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twenty-five twenty-sixteen at Succa America Pharmaceutical Inc.

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versus Hetero Labs Limited.

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Okay, Mr. Samuel.

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Ready?

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May I please the court?

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My name is Liam Samuel on behalf of Appellant's Hetero Labs, Hetero Labs Unit 3, and Canberra Pharmaceuticals.

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Oh, sorry, the time hasn't started.

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Oh.

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Oh, yeah.

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The time hasn't started.

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It'll get fixed.

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Go ahead.

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Oh, OK.

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We've reserved four minutes for rebuttal.

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This appeal arises from a preliminary injunction improperly enjoining appellants from launching the generic drug.

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The central issue is claim construction.

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The claim is directed to a method of treating a neurological disorder.

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It requires two compounds, dexamethorphan and guinidine.

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to be administered in a specified weight-to-weight ratio of 1 to 0.5 or less.

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The question is, Your Honor, how to calculate that ratio.

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Our construction is simple.

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The ratio compares the weight of dexamethylofam to the weight of quinidine as compounds, not the weight of their salts.

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How do you know that from the specification?

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So the specification teaches us

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in two instances.

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First, the specification talks about how.

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I should say, how do you know that from the claim also?

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OK.

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My question is, it doesn't say the effective dosage, the effective ratio.

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And the specification has some language in it that suggests that when it uses those terms, that it's referring to the salt forms as well.

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Okay, so let's start with the claims, Your Honour.

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The claims actually support our construction.

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And the claims recite Dexamethor, Phan, and Quinitine in a specified weight-to-weight ratio.

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This claim is agnostic as to delivery form and imposes no limitation as to the form of delivery.

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And when the inventors intended to claim salts, they did so specified clearly in the dependent claims themselves.

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Why wouldn't I understand that to mean that it's including?

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That these phrases, dextromethorphan and quinidine, includes the salt forms when the dependent claims refer to the salt forms.

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So that's going into the specification now, Your Honor.

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Do you want to finish off on the claims, or shall we jump into the specifications?

[00:02:40] Speaker 04:
No, I was talking about the dependent claims.

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The dependent claims are not saying they include

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The dependent claims are not saying dexymethorphan includes dexymethorphan hydrobromide.

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They're saying that they are administered in a pharmaceutical acceptable salt.

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That's not an invitation or an authorization to change the meaning of dexymethorphan and quinidine in the claimed ratio itself.

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Claim one is agnostic as to the delivery form itself.

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That doesn't change irrespective

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And it doesn't matter what the type of delivery form itself.

[00:03:19] Speaker 05:
But if you're saying that claim one is agnostic, that sounds like you're saying that claim one includes the salt forms as well as the free base form of dextromethorphan and quinammonine.

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Correct?

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Yes.

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It does include any kind of form.

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However, Your Honor.

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The ratio requires you to limit yourself to the active ingredient.

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Exactly, Your Honor.

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Which means that you're reading the term dextromethorphan

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at the beginning of claim one, for example, in a way that sounds like it's inconsistent with the meaning of the term at the end of the claim, where you get to the ratio.

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No, Your Honor.

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But you just told me, I think a moment ago, that in claim one, dextromethorphan includes the salt forms.

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No, that's not what I meant.

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OK.

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I thought that's what you said.

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The claim one includes all kinds of forms.

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However, the dextromethorphan term in claim one, whether it's using the range or whether it's using the range ratio, we're referring to the compounds.

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However, the drug itself can be administered in any kind of form.

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So the ratio itself, and now we can go to the specification.

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So by including it in salt, using a salt carrier doesn't exclude it from the coverage of the claim, but the reference is still to the active ingredient.

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Exactly, Iran.

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And that's what the specification teaches.

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The specification, in fact, talks about how dexymethorphane and punidine, they're well-known compounds.

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APPX55 shows a picture of dexamethorphan.

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APPX57 shows a picture of quinidine.

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These are well-known compounds.

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They were known by name and structure.

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And the patent explains quinidine's purpose and the purpose of this invention.

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It's to increase the dexamethorphan blood level and to yield more consistent and predictable results of dexamethorphan in the blood.

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In several places in your patent, I mean, sorry, in your briefing, you say the patent makes clear that the ratio in the claim is referring to what I'm going to say is base form ratio.

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Does that make sense to you?

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I don't have a, in other words, that it's the non-salt form

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For the ratio yes, it's called column 17 through column 18 for that position I think you know where I'm referring to I'm having a hard time seeing it as somebody who maybe doesn't have the Technical background and let me tell you some of the reasons why I just want to see what your response is I mean in this it's giving amounts both for the salt form and then for the freebase form and then

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And it talks about an effective dosage when it's talking about the free base form.

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But the claim doesn't say anything about an effective dosage.

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I mean, couldn't you have said effective dosage if that's what you meant?

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Well, that's Asuka's argument.

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But it's a misplaced argument, Your Honor.

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That's essentially trying to suggest that the word dexamethorphan has different meaning.

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Otherwise, this is the plain and ordinary meaning of dexamethorphan, the well-known compounds shown in the specifications.

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Nothing in the intrinsic record that suggests omitting that phrase converts that claim ratio into a salt-based measurement.

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And, Your Honor, if we go to... Well, it wouldn't make any sense, would it?

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Because the salt isn't, it's not therapeutic.

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It's just a carrier for the active ingredient.

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Exactly, Your Honor, and that's the whole... And at the point you look at the prosecution history, distinguishing the Smith patent, there's some fine lines being drawn here between 1 to 0.5 and 1 to 0.75.

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saying no this wasn't anticipated by the Smith Pack which has the same specification because we're using a different amount of active ratio of active ingredients.

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Exactly your honor.

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Can I go back to my questions about column 17 and 18.

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When I look at the amounts there's a couple examples that show that the salt forms result in I think the proper ratio

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but the corresponding effective dosage forms do not have the correct ratio in the claim or they don't have the ratio in the claim I'll give you like for example in column 18 line

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Six, it says 60 milligrams of dextromethorphane hydrobromide and 30 quinidine sulfate.

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So that would be falling within the ratio of the claim.

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But when I look at what none of the corresponding effective dosages fall within the ratio of the claim.

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So I am having a hard time seeing why I should read the claim in light of the specification to require that it be effective dosage as opposed to salt form dosage.

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So there's two points in that issue.

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Point number one is if you look anywhere in the specification, you're not going to find the claimed ranges and the claimed ratio disclosing the specification.

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You really kind of figure that out later after the claim.

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Well, that's assuming that the claim dosage and ratio is not for the salt form.

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Regardless of whether it's referred to as effective dose or not, it's just not disclosed in there.

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There's a range in the claim.

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But it's not in the specification.

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OK.

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The second point as to determining that ratio, because that's where the patent teaches that when you use that salt, you convert.

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That's a really critical point that really Atsuka doesn't

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reconcile with that issue.

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Why would you even disclose this if you're not going to convert?

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If your ratio is based on sulfur, what's the purpose of this language?

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Why is it being used?

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What does it serve?

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It doesn't answer that question.

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But the way to convert, for example, a good example is the 30 milligrams of dexamethorphine hydrobromide converts to 22 milligrams.

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It's roughly 83%.

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22 milligrams of dexamethorphane.

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And that's what a person's school would use in that ratio.

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Why?

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Because that's how you can get the consistent and predictable blood levels of dexamethorphane in the blood.

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That's how you know what you're putting into the human body.

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It's not some salt form in which some salts might have a higher weight, and you don't have as much dexamethorphane.

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And so that's what it's important.

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And so going into the prosecution history at Judge Dyck, you were right.

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The examiner understood the inventor's intention here, the intent here.

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And that's to, the examiner mapped the compound-based ratio.

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It's a compound-based prior reference, Smith.

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There was no discussion at all or a disclosure of a pharmaceutically acceptable salt.

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when salt was an issue.

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The discovery here was that the amount of quinine in the ratio, right?

[00:11:05] Speaker 01:
By reducing, the idea was that you could reduce the amount of quinine in the ratio from Smith patent that was 0.75 or whatever it was to 0.50, right?

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Correct.

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The whole focus was on the amount of active ingredient.

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Correct, Your Honor.

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And you can see that conversion play out also in the original claims that were filed.

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Original claim one, the claims were originally filed show the intention of the use of the trans-ectomy chlorophyll to mean the compounds.

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Original claim one capped quinidine at 50 milligrams, while original dependent claim nine capped it at 60 milligrams.

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Now, you can't have a dependent that has a weight range

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Greater than the independent that would improperly expand not narrow the scope of the dependent claim So the only way those claims can be reconciled is if we need in sulfate the weight of that we need in sulfate is Converted using that conversion table To put it in and determine the equivalent amount you're talking about cancelled claim nine Correct John, which is it doesn't appear in the current pattern

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Correct, but it still shows the intent of the inventors.

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And the inventors haven't changed that in any way throughout the prosecution history, that intent.

[00:12:26] Speaker 00:
I would just like to jump to, Your Honors, the reasons for why Asuka's construction is wrong.

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Asuka's construction wants you to look to the infringing product.

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That's what they're saying as the metric to determine this claim scope.

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Claims, as Judge Stoll you mentioned,

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at first hearing, that's not how you determine claim scope by the accused product.

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Second point is Atsuka misapplies the doctrine of claim differentiation.

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The focus of the claim is not on the delivery form.

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It's on the compound ratio, and it does not matter delivery form.

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Claim one is agnostic, and the claim structure itself does not redefine the meaning of dexymethorphan and quinidine.

[00:13:10] Speaker 00:
Finally, I want to point to, Your Honors, the fact that

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if we are to consume the same way that Atsuka's construction based on salt base, that would render the claim indefinite.

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In fact, if this record made no findings on indefiniteness, and had it made a finding on indefiniteness, it would have realized that if you apply the salt, if you apply that ratio, it would mean it could be the compound or the salt.

[00:13:38] Speaker 00:
And that would yield materially different results with different outcomes, no metric whatsoever for a person's skill in the art to determine what's the scope of the patent.

[00:13:47] Speaker 00:
In fact, that falls squarely in the four corners of Teva versus Sandal, where we had the claims deemed indefinite because the term molecular weight could be calculated in three different ways, each yielding three different results, and the patent did not specify which one to use.

[00:14:04] Speaker 05:
Now, would you agree that where the patent specification uses the word DM, the abbreviation DM, and the abbreviation Q, that that refers to either DM, extra-methyl, orphan, or, in the case of quinine, quinine or their salts?

[00:14:27] Speaker 00:
Regardless of how it's being used, Your Honor, for purposes of the ratio,

[00:14:31] Speaker 00:
It's still going to have to be the weight of the compounds.

[00:14:34] Speaker 05:
But the patents, I think you will agree with me, often uses DM and Q not to be limited just to the dextromethofen.

[00:14:43] Speaker 00:
So in some instances, Your Honor, there may be some shorthand as trying to refer to the product that's being used, that's being administered.

[00:14:54] Speaker 00:
That being said, when it came down to the application of that ratio,

[00:14:59] Speaker 00:
The intent of the inventors was clear, whether it's in the original claims, whether it's in response to the examiner, it's the ratios based on the compounds.

[00:15:08] Speaker 00:
I'd like to reserve a few minutes left.

[00:15:11] Speaker 01:
We'll give you two minutes.

[00:15:30] Speaker 03:
Good morning, and may it please the court.

[00:15:33] Speaker 01:
So I'm having trouble understanding how your claim construction makes any sense in terms of this patent.

[00:15:40] Speaker 01:
You've got these two active ingredients.

[00:15:43] Speaker 01:
You had an earlier Smith patent, which covered various ratios of the active ingredients.

[00:15:49] Speaker 01:
And in the prosecution history, you distinguished this ratio as being different and providing benefits because of the lower amount of quinidine.

[00:16:02] Speaker 01:
the whole focus is on the active ingredient.

[00:16:06] Speaker 01:
Why in heaven's name would it make sense to measure the ratio in terms of the product with the salt carrier which is not an active ingredient?

[00:16:16] Speaker 03:
Your Honor, the claims are focused on the administration.

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The focus on what is being administered.

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The word administered is used three times in claim one.

[00:16:28] Speaker 03:
I don't think you're

[00:16:32] Speaker 01:
The concern here is with the amount of active ingredient, not with whether it includes a salt form or not.

[00:16:40] Speaker 01:
And why does it make any sense to say that once it's administered in a salt form, that the ratio of active ingredient is somehow thrown out the window?

[00:16:52] Speaker 03:
The patent is not about blood levels.

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The claims are not about blood levels.

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The claims are focused on what is actually being administered to the patient, what is being put into the patient's mouth.

[00:17:02] Speaker 03:
That's the whole focus here.

[00:17:04] Speaker 03:
Yes, there is disclosure and discussion of blood levels, but there is no mention of blood levels, of AUC, of CBAS.

[00:17:12] Speaker 01:
What was the invention here?

[00:17:13] Speaker 01:
the 1 to 0.5 ratio.

[00:17:15] Speaker 01:
What was the invention?

[00:17:17] Speaker 01:
The invention was that you should have a lower dose of quinidine, which was beneficial, right?

[00:17:26] Speaker 03:
The original work by Smith used 150 milligrams of quinidine.

[00:17:31] Speaker 01:
No, you're not answering my question.

[00:17:34] Speaker 01:
This patent that we're talking about here

[00:17:36] Speaker 01:
The invention was being able to reduce the quinidine so that it's 1 to 0.5 of quinidine, right?

[00:17:46] Speaker 01:
And that was thought to have beneficial effects.

[00:17:49] Speaker 03:
that it was surprising that a much lower, a maximally therapeutic, I'm sorry, maximally inhibiting dose of quinine could still allow for the treatment of pseudobulbar.

[00:18:01] Speaker 01:
Right, and so why does it make any sense to say that the ratio varies depending on whether it's administered in a salt form or a base form?

[00:18:11] Speaker 03:
That is what the claim requires.

[00:18:14] Speaker 03:
The claim is discussing what is being administered to the patient.

[00:18:19] Speaker 01:
And the weight of that construction is... So the amount of active ingredient varies under the claim, depending on whether it's administered in a salt form or a base form?

[00:18:30] Speaker 03:
The active ingredient is the dexamethylofenhydrobromide or the dexamethylofenquinidine.

[00:18:36] Speaker 03:
If you look to the label that hetero submitted to the FDA, it states explicitly that the active ingredient is 20 milligrams dexamethylofenhydrobromide and 10 milligrams quinidine sulfate.

[00:18:49] Speaker 03:
So here the focus is on what is being administered.

[00:18:53] Speaker 01:
You mentioned the labeling, but in FDA labeling under the FDA salt policy, you describe the active ingredients, right?

[00:19:04] Speaker 01:
That's the way the labels are done.

[00:19:08] Speaker 01:
Are you familiar with the salt?

[00:19:09] Speaker 03:
I was answering your question, Your Honor.

[00:19:11] Speaker 03:
You asked me what the active ingredient is.

[00:19:12] Speaker 01:
Well, you talked about the labeling.

[00:19:14] Speaker 01:
I'm saying to you that FDA labeling requires that you specify the active ingredient, even if it's administered together with salt.

[00:19:25] Speaker 03:
So that is what hetero's label discloses to the world that is being administered in each pill.

[00:19:33] Speaker 04:
Is that in the appendix?

[00:19:35] Speaker 03:
Do you want to turn it over?

[00:19:37] Speaker 03:
Yes, Your Honor.

[00:19:43] Speaker 03:
that is 13 of our other

[00:20:12] Speaker 03:
It is on page 12 of the red brief.

[00:20:18] Speaker 03:
It's APPX 481.

[00:20:22] Speaker 03:
That states that it contains fixed-protein albumide, 20 milligrams, and quinine sulfate, 10 milligrams.

[00:20:31] Speaker 03:
Which page of the red brief is labeled here?

[00:20:35] Speaker 05:
Page 12.

[00:20:40] Speaker 03:
That was

[00:20:42] Speaker 03:
The location from the label in the description of the label at APPX 494.

[00:20:53] Speaker 03:
It goes on to say.

[00:21:02] Speaker 03:
You're looking at 481 and 494.

[00:21:04] Speaker 03:
At 494 under the description, section 11 of the label, dexamethopin hydrobromide is a pharmaceutically active ingredient.

[00:21:13] Speaker 03:
of dexamethylamine hydrobromide and quinine sulfate capsules.

[00:21:26] Speaker 03:
But with respect to Your Honor's initial question about how it could contain, how claim one could be focused on salt,

[00:21:36] Speaker 03:
based on the principles of claim differentiation, it has to, if you go down to dependent claim nine, for example.

[00:21:43] Speaker 01:
Under your construction, if it's administered in the base form, there's one ratio of the active ingredient.

[00:21:51] Speaker 01:
If it's administered in the salt form, there's a different ratio.

[00:21:54] Speaker 03:
If someone were to choose to administer, to actually administer in a free base form, you would use the amount of free base form.

[00:22:02] Speaker 03:
if one were to choose to administer.

[00:22:04] Speaker 01:
So that the ratio of active ingredient varies under the claim depending on whether it's administered in the freebase form or salt?

[00:22:13] Speaker 03:
Those are the different products, but yes, if you administered a different product you would have a different calculation.

[00:22:17] Speaker 03:
How does that make any sense?

[00:22:18] Speaker 03:
They're different products, Your Honor.

[00:22:20] Speaker 03:
You look to what is actually being administered.

[00:22:23] Speaker 03:
The focus remains on the material that is being put into the pill.

[00:22:30] Speaker 03:
If hetero were to put a different material into its pill, there could be a different calculation.

[00:22:36] Speaker 03:
But what they put into their pill was 10 milligrams dexamethylamide and 10 milligrams quinine sulfate.

[00:22:43] Speaker 03:
So there's no issue of ambiguity in the claim.

[00:22:48] Speaker 03:
the claim is focused on material being administered.

[00:22:50] Speaker 01:
If you go down to dependent claim nine... Why isn't it equally consistent with the language that it's referring to the active ingredient?

[00:23:00] Speaker 03:
What language are you referring to, Your Honor?

[00:23:02] Speaker 01:
The language of the claim.

[00:23:03] Speaker 03:
The language of the claim states that the amount of dexamethorphine administered comprises 20 milligrams to 80 milligrams per day, and the amount of quinine administered comprises 10 to less than 30.

[00:23:15] Speaker 01:
So why isn't there a saying, you calculate the amount of the active ingredient administered, whether it's the free base form or the salt form, and it's the same amount of active ingredient in each case?

[00:23:24] Speaker 03:
No, Your Honor.

[00:23:26] Speaker 03:
This is saying that you use the amount of what's actually being administered.

[00:23:30] Speaker 03:
The keyword here is administered in comparison to the language that's used in the specification describing the calculation, a corresponding effective dose.

[00:23:41] Speaker 03:
It does not say corresponding effective dose.

[00:23:43] Speaker 03:
It says administered.

[00:23:44] Speaker 03:
And if you go down to claim nine, the method of claim one, we're in about 20 milligrams quinamine sulfate is administered.

[00:23:51] Speaker 03:
the 20 milligrams of quinidine sulfate, the antecedent basis for the quinidine sulfate is the quinidine in claim one.

[00:24:01] Speaker 03:
And in the portion of the specification that I believe my friend was referring to, which is... Did you agree that administering it with a salt doesn't change the therapy?

[00:24:16] Speaker 01:
That the active ingredient is the same amount

[00:24:20] Speaker 01:
whether it's administered in a salt form or a free base form.

[00:24:24] Speaker 02:
If you're going to... Are you asking about what corresponding level would exist?

[00:24:29] Speaker 01:
The therapeutic effect is the same whether you administer a particular quantity in a free base form or you administer that same quantity together with a salt.

[00:24:43] Speaker 03:
I believe the therapeutic efficacy here is determined based upon the dose being administered.

[00:24:50] Speaker 03:
That was one of the main focus of the district court finding below.

[00:24:53] Speaker 01:
My question is the therapeutic effect is the same whether you administer it in pre-base form or together with a salt, correct?

[00:25:04] Speaker 03:
I believe what you're saying is accurate.

[00:25:07] Speaker 01:
If you have 10 milligrams of quinidine administered in free base form, or 10 milligrams administered together with a salt, the therapeutic effect of those two is the same, right?

[00:25:18] Speaker 03:
If you're talking about blood levels, Your Honor, I believe they would produce the same blood levels.

[00:25:22] Speaker 03:
But that is not what the claim is referring to.

[00:25:24] Speaker 03:
This is a claim about what is being administered to the patient.

[00:25:27] Speaker 03:
And the claims of specification of prosecution history confirm that.

[00:25:32] Speaker 03:
And we have not seen any

[00:25:34] Speaker 03:
lexicography or clear and unambiguous disavowal that would exclude salts from the words dexamethorfen and quinidine in claim one.

[00:25:43] Speaker 03:
In fact, the other claims necessarily would, sorry, the words dexamethorfen and quinidine in claim one necessarily are broad enough to include salts.

[00:25:54] Speaker 03:
based on the dependent claims and the specification, which states that for each embodiment, the quinidine includes quinidine sulfate and the dexamethorphine includes dexamethorphine hydrobromide.

[00:26:07] Speaker 03:
That's the red brief citing to the specification at ABPX 52 and 53.

[00:26:16] Speaker 03:
Similarly the portion of the specification that my friend cited at epx 59 column 17 to 18 Makes it clear that there is a distinction between what is administered and a corresponding?

[00:26:30] Speaker 03:
calculated effective dosage that portion of specification states 30 milligrams of dexamethoprenhydrobromide and

[00:26:38] Speaker 03:
and 30 milligrams quinine sulfate may be administered, administered the word that's in the claims, and then pren, corresponding to an effective dosage.

[00:26:46] Speaker 03:
Those words do not appear in the claims of approximately 22 milligrams sexmothorphine and 25 milligrams quinine.

[00:26:56] Speaker 03:
Then the last portion of the intrinsic evidence is prosecution history.

[00:27:02] Speaker 03:
In an office action, the examiner characterized the then pending claim one

[00:27:07] Speaker 03:
that claim appears at appendix 955 and like the issued claim one, it uses the terms dexmethorphin and quinidine.

[00:27:17] Speaker 03:
On appendix 973, the examiner explained that the claims cover the administration of dexmethorphin or dexmethorphin hydrobromide in combination with quinidine or quinidine sulfate.

[00:27:28] Speaker 03:
So the prosecution history actually supports Appellee's construction.

[00:27:34] Speaker 01:
In the prosecution history, you're trying to distinguish Smith, which included at least a ratio of active ingredient of 1 to 0.75, right?

[00:27:46] Speaker 03:
I don't believe Smith went down that low.

[00:27:49] Speaker 03:
It was using more than twice as much quinidine as Dexmethorphine.

[00:27:53] Speaker 01:
Well, that's what the examiner said.

[00:28:03] Speaker 01:
As I said, the Smith was a... Okay, but both the Smith patent and this patent are concerned with the ratio of the active ingredients, right?

[00:28:15] Speaker 03:
The Smith patent was an initial patent about the treatment of Pseudobulbar effect that used maximally inhibiting amounts of quinidine, essentially enough quinidine to knock out all of the CYP2D6 in a patient's body.

[00:28:30] Speaker 03:
The invention here was that something that was non-maximally inhibiting amount of quinidine, a very low amount in the range of 10 to 30 milligrams, which is what's claimed, would be sufficient to allow for therapeutic amounts of dexmothorpen.

[00:28:44] Speaker 03:
That's the context of the invention.

[00:28:46] Speaker 03:
The claims themselves, however, are focused on what is being administered to the patient.

[00:28:52] Speaker 03:
They are not about blood levels or about any other parameters.

[00:28:55] Speaker 01:
So if we had concluded that it's about the ratios designed to achieve a certain blood level, then your construction would be wrong.

[00:29:06] Speaker 03:
No, Your Honor, I don't believe the claim has anything to do with blood levels.

[00:29:10] Speaker 01:
No, no, no.

[00:29:11] Speaker 01:
You're not answering my hypothetical.

[00:29:13] Speaker 01:
If we were to conclude,

[00:29:15] Speaker 01:
that the claim is concerned with blood levels and that the ratio is designed to allow you to reduce the amount of quinidine in the blood.

[00:29:25] Speaker 01:
If that were the purpose, then your construction would be wrong, right?

[00:29:30] Speaker 03:
That's not the claim, but I also don't think I agree.

[00:29:34] Speaker 03:
You have to look at the actual amount.

[00:29:36] Speaker 01:
Answer my hypothetical, please.

[00:29:37] Speaker 01:
If that were the focus of the claim, your construction would be wrong.

[00:29:41] Speaker 03:
Are you changing the amounts of dexmethorfen and quinidine in the claim as well, or just the ratio?

[00:29:47] Speaker 01:
If you were concerned with the amount in the blood, then your construction

[00:29:56] Speaker 01:
would be wrong and you should focus only on the amount of the ratio of active ingredients, correct?

[00:30:03] Speaker 03:
I know, Your Honor, I don't know what the difference in the blood levels would be, but the claims have amounts of dexamethorpe and quinine as well as the ratio.

[00:30:11] Speaker 01:
You're not answering my question.

[00:30:12] Speaker 01:
My question is if

[00:30:14] Speaker 01:
The purpose of the ratio is to affect the blood level if that's the purpose of the claim Then your construction is wrong because it takes account of something which doesn't affect the blood levels.

[00:30:27] Speaker 03:
That is the salt content If the ratio was what was if you're saying the ratio is solely focused on blood levels, which it does not say then I Don't they still don't believe our construction to be incorrect

[00:30:43] Speaker 05:
Well, there's going to be slightly different ratios.

[00:30:45] Speaker 05:
Very slightly different, Your Honor.

[00:30:46] Speaker 05:
If you have salt, as opposed to if you don't have salt.

[00:30:50] Speaker 03:
If you do the math, you wind up with very slightly different ratios if you are calculating something and not using what's actually being administered.

[00:30:59] Speaker 05:
Well, if you're administering with salt, you get one result of blood levels.

[00:31:03] Speaker 05:
If you administer it in free base form, you get a slightly different level of blood level, right?

[00:31:09] Speaker 03:
Are you talking about two separate products, Your Honor?

[00:31:12] Speaker 05:
Sure, two separate administrations.

[00:31:13] Speaker 03:
Two separate products.

[00:31:14] Speaker 03:
Two separate patients.

[00:31:16] Speaker 03:
You could change two different salts, two different administrations.

[00:31:20] Speaker 03:
You could change the amount of anything you want, Your Honor, and you could create different ratios.

[00:31:24] Speaker 05:
The question then would be, taking a look at Smith, how close would you get if you did the math for the salt form of dextromethane?

[00:31:38] Speaker 05:
and quinine and versus the blood level in the case of versus the the freebase one how close would the salt

[00:31:50] Speaker 03:
The differences between salts, if you're doing a calculation of an effective dosage from a salt, the differences are very small, Your Honor.

[00:32:02] Speaker 03:
I have not calculated them for anything in Smith.

[00:32:05] Speaker 01:
They may be very small, but under your salt calculation approach, it would come within the prior art in terms of the percentage of active ingredients, right?

[00:32:14] Speaker 03:
I don't believe so, Your Honor.

[00:32:16] Speaker 05:
Not at the amount... This is the 1.75, I think, that Judge Scheik is referring to.

[00:32:20] Speaker 03:
Right.

[00:32:20] Speaker 03:
I believe that, though, if the ratio... You also have to look at the amounts of the Dexmethorphine and quinidine that are in Claim 1.

[00:32:29] Speaker 03:
Not just the ratio.

[00:32:31] Speaker 03:
I don't believe there's...

[00:32:34] Speaker 03:
Yeah, we would not get anywhere near Smith if you did the calculations based on the numbers there, but also you have to look at the amounts that are actually in the claim, including the 10 to 30 milligrams.

[00:32:46] Speaker 01:
You wouldn't get close to the ratio in Smith that the examiner referred to?

[00:32:52] Speaker 03:
You're not going to get close to the 1 to 0.5 if you were to

[00:33:00] Speaker 01:
The examiner said the ratio in Smith is 1 to 0.75 or lower.

[00:33:06] Speaker 03:
I do not believe that you would get anything close to the same ratio or have the same amounts of the dexprofenquinitine that are... Well, you can do the math, but my math is that using the salt forms, you get pretty close to the plantar art.

[00:33:27] Speaker 01:
It's at least almost 1 to 0.79.

[00:33:33] Speaker 03:
I again, I have not done any calculations based on Smith, but it does not meet the requirements of the claim.

[00:33:42] Speaker 03:
That's why it was allowed during prosecution.

[00:33:45] Speaker 03:
There is no clear non-improvisal vowel of the salts from the scope of dexamethylamine in claim one, which is focused on administration, not effective dosage.

[00:33:57] Speaker 05:
When the patent specification uses DM and Q, is it your understanding that

[00:34:03] Speaker 05:
Those terms are used to include the salt form.

[00:34:07] Speaker 03:
Absolutely.

[00:34:07] Speaker 05:
Or to be exclusively the salt form and never refer to the free base form or to be agnostic between the two.

[00:34:15] Speaker 03:
The patent uses dexperminquinidine sometimes to refer to salt and sometimes to refer to the free base form.

[00:34:21] Speaker 05:
And the shorthand DM and Q, would that be used sometimes to refer to one and sometimes the other or would it be used consistently?

[00:34:30] Speaker 03:
No, that is actually our point.

[00:34:33] Speaker 03:
It's used both in a context-dependent manner.

[00:34:37] Speaker 03:
That's why in Claim 1, it is broad enough to include both.

[00:34:41] Speaker 03:
So, for example, in clinical... Can I say DM?

[00:34:44] Speaker 05:
I'm actually talking about the initials.

[00:34:45] Speaker 03:
The letters.

[00:34:46] Speaker 03:
I agree with you, Your Honor.

[00:34:46] Speaker 05:
Because that shows up at various points in the set.

[00:34:48] Speaker 03:
Yes, Your Honor.

[00:34:49] Speaker 03:
When it's used, for example, to refer to a blood level of dexamethorphin,

[00:34:54] Speaker 03:
that will be the 3-Base.

[00:34:57] Speaker 03:
When it's used in, for example, clinical study 3, which is on APPX 63, which talks about what's being administered, which again is what claim 1 covers.

[00:35:06] Speaker 05:
Is the hydro bermide and the sulfate?

[00:35:10] Speaker 03:
Exactly right, Your Honor.

[00:35:11] Speaker 03:
So it can be used in a context-dependent manner to mean either the free-base form or the sole form.

[00:35:19] Speaker 03:
And that is actually, that is explicitly our point.

[00:35:22] Speaker 03:
And for the focus, you know what you're using for claim one because the focus is on what is being administered.

[00:35:28] Speaker 03:
If you were to use the SALT form, you calculate the ratio with what's administered, the SALT form.

[00:35:33] Speaker 03:
If you were to use a different product, a hypothetical product that used the freebase form, and that was what was administered, then you would calculate the ratio with the freebase form.

[00:35:43] Speaker 03:
You do not calculate, you do not do any type of math conversion of the SALT form to the freebase form when you go from the administration in the beginning of Claim 1 to the ratio at the end of Claim 1.

[00:35:56] Speaker 01:
Okay, but in FDA's labeling,

[00:35:58] Speaker 01:
common, is it not, with a product which is administered in salt form to be labeled according to the amount of active ingredient?

[00:36:10] Speaker 03:
The product that's administered in salt form... It's labeled in terms of the amount of active ingredient?

[00:36:17] Speaker 03:
Yes, Your Honor.

[00:36:19] Speaker 04:
Is that the case with your clients, Lady?

[00:36:22] Speaker 03:
The product uses the salt form, and that is specified as the active ingredient.

[00:36:26] Speaker 03:
That is the active ingredient, Your Honor.

[00:36:29] Speaker 01:
No, but in your product, the way it's labeled in actual practice, it refers, when it says crinidine, it gives the amount of active ingredient, right?

[00:36:43] Speaker 03:
Yes, Your Honor.

[00:36:47] Speaker 03:
Yes, the product uses dexamethylamine and hydrobromide, and it's labeled in terms of the amount of dexamethylamine and hydrobromide.

[00:36:54] Speaker 05:
So, yes.

[00:36:55] Speaker 05:
It seems to me that there may be a disconnect here.

[00:36:57] Speaker 05:
You're using the term active ingredient to include the salt.

[00:37:00] Speaker 05:
I think what Judge Dyke's question was is, his promise, I think, is that active ingredient includes only the free base form of the two compounds.

[00:37:11] Speaker 05:
So given that question, does the label, your label include the salt or does it exclusively refer to the free base form of the two compounds?

[00:37:24] Speaker 03:
in the weight.

[00:37:28] Speaker 03:
So when it says 20 milligrams of dexamethybromide, that is the weight of dexamethybromide.

[00:37:33] Speaker 05:
That's the weight of the salt.

[00:37:35] Speaker 03:
Yes, Your Honor.

[00:37:35] Speaker 05:
Which is what you're calling the active ingredient.

[00:37:38] Speaker 03:
And the label refers to as the active ingredient.

[00:37:40] Speaker 05:
That is what's administered.

[00:37:43] Speaker 05:
Is that in the appendix?

[00:37:46] Speaker 03:
The entire label is in the appendix.

[00:37:49] Speaker 04:
Yes, we might be helpful to point out.

[00:37:55] Speaker 04:
Yes, how the labels referring to the salt.

[00:37:59] Speaker 03:
Sure, if there's a question of the claim construction, which I which is is not you do not That's the second half once you claim construction, then we go to infringement and then I'm just helping you answer a question Thank you on the label the label appears and this is this is hetero's proposed label for head was proposed product it appears at appendix 481 and

[00:38:27] Speaker 03:
It spans a few pages.

[00:38:30] Speaker 03:
I was thinking about your label, but that's fine.

[00:38:37] Speaker 03:
The differences between the labels are that Otsuka's label uses the brand name New Dexta, where Hetero's label uses the words Dexmethorphin and Quinidine instead of New Dexta.

[00:38:50] Speaker 03:
Otherwise, they are successively the same.

[00:38:55] Speaker 03:
The description of the product is at 494.

[00:39:10] Speaker 03:
It should be the next page, Your Honor.

[00:39:15] Speaker 03:
The entire label does not appear.

[00:39:16] Speaker 03:
It's the front page and the portion that we were discussing the description.

[00:39:40] Speaker 01:
I think we're out of time.

[00:40:14] Speaker 00:
I want to start by addressing the comment that counsel made.

[00:40:20] Speaker 00:
He said, if Hedder put something in a different pill, it would be a different calculation.

[00:40:26] Speaker 00:
That means we can't really know what the claim is covered.

[00:40:30] Speaker 00:
Again, it goes back to the infringing product is how you determine the patent.

[00:40:34] Speaker 00:
That's not how you determine patent scope.

[00:40:37] Speaker 00:
And I want to go to your question, Judge Dyck.

[00:40:44] Speaker 00:
when a quinidine of 20 milligram freebase is put in the human body and a quinidine sulfate is put in a human body, quinidine sulfate will have less concentration of quinidine.

[00:40:58] Speaker 00:
In fact, quinidine sulfate has 83% quinidine.

[00:41:02] Speaker 00:
And so, yes, you're going to have a different ratio and different calculation when you're using salt versus freebase.

[00:41:08] Speaker 00:
And in fact, and I'm not trying to,

[00:41:13] Speaker 00:
This is not an eye exam referring to APPX 644, your honor.

[00:41:18] Speaker 00:
As you can see, there's green and red at 644.

[00:41:23] Speaker 00:
The ones in green would be deemed, under the calculations, would be considered non-infringing.

[00:41:30] Speaker 00:
And if you do the calculations, the ones in red would be infringing.

[00:41:35] Speaker 00:
And so there is no way to determine the scope of the pattern, just simply the way that Atsuka

[00:41:43] Speaker 00:
is proposing to construe.

[00:41:49] Speaker 01:
Their argument is that the patent's not concerned with blood levels.

[00:41:53] Speaker 00:
Of course it is.

[00:41:53] Speaker 00:
That's exactly what it's saying.

[00:41:54] Speaker 00:
That's what it's trying to treat the neurological disorder.

[00:41:57] Speaker 00:
Yes, they're administering assault.

[00:41:59] Speaker 00:
In fact, they're suggesting a whole slew of forms of administration.

[00:42:06] Speaker 00:
Each one has a different weight.

[00:42:08] Speaker 00:
Some have more, some have less.

[00:42:11] Speaker 00:
Your dexamethorphan is gonna constantly change.

[00:42:15] Speaker 00:
And so the only way to determine and to treat the patient is to know what that level is in the blood by controlling what goes in of dexamethorphan going into the blood, regardless of that cell form.

[00:42:30] Speaker 00:
And a claim construction that ignores that intent of

[00:42:36] Speaker 00:
of the inventors cannot be correct.

[00:42:39] Speaker 05:
But you know what the concentrations are going to be.

[00:42:42] Speaker 05:
It's an easy calculation.

[00:42:44] Speaker 05:
The spec tells us how to calculate it.

[00:42:46] Speaker 05:
So if you want to put in a salt that has less dextrometh orphan in it,

[00:42:56] Speaker 05:
And so be it.

[00:42:58] Speaker 05:
If you want to pump up the amount of dextromethorphan that goes into the body, you put a higher amount of the total salt.

[00:43:08] Speaker 05:
It's a pretty easy calculation, right?

[00:43:10] Speaker 05:
I mean, it's not as if you're fooling anybody in thinking how much dextromethorphan is going in.

[00:43:17] Speaker 00:
We need to provide a specific range of therapeutic treatment to a patient

[00:43:27] Speaker 00:
to treat that patient from a particular neurological disorder.

[00:43:30] Speaker 00:
That means that patient needs a specific dexamethylofen amount in that blood.

[00:43:35] Speaker 00:
Right?

[00:43:36] Speaker 05:
Which you would know, depending on whether you're using a salt or a free base form.

[00:43:41] Speaker 05:
You can easily determine what that amount is.

[00:43:45] Speaker 00:
We can't, because we can't do so when there's so many potential variables.

[00:43:51] Speaker 00:
You could be doing compound.

[00:43:54] Speaker 00:
Essentially what they're suggesting is it could

[00:43:56] Speaker 00:
The claim can be construed as a sexymethorphan or it's salt.

[00:44:04] Speaker 00:
And so with all these different variations, some of them may infringe and some of them may not.

[00:44:10] Speaker 00:
That goes to your point, Your Honor.

[00:44:11] Speaker 00:
And so yes, some of them may infringe and some of them may not, but that makes the claim indefinite.

[00:44:18] Speaker 05:
If you can calculate with respect to any salt, any combination of these salts, exactly what the ratio is going to be, then you know whether for that particular treatment you infringe or not.

[00:44:33] Speaker 05:
That seems to me pretty straightforward.

[00:44:35] Speaker 00:
But in doing so, because there are so many variables and the number of potential forms that can be used,

[00:44:46] Speaker 00:
There are no limits.

[00:44:48] Speaker 00:
And if we go back to Smith or any other references, you're looking at, again, no one had looked at it in the sense of, are we looking at it in the context of Smith, in the context of salt or compound?

[00:45:04] Speaker 00:
It was purely a compound-based comparison.

[00:45:08] Speaker 00:
The prosecution history

[00:45:10] Speaker 00:
completely confirms that interpretation, Your Honor.

[00:45:14] Speaker 00:
Their construction is incorrect.

[00:45:16] Speaker 00:
In fact, if it is, if you do adopt their construction, it would render that claim indefinite.

[00:45:21] Speaker 00:
And so in that situation, we would not be infringing, Your Honor.

[00:45:31] Speaker 00:
Now, one last comment.

[00:45:32] Speaker 01:
I think we're out of time.

[00:45:34] Speaker 01:
Thank you.

[00:45:35] Speaker 01:
Thank both Councils for the cases submitted.

[00:45:37] Speaker 01:
Thank you.