[00:00:55] Speaker 02:
Okay, the next case is number 17-115, Merck Shop and Dome Corporation against Husbeer Incorporated.

[00:01:04] Speaker 02:
Ms.

[00:01:04] Speaker 02:
Ellsworth.

[00:01:05] Speaker 00:
Good morning, Your Honors.

[00:01:06] Speaker 00:
Jessica Ellsworth on behalf of the appellant.

[00:01:09] Speaker 00:
Your Honors, this is not a typical obviousness case.

[00:01:13] Speaker 00:
In the typical obviousness case, all of the claim limitations can be found somewhere in the prior art.

[00:01:19] Speaker 00:
And the court's task is to determine whether there is a

[00:01:23] Speaker 00:
motivation to combine those elements and a reasonable success of doing so.

[00:01:28] Speaker 03:
But here you have all the the same elements.

[00:01:32] Speaker 03:
Isn't that the 323 pattern prior art?

[00:01:36] Speaker 00:
Absolutely the 323 pattern.

[00:01:38] Speaker 03:
It involves taking a pen M and a base and combining it with a CO2 source and the

[00:01:52] Speaker 03:
The 323 does the same thing.

[00:01:55] Speaker 03:
It's got a pen M and a base providing CO2.

[00:02:02] Speaker 00:
Your Honor, there are some very specific differences between the patents that I think are important.

[00:02:07] Speaker 00:
The first is that if you view the patents as a whole, they are solving a different problem.

[00:02:13] Speaker 00:
In the 323 patent, the question was how to solve a particular instability that the urtapenem molecule has.

[00:02:21] Speaker 00:
And that's the instability at the pyrrolidine nitrogen atom.

[00:02:25] Speaker 00:
You can see this because the 323 patent and the Almerson reference both define stabilized form as involving that pyrrolidine nitrogen atom.

[00:02:36] Speaker 02:
But this solution is described as if it were known to the inventors at the time and published.

[00:02:47] Speaker 00:
The solution in the 150 patent was not known to the inventors at the earlier time.

[00:02:52] Speaker 00:
And the key point is that the 150 patent provides a means of having long-term stability.

[00:02:58] Speaker 00:
It solves not just the problem of dimerization, which is the instability at that pyrrolidine nitrogen atom, but it also solves a separate degradation.

[00:03:09] Speaker 00:
And that's open ring degradation, which occurs through hydrolysis.

[00:03:13] Speaker 03:
Doesn't the 323 patent describe putting

[00:03:16] Speaker 03:
a boxing group on the Pyrrolidine ring, and isn't that what the 150 patent does?

[00:03:23] Speaker 00:
That is one aspect of what the 150 patent does.

[00:03:25] Speaker 00:
One aspect?

[00:03:26] Speaker 03:
That's the key aspect.

[00:03:27] Speaker 00:
With all due respect, Your Honor, it's not.

[00:03:29] Speaker 00:
The 150 patent is a manufacturing process to get to a final formulation product.

[00:03:35] Speaker 00:
And a final formulation product requires solving not just dimerization, but also open ring degradation, which is a significant problem

[00:03:45] Speaker 00:
Open ring degradation was something that was known in the prior art to affect all beta-lactams.

[00:03:52] Speaker 00:
And the prior art, in fact, taught away from using this pH of 6 to 9 when dealing with beta-lactams.

[00:03:59] Speaker 00:
You can see this in the district court's decision when it found that the 3-2-3 patent wasn't obvious over the prior 8-20 patent.

[00:04:07] Speaker 00:
One of the reasons it found that lack of obviousness was because for beta-lactams,

[00:04:13] Speaker 00:
The prior art taught to use a pH of 3.5 to 5 in order to find the maximum stability against hydrolysis.

[00:04:21] Speaker 03:
But the 323 taught the 6 to 9 ratio, didn't it?

[00:04:25] Speaker 00:
The 323 taught the 6 to 9 ratio only in connection with dimerization.

[00:04:30] Speaker 00:
It defined stabilized form of urtapenem as only dealing with dimerization.

[00:04:37] Speaker 00:
The 150 patent took on a bigger problem.

[00:04:39] Speaker 00:
It was not about short-term stability.

[00:04:42] Speaker 00:
It was not about just solving the problem of how to form the adduct.

[00:04:47] Speaker 00:
It was about how to have a manufacturing process that would simultaneously protect urtipenem against both dimerization and also open ring degradation.

[00:04:58] Speaker 03:
But that is not on the claims.

[00:05:00] Speaker 03:
What is in claim 21 of 150 of procedural steps

[00:05:05] Speaker 03:
of adding the pen M and base to a carbon dioxide source and then lyophilize it.

[00:05:13] Speaker 00:
Your honor, as the district court noted at appendix page 41, the steps set out in the 150 patent are not in the prior art.

[00:05:20] Speaker 00:
And there are a few specific ways that I would point out to this court that there are differences.

[00:05:25] Speaker 00:
The 150 patent, as you noted, starts by charging a solution of carbon dioxide source.

[00:05:30] Speaker 00:
Nothing in the 323 patent spoke to

[00:05:33] Speaker 00:
starting with a carbon dioxide source and solution.

[00:05:36] Speaker 00:
The second thing is that step two in the 150 patent speaks to adding a base and an active ingredient simultaneously.

[00:05:44] Speaker 00:
As the district court recognized that appendix page 39, there is nothing in the 323 patent that talks about the simultaneous addition.

[00:05:52] Speaker 00:
The only thing that the district court relied on in looking at the 150 patent and looking at these steps was Dr. Murgatroyd's hindsight testimony.

[00:06:01] Speaker 00:
And we know that that's hindsight testimony for a couple of reasons.

[00:06:05] Speaker 00:
It is not rooted in any prior art, the suggestion to start with the carbon dioxide source to simultaneously add the base and the active ingredient.

[00:06:14] Speaker 00:
Dr. Murgatroyd, Hespera's expert, simply said that was what he would do without any.

[00:06:20] Speaker 03:
These aren't reasonable variations permissible and known to one of skill in the art.

[00:06:29] Speaker 00:
We don't think they are, Your Honor, and there are a couple reasons for this.

[00:06:32] Speaker 00:
This Court has specifically offered some caveats on when it is appropriate for a court to use common sense or common knowledge in the art to impose or find claim limitations, missing claim limitations in an obviousness analysis.

[00:06:48] Speaker 00:
And I would direct the Court specifically to the Arendy v. Apple case from last year, which the Court said there are three caveats.

[00:06:55] Speaker 00:
The first is that

[00:06:57] Speaker 00:
Supplying a missing claim limitation, excuse me, the motivation to combine is generally about taking limitations that exist and combining them.

[00:07:08] Speaker 00:
It is not about supplying missing claim limitations.

[00:07:11] Speaker 00:
The second is that it is an exception rather than a rule to be able to say common knowledge provides a missing claim limitation.

[00:07:20] Speaker 00:
And the third is that a missing claim limitation should not be supplied through common knowledge

[00:07:25] Speaker 00:
where it plays a major role in the subject matter claimed.

[00:07:29] Speaker 00:
To our knowledge, there's only one case in which this court has ever allowed common sense or common knowledge to supply a missing claim limitation, and that was the Perfect Web case, in which the patent involved very simple technology, and the missing limitation did not play a major role in that technology.

[00:07:48] Speaker 00:
The Hearware case, which was cited in Arendy,

[00:07:53] Speaker 00:
even invokes that when a claim is before a patent examiner, the MPEP specifies that a patent examiner can only rely on common knowledge to support a rejection in very narrow circumstances.

[00:08:05] Speaker 00:
And those circumstances are where there is a basis in the prior art, or the facts are, quote, capable of instant and unquestionable demonstration of being well known.

[00:08:16] Speaker 00:
Now, that's before the patent examiner here.

[00:08:18] Speaker 00:
we have a patent in which Jaspierra was invoking two prior art patents, both of which were before the examiner at the time the 150 patent was issued.

[00:08:28] Speaker 00:
So not only do we have the presumption that the 150 patent is valid, but that's an enhanced burden that Jaspierra faced given that these two prior art references were in fact both before the patent examiner.

[00:08:41] Speaker 00:
So the district court erred in a couple of different ways.

[00:08:45] Speaker 00:
We've been talking about the use of common sense

[00:08:47] Speaker 00:
The other, I think, clear error was the use of the 150 patent as a template.

[00:08:52] Speaker 00:
Rather than starting with a 323 patent and saying, what would this make obvious to a practitioner, a skilled practitioner at the time of 2001, the district court started with the three process steps, broke them up into subparts and said, well, here's what subpart one says.

[00:09:10] Speaker 00:
Can I find anything that might have suggested you would start, you would go to subpart one?

[00:09:14] Speaker 00:
Then we moved to part two.

[00:09:16] Speaker 00:
Can I find anything that suggests you might have gone next to step two?

[00:09:21] Speaker 00:
But that's not the way the analysis is supposed to work.

[00:09:25] Speaker 03:
Doesn't the 3-2 patent describe a process for putting a carboxy group on the parole ring of this pen-in?

[00:09:33] Speaker 00:
It does, Your Honor, but that is not all.

[00:09:35] Speaker 03:
And isn't that what the 150 patent does?

[00:09:39] Speaker 00:
That is one aspect of what the 150... One aspect of it.

[00:09:42] Speaker 03:
Isn't that basically what's in the claim?

[00:09:44] Speaker 00:
I think, Your Honor, if you look at the fact that claim three, the introduction to claim 21 and claim three both talk about a final formulation product.

[00:09:54] Speaker 00:
And the district court's Markman definition of final formulation product was that a final formulation product was one that had low byproducts.

[00:10:03] Speaker 00:
And low byproducts include dimers and open ring degradants.

[00:10:08] Speaker 00:
So the 150 patent took what was in the 323 patent

[00:10:13] Speaker 00:
and took it significantly further.

[00:10:15] Speaker 00:
And it did that by finding what was really an unexpected result, which is that there was a way to resolve open ring degradation in a different pH range than the prior art had taught was the range that should be targeted for beta-lactams.

[00:10:30] Speaker 00:
The district court, at appendix 12, you can see the district court speaks specifically to the fact that beta-lactams are known, were known in the prior art to have maximum

[00:10:40] Speaker 00:
a stability in the range of 3.5 to 5.

[00:10:43] Speaker 00:
And the district court, in fact, used that as part of its reasoning and why the 3-2-3 patent was not obvious by pointing out that people trying to turn urtapenem into a pharmaceutical product would have been working in the 3.5 to 5 pH range in order to deal with a known hydrolysis problem.

[00:11:04] Speaker 00:
At the time the 1-5-0 patent was filed, that means that the prior art taught two things

[00:11:08] Speaker 00:
and it didn't teach one thing that are very critical to analyzing the 150 pattern.

[00:11:14] Speaker 00:
It taught that you could form an adduct in the pH range of six to nine.

[00:11:18] Speaker 00:
The prior art taught that to have maximum stability of beta-lactams, you wanted to be in a range of 3.5 to five.

[00:11:26] Speaker 00:
Of course, those two ranges cannot be simultaneously reached.

[00:11:29] Speaker 00:
And what it didn't teach was that within the range of six to nine, there was this divergent effect

[00:11:36] Speaker 00:
of pH on dimerization and open ring degradation.

[00:11:40] Speaker 00:
So the 150 patent not only solved the open ring degradation problem, but it also provided a solution to this previously undisclosed and unknown problem of how to deal with the divergent pH effect.

[00:11:54] Speaker 03:
Does the district court make any errors of law or any clearly erroneous fact findings?

[00:12:00] Speaker 00:
We have challenged primarily the legal errors that affected the district court's analysis, and that

[00:12:05] Speaker 00:
includes not considering the patent as a whole.

[00:12:08] Speaker 00:
And to be clear again, the patent as a whole is not just a manufacturing process for forming the adduct.

[00:12:14] Speaker 00:
That is what Haspera argues.

[00:12:17] Speaker 00:
It's what led Haspera to encourage the district court to view the 323 patent as a recipe.

[00:12:24] Speaker 00:
But of course, you can't have a recipe for something that doesn't tell you what you're making.

[00:12:27] Speaker 00:
And the 150 patent made something different.

[00:12:30] Speaker 00:
It made an urtapenem product, a final formulation product that had

[00:12:34] Speaker 00:
two plus years of stability.

[00:12:37] Speaker 00:
It took something that previously had, the stability data from the 323 and the Elmerson was in terms of hours and days.

[00:12:46] Speaker 00:
The 150 process, through that very specific manufacturing process, again, with steps that are not set forth, there's nothing that speaks to starting with a sea of carbon dioxide source and then simultaneously adding the base and the active ingredient at the same time,

[00:13:03] Speaker 00:
It was able to come up, Merck was able to come up with a manufacturing process that solved open ring degradation sufficient to have long term stability and therefore be able to have what really could then become a commercially available product on a hospital shelf.

[00:13:21] Speaker 00:
If I could just mention one other thing, the unexpected results are a critical aspect here of showing non-obviousness and the district court failed to mention or address

[00:13:31] Speaker 00:
Merck's argument on unexpected results, which was made.

[00:13:35] Speaker 00:
That, again, is a legal error.

[00:13:36] Speaker 00:
This court has required district courts to address the objective indicia of non-obviousness before reaching an obviousness conclusion, and here the district court did not do so.

[00:13:46] Speaker 03:
I think one of the quotes that really highlights this is that the district court... Well, what the district court said in terms of secondary indicia were contributed by the molecule itself.

[00:14:01] Speaker 03:
which was described in the 3-2-3 patent, right?

[00:14:05] Speaker 00:
The district court addressed, in talking about the 1-5-0 patent, the district court addressed copying, which it found Hospera had copied the manufacturing process.

[00:14:13] Speaker 00:
There was no question about that.

[00:14:15] Speaker 00:
It addressed commercial success, and it did not address unexpected results.

[00:14:19] Speaker 00:
That was something that Merck had briefed in its post-trial brief.

[00:14:23] Speaker 00:
Were these unexpected results, particularly on the open ring degradation problem and the divergent pH effect,

[00:14:29] Speaker 00:
which were not something that were previously discussed or described, or that there was any suggestion in the prior art that a pH range of 6 to 9 would do anything to resolve.

[00:14:40] Speaker 00:
If I could reserve the remainder of my time for rebuttal.

[00:14:43] Speaker 02:
Okay, we'll save you for rebuttal time, Ms.

[00:14:45] Speaker 02:
Ellsworth.

[00:14:46] Speaker 02:
Let's hear from Mr. Meloro.

[00:14:53] Speaker 01:
Thank you, Your Honor.

[00:14:54] Speaker 01:
It may please the Court.

[00:14:57] Speaker 01:
The District Court

[00:14:58] Speaker 01:
Appropriately ruled that the 150 patent would have been obvious because the 323 patent arms the person of ordinary skill in the art with the information that they need to practice and arrive at the 150 patent claims.

[00:15:14] Speaker 01:
The 323 patent teaches that urtapenem is a carbapenem antibiotic.

[00:15:21] Speaker 01:
It provides the structure for that molecule.

[00:15:25] Speaker 01:
It provides the stabilization

[00:15:28] Speaker 01:
of urtipenem.

[00:15:29] Speaker 01:
Critically, by reacting at that pyrrolidine nitrogen with a carbon dioxide source to stabilize the urtipenem molecule, it also teaches that the pH range of 6 to 9 is the pH range to use.

[00:15:48] Speaker 02:
But it doesn't discuss the particular order of addition and the details, the fine points, which we're told

[00:15:57] Speaker 02:
make the difference between success and failure?

[00:16:00] Speaker 01:
Two aspects to that question, Your Honor.

[00:16:03] Speaker 01:
The order of addition doesn't make the difference between success or failure.

[00:16:08] Speaker 01:
It's the reaction of that carbon dioxide source in the pH range of 6 to 9, and then lyophilization.

[00:16:16] Speaker 01:
That's what gets you success.

[00:16:19] Speaker 01:
All of that is in the 323 patent.

[00:16:20] Speaker 01:
The 323 patent specifically says to lyophilize.

[00:16:24] Speaker 01:
With respect to the specific

[00:16:27] Speaker 01:
order of addition of the ingredients.

[00:16:30] Speaker 01:
Essentially, the 150 patent claim tells you that you bring together your carbon dioxide source with your urtapenem and you lyophilize.

[00:16:42] Speaker 01:
One of ordinary skill in the art would understand that you want to be operating in that pH range of 6 to 9.

[00:16:49] Speaker 01:
That's what's in the 323 patent.

[00:16:52] Speaker 01:
That's what's in the 150 patent.

[00:16:54] Speaker 01:
That gives you information, if you're one of ordinary skill in the art, about how you bring these ingredients together.

[00:17:01] Speaker 01:
So Dr. Murgatroyd testified that one skilled in the art would know that you would first dissolve your carbon dioxide source because you have essentially a finite number of choices here.

[00:17:14] Speaker 01:
You can put all of your ingredients in together at once, or you can put one into solution and then the active into solution.

[00:17:23] Speaker 01:
One of ordinary skill in the art, Dr. Murgatroyd testified, Dr. Stanley confirmed as a matter of chemistry, and Judge Andrews found would understand that urtipenem having a pH below six, you would want to have that present with a base, sodium hydroxide, to counteract the pH of the urtipenem.

[00:17:48] Speaker 01:
So you would be within that maintained range of six to nine.

[00:17:52] Speaker 01:
the range that 323 teaches.

[00:17:54] Speaker 01:
Dr. Murgatroyd explained that, and Judge Andrews found that.

[00:17:59] Speaker 01:
Judge Andrews also understood from the testimony that you would not combine all three components together.

[00:18:07] Speaker 01:
Even Dr. Staley, Merck's expert, said that as a matter of chemistry, if you added all three components together, one skilled in the art would understand you'd have uncontrolled reactions.

[00:18:19] Speaker 01:
one skilled in the art, exercising the ordinary creativity.

[00:18:23] Speaker 03:
What about unexpected results, which the opposing counsel said the court didn't deal with, avoidance of domarization and hydrolysis?

[00:18:33] Speaker 01:
There is no unexpected result that is not accounted for totally by the 323 patent.

[00:18:40] Speaker 01:
The result of stability is taught in the 323 patent as a result of operating

[00:18:46] Speaker 01:
to form that adduct in the pH range of 6 to 9.

[00:18:50] Speaker 03:
And in fact, Dr. Stella... In other words, putting the hydroxy group on the pyrrolidine produces the results.

[00:18:57] Speaker 01:
In that pH range of 6 to 9 taught by 3-2-3, Dr. Stella himself, Merck's expert, testified with respect to the 3-2-3 patent that the 3-2-3 patent taught what he called a sweet spot, a sweet spot between preventing dimerization

[00:19:16] Speaker 01:
and also minimizing this ring-opening hydrolysis.

[00:19:20] Speaker 01:
And that's at page A1040.

[00:19:22] Speaker 01:
That was with respect to the 323 patent.

[00:19:26] Speaker 01:
Dr. Williams, one of the inventors on the 150 patent, confirmed that it was known that carbapenems, like artapenem, known in the art, were unstable hydrolytically at low pHs and high pHs.

[00:19:41] Speaker 01:
The unexpected result that counsel is arguing here

[00:19:45] Speaker 01:
is the unexpected result, if there is any, of following the 3-2-3 patent, bringing together the carbon dioxide source with the urtipenem in the sweet spot pH range of 6 to 9.

[00:19:58] Speaker 01:
There's nothing else claimed in the claims of 150 leading to an unexpected result.

[00:20:05] Speaker 01:
There's nothing else alleged to provide some unexpected property.

[00:20:09] Speaker 01:
Dr. Stella testified that the 3-2-3 patent

[00:20:13] Speaker 01:
doesn't just teach an adduct, it teaches a pharmaceutical composition sufficiently stable that it could be suitable for intravenous administration to humans.

[00:20:25] Speaker 01:
The 323 patent gives you a pharmaceutical that can be put on the shelf.

[00:20:31] Speaker 01:
The 150 patent adds nothing in that regard.

[00:20:34] Speaker 01:
The 150 patent has no claim to two years of stability, but even if there were some level of stability achieved, that level of stability

[00:20:43] Speaker 01:
is achieved following the 323 patent, forming the adduct in the pH range of 6 to 9.

[00:20:50] Speaker 01:
These were Merck's own experts who provided this supporting testimony.

[00:20:55] Speaker 01:
Dr. Stella is an eminent researcher.

[00:20:58] Speaker 01:
At trial, he testified to having invented several pharmaceutical products that have been approved by the FDA and are out in the field.

[00:21:07] Speaker 01:
And he said the 323 patent, when you follow it, gives you a pharmaceutical composition

[00:21:12] Speaker 01:
suitable for administration, intravenous administration to humans.

[00:21:17] Speaker 01:
Now, with respect to the expert testimony of Dr. Murgatroyd, Dr. Murgatroyd is an eminent practitioner in the field of lyophilization.

[00:21:30] Speaker 01:
He has decades of experience in the field.

[00:21:34] Speaker 01:
The expert from Merck, Dr. Staley, who was the primary expert on the validity of the 150 patent,

[00:21:42] Speaker 01:
admitted he has nowhere near the expertise of Dr. Murgatroyd when it comes to creating processes for lyophilizing pharmaceuticals.

[00:21:52] Speaker 02:
These aren't people of ordinary skill.

[00:21:55] Speaker 02:
These are people of superior skill.

[00:21:57] Speaker 02:
Dr. Murgatroyd.

[00:21:58] Speaker 02:
You might read the 323 and understand some things that the ordinary person might not.

[00:22:06] Speaker 01:
It is correct that Dr. Murgatroyd is an expert in the field, and Dr. Staley was accepted as an expert.

[00:22:12] Speaker 01:
And what Dr. Murgatroyd explained was what a person of ordinary skill in the art would know, not what only an expert would know.

[00:22:19] Speaker 01:
These are matters of routine chemistry.

[00:22:23] Speaker 01:
When reading the 323 patent, the 323 patent specifically taught that chemical reaction at the pyrrolidine nitrogen.

[00:22:30] Speaker 01:
One of ordinary skill in the art would understand that.

[00:22:34] Speaker 01:
One of ordinary skill in the art would understand the pH range of 6 to 9.

[00:22:38] Speaker 01:
So the experts were not providing expert testimony only known to experts.

[00:22:43] Speaker 01:
They were simply explaining.

[00:22:46] Speaker 01:
Dr. Murgatroyd was explaining what was in the 323 patent itself.

[00:22:50] Speaker 01:
Judge Andrews was well within his discretion in adopting Dr. Murgatroyd's testimony, much of which was confirmed by Dr. Stella or Dr. Williams or, in some instances, Dr. Staley.

[00:23:03] Speaker 01:
And none of the factual findings were clearly erroneous.

[00:23:07] Speaker 02:
But we're told also that it took quite some time before this inherently unstable compound was developed and a method of doing so was recognized.

[00:23:21] Speaker 02:
So are we not just imposing our own hindsight based on what finally worked?

[00:23:28] Speaker 01:
I saw some reference to an argument of that nature in Merck's brief.

[00:23:31] Speaker 01:
And just while patentability is not negative,

[00:23:35] Speaker 01:
by the manner in which the invention is made.

[00:23:38] Speaker 01:
I think it was the Merck v. Byercraft case that said neither does the fact that it takes the inventors a little bit of time to do their work makes it patentable in and of itself.

[00:23:49] Speaker 01:
One must look at what is known in the prior art and whether the differences would have been obvious to one of ordinary skill.

[00:23:57] Speaker 01:
Here, the 323 patent, which took some years after the invention of Ertepenem,

[00:24:03] Speaker 01:
arms the person of ordinary skill in the art with the information that they need in order to make a lyophilized urtapenem adduct with that carbon dioxide.

[00:24:14] Speaker 03:
Was the 323 patent upheld?

[00:24:16] Speaker 01:
The 323 patent was upheld at trial in the same trial as the 150 patents.

[00:24:23] Speaker 03:
Then was there an earlier patent on the penem that expired?

[00:24:31] Speaker 01:
That's correct, Your Honor.

[00:24:32] Speaker 01:
There was a patent called the 820 patent, which claimed urtapenem itself, the molecule.

[00:24:39] Speaker 01:
That patent was not challenged.

[00:24:42] Speaker 01:
The 323 patent claimed the urtapenem adduct and had pharmaceutical compositions suitable for intravenous administration.

[00:24:52] Speaker 01:
That patent was challenged at trial.

[00:24:56] Speaker 01:
Based on the 820 patent and knowledge of one of skill in the arts,

[00:25:00] Speaker 01:
Judge Andrews upheld the validity of the 323 patent.

[00:25:04] Speaker 01:
It was only the 150 patent, which is the simple lyophilization process that Judge Andrews found would have been obvious based on 323.

[00:25:15] Speaker 03:
Well, it was more than lyophilization.

[00:25:17] Speaker 03:
It was a little reversal of the process, two-step process for putting on the carbon dioxide.

[00:25:25] Speaker 01:
The process for putting on the carbon dioxide

[00:25:29] Speaker 01:
is the same.

[00:25:29] Speaker 01:
It's exposing the carbon dioxide source to the urtipenem in solution.

[00:25:35] Speaker 01:
And that happens in the 323 patent.

[00:25:37] Speaker 01:
It happens in 150.

[00:25:38] Speaker 01:
150 has the steps of first adding the carbon dioxide to solution, then adding the urtipenem with the base.

[00:25:47] Speaker 01:
One of ordinary skill in the art would have been motivated to take those steps based on the chemistry that was undisputed amongst the experts.

[00:25:55] Speaker 01:
Dr. Murgatroyd testified why one of skill in the art

[00:25:58] Speaker 01:
would have done it in that fashion.

[00:26:00] Speaker 01:
Dr. Staley confirmed, and Judge Andrews found that one skilled in the art would have known there were problems if you tried to do things a different way, like adding all three of the components at the same time.

[00:26:12] Speaker 01:
323 arms, one skilled in the art with the information they need.

[00:26:17] Speaker 01:
Judge Andrews properly found the facts, properly concluded that the 150 patent is obvious.

[00:26:24] Speaker 01:
There are no further questions.

[00:26:28] Speaker 02:
Okay.

[00:26:30] Speaker 01:
Thank you, Mr. Menoro.

[00:26:32] Speaker 02:
Thank you, Your Honor.

[00:26:33] Speaker 02:
Ms.

[00:26:33] Speaker 02:
Ellsworth.

[00:26:38] Speaker 00:
Your Honor, frankly, the 323 patent doesn't arm someone with what they need.

[00:26:43] Speaker 00:
It speaks about blending a powder of carbon dioxide source and urtapenem, and then it speaks about using a base at some later point upon dilution to give it to a patient or upon reconstitution.

[00:26:55] Speaker 00:
that is very different from the manufacturing steps set out in the 150 patent.

[00:27:01] Speaker 00:
And Dr. Murgatroyd, Haspira's expert, acknowledged at pages 658, 673, 748, and 749 of the appendix that those manufacturing steps were not set out.

[00:27:14] Speaker 00:
What he offered instead was his own say-so, that that's what he would have done, but that say-so was not rooted

[00:27:20] Speaker 00:
in any prior art.

[00:27:22] Speaker 00:
It wasn't rooted in anything that would give the factual underpinning that this Court has said is required to find that an expert's testimony has the sufficient protections against hindsight bias.

[00:27:37] Speaker 00:
Counsel for the other side suggested that there's nothing in the 150 patent that relates to two years of stability.

[00:27:44] Speaker 00:
With all due respect, I disagree.

[00:27:46] Speaker 00:
If you look at column 9 of the 150 patent, lines 1 to 9, there is a definition for solid state stability.

[00:27:54] Speaker 00:
This is the specific shortcoming that the 150 patent sets out as missing from the 323 patent and Olmerson.

[00:28:02] Speaker 00:
There's no way to take what's in the 323 and Olmerson and end up with solid state stability and reconstitution stability.

[00:28:10] Speaker 00:
That is what the 150 patent added to the knowledge at the time.

[00:28:16] Speaker 00:
The patent examiner who had the 323 and Elmerson in front of him when he issued the 150 patent certainly could have looked at those and did not think that they armed someone with what they would need.

[00:28:31] Speaker 00:
The main difference here is, yes, the 323 gets you a pharmaceutical composition.

[00:28:37] Speaker 00:
But it's a pharmaceutical composition

[00:28:39] Speaker 00:
that degrades in a matter of hours.

[00:28:41] Speaker 00:
So if you're making it in a lab and you have a patient right next door who you can run across the street and administer it to through an IV... Even with the CO2 molecule?

[00:28:52] Speaker 00:
Yes, Your Honor.

[00:28:53] Speaker 03:
On the nitrogen it degrades?

[00:28:55] Speaker 00:
That's correct, Your Honor.

[00:28:56] Speaker 03:
The only stability... Is that because it wasn't lyophilized?

[00:29:00] Speaker 00:
No, Your Honor.

[00:29:00] Speaker 00:
It's because it didn't prevent the open ring degradation.

[00:29:04] Speaker 00:
It's because the only stability was on that pyrrolidine nitrogen atom.

[00:29:08] Speaker 00:
It wasn't also on the beta-lactam ring.

[00:29:10] Speaker 00:
In order to get stability on the beta-lactam ring, you have to follow the specific steps in the specific order that are set out in the 150 patent.

[00:29:19] Speaker 00:
So what the 150 patent does is give away to have a simultaneous reduction of both dimers and open ring degradants so that you can get that two years of solid state stability

[00:29:32] Speaker 00:
that the 150 patent spells out in its definitions.

[00:29:37] Speaker 00:
Again, column nine lines one through nine.

[00:29:40] Speaker 02:
If it were as... Both of your friends as a person of ordinary skill would know that you have to preserve the pH in that range, and the way to do that is to do it the way the 150 does it.

[00:29:52] Speaker 00:
What's the answer?

[00:29:53] Speaker 00:
So there are a number of answers to that.

[00:29:55] Speaker 00:
One is that they don't point to any prior art that suggests that to be true.

[00:29:59] Speaker 00:
They are relying simply on common sense.

[00:30:01] Speaker 00:
And that reliance on common sense conflicts with what this Court has said about the appropriate use of common sense to fill in missing claim limitations in both the Arendy and the Hareware case.

[00:30:13] Speaker 00:
The other problem with it is that it conflicts with the prior art and what it taught about beta-lactams, which were that to treat beta-lactams in a way that would give them maximum stability, you had to be at a different pH range from what Dr. Murgatroyd was saying

[00:30:30] Speaker 00:
Somehow, it would be obvious to have been using to solve hydrolysis in the patent process set out in the 150.

[00:30:38] Speaker 00:
And again, there's no basis for doing that.

[00:30:40] Speaker 00:
Your Honor pointed out that it had taken five years to get from the 323 patent to the 150 patent.

[00:30:47] Speaker 00:
The process manual that's in the joint appendix spells out all of the significant work that was done during that year, including, importantly, moving from what's in the 323 patent, this blending of powder form,

[00:30:59] Speaker 00:
of urtapenem and a carbon dioxide source and instead moving to a situation where they started with carbon dioxide source dissolved in a solution and only then thought to add in the urtapenem, the active ingredient, along with the base simultaneously.

[00:31:17] Speaker 00:
Neither of those steps are set out or suggested anywhere in the 323 patent.

[00:31:22] Speaker 00:
And by not starting with the 323 patent and saying what would be obvious from there, forward-looking,

[00:31:29] Speaker 00:
The district court really engaged in the type of hindsight analysis that this court has consistently said is improper.

[00:31:36] Speaker 00:
You can't start with what's in the 150 patent and look backwards.

[00:31:39] Speaker 00:
But that's what the district court did.

[00:31:41] Speaker 00:
That's what Dr. Murgatroyd did.

[00:31:42] Speaker 00:
And with all due respect, that is a legal error that is one of the many legal errors in this case that warrant reversal.

[00:31:50] Speaker 00:
The court has no further questions.

[00:31:52] Speaker 00:
We respectfully ask that you reverse the district court's decision.

[00:31:55] Speaker 02:
Thank you.

[00:31:55] Speaker 02:
Thank you both.

[00:31:56] Speaker 02:
The case is taken under submission.

[00:31:58] Speaker 02:
That concludes this morning's arguments.