[00:00:00] Speaker 03:
Our first case for argument today is 20-1758 Juno Therapeutics versus Kite Pharma.

[00:00:09] Speaker 03:
Mr. Rosencrantz, please proceed when you're ready.

[00:00:13] Speaker 01:
Thank you, Your Honor.

[00:00:13] Speaker 01:
Good morning.

[00:00:14] Speaker 01:
May it please the court, Josh Rosencrantz representing Kite.

[00:00:18] Speaker 01:
Your Honor, has Juno achieved this massive $1.2 billion verdict through a combination of securing a patent

[00:00:27] Speaker 01:
that awarded it vastly more than it described, worked, or taught, impermissibly expanding the claim four and a half years after issuance.

[00:00:38] Speaker 01:
And it damages opinion that was manipulated to yield results that were many multiples of any reference license that Juneau's own expert described as comparable.

[00:00:50] Speaker 05:
If you thought the patent was so horrible, then why did you try so hard to license it?

[00:00:56] Speaker 01:
Well, so Your Honor, we tried to license it after the COC was issued.

[00:01:01] Speaker 01:
And of course, you always try to mitigate risk.

[00:01:05] Speaker 01:
But that can't be held against us, certainly not on something like validity.

[00:01:10] Speaker 01:
And so this morning, what I'd like to do is focus on the 112 issues and then turn to damages

[00:01:18] Speaker 01:
and maybe say a few words of time permits on the certificate of correction.

[00:01:23] Speaker 04:
Well, before you get to that, can I just ask you how those all work together, what you've described?

[00:01:28] Speaker 04:
We've got the written description validity and we've got the C of C. C of C is an infringement matter and validity, obviously, we know.

[00:01:37] Speaker 04:
So what are you asking us for?

[00:01:40] Speaker 04:
I mean, if we were to affirm

[00:01:42] Speaker 04:
to reverse on the certificate of correction.

[00:01:45] Speaker 04:
Where does that leave us with validity contentions?

[00:01:47] Speaker 04:
Are they still on the table?

[00:01:49] Speaker 01:
Yes, they would be, Your Honor.

[00:01:50] Speaker 01:
I mean, the way this court typically addresses these issues is you start with validity.

[00:01:55] Speaker 01:
Validity would be a clear win for us if the patent is valid.

[00:01:59] Speaker 04:
OK, so on that point, if you were to prevail hypothetically on the validity question, would that help get rid of the CFP question?

[00:02:08] Speaker 01:
Yes, Your Honor.

[00:02:08] Speaker 01:
There would be no reason for the court to address COC.

[00:02:11] Speaker 01:
It's a much more fact-specific, case-specific issue.

[00:02:14] Speaker 05:
So on 112... We'll let you get back into it in a second.

[00:02:18] Speaker 05:
Of course.

[00:02:18] Speaker 05:
Specifically with respect to what Judge Crost said, I mean, you say the way this court typically does it, but often, partners will say, what we care about is whether we infringe this patent.

[00:02:28] Speaker 05:
If we don't infringe it, we don't care about validity.

[00:02:31] Speaker 05:
I mean, so it's often waivable, and that's, I think,

[00:02:33] Speaker 05:
That's what we're trying to find out.

[00:02:35] Speaker 01:
Oh, thank you, Your Honor.

[00:02:37] Speaker 01:
We would not be inclined to waive the validity question, but certainly this court has the option of addressing infringement and not addressing validity.

[00:02:48] Speaker 03:
How do we have that option under Cardinal Chemical?

[00:02:51] Speaker 03:
And you raised counterclaims.

[00:02:52] Speaker 03:
I don't actually think we do have that option, sir.

[00:02:55] Speaker 01:
Fair enough.

[00:02:56] Speaker 01:
So we are not waiving validity.

[00:02:58] Speaker 01:
And I'd like to start with validity, because that is

[00:03:01] Speaker 01:
just under this court's precedent, a clear winner, and just to underscore, it wasn't just written description, but also enablement.

[00:03:12] Speaker 01:
But I'll start with written description, because Juno does not even try to argue that it meets Ariad.

[00:03:18] Speaker 04:
So Juno tries... Let me ask you that.

[00:03:21] Speaker 04:
Sorry to keep interrupting, but that's what we're here for.

[00:03:22] Speaker 04:
We're out of practice, so we're a little excited about that.

[00:03:25] Speaker 01:
That's what I'm here for, Your Honor.

[00:03:26] Speaker 04:
You've criticized Juno repeatedly in your brief for saying that the common structural features of representative CT tests of area is only for a new genus.

[00:03:36] Speaker 04:
Well, that seems true that the test is not only for a new genus.

[00:03:41] Speaker 04:
There's got to be some practical boundary for when we require examples and when we can rely on background knowledge of a person's skills in the art.

[00:03:52] Speaker 04:
So if we take the narrower claims here, the ones against CD-19, what would be enough background knowledge to support these claims?

[00:04:01] Speaker 01:
Well, Your Honor, it would have to be vastly more than there was here.

[00:04:04] Speaker 01:
So here there were just four or five known CD-19 specific SCFDs.

[00:04:11] Speaker 01:
OK, so that's five as compared to, for example, in Amgen.

[00:04:18] Speaker 01:
So Amgen 1 was the

[00:04:20] Speaker 01:
uh... written description case they were twenty six and they were fully described in people knew the three-dimensional structure engine here there were just five only two only one actually that had ever actually been attached to a car uh... and they were not at all described seating nineteen was not a fully described antigen so you would need for

[00:04:43] Speaker 04:
I mean, remember, these are pieces of- But the district court tells us a lot of this stuff has been around for a very long time, dating back to the 90s and 2000s.

[00:04:52] Speaker 01:
Sure, Your Honor.

[00:04:52] Speaker 01:
So this stuff, meaning SCFVs, antibodies have been around for vastly longer, yet this court, in cases like Centicor and Amgen, has held that even though antibodies are well known, you can't just announce that you have an antigen.

[00:05:11] Speaker 01:
and then claim everything that binds to that antigen.

[00:05:15] Speaker 01:
This would be clearly impermissible just on that one claim element alone under this court's precedent.

[00:05:22] Speaker 01:
Take, for example, centicor.

[00:05:24] Speaker 01:
Antibodies were really well known.

[00:05:27] Speaker 01:
And the patentee described an antibody that was from a mouse and an antibody that was chimeric, but not a human antibody.

[00:05:38] Speaker 01:
Here Juno has claimed everything, including human antibodies, and they haven't even made a human antibody for seven years.

[00:05:45] Speaker 01:
And so let me just say a few more words about why Juno fails Ariad, and it's all based upon the undisputed record.

[00:05:55] Speaker 01:
Juno does not dispute the facts that would establish failure of written description under identical Boston scientific Carnegie Mellon.

[00:06:04] Speaker 01:
So first,

[00:06:05] Speaker 01:
The structural limitations in the narrowing claims describe a genus of millions of billions of potential candidates.

[00:06:16] Speaker 01:
That's undisputed, and it's candidates from any source.

[00:06:19] Speaker 01:
Second, only some unknown fraction of SCFBs in CARs satisfy the functional specific binding limitation that is binding to CD19.

[00:06:31] Speaker 01:
Not that any correlation would help,

[00:06:33] Speaker 01:
because the patent doesn't disclose even the structure of the one CD9 specific SCFB that it does mention.

[00:06:42] Speaker 01:
And the record is full of examples of cars that failed and SCFBs that failed.

[00:06:49] Speaker 03:
And third... Well, Counsel, when you're giving us these statistics and expressing how many options there are among small chain SCs that possibly

[00:07:03] Speaker 03:
could bind to the CD19 antigen on the surface of the cancer cell, that's all relevant to claim five.

[00:07:13] Speaker 03:
But isn't claim three also an issue in this case?

[00:07:18] Speaker 03:
And claim three is even much broader because it's not even just CD19.

[00:07:23] Speaker 03:
It's any antigen of any kind and any small chain SV that would then bind to any

[00:07:31] Speaker 03:
antigen of any kind.

[00:07:34] Speaker 01:
So that is correct.

[00:07:35] Speaker 01:
And let me start to quibble, but these are not small chains.

[00:07:37] Speaker 01:
These are actually really big chains.

[00:07:39] Speaker 01:
The SCFDs themselves

[00:07:41] Speaker 03:
are big chains of... SCFC stands for small chain SC, right?

[00:07:44] Speaker 01:
Right, but I've compared... Okay, I want to make sure I am understanding that.

[00:07:47] Speaker 01:
Yes, you're right.

[00:07:48] Speaker 01:
As compared to the rest of the car, it is smaller.

[00:07:52] Speaker 01:
Or as compared to an antibody, but let me just... Okay, Mike, yes, Mike corrected us both.

[00:07:57] Speaker 03:
He says it's single chain SC.

[00:07:58] Speaker 03:
Is that right?

[00:07:59] Speaker 01:
Yes.

[00:08:00] Speaker 01:
Okay.

[00:08:00] Speaker 01:
Okay.

[00:08:01] Speaker 01:
So, but your point is well taken, Your Honor.

[00:08:04] Speaker 01:
They're claiming the ability to bind to anything, whether that thing was even known at the time.

[00:08:10] Speaker 01:
The vast majority of cancer cells had no known antigens at the time.

[00:08:15] Speaker 03:
And I was saying the third item is that this is- Is there testimony in the record to that effect?

[00:08:20] Speaker 03:
The vast majority of cancer cells had no known antigens at the time.

[00:08:24] Speaker 01:
Yes.

[00:08:25] Speaker 01:
Yes, Garcia testified to that, Your Honor.

[00:08:28] Speaker 03:
I mean, I don't suppose you know where in the record that is by any chance.

[00:08:32] Speaker 01:
I do.

[00:08:33] Speaker 01:
If you give me a moment.

[00:08:36] Speaker 03:
You can also just tell us on rebuttal if you want.

[00:08:38] Speaker 01:
Yeah, let me tell you on rebuttal.

[00:08:39] Speaker 01:
One of your helpers could come up with that for you.

[00:08:42] Speaker 03:
Hm?

[00:08:42] Speaker 03:
One of your helpers could come up with that.

[00:08:43] Speaker 01:
No, I have it here.

[00:08:46] Speaker 01:
But I do want to get out the third item, which is that it is highly unpredictable whether an SCFV or a car

[00:08:55] Speaker 01:
will specifically bind to the target CD9.

[00:08:58] Speaker 03:
So one of the questions, or one of the issues that you raised, one of the pieces of evidence was that Juno itself had tried more than a billion single chain SBs and had only come up with 60 out of that billion that would be workable.

[00:09:17] Speaker 03:
Am I remembering those facts right?

[00:09:19] Speaker 01:
A 60 out of the billion that would actually bind specifically.

[00:09:24] Speaker 01:
Yes, that's correct.

[00:09:25] Speaker 01:
And by the way, that was not the only.

[00:09:27] Speaker 01:
Like binding to CG-90?

[00:09:28] Speaker 01:
Yes, yes, that's correct.

[00:09:29] Speaker 05:
60 out of the billion they tried or 60 out of the billion that you say could possibly bind?

[00:09:35] Speaker 01:
No, no, there are millions of billions of possible candidates.

[00:09:38] Speaker 01:
They tried a billion human SCFBs.

[00:09:42] Speaker 01:
And only 60 of those bound to CD19.

[00:09:46] Speaker 05:
How many sequences do you think would have to be disclosed?

[00:09:49] Speaker 05:
I mean, part of the problem here is that we have allowed genus claiming.

[00:09:54] Speaker 05:
So are we supposed to say that they have to disclose everything?

[00:09:58] Speaker 01:
Well, Your Honor, discord has never allowed genus claims to antibodies like this when they are so wildly unpredictable.

[00:10:04] Speaker 01:
And just bear in mind, the FCFVs are taken from components of antibodies.

[00:10:09] Speaker 01:
They are taken from the most variable

[00:10:11] Speaker 01:
components of the antibodies.

[00:10:13] Speaker 01:
So how many would be hard to answer that question without knowing more about the specific antigen?

[00:10:21] Speaker 01:
So you would have to know tons about the antigen.

[00:10:24] Speaker 01:
You would have to know its structure.

[00:10:25] Speaker 01:
You would have to know a lot of things, and I would say in a very narrow range,

[00:10:30] Speaker 01:
that would bind to that.

[00:10:33] Speaker 03:
Wouldn't it rather than a number, like in terms of how many, wouldn't the answer be if the patent taught, for example, the structural attributes of which ones would be likely to be the successful ones or which classes in particular.

[00:10:48] Speaker 03:
If the patent gave you a roadmap to being able to weed through the millions of billions

[00:10:53] Speaker 03:
That would be the answer, right?

[00:10:55] Speaker 03:
Not 17 or 100 or 10,000 or whatever.

[00:10:59] Speaker 03:
It would have to be some sort of roadmap to allow a skilled artisan to identify them.

[00:11:04] Speaker 01:
Correct, Your Honor.

[00:11:05] Speaker 01:
And it would be very, very hard to do because the record here shows if you take an SCFV that binds, so clearly it was in the literature that bound, you change three amino acids, and you all of a sudden have an SCFV that doesn't bind.

[00:11:20] Speaker 01:
These are highly variable.

[00:11:22] Speaker 04:
I just, do you know why in your view things went so awry in this case based on your view?

[00:11:30] Speaker 04:
I know you complain about the jury instruction not being specific enough for this kind of case.

[00:11:36] Speaker 04:
But it seems like, you know, in your view at least, on apportionment, on the damages piece, on the CFC, and certainly on the written description, the jury just

[00:11:49] Speaker 04:
misunderstood or didn't get it.

[00:11:51] Speaker 04:
Do you have a view on how things went down and why?

[00:11:53] Speaker 01:
Well, sure, your honor.

[00:11:54] Speaker 01:
I mean, when you get a jury verdict, excuse me, when you have a jury and the jury is not even told what the area test is, and you put on an expert and said, well, all these structures were the same.

[00:12:08] Speaker 01:
When in fact, the structures were not all the same.

[00:12:11] Speaker 01:
The structures of SCFDs are the same, but not that which defines

[00:12:14] Speaker 01:
The gene is the Chief Judge Moore's question about what specific you would have to know.

[00:12:20] Speaker 05:
But is it really the honest answer that the patentee has such a great story here about your clients being the bad guys and tricking the inventor into disclosing his information, and even though they thought they had the license, they didn't do it, and they went ahead anyway?

[00:12:37] Speaker 05:
I mean, it's a really good jury trial story, right?

[00:12:42] Speaker 01:
Well, Your Honor, so Joe had a story, we had a different story, but yes, that could easily have, the jury could easily have decided that all of the rhetoric that has nothing to do with either written description or enablement or the validity of the COC was enough to persuade.

[00:12:59] Speaker 05:
And there was plenty of evidence to support the conclusion that there was willful infringement.

[00:13:04] Speaker 01:
We do challenge willful infringement, and in particular whether you can call this egregious when you've invested in a drug and had very strong defenses.

[00:13:18] Speaker 01:
and 10 months before you got a market was the first time that the IPR was turned down.

[00:13:26] Speaker 01:
But I see I'm eating well into my time.

[00:13:29] Speaker 03:
No, we would like you to continue.

[00:13:31] Speaker 03:
This is a very complicated case and we want to understand it.

[00:13:34] Speaker 03:
Can we go back for a second to the 60 of the billion that Juno tried that it found, the single chain FCs that bound to CD19?

[00:13:46] Speaker 03:
How hard were those tests?

[00:13:48] Speaker 03:
And here's what I mean by that.

[00:13:50] Speaker 03:
For enablement purposes, you want us to find undue experimentation, and that's one of the pieces of evidence you point to, is that this trial and error would have to occur a billion times to come up with the possible appropriate small chain or single chain FEs.

[00:14:10] Speaker 03:
My question is how hard is it?

[00:14:11] Speaker 03:
Is this like DNA sequencing where you turn the computer on at night and come back in the morning and it's all spit out on the spreadsheet?

[00:14:18] Speaker 03:
I mean, how hard, for you, you argued undue experimentation and you want me to overturn a jury verdict that said it wasn't undue experimentation.

[00:14:26] Speaker 03:
What was presented in the way of evidence in this case about the level of complexity or the difficulty associated with performing these trial and error tests?

[00:14:35] Speaker 01:
So your honor, it is very difficult to make a car.

[00:14:37] Speaker 01:
So it was described by Juno's expert as standard.

[00:14:42] Speaker 01:
Standard does not mean fast.

[00:14:44] Speaker 01:
The testimony on the date of priority, the testimony was that as of the date of priority, which is 2002, making a car, making an SCFV

[00:14:57] Speaker 01:
could take months to over a year.

[00:15:01] Speaker 03:
It's hard for me to believe.

[00:15:03] Speaker 03:
They tried a billion of them and each one took months to over a year.

[00:15:06] Speaker 03:
That would be a billion years.

[00:15:08] Speaker 01:
Chief Judge Boyd, that was 15 years later when the technology had developed vastly.

[00:15:15] Speaker 01:
So they were not taking a year per car.

[00:15:18] Speaker 01:
But by the way, as of the date of priority in 2002,

[00:15:22] Speaker 01:
and and you know expert never disagree with it the testimony at thirty three six eighty five with that it would take months to well to well over a year and you know the only expert that voice fully human fcp

[00:15:36] Speaker 01:
It is extremely difficult.

[00:15:37] Speaker 01:
That's the 33-9-55.

[00:15:39] Speaker 05:
That testimony was very cryptic.

[00:15:42] Speaker 05:
I mean, it's essentially a sentence without any basic foundation being laid for it.

[00:15:47] Speaker 01:
Right.

[00:15:47] Speaker 01:
So that's the problem.

[00:15:49] Speaker 01:
What Junot did here is what every patentee does in these 112 cases in response to very specific testimony about how long it takes or how large the numbers are.

[00:16:01] Speaker 01:
They say things like, oh, it's not that big, or it's standard, but they don't actually create a material.

[00:16:07] Speaker 05:
Yeah, but I read that expert testimony that you're relying on, and I didn't see much description or background foundation for why that opinion was expressed.

[00:16:17] Speaker 05:
He just simply said it.

[00:16:19] Speaker 01:
Well, so right, this was, I mean, the parties were crammed into a very short trial.

[00:16:23] Speaker 01:
His expert report explains, actually, his testimony explains in significant detail what you have to do

[00:16:30] Speaker 01:
to create an SCFB.

[00:16:31] Speaker 01:
So to be clear, you have to first have an antibody.

[00:16:35] Speaker 01:
To create an antibody, you have to inject the antigen into the mouse, let's say.

[00:16:40] Speaker 01:
You're just focusing on mice.

[00:16:42] Speaker 01:
Then you don't have an SCFB from that.

[00:16:45] Speaker 01:
You wait several weeks for many, many antibodies to generate.

[00:16:49] Speaker 01:
Then you purify the antibody.

[00:16:51] Speaker 01:
Then you take that purified antibody, and you have to clone it to sequence the DNA to get the amino acid.

[00:16:57] Speaker 01:
Right.

[00:16:57] Speaker 01:
It's a three-step process.

[00:16:58] Speaker 05:
The point, your point being it's a three-step process.

[00:17:02] Speaker 01:
Oh, it's way more than three steps.

[00:17:03] Speaker 01:
I've only described getting the small and large, excuse me, the two chains, the two variable chains of the antibody.

[00:17:16] Speaker 01:
You then have to take those and turn them into SCFVs.

[00:17:20] Speaker 01:
So you've got to decide the order and test that.

[00:17:22] Speaker 01:
You've got to decide the right linker.

[00:17:24] Speaker 01:
And that's before you get to putting it onto a car, which takes another several months to a year, according to the testimony here.

[00:17:32] Speaker 01:
And by the way, that billion, even 15 years later, took months to over a year.

[00:17:41] Speaker 05:
Can we talk about the certificate of correction?

[00:17:43] Speaker 05:
Sure.

[00:17:44] Speaker 05:
Go ahead.

[00:17:44] Speaker 05:
Can we just do that before you sit down?

[00:17:47] Speaker 01:
Yes.

[00:17:47] Speaker 01:
And if I may, I want to make sure to say just something about damages, if the court will let me.

[00:17:52] Speaker 01:
But absolutely, I want to go over the report once again.

[00:17:55] Speaker 05:
Okay.

[00:17:55] Speaker 05:
So the certificate of correction issue, now the trial court found that, you know, you had a large hill to climb to overcome the jury's factual conclusions.

[00:18:07] Speaker 05:
And there was a lot of factual evidence about what a post-it would understand from this history.

[00:18:16] Speaker 05:
It's pretty clear they were trying to fix it and that they knew what the problem was.

[00:18:22] Speaker 05:
Why isn't that enough?

[00:18:25] Speaker 01:
Well, Your Honor, so what you're talking about is the RCE.

[00:18:29] Speaker 01:
The RCE proposed three changes.

[00:18:32] Speaker 01:
It ends up at the end of the day following through with two of them, but not the third.

[00:18:38] Speaker 01:
But there's no explanation that would be clear to a person of skill as to why they didn't pursue

[00:18:45] Speaker 05:
that particular change, why they reinstated the sequence and the... Well, it looked to me like it was pretty obvious that whoever was doing the prosecution simply made a mistake and had the third RC apply to the second application instead of the first one, which is what undid the sequencing change.

[00:19:05] Speaker 05:
I mean... Well, so... Why couldn't the jury accept that proposition?

[00:19:11] Speaker 01:
It isn't clear.

[00:19:12] Speaker 01:
I mean, as a matter of law, that would not be clear to a person of skill in the art, because there are any number of other explanations, including an explanation that the district court gave on claim construction.

[00:19:25] Speaker 01:
So one of them could be Saddlin's own articles for five years had exactly that same chain published.

[00:19:35] Speaker 05:
So it could well be that they were like... When you say the same, you mean the original chain?

[00:19:38] Speaker 01:
Yeah, the chain has originally claimed in sequence ID number six.

[00:19:45] Speaker 01:
So a person of skill could easily have said, oh, wait a minute, the patent prosecutor got it wrong and realized that the articles were correct.

[00:19:55] Speaker 01:
They could have been doing it to avoid prior art, so that is to reinstate the COC.

[00:20:00] Speaker 01:
But there, excuse me, to reinstate that original sequence ID number six.

[00:20:05] Speaker 01:
But then there were all sorts of other clues throughout the patent that it was actually correct.

[00:20:12] Speaker 05:
And I just want to step back and say... But the trial court found that there were also clues the other way.

[00:20:17] Speaker 05:
And so it's up to the jury to weigh those clues, right?

[00:20:20] Speaker 01:
So agreed, Your Honor.

[00:20:22] Speaker 01:
The judge, there were clues in the other direction.

[00:20:25] Speaker 01:
And the question here is, what's clear?

[00:20:27] Speaker 01:
And I know the parties have hit the court with a lot of detail, but that's exactly the point.

[00:20:32] Speaker 01:
The question here is whether any person of skill in the art would take one look at this patent and the prosecution history and say, aha, there's a mistake here.

[00:20:41] Speaker 01:
I know what it is, and I know exactly how to fix it.

[00:20:44] Speaker 05:
What about the other point?

[00:20:47] Speaker 05:
By definition, there's a substantive difference between the as claimed and as corrected, right?

[00:20:53] Speaker 05:
Yes, right.

[00:20:54] Speaker 05:
So why are we spending so much time on what someone would figure out the mistake was versus saying whether or not something that creates a substantive difference could possibly be a minor correction?

[00:21:11] Speaker 01:
Well, so minor correction.

[00:21:13] Speaker 01:
So I agree with Your Honor on the question.

[00:21:16] Speaker 01:
Minor corrections under this court's law can change claim scope, but only if they are clear and only if the fix is clear.

[00:21:27] Speaker 01:
So all of these signs that Juno points to may make you question whether there's a mistake, but it doesn't tell you that the correct answer to this is to reinstate the RCE to the extent that it had not been fully implemented.

[00:21:44] Speaker 05:
Which claim?

[00:21:45] Speaker 05:
Clearly, under one, there's no infringement, and under the other, there is, or at least that's what the party seems to consider.

[00:21:54] Speaker 05:
Which claim is broader?

[00:21:57] Speaker 01:
So what Juno did was to broaden the claim because it encompasses more than, you know, rather than encompassing a chain of amino acids of X length, it encompasses coding for a chain of amino acids of X length minus one.

[00:22:16] Speaker 01:
And so it embraces more.

[00:22:18] Speaker 01:
It goes from 114 to 113.

[00:22:21] Speaker 01:
Before it did not capture our product, and now it does capture our product, so it's broader.

[00:22:27] Speaker 03:
Can I ask you to back up for one more second?

[00:22:29] Speaker 03:
I want to go back to your claim that it would take months up to a year to come up with the single-chain SV.

[00:22:40] Speaker 03:
There was testimony by Juno's expert, Brocker, I think his name was, that the Orlandi method was a cookbook.

[00:22:47] Speaker 03:
That was the word he used, a cookbook for making

[00:22:51] Speaker 03:
And then there was some, I remember some testimony somewhere and the district court even cited it about how some laboratory dishwasher was asked to make one and was able to readily make one.

[00:23:05] Speaker 03:
So what is your response?

[00:23:08] Speaker 03:
Is it that those things didn't occur in 2002 but were occurring 15 years later?

[00:23:13] Speaker 03:
Or what, because we are reviewing the evidence to find substantial evidence, not de novo assessing it on our own.

[00:23:20] Speaker 03:
So what would your response be to why it was improper for the district court to defer to that evidence?

[00:23:27] Speaker 01:
Well, so you're right.

[00:23:28] Speaker 01:
So Orlando did predate the priority date.

[00:23:33] Speaker 01:
But Orlando taught how to take an antibody that was already identified

[00:23:39] Speaker 01:
and then shear off the variable regions and connect them back together.

[00:23:45] Speaker 01:
It did not capture the universe of the antibodies that had not yet been developed, and therefore it did not capture the universe.

[00:23:51] Speaker 03:
Well, is CD19 an already developed antibody in 2002?

[00:23:54] Speaker 01:
There were antibodies to CD19.

[00:23:57] Speaker 01:
There were only mouse antibodies.

[00:23:59] Speaker 01:
Oh, I see.

[00:24:00] Speaker 01:
But there wasn't the full range of every possible antibody.

[00:24:05] Speaker 01:
Patton mentions only one.

[00:24:07] Speaker 01:
The art talks about another one.

[00:24:10] Speaker 03:
And the patent doesn't even disclose the immunized sequence for the one it mentioned.

[00:24:13] Speaker 01:
Correct.

[00:24:13] Speaker 01:
So you couldn't draw any structural correlation out of it.

[00:24:18] Speaker 01:
And to the extent that you would go to the literature and say, oh, it must be this one, the one in the literature was actually wrong, although it also wasn't the one that Juno had developed.

[00:24:29] Speaker 01:
And then secondly, the second answer to the court's question about Orlandi is,

[00:24:34] Speaker 01:
that just because you have a cookbook, that was true in IDENTICS, in Boston Scientific, in Carnegie Mellon, and in Amgen.

[00:24:41] Speaker 01:
People knew how to make each of those possible candidates, but it took a while.

[00:24:47] Speaker 01:
So just because there was a cookbook that told you how to make it does not mean that it was at all fast.

[00:24:54] Speaker 03:
Okay.

[00:24:54] Speaker 03:
Okay, Mr. Rosencrantz, we need to hear from Mr. Chu.

[00:24:56] Speaker 03:
We will restore your rebuttal time.

[00:24:58] Speaker 01:
Your Honor.

[00:25:17] Speaker 03:
Mr. Chu, obviously, Mr. Rosencrantz went quite a bit over, and you don't worry about the time.

[00:25:24] Speaker 03:
You have the same luxury if you want it.

[00:25:27] Speaker 02:
May it please the court.

[00:25:29] Speaker 02:
Morgan Chu on behalf of Sloan Kettering and Juno Therapeutics.

[00:25:34] Speaker 02:
This case is about a pioneering invention from Sloan Kettering.

[00:25:39] Speaker 02:
The invention is the first living drug.

[00:25:43] Speaker 02:
It created a new paradigm for treating

[00:25:47] Speaker 02:
And I would dare say possibly curing cancer.

[00:25:51] Speaker 05:
What's the impact though of the fact that you all were never able to implement it?

[00:25:57] Speaker 05:
Never put it into practice?

[00:26:00] Speaker 02:
That is not the case.

[00:26:02] Speaker 02:
What happened is there were competing projects at Juneau.

[00:26:08] Speaker 02:
And this project that was using the 190 technology was for a different indication.

[00:26:14] Speaker 02:
a very difficult disease to treat.

[00:26:18] Speaker 02:
It's adult leukemia.

[00:26:20] Speaker 02:
And what Juno decided was to put that on ice in turn to developing a treatment for the exact same indication.

[00:26:31] Speaker 02:
Now, it was using different technology.

[00:26:33] Speaker 02:
In addition, the 190 patent hardly failed at all.

[00:26:38] Speaker 02:
It had 56

[00:26:40] Speaker 02:
percent of the patients in the clinical trial with positive results.

[00:26:46] Speaker 05:
But didn't the FDA shut down the clinical trial because of all the deaths?

[00:26:50] Speaker 02:
The FDA put it on hold because of some patient deaths, but they did not shut it down.

[00:26:58] Speaker 02:
And every one of these patients, there's testimony to the effect that on average they would die in 12 weeks.

[00:27:09] Speaker 02:
The scientists and physicians knew that this group of patients who were in clinical trials had failed every other kind of therapy.

[00:27:19] Speaker 02:
Now, the key to the invention was a new inventive backbone, which is very specifically claimed.

[00:27:26] Speaker 02:
It's amino acids 114 to 220 in combination with CD3 Zeta.

[00:27:32] Speaker 02:
That is the inventive backbone that provides the therapy.

[00:27:37] Speaker 05:
But don't you claim more than just the backbone?

[00:27:40] Speaker 02:
Yes.

[00:27:41] Speaker 02:
A third part is the SCFD.

[00:27:43] Speaker 02:
You have to meet the utility requirement for a patent claim.

[00:27:48] Speaker 02:
And the SCFD is like a fastener.

[00:27:51] Speaker 02:
It's a means to bind to or attach to the antigen.

[00:27:58] Speaker 02:
And by the priority date of the patent, it was 15-year-old technology.

[00:28:03] Speaker 02:
It was very well developed.

[00:28:05] Speaker 03:
When you say it was 15-year-old technology, it was very well developed.

[00:28:09] Speaker 03:
People knew about SCFE.

[00:28:12] Speaker 03:
They knew how to make SCFE.

[00:28:14] Speaker 03:
My difficulty with your patent is that the claim says a binding element, that's the SCFE, right, that specifically interacts with a selected target.

[00:28:26] Speaker 03:
That would be the antigen.

[00:28:27] Speaker 00:
Yes.

[00:28:28] Speaker 03:
The problem is you haven't defined

[00:28:31] Speaker 03:
or given any sort of road map for how you would identify which SCFC might work with which antigen.

[00:28:41] Speaker 03:
There are many, many of each.

[00:28:44] Speaker 03:
It's like saying, your patent feels a lot like saying people knew about antibiotics, people knew that there was bacteria out there.

[00:28:52] Speaker 03:
But what people didn't know is what antibiotics might work with what kind of bacteria.

[00:28:58] Speaker 03:
And there may be lots and lots of both.

[00:29:00] Speaker 03:
So your patent seems like it gave what was an idea, but not clear guidance on how to solve the problem.

[00:29:10] Speaker 02:
There was a clear road map in the original patent application.

[00:29:15] Speaker 02:
And if one looks at column four, starting at about line 52, and on column- Hold on, give me a sec.

[00:29:21] Speaker 03:
Let me get to it.

[00:29:23] Speaker 03:
Column four.

[00:29:25] Speaker 02:
Yes.

[00:29:28] Speaker 02:
Starting at about line 52.

[00:29:31] Speaker 02:
It starts with the binding elements.

[00:29:36] Speaker 02:
And you'll see in the first several sentences, the patent T says, single chain antibodies may be cloned from the V region, and it goes on.

[00:29:47] Speaker 02:
And then it says, the production of such hybridomas, this is referring to the way to make SEFs, has become routine.

[00:29:56] Speaker 02:
and the procedure will not be repeated here.

[00:29:59] Speaker 03:
Yes, no one is disputing that everyone at the time routinely knew how to make SCFEs.

[00:30:06] Speaker 03:
The problem is what your patent doesn't show the inventor possessed is any way to identify which SCFEs are going to work with which antigens to bind to which.

[00:30:20] Speaker 03:
That's the problem.

[00:30:21] Speaker 03:
SCFEs are well known.

[00:30:22] Speaker 03:
I read every piece of testimony in this record.

[00:30:25] Speaker 03:
And that's what they talked about, generalities, SCFVs being well known.

[00:30:30] Speaker 03:
What they didn't talk about is which SCFVs or how to identify which SCFVs would work with any antigen, not even SC19.

[00:30:43] Speaker 02:
What the patent does describe is two representative examples and

[00:30:50] Speaker 02:
in the prior, first of all.

[00:30:51] Speaker 03:
You say representative examples.

[00:30:53] Speaker 03:
Representative of what?

[00:30:54] Speaker 03:
Because the problem is, even your two examples have no overlapping structural similarities, nor do they have any structural similarities with, yes, yes, CARTA, I don't know if I'm pronouncing it right, the SCSC used in the Juno product, it actually works.

[00:31:09] Speaker 03:
So when you say representative, representative of millions of billions of possibilities, but with no

[00:31:15] Speaker 03:
similarities that would draw one to a class of SCFEs that would be workable.

[00:31:22] Speaker 02:
So let me go to the evidence that addresses the question that Your Honor is raising.

[00:31:28] Speaker 02:
Dr. Brocker and Dr. Satteline, who is one of the inventors, both testified.

[00:31:35] Speaker 04:
You want to give it an appendix site?

[00:31:37] Speaker 02:
Yes.

[00:31:38] Speaker 02:
Okay.

[00:31:38] Speaker 02:
Let me start with Dr. Brocker.

[00:31:42] Speaker 02:
Uh, 33932.

[00:31:43] Speaker 03:
Is it possible to identify which appendix it is?

[00:31:49] Speaker 02:
Uh, well, I'm identifying the page number.

[00:31:52] Speaker 03:
Hold on, let's just take a second to recall that it's, uh, Appendix 2.

[00:31:55] Speaker 02:
It's the first volume.

[00:31:58] Speaker 02:
What?

[00:31:59] Speaker 02:
Volume 2.

[00:31:59] Speaker 03:
33932.

[00:32:00] Speaker 02:
Uh... Okay, in that page,

[00:32:11] Speaker 02:
Dr. Brockler is saying SCFBs were in the car field for more than a decade, nearly 15 years.

[00:32:19] Speaker 02:
Also, that it's basically standard lab work, routine work.

[00:32:23] Speaker 02:
You can easily test.

[00:32:24] Speaker 02:
If you go two more pages, I'll give the last three digits because these pages all start with 3-3.

[00:32:31] Speaker 02:
So, 9-3-4.

[00:32:32] Speaker 02:
Dr. Brockler says.

[00:32:34] Speaker 03:
So, all this is exactly what everyone has admitted.

[00:32:38] Speaker 03:
which is SCFCs were known.

[00:32:41] Speaker 03:
It was known how to make them.

[00:32:42] Speaker 03:
It was even known they could bind.

[00:32:44] Speaker 03:
So I'm hoping the next page you're going to direct me to is some way to identify out of a billion possible SCFCs which ones would bind to particular antigens.

[00:32:54] Speaker 03:
Page 934 is where you want me to go.

[00:32:57] Speaker 02:
Well, let me just jump a page later.

[00:33:01] Speaker 02:
Which page?

[00:33:03] Speaker 02:
935.

[00:33:03] Speaker 02:
33935.

[00:33:05] Speaker 02:
Yes.

[00:33:07] Speaker 02:
And Dr. Brockard,

[00:33:08] Speaker 02:
states that Dr. Garcia, the kind expert, was neglecting 40 years of science, 40 years of textbook knowledge, and then 938, he goes on.

[00:33:19] Speaker 03:
Stop, stop.

[00:33:20] Speaker 02:
I'm sorry.

[00:33:21] Speaker 03:
I mean, you're not actually helping.

[00:33:23] Speaker 03:
935, he was neglecting four years of science.

[00:33:26] Speaker 03:
What does that mean?

[00:33:27] Speaker 03:
What am I supposed to take from that?

[00:33:29] Speaker 03:
Is that substantial evidence to the jury that you established and proved and demonstrated clearly that your patent taught how to identify which SCFVs

[00:33:38] Speaker 03:
would bind to which antigen?

[00:33:42] Speaker 02:
Yes.

[00:33:43] Speaker 03:
And let me go to some... A statement by your expert that someone else neglected 40 years of science is the specific testimony that is otherwise lacking.

[00:33:52] Speaker 02:
Okay.

[00:33:53] Speaker 02:
Let me, if I may, go to some more specific testimony where Dr. Brocker refers to the fact that the SCFBs maintain these structures.

[00:34:07] Speaker 02:
in order to work as the binding element.

[00:34:10] Speaker 02:
That's 938.

[00:34:11] Speaker 02:
938.

[00:34:13] Speaker 03:
What line?

[00:34:15] Speaker 03:
938.

[00:34:16] Speaker 03:
Is there a line number?

[00:34:18] Speaker 02:
I can get that for you in a moment.

[00:34:56] Speaker 03:
I'm on page 93A.

[00:35:00] Speaker 03:
And as he's talking about is how SCFVs have a common structure.

[00:35:07] Speaker 03:
This is much like saying an antibody has a common Y shape with, what is it, H and L?

[00:35:15] Speaker 03:
Yes, not yes, I got that right.

[00:35:17] Speaker 03:
Okay, H and L. So having a general, have an expert say all SCFVs, it's like saying a car has four wheels.

[00:35:24] Speaker 03:
You know, it's not, that doesn't do anything to tell you which SCFVs are going to bind to which antigens.

[00:35:33] Speaker 03:
It doesn't tell you anything about whether the structure of the one or two that you disclosed has certain common traits that make it capable of analogizing and identifying other SCFVs that would have a similar structure and work.

[00:35:50] Speaker 03:
This is just generalized testimony.

[00:35:52] Speaker 02:
Let me address the court's question directly.

[00:35:56] Speaker 02:
Bear with me for a 30-second description of how the SDFDs over the 15 years before the priority date were created.

[00:36:07] Speaker 02:
A mammal is injected with an antigen.

[00:36:10] Speaker 02:
The mammal's own immune system makes antibodies.

[00:36:14] Speaker 03:
Yes, we know all this.

[00:36:16] Speaker 03:
You inject it in the mouth.

[00:36:17] Speaker 03:
It makes antibodies.

[00:36:18] Speaker 03:
You extract it.

[00:36:19] Speaker 03:
You purify it.

[00:36:19] Speaker 02:
We know that.

[00:36:21] Speaker ?:
Okay.

[00:36:22] Speaker 02:
The SCFD involved the two arms of the Y, the heavy and light chains.

[00:36:31] Speaker 02:
The structures were very well known, and they would bind to the antigen.

[00:36:36] Speaker 02:
All of that.

[00:36:37] Speaker 05:
But your expert says right here that not every SCFD has the same amino acid sequence, because then they'd all recognize the same antigen.

[00:36:47] Speaker 05:
But you don't provide any sequence in here.

[00:36:50] Speaker 05:
Are you saying that?

[00:36:52] Speaker 05:
that everybody would know what sequences would bind to what?

[00:36:57] Speaker 02:
Let me address that directly based on a decision by this court.

[00:37:01] Speaker 02:
It's the Capon decision.

[00:37:04] Speaker 02:
It's referring to the state of art on SCFDs in the 1990s, that at least by 1995, this court had decided to reverse a decision

[00:37:18] Speaker 02:
of the Board of Patent Appeals and Interferences, which found no written description with respect to SCFBs.

[00:37:29] Speaker 02:
And then the court said, you don't need to provide sequences, because as of that time, it was so well-known.

[00:37:37] Speaker 03:
The fact of an SCFB is so well-known, but the problem for you in this case

[00:37:44] Speaker 03:
is everybody knew SCFVs, everybody knew they binded to things, everybody knew generally the structure of one, but what they didn't know is which ones with which kinds of amino acid sequences would bind to specific targets.

[00:37:59] Speaker 03:
Your claims are very different from the case you just pointed me to.

[00:38:03] Speaker 03:
Your claims have functional limitations.

[00:38:05] Speaker 03:
Your SCFV has to bind to a specific target and in claim five it has to bind

[00:38:12] Speaker 03:
to CD19.

[00:38:13] Speaker 03:
The claims in the patent you were referring to didn't have anything like that.

[00:38:17] Speaker 03:
And so you have to disclose the full scope of your claim, which is the way in which we can identify SCFVs that will, in fact, bind to specific targets.

[00:38:29] Speaker 02:
In the Capon case, there was a specific question of whether sequences had to be disclosed.

[00:38:38] Speaker 02:
And it was directly addressed by this court

[00:38:42] Speaker 02:
in holding that specific SCFB sequences did not need to be disclosed.

[00:38:50] Speaker 05:
There was no written description issue in that case, was there?

[00:38:53] Speaker 02:
There was.

[00:38:54] Speaker 02:
The Board of Patent Appeals and Interferences was having an interference.

[00:39:01] Speaker 02:
One was a patent application and one was an issued patent.

[00:39:05] Speaker 02:
And the board held that the written description requirement was not met

[00:39:11] Speaker 02:
by either party.

[00:39:13] Speaker 02:
That was the exact issue on appeal in Capon.

[00:39:18] Speaker 05:
Was there actually a challenge to the written description finding?

[00:39:22] Speaker 02:
Yes.

[00:39:23] Speaker 02:
So what this court did was it reversed the board's decision on written description and remanded it.

[00:39:32] Speaker 02:
And here's what the court said.

[00:39:34] Speaker 03:
Mr. Hsu, to be clear, I have no problem with that case or its holding in light.

[00:39:38] Speaker 03:
It was an interference in light of the counts that were issued in that claim.

[00:39:41] Speaker 03:
In that case, your claim is quite different.

[00:39:44] Speaker 03:
And by the way, no one has suggested that the law requires you to identify a particular sequence.

[00:39:51] Speaker 03:
But the problem is you've identified no means in this claim for identifying structurally similar or functionally similar SCFVs for even CD19 that you've given nothing.

[00:40:07] Speaker 03:
One way to do it may have been to disclose amino acid sequences

[00:40:11] Speaker 03:
That might have been something you could have done to satisfy it.

[00:40:14] Speaker 03:
It's not required.

[00:40:15] Speaker 03:
Another way could have been that you identify structural similarities or particular groups of species within genuses or disclose a particular number of SCFCs that would otherwise make identifying the universe of the very broad universe of your claims look as though it was in fact possessed by the inventors.

[00:40:37] Speaker 03:
But you did none of those things.

[00:40:39] Speaker 03:
So I don't think Judge O'Malley's question was meant to suggest that you had to disclose an amino acid sequence.

[00:40:45] Speaker 03:
I think Judge O'Malley's question was meant to point out that there are many ways in which you could have shown that your inventors possessed this very, very broad genus, but you didn't do any of them.

[00:40:56] Speaker 03:
Not you personally, but your clients.

[00:40:58] Speaker 02:
In the trial record, Dr. Brockert testified clearly several times, and I'll be part of

[00:41:05] Speaker 02:
one quote and direct you to the site.

[00:41:08] Speaker 02:
Quote all... Please direct us to the site first.

[00:41:14] Speaker 02:
Okay.

[00:41:14] Speaker 02:
33959.

[00:41:22] Speaker 02:
I'm sorry, can you give me... Yes.

[00:41:29] Speaker 02:
33959.

[00:41:39] Speaker 02:
And if you start at about line 12, the question, you believe that SCFDs, the fall within the scope of the claims, have a common structure.

[00:41:52] Speaker 02:
Answer, all SCFDs have a common structure.

[00:41:57] Speaker 02:
This is very different from the... Yes, exactly.

[00:41:59] Speaker 03:
That's the general statement, that all antibodies have a Y shape.

[00:42:03] Speaker 03:
That's what he's saying.

[00:42:05] Speaker 03:
Generally, they do.

[00:42:06] Speaker 03:
All SCFAs do have a common structure.

[00:42:08] Speaker 03:
Absolutely.

[00:42:09] Speaker 03:
No one, I don't believe Mr. Rosencrantz is going to stand up and dispute that when he stands up.

[00:42:14] Speaker 03:
But that's not the same as saying you disclosed enough for people to identify which one.

[00:42:23] Speaker 02:
But it was common, standard.

[00:42:26] Speaker 03:
Okay, so let's say I go to a car dealership and I tell my children to pick up the car.

[00:42:32] Speaker 03:
And the car dealership has a lot of 1,000 cars on it.

[00:42:35] Speaker 03:
And I say, ah, well, mine is the car with four wheels.

[00:42:41] Speaker 03:
Every car has a common structure.

[00:42:43] Speaker 03:
It has four wheels.

[00:42:44] Speaker 03:
I haven't helped my children identify which car to drive off the lot.

[00:42:49] Speaker 02:
The science here is if you have a particular antigen and you want to bind to it, it was standard laboratory work to create the SCFBs.

[00:43:01] Speaker 02:
There were articles much earlier that addressed it in my name.

[00:43:04] Speaker 03:
And why did it take Juno a billion tries to find 60 just for CD19, an antigen they already knew about, two SCFDs of which they were already aware of?

[00:43:18] Speaker 03:
Why did it take them a billion tries?

[00:43:22] Speaker 02:
It didn't.

[00:43:23] Speaker 02:
If I can explain that article, it's the Sommar-Meyer article.

[00:43:31] Speaker 02:
This was an attempt to optimize SCFBs.

[00:43:37] Speaker 02:
And the researchers said, hmm, how do we do this?

[00:43:42] Speaker 02:
And they took antibodies from 20 individual human beings.

[00:43:49] Speaker 02:
All of our bodies have tens, maybe hundreds of thousands of antibodies.

[00:43:54] Speaker 02:
Many of them are for targets

[00:43:56] Speaker 02:
where we don't know what the disease was.

[00:43:58] Speaker 02:
It could be many millennia ago.

[00:44:01] Speaker 02:
Those antibodies aren't used.

[00:44:02] Speaker 02:
So there are millions and millions or maybe billions of different antibodies.

[00:44:08] Speaker 02:
And then they went through some standard laboratory procedures.

[00:44:13] Speaker 02:
And they were focused on binding on a particular site only.

[00:44:18] Speaker 02:
It's identified as FMC 63, well known in the literature.

[00:44:24] Speaker 02:
The Nicholson article from

[00:44:26] Speaker 02:
1997 actually identifies that site.

[00:44:33] Speaker 02:
And they said, let's see which had elevated binding for that particular site.

[00:44:39] Speaker 02:
And what they found was through this procedure, they discarded most of the billion.

[00:44:46] Speaker 02:
They did first assemble this large, I call it a suit of possibility.

[00:44:51] Speaker 02:
But they quickly discarded it using standard laboratory procedures

[00:44:55] Speaker 02:
and quickly found 60 with elevated binding.

[00:45:00] Speaker 02:
And contrary to Kite's argument in the read, there wasn't a testing of a billion different ones.

[00:45:07] Speaker 02:
They quickly isolated 60, and they tested the binding affinity.

[00:45:12] Speaker 02:
So it's only testing 60.

[00:45:15] Speaker 03:
The billion that they assembled and the 60 they identified, did this take place 15 years after the patent?

[00:45:21] Speaker 03:
Yes.

[00:45:22] Speaker 00:
Yes.

[00:45:22] Speaker 03:
So, but Mr. Rosencrantz said that the evidence at the time with each one of these things took months, even a year.

[00:45:30] Speaker 03:
You're saying 15 years later they assembled a billion of them and quickly, although you haven't given me a time frame, tested 60 of them.

[00:45:37] Speaker 03:
But that's not the technology that existed 15 years earlier in 2002.

[00:45:43] Speaker 02:
Mr. Rosencrantz's argument was hotly contested

[00:45:49] Speaker 02:
by actual testimony at trial by Dr. Brocker and Dr. Sadowline.

[00:45:55] Speaker 02:
So for example, Dr. Sadowline testified with respect to CD19 that he used upward of 30 different SCFDs, and they all worked.

[00:46:10] Speaker 03:
At what point in time?

[00:46:13] Speaker 02:
He's referring to slightly later than the priority date

[00:46:19] Speaker 02:
as to when he was continuing to test.

[00:46:23] Speaker 02:
And with respect to his car, his testimony was that he tested it with a multitude of different SCFDs.

[00:46:35] Speaker 02:
This is for different antigens.

[00:46:37] Speaker 02:
And they all worked.

[00:46:38] Speaker 02:
Dr. Brocker on the same subject.

[00:46:41] Speaker 05:
Going back to Dr. Brocker's testimony that we were talking about before, what he said is that

[00:46:47] Speaker 05:
if you change an amino acid within the sequence, it changes its binding ability, or what it will bind to, correct?

[00:46:55] Speaker 01:
It could, yes.

[00:46:57] Speaker 05:
All right.

[00:46:57] Speaker 05:
And so what you're talking about here is when you're testing, you're testing by playing with the amino acid sequence in a particular SCFB, right?

[00:47:06] Speaker 02:
Well, the article we were talking about was just focused on one epitode or binding site,

[00:47:15] Speaker 02:
looking only for elevated binding and testing those 60.

[00:47:20] Speaker 02:
And then the author said, we found three had comparable binding to what had already been disclosed by the patent and the priority.

[00:47:31] Speaker 02:
So they were trying to optimize.

[00:47:33] Speaker 02:
And what they found was, well, of the 60 with elevated binding, the best of the rest, it was three with comparable binding.

[00:47:42] Speaker 02:
It was very easy to do.

[00:47:45] Speaker 02:
No elongated period of time.

[00:47:49] Speaker 05:
But so you went in backwards.

[00:47:51] Speaker 05:
Instead of saying let's identify the amino acid sequence that will bind to what we want it to bind to, then we're just going to just throw it out there and see if we can find one SCFV that might have the correct amino acid sequence, right?

[00:48:08] Speaker 02:
That's the basic science and Dr. Garcia agreed with that.

[00:48:12] Speaker 05:
How does that tell one of skill in the art?

[00:48:14] Speaker 05:
How to do what you're doing?

[00:48:16] Speaker 02:
The Olandi article was a recipe, a cookbook.

[00:48:21] Speaker 02:
It provided a roadmap for it.

[00:48:24] Speaker 02:
It was a well-known 1989 article.

[00:48:27] Speaker 02:
It is cited in the patent at column four, line 61.

[00:48:39] Speaker 02:
There was no dispute.

[00:48:40] Speaker 02:
that it was a roadmap or a cookbook for making SCFDs that would bind to a particular target.

[00:48:50] Speaker 03:
But the targets aren't even known, right?

[00:48:53] Speaker 03:
You have covered any binding element that binds to any target.

[00:48:59] Speaker 03:
That's what you've covered in your claim.

[00:49:00] Speaker 03:
This claim three is remarkably broad, and claim one is even broader.

[00:49:07] Speaker 03:
Any binding element

[00:49:09] Speaker 03:
that will claim down to any target, right?

[00:49:14] Speaker 02:
That's what the claim comes from.

[00:49:15] Speaker 02:
If you look at the broadest claim, which would still require the amino acid sequence 114 to 220 in combination with 3D3 zeta, then yes, it could work.

[00:49:34] Speaker 02:
with respect to other targeted antigen?

[00:49:38] Speaker 03:
When you say it could work, no.

[00:49:40] Speaker 03:
Your claim has covered any antigen, which is the target, and any SCFV.

[00:49:50] Speaker 03:
So what incentive is there for any other company to do all the legwork that you all didn't do to come up with and identify both the antigen and then to identify the SCFV

[00:50:04] Speaker 03:
that will bind to that antigen and cure the various forms of cancer.

[00:50:08] Speaker 02:
It was very easy.

[00:50:10] Speaker 02:
If someone says.

[00:50:11] Speaker 03:
If it was so easy, why isn't it all done already?

[00:50:14] Speaker 03:
Why don't we have?

[00:50:16] Speaker 03:
Why don't you have?

[00:50:17] Speaker 03:
It's so easy.

[00:50:19] Speaker 03:
Why doesn't your company have a million products that do this?

[00:50:22] Speaker 03:
Heck, why the heck doesn't Kite have a lot more than just Yes Carta, if it's so easy?

[00:50:27] Speaker 02:
OK.

[00:50:27] Speaker 02:
I'm back to Dr. Sattelan, where he created and tested

[00:50:33] Speaker 02:
with different SCFEs.

[00:50:35] Speaker 03:
We're talking about curing cancer.

[00:50:36] Speaker 03:
This is an amazing drug.

[00:50:39] Speaker 03:
It cures cancer.

[00:50:40] Speaker 03:
This isn't chemotherapy where you lose your hair.

[00:50:43] Speaker 03:
This is curing cancer.

[00:50:44] Speaker 03:
And it has been identified for non-Hodgkin's lymphoma in a small category.

[00:50:50] Speaker 03:
But it's so easy to identify the antigens and identify the SCFEs.

[00:50:54] Speaker 03:
Why haven't we cured all of the cancers?

[00:50:57] Speaker 02:
Let me address two parts of this.

[00:50:58] Speaker 02:
One is CD19, as I think the court had recognized,

[00:51:02] Speaker 02:
5 and 11, they're the narrower claims that are limited to CD19.

[00:51:07] Speaker 02:
Okay?

[00:51:09] Speaker 02:
The state of the knowledge was, at the time, included what's in the patent, the Olandi recipe, and also articles that were known in the prior art.

[00:51:20] Speaker 03:
Okay, so you're focusing on CD19, which I understand why it's narrower.

[00:51:23] Speaker 03:
Does that mean you are now abandoning claim 3?

[00:51:26] Speaker 03:
In light of, that is one of the claims at issue and that's the broader one, not limited to CD19.

[00:51:32] Speaker 03:
Remember, it's limited to any agent, any binding agent.

[00:51:36] Speaker 02:
Let me just, if I may, answer the first part of what your honor was asking.

[00:51:44] Speaker 02:
As of the priority date, people had, some people, other researchers, had focused and published on CD19.

[00:51:55] Speaker 02:
That's the 1995 Bayeck article, the 1996 Kiprioff article, the 1997 Nicholson article on CD19.

[00:52:08] Speaker 02:
Dr. Sadolin was asked whether he used different SCFBs targeting different antigens.

[00:52:20] Speaker 02:
And he testified he targeted a multitude

[00:52:25] Speaker 02:
of different antigens.

[00:52:27] Speaker 02:
This is at 32-917.

[00:52:31] Speaker 02:
And he said they all worked.

[00:52:35] Speaker 02:
Dr. Brocker was asked about this subject, and he testified that he did not know of any that did not work when used in conjunction with a car.

[00:52:49] Speaker 02:
When I referred earlier and said I think could work, the question is,

[00:52:55] Speaker 02:
whether the innovative backbone would be successful in working with particular tumor cells.

[00:53:03] Speaker 02:
It wasn't a question as to whether the SCFB would bind.

[00:53:08] Speaker 02:
It was well known among all scientists at the time that the SCFBs that were created in the cookbook recipe manner would, in fact, bind.

[00:53:21] Speaker 02:
Now, let me go to

[00:53:25] Speaker 02:
I can go to other sites on, yes.

[00:53:27] Speaker 04:
Can I just follow up with, in great brief, I think at page 12, your friend makes the argument that your claims cover SDFDs from any source, including human SDFDs.

[00:53:40] Speaker 04:
But as of the priority date, there's no evidence that anyone has made a human CB-19 SDFD.

[00:53:46] Speaker 02:
Are they correct?

[00:53:48] Speaker 02:
That is not true.

[00:53:49] Speaker 02:
And let me go through what the evidence is.

[00:53:55] Speaker 02:
There's a series of articles in addition to Orlandi that are cited in the patent.

[00:54:04] Speaker 02:
Number 31 at the bottom of column 13 is the Finney article.

[00:54:09] Speaker 02:
The Finney article was a human or humanized SCFB, obviously, as of the priority date.

[00:54:21] Speaker 02:
It's column 13 at the bottom.

[00:54:25] Speaker 02:
The site number is 31 at the very bottom of that column.

[00:54:31] Speaker 02:
You see Finney?

[00:54:33] Speaker 02:
And it's a 1998 article that discusses human or humanized SCFDs.

[00:54:40] Speaker 02:
In addition, the Olandi article also discussed human or humanized SCFDs.

[00:54:48] Speaker 02:
That was a 1997 article.

[00:54:51] Speaker 02:
The Byrd article

[00:54:52] Speaker 02:
from 1988, and I'll give you the site for that.

[00:54:56] Speaker 04:
Is that an answer?

[00:54:57] Speaker 04:
Discussing is the same as making the U.N.

[00:55:02] Speaker 04:
CC19 FDFC?

[00:55:03] Speaker 02:
Yes.

[00:55:04] Speaker 02:
These are articles Finney and the others were making.

[00:55:09] Speaker 02:
So the Byrd article is referenced that Appendix 36165 and 66.

[00:55:16] Speaker 05:
Is CIDI actually talking about FDFCs?

[00:55:21] Speaker 05:
Excuse me.

[00:55:21] Speaker 05:
Is Phinney actually talking about SCFVs or is it talking about CD20?

[00:55:25] Speaker 02:
Yes.

[00:55:28] Speaker 02:
Well, part of the article is talking about SCFVs.

[00:55:35] Speaker 02:
The articles frequently say, okay, we're going to try human or humanized SCFVs or cars that are human or humanized.

[00:55:45] Speaker 02:
And Dr. Brockert testified that human or humanized

[00:55:50] Speaker 02:
SCFBs have the exact same common structure, and I can explain the testimony that Judge O'Malley, I believe, asked about earlier, where there was a cryptic question, and he starts out as Dr. Brockert saying, if you knew how difficult it is, the question is referring to humans, if you knew how difficult it is, it's extremely difficult, and then he's cut off, and he says, I can explain that,

[00:56:19] Speaker 02:
if I can answer more than yes or no.

[00:56:21] Speaker 02:
Here's the explanation.

[00:56:24] Speaker 02:
There are ethical rules and lots of good rules that scientists have to jump through.

[00:56:31] Speaker 02:
And our society is particularly concerned about injecting human beings with antigens for obvious reasons.

[00:56:40] Speaker 03:
Is there a place in the appendix that you could refer us to this testimony?

[00:56:44] Speaker 02:
His testimony stops right where

[00:56:49] Speaker 02:
judge O'Malley.

[00:56:51] Speaker 02:
He's sort of saying, I can explain this, but he doesn't go on.

[00:56:56] Speaker 03:
So everything you're doing right now is attempting to testify for an expert stuff that he didn't testify to?

[00:57:02] Speaker 02:
What I just said in explaining the testimony, I'm explaining that, that's correct.

[00:57:08] Speaker 03:
That's not in the record.

[00:57:10] Speaker 02:
That's correct.

[00:57:11] Speaker 03:
Okay, so let's get on from that.

[00:57:13] Speaker 03:
One of the problems I have is that when you're saying everybody knew how

[00:57:18] Speaker 03:
all of these SCFs have the same structure or that any of them could be attached to a car, a backbone.

[00:57:26] Speaker 03:
Again, I'm pretty sure Mr. Rosencrantz isn't going to dispute either of those two points.

[00:57:31] Speaker 03:
I'm pretty sure he's going to stand up and say, however, what people didn't know is which ones, yes, you could build the three-part car with any SCFE and yes, SCFs had similar structures and yes,

[00:57:46] Speaker 03:
they could be used to form the CAR.

[00:57:49] Speaker 03:
But what you didn't know is then which of those would bind to which antigen.

[00:57:55] Speaker 02:
You would.

[00:57:56] Speaker 02:
It was all picked up in the following steps.

[00:57:59] Speaker 02:
The mammals immune system is going to make the antibodies and you take the heavy and light variable chains and you use that to make the SCFE.

[00:58:14] Speaker 02:
You get rid of the constant

[00:58:16] Speaker 02:
And you're using the same thing the antibody did to bind to the antigen.

[00:58:23] Speaker 02:
So it's going to work.

[00:58:25] Speaker 02:
It's going to work every time.

[00:58:26] Speaker 03:
And that's why... It requires knowing in advance which SCFV to use and knowing in advance which antigen you want to go after.

[00:58:37] Speaker 02:
You use any or all of the SCFVs derived from the antibodies

[00:58:46] Speaker 02:
that bound to the antigen.

[00:58:49] Speaker 03:
Okay, that's answering the question with the answer to the question in a way, or the question itself.

[00:58:54] Speaker 03:
The whole problem is nobody knew which SCFs were going to bind to the antigen.

[00:59:00] Speaker 03:
That's the problem.

[00:59:02] Speaker 02:
They did.

[00:59:02] Speaker 03:
No, they knew.

[00:59:03] Speaker 03:
You disclosed two, and the state of the primary arc at the time knew four to five only, by the way, with regard to CD19.

[00:59:12] Speaker 02:
So for every antigen,

[00:59:17] Speaker 02:
So obviously there are other antigens, not discussed in the patent.

[00:59:21] Speaker 02:
A scientist using routine procedures could get the mammal to produce antibodies.

[00:59:29] Speaker 02:
The antibodies would bind.

[00:59:31] Speaker 02:
Because the binding component of the antibodies become the SCFVs, they would work.

[00:59:38] Speaker 02:
They'd work every time.

[00:59:39] Speaker 02:
And I want to come back to the beginning.

[00:59:41] Speaker 03:
So every time you can take any SCFV of the billions that are out there,

[00:59:46] Speaker 03:
stick it on a car and it's going to bind to any antithesis.

[00:59:52] Speaker 02:
It's not billions.

[00:59:55] Speaker 03:
There's not billions of STFVs out there?

[00:59:59] Speaker 02:
Correct.

[01:00:00] Speaker 02:
Let me explain.

[01:00:00] Speaker 03:
There's not billions of STFVs?

[01:00:03] Speaker 02:
I don't believe so.

[01:00:05] Speaker 02:
Well, first of all, where does that testimony comes from?

[01:00:10] Speaker 02:
Part of the source is Dr. Garcia.

[01:00:13] Speaker 02:
And what he did

[01:00:14] Speaker 02:
was to pretend in a theoretical way that you could take and replace amino acids one by one.

[01:00:22] Speaker 02:
So he did a math exercise.

[01:00:25] Speaker 02:
So if there's one amino acid, there are 20 possibilities.

[01:00:30] Speaker 03:
OK.

[01:00:30] Speaker 03:
Didn't you tell me that Juno started with a billion SCFE?

[01:00:35] Speaker 02:
No.

[01:00:38] Speaker 02:
And I apologize.

[01:00:39] Speaker 02:
I was probably unclear.

[01:00:41] Speaker 02:
In the Sommermeier article,

[01:00:45] Speaker 02:
Because they were starting with 20 human beings, they said, we'll take all of their antibodies for every current disease that any of the 20 have ever had or experienced.

[01:00:56] Speaker 02:
And their ancestors over millennia may have experienced.

[01:01:01] Speaker 02:
And they were using that material, basically chopping it up and then saying, OK, we've got this big soup.

[01:01:11] Speaker 02:
Now let's see what is going to bind to this particular site.

[01:01:16] Speaker 02:
So they weren't creating a billion SCFEs or testing a billion SCFEs.

[01:01:23] Speaker 02:
They quickly threw away everything that didn't have some elevated binding.

[01:01:29] Speaker 02:
So as Dr. Brockert testified in response to Dr. Garcia's testimony, a person of skill in the art wouldn't do what Dr. Garcia was saying.

[01:01:39] Speaker 02:
which was to replace every amino acid position with 19 other possible amino acids.

[01:01:48] Speaker 02:
He went on to testify that that wouldn't create anything useful in all likelihood because the proteins would degenerate and would degrade.

[01:01:59] Speaker 02:
So he was assuming that, Dr. Garcia, let's say you have two amino acids, a really small string,

[01:02:07] Speaker 02:
You have 20 possibilities in each position.

[01:02:09] Speaker 02:
So that's 400, 3, 8,000.

[01:02:13] Speaker 02:
And that's how it got his billion.

[01:02:15] Speaker 05:
Did you put on any testimony rebutting that statement?

[01:02:19] Speaker 02:
Yes.

[01:02:20] Speaker 02:
Dr. Brockard directly rebutted it and made it very clear that no person of skill would do it that way.

[01:02:29] Speaker 02:
Dr. Garcia didn't say a person of skill would do it that way.

[01:02:33] Speaker 02:
Because a person of skill in the art

[01:02:36] Speaker 02:
would allow the immune system to make the antibodies and then create the SCFDs.

[01:02:43] Speaker 02:
The SCFDs are artificial in the sense that it's just part of the antibody, but it's exactly the part of the antibody that binds to the antigen.

[01:02:52] Speaker 02:
That's what they would do.

[01:02:53] Speaker 02:
That millions on billions by Dr. Garcia was just a math exercise.

[01:03:03] Speaker 02:
That's all it was.

[01:03:04] Speaker 02:
I wanted to come back to human for just a moment.

[01:03:08] Speaker 02:
One sentence.

[01:03:13] Speaker 02:
This is, with due respect, a made up argument on appeal.

[01:03:19] Speaker 02:
Dr. Garcia never discussed anything about human or humanized SEFEs.

[01:03:28] Speaker 02:
He never told the jury that somehow it was difficult to deal with human or humanized and that because of that, it would violate the rules with respect to written description or enablement.

[01:03:42] Speaker 02:
Kite had plenty of other expert witnesses, not a single one discussed human or humanized.

[01:03:49] Speaker 02:
Kite has a lot of scientists, PhDs, not a single one said anything about difficulties of dealing with human or humanized.

[01:03:58] Speaker 05:
Okay, can I, I want to turn to certificate of correction issue?

[01:04:02] Speaker 05:
Sure.

[01:04:02] Speaker 05:
The first thing I want to do is, I think there might be a gap in our law, but everybody proceeds on the assumption that a clerical change and a typographical change can actually impact the substantive scope of a patent.

[01:04:21] Speaker 05:
But have we ever said that something that impacts the substantive scope, no matter which way,

[01:04:27] Speaker 05:
can constitute a minor correction?

[01:04:32] Speaker 02:
Let me separate the various COC issues.

[01:04:38] Speaker 02:
Oftentimes, there's a certificate of correction, it's clear typo, no problem at all, no substantive effect.

[01:04:45] Speaker 02:
What this court has said, there are cases that could be a broadening of the claim.

[01:04:55] Speaker 02:
And this case,

[01:04:57] Speaker 02:
could fit in that box because the actual sequence that the patentee tried to patent was amino acids 114 to 220.

[01:05:10] Speaker 05:
And that's... But I want to clarify.

[01:05:11] Speaker 05:
So I'm trying to get to what the loss is so that... And I'd like to start with the statute so that... But you're putting your change in the box of minor correction, correct?

[01:05:24] Speaker 02:
No.

[01:05:26] Speaker 02:
I need to...

[01:05:27] Speaker 02:
spend at least four or five sentences to explain.

[01:05:30] Speaker 05:
Well, there's three things in the statute, clerical, typographical, or a mistake of minor character.

[01:05:37] Speaker 05:
You're going with three, right?

[01:05:39] Speaker 05:
Yes.

[01:05:40] Speaker 05:
All right.

[01:05:40] Speaker 05:
So are you aware that the regulations implementing 252 and MPEP expressly say that while the first two can impact the scope

[01:05:51] Speaker 05:
of the scope of the claim, that it says that a mistake is not considered to be of minor character required for the issuance of a certificate of correction if the request to change would materially affect the scope or meaning of the patent.

[01:06:05] Speaker 05:
Either way, that's what both the regulations and the MPE piece say.

[01:06:10] Speaker 05:
And the question is, has our case law ever said they disagree with those?

[01:06:15] Speaker 02:
And then... I do not think...

[01:06:18] Speaker 02:
of your case law has disagreed with analogous facts to what we have here.

[01:06:26] Speaker 02:
The point I was trying to make is that this court's case law has said whatever little slot one puts it in, that if there is a broadening of the claims, then it has to meet other tests, which were part of the jury's... But you agree, though, that broadening or not, it does impact

[01:06:47] Speaker 05:
the material character of the claims, right?

[01:06:53] Speaker 02:
In this case?

[01:06:54] Speaker 05:
Yes.

[01:06:55] Speaker 02:
Yes, but it is because it was broadening.

[01:06:58] Speaker 02:
And the reason is the argument that Kite made at trial was that the claims covered 113 to 220 instead of 114 to 220.

[01:07:10] Speaker 05:
Okay, so you can see that the correction was broadening.

[01:07:15] Speaker 02:
Yes, because

[01:07:17] Speaker 02:
If it's 114 to 220, then you could add on other things, as opposed to if it's 113, it has to be narrower, because you've added one amino acid.

[01:07:30] Speaker 02:
But I will point out, even before the request for continuing, before the RCE, so let me create the time and context.

[01:07:42] Speaker 05:
The fact that you've

[01:07:46] Speaker 05:
chose to use RCEs, you know, the first three times indicate that you didn't think this was fixable with a certificate of correction?

[01:07:55] Speaker 05:
Isn't the mere fact that you chose to use RCEs the first three times, even though it was unsuccessful, doesn't that imply that you didn't think it was fixable with a mere COC?

[01:08:09] Speaker 02:
No, the patent had an issue.

[01:08:11] Speaker 02:
So it was still in prosecution.

[01:08:14] Speaker 02:
It was about to issue.

[01:08:16] Speaker 02:
The mistake was discovered.

[01:08:19] Speaker 02:
So the RCE was then filed, and the extra nucleotides were crossed out.

[01:08:28] Speaker 02:
There was a scientific detailed explanation as to why those extra nucleotides shouldn't be there, why it is a mistake, why there was this clerical error.

[01:08:40] Speaker 02:
It's all laid out in the RCE.

[01:08:42] Speaker 04:
Let me just follow up on that.

[01:08:44] Speaker 04:
I mean, the goal here is public notes.

[01:08:46] Speaker 04:
the public has notice of what's been claimed.

[01:08:49] Speaker 04:
And you seem to use the fact that this was in the RCE and then it didn't make in to your advantage.

[01:08:58] Speaker 04:
And I don't see, maybe we just do too much statutory interpretation and statutory construction here.

[01:09:03] Speaker 04:
But if you've got a statute and somebody proposed it in Congress or it was in the original bill and it gets deleted, you don't use that to say they must have included it.

[01:09:14] Speaker 04:
It suggests the reverse.

[01:09:16] Speaker 04:
that they intentionally didn't do it.

[01:09:17] Speaker 04:
So I'm perplexed by your argument that because it was in the RCE, but didn't get in, shows that it was intended to be there.

[01:09:26] Speaker 02:
I'm just not computing.

[01:09:27] Speaker 02:
It's not just the RCE.

[01:09:30] Speaker 02:
The original application, the claims as issued, refer to amino acids.

[01:09:35] Speaker 02:
So it's discussing the amino acid sequence.

[01:09:39] Speaker 02:
The specification of the patent in the original application

[01:09:44] Speaker 02:
refers to an amino acid sequence.

[01:09:48] Speaker 02:
When it refers to the amino acid sequence, it's 114 to 220.

[01:09:52] Speaker 02:
There's no ambiguity there.

[01:09:56] Speaker 02:
It also refers to particular primers.

[01:09:59] Speaker 02:
The primers are used to amplify a particular sequence.

[01:10:03] Speaker 02:
In fact, when Dr. Cytoline and Dr. Rosenberg were discussing Dr. Cytoline's invention and the subject of SCFBs came up,

[01:10:13] Speaker 02:
Dr. Sideline said, here are the primers to use.

[01:10:17] Speaker 02:
So it's the best evidence.

[01:10:18] Speaker 02:
The primers, also in the original application, were being used for 114 to 220.

[01:10:25] Speaker 02:
This is before the RCE.

[01:10:28] Speaker 02:
So when the mistake was discovered, then the RCE was used to correct the mistake.

[01:10:35] Speaker 02:
Any person of skill reading that and the detailed explanation, seeing what was being

[01:10:42] Speaker 02:
the extra nucleotides being crossed out with the explanation why it was a mistake and the science behind it, all of that would have been understood by a skilled artisan without question.

[01:10:54] Speaker 02:
Now, you, of course, read that there was a mistake in the final listing.

[01:11:07] Speaker 04:
Yeah, that's what my question was about, that final

[01:11:10] Speaker 04:
where it didn't make it in, and you're using the fact that it was in the proposed RCE as somehow suggesting that the public should have had notice, even though it didn't make it in the final set.

[01:11:22] Speaker 04:
And I was confused about that rationale.

[01:11:24] Speaker 02:
Yeah.

[01:11:24] Speaker 02:
So I do think the public would have noticed.

[01:11:28] Speaker 02:
Also, too, Kite was trying to license the patent before the certificate

[01:11:39] Speaker 02:
of correction.

[01:11:41] Speaker 02:
Opposing counsel was addressing a question, I think, from Judge O'Malley.

[01:11:47] Speaker 02:
Kai tried to license the patent before the COC in the fall of 2013.

[01:11:53] Speaker 02:
This is testimony of Dr. Dash, who was a licensing person for Sloan Kettering, and it's at Appendix

[01:12:04] Speaker 02:
33042.

[01:12:05] Speaker 03:
So one of my problems with Certificate of Correction is when I read the specification, I saw sort of confusing information as to whether it was meant to include 113 or meant to start at 114.

[01:12:21] Speaker 03:
And in particular, what I'm talking about is column four versus column seven.

[01:12:25] Speaker 03:
You know what I'm referring to?

[01:12:27] Speaker 03:
Column four seems to suggest to someone that you were meaning to use 114.

[01:12:33] Speaker 03:
But column 7 seems to suggest you are meaning to use 113.

[01:12:38] Speaker 03:
Is that fair?

[01:12:39] Speaker 03:
Is that a fair assessment?

[01:12:44] Speaker 02:
It's only column 4, and it's at line 24 where, excuse me, line 25 where the amino acid sequence

[01:13:00] Speaker 02:
is referred to as 114 to 220.

[01:13:06] Speaker 02:
Again, that's column four, line 25.

[01:13:11] Speaker 03:
And then there are reference... Column four, line 25.

[01:13:15] Speaker 03:
I'm sorry, I must be in the wrong thing.

[01:13:20] Speaker 05:
It says 114 to 220, but what about column seven?

[01:13:23] Speaker 02:
Okay.

[01:13:23] Speaker 02:
Column seven doesn't refer to amino acid sequences at all.

[01:13:29] Speaker 02:
Remember the claim?

[01:13:30] Speaker 02:
refers to the amino acid sequence.

[01:13:33] Speaker 02:
Instead, column seven is talking about some nucleotides.

[01:13:38] Speaker 03:
Yes, but the nucleotides correspond to the amino acid sequence, right?

[01:13:43] Speaker 03:
Well, they might, but the problem- It's like talking about a week or talking about seven days in a week, right?

[01:13:48] Speaker 03:
Talk about a week, people know it's seven days.

[01:13:50] Speaker 03:
Here it seems like the nucleotides 336 to 660 of CD28 are known to be 113.

[01:13:59] Speaker 02:
A person of skill in the art

[01:14:01] Speaker 02:
looking at the reference to nucleotides as opposed to amino acid would know that there was a mistake.

[01:14:09] Speaker 02:
Because the number, there were three.

[01:14:12] Speaker 03:
Okay, so you're saying they would know there's a mistake.

[01:14:15] Speaker 03:
Inherent in that is yes, Judge Moore, column seven would suggest to someone 113, right, is included?

[01:14:26] Speaker 02:
I actually would say that it wouldn't.

[01:14:29] Speaker 02:
because the number of nucleotides must be divisible by three.

[01:14:35] Speaker 02:
And the fact is that it has four nucleotides at the beginning, making it not divisible by three.

[01:14:43] Speaker 03:
The question there is, is this a whole car that has seven nucleotides divisible by three, or only this second part, which I don't remember the name of.

[01:14:54] Speaker 02:
This part has to be divisible by three.

[01:14:59] Speaker 02:
we're talking about is called the co-stimulatory domain.

[01:15:04] Speaker 02:
And that's the 114 to 220.

[01:15:08] Speaker 02:
So whatever the amino acids are there, expressed as amino acids or nucleotides, the nucleotides have to be divisible by three.

[01:15:22] Speaker 02:
There was testimony by Professor Quackenbush, who said that

[01:15:28] Speaker 02:
his Harvard students.

[01:15:30] Speaker 02:
That's a tough name for an expert.

[01:15:33] Speaker 03:
Sorry, go ahead.

[01:15:35] Speaker 02:
I'm sure he loves his mom and dad for the name.

[01:15:40] Speaker 02:
But he would say he would give his students exercises.

[01:15:47] Speaker 02:
And if someone responded with something other than was divisible by three, he would give them a failing grade.

[01:15:55] Speaker 02:
So a person of skill looking at this would say, it's got to be wrong, because it's not divisible by three.

[01:16:03] Speaker 02:
And then there's the other error in the reference to the nucleotides, because the last three nucleotides are what's called a stop codon.

[01:16:14] Speaker 02:
It says, no need to code anymore, and you wouldn't include the stop codon in a nucleotide listing, because it's just not part of it.

[01:16:25] Speaker 02:
So a person of skill who is just looking at the nucleotides and not looking at the rest of the prosecution history or the rest of the patent would say, that's a mistake.

[01:16:36] Speaker 02:
The nucleotide listing is a mistake.

[01:16:39] Speaker 02:
It would be clearly evident to one of ordinary skill.

[01:16:44] Speaker 03:
OK.

[01:16:44] Speaker 03:
I think that we're for sure out of time at this point.

[01:16:47] Speaker 03:
Thank you, Mr. Hsu.

[01:16:49] Speaker 03:
Let's give Mr. Rosencrantz his full four minutes of rebuttal.

[01:17:03] Speaker 02:
Thank you very much, Alanis.

[01:17:12] Speaker 01:
So a lot to respond to, but I'll make just four points.

[01:17:16] Speaker 01:
First, to answer Chief Judge Moore's question about the unknown antigens, Garcia did say it at 33, 677 at the bottom of the page, but the two inventors said it too.

[01:17:28] Speaker 01:
At 32, 993.

[01:17:31] Speaker 01:
That's Satellane and a 26411, that's Brenton's, and I'll quote, a whole piece of research still has to be done today to identify suitable targets for solid tumors for CAR T therapy.

[01:17:45] Speaker 01:
That's the inventor Satellane, and Brenton's says, quote, finding ideal target antigens for cancer, certainly in solid tumors, is a difficult chore and will require much more work on our part.

[01:17:59] Speaker 01:
Second, Chief Judge Moore, you are exactly right.

[01:18:02] Speaker 01:
The 190 patent gave an idea about how to use an SCFB as a binding element in a car.

[01:18:10] Speaker 01:
But from there, a skilled artisan has huge amounts of research to do in order to figure out which ones will work.

[01:18:19] Speaker 01:
You also asked for an established correlation between structure and function.

[01:18:24] Speaker 01:
There is a killer quote from Dr. Brockert, Juno's own expert, that there was no established correlation.

[01:18:32] Speaker 01:
That's at 33955B.

[01:18:33] Speaker 01:
It's at the end of volume two.

[01:18:36] Speaker 01:
He says the patent does not, quote, teach any correlation between amino acid sequence of an STFC and its ability to bind to a target antigen.

[01:18:48] Speaker 01:
And, of course, because it's so unpredictable.

[01:18:52] Speaker 01:
Third, Chief Szechmoor, you also

[01:18:54] Speaker 03:
Mr. Chu was concerned about the court potentially running into problems with its own precedent if it were to say that they had to have disclosed the amino acid sequence, for example, of the two SCFE's that it had in fact.

[01:19:11] Speaker 01:
Oh, so your key point is very clear on this.

[01:19:13] Speaker 01:
There is no requirement that you disclose the full amino acid sequence if

[01:19:19] Speaker 01:
The amino acid sequence is published elsewhere, but there's a regulation that requires you to publish an amino acid or a DNA sequence if you're going to claim it.

[01:19:30] Speaker 01:
But our point is what?

[01:19:31] Speaker 03:
I would say wouldn't your point in this case be even broader?

[01:19:34] Speaker 03:
Even if the two sequences were disclosed, unless there was evidence that those sequences had within them something that taught a skilled artisan how to identify other sequences, it still wouldn't be enough.

[01:19:45] Speaker 01:
Exactly, Your Honor.

[01:19:46] Speaker 01:
And that's the point I was just going to make, which is,

[01:19:49] Speaker 01:
That's not representative of the millions of billions that allow you to envision the full genus.

[01:19:57] Speaker 01:
And that really is the, you're making a lot of the point that is I think the key to this dispute that Juno tries to avoid, these claims create or they recite a function and it's the SCFB

[01:20:12] Speaker 01:
that provides the function just look at the claim itself this is not some mechanical component Mr. Chu called it a fastener it's not a mechanical component that you plug and play the claim is to a single chain it's to a long genetic a long chain of genetic material and it codes a single thing which is a protein with segments that interact with one another the only claimed function

[01:20:40] Speaker 01:
in this entire patent is the specific binding function and that is performed by the SCFB and everything that happens down chain is triggered by the SCFB.

[01:20:54] Speaker 01:
Third, the Sotomayor article about the billion, the only expert testimony in this record about that billion candidates

[01:21:04] Speaker 03:
So am I right?

[01:21:06] Speaker 03:
I mean, I kind of put a lot of words in your mouth and you're out of time, but at least answer me this question.

[01:21:11] Speaker 03:
Was there anything that I said when I said, well, I think even Mr. Rosencrantz would agree with that.

[01:21:16] Speaker 03:
Did I say anything that you don't agree with, which I attributed to you as agreeing with?

[01:21:21] Speaker 01:
Everything you said that you attributed to me as agreeing with, yes.

[01:21:24] Speaker 01:
Those are table stakes in all written descriptions or one-to-all descriptions.

[01:21:29] Speaker 03:
But for example, things like SCFE's were well-known.

[01:21:32] Speaker 03:
How to make SCFE's were well-known.

[01:21:34] Speaker 03:
Even that Mr. Brocker testified that now, in light of this car backbone structure, any SCFE could be attached to the car.

[01:21:45] Speaker 03:
The real issue, it seems to me, is in the binding to a specific target.

[01:21:50] Speaker 01:
Correct.

[01:21:50] Speaker 03:
Is that the problem?

[01:21:51] Speaker 01:
That is the problem.

[01:21:52] Speaker 03:
Those other things were either well-known or sufficiently taught by this patent.

[01:21:56] Speaker 03:
But what isn't taught by this patent

[01:21:59] Speaker 03:
is which STSEs will bind to which targets.

[01:22:04] Speaker 01:
That is correct.

[01:22:04] Speaker 01:
And then when you put them in cars, whether they will continue to bind, that was also not known back in 2002.

[01:22:11] Speaker 01:
And the reason I said this is table stakes is because the same arguments were made in identics.

[01:22:16] Speaker 01:
I mean, everyone knew how to make a nucleoside.

[01:22:19] Speaker 01:
That was the clear testimony in the case.

[01:22:21] Speaker 01:
Give me a structure I know how to make it.

[01:22:23] Speaker 01:
or Boston Scientific, everyone knew how to make those macrocyclic rings, or Carnegie Mellon, or Amgen, everyone knows how to make antibodies.

[01:22:34] Speaker 01:
Last point on 112 is, as Chief Judge Moore said, if it was so easy for Juno to do this, Juno would have done it, and it would have done it 19 years earlier than it ended up doing it.

[01:22:48] Speaker 01:
Mr. Chu talked about CD19,

[01:22:51] Speaker 01:
Juno tried to make a CD9 scene-specific SCFB with the 190 patent, and it failed.

[01:22:59] Speaker 01:
It transferred to another technology.

[01:23:02] Speaker 05:
If I may say one last thing on... I just want to make sure that I'm right.

[01:23:07] Speaker 05:
And Mr. Chu is correct, is he not, that there is specific testimony in the record that the licensing efforts occurred before the correction.

[01:23:16] Speaker 05:
And that your statement to me that that wasn't true,

[01:23:20] Speaker 05:
assumes that we disbelieve the testimony from Song Kettering.

[01:23:25] Speaker 01:
So, Your Honor, there was no testimony that... I'm sorry.

[01:23:31] Speaker 01:
That is correct.

[01:23:33] Speaker 01:
You would have to disbelieve the testimony of the Juneau executive who said there were licensing conversations going on before that.

[01:23:44] Speaker 01:
But the only evidence in the record other than that is actually an inquiry about collaboration on immunotherapy.

[01:23:52] Speaker 01:
And then Juno reaching out to talk about a license, an email to which our inventor never responded.

[01:24:05] Speaker 01:
Let me just make one last point about the COC.

[01:24:09] Speaker 01:
And it's the Chief Judge Moore talks about confusing

[01:24:14] Speaker 01:
information.

[01:24:15] Speaker 01:
This is all a jumble of confusion.

[01:24:18] Speaker 01:
A broadening COC is supposed to be about obvious errors, typos right on the face of the patent.

[01:24:24] Speaker 01:
The burden should be on the inventor to state the meets and bounds of his invention clearly.

[01:24:31] Speaker 01:
The burden shouldn't be on the public to try to parse through dense text and figure out, like I'll stare at an RCE,

[01:24:40] Speaker 01:
Compare the amino acid sequences, realize that there is a discrepancy, and then figure out what it is.

[01:24:47] Speaker 01:
And to answer Judge O'Malley's question about this court's law, the answer is no.

[01:24:52] Speaker 01:
If a broadening correction cannot be of minor character, Superior Fireplace says that a broadening amendment cannot be minor.

[01:25:04] Speaker 01:
So if there are no further questions, we respectfully request that the court reverse.

[01:25:09] Speaker 03:
We thank both counsels for the argument.

[01:25:11] Speaker 03:
It was very helpful and thank you very much.

[01:25:15] Speaker 03:
Let's move on to our next case.