[00:00:53] Speaker 04:
Okay.

[00:00:55] Speaker 04:
We've not only got split arguments, but we've got a cross-appeal in this case, too.

[00:01:00] Speaker 04:
So we'll try to keep it all straight.

[00:01:02] Speaker 04:
Mr. Dinger, you represent Teva.

[00:01:05] Speaker 04:
And you're going to go forward for nine minutes.

[00:01:08] Speaker 00:
I'm going for nine minutes.

[00:01:09] Speaker 00:
And Ms.

[00:01:11] Speaker 00:
Mizoki, who is arguing after me for Lupin, is going to sit.

[00:01:15] Speaker 00:
stick a note in front of me with about 30 seconds left at my request.

[00:01:20] Speaker 04:
Well, we are going to run the clock separately.

[00:01:22] Speaker 04:
So you'll have your nine minutes.

[00:01:23] Speaker 04:
You'll know when your time is up.

[00:01:25] Speaker 04:
OK.

[00:01:26] Speaker 00:
All right.

[00:01:26] Speaker 00:
Proceed, please.

[00:01:28] Speaker 00:
Good morning.

[00:01:29] Speaker 00:
The district court in this case made findings that, frankly, led to the conclusion that the claims in suit were obvious.

[00:01:36] Speaker 00:
The court stumbled in its final analysis because it made a legal error.

[00:01:41] Speaker 00:
It defined what constitutes a reasonable exit.

[00:01:43] Speaker 04:
You want us to just simply accept all

[00:01:45] Speaker 04:
the lower court's findings.

[00:01:48] Speaker 00:
No, Your Honor.

[00:01:49] Speaker 00:
I'll identify some places, but for the most part I'm going to be arguing for the legal error.

[00:01:52] Speaker 00:
We argue in our brief that several of the findings, for example, that concerns about

[00:02:00] Speaker 00:
about cross resistance would in fact discourage a person from combining the drugs in question.

[00:02:08] Speaker 00:
We think that's clearly erroneous.

[00:02:10] Speaker 00:
We think the finding that the prior arc, there was no publication in the prior arc that suggested that combining drugs that worked on different bases was also clearly erroneous.

[00:02:25] Speaker 00:
And we've argued that in our brief.

[00:02:26] Speaker 00:
But I'd like to focus, if I may,

[00:02:28] Speaker 00:
on what we think is a fundamental legal error that essentially infected all of the district court's rulings on obviousness.

[00:02:39] Speaker 00:
The district court found that by March 1995, combination therapy was generally thought to offer better treatment opportunities.

[00:02:50] Speaker 00:
The court found that Abacavir was a right candidate for researching new combination therapies for many reasons that are set forth at page 32 and 33 and 53 of the brief.

[00:03:00] Speaker 00:
The court found that both 3-TC and Abacavir were potent, less toxic than AZT, and synergistic with other NRTIs.

[00:03:09] Speaker 00:
The court found that despite the success of the AZT-3-TC combination,

[00:03:17] Speaker 00:
Many patients could not or would not take AZT because of its side effects.

[00:03:23] Speaker 00:
The district court stopped short, though, of concluding that the combination of Avacabir and 3TC to treat HIV infection was obvious because in the district court's view, skilled artisans would not reasonably expect the Avacabir-3TC combination to be successful.

[00:03:42] Speaker 00:
The court concluded the scale of artisans would not expect that that combination would sustain effectiveness before resistance to filter.

[00:03:51] Speaker 04:
We've got a mixture of law and fact here, whatever.

[00:03:54] Speaker 04:
I just want to call out your argument and see, at bottom, on the legal question of where you say there was legal error, can you point us to what sentences or what tests the district court used that you allege?

[00:04:08] Speaker 00:
Sure.

[00:04:08] Speaker 00:
I'll give you an example.

[00:04:09] Speaker 00:
A55, the court says, it is clear that the art of HIV treatment

[00:04:14] Speaker 00:
was littered with failures.

[00:04:17] Speaker 04:
I'm looking at the page.

[00:04:18] Speaker 04:
Can you tell me the last paragraph, the middle or last paragraph, is that what you're reading from?

[00:04:22] Speaker 00:
Let me actually get to it, Your Honor.

[00:04:29] Speaker 00:
It is clear that the art of HIV treatment was littered with failures as of March 30, 1990.

[00:04:40] Speaker 00:
Only a single combination, AZT3TC, had shown any significant sustained effectiveness against the virus.

[00:04:48] Speaker 00:
And then again on page 70 of the

[00:04:53] Speaker 04:
Well, that seems to me a question of, I mean, that's just a fact.

[00:04:57] Speaker 04:
I mean, he's saying only a single combination had shown any sustained effectiveness.

[00:05:02] Speaker 00:
But that's a statement of fact.

[00:05:04] Speaker 00:
That's the only success, your honor.

[00:05:06] Speaker 00:
The court said that that sustaining clinical effectiveness in that sense was the only success.

[00:05:12] Speaker 04:
And another point, a finding of obvious mistake.

[00:05:16] Speaker 04:
If you look at this first statement in context,

[00:05:19] Speaker 04:
What the trial court is saying is, was there a failure of others?

[00:05:24] Speaker 04:
So that's a factual finding that relates to whether there was any failure of others.

[00:05:29] Speaker 04:
So what is legal error about that statement?

[00:05:34] Speaker 00:
Because the district court consistently, through the opinion, defined success solely with reference.

[00:05:41] Speaker 00:
The only success that the district court identified was AZT 3TC.

[00:05:45] Speaker 00:
And the only reason that was successful

[00:05:48] Speaker 00:
was that it was able to sustain clinical effectiveness for a period longer than other therapies had been able to do.

[00:05:58] Speaker 00:
HIV was slower to develop resistance to the AZT3TC combination than the virus was.

[00:06:06] Speaker 04:
OK, I'm really unclear.

[00:06:08] Speaker 04:
Let me tell you what I thought your argument was.

[00:06:12] Speaker 04:
And then you can tell me where I'm off, because you seem to be saying different things here.

[00:06:16] Speaker 04:
I thought that your argument was, leaving aside that I can understand some confusion here, because with regard to claim construction, you're arguing synergy.

[00:06:25] Speaker 04:
So let's leave that aside.

[00:06:26] Speaker 04:
But with respect to obviousness, I understood your argument to be the standard is whether something would lead to a reasonable expectation of success, and that the district court defines success

[00:06:38] Speaker 04:
at too high a level, because what he required was sustained therapeutic effects, sustained political efficiency, and there's nothing in the claims that requires that.

[00:06:51] Speaker 04:
Because I didn't quite glean that from what you were telling us this morning.

[00:06:55] Speaker 00:
Well, then I spoke badly, because that is precisely my argument.

[00:06:59] Speaker 00:
The error of law that the district court made was defining the success that a person of skill in the art must reasonably expect.

[00:07:07] Speaker 00:
not to be what the patent claimed, but something else.

[00:07:12] Speaker 00:
Something more.

[00:07:13] Speaker 00:
Something more.

[00:07:14] Speaker 00:
As Chief Judge Prost said in the Allergan versus Santos case, the person of ordinary skill need only have a reasonable expectation of success

[00:07:24] Speaker 00:
of developing the claimed invention.

[00:07:27] Speaker 04:
Now the difficulty though in your argument is the district court's opinion is amazingly thorough and I think I see your point that some of the fact finding there cuts your way.

[00:07:38] Speaker 04:
I mean he was very measured, very balanced, clearly considered every piece of evidence and took it all very seriously.

[00:07:45] Speaker 04:
So it's really hard to pinpoint

[00:07:48] Speaker 04:
Assuming we're understanding the same legal argument from your perspective, it really is hard to pinpoint where the district court really applies the wrong standard.

[00:07:57] Speaker 04:
His opinion is so thorough and so fulsome that he's saying a lot of things.

[00:08:03] Speaker 04:
And I really had a hard time identifying precisely where that legal error occurs, frankly, I'll tell you.

[00:08:10] Speaker 00:
The findings of the district court support the inference.

[00:08:13] Speaker 00:
that a person of skill in the art would expect the combinations of this patent to treat HIV infection, at least for a time.

[00:08:24] Speaker 00:
There really wasn't any significant dispute about that.

[00:08:28] Speaker 00:
The reason the district court did not draw the inference that a skilled artisan would expect

[00:08:36] Speaker 00:
The combination of drugs to do what they did individually was that, he said, they would be worried about cross-resistance.

[00:08:46] Speaker 00:
And cross-resistance matters because it would lead, in the view of the district court, to an expectation that resistance would come sooner than it would with the ACT-3TC combination.

[00:08:59] Speaker 00:
The court couldn't have been clearer.

[00:09:01] Speaker 03:
Are you disputing his fact finding when he says it's clear that the art of HIV treatment was littered with failures as of March of 95?

[00:09:09] Speaker 03:
Are you saying that he is evaluating failures as something only, it's only a success if it would work longer term?

[00:09:18] Speaker 03:
That his, that in fact the facts don't support that these things were failures, they support the fact that they don't

[00:09:26] Speaker 03:
have success over as long over time?

[00:09:29] Speaker 00:
Yes.

[00:09:29] Speaker 00:
Is that your point?

[00:09:30] Speaker 00:
That is exactly my point.

[00:09:32] Speaker 00:
And that is a good indication of where the district court's reasoning led them to legal error and not factual.

[00:09:40] Speaker 00:
You can accept the fact that AZT 3TC appeared at the relevant time to have

[00:09:49] Speaker 00:
sustained efficacy longer than the previous ones, but monotherapies were still being used.

[00:09:55] Speaker 04:
Other combinations- And that's actually important because one of the things that the trial courts found is that some two drug combinations worked for a while and others didn't seem to work very well at all and certainly didn't work better than certain monotherapies.

[00:10:08] Speaker 04:
So, I mean, what the trial court did was find that this whole two drug combination therapy was in a state of flux.

[00:10:18] Speaker 04:
And sometimes it was good, sometimes it wasn't good.

[00:10:21] Speaker 04:
Made those factual findings.

[00:10:22] Speaker 00:
Your Honor, I think this is another place where I think the district court made a clear error of fact.

[00:10:29] Speaker 00:
In fact, all of the prior art discussion of combinations of NRTIs, the drug category in which these drugs came from, said that they were all synergistic or additive to synergistic.

[00:10:45] Speaker 00:
The court said that there was one combination that was antagonistic.

[00:10:51] Speaker 00:
In other words, they combined and made things worse.

[00:10:53] Speaker 00:
But the only evidence of that was from the lab notebooks of one of the identics, which is not prior art.

[00:10:59] Speaker 00:
The prior art consistently taught that these combinations would generally be better, be more effective than monotherapies.

[00:11:14] Speaker 00:
Most of the combinations that were reported in the prior art show that they delayed resistance longer than monotherapies.

[00:11:22] Speaker 00:
not as long as AZT3TC, but sustained it.

[00:11:27] Speaker 00:
And this was a time when physicians were prescribing drugs to hold off resistance, to hold off AIDS.

[00:11:37] Speaker 00:
And drugs that did that even for a time, even for a period of months, were considered effective and important.

[00:11:45] Speaker 04:
You are in your time, so why don't we hear from Ms.

[00:11:49] Speaker 04:
Sochi?

[00:11:59] Speaker 02:
I'm going to try to not repeat what Teva said because we obviously have some of the same concerns about the legal analysis that the district court performed in terms of making it too high of a standard on expectations of success and criteria that could be identified as problems that needed to be solved.

[00:12:20] Speaker 02:
But in the context of the triple combination, here again, the district court's fact findings, many of them, we think, actually support the ultimate conclusion of non-obviousness.

[00:12:33] Speaker 02:
Right, and he said that.

[00:12:34] Speaker 02:
Right, exactly.

[00:12:36] Speaker 02:
And the findings that he offered, that AZT3TC was the best combination

[00:12:41] Speaker 02:
that ABC was right for use in combination therapy.

[00:12:45] Speaker 02:
It was known to be an up and coming anti-HIV drug that had some better side effects, better improved bioavailability.

[00:12:54] Speaker 02:
Those facts

[00:12:56] Speaker 02:
are reasons to combine them into the triple combination.

[00:13:00] Speaker 02:
So where did he go astray?

[00:13:02] Speaker 02:
I think he went astray in the sense that he said, for example, well, there were instances where you had a triple NRTI combination, AZT3TC and DDI, which was an already FDA approved drug.

[00:13:18] Speaker 02:
He said, well, the clinical results weren't in on that yet.

[00:13:20] Speaker 02:
So how can that inspire imitation?

[00:13:23] Speaker 02:
Well, that's not really the standard in terms of teaching, suggestion, motivation, or having a reason to combine.

[00:13:30] Speaker 02:
The district court simultaneously made fact findings that abacavir was a recognized improvement over DDI.

[00:13:38] Speaker 02:
Smaller pill burden.

[00:13:40] Speaker 02:
It had synergy with AZT.

[00:13:42] Speaker 02:
It was more potent.

[00:13:43] Speaker 02:
It had fewer side effects.

[00:13:46] Speaker 02:
The clinical trial didn't have to have results in to be a guarantee of success in order for the person of ordinary skill in the arts to be motivated to use ABC within that combination.

[00:14:00] Speaker 03:
He credited Dr. Ho's testimony that one of skill in the arts

[00:14:06] Speaker 03:
wouldn't be motivated to make the combination because they wouldn't believe that combination could possibly outperform AZT3TC, so they wouldn't be motivated to do it.

[00:14:17] Speaker 02:
And that's the error of law, because when it comes to the actual claims that are asserted here, the triple combination claims and even the double combination claims don't provide any comparative efficacy parameters.

[00:14:31] Speaker 02:
If the claims had said a method for treating whereby this triple combination achieves efficacy superior to AZT3TC... What about toxicity?

[00:14:45] Speaker 03:
Maybe they wouldn't be doing it on efficacy, but wouldn't they be worried about toxicity, dumping all these drugs into an immune-suppressed patient?

[00:14:52] Speaker 03:
No, in fact... Isn't that what the record shows?

[00:14:54] Speaker 02:
No, in fact, quite the opposite.

[00:14:56] Speaker 02:
The record showed that you had a combination of AZT3TC and DDI

[00:15:01] Speaker 02:
And the judge found that abacavir was going to be a less toxic NRTI.

[00:15:07] Speaker 04:
Right, but because of the cross resistance, he said there would be no motivation to confine it.

[00:15:11] Speaker 02:
For the ABC3TC.

[00:15:14] Speaker 02:
But when it comes to abacavir, it actually includes the same mutation that resensitizes the combination back to AZT.

[00:15:25] Speaker 02:
So that does not... And you're saying that he made it factual here.

[00:15:28] Speaker 02:
No, he made that finding.

[00:15:31] Speaker 02:
It was not disputed below that DDI and abacavir produce similar cross-mutation patterns and that one of the mutations, not only the M184 but the L75V, that both of those mutations that ABC produced resensitized back to ABC.

[00:15:49] Speaker 02:
Right, but the cross-resistance with the 3TC was an issue that he was concerned about.

[00:15:54] Speaker 02:
for the double combination.

[00:15:56] Speaker 02:
But for the triple combination, when you're putting AZT back in it, then it works.

[00:16:01] Speaker 02:
And again, it gets back to, first of all, not only what is claimed, because the 191 patent doesn't claim a combination that avoids cross resistance or that comparatively avoids cross resistance,

[00:16:16] Speaker 02:
Cross resistance is not a problem that the 191 patent purports to solve.

[00:16:21] Speaker 02:
And that's a problem because under Merck v. Teva and Alcon v. Abatec, which actually this entire panel was on,

[00:16:34] Speaker 02:
The fact that you might have some generalized safety concerns that are not resolved by the patent specification, that's not a valid problem that you can be focusing on.

[00:16:45] Speaker 02:
Same thing with the Murphy-Teva-Allendron case.

[00:16:47] Speaker 03:
No, but that all goes very much to whether one of skill and the art would be motivated to make that combination.

[00:16:52] Speaker 02:
But the person of ordinary skill, what you're basically saying is that because of this problem, the person of ordinary skill in the art would be skeptical that the combination would work.

[00:17:03] Speaker 02:
And in Merck v. Teva, this court specifically said, no, no, no, you can't do that.

[00:17:08] Speaker 02:
If the patent itself doesn't try to solve the problem, you can't say that that represents skepticism.

[00:17:14] Speaker 02:
Because Merck tried to make the same argument in Merck v. Teva.

[00:17:17] Speaker 04:
The trial court didn't make a skepticism finding.

[00:17:21] Speaker 04:
The trial court specifically found against the patent holder on the skepticism issue.

[00:17:27] Speaker 04:
So I mean, you're mixing apples and oranges here.

[00:17:29] Speaker 04:
What the trial court was saying is that there's got to be some motivation to put these things together.

[00:17:35] Speaker 04:
And you rely on very limited things.

[00:17:37] Speaker 04:
You rely on abstracts, too little abstracts, which is kind of funny about whether you can rely on abstracts or not.

[00:17:44] Speaker 03:
But aren't all abstracts little?

[00:17:46] Speaker 04:
Yes, yes, yes.

[00:17:48] Speaker 04:
So put two abstracts and the larger application, which

[00:17:51] Speaker 04:
It's very generalized and has a huge number of combinations.

[00:17:55] Speaker 04:
So that's what the trial court was trying to say is, is there enough in there to motivate someone to take a particular combination and put them together?

[00:18:04] Speaker 04:
Skepticism was not the issue.

[00:18:05] Speaker 04:
He found it in your favor.

[00:18:07] Speaker 02:
But I think that this idea that there's somehow a problem out there that could discourage the motivation to do the combination.

[00:18:16] Speaker 02:
We have the motivation to do the combination because the back here is a new up and coming NRTI.

[00:18:21] Speaker 02:
He said that doctors would be willing to try anything as long as there wasn't a reason against it.

[00:18:26] Speaker 02:
And he also found that this was a more potent drug that solved some of the problems with the existing NRTIs that were in fact already used in a triple combination, both DDI as well as Carbavir in the Larder application.

[00:18:39] Speaker 02:
We also have the question of even if in the abstract you wanted to create a triple combination, AZT3TC is the best one to start with.

[00:18:47] Speaker 02:
And then if you want to add in a third because you want to hit hard, hit early, and he recognized that principle, then what drug are you going to use?

[00:18:54] Speaker 02:
You're going to use

[00:18:55] Speaker 02:
So one of the very few drugs that is actually in human clinical trials that's being touted, which was a baccalaureate, because that's the one drug that was out there that in that triple combination... You say the one drug.

[00:19:07] Speaker 04:
There were lots of drugs out there.

[00:19:09] Speaker 04:
Lots of drugs.

[00:19:10] Speaker 04:
And that was his point.

[00:19:11] Speaker 04:
And he's saying, among those lots of drugs, am I going to pick the one that has the cross-resistance problem?

[00:19:17] Speaker 02:
But that's the problem, is that if you want to start talking about, I want to rule out something based on cross-resistance, all the other drugs in the other classes, they had equal, if not worse, issues with cross-resistance.

[00:19:30] Speaker 02:
None of them had been shown to work in combination to avoid cross-resistance.

[00:19:34] Speaker 02:
That was true with nevirapine, that was true with lovaride, that was true with... I don't understand how that helped you.

[00:19:39] Speaker 03:
The fact that people try things that might not have been viewed at the outset of potentially being successful doesn't mean they would have tried this thing.

[00:19:48] Speaker 02:
The reason why my point is that if you want to say, here's all these other drugs that I'm going to put on the table, but I want to consider cross resistance as my preeminent thing, even though cross resistance and avoiding cross resistance is not something that's claimed,

[00:20:05] Speaker 02:
and not something that you need to achieve in order to have reasonable expectations of success to achieve what is claimed, that's still not a reason to say, I won't pursue it.

[00:20:16] Speaker 02:
The Mercury Biocraft case, there were 1,200 possible combinations.

[00:20:20] Speaker 02:
And the particular one that was selected out of it was still viewed as being obvious.

[00:20:27] Speaker 04:
But in your case, a backup error wasn't even mentioned in LARGIR.

[00:20:31] Speaker 04:
You have to then jump another step and say, well, they would have picked

[00:20:36] Speaker 04:
is that how you pronounce it?

[00:20:38] Speaker 04:
Out of Larder.

[00:20:39] Speaker 04:
And then you would have found an analog that they would have taken another step.

[00:20:43] Speaker 04:
So I mean, you're really taking us far down the road.

[00:20:46] Speaker 02:
No, I disagree with that.

[00:20:47] Speaker 02:
Because the Larder patents that I hereby include this category of certain types of NRTI categories.

[00:20:55] Speaker 02:
To specifically exemplify one of those, he identified Carbavir.

[00:21:00] Speaker 02:
It was undisputed below that Abacavir and Carbavir metabolized

[00:21:04] Speaker 02:
to produce the identical compound that actually does the therapeutic work in vivo.

[00:21:10] Speaker 02:
A Bacavir, the district court found, was specifically designed to avoid toxicity problems that were associated with Carbavir.

[00:21:18] Speaker 02:
So it's natural for the person of ordinary spill in the air to say, if I see this triple combination that's got Carbavir, the obvious choice to improve upon it is to use a Bacavir because a Bacavir was specifically designed to resolve known problems with Carbavir.

[00:21:35] Speaker 03:
One quick question.

[00:21:36] Speaker 03:
Does this actually matter to your client?

[00:21:38] Speaker 03:
Your client was found not to infringe.

[00:21:40] Speaker 03:
Right?

[00:21:40] Speaker 03:
Not true French.

[00:21:42] Speaker 03:
So you decide to cross the field of blue brief on obvious.

[00:21:46] Speaker 03:
Again, there's lots of tactical reasons you may decide to do that.

[00:21:48] Speaker 03:
But you're client one.

[00:21:51] Speaker 02:
I understand that, but Veev is also asserting the same patent against my client in another.

[00:21:56] Speaker 02:
In the district court.

[00:21:57] Speaker 03:
But that's the same infringement.

[00:21:58] Speaker 03:
If we affirmed on non-infringement, that case would be over there too, right?

[00:22:02] Speaker 03:
Your client wants either way.

[00:22:03] Speaker 03:
If you prevail on the, for that too, is there another, you mentioned another case.

[00:22:08] Speaker 03:
It's the same claims.

[00:22:10] Speaker 04:
The same claims.

[00:22:11] Speaker 04:
Yes.

[00:22:12] Speaker 04:
Thank you.

[00:22:13] Speaker 04:
Mr. Quinn.

[00:22:15] Speaker 01:
Mr. Oakwood, I'm sorry.

[00:22:19] Speaker 01:
I thank you, Chief Judge Croston, and may it please the court.

[00:22:22] Speaker 01:
Just one clarification.

[00:22:23] Speaker 01:
The case that's pending in the district court involves the assertion of additional claims.

[00:22:26] Speaker 01:
So it's not, it wouldn't be, it doesn't involve just the claims that were issued in this case.

[00:22:33] Speaker 04:
But was there infringement findings, the non-infringement finding here, if we are public, would that control in that case?

[00:22:40] Speaker 01:
Not with respect to all the claims that have been asserted in that case.

[00:22:42] Speaker 01:
That's my understanding, Judge O'Malley.

[00:22:44] Speaker 01:
I'm turning back to the issue of obviousness and then I do want to come to the issue of infringement.

[00:22:50] Speaker 01:
The district court's finding of non-obviousness after a trial involving some ten experts is well grounded in the facts.

[00:22:56] Speaker 01:
Dr. Barry in the St.

[00:22:57] Speaker 01:
Clair's discovery of the claimed pharmaceutical combinations was the product of their unique insight from their experience in this field for over a decade.

[00:23:06] Speaker 03:
Just to back up, when you say there are other claims asserted, you mean from a whole different unrelated patent, right?

[00:23:10] Speaker 01:
No, no judgment.

[00:23:11] Speaker 01:
There are other claims.

[00:23:12] Speaker 01:
From the same patent, the derivative claim?

[00:23:15] Speaker 01:
No, some of them may be derivative claims, but there are claims that are asserted, independent claims that are asserted.

[00:23:23] Speaker 01:
in the actions pending in the district court that are not the same as all of the claims that are asserted in this case.

[00:23:28] Speaker 01:
And I believe some of them are also independent claims that did not go to trial in this case.

[00:23:34] Speaker 04:
And what's the status in that case?

[00:23:38] Speaker 01:
Well, there are claims that involve physiologically functional derivatives.

[00:23:41] Speaker 01:
And the status of that case is I think it's relatively early in that case.

[00:23:47] Speaker 04:
When does this patent expire?

[00:23:48] Speaker 01:
This patent expires in March of 2016.

[00:23:52] Speaker 01:
And Judge O'Malley, some of the claims asserted in that case do involve physiologically functional derivatives.

[00:23:58] Speaker 01:
Those are more than just solved claims.

[00:23:59] Speaker 01:
Physiological functional derivatives contain things that are more than solved.

[00:24:03] Speaker 01:
They include esters, ethers, salts of esters, and indeed they give rise to things

[00:24:08] Speaker 01:
not to jump ahead to the issue of infringement, but they give rise to things that create active ingredients different than the active ingredient of tobacco beer.

[00:24:21] Speaker 01:
So it's not the case that physiological functional derivatives

[00:24:25] Speaker 01:
all necessarily give you a back of ear.

[00:24:27] Speaker 01:
Some of them give you other metabolites of a back of ear and don't go through the step of becoming a back of ear.

[00:24:34] Speaker 01:
And that is why the district court fundamentally erred on the issue of infringement here.

[00:24:40] Speaker 01:
There are three separate reasons that the district court erred infringement.

[00:24:44] Speaker 01:
One is the interpretation of the claims under this court's teaching in Merck versus Teva.

[00:24:50] Speaker 01:
Actually, it's different Merck versus Teva cases than my colleague was discussing.

[00:24:53] Speaker 01:
Second is that regardless of how the claims are actually construed, there's no factual dispute that the method claims would actually be infringed.

[00:25:06] Speaker 01:
And that's because a patient is in fact treated with abacavir free base because abacavir sulfate immediately dissolves into abacavir.

[00:25:20] Speaker 01:
And the patient is, in fact, therefore treated with a back of ear free base.

[00:25:23] Speaker 01:
That's not disputed.

[00:25:24] Speaker 01:
Their expert, Lupin's expert, Dr. Arnold, at appendix 441, testified that Lupin's product, quote, provides a back of ear.

[00:25:35] Speaker 01:
That is the active ingredient.

[00:25:37] Speaker 01:
Otherwise, the product won't work, end quote.

[00:25:39] Speaker 01:
And indeed, if you look at the label on Lupin's product at A5782,

[00:25:44] Speaker 01:
It says, quote, in vivo, abacavir sulfate disassociates to its free base abacavir.

[00:25:51] Speaker 01:
And for that reason, the dosages on the labels themselves are in terms of abacavir as opposed to abacavir sulfate.

[00:25:58] Speaker 01:
And in the 5812, the label refers to abacavirs being the active ingredient.

[00:26:02] Speaker 01:
And so what you have is a situation where

[00:26:05] Speaker 01:
All of the elements for method claims in 39 are literally met even if the abacavir chemical formula term were construed as just encompassing abacavir free base and not also encompassing abacavir sulfate.

[00:26:23] Speaker 01:
And the reason for that is because abacavir sulfate is, the patient is treated with abacavir sulfate because it disassociates into it.

[00:26:31] Speaker 01:
The patient is treated with

[00:26:34] Speaker 01:
with ADT and the patient is treated with 3-TC.

[00:26:39] Speaker 01:
And if you look at the elements for claims 30 and 39, that's all that they require.

[00:26:45] Speaker 01:
The district court didn't actually really grapple with this particular issue of non-infringement.

[00:26:51] Speaker 03:
I'd like to move to obviousness.

[00:26:53] Speaker 01:
I'd be happy to, Judge Moore.

[00:26:56] Speaker 03:
ADT and 3-TC was the gold standard.

[00:26:59] Speaker 03:
I don't remember where, but somewhere in the opinion that was what he found, right?

[00:27:03] Speaker 01:
I don't know if he used those words, but I'm sure those words were used at trial, Judge Moore.

[00:27:07] Speaker 03:
50 of his opinion, A55 of the record actually.

[00:27:12] Speaker 03:
It says, ADT-3TC was known as the gold standard of HIV treatment in March of 1995.

[00:27:18] Speaker 03:
So I think I'll treat that as a fact-finding.

[00:27:20] Speaker 03:
So if that's the gold standard that everyone's using, yet

[00:27:24] Speaker 03:
it's still wearing off and it's not, I mean certainly not solving all the problems and doctors are still out there repeatedly and often trying other combinations to see if they can get a little more out of the effectiveness.

[00:27:38] Speaker 03:
Why wouldn't

[00:27:40] Speaker 03:
Can I call it ABC?

[00:27:41] Speaker 01:
Is that... Sure, ABC.

[00:27:43] Speaker 01:
Abacavir is sometimes referred to as ABC.

[00:27:46] Speaker 03:
Yes, all the acronyms are tough, but so are the words for me.

[00:27:50] Speaker 03:
Okay, Abacavir.

[00:27:51] Speaker 03:
So why wouldn't it have been obvious since Abacavir had been one of the other chemicals that have been used in monotherapy to just sort of... I mean, it seemed like a bit of a free-for-all from a medical standpoint in terms of, okay, here are a bunch of things.

[00:28:05] Speaker 03:
as monotherapies there, it's a little effective but not good for this, it's a little effective but not good, and then they're mushing things together.

[00:28:11] Speaker 03:
I mean, it seemed like a Wild West sort of approach to combining things.

[00:28:16] Speaker 03:
Why would it not have been obvious to add a back of ear to what is the gold standard?

[00:28:23] Speaker 01:
First, if you're looking at this through the analysis of an obvious to try analysis, you're dealing with a world where there were hundreds if not thousands of possible combinations that a person of ordinary skill and art would potentially be exploring.

[00:28:38] Speaker 01:
And this court has repeatedly suggested that in the medical arts and in the chemical arts,

[00:28:43] Speaker 01:
The obvious to try analysis typically doesn't fit because you can't predict how things are going to behave.

[00:28:49] Speaker 01:
And that's exactly what the case was.

[00:28:51] Speaker 01:
That yes, it's true, different combinations were being tried.

[00:28:54] Speaker 03:
But there are only 28 drugs in clinical trials, and the fact that there was one of them.

[00:28:57] Speaker 03:
So while theoretically there might be thousands, truthfully we're talking about a universe of 28 at this point in time.

[00:29:03] Speaker 01:
No, we're not, Judge Moore.

[00:29:04] Speaker 01:
Emphatically we are not.

[00:29:05] Speaker 01:
And in fact, if you look at what the defendant's own experts testified about,

[00:29:10] Speaker 01:
Dr. Arnold and Dr. Pontiac both were asked – they were working in this field at the time.

[00:29:18] Speaker 01:
What did you do?

[00:29:18] Speaker 01:
What were you doing then?

[00:29:20] Speaker 01:
And what they were doing, they were working with a number of different types of compounds, NNRTIs, protease inhibitors.

[00:29:28] Speaker 01:
And Dr. Parniat was specifically asked and specifically testified.

[00:29:31] Speaker 01:
He was working with drugs that not only were not in clinical trials, they hadn't even been tried in animal studies.

[00:29:37] Speaker 01:
The idea that a person of ordinary skill in the art would- That's troubling for a whole different set of reasons.

[00:29:42] Speaker 03:
I don't think that necessarily gets you to the lack of motivation to combine.

[00:29:47] Speaker 01:
What it does, Judge Moore, is it gets you that you're not in a universe of 28 drugs.

[00:29:53] Speaker 01:
And you're not in a universe where the spotlight should be appropriately shined on a back of your.

[00:29:58] Speaker 01:
The only reason to focus on a back of your today is through the rubric of hindsight.

[00:30:03] Speaker 01:
I mean, at that time, in March of 1995, there were no clinical results with respect to a back of your.

[00:30:10] Speaker 01:
It's true that it was in front.

[00:30:12] Speaker 03:
But it was identified.

[00:30:13] Speaker 03:
There were only 28 clinical trials that were going on at that time, which is actually a lot.

[00:30:17] Speaker 03:
I shouldn't say only.

[00:30:19] Speaker 03:
But there are 28 clinical trials that are going on.

[00:30:21] Speaker 03:
And that is one of the 28 of the millions of possible drugs.

[00:30:25] Speaker 03:
Obviously, somebody thought that one had enough potential at that time.

[00:30:29] Speaker 03:
I mean, clinical trials are not cheap.

[00:30:32] Speaker 03:
oversight.

[00:30:33] Speaker 03:
I mean somebody thought that was one of the most promising possibilities.

[00:30:38] Speaker 01:
Judge Moore, the inventors had identified a back of ear as being a promising possibility.

[00:30:44] Speaker 01:
The quote that the defendants rely on

[00:30:47] Speaker 01:
comes from an abstract that Ms.

[00:30:51] Speaker 01:
St.

[00:30:51] Speaker 01:
Clair herself was one of the authors of.

[00:30:55] Speaker 01:
Yes, the inventors in this case who also, Ms.

[00:30:59] Speaker 01:
St.

[00:31:00] Speaker 01:
Clair was involved in identifying the activity specifically of AZT, specifically the activity of abacavir and early studies with 3TC itself.

[00:31:09] Speaker 01:
And that was the insight that she was able to bring to bear here.

[00:31:12] Speaker 01:
Yes, she had identified a back of ear as being something for further study.

[00:31:16] Speaker 01:
And the reason that the district court found that is because the district court was rejecting the argument that someone would completely exclude a back of ear, that you wouldn't consider a back of ear at all.

[00:31:28] Speaker 01:
And saying no, it was something that you would consider trying like you would consider trying a lot of other things.

[00:31:34] Speaker 01:
But the point is the district court rejected the notion

[00:31:36] Speaker 01:
that this is a world that was limited to 28

[00:31:43] Speaker 01:
to 28 drugs that were in clinical trials.

[00:31:48] Speaker 01:
And even if you're talking about 28, you're talking about different dosages, different formulations, different delivery.

[00:31:56] Speaker 01:
So you're not talking about a narrow universe.

[00:31:59] Speaker 03:
But then on top of that... But I didn't think that's what we were really disputing, these particular claims, was that dosage levels made it non-obvious for the formulation.

[00:32:08] Speaker 03:
I thought it was

[00:32:09] Speaker 03:
the combination of these three drugs that was really the heart of what we're trying to figure out.

[00:32:13] Speaker 01:
My point Judge Moore is that the fact that you have certain drugs that are out there in clinical trials doesn't mean that you're in a universe of obvious to try because there are lots of different trials that would then have to follow

[00:32:24] Speaker 01:
even if you were starting with those 28.

[00:32:27] Speaker 01:
But on top of that, you have specific testimony that the district court credited from Dr. Ho, this is an A1443-1444, on why a person of ordinary skill in the art wouldn't have been motivated to take the AZT-3TC combination and add a back of ear to it.

[00:32:44] Speaker 01:
He said, quote,

[00:32:45] Speaker 01:
If you're going to build on ADT and 3TC at that time, certainly it's more logical to use the PIs, the protease inhibitors, and the NNRTIs because they were further along with the clinical data and showing a great deal of potency in patients.

[00:32:59] Speaker 01:
And then on top of that, Dr. Ho also testified about concerns with toxicity with triple NRTI combinations at A1440.

[00:33:07] Speaker 03:
But the court found that the toxicity wouldn't be as high with ABC as it was with

[00:33:12] Speaker 03:
Carbonyte?

[00:33:13] Speaker 03:
I'm not going to say it right, because I know that's not whatever.

[00:33:15] Speaker 03:
Carbonyte.

[00:33:17] Speaker 03:
So he made an express finding that toxicity wouldn't be as much of a concern with the ABC.

[00:33:23] Speaker 01:
With respect to that one in particular, and Dr. Ho did talk about that there was a risk of synergistic toxicity between AZT and abacavir.

[00:33:34] Speaker 01:
In part, that risk came out of concerns over carbavir.

[00:33:38] Speaker 01:
But separate and apart from that, Dr. Ho testified at A1440, quote, there was a lot of concern that we might be doing too much chain termination for normal DNA.

[00:33:48] Speaker 01:
And by and large, people avoided the combination of a triple NRTI in part for that reason.

[00:33:53] Speaker 04:
And in fact, there was a- So it ends between two triple NRTIs.

[00:33:57] Speaker 04:
a back-of-hear might have been a little bit better.

[00:34:00] Speaker 04:
But as between triple NRTIs and other combinations, that's what the district court was focusing on, right?

[00:34:07] Speaker 01:
Right.

[00:34:07] Speaker 01:
In other words, you have two drugs here.

[00:34:09] Speaker 01:
One is a double combination of back-of-hear and TPC.

[00:34:13] Speaker 01:
That runs headlong into concerns about cross-resistance.

[00:34:17] Speaker 01:
It was well-known

[00:34:18] Speaker 01:
that both Bacavir and 3TC selected for that has resulted in the same primary mutation, the M184V mutation.

[00:34:28] Speaker 01:
It was also well known that the M184V mutation basically rendered 3TC almost immediately ineffective.

[00:34:34] Speaker 01:
So the idea that you would start with 3TC or start with the Bacavir and think to put the two of them together

[00:34:40] Speaker 01:
is entirely built out of hindsight.

[00:34:42] Speaker 01:
And then with respect to whether you would take AZT and 3TC and then add to it a back of ear, there was only one example in the prior art, two abstracts, one of which came from the inventors, of any triple NRTI combination.

[00:35:00] Speaker 01:
That was the one involving BDI.

[00:35:02] Speaker 01:
It wasn't as though there was some particular reason.

[00:35:05] Speaker 01:
The art didn't say you should explore triple R to NRTI combinations for this reason and there is a reason to then go back in and take BDI out and put a back of the ear in.

[00:35:15] Speaker 01:
That's constructed completely out of hindsight.

[00:35:18] Speaker 01:
What you have is the opposite, and this is the testimony from Dr. Ho, that in general there would be a desire to avoid triple NRTi combinations because what that does is it stops the normal functioning of B and A. And instead what a person of ordinary skill in the art would be motivated to do is exactly what Dr. Ho did, which is to look at other classes of compounds.

[00:35:39] Speaker 01:
The NRTIs look at one step in how HIV replicates within the human body.

[00:35:47] Speaker 01:
There are a lot of other different steps.

[00:35:50] Speaker 01:
And what made sense is to take a backbone and then add other things to it.

[00:35:55] Speaker 01:
And that's exactly what Dr. Hogue successfully pursued separately in a different direction.

[00:36:00] Speaker 04:
Now, you wanted to reserve some of your time for rebuttal on the cross appeal.

[00:36:04] Speaker 04:
That's up to you.

[00:36:05] Speaker 01:
I did.

[00:36:05] Speaker 01:
I believe the clock started at 18.

[00:36:07] Speaker 01:
And so I think, but I'm happy if the court has.

[00:36:11] Speaker 04:
Oh, I'm sorry.

[00:36:12] Speaker 04:
You're right.

[00:36:13] Speaker 04:
I apologize.

[00:36:14] Speaker 01:
If the court has no further questions with respect to obviousness or any of the other issues that were raised in the appeal, I'm happy to rest and reserve the balance of my time for rebuttal that would only be on the issue of

[00:36:29] Speaker 01:
of infringement, but if there are other questions on the issue of obviousness or anything else, I'd be happy to address those.

[00:36:55] Speaker 00:
I'm pleased with the court.

[00:36:57] Speaker 00:
I'm just going to make a couple of quick points because I don't have much time.

[00:37:00] Speaker 00:
First of all, abacavir was not just another drug.

[00:37:04] Speaker 00:
If you look at the district court's opinion in pages 31 and 33 of the appendix, it identifies all of the reasons why abacavir was not just another drug.

[00:37:13] Speaker 00:
It was at the top of the list.

[00:37:16] Speaker 04:
But there is this important point about the difference between just three NRTIs and the two NRTIs.

[00:37:23] Speaker 04:
This isn't just a minor level of toxicity.

[00:37:27] Speaker 04:
We're talking about making people severely ill and anemic and gastrointestinal problems and everything else, right?

[00:37:35] Speaker 00:
That cuts, I suggest, the other way, Your Honor, because one of the principal motivations, the judge found that no one in their right mind would break up the combination of AZT-3TC and substitute a Bacavir for the AZT.

[00:37:53] Speaker 00:
That's simply wrong.

[00:37:55] Speaker 00:
I mean, there was a clear motivation.

[00:37:57] Speaker 00:
The biggest problem with AZT3TC is that there was a substantial subpopulation of patients who could not take it or would not take it.

[00:38:05] Speaker 04:
Right, but you made specific findings of fact and credibility determinations on that issue.

[00:38:09] Speaker 04:
I mean, you've got a huge uphill climb.

[00:38:11] Speaker 00:
I don't think there was any dispute that that was a problem, that toxicity was a problem with the AZT3TC combination.

[00:38:19] Speaker 04:
Well, of course not.

[00:38:19] Speaker 00:
It was a problem for everybody.

[00:38:20] Speaker 00:
But the prior report was also quite clear that a back of beer was not nearly as toxic

[00:38:25] Speaker 04:
But the problem is if you take out the AZT and you just combine it with 3TC, that's when you have the cross resistance and other toxicity issues.

[00:38:36] Speaker 00:
Cross resistance is not a toxicity issue, Your Honor.

[00:38:39] Speaker 00:
Cross resistance is an issue that deals with how long the judge will suppress HIV reproduction

[00:38:47] Speaker 00:
before resistance strains of HIV emerge that are unaffected by the drug.

[00:38:54] Speaker 00:
The cross resistance problem is that, as the district judge thought of it, was that a person of skill in the art would be concerned that the Bacavir-3TC combination would not suppress viral reproduction for as long a period of time.

[00:39:15] Speaker 00:
the AZT-3TC combination.

[00:39:18] Speaker 00:
There is no doubt that it would be less toxic.

[00:39:23] Speaker 00:
Thank you.

[00:39:29] Speaker 02:
Let me address just a couple of quick things on obviousness and then I'll jump into the non-infringement.

[00:39:36] Speaker 03:
Could you first say, was he correct?

[00:39:38] Speaker 03:
I asked you if the district court litigation as to your client would be entirely resolved if we were affirming on non-infringement here.

[00:39:46] Speaker 03:
Is he correct that it's not the case that it would be?

[00:39:50] Speaker 02:
I don't know whether they're going to continue to assert all the claims at trial that they did in this case.

[00:39:58] Speaker 02:
Presumably if they decide to assert more claims even if they're invalidated.

[00:40:04] Speaker 02:
Even if we find non-infringement here, that's still going to create a separate set of claims.

[00:40:10] Speaker 03:
Are there claims asserted in the other litigation to which the non-infringement decision here would not apply?

[00:40:17] Speaker 04:
I believe there are.

[00:40:20] Speaker 04:
And how could there be a second lawsuit without an argument that the cause of action was split?

[00:40:28] Speaker 02:
I mean, I'm not prepared today to talk about issues of potential claim preclusion or collateral at stop-all, but I do know that one of the reasons why we chose to file this cross-appeal on the invalidity issues is because we want to ensure that we are not prejudiced in the

[00:40:47] Speaker 02:
follow-on litigation.

[00:40:49] Speaker 02:
I mean, again, there's an IPR pending against this patent.

[00:40:52] Speaker 02:
Obviously, if that is resolved to invalidate the patent, that's going to impact the other litigation too, but we're not... Go ahead.

[00:40:59] Speaker 02:
Get on to your rebuttal.

[00:41:00] Speaker 02:
Sure.

[00:41:01] Speaker 02:
No, I did want to say that for Dr. Ho, Dr. Ho's testimony about

[00:41:07] Speaker 02:
why he thought you would want to use as a third drug the protease inhibitors.

[00:41:13] Speaker 02:
He specifically said that he was basing that on his own personal experience within his lab where he had access to all kinds of non-public data regarding the protease inhibitors.

[00:41:25] Speaker 02:
And he conceded, and we put the sites in our brief, that that was not disclosed until 1996.

[00:41:30] Speaker 02:
So that teaching about the protease inhibitors cannot serve as a valid motivation teaching when we're looking at the relevant March 1995 time period here.

[00:41:41] Speaker 02:
Further, Dr. Ho also admitted, and this is at A1513, contrary to council's representation, he acknowledged that doctors had been prescribing triple NRTI combinations.

[00:41:54] Speaker 02:
No, separate and apart from the ZDI combination in the clinical trials, they had combined AZT-DDC

[00:42:01] Speaker 02:
and DDI.

[00:42:02] Speaker 02:
So doctors had, in fact, done a triple NRTI combination, notwithstanding all of these existing cross-resistance concerns and what have you.

[00:42:12] Speaker 02:
And I would also like to note that the abstract, you know, small though it may be, it did actually say that the AZT3TC-DDI combination when it was tested in vitro

[00:42:23] Speaker 02:
was actually one of the most potent combinations, particularly when given to patients early.

[00:42:29] Speaker 02:
So then what did they do?

[00:42:30] Speaker 02:
They then went into clinical trials and started giving it to children who were early on in the disease.

[00:42:36] Speaker 02:
So I think that the person of ordinary skill in the art can actually learn quite a lot from those two abstracts about why this is happening.

[00:42:44] Speaker 02:
You've got the AZT3TC combination.

[00:42:46] Speaker 02:
You see what was done with the FDA approved drug on the market, DDI, how they added it to the combination.

[00:42:52] Speaker 02:
So you know that abacavir is also synergistic with AZT, and that it's got some properties that are better than DDI, that's a reason to include it in the combination.

[00:43:05] Speaker 04:
But from that, you'd have to actually change two drugs from what was described in the abstract, correct?

[00:43:12] Speaker 02:
No, just one.

[00:43:14] Speaker 02:
You would take the DDI, which was already on the market, and because abacavir was known to perform heavily,

[00:43:22] Speaker 02:
attributes that were better than DDI, that would be the one that you would substitute.

[00:43:28] Speaker 02:
You would preserve the very successful AZT-3TC combination and then say, all right, but DDI, it has some known drawbacks.

[00:43:37] Speaker 03:
But the district court made fact-finding about cross-resistance.

[00:43:40] Speaker 03:
And whether I agree with you or not, I've got to go give those clear errors deference.

[00:43:45] Speaker 03:
I mean, maybe you're right.

[00:43:45] Speaker 03:
Maybe, you know, oh, well, you know, my

[00:43:49] Speaker 03:
understanding of the complexity of this technology, DDI and ABC, aren't that different from each other in lots of relevant respects.

[00:43:58] Speaker 03:
However, the district court said cross resistance was a problem.

[00:44:01] Speaker 03:
People were concerned about it.

[00:44:03] Speaker 03:
Those were his fact findings.

[00:44:04] Speaker 03:
How can I just disregard them because there happened to be a single or two single abstracts that proposed a free drug combination like that.

[00:44:12] Speaker 02:
Well, there was also physicians who had done the three-drug combination.

[00:44:16] Speaker 02:
They'd actually prescribed it.

[00:44:17] Speaker 03:
Yes, but he made a fact-finding that people with skills in the art were worried about cross-resistance, and that's why they wouldn't do this.

[00:44:22] Speaker 03:
And yes, there is some limited evidence of some people doing it.

[00:44:26] Speaker 03:
But even the fact-finding, how do I say it's clearly erroneous?

[00:44:30] Speaker 02:
Because it's not teaching away.

[00:44:32] Speaker 02:
The fact that there might be some cross-resistance doesn't automatically mean that the triple-drug combination is not going to achieve what is actually claimed, which is

[00:44:42] Speaker 02:
reducing the amount of HIV in the bloodstream.

[00:44:45] Speaker 04:
That's the key distinction.

[00:44:46] Speaker 04:
He didn't say it was teaching away.

[00:44:48] Speaker 04:
What he said is you have the burden of proving that there is a motivation that exists in the prior art.

[00:44:55] Speaker 04:
It's not just a simple question of whether or not people were willing to take crapshoots.

[00:44:59] Speaker 04:
You have to actually say, was there a motivation that you can point to in the prior art that would make this obvious and that would provide a motivation to combine?

[00:45:09] Speaker 04:
And the trial court found that there was.

[00:45:11] Speaker 04:
No, I disagree.

[00:45:12] Speaker 02:
The trial court found that there were reasons to include ABC in a combination.

[00:45:20] Speaker 02:
When he started focusing on cross-resistance, what he's basically doing is he's putting himself in the mindset of the inventors.

[00:45:26] Speaker 02:
And then, well, what were the inventors interested in?

[00:45:28] Speaker 02:
They were interested in cross-resistance, so I'm going to impute that to the person of ordinary skill in the arts.

[00:45:33] Speaker 04:
And then he said, the question is not whether there is any motivation to put any particular drug into a combination generally, but is there a motivation to put this drug in this combination?

[00:45:46] Speaker 02:
I understand that, and the problem is that when it comes to cross resistance, that should not be a discouraging factor that can counter motivation because the 191 patent itself doesn't solve the cross resistance problem.

[00:46:01] Speaker 02:
If you want to basically say that cross resistance is the end-out-be-all that's going to allow a person of ordinary skill and the art to credibly believe that this combination is going to work, then the 191 patent claims themselves have to fall as non-enabled because they don't express a credible utility.

[00:46:15] Speaker 02:
I mean, that's the fundamental problem.

[00:46:17] Speaker 02:
The 191 patent doesn't solve the problem, and this court's precedent that we've cited is clear, that you can't argue against a motivation based on a problem that the patent itself doesn't pretend to solve over the prior art.

[00:46:30] Speaker 02:
If I may, let me turn briefly to the non-infringement.

[00:46:33] Speaker 02:
issues.

[00:46:34] Speaker 02:
First, I did want, oh, I'm sorry, and there actually was testimony in the record, I will find it, where Dr. Blick actually testified that he prescribed drugs even though they were cross resistant and that cross resistance would not factor into his prescribing decisions.

[00:46:49] Speaker 02:
Now, when it comes to the cross appeal on claim construction, the district court

[00:46:55] Speaker 02:
specifically stated, and this is at 821, that our expert, Dr. Arnold, persuasively explained how the salt form is chemically distinct from the pure or free base form of the back of ear, that the court cannot find the person skilled in the art would have understood the pure or free base form of the back of ear to be the same thing as or to encompass the salt form.

[00:47:16] Speaker 02:
Those are findings of fact and they do deference here.

[00:47:19] Speaker 02:
On the literal infringement question, we dispute plaintiff's characterization.

[00:47:24] Speaker 04:
Are they finding the facts relating to claim construction?

[00:47:26] Speaker 04:
Is that your view on this?

[00:47:28] Speaker 02:
I think that he made a finding of fact that the person of ordinary skill in the art would not view the 1S methanol chemical language and encompassing salts.

[00:47:38] Speaker 02:
And that's exactly what takes this case out of the realm of Murphy-Teva.

[00:47:42] Speaker 02:
It takes it out of the realm of the Stevens case.

[00:47:44] Speaker 02:
that plaintiff cited in their reply brief.

[00:47:46] Speaker 02:
He found the person of ordinary spill in the air would not view the chemical nomenclature in the claims to implicitly include the salt, and that's entitled to deference here, particularly in view of the recent Supreme Court Teva decision.

[00:48:01] Speaker 02:
Now when it comes to the literal infringement issue, the district court likewise found that the abacavir free base was not still in there in the salt, that it had been chemically modified in a way that took it outside the claims.

[00:48:16] Speaker 02:
Now when plaintiffs say, oh, but somebody admitted that in vivo you can actually destroy the sulfate salt and get some abacavir free base before it gets metabolized to carbavir triphosphate,

[00:48:28] Speaker 02:
That is fundamentally irrelevant because these claims that are at issue here have more in them than just here is a back of ear being used

[00:48:37] Speaker 02:
in a patient.

[00:48:38] Speaker 02:
What these claims require are all kinds of additional elements relating to being in a combination with either one other drug or two other drugs being administered as a unit dose, et cetera.

[00:48:51] Speaker 02:
And the plaintiffs did not separately post out their method claims this way.

[00:48:55] Speaker 02:
So when it comes to each and every element being infringed, when it comes to what's going on inside the body, they never tried to show each and every element of their claims was satisfied.

[00:49:07] Speaker 02:
when you were in vivo.

[00:49:09] Speaker 02:
And that's a fundamental failure proof.

[00:49:10] Speaker 02:
They didn't even try to prove that at the district court.

[00:49:13] Speaker 02:
And sorry.

[00:49:14] Speaker 04:
We'll conclude your argument way over time.

[00:49:16] Speaker 04:
And Mr. Oaks, for final statements, just on the non-infringement issue, the subject of your cross-examination.

[00:49:23] Speaker 01:
Yes, Chief Judge, first.

[00:49:24] Speaker 01:
Thank you.

[00:49:26] Speaker 01:
First, Judge O'Malley, in answer to your question, the reason there's another lawsuit is they filed another Ando with respect to a different drug.

[00:49:32] Speaker 01:
And this patent is asserted with respect to that drug.

[00:49:36] Speaker 01:
Turning to the issue of infringement, again there are three independent reasons why Lupin's product infringes.

[00:49:45] Speaker 01:
The first is that the method claims, what my colleague was just talking about, the method claims

[00:49:51] Speaker 01:
All of the elements are met when a patient is treated with lupin's product.

[00:49:56] Speaker 01:
They're all literally met.

[00:49:57] Speaker 01:
However, the chemical formula term for abacavir is construed, whether it's construed as just being the free base or it's construed as you think it should be as encompassing the salt forms as well.

[00:50:09] Speaker 01:
Either way, they're all construed.

[00:50:11] Speaker 01:
And my colleague made points about, well, there are other things that haven't been proved up.

[00:50:17] Speaker 01:
Respectfully, that's just not true with respect to method claims 30 and 39.

[00:50:22] Speaker 01:
If you look at method claims 30 and 39, they depend on independent claims 20 and 32.

[00:50:29] Speaker 01:
And what does it say?

[00:50:30] Speaker 01:
A method for the treatment or prevention of the symptoms or effects of an HIV infection in an infected animal, treating said animal with a therapeutically effective amount of a combination comprising

[00:50:41] Speaker 01:
a back of ear and one of them is a back of ear in 3TC and the other is a back of ear ADT in 3TC.

[00:50:51] Speaker 01:
And what all the claims 30 and 39 add to the independent claim is that said animal is a human.

[00:50:57] Speaker 01:
And you have other dependent claims that show it doesn't matter the sequence in which they're administered.

[00:51:02] Speaker 01:
So if you look at claims 27, 28, 29, 27 talks about simultaneous, 28 talks about sequential, 29 talks about a single combined formulation.

[00:51:13] Speaker 01:
But that is a subset of what's covered by independent claims 20 and a counterpart 32.

[00:51:22] Speaker 01:
And the only thing that dependent claims 30 and 39 add, which are asserted here, is that it be a human.

[00:51:29] Speaker 01:
And there's no dispute about that.

[00:51:32] Speaker 01:
The drugs are all that a person, a patient, a human is treated with a back of your free face and not as just some person testified, but their expert on non-infringement.

[00:51:44] Speaker 01:
Dr. Arnold specifically testified, quote,

[00:51:48] Speaker 01:
Lupin's product provides a back of beer.

[00:51:50] Speaker 01:
That is the active ingredient.

[00:51:52] Speaker 01:
Otherwise, it wouldn't work.

[00:51:54] Speaker 01:
And that leads me directly into the issue of infringement under the doctrine of equivalence.

[00:51:59] Speaker 01:
Because even if for some reason, there was some reason not to find that there's literal infringement of the method claims.

[00:52:06] Speaker 01:
This is clearly a case that falls within the doctrine of equivalence.

[00:52:09] Speaker 01:
Dr. Langer, our expert, explained that abacavir sulfate is used like abacavir to treat HIV symptoms the same way, by delivering the same active ingredient, abacavir,

[00:52:23] Speaker 01:
to inhibit HIV replication in the same way.

[00:52:26] Speaker 01:
That's at A351 to 356.

[00:52:27] Speaker 01:
That's the function way result test every time.

[00:52:32] Speaker 01:
And the only responses to that that were offered either by the district court or by Lupin are, well, you don't know that it necessarily has the same handling properties.

[00:52:42] Speaker 01:
That's not relevant to the claims that are asserted.

[00:52:44] Speaker 01:
And it's certainly not relevant to the asserted method claims.

[00:52:48] Speaker 01:
or to suggest that there should be some per se rule against applying the doctrine of equivalence this way because there are other claims that could have been asserted that might also cover these things as well.

[00:53:03] Speaker 04:
Let me ask you about that.

[00:53:04] Speaker 04:
So why didn't you assert the claim that specifically referenced the salt derivative?

[00:53:11] Speaker 01:
Judge O'Malley, I'm not privy to that.

[00:53:14] Speaker 01:
I mean, trials about choices, about narrowing things down.

[00:53:17] Speaker 01:
And the parties narrowed a number of things and dropped defenses and dropped claims as well.

[00:53:24] Speaker 01:
And as the claims were being dropped, the claims that were asserted were the ones that were being asserted.

[00:53:31] Speaker 04:
But you can understand the trial court's concern.

[00:53:33] Speaker 04:
So you've got a patent, and maybe the patent has five claims, and you choose to assert one.

[00:53:38] Speaker 04:
And when you lose on infringement on that one, you say, well, under DOE, we can get what could have been asserted under claim three.

[00:53:47] Speaker 01:
But Judge O'Malley, that concern would come up in every single case.

[00:53:51] Speaker 01:
That would create a prospect where a party would essentially run the risk if you don't assert all of the claims in your patent, then you're going to lose scope of DOE that you would otherwise have.

[00:54:03] Speaker 01:
That is inconsistent with the Graver-Tank decision itself.

[00:54:06] Speaker 01:
And this court walked through that in Johnson & Johnson, where you had claims that would have been literally infringed, except it turns out those were invalidated.

[00:54:15] Speaker 01:
It's not just that they weren't asserted, they were invalidated.

[00:54:18] Speaker 01:
And later the Supreme Court held that the claims that remained, that were asserted, would capture that scope under the doctrine of equivalence.

[00:54:25] Speaker 01:
And this court has recognized in a number of cases, multi-form desiccants, 133 F3rd at 1480,

[00:54:32] Speaker 01:
The, quote, claims that are written in different words may ultimately cover substantially the same subject matter.

[00:54:39] Speaker 01:
Claims are looked at, they rise and fall independently, both for infringement purposes and for invalidity purposes.

[00:54:44] Speaker 01:
And so to go the way that the district court did would need to be making a policy choice.

[00:54:52] Speaker 01:
And that is exactly what the Supreme Court has reiterated in Warner Jenkins and Fesso that the courts are not supposed to be doing with respect to the doctrine of equivalence.

[00:55:01] Speaker 01:
And to come up with some sort of a per se rule here, I think would A, be inconsistent with that, and B, I think it would create bad incentives in district court and make it hard for parties to narrow the claims that are being asserted without running the risk of exactly what you were just talking about, Judge O'Malley.

[00:55:19] Speaker 01:
But in any event, we think this is also a straightforward case for literal infringement, precisely because there can't be any serious dispute that all three of the claimed elements

[00:55:33] Speaker 01:
are what a patient is treated with.

[00:55:35] Speaker 01:
I mean, it's right there on their own label.

[00:55:37] Speaker 01:
I mean, you ask, why would you have narrowed some claims?

[00:55:40] Speaker 01:
I mean, you look at the label, A5782, in vivo, abacavir sulfate disassociated to its free base of abacavir.

[00:55:47] Speaker 01:
No dispute over that.

[00:55:49] Speaker 01:
And then finally, and the court certainly doesn't have to reach this in order to reverse with respect to the method claims.

[00:55:57] Speaker 01:
But we also have the argument that, in fact, the chemical formula term of Acavir appearing in the claims would be construed by a person of ordinary skill in the art as encompassing the salt forms as well, just as this court held in Merck versus Teva.

[00:56:12] Speaker 01:
And the only argument that my colleague makes to the contrary is to say, well, there's testimony that a person of ordinary skill in the art understood these were different chemical formulas.

[00:56:22] Speaker 01:
They're different chemicals, different chemical weights, and so forth.

[00:56:28] Speaker 01:
That's not disputed, and it's also not relevant.

[00:56:31] Speaker 01:
In fact, this court in Merck versus Teva specifically rejected that kind of argument, that kind of reasoning, saying the question is not whether a person of ordinary skill in the art would understand whether they're different chemicals.

[00:56:41] Speaker 01:
The question is whether they would understand in the context of the claims, the context that they're written,

[00:56:47] Speaker 01:
that by using it, you're meant to encompass the active ingredient, however it was administered, whether in its free base or free acid or salt form.

[00:56:56] Speaker 01:
If the court has further questions, I'm happy to take those.

[00:56:58] Speaker 01:
Otherwise, thank you very much.

[00:57:00] Speaker 01:
We ask that the court...