[00:00:00] Speaker 01:
I don't plan to touch the constitutional issue because I think we've had we've had a thorough ventilation of it unless there are any further questions that we haven't that we haven't taken care of

[00:00:22] Speaker 04:
So we turn now to the 501 patent, which is on the original STEPS program.

[00:00:28] Speaker 04:
We say that the board's principal error here was in its misreading of the Powell reference.

[00:00:32] Speaker 04:
In particular, its reference to, quote, no effects on male sperm are recognized.

[00:00:38] Speaker 04:
The board said that this reference referred to contraceptive effects.

[00:00:42] Speaker 04:
Neither party argued this.

[00:00:44] Speaker 04:
No expert said that.

[00:00:45] Speaker 04:
The board made it up on its own.

[00:00:46] Speaker 01:
But that wasn't the exclusive basis for the board's reliance, right?

[00:00:49] Speaker 01:
They relied on the expert testimony and his reference to man and the prior art in existence at the time as establishing this.

[00:00:58] Speaker 01:
Right.

[00:00:58] Speaker 04:
And of course, the obviousness analysis has to take account of the entirety of the prior art.

[00:01:03] Speaker 04:
And that goes exactly to why this error requires reversal.

[00:01:06] Speaker 01:
So you think Powell is a teaching away?

[00:01:08] Speaker 04:
Powell comes very close to teaching away, but at the very least, what Powell is, is a more contemporaneous.

[00:01:16] Speaker 04:
It's a 1994 reference.

[00:01:18] Speaker 04:
It postdates Mann by 30 years.

[00:01:21] Speaker 04:
It under this court's decisions, and Leo Pharmaceuticals is a good example,

[00:01:25] Speaker 04:
When there's that sort of gap, and the more recent actual prior art, by the way remember man is not actually a prior art reference, it was just cited by the expert as being part of the broad general understanding of a person of ordinary skill.

[00:01:40] Speaker 04:
But by misunderstanding Powell, the board was able to take Powell and say, Powell doesn't have anything to do with this, in fact the board called it

[00:01:50] Speaker 04:
significant, the word is actually significantly about Powell being limited to contraception in weighing the prior art.

[00:01:58] Speaker 04:
So at the very least, this ought to require a remand, but we do think that this error actually just demonstrates that CFAD didn't meet its burden and that we should get our patent back.

[00:02:08] Speaker 04:
And if the court needs more information about why Powell was misread here, and we understand this is a substantial evidence standard, but we don't shrink from that here at all, because substantial evidence still requires the board to have acted as a reasonable board would have in arriving at that decision.

[00:02:27] Speaker 04:
And we don't think that Powell can be read in any reasonable fashion as referring to contraceptive effects on men, not even ambiguously.

[00:02:35] Speaker 04:
And I'll take you through the document very quickly.

[00:02:38] Speaker 04:
This quote that was used by the board appears in a paragraph three of the patient information sheet.

[00:02:44] Speaker 04:
That paragraph three is entitled in italics, Damage to Babies.

[00:02:49] Speaker 04:
The first sentence after that title is, this is very important for all women.

[00:02:56] Speaker 04:
considering thalidomide.

[00:02:57] Speaker 04:
That's at 326 of the appendix.

[00:02:59] Speaker 04:
It continues with toxicity to the developing baby.

[00:03:03] Speaker 04:
So it's talking about a pregnant woman, damage to the baby, again, the need for adequate contraception to avoid conceiving a baby, and the command that taking thalidomide, quote, must stop if pregnancy occurs.

[00:03:21] Speaker 04:
It ends by saying, your doctor can advise you about adequate contraception.

[00:03:25] Speaker 04:
And then it adds, no effects on male sperm are recognized.

[00:03:29] Speaker 04:
So that you is the woman that is referred to at the beginning of paragraph 3, damage to babies.

[00:03:35] Speaker 04:
This is very important for all women.

[00:03:37] Speaker 04:
Now, the rest of the article further underscores that this is the only reasonable reading of Powell.

[00:03:43] Speaker 04:
Page 324 of the appendix, paragraph 3.

[00:03:45] Speaker 03:
Are you asking us to read out entirely that sentence relating to males?

[00:03:51] Speaker 04:
I'm sorry, Judge Rainey, I couldn't hear you.

[00:03:53] Speaker 03:
Aren't you asking us to read out entirely, to totally disregard that sentence regarding males?

[00:04:00] Speaker 03:
Oh, no.

[00:04:01] Speaker 04:
In fact, I want you to read that sentence regarding males.

[00:04:05] Speaker 03:
Because that sentence regarding males... Why shouldn't we read it in the context of the entire paragraph, then?

[00:04:10] Speaker 04:
You should, absolutely.

[00:04:12] Speaker 04:
And the context that's provided by that paragraph is not talking about contraceptive effects of the drug on women or babies.

[00:04:21] Speaker 04:
It's talking about teratogenic effect.

[00:04:24] Speaker 04:
of the drug on babies.

[00:04:25] Speaker 03:
And how to prevent those effects?

[00:04:27] Speaker 04:
Well, it says that you need to be taking contraception.

[00:04:31] Speaker 04:
But then when it says no effects on male sperm are recognized, there's no question that that's referring not to the contraceptive effects of thalidomide, but to the teratogenic effects of thalidomide.

[00:04:42] Speaker 04:
And if you have any doubts, Judge Rainier, look to the rest of the article.

[00:04:46] Speaker 04:
At 324, paragraph 3D and E, it excludes patients, it excluded as patients, quote, women who wish to become pregnant.

[00:04:55] Speaker 04:
Now, it doesn't say there men who wish to impregnate a woman.

[00:05:00] Speaker 04:
It talks about women of childbearing potential who are not, will not, or cannot take contraception.

[00:05:07] Speaker 04:
In paragraph 5, it talks about women of childbearing potential who should agree to stop taking thalidomide immediately should they miss a period.

[00:05:15] Speaker 04:
On that same page 325 in paragraph 6, it says women of childbearing potential who discontinue treatment with thalidomide should agree to take reliable contraceptive precautions for three months after discontinuing thalidomide.

[00:05:28] Speaker 04:
And Judge Rainier, to your point, if that sentence that the board said referred to contraception actually did, you would expect a sentence there saying, men do not need to worry about this because there is no effect on male sperm.

[00:05:43] Speaker 04:
And then under labeling F, finally, this is what it says at 327, thalidomide causes serious damage to babies if taken by women during pregnancy.

[00:05:54] Speaker 04:
Not a mention of damage to babies if taken by men who inseminate a woman.

[00:06:01] Speaker 04:
Not one.

[00:06:02] Speaker 04:
That's not what this reference is about.

[00:06:05] Speaker 04:
It didn't disclose warning next.

[00:06:06] Speaker 01:
Yeah, but in the absence of that, we're left with the expert testimony, even though it predated this, and the studies in man that dealt with male sperm.

[00:06:18] Speaker 04:
Well, it dealt with rabbit sperm.

[00:06:20] Speaker 02:
Well, nobody's going to do a test on animals.

[00:06:22] Speaker 04:
Well, that's right.

[00:06:23] Speaker 04:
But the article.

[00:06:24] Speaker 02:
We were stuck with animals.

[00:06:26] Speaker 04:
Well, you are stuck with rabbits.

[00:06:28] Speaker 04:
But you also have to take into account that man also says, and again, remember, man is just part of the ordinary understanding of the person of ordinary skill in this case.

[00:06:36] Speaker 02:
Which is what the expert said.

[00:06:37] Speaker 04:
Right.

[00:06:38] Speaker 04:
But man also says, this may not apply across species.

[00:06:43] Speaker 04:
There are substantial interspecies variations.

[00:06:46] Speaker 04:
So we have an ancient reference to rabbits.

[00:06:50] Speaker 04:
We have 30 years later a reference that says, in no uncertain terms, no effects on male sperm.

[00:06:57] Speaker 04:
And of course, it sort of sounds funny to say this, but Powell was not a guidance for rabbits.

[00:07:05] Speaker 04:
Powell was a guidance for human beings.

[00:07:07] Speaker 04:
And the only human beings that it addressed were women at every stage of Powell.

[00:07:11] Speaker 04:
Now, yes, if you eliminate Powell, you're left with it.

[00:07:16] Speaker 04:
But if you add Powell and say, well, Powell tells you that at least in 1994, the state of the art was no effects on male sperm are recognized, then the board's calculus in evaluating the entirety of the prior art is very different.

[00:07:32] Speaker 04:
Dr. Fudden didn't take any account of this statement in his declaration at all.

[00:07:38] Speaker 04:
He didn't.

[00:07:39] Speaker 04:
He simply said, here's Mann.

[00:07:40] Speaker 04:
And he says, Mann says this.

[00:07:42] Speaker 04:
Therefore, that's in the prior art.

[00:07:45] Speaker 04:
That's part of the state of knowledge.

[00:07:48] Speaker 04:
He doesn't take into account this statement.

[00:07:50] Speaker 04:
And it's a very different record if this statement is part of the obviousness calculus.

[00:07:55] Speaker 04:
The board, by ignoring the arguments that have been made by the parties, completely eliminated giving any weight whatsoever to Powell by reading it in a way that made that statement irrelevant.

[00:08:08] Speaker 04:
The only other point I want to make on this, I'll leave the claim construction issue to the briefs unless you have questions.

[00:08:14] Speaker 04:
But with regard to the claim construction, the only thing I'd point you to is the discussion of Sloan, which couldn't be clearer that it's referring not only to centralizing information, but also centralizing the medium.

[00:08:27] Speaker 04:
And finally, the secondary considerations.

[00:08:29] Speaker 04:
The board gave incredibly short shrift to the secondary considerations here.

[00:08:35] Speaker 04:
The prior art.

[00:08:38] Speaker 04:
The programs for Accutane, the program from the VA, were nowhere near as effective as this one was.

[00:08:49] Speaker 04:
In Mitchell, which is the reference dealing with exposure to Accutane, there were 402 pregnancies.

[00:08:55] Speaker 04:
402 pregnancies was nowhere near what could be allowed for thalidomide.

[00:09:00] Speaker 04:
And this one took it down to zero.

[00:09:04] Speaker 04:
And Dishman,

[00:09:06] Speaker 04:
which was the Clozapine case involving the VA's program, had 3,300 adverse events out of slightly under 100,000 prescriptions.

[00:09:16] Speaker 04:
Again, wildly unsatisfactory here.

[00:09:21] Speaker 04:
The board said, well, there were four exposures and no actual abnormalities here, and said, that's not enough.

[00:09:28] Speaker 04:
That's pretty much like Dishman and Mitchell.

[00:09:31] Speaker 04:
That's not good enough.

[00:09:32] Speaker 04:
That gives secondary consideration, which this court has said in cases like Transocean and others, is so important to bringing the real world of obviousness to bear on things.

[00:09:44] Speaker 04:
And the board simply refused to do that here.

[00:09:47] Speaker 04:
I think I've kept my promise, and I'm giving you back some time.

[00:09:53] Speaker 00:
May it please support I will begin with the issue about the male patients First what the board begin with is it fair to say in your view that the board misconstrued Powell

[00:10:08] Speaker 00:
I actually think what the board recognizes that Powell is not clear and I'll get to that why I think it's unclear but I think first off what the board found is that looking to the evidence that it had before it which was the food and declaration it was the reference from Mon showing the effects in rabbits and also it pointed

[00:10:33] Speaker 00:
Coalition had pointed to Celgene, a study, I'm sorry, at 52.97 of the record.

[00:10:39] Speaker 00:
They had pointed to the fact that Celgene, when it decided to counsel male patients, was actually relying on those rabbit studies.

[00:10:46] Speaker 00:
So in terms of the rabbit to the human connection, Celgene was satisfied that that was a legitimate connection.

[00:10:55] Speaker 00:
But what the board said that I think is important is it said, and that

[00:11:08] Speaker 00:
At page 17 of the record, what the board says is that that isolated statement in Powell, standing alone, doesn't defeat the sufficiency of petitioner's evidence.

[00:11:19] Speaker 00:
So after it went through petitioner's evidence, it said, regardless of what Powell says, it doesn't defeat that other evidence.

[00:11:25] Speaker 00:
I think the court can simply stop there.

[00:11:28] Speaker 00:
We think that basically what the board found is that given the other overwhelming evidence in support, that

[00:11:36] Speaker 00:
Powell we didn't even really need to go look to Powell but what it went on to say was that even when we look to Powell we think it's unclear and I think what they're reading is actually Not is a fair reading looking to Powell as we As opposing counsel mentioned that the statement the paragraph starts out and this is at 326 of the record

[00:12:02] Speaker 00:
The paragraph starts out by talking to damage to babies.

[00:12:06] Speaker 00:
But then it says, this is very important for all women.

[00:12:10] Speaker 00:
And I think that's exactly what our closing counsel said.

[00:12:12] Speaker 00:
It's directed to women.

[00:12:14] Speaker 00:
And it goes through and talks about contraception.

[00:12:17] Speaker 00:
And it gets to the end.

[00:12:18] Speaker 00:
And it says, no effect to automation.

[00:12:19] Speaker 02:
Where are you reading from again?

[00:12:20] Speaker 00:
I'm sorry, page 326 of the record?

[00:12:24] Speaker 00:
Yes.

[00:12:25] Speaker 00:
And it's paragraph three.

[00:12:27] Speaker 00:
Yes.

[00:12:28] Speaker 00:
So it starts out, talks about damage to babies, then says, this is very important for all women.

[00:12:33] Speaker 00:
And as I think the opposing council mentioned, this is targeted to women.

[00:12:37] Speaker 00:
And it goes on, and the rest of the paragraph is talking about contraception.

[00:12:40] Speaker 00:
And then it finishes at the end by saying there are no effects on male sperm are recognized.

[00:12:46] Speaker 00:
We're addressing women.

[00:12:47] Speaker 00:
We're not talking to male patients.

[00:12:49] Speaker 00:
We're talking to women.

[00:12:50] Speaker 00:
And what the board said, what this is saying

[00:12:52] Speaker 00:
to these women is that when you're taking thalidomide, that is not going to have a contraceptive effect against the male sperm.

[00:13:00] Speaker 00:
So if you're engaged in sexual activity, you're a woman, don't think that this thalidomide is going to kill the male sperms.

[00:13:07] Speaker 00:
That's not going to act as a contraception.

[00:13:10] Speaker 00:
And that was, I think, a fair reading of this sentence.

[00:13:14] Speaker 02:
But the sentence, no effects on male sperm are recognized.

[00:13:19] Speaker 02:
seems to say that the thalidomide will not have an effect on male sperm, does it not?

[00:13:25] Speaker 00:
Through the women.

[00:13:26] Speaker 00:
The sentence is targeted to women who are taking thalidomide.

[00:13:30] Speaker 00:
not to male patients.

[00:13:31] Speaker 00:
I think as I think as opposing counsel would agree, it's targeted to women.

[00:13:35] Speaker 00:
It's not targeted to men.

[00:13:37] Speaker 00:
And saying anything about male patients, you shouldn't take it because it's going to affect your sperm.

[00:13:41] Speaker 00:
It's saying female patients don't think that when you take it, this is going to have an effect on male sperm.

[00:13:47] Speaker 00:
We think that is a fair reading of what it says.

[00:13:49] Speaker 00:
We think it's

[00:13:50] Speaker 00:
At any event, we think the sentence is very ambiguous.

[00:13:54] Speaker 00:
And we think that when there is more than one interpretation at this court's cases, like Jolly and by our active Gazelshoff that we said in our brief at page 25, when there are multiple conclusions that can be drawn from the evidence that the board's decision should be given deference.

[00:14:13] Speaker 00:
But beyond that, we also think that the board didn't actually need to get to that because it found

[00:14:20] Speaker 00:
that the other evidence was so overwhelming that this single statement in Powell was not sufficient to defeat that other evidence.

[00:14:28] Speaker 00:
And I just want to point out lastly that the article that they referred to about no effect

[00:14:36] Speaker 00:
which was, it's an article that was cited, it's not actually part of the record, but the article that opposing counsel referred to is cited in Mann, and where they were trying to suggest that there would not be an effect, or you would know from animal to animal,

[00:14:52] Speaker 00:
And if you read the full sentence, it says, it is fully recognized that the results of experiments limited to one species of laboratory animals must not be taken as necessarily carrying a great weight in validity for humans.

[00:15:04] Speaker 00:
But it goes on to say, nevertheless, they serve as a useful monitoring device and in that capacity may alert the medical profession to the appropriative risk inherent in medication of the male with thalidomide.

[00:15:17] Speaker 00:
So I think it goes much further than that in suggesting that one should

[00:15:21] Speaker 00:
based on the rabbit studies, think about counseling male patients, which is exactly what was the basis for Celgene deciding to counsel male patients was these rabbit studies.

[00:15:33] Speaker 02:
Well, sentences like that that you don't necessarily infer a similar effect in humans from effects in animals show up all the time in these

[00:15:45] Speaker 02:
research papers I suppose.

[00:15:49] Speaker 00:
Certainly there's not it's not necessary but it certainly would lead someone as the article goes on to say would lead one to be cautious and to certainly counsel patients which is all that the claim actually requires.

[00:16:02] Speaker 00:
There's no step in there about actually even changing whether or not you administer the drug to male patients and simply counsel male patients about this potential effect.

[00:16:13] Speaker 00:
Turning now to the claim construction issue, I think that the board's decision was sound.

[00:16:19] Speaker 00:
It relied on the fact that there was no centralized in the claim.

[00:16:22] Speaker 01:
It relied on what is in the specification, which is open to- Well, your friend lied in his discussion of claim construction relying on the briefs.

[00:16:30] Speaker 01:
So I think maybe we should leave it at that.

[00:16:31] Speaker 00:
Okay, well he also talked about the prosecution history, and I don't think that the prosecution history is as clear as he says, and I think the board's decision explains that.

[00:16:45] Speaker 00:
Because in the prosecution history, it was talking about the Sloan reference and distinguished on the basis that it was directed to the internet, whereas their claim was to a computer-readable storage medium.

[00:16:57] Speaker 00:
And to the extent that talked about centralizing information, that, as the board said, is not the same thing as a centralized computer-readable storage medium.

[00:17:06] Speaker 00:
Moreover, given the claims and the specification, there was more than evidence to support its construction.

[00:17:12] Speaker 00:
And it also went on to say it would be obvious even if you adopted Seljand's construction.

[00:17:17] Speaker 01:
Do you want to say anything about the secondary consideration?

[00:17:20] Speaker 00:
Yes, with respect to secondary considerations, I think it's important to look to what was actually an issue before the board and their evidence.

[00:17:29] Speaker 00:
Was about three and a half pages and it begins at 38 64 to 38 68 And so the evidence that they presented before the board was all addressed by the board And their arguments were principally about

[00:17:47] Speaker 00:
Well, with respect to the unexpected results, which is what opposing counsel seems to be focused on, all that was said was that the Stout's method was 100% effective.

[00:18:00] Speaker 00:
And the board addressed that and said it was an unsupported assertion.

[00:18:04] Speaker 00:
In fact, that's true.

[00:18:05] Speaker 00:
The two experts simply relied, again, on this sentence or conclusory sentence by Seljean's representative, Mr. Freeman.

[00:18:13] Speaker 00:
And then secondly, the board said,

[00:18:16] Speaker 00:
that noted that this other study which had been submitted by

[00:18:24] Speaker 00:
By coalition, there was a study by Boyer that indicated that there were actually four confirmed fetal exposures.

[00:18:32] Speaker 00:
And the board said that is actually what the claim is directed to.

[00:18:36] Speaker 00:
So given that, this conclusionary statement about zero birth defects, the board said that would give it little weight, because it's not actually what is claimed.

[00:18:49] Speaker 00:
But this whole notion of these other evidence that he is discussing, the 402 pregnancies and the 3,300 adverse effects with Dishman, those were not figures that were

[00:19:03] Speaker 00:
here in the brief before the board.

[00:19:05] Speaker 00:
Those were, I think, I don't even think the 3,300 address effects was in the brief at all.

[00:19:11] Speaker 00:
They mentioned in the background section about the 402 pregnancies in Mitchell, but it was in part of their brief discussing the unexpected results.

[00:19:21] Speaker 00:
Moreover, we addressed that in our brief.

[00:19:23] Speaker 00:
We're comparing apples and oranges here.

[00:19:25] Speaker 00:
What's at issue is the number, what's claimed is the number of fetal exposures and these pregnancies.

[00:19:36] Speaker 00:
First of all, the percentage in both of these is extremely small when you look at the percentage and not the absolute numbers.

[00:19:43] Speaker 00:
They're much below 100%.

[00:19:44] Speaker 00:
We've addressed this in our brief.

[00:19:46] Speaker 00:
And moreover, in Mitchell, yes, there were 402 pregnancies.

[00:19:51] Speaker 00:
But you can't compare that to the four-fetal exposures.

[00:19:54] Speaker 00:
Those are different things.

[00:19:55] Speaker 00:
In effect, in Mitchell, what they said was the vast majority of those women aborted their pregnancies.

[00:20:02] Speaker 00:
And then they talked about the very small, I think, one

[00:20:08] Speaker 00:
Fetus that had some abnormalities and six or one with major abnormalities and six with with minor abnormalities So these these numbers that they're presenting here are red herring and similar with Dishman The numbers that they're comparing are just just different.

[00:20:25] Speaker 00:
They're just looking at different things So I will leave it at that if the court Thank you

[00:20:51] Speaker 04:
The entirety of the board's treatment of the Powell reference is at the bottom of page 17 in a single paragraph.

[00:21:01] Speaker 04:
It's Appendix 0017.

[00:21:04] Speaker 04:
My friend said that the board made alternative holdings here.

[00:21:10] Speaker 04:
You can't find it.

[00:21:11] Speaker 04:
The board did not say, regardless of whether this is the reading of this statement.

[00:21:17] Speaker 04:
My friend said to you, this is basically what the court found.

[00:21:20] Speaker 04:
I wrote down her words verbatim.

[00:21:22] Speaker 04:
That is not basically what the court found.

[00:21:26] Speaker 04:
My friend said that this is unclear, and the board found it unclear.

[00:21:29] Speaker 04:
You won't find the word unclear or any of its synonyms here.

[00:21:34] Speaker 04:
The closest you get is an isolated statement, but that doesn't say it's unclear.

[00:21:38] Speaker 04:
In fact, the board quite clearly says in the last sentence of this paragraph how it read Powell.

[00:21:45] Speaker 04:
My friend says this was a fair reading.

[00:21:47] Speaker 04:
Powell if it was a fair reading of Powell CFED's expert didn't come with it come up with it CFED didn't come up with it our expert certainly didn't come up with it the board made it up it's not inappropriate it's not a fair reading it's not an ambiguous reference at all in this regard on

[00:22:08] Speaker 04:
The question of secondary considerations, we relied both on unexpected results and long felt need.

[00:22:16] Speaker 04:
The comment about the conclusory sentence by a Celgene representative, we answered that in our reply brief.

[00:22:22] Speaker 04:
I'd also add that the board never questioned the veracity of the figures given there.

[00:22:26] Speaker 04:
And with regard to the final comments made by my friend about Celgene never relying on the numbers that were set forth in the Accutane and Clozapine references, that's wrong.

[00:22:38] Speaker 04:
Particularly Clozapine is the Dishman reference of A3819 and 20.

[00:22:43] Speaker 04:
That's in the background section of the patent donor's response.

[00:22:46] Speaker 04:
And then that section is referred to.

[00:22:48] Speaker 04:
in the argument on secondary considerations.

[00:22:52] Speaker 04:
So the notion that we didn't make this argument before the board is demonstrably incorrect.

[00:22:57] Speaker 04:
We urge this board, this court, we now know the difference to reverse.

[00:23:02] Speaker 04:
Thank you.

[00:23:03] Speaker 01:
Thank you.

[00:23:04] Speaker 01:
We thank both sides.

[00:23:05] Speaker 01:
I think I neglected to say it at first, but both of the prior appeal and this one are submitted.

[00:23:12] Speaker 01:
Thank you.