[00:00:01] Speaker 03:
Our final case this morning is in Ray Depamed.

[00:00:05] Speaker 03:
Ms.

[00:00:06] Speaker 03:
Chao.

[00:00:12] Speaker 01:
May it please the court?

[00:00:13] Speaker 01:
Arlene Chao on behalf of Depamed.

[00:00:16] Speaker 01:
The board made a series of legal errors which warrant reversal.

[00:00:20] Speaker 01:
First, the board ignored the undisputed, unexpected results due to the PEO and HPMC combination in the gastric retentive and controlled release dosage form.

[00:00:30] Speaker 01:
There was.

[00:00:31] Speaker 03:
What do you mean by that?

[00:00:32] Speaker 03:
Because if I understand the record correctly and what was argued, that you said the unexpected results were that it performed better than each of the two components individually.

[00:00:46] Speaker 03:
Am I correct about that?

[00:00:47] Speaker 00:
Yes.

[00:00:48] Speaker 03:
But didn't the prior art suggest that making a combination like that would achieve a better result than the ones individually?

[00:01:00] Speaker 01:
There is no such suggestion in the prior art.

[00:01:04] Speaker 01:
In Shell, there was no suggestion to even combine PEO and HPMC.

[00:01:09] Speaker 01:
HPMC and PEO, individually, they provided adequate control release.

[00:01:14] Speaker 03:
They meant the funds... Well, I thought they were described as particularly preferred.

[00:01:18] Speaker 01:
They were on a short list for individual use, but not on a short list... No, no, no, wait, wait.

[00:01:23] Speaker 03:
Isn't it correct that they were described as particularly preferred?

[00:01:27] Speaker 01:
Yes, but for individual use, Your Honor.

[00:01:29] Speaker 01:
There is a general statement in Shell that the water-soluble polymers can be used individually or in combination.

[00:01:39] Speaker 03:
But it's important that that sentence is followed by the statement that certain combinations... By the way, you haven't properly numbered the pages of the appendix, which makes it extremely difficult to work with.

[00:01:52] Speaker 01:
So the start of Shell, Your Honor, is at Appendix 321.

[00:01:54] Speaker 01:
Do you understand what I'm saying?

[00:01:55] Speaker 01:
Yes, I do.

[00:01:56] Speaker 01:
And so page 6 of Shell, so if you go to appendix at 321, that's the first page of Shell, and then you go to Shell page 6.

[00:02:04] Speaker 03:
Wait, wait, wait, wait, wait.

[00:02:12] Speaker 03:
I'm having trouble dealing with this with the unnumbered pages.

[00:02:16] Speaker 03:
What page are you referring to?

[00:02:17] Speaker 01:
Page 6, Your Honor.

[00:02:18] Speaker 03:
Page 6 of Shell?

[00:02:20] Speaker 01:
Yes.

[00:02:21] Speaker 03:
Is that W-O-9855?

[00:02:24] Speaker 01:
Indeed it is, Your Honor.

[00:02:26] Speaker 01:
So in the middle, in lines 21 through 23, there's specific controlled release criteria where it states the amount of polymer will be sufficient, however, to retain at least about 40% of the drug within the matrix one hour after ingestion.

[00:02:42] Speaker 01:
PEL and HPMC met that specific criteria.

[00:02:46] Speaker 03:
But doesn't the same page here say certain combinations will often provide a more controlled release of the drug than their components when used individually?

[00:02:54] Speaker 01:
Indeed, and those combinations, a person of ordinary skill and the art would understand, would be ones where the individual polymers were deficient.

[00:03:02] Speaker 01:
And indeed, xanthan gum, which is noted as XG in the figures, and HEC, which is hydroxyethyl cellulose,

[00:03:09] Speaker 01:
those polymers individually were deficient.

[00:03:12] Speaker 01:
They did not meet the specific performance criteria that I just listed.

[00:03:16] Speaker 01:
And that is why they were in combination.

[00:03:19] Speaker 01:
And so such combinations that are called for and that a person with ordinary skill in the art would do, in light of Shell, are only ones where there is a deficient polymer in place.

[00:03:29] Speaker 01:
Now, in terms of Papa Demetrio.

[00:03:32] Speaker 02:
So in your position, that's the only way to read that sentence?

[00:03:35] Speaker 02:
Is this saying there's only where they won't work alone?

[00:03:37] Speaker 02:
Would you combine the two of them?

[00:03:39] Speaker 01:
Well, a person with an ordinary skill in the art would look at the data in order to give those sentences context.

[00:03:47] Speaker 01:
Certain combinations will work to improve.

[00:03:49] Speaker 01:
And those certain combinations were ones where a polymer was in aid of the deficient polymers, such as here, xanthan gum and HEC.

[00:03:59] Speaker 01:
That is why the figures, figures.

[00:04:01] Speaker 03:
What's your basis for that reading, your limited reading of the reference that

[00:04:06] Speaker 01:
A person of ordinary skill would understand that there's no teaching of any.

[00:04:11] Speaker 03:
How do I know that?

[00:04:12] Speaker 01:
Because none of the polymers.

[00:04:15] Speaker 03:
Where in the record?

[00:04:17] Speaker 03:
I mean, you stand here and you say that.

[00:04:19] Speaker 03:
Where is that in the record?

[00:04:21] Speaker 01:
In the record, Dr. Hoffmanberg, our expert,

[00:04:26] Speaker 01:
explain how a person of ordinary skill and the art would interpret this data.

[00:04:31] Speaker 01:
And it's very clear that there are only, only combinations where there's a deficient polymer.

[00:04:36] Speaker 03:
Where does he say that that sentence would be viewed in the limited way that you do?

[00:04:41] Speaker 01:
I think what he said, he didn't say it specifically in a limited way.

[00:04:44] Speaker 01:
What he said was that there's no suggestion to combine HPMC and PEO in shell.

[00:04:49] Speaker 01:
There is no suggestion whatsoever.

[00:04:51] Speaker 01:
And in so doing, he identified the specific performance criteria and the fact that HPMC and PEO independently met that criteria, which is why you do not see them in combinations only unless the other polymers are deficient.

[00:05:05] Speaker 01:
That's why there are only combinations involving XG and PEC.

[00:05:11] Speaker 01:
HEC.

[00:05:12] Speaker 01:
Also, and Your Honor, it's important to also stress that because of the legal errors where the undisputed unexpected results and the unrevoted

[00:05:23] Speaker 01:
long-felt unmet need, we're not considered that these references, both Shell and Papa Demetrio, they were viewed solely in hindsight.

[00:05:31] Speaker 01:
I mean, I think it's important to underscore the fact that that combination, the result was unpredictable.

[00:05:39] Speaker 01:
The synergy was unexpected.

[00:05:41] Speaker 01:
And in fact, if you look at the characteristics of each individual polymer, HPMC swells less than PEO.

[00:05:49] Speaker 01:
That means that it would have, if placed in the combination, one would have expected it to have worse gastric retention.

[00:05:56] Speaker 03:
But there's no testimony in the record about what was expected of the combination and how the combination exceeded the expectations of the combination.

[00:06:06] Speaker 03:
There's only testimony that exceeded the compounds individually.

[00:06:13] Speaker 01:
There is testimony that polymer combinations are inherently unpredictable.

[00:06:17] Speaker 01:
There's substantial testimony

[00:06:19] Speaker 01:
that there was unexpected results and long-fit unmet need.

[00:06:23] Speaker 03:
This patent is the difference.

[00:06:25] Speaker 03:
Please address my question.

[00:06:28] Speaker 03:
I do know there's testimony in there that this exceeded the results that would be achieved by using one compound individually.

[00:06:37] Speaker 03:
Is there testimony that the combination exceeded what would have been expected of the combination?

[00:06:45] Speaker 01:
Yes, your honor, I think the patent itself has, sorry, Srika, so if there's testimony as to whether or not the combination would have exceeded the expectation of the combination, the testimony is that polymer combinations are inherently unpredictable.

[00:07:03] Speaker 03:
There's no way to predict that.

[00:07:04] Speaker 03:
Is there testimony that the combination exceeded what one would expect of the combination?

[00:07:11] Speaker 01:
There is testimony.

[00:07:12] Speaker 01:
Sorry, your honor, I am trying to answer your question because the testimony is that there would have been no expectations in relation to those combinations because polymers are inherently unpredictable.

[00:07:23] Speaker 01:
So to be clear, the unexpected results are due to the fact that the synergy is unexpected.

[00:07:31] Speaker 01:
It could have gone worse.

[00:07:32] Speaker 01:
It could have been the same.

[00:07:33] Speaker 01:
It could have been the same as the combination.

[00:07:35] Speaker 01:
The combination exceeded what one would have expected, but there is no expectation because

[00:07:40] Speaker 01:
Plenamentally, the polymers are unpredictable in combination.

[00:07:44] Speaker 02:
But the reference says specifically, doesn't it?

[00:07:46] Speaker 02:
It says here are the lists of the polymers, and then it says the water-soluble polymers can be used individually or in combination.

[00:07:53] Speaker 02:
I mean, it sounds as if you're making almost a teaching away argument at this point, and I see the reference actually teaching.

[00:08:00] Speaker 02:
It says here are some polymers that you can use, and then it says they can be used individually or in combination.

[00:08:06] Speaker 02:
Yes, it gives some examples, but it just says those are examples.

[00:08:09] Speaker 02:
It doesn't say that they're limiting examples.

[00:08:12] Speaker 01:
I think a person who already has skill in the art would see the way how individual polymers were combined.

[00:08:18] Speaker 01:
And to be clear, the Shell reference doesn't teach the synergistic effect, which ties into the unrebutted, unexpected results of this invention, and also the long-felt, unmet need.

[00:08:29] Speaker 01:
Because the 340 patent, Your Honors, is the difference between having a once-a-day dosage form with less side effects versus the immediate release form that was already in the prior art.

[00:08:39] Speaker 01:
That difference is significant.

[00:08:41] Speaker 01:
It's significant because it materially impacted the quality of life of patients who are both diabetic and had post-herpetic neuralgia.

[00:08:49] Speaker 01:
This is a very significant difference.

[00:08:51] Speaker 01:
Only because of the PEO and HPMC combination in a controlled release gastric release dosage form was that once a day dosage form allowed to occur.

[00:09:00] Speaker 01:
So to underscore the unpredictability of polymers, your honors, SHEL.

[00:09:04] Speaker 01:
SHEL stands for the unpredictability of polymer combinations.

[00:09:08] Speaker 01:
If you take figure six of SHEL,

[00:09:11] Speaker 01:
which is near the end, that HPMC and HEC did not improve the poor gastric retention of HEC alone.

[00:09:21] Speaker 01:
And yet, PEO and HEC and HEC and xanthan gum did.

[00:09:25] Speaker 01:
So even Shell, when Shell was doing things in combination and using a so-called deficient polymer,

[00:09:32] Speaker 01:
there was no prediction of which ones would work.

[00:09:35] Speaker 01:
And indeed, one of them failed.

[00:09:36] Speaker 01:
One out of three failed.

[00:09:39] Speaker 01:
So shell itself stands for that unpredictability.

[00:09:42] Speaker 01:
What also stands for that unpredictability is a one and a half year of what we would call undue experimentation by the inventors.

[00:09:50] Speaker 01:
Shell 1998 is deployment R. It is, albeit, by different inventors.

[00:09:55] Speaker 01:
And it's important to stress the fact that even with Shell in place, and even with deployment being the market leader in controlled release and gastric retention dosage forms, it took them a year and a half to invent the 340 patent.

[00:10:08] Speaker 04:
Typically, when we hear these cases, we see a real infinite number of possibilities that exist when we get an argument about undue experimentation.

[00:10:19] Speaker 04:
But here, Shell referenced only seven preferred polymers.

[00:10:25] Speaker 04:
What is it about that that makes it, that needs to undo experimentation?

[00:10:32] Speaker 01:
There was no indication, Your Honor, that HPMC and PEO together would work, let alone have that synergistic benefit where there was superior gastric retention control.

[00:10:44] Speaker 04:
But you just started out with those two polymers.

[00:10:47] Speaker 01:
Pardon?

[00:10:48] Speaker 04:
Your testing started out with post-tupon.

[00:10:50] Speaker 01:
Oh, no, Your Honor.

[00:10:51] Speaker 01:
Actually, the lab notebooks, because development did start with PEO, one month later, there was a notational lab notebook that the inventors were considering HPMC.

[00:11:02] Speaker 01:
But it's not clear that it is in combination with PEO.

[00:11:05] Speaker 01:
In fact, the lab notebook, anything, it could be indicating that HPMC is in lieu of or in place of PEO.

[00:11:12] Speaker 01:
So the lab notebook is that they were considering HPMC as one of many options.

[00:11:18] Speaker 01:
as an option, as an alternative to PEO.

[00:11:21] Speaker 01:
There is no indication that, A, they tested at that time, and they didn't.

[00:11:24] Speaker 01:
But all that best that you have in the lab notebook is that it is a possible potential candidate.

[00:11:29] Speaker 01:
And that is why DevilMed tested dozens of formulations, Your Honor, dozens of formulations.

[00:11:34] Speaker 01:
And in fact, because there was no predictability in this area, they also had to perform a lot of rigorous testing.

[00:11:40] Speaker 01:
They had to develop their own erosion and swelling assays because the standard assays at the time were not robust and predictable enough for what would occur in the body.

[00:11:51] Speaker 01:
And if I could just bring in Papa Demetrio briefly.

[00:11:54] Speaker 02:
I'm in pop it to me.

[00:11:58] Speaker 02:
No, no, that's the noble your honor.

[00:12:07] Speaker 01:
That's a legal error.

[00:12:08] Speaker 01:
That was the subject.

[00:12:09] Speaker 02:
I mean, they have in their

[00:12:12] Speaker 02:
their opinion that they've considered it, it's not convincing to them to change their conclusion.

[00:12:20] Speaker 02:
Why is that not a factual issue?

[00:12:21] Speaker 01:
Your Honor, we submit that it's legal error and de novo because they discounted it in its entirely when it was unrebutted.

[00:12:28] Speaker 01:
Both the long-felt unmet need and the unexpected results were unrebutted.

[00:12:33] Speaker 01:
And Endo did not dispute either of these two critical objective considerations of non-obviousness.

[00:12:40] Speaker 01:
And the board gave it absolutely no weight.

[00:12:42] Speaker 01:
I'd say they discounted it.

[00:12:43] Speaker 01:
They discredited it.

[00:12:44] Speaker 01:
They did not even take into account, which is why their assessment of Shell and Papa Demetrio is wholly out of hindsight bias.

[00:12:51] Speaker 03:
If I- You're into your rebuttal time.

[00:12:53] Speaker 03:
Do you want to save it?

[00:12:55] Speaker 01:
Yes.

[00:12:56] Speaker 01:
Okay.

[00:12:56] Speaker 01:
Thank you.

[00:13:05] Speaker 03:
Ms.

[00:13:05] Speaker 03:
Caprahan?

[00:13:11] Speaker 00:
Thank you, Your Honors.

[00:13:12] Speaker 00:
May it please the court.

[00:13:14] Speaker 00:
Deba Mitt's challenge claims here are directed to controlled release of a water-soluble drug combined with PEO and HPMC to provide gastric retention and controlled release.

[00:13:28] Speaker 00:
Now, using PEO and HPMC to provide gastric retention and controlled release was known in the art.

[00:13:37] Speaker 00:
The shell reference disclosed that.

[00:13:40] Speaker 00:
The Shell reference disclosed, as your honors noted, that HPMC and PEO were particularly preferred for this purpose, for this very purpose.

[00:13:50] Speaker 00:
And Shell further disclosed that one could optimize the controlled release dissolution profile by combining polymers.

[00:14:00] Speaker 00:
Although Shell did not specifically disclose combining HPMC and PEO,

[00:14:06] Speaker 00:
Because there were only a finite number of possibilities that were disclosed in Shell, the board properly found that one of skill in the art had a reasonable expectation of success in combining those polymers and providing a controlled release tablet that swelled in the gastric environment and provided that dissolution profile.

[00:14:26] Speaker 02:
What is the government's position on the board's statement that the patentee has to offer evidence to others tried and failed in order to demonstrate long felt need?

[00:14:37] Speaker 00:
So in terms of demonstrating long felt need, what the board found here is that they didn't give much weight to that evidence because they did not present evidence of failure of others.

[00:14:49] Speaker 00:
So it is not that the evidence of failure of others is required.

[00:14:53] Speaker 00:
It is that because there was no evidence of failure of others, that evidence was not given much weight.

[00:14:59] Speaker 00:
And this is because that in this art, it was known that PEO and HPMC would provide this type of dissolution profile for water soluble drugs.

[00:15:13] Speaker 00:
And so it is the director's position that the failure of others is not required.

[00:15:20] Speaker 00:
But it is probative in determining whether or not there was a long-held need here in this art.

[00:15:28] Speaker 04:
At what point were the objective indicia criteria considered?

[00:15:34] Speaker 04:
When I look at the board's decision, it seems to me, and I'm looking at Appendix 34, since the withholder petition is not shown by a preponderance of evidence, and it goes on with the

[00:15:47] Speaker 04:
with its holding, and then it goes into secondary considerations.

[00:15:53] Speaker 04:
Is this a decision first on the August-ness portion, and then you address after that objective condition?

[00:16:06] Speaker 00:
Well, I think what the board did was walk through first finding whether or not the art itself taught whether this type of formulation would be obvious.

[00:16:15] Speaker 04:
And then made its decision?

[00:16:17] Speaker 00:
The court made that determination, but then the court also considered the weight of the evidence.

[00:16:22] Speaker 04:
But it made the determination first, right?

[00:16:25] Speaker 00:
It made the determination first that there would have been a reasonable expectation of success, both either by Schell alone or Schell and Papadimitriou to

[00:16:35] Speaker 00:
would have been able to formulate these controlled release products.

[00:16:39] Speaker 00:
But then the court went, or I'm sorry, the board went on to look at the secondary considerations of non-obviousness that Devin Mead presented in his patented response.

[00:16:48] Speaker 03:
And- Will you describe on Appendix 40 how they did that?

[00:16:55] Speaker 00:
So first the board did look at- In the accordingly sentence?

[00:16:59] Speaker 00:
Excuse me?

[00:17:00] Speaker 03:
In the accordingly sentence on page 40?

[00:17:06] Speaker 00:
And on page 40, the board noted that they gave little weight to patent owners' arguments that evidence of alleged unexpected results overcame the petitioner's showing of obviousness in this case.

[00:17:16] Speaker 00:
And what the board was doing there was giving little weight to the evidence that was presented.

[00:17:21] Speaker 04:
So did the board first establish a decision as to petitioner's showing of obviousness before it considered the objective condition?

[00:17:31] Speaker 00:
Well, I think what the board did is they looked at all of the evidence before them, and because the evidence of unexpected results did not have proper weight, or they didn't give it proper weight, they found that it didn't overcome the obviousness determination that it found based on the prior art of record.

[00:17:52] Speaker 00:
And because here the prior art specifically taught that PEO and HPMC provide both gastric retention and controlled release,

[00:18:01] Speaker 00:
that it was obvious for one of scale in the arc to formulate controlled release tablets using that formulation.

[00:18:08] Speaker 00:
And it's, I think, also instructive to look at the claims themselves.

[00:18:11] Speaker 00:
In the claims, depamid does not claim a specific dissolution profile for the combination of HPMC and PEO.

[00:18:19] Speaker 00:
All depamid claims is that combining a water-soluble drug with HPMC and PEO provides gastric retention and controlled release.

[00:18:30] Speaker 00:
And just one other thing I would like to know.

[00:18:32] Speaker 00:
Are there any other questions?

[00:18:34] Speaker 04:
Just one.

[00:18:35] Speaker 04:
So I guess what I'm getting at, and what I'd like for you to address, is whether the board adopted a two-step process here with respect to the issue of Augustus, and then looking at the objective condition in Augustus.

[00:18:53] Speaker 00:
I mean, I think the board did do it in two steps.

[00:18:56] Speaker 00:
I think they first looked at the prior art of record and determined whether or not one of scale and the art would have had a reasonable expectation of success to perform the claimed invention.

[00:19:05] Speaker 00:
And then the board did look at the evidence that was presented by DAPAMED and found that it simply did not have sufficient weight to overcome that finding that the board found with respect to the prior art.

[00:19:16] Speaker 04:
All right.

[00:19:16] Speaker 04:
Thank you.

[00:19:17] Speaker 00:
Thank you.

[00:19:25] Speaker 03:
Okay, Ms.

[00:19:26] Speaker 03:
Chow, you've got a little over two minutes.

[00:19:28] Speaker 01:
Thank you.

[00:19:29] Speaker 01:
Your Honors, I would like to direct your attention, this is in relation to unexpected results, to page 39 of the board's final written decision.

[00:19:39] Speaker 01:
So pages 39 and pages 40, the heading is undo experimentation and unexpected results.

[00:19:47] Speaker 01:
What I'd like to stress is the fact that when you look at the paragraphs in this portion of the opinion,

[00:19:52] Speaker 01:
The first paragraph is dealing with undue experimentation, but there is no discussion of unexpected results.

[00:20:00] Speaker 01:
So there is no consideration whatsoever as to the evidence of unexpected results, which was submitted by DEPOMED and is reported in the patent itself.

[00:20:14] Speaker 01:
It really truly is both unrebutted by ENDO, but is also not considered at all.

[00:20:20] Speaker 01:
And yet, the undisputed, unexpected results and the long-held unmet need here are very compelling, as I said before, because that is a difference between a once-a-day dosage form with less side effects and greater compliance for both post-herpetic neuralgia patients as well as diabetic patients.

[00:20:40] Speaker 01:
These considerations were critical here.

[00:20:42] Speaker 01:
And we would direct Your Honor's attention to the Santa Fe Aventas case.

[00:20:47] Speaker 01:
This is 748 F-1354.

[00:20:49] Speaker 01:
There, too, the difference between the result of the patent at issue was a once a day dosage form versus an immediate release dosage form in the prior art.

[00:21:01] Speaker 01:
Because of the combination that was unexpected in Santa Fe Aventus, what was ultimately achieved was a once a day hypertensive controlled dosage form

[00:21:11] Speaker 01:
with improved kidney and blood vessel function compared to the immediate release dosage from the prior art.

[00:21:17] Speaker 01:
Your Honor, we submit that sanofi eventus and here, this case here, that there are strong parallels.

[00:21:24] Speaker 01:
And that because of the legal errors by the board in relation to these objective considerations, that reversal is warranted here.

[00:21:36] Speaker 03:
OK.

[00:21:36] Speaker 03:
Thank you, Ms.

[00:21:36] Speaker 03:
Chan.

[00:21:37] Speaker 03:
Thank both counsels.

[00:21:38] Speaker 03:
The case is submitted.

[00:21:39] Speaker 03:
That concludes our session for today.