IPR2016-00006, Paper No. 81
`March 1, 2017
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`trials@uspto.gov
`571-272-7822
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`RECORD OF ORAL HEARING
`UNITED STATES PATENT AND TRADEMARK OFFICE
`- - - - - -
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`STEADYMED LTD.,
`Petitioner,
`vs.
`UNITED THERAPEUTICS CORPORATION,
`Patent Owner.
`- - - - - -
`Case IPR2016-00006
`Patent 8,497,393 B2
`Technology Center 1600
`Oral Hearing Held: Tuesday, November 29, 2016
`
`Before: LORA M. GREEN, JONI Y. CHANG, and
`JACQUELINE T. HARLOW (via video link) Administrative Patent Judges.
`
`The above-entitled matter came on for hearing on Tuesday,
`November 29, 2016, at 1:00 p.m., Hearing Room B, taken at the U.S. Patent
`and Trademark Office, 600 Dulany Street, Alexandria, Virginia.
`REPORTED BY: RAYMOND G. BRYNTESON, RMR,
`
`CRR, RDR
`
`
`March 1, 2017
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`trials@uspto.gov
`571-272-7822
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`
`
`RECORD OF ORAL HEARING
`UNITED STATES PATENT AND TRADEMARK OFFICE
`- - - - - -
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`- - - - - -
`STEADYMED LTD.,
`Petitioner,
`vs.
`UNITED THERAPEUTICS CORPORATION,
`Patent Owner.
`- - - - - -
`Case IPR2016-00006
`Patent 8,497,393 B2
`Technology Center 1600
`Oral Hearing Held: Tuesday, November 29, 2016
`
`Before: LORA M. GREEN, JONI Y. CHANG, and
`JACQUELINE T. HARLOW (via video link) Administrative Patent Judges.
`
`The above-entitled matter came on for hearing on Tuesday,
`November 29, 2016, at 1:00 p.m., Hearing Room B, taken at the U.S. Patent
`and Trademark Office, 600 Dulany Street, Alexandria, Virginia.
`REPORTED BY: RAYMOND G. BRYNTESON, RMR,
`
`CRR, RDR
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`
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`APPEARANCES:
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`ON BEHALF OF THE PETITIONER:
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`STUART E. POLLACK, ESQ.
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`DLA Piper LLP (US)
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`1251 Avenue of the Americas
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`New York, New York 10020-1104
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`212-335-4500
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`MAYA PRAKASH CHOKSI,
`DLA Piper LLP (US)
`33 Arch Street, 26th Floor
`Boston, Massachusetts 02110-1447
`617-406-6000
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`DAVID NASSIF, ESQ.
`JONATHAN RIGBY, CEO
`SteadyMed Ltd.
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`STEPHEN B. MAEBIUS, ESQ.
`GEORGE E. QUILLIN, ESQ.
`Foley & Lardner LLP
`Washington Harbour
`3000 K Street, N.W., Suite 600
`Washington, D.C. 20007-5109
`202-672-5310
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`DOUGLAS H. CARSTEN, ESQ.
`Wilson, Sonsini, Goodrich & Rosati
`12235 El Camino Real, Suite 200
`San Diego, California 92130-3002
`858-350-2300
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`ROBERT A. DELAFIELD, ESQ.
`Wilson, Sonsini, Goodrich & Rosati
`900 South Capital of Texas Highway
`Las Cimas IV, Fifth Floor
`Austin, Texas 78746-5546
`512-338-5400
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`SHAUN R. SNADER, ESQ.
`United Therapeutics Corp.
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`Patent 8,497,393 B2
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`P R O C E E D I N G S
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`(1:00 p.m.)
`JUDGE HARLOW: Good afternoon. We will hear
`argument now in Case No. IPR2016-00006, SteadyMed versus
`United Therapeutics, concerning U.S. Patent Number
`8,497,393 B2.
`At this time would counsel please introduce
`themselves and their colleagues, beginning with Petitioner?
`MR. POLLACK: Good afternoon, Your Honors.
`Stuart Pollack on behalf of SteadyMed Limited. I'm joined
`here today by my colleague Maya Choksi from my office at
`DLA Piper.
`Also with me today is the CEO of SteadyMed,
`Mr. Jonathan Rigby. Jonathan, if you could stand up for a
`second. And also with us is David Nassif from SteadyMed.
`David is an attorney.
`JUDGE HARLOW: Thank you. For Patent
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`Owner?
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`MR. MAEBIUS: Good afternoon, Your Honors.
`Steve Maebius for United Therapeutics, Patent Owner. And
`with me I have George Quillin, also from Foley & Lardner.
`And in the back here I have Shaun Snader, the
`Chief Patent Counsel for United Therapeutics, and Doug
`Carsten, co-counsel in this IPR. Bobby Delafield is
`co-counsel in the IPR, and also from Wilson Sonsini.
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`JUDGE HARLOW: Thank you and welcome to the
`Board. Before we turn to the business of today, we have a
`little bit of housekeeping to take care of regarding yesterday's
`objections to certain demonstrative exhibits that we just
`wanted to put on the record.
`As discussed yesterday, we considered the parties'
`objections to each other's demonstratives, and ruled on the
`objections as follows: Patent Owner's objection to
`Petitioner's originally-filed demonstrative, slide number 11,
`was sustained because Petitioner did not identify record
`support for the diagram depicted on that slide.
`Accordingly, we will expunge the originally-filed
`demonstratives from the record, since Petitioner has already
`re- filed its demonstratives excluding slide 11 which we will
`use in today's proceeding.
`The parties' remaining objections are overruled as
`each of the disputed slides presented material that is of record
`and each slide clearly identified the source of that material.
`With regard to Patent Owner's concerns as to the
`potential waiver of arguments, we note that any argument
`concerning Phares figure 18 and Patent Owner's motion to
`exclude has not been waived.
`If there are no questions regarding that bit of
`housekeeping we can turn to today's hearing. Consistent with
`our prior order, each party will have 45 minutes to present its
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`Case IPR2016-00006
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`arguments today. Petitioner will proceed first to present its
`case as to the challenged claims and may reserve rebuttal
`time. Thereafter Patent Owner will have the opportunity to
`respond to Petitioner's case.
`We do remind the parties that Petitioner bears the
`burden of proving any proposition of unpatentability by a
`preponderance of the evidence. We also remind the parties
`that this hearing is open to the public and that a full transcript
`of it will become part of the record.
`For clarity of the record and because I'm
`participating remotely and cannot see the demonstratives as
`you display them on the screen, please be mindful of
`identifying each slide you discuss by its number in the filed
`versions of the demonstratives.
`With that I would like to invite Mr. Pollack to
`begin and ask if he would like to reserve any rebuttal time?
`MR. POLLACK: Thank you, Your Honor. Yes,
`we would like to reserve 30 minutes for rebuttal. So I will do
`15 now, just give an overview of our arguments, and then I
`will reserve 30 minutes for rebuttal.
`JUDGE HARLOW: Okay. Thank you. You may
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`proceed.
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`MR. POLLACK: Thank you, Your Honor. All
`right. Let me start with slide 2 of our presentation. Here are
`the arguments we're going to go over today.
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`JUDGE CHANG: Excuse me. Do you have any
`demonstratives for the court reporter, a copy of the
`demonstratives for the court reporter?
`MR. POLLACK: We could hand him one.
`JUDGE CHANG: Okay. Thank you.
`MR. POLLACK: Can I proceed while we're
`getting that?
`JUDGE CHANG: Sure.
`MR. POLLACK: Okay. So for now I'm just going
`to go over the first three topics, the legal concepts, the key
`scientific concepts, and an overview. But just to make this a
`little more interesting I'm not going to do it in the order that I
`have the slides in. I'm going to start with an overview of the
`prior art.
`
`So I'm going to ask you to turn to slide 19 in
`Exhibit 1029, the overview, and actually I will ask you to turn
`to slide 20. Slide 20 shows the first of the independent claims
`we're going to be discussing. This is claim 1. And you will
`see in our papers, it is of record that there are hundreds of
`thousands of compounds approximately in this claim.
`I've cut the claim down so it wouldn't list all of
`the numerous possibilities for all of those groups. So what
`I'm showing here are the essentials. And I've also divided the
`claim left and right. And the reason I did that is on the left
`are steps A and B. And those were acknowledged to be in the
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`prior art. That's the so- called Moriarty method of making
`treprostinil. And what is supposed to be new here is step C
`and perhaps D, which is only an optional step. And that's a
`purification procedure of the treprostinil that has already been
`made using the prior art method. So step C forms a salt and
`then step D is an optional step.
`And similarly we have claim 9 here on slide 21.
`What we see here on slide 21 is claim 9. It doesn't have as
`many compounds but it still has numerous compounds in it
`because it includes all of the pharmaceutically-acceptable
`salts. That would be your dicyclohexylamine salts, your
`diethanolamine salts, all of those salts listed in some of the
`dependent claims.
`So those are all included in claim 9 and there is
`not much information on the record about most of those salts
`other than the diethanolamine salt. On the left side, again,
`I've divided it. Steps A and B are the method of making
`treprostinil already taught in the prior art, the Moriarty
`method, and step C is the purification method that is supposed
`to be novel.
`Looking at slide 22, this is one of the key pieces
`of prior art we're going to rely on. That's Moriarty, the steps
`A and B. And according to Moriarty, which is Exhibit 1004,
`if you look at page 13, it indicates that the purity of Moriarty
`treprostinil is 99.7 percent.
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`JUDGE HARLOW: Counsel, do we know how
`Moriarty arrived at that purity calculation?
`MR. POLLACK: Yes, this is a -- so if you look at
`the text there it gives the method of HPLC assay analysis. It
`tells you what kinds of detectors are there, the UV detectors,
`so all of those details are provided and so that's what type of
`analysis is done. This is what is standard in the art. This is
`not a particularly surprising method of HPLC analysis.
`Oh, and it's HPLC, just to make that clear. I didn't
`highlight that. I only highlighted the purity. But if you look
`at the text you will see it's stated there.
`Slide 23, just as a comparison with the claims,
`claim 10, which is one of the narrowest claims, has a purity of
`at least 99.5 percent but, as you can see, the prior art was
`already achieving 99.7. And if you look in the '393 patent
`itself, you will also see references to much lower purities, 99,
`95, as being the result of the invention.
`Going to slide 24, this is the other key reference
`we're going to be relying on, the so-called Phares reference.
`And by the way, both Phares and Moriarty are papers and
`documents actually created by United Therapeutics itself, so
`this prior art actually all belongs to them. They are the
`creators of this art. It is their scientists.
`So Phares, as the Board pointed out in its
`Institution Decision, has the same treprostinil diethanolamine
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`salt as in the patent. Here I show on the left from Phares a
`drawing of that salt and on the right there is a drawing from
`the patent itself of that salt and, as the Board correctly
`pointed out in the Institution Decision, these are the identical
`compounds.
`Actually you can see there at the bottom it says,
`on slide 24, on the portion from Exhibit 1001, that the purity
`can be 90 percent, 95, 99, 99.5 from the invention.
`Going to slide 25, I don't expect you to actually
`understand the formulas on this slide. We won't be talking
`about that. But what I do want to get across is that melting
`point can be used as a measure of purity. So the lower a
`melting point is, the less pure a sample is. And we will be
`talking about that later in connection with the Phares
`reference.
`And the point we are going to make, going to slide
`26 here, if you look in the Phares reference, Form B of
`treprostinil diethanolamine salt -- and I will explain that Form
`B language in a second -- that salt has a melting point of 107
`degrees C. If you look in the patent there are some batches
`that have a melting point near 107 degrees C.
`But there are many batches, and I show one here,
`batch 1, which have a lower melting point. And what that
`means as a matter of science is that the treprostinil
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`diethanolamine salt in the patent has a lower purity than the
`Phares salt.
`JUDGE HARLOW: Counsel, how are we to
`understand Patent Owner's argument regarding the width of
`the melting point spike in Phares? Will you go into that now
`or, if you want to go into that in your anticipation discussion,
`that's fine, too?
`MR. POLLACK: Let me go into that now briefly
`since you asked and then I will go into it in more detail in my
`later discussion.
`Two points: Point 1 is, as a matter of science, no
`matter what, if a melting point is higher, I'll show you this,
`this is an equation that is required by something called the
`second law of thermal dynamics.
`And what the equation says, I won't go through
`every detail of it, but there is something called T naught,
`that's the melting point of a pure material, and then there is an
`Xi that is related to the amount of impurities in it. And you
`see there is a negative sign in between. So what the equation
`says is a melting point will always drop when there are
`impurities in it.
`So no matter how wide or narrow the peak is, if
`the melting point is higher, the scientific rule is it has got to
`be purer. It is an absolute law that you can't get around.
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`Then we talk about the alleged width of this peak.
`If you look at Dr. Rogers' declaration, he explains that this is
`actually quite a narrow peak. The peak only has a width of a
`couple of degrees C. So the peak is actually quite, quite
`narrow. It is not a broad peak. And he is an expert on
`precisely this area. So Dr. Rogers has testified that's a very
`narrow peak. And for whatever reason Patent Owner chose
`not to cross-examine Dr. Rogers, but that is his declaration.
`I'm going to make you move around a lot. Let's
`move to slide 11. Here I'm just going to talk briefly about
`some key scientific concepts. And in particular slide 12, step
`C and D are a purification process known as recrystallization.
`So what is recrystallization? It is a way of
`purifying materials by having them in suspension, dissolving
`them in solution and then having the crystal -- you dissolve
`them in solution by heating up the solution and the crystals
`form when the solution is cooled. And because they are
`forming a crystal they will be purer and the impurities will
`stay in solution. It will be thrown out and you collect the
`crystal.
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`So how long has that technique been around?
`Well, we asked, the testimony here on slide 12 from Exhibit
`2058, the pages are cited there, 175 to 176 and 179. We asked
`the Patent Owner's expert, Dr. Ruffolo, who used to be the
`head of R&D at Wyeth, you know, was he familiar with
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`recrystallization? He said, oh, yes, it is a technique that goes
`back decades. He learned about it back in college in 1968.
`And as we will talk about later, he learned about it in all of
`his elementary chemistry courses.
`Here is that melting point equation again. I think
`we've talked about that enough. But here is a point on slide
`14 that was raised by Patent Owner. And that is, well,
`couldn't there be different polymorphs. So, in fact, the Phares
`reference refers to different polymorphs.
`These are different crystal forms of the same
`chemical. There is a Form A and a Form B that are
`recognized in the art and in the prior art as shown here. And
`they do have different melting points as measured by the best
`way of measuring it, called differential scanning calorimetry.
`So you see on the right, Form B has 170 degrees
`and Form A is only 103 but, as we will see from the record,
`the '393 patent is clear that the form that's made and described
`there is Form B. So we can compare like-with-like. The
`value of T naught is unique for all Form B crystals. And so if
`we see a lower melting point we know that that is a less pure
`material.
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`The spelling here on slide 17, it should say "HPLC
`and purity" there. I want to talk briefly about HPLC assay.
`This is the only method of purity discussed anywhere in the
`'393 patent. It is the standard way of measuring purity. As
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`you will see here, they have one batch with a purity made by
`the '393 patent, 100.4. Another batch which was less pure,
`99.8. You will see also the melting points correspond. Okay.
`The higher melting point corresponds with the 100 percent
`pure material, and the lower melting point with the 99.8.
`The other thing you will see here is the HPLC for
`this measurement is above 100 percent. Why is that? As with
`all instrumentation there is a standard error in the
`measurement. That doesn't mean someone made a mistake.
`All equipment, it is a matter of science, all equipment has
`what is called an error to it.
`And you can see here that error is obviously at
`least .4 percent. And, in fact, as Dr. Winkler testified, the
`relative error is at least plus or minus 1 percent. And, in fact,
`as United Therapeutics stated in their own documents, here
`Exhibit 2006, which they provided to the FDA and in this
`case, they state the variability -- and here they are also
`including some other variabilities -- but they state the
`variability of the assay is about 2 percent.
`So that is standard for an HPLC measurement. So
`it is very difficult to distinguish two samples that are only
`tenths apart in purity.
`JUDGE HARLOW: I have a question for you on
`HPLC. Apologies. First regarding the 100.4 percent number
`that's presented in the table on slide 17, I understand that
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`Patent Owner has taken the position that the 100.4 percent
`number is actually because it is a comparison to a reference
`standard and, therefore, there is a relative increase.
`Is it your position that the .4 percent is error or do
`you agree with Patent Owner that we're comparing to a
`reference standard and, therefore, can exceed 100 percent?
`MR. POLLACK: I agree with both arguments.
`Reference standard is part of every HPLC measurement.
`There is no HPLC measurement that doesn't use a reference
`standard. That is one of the sources of error in HPLC. That's
`normal for HPLC. It is not a problem or a mistake or
`anything else.
`So you always have a reference standard. But
`when we look at, say, Moriarty, why does he report a purity?
`Well, because it's normal to compare purities to a reference
`standard, whatever one you have. They are all very near 100
`percent. Error is just something that can't be avoided.
`But we report these things because they are valid.
`These numbers are valid numbers. So if it is 100 percent, plus
`or minus 2 percent, that is a valid response from the
`instrument. Nothing wrong with that.
`The reference standard is simply a source of error.
`It is not something different from the error. It is one of the
`things that causes error in an HPLC analysis. Does that
`answer your question?
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`JUDGE HARLOW: Sort of. Perhaps I misheard.
`When you were speaking I took your argument or your
`comment to be that because the batch 1 value was above 100
`percent, that .4 must be error. But that's neither here nor
`there.
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`The question I'm more interested in is with regard
`to the 2 percent error. Is that 2 percent error related to HPLC
`equipment and measurements or does that incorporate other
`potential sources of error?
`I guess what I'm trying to understand, is that an
`absolute error a limitation on the measurement apparatus or
`does it incorporate other things?
`MR. POLLACK: The 2 percent, as you will see
`from their description, they say it is a 2 percent variability in
`the assay. So that is the number they are giving. I will tell
`you that our expert said plus or minus 1 percent is typical for
`HPLC assay. That's a relative error, by the way.
`So on 100, it so happens 1 percent of 100 is 1, or
`if you had, say, 1 percent, if you are measuring something that
`was 1 percent, a 1 percent error would be plus or minus .01.
`Does that make sense?
`JUDGE HARLOW: It does. And I would like to
`let you know that I believe you are just a bit over. It has been
`about 16 minutes.
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`Case IPR2016-00006
`Patent 8,497,393 B2
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`MR. POLLACK: All right. Thank you, Your
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`Honor.
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`(Pause)
`MR. MAEBIUS: We will give a copy of our slides
`to the court reporter.
`I would like to pick up with the 2 percent
`discussion first and here I'm on slide 16 for Judge Harlow. I
`think that the Petitioner is conflating the allowance in the
`FDA specification for treprostinil with an error rate.
`And what Dr. Winkler was mistaken about was that
`assay purity is relative to a standard and so the purity depends
`on what the standard is. And if the standard changes then the
`HPLC purity measurement is going to change for that.
`The 2 percent is actually an allowance above and
`below the mean purity that allows for batch-to-batch
`variation. So that if a given batch is, relative to the standard,
`is only 99 percent, even though the mean is 100 percent, it
`still falls within the specification and we would be allowed to
`sell that batch. So I just wanted to clarify that for you.
`JUDGE GREEN: Does the challenged patent give
`a reference standard?
`MR. MAEBIUS: I'm sorry, what was the question?
`JUDGE GREEN: Does the challenged patent
`provide a reference standard? Does it tell us what it is
`comparing it to, what that 100.4 percent represents?
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`Case IPR2016-00006
`Patent 8,497,393 B2
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`MR. MAEBIUS: The specification of the '393
`patent does not identify the reference and neither does the
`Moriarty reference.
`JUDGE GREEN: No, I know, but it's one way that
`you attack Moriarty but you don't have that -- you have the
`same issue.
`MR. MAEBIUS: Yeah, I understand the question
`and it doesn't disclose where the reference standard came
`from. But with respect to the examples that are presented in
`the '393 specification, they are selected by the inventors and
`they were against a common reference standard, otherwise
`they wouldn't have filed the application and signed the
`declaration indicating that they weren't --
`JUDGE GREEN: I understand that but we can also
`assume that Moriarty used a common reference standard. I
`mean, this is from the same group and everything else. So I
`think that that -- I don't know how much that is telling us that
`Moriarty didn't tell us what the reference standard is.
`MR. MAEBIUS: Understood. Understood. If I
`could go back to slide 13 at this point. I wanted to address a
`point that Petitioner has made with respect to the absence of
`functional differences. And here we show the various
`diethanolamine, Form B, the sample results from a very
`different process. It is derived from Form A.
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`Case IPR2016-00006
`Patent 8,497,393 B2
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`And what is shown in figure 21 as Form B is not
`actually a large-scale product but rather it is an analytical
`sample that was used for the polymorph screen. And we talk
`about this large-scale distinction in the Patent Owner
`Response at page 25 as well as in the Williams declaration at
`paragraph 73. And I think that being able to produce the
`pharmaceutical product on a large scale while meeting a
`purity specification encouraged by the FDA is, in fact, an
`important functional advantage of the '393 products.
`JUDGE GREEN: But none of that is reflected in
`the claims, correct? I mean, it doesn't require any scale, any
`amount, any -- claim 1 requires no purity level?
`MR. MAEBIUS: Right. The claim does not
`actually refer to it as a large-scale product. But the Patent
`Owner Response talks about how the large scale products --
`JUDGE GREEN: I understand that, but, you know,
`we need to focus on the claim. That was my only concern.
`MR. MAEBIUS: I think that if you focus on the
`claims they do recite steps A through C and the product that
`results inherently from steps A through C is, in fact, a
`large-scale product. By contrast --
`JUDGE GREEN: So you couldn't do those steps
`on a small scale?
`MR. MAEBIUS: What?
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`Case IPR2016-00006
`Patent 8,497,393 B2
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`JUDGE GREEN: You couldn't perform those steps
`on a small scale? Because you are telling me it has to be a
`large scale. But I don't see any reason why you couldn't
`perform that on a small scale, and is there anything in the
`specification that reflects that?
`MR. MAEBIUS: So we don't have any evidence
`one way or the other whether the process of deriving Form B
`from Form A could be performed on a large scale. That
`information isn't in the Phares reference and it wasn't
`provided by Petitioner as part of its petition.
`JUDGE GREEN: And your claims aren't drawn to
`any particular polymorph either, correct?
`MR. MAEBIUS: That's correct. The claims are
`generic. But, again, the prior art doesn't provide a -- for
`purposes of anticipation, there is not an actual specific
`example of Form B that was produced in this record.
`This slide also points out the physical difference
`of the '393 products compared to Phares. In fact, Dr. Rogers,
`Petitioner's expert, acknowledged that there were different
`melting point ranges between the '393 products and those of
`the prior art.
`And if you look at paragraph 72 and 82, he further
`states the different melting points mean different impurities.
`So regardless of the purity level, there is a different impurity
`profile between these products. And the impurity profile, the
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`Case IPR2016-00006
`Patent 8,497,393 B2
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`relative amounts of individual impurities is like a fingerprint
`that results from performing steps A through C, and that
`fingerprint is unique to the claims of the '393 patent.
`JUDGE GREEN: So are you reading the impurity
`profile into the claims by the use of the term "product" or are
`you using it by the term "steps" because comprising, one
`allows additional impurities and also allows additional steps,
`so I'm trying to understand how we are reading the impurity
`profile into claim 1?
`MR. MAEBIUS: If I could go back to slide 4, for
`Judge Harlow. Here we start to talk about claim construction.
`And I believe that if you consider the repeated references in
`the specification as well as what happened in the prosecution
`history, there is a clear disavowal of the subject matter and it
`relates to the fact that the claim uses the word "product" in
`two different places.
`So in the preamble of both independent claims you
`see that there is product at the very beginning and then there
`is a second reference to a product prepared by a process
`comprising steps A through C. And although the word
`comprising is present in both instances, you can't completely
`erase the meaning of steps A through C which are recited after
`that preamble.
`So it is our position that when you look at the
`claim as a whole and you look at what happened both in the
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`Case IPR2016-00006
`Patent 8,497,393 B2
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`specification where we have a side-by-side comparison -- and
`I'm going to slide 5 now, Judge Harlow -- we have a large
`scale side-by-side comparison in example 6 between the '393
`process and the Moriarty process.
`And we first indicate in the slide that there is a
`purity level that is higher in the case of '393, and then, going
`to slide 6, we further -- we continue example 6 in this slide.
`And the conclusion reached in the specification is
`that the impurities carried over from intermediate steps,
`alkylation of triol and hydrolysis of benzindene nitrile, are
`removed. So I think that is a reference to impurity profile in
`the specification.
`And then on top of that, we go to slide 7, where
`the prosecution history expressly refers to a difference in
`impurity profile and that is what is in the Walsh declaration
`where certain representative batches were compared to try to
`show the difference in impurity profiles.
`JUDGE HARLOW: Counsel, recognizing your
`discussion of the comparison of certain impurities between the
`Moriarty process and the '393 process, there is no where in
`the specification or in the file history where anybody, UTC or
`the Examiner says that the product is treprostinil plus the
`impurities left over after the '393 process. Isn't that correct?
`MR. MAEBIUS: That's correct. It doesn't use
`those exact words but it does say the impurity profiles are
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`Case IPR2016-00006
`Patent 8,497,393 B2
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`different. An impurity profile is a reference to the difference
`in individual impurities which are shown by name in the
`Walsh declaration.
`JUDGE HARLOW: But doesn't the wording of the
`claims themselves, and in particular I'm focusing on
`independent claim 9 and dependent claim 10, suggest that
`there is actually room for variation in the purity levels?
`So, for example, claim 10 specifically requires a
`purity of at least 99.5 percent which notably is lower than the
`purity arrived at in example 6, but there seems to be room in
`the claims for a variety of purity levels and it's difficult to
`reconcile that fact and the absence of any explicit definition
`of product with your position that we should deviate from the
`regularly legally-accepted meaning of the term product in this
`case.
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`MR. MAEBIUS: Yes, I understand that the
`independent claims don't recite a numeric impurity level. And
`because there is a dependent claim that does recite a purity
`level, you are struggling with that issue.
`But I think the prosecution history shows that we
`disclaimed a purity level that results from the Moriarty
`process. And whatever our purity level is, it is above
`Moriarty. And even if there is, you know, some equivalence
`or similarity in purity levels, the impurity profile, which,
`again, is that fingerprint of the relative amounts of individual
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`Case IPR2016-00006
`Patent 8,497,393 B2
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`impurities in the Certificates of Analysis that were presented
`in the Walsh declaration, at least that will be different and a
`unique way of identifying the product that results from the
`process.
`
`JUDGE HARLOW: Two questions in that regard:
`Moriarty itself reports a purity level of 99.7 percent. Is it
`your position then that the prosecution history would disclaim
`any purity below 99.7 percent as set forth in the reference?
`MR. MAEBIUS: Well, that's not our position
`because we don't know what reference standard the Moriarty
`publication was using.
`JUDGE HARLOW: But you don't know what
`reference standard the '393 patent used either.
`MR. MAEBIUS: Well, we know that it results
`from performing steps A through C and that the product as a
`result of performing the salt purification step will be higher
`impurity than a comparable product that was carried out in
`Moriarty. And, again, I go back to example 6, as that
`side-by-side comparison.
`JUDGE HARLOW: But aren't you ignoring the
`various reagents used in the '393 process that aren't recited in
`the claim as well as the reaction conditions and any other
`number of aspects of the process you actually used to create
`treprostinil that may have contributed to the impurity level?
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