[00:00:03] Speaker 02:
We have one case on the calendar this morning, based on an emergency motion.

[00:00:09] Speaker 02:
Mylan Institutional versus Orobindo Farmer, 2017-16-45, Mr. Patel.

[00:00:17] Speaker 02:
Good morning, Your Honor.

[00:00:23] Speaker 02:
Please approach the capture.

[00:00:26] Speaker 02:
Before you begin, and please don't run the clock,

[00:00:30] Speaker 02:
Not yet.

[00:00:32] Speaker 02:
I want to ask you, several of your submissions were rejected.

[00:00:37] Speaker 02:
Why is it so difficult to comply with our rules?

[00:00:40] Speaker 01:
Your Honor, we apologize for that.

[00:00:42] Speaker 01:
I think it was one of our teams for the first couple of filings.

[00:00:48] Speaker 02:
All right.

[00:00:48] Speaker 02:
OK.

[00:00:48] Speaker 02:
Well, please proceed.

[00:00:51] Speaker 01:
May it please the court.

[00:00:53] Speaker 01:
Your Honors, thank you for scheduling this hearing on an expedited basis.

[00:00:57] Speaker 01:
Your Honors, this is not a Hatch-Waxman case.

[00:00:59] Speaker 01:
Both Myelin and Oribindo made generic versions of the branded isosulfan blue product that had been approved by the FDA since 1982.

[00:01:09] Speaker 01:
Apicor obtained three patents on certain aspects of isosulfan blue.

[00:01:16] Speaker 01:
Two patents, the 992 and 616, are directed to a process for making isosulfan blue.

[00:01:21] Speaker 01:
And the third patent, the 050 patent, which we call the purity patent, is directed to a claim that

[00:01:28] Speaker 01:
is a 99% pure version of isosult and gluten.

[00:01:34] Speaker 02:
Well, let me ask you about that.

[00:01:36] Speaker 02:
It's really a compound patent.

[00:01:39] Speaker 02:
Wasn't there a long-felt need in commercial success with respect to this product?

[00:01:48] Speaker 02:
predecessors had gone out of business, there were shortages, and here this nearly pure 99% plus fuel compound was obtained.

[00:02:04] Speaker 02:
Why don't we uphold preliminary injunction as that being likely valid?

[00:02:11] Speaker 01:
Your Honor, there was no long felt but unmet need.

[00:02:14] Speaker 01:
Let me start with that.

[00:02:17] Speaker 01:
Lymphazurin product was approved in 1982.

[00:02:20] Speaker 01:
In the record, there's only evidence of one time period of shortage, which was in the 2006 time frame.

[00:02:27] Speaker 01:
And that was when Ally Chemical, the supplier for the API for isosulfan blue, went out of business.

[00:02:34] Speaker 01:
It's undisputed that for over 29 years, the market was satisfied with lymphazurin product.

[00:02:43] Speaker 01:
And it was found to be safe and efficacious.

[00:02:45] Speaker 01:
And when it was withdrawn,

[00:02:47] Speaker 01:
it was not withdrawn for any safety or efficacy reasons.

[00:02:50] Speaker 01:
It was just a business decision that was made by the COVID-19 at the time.

[00:02:56] Speaker 01:
And so with respect to Longfellow put on the need in terms of shortages, we have to look at the whole history of that 30-year period in which lymphazorin was sold and not just focused on that 2005 time period where there was a business reason for a supply shortage.

[00:03:12] Speaker 01:
There's no evidence in the record that that shortage was a result of

[00:03:17] Speaker 01:
some problem with the prior art process?

[00:03:21] Speaker 01:
Secondly, in terms of a long felt-but-unmade deed, it's clear.

[00:03:24] Speaker 02:
Well, the prior art process didn't yield a virtually pure product.

[00:03:28] Speaker 02:
And sure, it is always important administering a drug to a human.

[00:03:33] Speaker 01:
The prior art process did result in a pure enough, sufficiently pure product that it was approved by the FDA.

[00:03:41] Speaker 01:
And critically, myelin, as a generic version, as a generic substitute,

[00:03:45] Speaker 01:
does not claim any advantage or benefit or market it for any benefit over the lymphozerone product.

[00:03:53] Speaker 04:
It looks like the marketplace dictated otherwise, right?

[00:03:58] Speaker 04:
I mean, once the 99% pure isosulfur was developed, then the market went for that.

[00:04:07] Speaker 01:
The market, it was not for the 99%.

[00:04:11] Speaker 01:
didn't have any knowledge of the 99%, meaning the hospitals, customers, if you look all the way down the chain, Mylan markets its product as being equivalent and in fact on its website provides lymphazurin data for safety and efficacy.

[00:04:25] Speaker 01:
So the market shifted to Mylan as is typical when a generic product comes out because of price reasons.

[00:04:32] Speaker 01:
The pricing was much

[00:04:33] Speaker 01:
Mylon priced it lower, and therefore the market accepted the Mylon product.

[00:04:40] Speaker 01:
There's no evidence that it was wrong.

[00:04:42] Speaker 02:
You say that this is not a Hatch-Waxman case.

[00:04:45] Speaker 02:
Who are you both copying?

[00:04:50] Speaker 02:
And whose NDA are you both working from, or did you each supply your own?

[00:04:57] Speaker 01:
That's a good question, Your Honor.

[00:04:58] Speaker 01:
The NDA holder was a company named Covidian.

[00:05:01] Speaker 01:
Initially, it was Hirsch Industries who developed the product in 1982, and Covidian was the NDA holder.

[00:05:10] Speaker 01:
When Myelin filed its ANDA, it had to show that it was bioequivalent to the lymphazoid product.

[00:05:18] Speaker 01:
And in 2012, I believe, when Covidian left the market,

[00:05:24] Speaker 01:
Mylan's product, because no other lymphazurin product is on the market, it was listed as the reference listed drug product that if any other generic company wanted to make a generic version, they had to use data from the Mylan ISP product.

[00:05:40] Speaker 01:
So, Your Honors, we believe that the long felt but unmet need, there was none that was satisfied by Mylan's ISP product that wasn't already satisfied by lymphazurin.

[00:05:53] Speaker 01:
And the district court abused its discretion and made at least three clear errors that we would like to talk about today.

[00:06:01] Speaker 01:
We believe there are a number of other errors.

[00:06:03] Speaker 01:
The first error was in reading out the causal nexus requirement, finding it largely irrelevant for FDA-approved products and so-called simple products.

[00:06:14] Speaker 01:
The second error is that it clearly erred in finding infringement under the doctrine of equivalence

[00:06:20] Speaker 01:
despite uncontroverted evidence that Orebindo's different process using manganese dioxide and an acid performs in a substantially different way and gets a substantially different result, whether you look at it in purity or in yield.

[00:06:34] Speaker 02:
What's the difference result?

[00:06:35] Speaker 02:
Didn't it yield pure product?

[00:06:40] Speaker 02:
I'm sorry.

[00:06:40] Speaker 02:
Didn't they both yield pure product?

[00:06:43] Speaker 02:
So why was there a different result?

[00:06:45] Speaker 01:
So the different result, your honor, you have to look at what Orbindo did is that it used a conventional preparative HPLC step to get up to the 99%.

[00:06:58] Speaker 01:
So the oxidation reaction.

[00:07:00] Speaker 02:
Was that HPLC step used to get to the pure product or to verify that it was pure?

[00:07:07] Speaker 01:
The HPLC is used to get to the pure product.

[00:07:10] Speaker 02:
I thought that was crystallization.

[00:07:13] Speaker 01:
No, the crystallization is performed and then Ourobindo uses preparative HPLC to further purify it to 99%.

[00:07:21] Speaker 01:
For recrystallization, Ourobindo gets 94% pure product.

[00:07:26] Speaker 02:
So that's your argument for a different way.

[00:07:29] Speaker 01:
One of the arguments for a different way and that's similar to the Netzer versus Shell case where the facts were very similar and Shell was using the conventional

[00:07:40] Speaker 01:
purification process to get to the claim purity level.

[00:07:46] Speaker 01:
The other different way is that manganese dioxide is a strong accident.

[00:07:52] Speaker 01:
And the proof is in the pudding.

[00:07:54] Speaker 04:
The judge was... But the claims don't claim any type of limitation dealing with the strength of oxidization, correct?

[00:08:02] Speaker 01:
That is absolutely correct.

[00:08:04] Speaker 01:
And we believe that... And then why does it matter?

[00:08:06] Speaker 01:
We believe that the district court here

[00:08:09] Speaker 01:
in citing Intendis.

[00:08:12] Speaker 01:
The Intendis case stands for the exact opposite position in that you can, when you're looking at the different way, you have to look at the different chemical properties of the compound to see how a person of boarding skill in the art would understand whether or not it's operating in a different way.

[00:08:35] Speaker 01:
So even though it's not part of the claim, one would have to look at

[00:08:40] Speaker 01:
How strong is it?

[00:08:41] Speaker 01:
How is it reacting?

[00:08:42] Speaker 01:
And does it provide a different result?

[00:08:45] Speaker 01:
And the judge was right on page 24 when he said that if it was a strong oxidant, one would expect a different result.

[00:08:53] Speaker 01:
And he made a mistake.

[00:08:54] Speaker 01:
He looked at the yield in the Orbindo Indian patent application, assuming that that was representative of our product.

[00:09:01] Speaker 01:
But that is not.

[00:09:02] Speaker 01:
You have to look at our ANDA submission, which shows that we only have yield of 88%.

[00:09:07] Speaker 01:
And when you look at the correct metric, which is purity, which is what these patents are trying to achieve, we get 94% after the oxidation step, and then have to use a conventional preparative HPLC to get it up to 99%.

[00:09:23] Speaker 01:
So there was a clear error in the finding of doctrine of equivalence on the 992 and 616 patents.

[00:09:32] Speaker 04:
Does the doctrine of equivalence have a different application in the chemical,

[00:09:36] Speaker 04:
field as opposed to, let's say, mechanical or other fields?

[00:09:42] Speaker 01:
Your Honor, my understanding is the doctorate of equivalence is the same, regardless of the field of technology.

[00:09:47] Speaker 01:
This court and Supreme Court in Warren and Jenkinson has held that whether you look at it from insubstantial differences or function way or result, it's Warren parties not to get caught up in the semantics of the two.

[00:10:04] Speaker 01:
function way result is really just a tool for determining whether or not there are insubstantial differences.

[00:10:11] Speaker 01:
And in this case, we focused on function way and result because it was a better tool to look at, you know, what exactly, what is the function that's being played by these various... Do you know the structures of aspirin and ibuprofen?

[00:10:27] Speaker 01:
Not off the top of my head, your honor.

[00:10:30] Speaker 02:
Most chemists would consider them very different in structure.

[00:10:34] Speaker 02:
hardly equivalent, but they operate, do the same function in the same way to give the same result.

[00:10:40] Speaker 02:
So that's perhaps why the Supreme Court said that it is sometimes difficult to apply FWR in a chemical context.

[00:10:53] Speaker 01:
Yes, in that case, you're right.

[00:10:54] Speaker 01:
If they do have the same function way result, but structurally they're very different, one may find that there are still substantial differences between aspirin and ibuprofen.

[00:11:04] Speaker 04:
How about if the differences are marked, I mean, just very clear?

[00:11:12] Speaker 04:
Isn't silver, oxide, and manganese dioxide come from different elements on the table of elements?

[00:11:22] Speaker 01:
Yes, absolutely, Your Honor.

[00:11:24] Speaker 04:
Right off, don't you start with the notion that we're dealing with something that's substantially different.

[00:11:31] Speaker 01:
We would agree with that.

[00:11:32] Speaker 01:
That is substantially different.

[00:11:33] Speaker 01:
And there's no dispute here that we don't literally infringe.

[00:11:38] Speaker 01:
We designed around this process using a different oxidation agent that functions in a different environment as well.

[00:11:47] Speaker 01:
Manganese dioxide only oxidizes with acid.

[00:11:50] Speaker 01:
And the patentee during prosecution distinguished the prior processes that used acid.

[00:11:59] Speaker 01:
said that the use of silver oxide without acid was one of the things that allowed it to get to this.

[00:12:05] Speaker 03:
If you prevail on this doctrine of equivalence argument, the preliminary injunction still needs to be affirmed unless we also are willing to agree with you on the validity of the 050.

[00:12:15] Speaker 03:
Is that right?

[00:12:17] Speaker 01:
On the 050 or on the causal nexus piece.

[00:12:19] Speaker 01:
The causal nexus piece runs across all three patents for the word.

[00:12:25] Speaker 01:
If the court finds that the causal nexus requirement

[00:12:29] Speaker 01:
was not met.

[00:12:31] Speaker 03:
But one of your problems with your causal nexus argument is throughout you seem to think the causal nexus has to be to the novel features as opposed to the patented features.

[00:12:41] Speaker 03:
It's like you want, I don't know, I feel like this is the week where people want us to return to the gist or the heart of the invention idea that you all want every doctrine to be tied to some identification of novelty as opposed to the patent claim limitations itself and I just don't think that

[00:12:58] Speaker 03:
is consistent with our law, or makes any good sense.

[00:13:02] Speaker 01:
Your Honor, I disagree.

[00:13:03] Speaker 01:
I believe that the Apple v. Samsung line of cases and others, when it's talking about the... I have some degree of familiarity with them.

[00:13:09] Speaker 03:
I don't think they stand for that proposition.

[00:13:13] Speaker 01:
I think that one should look at the novel features to see if it's driving the demand.

[00:13:18] Speaker 01:
Otherwise, consumers really are buying it because it's a generic substitute of lymphazorin, for no other reason than it's a generic substitute of lymphazorin.

[00:13:28] Speaker 01:
And finally, Your Honor, with respect to the 0-5-0 patent, I think I'm in my rebuttal time, we believe that the district court erred in, even after finding that there is no difference in degree, he found that the claim could still not be obvious because a process to go from 95% to 99% could be patentable.

[00:13:51] Speaker 01:
But as the court knows, that claim is just a compound claim and has no process limitations.

[00:13:56] Speaker 02:
We will give you your three minutes of rebuttal back.

[00:14:02] Speaker 02:
Ms.

[00:14:02] Speaker 02:
Stafford.

[00:14:05] Speaker 00:
Good morning.

[00:14:07] Speaker 00:
My name is Nicole Stafford, and I represent or am speaking on behalf of Milan Institutional and APICOR this morning.

[00:14:13] Speaker 00:
Your honors, I would like to first focus on some new arguments that were raised by Ourobindo in their appeal, specifically in raised in the reply, since APICOR and Milan did not have an opportunity to provide rebuttal to those.

[00:14:24] Speaker 00:
Now in challenging the district court's factual finding under doctrinal equivalence, Aurobindo claims that after analyzing only the function of manganese dioxide in Aurobindo's process, that is to act as the oxidizing agent, the district court concluded that Aurobindo's process infringes by equivalence.

[00:14:39] Speaker 00:
As an initial matter, Ourobindo's non-infringement positions throughout the PI briefing and appeal have been shifting.

[00:14:45] Speaker 00:
To be clear, Ourobindo's technical expert only testified in his declaration that silver oxide and manganese dioxide have different functions under the function-way result test.

[00:14:55] Speaker 02:
But look, they are substantially different, aren't they?

[00:15:00] Speaker 02:
Manganese works with acid, and silver doesn't need acid.

[00:15:06] Speaker 02:
They're in different groups of the periodic table.

[00:15:11] Speaker 02:
One has a plus four valence oxidation state and one is plus one.

[00:15:17] Speaker 02:
Why aren't those substantially different and therefore not equivalent, at least for preliminary injunction purposes?

[00:15:26] Speaker 00:
Well, I believe that they are only insubstantially different because they perform the same function in the same way and achieve substantially the same result.

[00:15:34] Speaker 02:
Some of these arguments... But I'm just asking, there are really two possible ways of looking at equivalents, FWR and insubstantiality of the differences.

[00:15:44] Speaker 02:
And I'm asking why they aren't substantially different for the reasons I outlined.

[00:15:52] Speaker 00:
Well, we believe that they are only insubstantially different.

[00:15:56] Speaker 00:
They both serve the same function.

[00:15:58] Speaker 00:
The arguments with respect to the valence state and them being in different groups of elemental table, that wasn't raised below by appellants.

[00:16:08] Speaker 00:
The idea that you can't use silver oxide with an acid, if you look at the actual testimony from Dr. Sessler that they're citing, I think it's APPX 7334 or 333.

[00:16:19] Speaker 00:
It doesn't say that.

[00:16:20] Speaker 00:
It says you wouldn't use silver oxide with 60% sulfuric acid because that would be hazardous.

[00:16:25] Speaker 00:
The very next page at APPX 7334, Dr. Sessler goes on to talk about how a mild acid like phosphoric acid is totally consistent.

[00:16:35] Speaker 04:
The claims themselves do not disclaim the use of acid.

[00:16:38] Speaker 00:
They do not.

[00:16:38] Speaker 00:
They in fact call for a polar solvent.

[00:16:41] Speaker 00:
Water with acid is a polar solvent.

[00:16:43] Speaker 00:
So the idea that acid and aqueous solutions with acid are not part of the claims, they are literally part of the claims.

[00:16:50] Speaker 00:
The claims are also comprising claims.

[00:16:51] Speaker 00:
So they're open to other elements.

[00:16:54] Speaker 00:
There would be no question that if they were using silver dioxide with water and acid, that that would literally fall within the scope of the claims.

[00:17:02] Speaker 02:
Well, I didn't be caught error in saying there was no disclaimer over Culcani.

[00:17:10] Speaker 02:
Your inventor said, the use by applicants of silver oxide without acid is significantly different from the use in kolkhani of the sulfuric acid.

[00:17:24] Speaker 02:
Why wasn't that a disclaimer of a process of using acid?

[00:17:29] Speaker 02:
And of course, they're using acid with manganese.

[00:17:31] Speaker 00:
Because the actual nature of the distinction was the use of hazardous toxic oxidants.

[00:17:37] Speaker 00:
So the Colcarney, which isn't prior art, the unrefuted testimony is that it's not prior art, but the Colcarney reference uses a chromate, which is incredibly toxic.

[00:17:46] Speaker 00:
It also uses sulfuric, fuming 60% sulfuric acid, which is toxic and hazardous to work with.

[00:17:54] Speaker 00:
Those were the distinctions.

[00:17:55] Speaker 00:
There was no limitation that was required to be added to the claims to disclaim the use of a mild acid.

[00:18:02] Speaker 00:
Mild acid like phosphoric acid was the buffer that's actually used when you inject lymphozerine into the body.

[00:18:07] Speaker 00:
So the idea that you couldn't use even a mild acid doesn't make any sense, particularly in the context where the claims require a polar solvent.

[00:18:15] Speaker 00:
And water and acid is definitely a polar solvent.

[00:18:18] Speaker 00:
Also, with respect to this argument that manganese dioxide can't be used without acid,

[00:18:23] Speaker 00:
That is empirically disproven by their own DMF.

[00:18:27] Speaker 00:
So if you look at APPX4626 and APPX4627, these are their initial studies where they're trying to model and swap in manganese dioxide for the claimed silver oxide.

[00:18:38] Speaker 00:
The third entry from the bottom on APPX4626 shows that it is, or 4726, shows that the results with a pH of two to three in manganese dioxide

[00:18:51] Speaker 00:
If you go to the very next page, the table at the top of that page, shows the results from manganese oxide just in water with no indication that the pH is adjusted, which is what an organic chemist would understand to be not an acid.

[00:19:03] Speaker 02:
All of these raised factual questions.

[00:19:06] Speaker 02:
So why was the preliminary injunction justified?

[00:19:12] Speaker 00:
It was justified because we established that they had not raised... They say the opposite of you in several respects.

[00:19:17] Speaker 00:
But the district court made those determinations.

[00:19:20] Speaker 00:
And so he's the fact finder with respect to the granting of a preliminary injunction.

[00:19:24] Speaker 02:
In other words, there's no genuine issue of material fact?

[00:19:28] Speaker 00:
Actually, I don't believe there is.

[00:19:30] Speaker 02:
Tell us, defend the holding of the grant of the injunction on the purified compound patent.

[00:19:38] Speaker 02:
Well, there's no question.

[00:19:39] Speaker 02:
Because after all, it was a 95% pure prior art, right?

[00:19:45] Speaker 02:
And so those that spill in the art

[00:19:49] Speaker 02:
have tools to purify and get rid of the remaining 5% impurity.

[00:19:56] Speaker 02:
So why wasn't that obvious?

[00:19:58] Speaker 00:
Because you couldn't do it.

[00:20:00] Speaker 00:
So the Hirsch reference that's dated in 1982, it talks about how it reached apparently a 94.5% purity level by HPLC.

[00:20:08] Speaker 00:
But it said the remaining 5.5% were closely related isomers.

[00:20:12] Speaker 00:
We know from all the documents that were produced that they were never able to get

[00:20:16] Speaker 02:
a higher purity product because they couldn't separate out the... Was the HPLC used to purify it or to verify that it was pure?

[00:20:25] Speaker 00:
It can be used both ways, but when they're used differently, it's different.

[00:20:29] Speaker 04:
So just because you can separate something and turn... But in this case, my impression was that HPLC was used to verify.

[00:20:36] Speaker 00:
In the claims it is.

[00:20:38] Speaker 00:
And it was used in the Hirsch reference to verify.

[00:20:41] Speaker 00:
However, I would contend that it was disputed as to whether or not the lymphazone was actually as pure as 94.5% because there was the Hirsch letter to FDA where they indicated the purity was much, much lower.

[00:20:54] Speaker 00:
And they asked for help from FDA so they could identify the impurities and make it pure.

[00:20:58] Speaker 00:
And we know that there was a motivation to make a pure blue dye from the 1970s.

[00:21:04] Speaker 00:
And yet nobody was able to do it.

[00:21:06] Speaker 00:
And it was because nobody until the apicor inventors

[00:21:09] Speaker 00:
recognized that it was the nature of the oxidation step and the oxidant's use and the fact that you were obtaining your isosulfan blue in a particular mixture.

[00:21:20] Speaker 00:
That mixture was what you could purify it and you could get the other impurities out.

[00:21:27] Speaker 00:
Now with respect to lymphozerine, that was not the case because it had closely related isomers.

[00:21:32] Speaker 00:
Things like preparative HPLC don't work well if you're talking about separating closely related isomers because they're going to travel at a similar speed through the columns.

[00:21:42] Speaker 00:
Now, just because you can quantitatively determine the purity of something via analytical HPLC doesn't mean that you can separate the ingredients and get one that's pure from the other.

[00:21:55] Speaker 00:
So, for example, there are mathematical models that would allow you if you have two peaks that closely overlap.

[00:22:02] Speaker 00:
You could do an integration under the curve, and you can determine, yes, it's 94% this peak and 5% this peak, but you will never get enough separation to be able to actually use preparative HPLC to separate those out.

[00:22:14] Speaker 00:
Now, with respect to their purity levels in this argument that the desethyl impurity means that they had over-oxidation, that's new.

[00:22:24] Speaker 00:
That was totally brand new in their reply brief.

[00:22:26] Speaker 00:
That was never argued.

[00:22:28] Speaker 00:
their expert did not rely upon their ANDA or their DMF process in reaching his opinions.

[00:22:33] Speaker 00:
He relied on textbooks.

[00:22:35] Speaker 00:
The undisputed evidence is that the strength of oxidation and the way that something is going to function in a particular process is going to vary based on pH, reactants, temperature, and other conditions, including molar equivalents.

[00:22:50] Speaker 00:
They use right between two and three molar equivalents at 2.5 of manganese dioxide, which is the claims of the 992 patent.

[00:22:59] Speaker 00:
And so this idea that they have desethyl, meaning that they have over-oxidation, is just not supported.

[00:23:06] Speaker 00:
Also, if you go look at the appendix page that they cite, that their expert never cited, at APPX 4628, I believe, it does not describe this desethyl impurity as being an over-oxidized impurity.

[00:23:21] Speaker 00:
Now, with respect to the actual purity patents themselves, they literally, in French,

[00:23:27] Speaker 00:
They never presented to the district court below specific combinations of prior art.

[00:23:32] Speaker 00:
Their expert gave a list of 11 references.

[00:23:34] Speaker 02:
That's not on appeal here.

[00:23:36] Speaker 02:
Only validity for the compound.

[00:23:38] Speaker 00:
Exactly.

[00:23:39] Speaker 00:
Exactly.

[00:23:40] Speaker 00:
And I don't believe that they've shown that they've raised the substantial question of validity with respect to the impurity patents.

[00:23:47] Speaker 00:
The district court found copying.

[00:23:49] Speaker 00:
The district court found praise of others by Aurobindo.

[00:23:52] Speaker 00:
The district court found commercial success.

[00:23:54] Speaker 00:
They never contested any of those things.

[00:23:57] Speaker 00:
The district court also found unexpected results, which they didn't contest, and found long felt but unmet need, which they contested.

[00:24:05] Speaker 00:
But we agree with the district court, and we disagree with theirs, with their analysis.

[00:24:10] Speaker 00:
There wasn't just one shortage.

[00:24:11] Speaker 02:
There were shortages.

[00:24:12] Speaker 02:
The opponent says Covidean dropped out for business reasons.

[00:24:16] Speaker 00:
Covidean?

[00:24:17] Speaker 02:
In other words, there wasn't a long felt need.

[00:24:19] Speaker 00:
Well, that's just not true.

[00:24:20] Speaker 00:
There was a long felt need since Hiranaka in 1975 to try to characterize and purify these blue dyes.

[00:24:26] Speaker 00:
That was also evidenced in a 1982 Hirsch publication as well as in Hirsch Industries letter to FDA dated 1990 where they said, our purity is much lower.

[00:24:36] Speaker 00:
We need special permission to release a batch of this material so that there's not a shortage.

[00:24:42] Speaker 00:
And we need FDA's help to determine what the impurities are and determine how to get rid of them.

[00:24:47] Speaker 00:
And yet despite all of that motivation and desire, there was never a pure isosulfan blue product

[00:24:54] Speaker 00:
until APICOR's invention.

[00:24:57] Speaker 02:
So do you agree that, is it correct, that Mylan is operating on Covidians or Hirsch's NDA, and that they were simply allowed to do it by the FDA, anyone who can beat the specs?

[00:25:12] Speaker 00:
Well, I mean, we relied upon lymphozerine as the reference list of drugs for bioequivalence purposes, but we're not to the same specifications.

[00:25:20] Speaker 00:
I think their specifications were like 80% purity.

[00:25:23] Speaker 00:
Myland institutional and APICOR specifications required greater than 99% purity.

[00:25:29] Speaker 00:
So do Ourobendo's.

[00:25:30] Speaker 00:
If really there was no concern about the purity, why did an Ourobendo make lymphozeric?

[00:25:35] Speaker 00:
Why did they make the 90% pure?

[00:25:37] Speaker 00:
Why did they instead go after the 99% purity even though they knew about our claims?

[00:25:43] Speaker 00:
We had informed them before the lawsuit about this, and they were aware of the 992 patent and its related application with the purity claims.

[00:25:52] Speaker 00:
That's copying is the best form of flattery.

[00:25:54] Speaker 03:
One thing I'm still confused about

[00:25:59] Speaker 03:
Certainly, purity is an incredibly important component of all of this, and what you argue was the basis of the commercial success and the success of the patent, and for obviousness purposes and everything.

[00:26:15] Speaker 03:
But for DOE, their product results in a far less pure form of ISB.

[00:26:24] Speaker 03:
And they argue it doesn't work without acid.

[00:26:28] Speaker 03:
And that's what they argued below in response to the R&R by the magistrate.

[00:26:33] Speaker 03:
They argued it in their blue brief.

[00:26:34] Speaker 03:
They argued it in a gray brief.

[00:26:35] Speaker 03:
And today you came in and you start making some argument about the lack of a reference to pH in something.

[00:26:40] Speaker 03:
I didn't see that argument in your red brief, and I don't even understand it.

[00:26:44] Speaker 03:
And you started by saying, well, any chemist would know.

[00:26:46] Speaker 03:
And maybe Judge Laurie understood whatever the heck you were talking about, but I sure didn't.

[00:26:50] Speaker 03:
And I didn't see that argument in your red brief.

[00:26:52] Speaker 03:
So maybe you should take a minute and either tell me where it is or explain it to me better because I'm a little concerned maybe you didn't raise any of those arguments because I only understood your red brief.

[00:27:02] Speaker 03:
I didn't understand your red brief to say it doesn't need to have an absence of acid or it needs to have acid.

[00:27:08] Speaker 03:
I understood you'd be making a very different argument.

[00:27:11] Speaker 03:
So I don't know how to get around this based on the arguments you made in your red brief.

[00:27:16] Speaker 03:
And I kind of think the ones you made today are different from what are in your red brief.

[00:27:21] Speaker 03:
But I'll be the first one to admit this technology is complex.

[00:27:24] Speaker 03:
Maybe I'm missing something.

[00:27:25] Speaker 03:
So take a few minutes and try to explain it to me.

[00:27:27] Speaker 00:
Sure.

[00:27:27] Speaker 00:
Well, some of the arguments were responding to new arguments in R. Rabindranath's reply.

[00:27:32] Speaker 03:
Well, there was no new argument in their reply with regard to whether or not the oxidation process would not work without N-acid.

[00:27:40] Speaker 03:
That's something they raised all the way throughout.

[00:27:41] Speaker 03:
It's blue brief page 26.

[00:27:43] Speaker 03:
It was in response to the RNR below.

[00:27:45] Speaker 03:
So that's not a new argument.

[00:27:47] Speaker 03:
So your new citation of lack of pH reference, which I don't even understand, is not in your red brief despite the fact that this acid argument was in their blue brief.

[00:27:56] Speaker 00:
Well, the evidence below that the district court accepted was that silver oxide can be used with a mild acid.

[00:28:01] Speaker 03:
Did the district court make a fact finding to that extent?

[00:28:03] Speaker 03:
I never saw it anywhere.

[00:28:04] Speaker 03:
Is there a district court fact finding that I need to give deference to about that?

[00:28:09] Speaker 00:
No, there's not.

[00:28:10] Speaker 00:
With respect to the purity on their product versus our product in the process,

[00:28:17] Speaker 00:
This comparison they're making in their reply brief is brand new.

[00:28:20] Speaker 00:
And it is comparing apples and oranges.

[00:28:22] Speaker 00:
They're comparing the Hirsch purity of 94.5%, which is after all the possible purification that Hirsch could do, to their crude and saying, well, our crude only has a purity of like 89% or 90%.

[00:28:37] Speaker 00:
Well, the patent talks about and teaches, the assertive patents, teach that you obtain a crude isosulfan blue product from oxidation

[00:28:45] Speaker 00:
but that you then go on and you purify it to the greater than 99% purity.

[00:28:50] Speaker 00:
And the invention is the understanding that it's the oxidation step, and it's the nature of the mixture that the isosulfan blue is present in that allows you to obtain something that can be purified to 99%.

[00:29:07] Speaker 00:
And so the comparison should be the Oribendo product after it's undergone, after the crude isosulfan blue has undergone a purification,

[00:29:15] Speaker 00:
with the patent claims with Hirsch and the other prior art that was never, never able to obtain that level of purification.

[00:29:24] Speaker 00:
I think I've used up my time if you have any other questions.

[00:29:27] Speaker 02:
Thank you, counsel.

[00:29:29] Speaker 02:
Mr. Patel has three minutes for rebuttal if he needs to.

[00:29:39] Speaker 01:
Your Honors, there's nothing in the record that shows that

[00:29:43] Speaker 01:
Hirsch was trying to achieve greater purity than what was required for a pharmaceutical grade ISB product.

[00:29:50] Speaker 01:
In the Hirsch article, he just did analytical HPLC and identified, and was clearly able to identify that 94.5% of the mixture that he got was ISB, and the other 5.5% was closely related impurities.

[00:30:06] Speaker 01:
There were prior references that we presented at the lower court, such as Snyder and Dahane,

[00:30:12] Speaker 01:
would teach a person of ordinary skill in the art that if you're analytically able to separate out the peaks of the two components, that one could use preparative HPLC to then collect out a purified compound.

[00:30:25] Speaker 01:
So we believe that there was a prima facie case of obviousness made at the district court level based on the prior art of Hirsch and Snyder and DeHain, which went so far as to say that

[00:30:39] Speaker 01:
and taught a person of learning skill in the art to use chromatography for vital dyes such as isosulfan blue.

[00:30:46] Speaker 01:
The other issue is that in terms of trying to get to 99% purity, when Hirsch filed his application in 1982, the key factor here is that the FDA did approve his product as being safe and effective

[00:31:08] Speaker 01:
for lymphatic mapping.

[00:31:11] Speaker 01:
There was no need in that 25 period that anybody knows of for a pure version of Lymphazurin.

[00:31:18] Speaker 01:
It was a safe and effective product.

[00:31:20] Speaker 01:
And if Mylan Indeed developed something better, they could have filed an NDA for a better version of Lymphazurin.

[00:31:28] Speaker 01:
But they didn't do that.

[00:31:29] Speaker 01:
They filed a copycat, a generic, they went through the Andira, just like us.

[00:31:36] Speaker 01:
So there is no

[00:31:38] Speaker 01:
difference in that sense.

[00:31:40] Speaker 02:
You're a copycat too, right?

[00:31:42] Speaker 01:
Yes, we are.

[00:31:43] Speaker 01:
We are a... Two copycats.

[00:31:48] Speaker 01:
Your Honor, going back to the 050 patent, so there's two lines of invalidity, one based on the prior... So you want us to disregard that four or five percent delta, correct?

[00:31:58] Speaker 04:
Did you copy that delta?

[00:32:00] Speaker 01:
The four or five percent delta, first we didn't copy that delta.

[00:32:04] Speaker 01:
We set that parameter

[00:32:06] Speaker 01:
well before the 050 patent had even issued.

[00:32:10] Speaker 01:
So that was in 2012.

[00:32:11] Speaker 01:
And even if it is copying, even if we did copy it, the Apple v. Samsung cases hold that copying alone is not sufficient to establish causal nexus.

[00:32:25] Speaker 01:
And this court has held that, especially in the Hans Waxman context for products that need to be bioequivalent, copying is a much less probative factor.

[00:32:37] Speaker 01:
Your Honor, I think I'm running out of time.

[00:32:39] Speaker 01:
So we respectfully request that in view of all of the legal and factual errors that were made at the district court level, that this court vacate the preliminary injunction.

[00:32:51] Speaker 01:
And we humbly request that it do it in an expedited basis because the injunction is in place and recall has been put into effect.

[00:32:59] Speaker 02:
In other words, in reviewing the district court decision, you want us not to be a copycat.

[00:33:05] Speaker 01:
That's correct.

[00:33:07] Speaker 02:
Thank you.

[00:33:08] Speaker 02:
The case will be taken under revised.