 00:
Thank both counsels.

[00:38:46] Speaker 00:
The case is submitted.