[00:00:37] Speaker 03:
The next case is Spectrum Pharmaceuticals v. Sandoz, 2015-1407.

[00:00:43] Speaker 03:
Mr. Israel.

[00:00:46] Speaker 01:
May you please record.

[00:00:52] Speaker 01:
Two grounds for obviousness are presented on appeal, each of which violate a fundamental principle.

[00:00:58] Speaker 00:
Let me ask you sort of a housekeeping kind of question first.

[00:01:01] Speaker 00:
At several points both in the principle and reply brief, you claim some facts are undisputed.

[00:01:08] Speaker 00:
And one of them is the undisputed evidence showed no prior method enabled the purification of the prior 50-50 combination.

[00:01:17] Speaker 00:
to yield a mixture enhanced in the 6S isomer.

[00:01:23] Speaker 00:
No evidence that anyone ever succeeded using Kosilic's method.

[00:01:31] Speaker 00:
The problem I have with that is you say these are undisputed facts and yet in the record the district court discusses testimony by various experts and says

[00:01:46] Speaker 00:
Martin, Suckling, and Moran all testified they believed Kasulich did that and there's no evidence that that didn't happen and the journal article was never withdrawn.

[00:02:03] Speaker 00:
So how is that undisputed?

[00:02:05] Speaker 00:
I mean, I can see you could argue that it was misinterpreted or some such, but it's clearly not undisputed.

[00:02:13] Speaker 01:
No, the question is one of enablement.

[00:02:16] Speaker 01:
And whether Kowsulich herself got it once is distinct from whether she contributed a method to the art that others can repeat.

[00:02:25] Speaker 01:
which is ultimately what's required for an enabling disclosure of a method to purify the 50-50 mixture of isomers.

[00:02:30] Speaker 01:
She might have gotten them.

[00:02:31] Speaker 01:
Again, that was a rather irrelevant issue to the trial as far as we were concerned, because the question is, in 1986, did she contribute an operable method to purify the isomers?

[00:02:42] Speaker 01:
If she did, we would fall dangerously close.

[00:02:46] Speaker 00:
But all these people said they believed that she did.

[00:02:48] Speaker 01:
They believed she might have gotten the right product.

[00:02:51] Speaker 01:
They don't believe, nobody testified that indeed it works for anybody else.

[00:02:56] Speaker 03:
If she got the right product, the pure S-isomer was known, right?

[00:03:05] Speaker 01:
Having been made via an enzymatic process.

[00:03:08] Speaker 03:
One method or another, it was known, the pure S-isomer.

[00:03:15] Speaker 01:
It had been made by an enzymatic process.

[00:03:16] Speaker 01:
It was known.

[00:03:17] Speaker 01:
Separate from process, indeed.

[00:03:18] Speaker 03:
Maybe it wasn't a terrific method, but a better method is not claimed here.

[00:03:25] Speaker 03:
This is a composition claim, right?

[00:03:27] Speaker 03:
Indeed.

[00:03:28] Speaker 03:
Not a method claim.

[00:03:29] Speaker 01:
We don't claim what we, these inventors claim what they were the first to enable, what a number of groups were trying to enable.

[00:03:35] Speaker 01:
That is, the ability to make a commercial scale in a practical way, what is a mixture of isomers.

[00:03:42] Speaker 01:
We claim a mixture of isomers for the very purpose that when you start with a mixture, as Caslet's tried to.

[00:03:47] Speaker 01:
you always end up with a mixture.

[00:03:49] Speaker 03:
The question is, if the pure isomer is known, is a somewhat less pure isomer not obvious?

[00:03:58] Speaker 01:
Indeed.

[00:03:59] Speaker 01:
If we are grounding, indeed it's not obvious.

[00:04:01] Speaker 03:
What's so good about a somewhat less pure isomer?

[00:04:05] Speaker 03:
Does it have advantages over the pure isomer?

[00:04:08] Speaker 01:
It does not have a clinical advantage over the pure isomer.

[00:04:12] Speaker 01:
Indeed, if Sandoz or any other generic company wanted to use 100% pure, they're more than welcome to.

[00:04:20] Speaker 01:
But indeed, it's not obvious.

[00:04:23] Speaker 01:
We have to ground ourselves in the prior art, in obviousness we always must.

[00:04:28] Speaker 01:
If the prior art is an enzymatically prepared

[00:04:31] Speaker 01:
100% pure.

[00:04:32] Speaker 02:
You keep talking about the method of preparation though, but this is not a method claim, it's a composition claim.

[00:04:38] Speaker 02:
So what does it matter whether the prior art should one way or another?

[00:04:44] Speaker 02:
there is known in the art a pure form.

[00:04:47] Speaker 02:
Why isn't every other form known as well?

[00:04:50] Speaker 02:
Because it certainly, you can go from the pure form all the way back down through the non-pure forms.

[00:04:55] Speaker 01:
Because the only reason you would have to do that is a hindsight reconstruction of this invention.

[00:04:59] Speaker 01:
And that is the problem.

[00:05:01] Speaker 01:
The invention is a particular composition.

[00:05:03] Speaker 01:
It's not a method for getting it out.

[00:05:05] Speaker 01:
We still need a

[00:05:06] Speaker 01:
If we're going to focus on the 100% pure and the prior art, you still need a logical reason, don't we, after KSR to modify that.

[00:05:14] Speaker 03:
Isn't this a claim to a substantially pure material?

[00:05:19] Speaker 03:
Indeed.

[00:05:19] Speaker 03:
95%?

[00:05:20] Speaker 03:
92%?

[00:05:21] Speaker 01:
Indeed it is.

[00:05:22] Speaker 01:
And so what logical reason existed to modify what I would say contaminate what was already 100% with the undesirable known to be potentially deleterious impurity?

[00:05:35] Speaker 01:
There is none.

[00:05:38] Speaker 03:
That's a very strange argument.

[00:05:40] Speaker 03:
We've had arguments

[00:05:41] Speaker 03:
for years.

[00:05:43] Speaker 03:
You know them all, you know all the cases.

[00:05:46] Speaker 03:
When you have a mixture, to get to the pure compound may be non-obvious, but to go backwards.

[00:05:56] Speaker 01:
We still are grounded in the prior art here and we still have to find a reason to modify.

[00:06:04] Speaker 01:
We all agree it's a non-obvious alteration of the prior art.

[00:06:08] Speaker 01:
There's no reason why you would do it but for the invention, but for to invalidate this claim.

[00:06:14] Speaker 01:
We all agree there's a motivation to purify the 50-50 mixture.

[00:06:19] Speaker 01:
There's no enabling process to do it until the invention.

[00:06:23] Speaker 02:
But you didn't patent the process.

[00:06:26] Speaker 02:
We did patent the process.

[00:06:28] Speaker 02:
Right, but that's not the patent we're arguing about here today.

[00:06:32] Speaker 02:
So I understand, and I may be repeating my colleague's point, that if there's this mixture out there,

[00:06:41] Speaker 02:
and nobody has discovered a pure form and you patent the pure form, then that may be patentable as a composition claim.

[00:06:49] Speaker 02:
But when the pure form is already prior art and you're not saying that some mixture of pure and non-pure has advantages over the pure, then how is not the 100% pure

[00:07:03] Speaker 02:
render anything below that obvious without resorting to language of how you do it.

[00:07:10] Speaker 01:
I think your honors are referring to the analysis akin to titanium metals.

[00:07:16] Speaker 01:
If it's sort of close enough, it's obvious.

[00:07:19] Speaker 01:
But even in titanium metals, the understanding was that the optimization around endpoints in titanium metals was an appropriate motivation.

[00:07:28] Speaker 03:
What you're saying is what makes no sense, in other words going to a less pure material, what makes no sense is non-obvious.

[00:07:38] Speaker 01:
Maybe you're right.

[00:07:38] Speaker 01:
And indeed they can use the 100% pure.

[00:07:41] Speaker 01:
We are not trying to block others from using the prior art.

[00:07:45] Speaker 01:
They're more than happy to allow that.

[00:07:47] Speaker 01:
But that's not what they're choosing to do, because the more practical way to get the material is still the preferred way to get the material.

[00:07:54] Speaker 01:
And the first to enable the mixture is able to... That's the preferred method.

[00:07:59] Speaker 01:
The first to enable the claim compound is entitled to claim the compound itself, because the compound isn't in the prior art.

[00:08:07] Speaker 01:
The mixture isn't in the prior art.

[00:08:09] Speaker 00:
The court found that you were arguing that there was no evidence that Kissilich obtained highly pure success lucuborin and in fact

[00:08:27] Speaker 00:
Drs.

[00:08:29] Speaker 00:
Martin, Suckling, and Moran all testified they believed Dr. Vasulich did so, and the court accepted that testimony as true.

[00:08:36] Speaker 01:
And it does not make Vasulich enabling.

[00:08:38] Speaker 01:
And these four groups tried, including the inventors during the prosecution of this patent, proved, they tried to repeat Vasulich and proved it doesn't work.

[00:08:46] Speaker 01:
Even American Cyanamid admitted, the owner of the casket, the owner of the casket's patent admitted it didn't work.

[00:08:53] Speaker 01:
All right, and that's in evidence, that's at A-4242.

[00:08:57] Speaker 00:
So the court is in error in its summation of the testimony that they believe, the doctors believe that it was done.

[00:09:07] Speaker 01:
No, Your Honor, they were not in error to conclude that Kauselic described having done it.

[00:09:14] Speaker 01:
Indeed, that's what Kauselic described.

[00:09:16] Speaker 00:
And that they believed, indeed, it had been done.

[00:09:19] Speaker 01:
Indeed, they believe the data was consistent with what Kauselic says she got.

[00:09:24] Speaker 01:
But there's no doubt that the district court did not reach the issue of whether cow sludge was enabling.

[00:09:28] Speaker 01:
She said as much when she said, I do not rely on cow sludge as an enabling process.

[00:09:33] Speaker 01:
What I rely on what's enabling is the idea that you can contaminate the 100% material, a completely non-obvious thing to do.

[00:09:40] Speaker 01:
So I'm sensitive to your honor's concern that we're withdrawing something in the prior art that was already in the prior art.

[00:09:46] Speaker 01:
But again, if somebody wants to use the 100% material, we're more than happy to permit that.

[00:09:52] Speaker 01:
Our claims do not cover that.

[00:09:57] Speaker 03:
Isn't it likely that when one is on the way to obtaining a pure product, one goes through a less pure product?

[00:10:07] Speaker 01:
I'm glad your honor asked that question.

[00:10:09] Speaker 01:
I think there was some element of confusion in the district court and perhaps in the briefing because the enzymatic process does not at all ever make a mixture.

[00:10:17] Speaker 01:
It never starts with a mixture.

[00:10:19] Speaker 01:
It completely

[00:10:20] Speaker 01:
goes around the idea of making a mixture and synthetically only makes one.

[00:10:24] Speaker 01:
It was going to be a trial issue.

[00:10:26] Speaker 01:
Sandoz dropped the issue whether this enzymatic process inherently made some of a mixture.

[00:10:32] Speaker 01:
They dropped that before trial, instead admitting that it's 100% pure.

[00:10:36] Speaker 01:
So no, the enzymatic processes only make 100%.

[00:10:41] Speaker 01:
That's admitted by Sandoz.

[00:10:44] Speaker 01:
So the question before this court is whether a logical reason is still required to modify the prior art.

[00:10:52] Speaker 01:
And indeed, that's the only way you can find these frames are obvious over the 100% small amount of 100% material which nobody wants to use.

[00:11:02] Speaker 01:
is to conclude that, well, it just doesn't matter that there's no reason to contaminate it.

[00:11:06] Speaker 03:
So we issue patents these days on products less desirable than the prior of.

[00:11:14] Speaker 01:
I think we're operating in a fictional world that this enzymatic process actually solved any sort of need to produce a pharmaceutical product.

[00:11:24] Speaker 01:
The reality was, and I can give you a site to our expert, there wasn't enough enzyme to even make 10 grams of this material.

[00:11:30] Speaker 01:
The solution to the problem that was contributed by the inventors was a significant one.

[00:11:35] Speaker 03:
The solution to the problem was the process, which isn't claimed.

[00:11:38] Speaker 01:
Which enabled the claim to composition, which is the key.

[00:11:42] Speaker 01:
And under Henry Hoeksema and later case law, that entitles Spectrum to claim the composition that they've enabled.

[00:11:51] Speaker 03:
We'll save the rest of your time for a bottle if you like.

[00:11:54] Speaker 03:
Or continue, it's your time.

[00:11:57] Speaker 01:
I think I will.

[00:11:58] Speaker 01:
Thank you.

[00:12:00] Speaker 03:
Ms.

[00:12:04] Speaker 04:
Maynard.

[00:12:19] Speaker 04:
It was well known, in fact, that the evidence was replete in the record, that the success isomer was the one that had all the therapeutic benefits.

[00:12:29] Speaker 04:
The district court found that the isomer had been both purified from the 50-50 mixture to a highly pure form.

[00:12:37] Speaker 03:
Doesn't the opposing council have an argument, a reasonable argument, that if you have a pure product,

[00:12:45] Speaker 03:
Who would contaminate us?

[00:12:46] Speaker 03:
Isn't that non-obvious?

[00:12:49] Speaker 03:
Isn't that what they're claiming?

[00:12:51] Speaker 04:
That is a fair information of what he's saying, Your Honor, but I think there's one problem with that is

[00:12:57] Speaker 04:
It is relevant that there was this way to make it in the art because that takes them out of the Hexenma world where you're just talking about theoretical compound.

[00:13:05] Speaker 04:
There was a known way to make it here.

[00:13:07] Speaker 04:
That would have been easy if the district court found.

[00:13:08] Speaker 04:
But more importantly, under titanium metal, there's no patentable difference between the 100% pure and the 92% to 99.99% claimed in these claims.

[00:13:20] Speaker 04:
And the district court made findings that require this.

[00:13:22] Speaker 04:
The district court found that there is no meaningful difference.

[00:13:26] Speaker 04:
between the compound and the claims and the 100% pure.

[00:13:30] Speaker 04:
The district court found and their witness, Dr. Ryder, testified that the body would not know the difference between a 90% plus and a 100% pure.

[00:13:43] Speaker 04:
So absent anything else, there's nothing patentable and it is obvious.

[00:13:49] Speaker 04:
All we're talking about here is compounds.

[00:13:52] Speaker 04:
If they had a better way to scale it up, they had a methapatin, the methapatin expired, that's not being asserted here.

[00:13:59] Speaker 04:
The district court found, in fact, that the enzymatic process, which is the process that makes 100% pure, and the district court found in fact that the 100% pure, the enzymatic process, actually had only 95% success.

[00:14:14] Speaker 04:
The other impurities, and Sandoz did not conceive, but Sandoz did not try to prove at trial that the other impurities might or might not contain some 6R, but in any event,

[00:14:22] Speaker 04:
The important point is the district court found there's no meaningful difference to the body between the compound that's claimed here and the compound in the prior art.

[00:14:31] Speaker 04:
That makes it obvious under titanium metals.

[00:14:34] Speaker 04:
It's also obvious under Aventus because this was the factual

[00:14:39] Speaker 04:
Everyone knew that success was the act of eichler.

[00:14:43] Speaker 04:
Dr. Kosulich in fact separated it in 1952.

[00:14:47] Speaker 04:
Finding a fact, 94, she obtained highly pure success.

[00:14:56] Speaker 04:
Their witnesses didn't dispute that.

[00:14:59] Speaker 04:
They did try to show... They could not replicate it.

[00:15:03] Speaker 04:
They put in proof that several people could not replicate it.

[00:15:06] Speaker 04:
They sought a finding of fact from the district court that Dr. Kosulich's patent was not enabled.

[00:15:11] Speaker 04:
That's their requested finding of fact 38.

[00:15:14] Speaker 04:
The district court did not make that finding.

[00:15:17] Speaker 04:
The district court instead found that Dr. Kosulich had in fact succeeded.

[00:15:21] Speaker 04:
The district court also found, and the patent specification here concedes in column two,

[00:15:27] Speaker 04:
that prior art methods had succeeded in separating the 50-50 mixture, both by fractional crystallization, which is the method Dr. Cressula used, and by chromatography.

[00:15:37] Speaker 04:
The specification also concedes that the prior art had succeeded in making enzymatically 100% pure F. The district were relied on all of this information to conclude that a person of skill in the art would have had reasonable success in separating the isomers one way or the other.

[00:15:56] Speaker 04:
And that under Aventis, that's a stronger case than obviousness under Aventis.

[00:16:01] Speaker 04:
Because here we had an explicit teaching in the art that the success, it was known, as Judge Lloyd pointed out, that the success was the act of isomer.

[00:16:08] Speaker 04:
It had in fact been separated.

[00:16:11] Speaker 04:
Someone had already in fact created substantially pure success.

[00:16:18] Speaker 04:
The question for obviousness is not whether the Kasulich patent is itself enabled, although of course it's presumed enabled and the district court didn't find that they proved it wasn't.

[00:16:28] Speaker 04:
The question is whether all of the art, including those that the district court found, would suggest that a person of skill in the art would have success at arriving at the invention, and the facts here establish that in spade.

[00:16:40] Speaker 04:
Indeed, the district court found that the motivation, a strong motivation, developed in the mid-1980s to separate these isomers because of a new treatment that had begun in the early 1980s, the 5-FU treatment.

[00:16:52] Speaker 04:
They used much more leukoborin.

[00:16:55] Speaker 04:
and there was a research hypothesis that the 6R might inhibit the effectiveness of the glucoborne.

[00:17:03] Speaker 04:
The dish report further found that multiple groups responded to the strong motivation to separate the isomers and that in short time many succeeded.

[00:17:15] Speaker 03:
But if the pure material is known, what's the motivation to contaminate it to make it impure, which is what the claims cover?

[00:17:26] Speaker 04:
Well, we don't have to show that motivation, Judge Rory, as the District Court correctly found.

[00:17:30] Speaker 04:
The fact that the 92 to 99.99% is

[00:17:37] Speaker 04:
insubstantially different, biologically equivalent to the body to the 100% pure is alone enough.

[00:17:43] Speaker 04:
That's why no one would do it, because you're just adding impurities to it.

[00:17:47] Speaker 04:
But that doesn't make it patentable.

[00:17:49] Speaker 04:
In fact, that just under titanium metals, that makes it obvious.

[00:17:52] Speaker 03:
If no one would do it, isn't it non-obvious?

[00:17:56] Speaker 04:
No, Your Honor.

[00:17:57] Speaker 04:
It's not under the law.

[00:17:58] Speaker 02:
Now, to be sure, if they might have been able to show some unexpected properties or other secondary considerations, we might have... If the 92 to 95 percent mixture were better because it had some R in it than the 100 percent, then that might be patentable.

[00:18:13] Speaker 04:
That would be a much tougher case.

[00:18:15] Speaker 04:
But in fact, we have the opposite here.

[00:18:17] Speaker 04:
Their witness conceded there was no benefit.

[00:18:19] Speaker 04:
And he conceded here.

[00:18:21] Speaker 04:
And the district court found, which is the most important thing.

[00:18:23] Speaker 04:
The district court made a finding of fact.

[00:18:25] Speaker 04:
There was no meaningful difference between the compounds claimed and the 100% pure.

[00:18:30] Speaker 04:
If the court would like, I would address the, if you have questions about the non-infringement arguments, I would like to address that.

[00:18:35] Speaker 04:
If not, however, I'll.

[00:18:40] Speaker 03:
Apparently not.

[00:18:41] Speaker 03:
Mr. Izraelowitz has a little under four minutes for rebuttal.

[00:18:53] Speaker 01:
As Judge Lurie, as you pointed out, it's a completely non-obvious thing to do.

[00:19:05] Speaker 01:
I almost need to say no more, because if KSR still requires a motivation to modify the art, again, we always have to start with the prior art.

[00:19:16] Speaker 01:
Calcelus must be enabling.

[00:19:18] Speaker 01:
It would be on all fours of Aventus if Calcelus was enabling.

[00:19:21] Speaker 01:
Aventus is quite distinct.

[00:19:22] Speaker 01:
There were two different prior references that said, here's the way to do it, and you can purify the 50-50 mixture.

[00:19:28] Speaker 01:
There was an enabling art to get to where you needed to go in Aventus.

[00:19:33] Speaker 01:
That's why we spent so much time at trial showing that cow sludge was not an able one.

[00:19:37] Speaker 01:
Not that cow sludge got the data, the optical rotation that was appropriate, that she didn't contribute a method to purify the isomers to one-of-order skill in the art.

[00:19:45] Speaker 01:
One-of-order skill in the art in 1986 couldn't make this composition but for the invention.

[00:19:50] Speaker 01:
Now, could they adulterate the little bit of 100% that was in the prior art?

[00:19:56] Speaker 01:
Yeah, I think they probably could have taken a medicine dropper and have done that, but why would they do that?

[00:20:01] Speaker 01:
We're not required to show unexpected results.

[00:20:03] Speaker 01:
They're required to show a motivation to modify the art.

[00:20:08] Speaker 01:
Ultimately, the burden rests with them to show by clear convincing evidence that there was a motivation.

[00:20:13] Speaker 01:
Council, my friend, was just up here saying, we don't need to show that.

[00:20:17] Speaker 01:
Indeed, you always need to show a motivation to modify the prior art.

[00:20:20] Speaker 01:
If the prior art starting place is

[00:20:22] Speaker 01:
50-50 mixture, we have motive all day.

[00:20:25] Speaker 01:
We just don't have an enabling way to do it.

[00:20:27] Speaker 01:
If the prior art is 100%, we have an enabling way to do it, but no motivation to get there.

[00:20:34] Speaker 01:
So whether your honors think this is just a little bit worse than the prior art, it isn't.

[00:20:39] Speaker 01:
There's no way to make buckets of this stuff to make a pharmaceutical.

[00:20:43] Speaker 01:
Ultimately, we claim a pharmaceutical.

[00:20:45] Speaker 01:
No pharmaceutical company in their right mind in 1986 would have made a pharmaceutical based on an enzymatic process that yielded less than a gram of material and could be scaled up maybe to 10 grams.

[00:20:56] Speaker 03:
So you invented a process?

[00:20:58] Speaker 01:
No, we were the first to enable what was needed to make this drug, and that's why we can claim the drug.

[00:21:06] Speaker 03:
Thank you.

[00:21:08] Speaker 03:
We'll take the case under advisement.

[00:21:10] Speaker 00:
Mr. Zarellowitz, I see you tried the case.

[00:21:12] Speaker 00:
I hope you had an opportunity to visit some of Las Vegas' swell restaurants.

[00:21:19] Speaker 00:
I practiced law there for 19 years.

[00:21:20] Speaker 00:
All right.

[00:21:23] Speaker 03:
The honorable court is adjourned until tomorrow morning.

[00:21:28] Speaker 03:
It's an o'clock a.m.