Trials@uspto.gov
`571-272-7822
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`Paper No. 55
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________
`
`AMNEAL PHARMACEUTICALS LLC, AMNEAL
`PHARMACEUTICALS OF NEW YORK, LLC, and MYLAN
`PHARMACEUTICALS INC.,
`Petitioners
`
`v.
`
`ALMIRALL, LLC,
`Patent Owner.
`
`__________
`
`Case IPR 2019-00207
`Patent 9,517,219 B2
`
`
`__________
`RECORD OF ORAL HEARING
`Oral Hearing Held: February 7, 2020
`
`__________
`
`
`Before SUSAN L. C. MITCHELL, CHRISTOPHER G. PAULRAJ,
`and RYAN H. FLAX, Administrative Patent Judges.
`
`
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`571-272-7822
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`
`
`
`Paper No. 55
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________
`
`AMNEAL PHARMACEUTICALS LLC, AMNEAL
`PHARMACEUTICALS OF NEW YORK, LLC, and MYLAN
`PHARMACEUTICALS INC.,
`Petitioners
`
`v.
`
`ALMIRALL, LLC,
`Patent Owner.
`
`__________
`
`Case IPR 2019-00207
`Patent 9,517,219 B2
`
`
`__________
`RECORD OF ORAL HEARING
`Oral Hearing Held: February 7, 2020
`
`__________
`
`
`Before SUSAN L. C. MITCHELL, CHRISTOPHER G. PAULRAJ,
`and RYAN H. FLAX, Administrative Patent Judges.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Case IPR 2019-00207
`Patent 9,517,219 B2
`
`
`
`
`APPEARANCES:
`
`ON BEHALF OF THE PETITIONERS:
`DENNIES VARUGHESE, Pharm. D., ESQ.
`ADAM C. LaROCK, ESQ.
`of: Sterne, Kessler, Goldstein & Fox
`1100 New York Avenue NW
`Suite 600
`Washington, D.C. 20005
`(202) 371-2600
`dvarughe@skgf.com
`alarock@sternekessler.com
`
`
`ON BEHALF OF THE PATENT OWNER:
`
`
`JAMES TRAINOR, ESQ.
`ELIZABETH HAGAN, Ph.D., ESQ.
`of: Fenwick & West, LLP
`902 Broadway, Suite 14
`New York, New York 10010
`212-430-2600
`jtrainor@fenwick.com
`ehagan@fenwick.com
`
`
`
`
`The above-entitled matter came on for hearing on Friday,
`
`February 7, 2020, commencing at 1:00 p.m. at the U.S. Patent
`and Trademark Office, 600 Dulany Street, Alexandria, Virginia
`
`
`
`Case IPR 2019-00207
`Patent 9,517,219 B2
`
`
`
`P-R-O-C-E-E-D-I-N-G-S
`
` 1:01 p.m.
`JUDGE FLAX: Okay. Good afternoon, everybody.
`MR. VARUGHESE: Good afternoon, Your Honor.
`JUDGE FLAX: I'm Judge Flax and we are here with Judge
`Mitchell and Judge Paulraj.
`We are here today for IPR 2019-00207, and to that has been
`joined IPR 2019-01095.
`If you all are not here for those, you are in the wrong room.
`I know that we've got a lot of issues to deal with today, the
`first of which, I know that someone intends to show some confidential
`information, or discuss confidential information during the hearing.
`Is that still accurate?
`MR. VARUGHESE: Good afternoon, Your Honor. Dennis
`Varughese for Petitioner Amneal. The confidential information, I
`think, implicated a deposition transcript of Inventor Warner that we
`received a few weeks ago.
`We included some flagged demonstratives in our
`demonstrative kit, but we are happy to rest on our supplemental
`briefing and not delve into any of that at this public hearing, if that
`resolves the issue.
`JUDGE FLAX: Well, I won't tell you what to do, of course,
`that would probably be the easiest way to do it. We wouldn't have to
`decide who stays in the room and who doesn't stay in the room. So --
`MR. VARUGHESE: We're happy to do that.
`JUDGE FLAX: -- if that is how you want to do it, that is
`fine. All right, then, if everyone is ready we can begin.
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`Case IPR 2019-00207
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`So, we'll start with Petitioner's case. Each side is going to
`have an hour to make their arguments. But when you get up and
`introduce yourself you can let me know if you want to reserve some
`time for rebuttal afterwards.
`So, that being said, if Petitioner's case wants to proceed --
`when you are ready.
`MR. VARUGHESE: Good afternoon, Your Honors. If it
`pleases the Board, my name is, once again, Dennies Varughese, from
`the law firm of Sterne, Kessler, Goldstein and Fox and we represent
`Petitioner.
`Joining me today is Adam LaRock and Tyler Liu, also of
`Sterne Kessler. And the client representative, Mr. Bryan Sonmese, is
`here from Amneal.
`MR. MALIK: Your Honor, also, I'm Jitendra Malik. I'm
`counsel for Amneal.
`JUDGE FLAX: And sir, do you want to reserve any time for
`rebuttal?
`MR. VARUGHESE: Yes. I would like to reserve 15 minutes
`for rebuttal, Your Honor.
`JUDGE FLAX: Okay.
`MR. VARUGHESE: Slide 2.
`Your Honors, both sides have submitted a voluminous record
`for the Board to consider and it's certainly not my intention to go over
`every single point of our case. But in terms of a quick overview, I'd
`like to discuss the three references that form the basis of both of the
`grounds: the Garrett Reference, Nadau-Fourcade, and Bonacucina,
`and discuss where each and every limitation of the claims is disclosed
`in those references and then spend a few minutes addressing some of
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`Case IPR 2019-00207
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`the arguments that Almirall has put forward here in trying to rebut
`what we believe is a strong prima facie case and then conclude by
`discussing the relevant objective indicia and how they don't apply here
`to save the patent from the prima facia case.
`Slide 4.
`Your Honor --
`JUDGE FLAX: Could I ask you a quick question before you -
`- we get into it?
`MR. VARUGHESE: Yes.
`JUDGE FLAX: Are the definitions between the parties of the
`person of ordinary skill in the art the same, or are they not the same,
`and are they being argued today?
`MR. VARUGHESE: To my knowledge, Your Honor, I don't
`think we have disputed the level of skill or whether, to the extent there
`is any minor differences, whether they impact case, that's our
`approach. I was not intending to argue that today.
`JUDGE FLAX: Okay.
`MR. VARUGHESE: So, on Slide 4, the '219 Patent contains
`eight claims -- two independent claims that are nearly identical.
`So, this is Claim 1, and I don't think there is a dispute. The
`Parties have been operating as if all claims rise and fall together.
`There has been no special arguments put forward for any of the
`claims.
`Claim 1 recites a method of treating a dermatological
`condition consisting of acne and rosacea. Using a formulation that
`contains about seven and a half percent of dapsone, about 30 to 40
`percent of a solvent known as DGME --
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`Patent 9,517,219 B2
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`JUDGE FLAX: Now, I have a question about that
`introduction. You had described this as treating acne and rosacea.
`MR. VARUGHESE: Or.
`JUDGE FLAX: It is or, right?
`MR. VARUGHESE: Yes.
`JUDGE FLAX: So, we don't really need to focus on rosacea
`very much at all here.
`MR. VARUGHESE: That is Petitioner's position, Your
`
`Honor.
`
`JUDGE FLAX: Okay. Go ahead.
`MR. VARUGHESE: The next limitation is about two percent
`to about six percent of a polymeric viscosity builder. And I am not
`going to butcher the full name -- the scientific name, but we will refer
`to it as the gelling agent, the thickener, PVB, the copolymer -- these
`are all synonymous. And I don't think there is a dispute about this,
`but we will hear from Mr. Trainor later. We are treating that
`limitation as being synonymous with a commercially available
`product called Sepineo.
`Sepineo is a commercially available brand of the acrylamide
`copolymer. In the Claim 1 also has water in the formulation and then
`recites that the formulation does not contain adapalene.
`Slide 5. Independent Claim 6 is essentially identical to Claim
`1, except for the three numerical ranges or except for the two ranges
`for the solvent and the copolymer. Claim 6 recites -- specifies a
`specific numeric value -- so, 30 percent for the solvent and four
`percent for the copolymer. Slide 7.
`With that Your Honors, as we put forward in our papers, the
`combination of references for each of the ground: Garrett and Nadau-
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`Case IPR 2019-00207
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`Fourcade for Ground 1, and Garrett and Bonacucina for Ground 2,
`disclose every limitation of challenge claims. Slide 8.
`Let's start with Garrett, the primary reference in both grounds.
`Garrett discloses a method of treating acne and rosacea comprising a
`formulation that has dapsone. Slide 9.
`And this is a little bit of a busy slide with a lot of color, so I
`just want to spend about 30 to 60 seconds walking Your Honors
`through it. This is the disclosures in Garrett that teaches essentially
`all of the other limitations of Claim 6.
`In orange, we have Garrett disclosing five to ten percent of
`dapsone and the claim seven and a half percent falls rarely within that
`range. In yellow, we have Garrett disclosing ten -- about ten to 30
`percent of ethoxydiglycol. And that overlaps with -- well, it captures
`the 30 percent recited in Claim 6 and overlaps with the 30 to 40
`percent of the solvent in Claim 1. And in green, we have Garrett
`disclosing the use of water in this formulation.
`In the red box we make it a point that Garrett omits any
`mention of adapalene. And in our papers we've put forward Federal
`Circuit cases that say that type of omission is sufficient to meet the
`negative limitation of no adapalene.
` But beyond that, we are going to talk about some of the
`positions that patent owners take into prosecution that reinforces our
`position.
`And in the red underline -- that is the only limitation that is not
`expressly taught in Garrett, that's in the claims. Which is the -- yes --
`JUDGE PAULRAJ: Counsel, with respect to the DGME,
`requirement 30 percent, so, it's your position that that's an overlap at
`the 30 percent point? Is that right?
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`Case IPR 2019-00207
`Patent 9,517,219 B2
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`MR. VARUGHESE: Yes, Your Honor. Our position is that
`it's an overlap because Garrett talks about -- about 10 to 30 percent.
`JUDGE PAULRAJ: Okay. Is there anything in the record
`from your expert about what -- about what type of deviation would
`about would encompass in these percentages.
`
`MR. VARUGHESE: I don't believe we've had our expert
`opine on the level of deviation for about.
`JUDGE PAULRAJ: Okay. And my next question on this
`point is, isn't there Federal Circuit case law more or less saying that
`the disclosure of an end-point is no more a disclosure than any other
`point within the range?
`So, you know, it does seem a bit tenuous to say that 10 to 30
`percent is necessarily teaching of 30 percent.
` Is -- can you address that case law to us if you are familiar
`with it?
`MR. VARUGHESE: I can. I'm going to ask my colleague to
`maybe -- to find a specific cite. I recall in our papers, we discuss case
`law that talks of abutting ranges, which is, you know, interfacing with
`the ranges Your Honor mentioned.
`We've also taken the position that Garrett's disclosure of about
`30 percent goes beyond. To what extent, we have not had an expert
`opine on the extent, but certainly -- about -- it is well settled that it
`goes beyond the actual numerical figure.
`JUDGE PAULRAJ: Okay. And I think you hit the nail on the
`head there, because I think there is a distinction in our analysis
`between abutting ranges and overlapping ranges. Because, as you
`know, in the DuPont case, which was discussed extensively in the last
`round when we were here, there is a presumption of obviousness with
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`respect to overlapping ranges. I don't know if that presumption
`applies to abutting ranges. Do you agree with that?
`MR. VARUGHESE: Your Honor, I think the presumption
`does apply with abutting ranges, but give me a chance to maybe, clear
`the record there.
`JUDGE PAULRAJ: Okay. Thank you. I understand. I'll let
`you pursue it. Thank you.
`MR. VARUGHESE: Since Your Honor brought up this point,
`I'd like to maybe skip ahead to another slide.
`
`MR. VARUGHESE: Slide 60.
`This is a separate teaching in the prior art. From a reference --
`and I want to talk about this a little bit later on for some other points --
`but this is from the Osborne reference. This is a prior art reference
`that Patent owner relies on for some of its arguments.
`Osborne, coincidentally, is also the same Dr. Osborne that
`served as an expert in this proceeding. In this reference, Dr. Osborne,
`in discussing the prior art five percent dapsone gel product, says that
`approximately one-third of the dapsone is dissolved and two-thirds of
`the dapsone is suspended. So, in his view, that was an optimal ratio of
`dissolved to undissolved.
`And this graph comes straight from that prior art reference.
`And Dr. Michniak-Kohn, in her report, took this graph --
`JUDGE FLAX: When -- either the '219 patent or Garrett talk
`about amounts of dapsone in their gels?
`MR. VARUGHESE: They do not. Garrett -- Garrett talks
`about -- well, they talk about the concentration of dapsone, but neither
`Garrett nor the '219 patent talks about what ratio should be dissolved
`or undissolved.
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`JUDGE FLAX: Right. That's fine. But when they are talking
`about the percentage of the gel that is dapsone, are they referring to
`that generally in terms of how much is dissolved and how much is not
`dissolved, meaning either/or, or both together, or how are they
`describing them?
`MR. VARUGHESE: I think the seven and a half percent
`refers to the entire dapsone in the formulation itself. It does not
`demarcate according to how much of that percentage is in the dissolve
`phase or and undissolved phase. But Garrett teaches you can have
`dissolve, undissolved, or a mixture of the two in a microparticulate.
`It further teaches a POSA, that depending on what the POSA
`desires, they can manipulate different parameters to choose the
`desired gel viscosity and the ratio. This is a specific teaching that says
`that, one third dissolve to two thirds suspended is particularly
`beneficial. And then, a POSA would be aware of this. And what Dr.
`Michniak-Kohn did looking at graph, a POSA wanted to do seven and
`a half percent, using this chart, which is the known solubility curve of
`dapsone in DGME. One-third of seven and a half percent would be
`two and a half percent. When you go to the Y-axis the two and a half
`percent and you just follow that curve predictably, it puts you smack
`dab in that 30-40 range and right near 30.
`So, this is an additional teaching that would provide a POSA
`with knowledge on exactly how much DGME to use for the desired
`amount of dapsone.
`JUDGE FLAX: So, that is an interesting point that you are
`bringing up.
`So, this is an Osborne patent and in the record there is a lot of
`other prior art patents that are not necessarily part of the combination
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`Case IPR 2019-00207
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`of prior art that you are asserting. It is not Garrett and
`Nadau-Fourcade and it's not Garrett and Bonacucina.
`Is your position that that's just supportive of the general
`knowledge that is out there and what the skilled artisan would be
`bringing to the table when they were making this new formulation? Is
`that why you are citing it?
`MR. VARUGHESE: Yes, Your Honor. It speaks to a person
`of ordinary skill's knowledge base.
`Now certainly, our grounds are based on Garrett and
`Nadau-Fourcade and then Garrett and Bonacucina and we believe that
`all the limitations are taught there and a POSA would have had
`various motivations to combine those references as taught.
`
`However, both sides have discussed various other prior art
`literature to provide context for what that POSA's knowledge base is.
`A POSA is presumed to be aware of all the prior art and if a POSA
`doesn't, you know, look at the references in a vacuum, a POSA looks
`at it with ordinary skill and ordinary knowledge. Slide 11.
`Now DGME was known in the art both through Garrett, which
`refers to DGME as a preferred solvent and specifically discussing it in
`the context of a dapsone topical formulation. And then, DGME was
`also known to be the solvent that was used in the predecessor
`ACZONE five percent product. And this is the ACZONE label that
`shows that DGME was used as a solvent. Slide 13.
`JUDGE FLAX: That is Patent Owner's product?
`MR. VARUGHESE: That is Patent Owner's product.
`PARTICIPANT: ACZONE five percent?
`MR. VARUGHESE: Yes.
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`Slide 13. Garrett further teaches a POSA that the relative
`percentages for each of the reagents used in the present invention may
`vary depending upon the desired strength of the target formulation,
`gel viscosity, and the desired ratio of microparticulate to dissolved
`dapsone.
`So, this is all within the purview of a POSA, here a highly
`trained, highly experienced pharmaceutical formulator. Garrett is
`telling a POSA, depending on what the POSA desires, you can
`manipulate the formulation to achieve that.
`So, with luck, you soften the Osborne reference. One POSA
`was teaching the public that one-third dissolved to two-thirds
`dissolved is optimal. But, a POSA may want a different ratio and they
`can achieve that by manipulating the formulation.
`JUDGE FLAX: I know that one of the arguments that was
`made by patent owner was that no skilled artisan would go to Garrett,
`because they say, for one example, that at the time of 2012 dapsone
`was not in favor, people didn't think it worked -- that is one argument.
`And there is another argument, they said that the class of
`patients -- the DG -- I'm sorry -- you -- help me with it -- DG --
`MR. VARUGHESE: DGME?
`JUDGE FLAX: No, D -- I'm sorry, G6PD deficient patients,
`that are warned on the FDA labeling of the ACZONE product, that
`they need to be specially cared for because dapsone on its own can
`cause some problems for these people.
`But, by the time of 2012, that had generally been dispelled,
`even though the label still said that this was a class of patients that
`needed to be taken care of.
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`So, what is your response to that -- that Garrett was not going
`to be a reference that they would look at for those reasons?
`MR. VARUGHESE: So, I would like to ask Your Honor's
`question in the reverse, if that's okay?
`JUDGE FLAX: Sure.
`MR. VARUGHESE: With the concern over the G6
`deficiency, as Your Honor recognized and we put forward in our
`papers, all those concerns were resolved.
`But, even if -- let's say those concerns still persisted, we
`identified a case law, both from this Board and from the Federal
`Circuit, that says that concern over side effects is not a prohibition, it's
`a caution. If anything, being aware of a certain side effect actually
`tends to show more obviousness, that a POSA was aware of these
`considerations and a POSA -- here you have two POSAs -- you have a
`formulator and a clinician -- a POSA would know how to screen
`patients and make sure that patients with that deficiency are properly
`addressed.
`And keep in mind, dapsone -- oral dapsone -- was more of a
`concern for that deficiency than topical dapsone, even though that
`caution was still on the label.
`JUDGE FLAX: So, I -- I sort of took it, your argument, to be
`that, and correct me if I'm wrong, that you've got a five percent
`product on the market. It has this label that warns you about the
`G6PD deficient patients. The general knowledge in the field became
`that that was not so much of a concern anymore. So, that was
`somewhat of a reason to up the dose.
` Is that -- am I mistaken in that?
`MR. VARUGHESE: You are not mistaken.
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`I think our position was, given that that concern was being
`resolved, it's certainly not a reason to dissuade a POSA. Right?
`Garrett teaches the seven and a half range in the five to ten range that
`it discloses. So, it teaches a seven and a half percent.
`Almirall's argument was, well, a POSA wouldn't have thought
`to go from five to seven and a half because of these concerns. And
`what we are saying is, no, those concerns are not a teaching away.
`Those concerns would not have dissuaded a POSA. In fact, given the
`fact that those concerns had been alleviated by 2012, a POSA would
`have readily sought to increase the formulation without those
`problems.
`JUDGE FLAX: It seemed to me upon a reading Garrett, that
`what it was doing was confirming what was known in the field, which
`was that this class of patients was really not that much of a concern,
`therefore, here is a range up to ten percent that you might want to
`consider for dapsone.
`MR. VARUGHESE: And that is how we discussed Garrett.
`That is exactly right.
`JUDGE FLAX: Which is why they showed the safety data
`relating to the commercial product.
`MR. VARUGHESE: Correct.
`JUDGE FLAX: Am I understanding it correctly?
`MR. VARUGHESE: You are understanding it and that is how
`we've characterized Garrett also, both in the, our -- in the reply and
`then also in our petition.
`And then to your first question, that dapsone doesn't work, or
`dapsone is not that good -- dapsone works. It's FDA approved. It is
`in the prior art.
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`Other than that, their own experts, Dr. Kircik in this
`proceeding, Dr. Harper in another related proceeding, over the related
`patent, prior to 2012, published multiple times and publicly spoke
`about the effectiveness of dapsone for acne. Moreover, we are not
`here to say that dapsone is the best treatment for acne. If Almirall's
`point is, there might be other treatments that are more favored or more
`popular with physicians, it is black letter Federal Circuit Law, but that
`doesn't negate obviousness.
`Something doesn't have to be the most obvious solution in
`order to be unpatentable. Slide 15.
`And just for completeness on that, I'm not going to spend
`much time here. This is just a slide that depicts where the rest of the
`limitations from the dependent claims can be found in Garrett.
`Slide 17 -- actually, slide 16.
`So, Your Honor, we talked about where the limitations are
`found. The central question in this case is, would a POSA, having --
`looking at Garrett, have a reason to switch out the Carbopol; that is
`the copolymer, the hydrophilic copolymer disclosed in Garrett, and
`use Sepineo instead? Any reason?
`And, by preponderance of the evidence, and we submit that
`the evidence we've put forward in this record is overwhelming that a
`POSA had more than ample reason to use Sepineo instead of the
`Carbopol in Garrett. Slide 17.
`Garrett teaches that hydrophilic and hydroalcoholic gelling
`agents are frequently used for this type of formulation. And Garrett,
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`again, deals specifically with dapsone. Nadau-Fourcade teaches a
`POSA that Sepineo is a particularly preferred hydrophilic gelling
`agent. And Slide 18.
`Dr. Michniak-Kohn opined after reading Nadau-Fourcade that
`Nadau-Fourcade was Sepineo and Carbopol side-by-side in a finite
`list of four different gelling agents that can be used. So, I think under
`the Federal Circuits case, as we put up forward there, this case
`presents a strong case of obviousness based on the prior art references
`of record. All that was required to obtain the claim combination was
`to substitute one, well known gelling agent for another. This is a
`textbook case of interchangeability.
`JUDGE FLAX: Well, I don't necessarily disagree with what
`you are saying here, but I do have a question about it.
`The Carbopol that is used in Garrett, is used at certain
`percentages in the overall formulation. Assuming that one could
`substitute Sepineo for Carbopol in some way, are the percentages
`going to be the same? And how do we know that?
`Because what I see from some of your evidence, is that -- and
`let's talk about, for example, the work that Dr. Warner had done
`building up to his patent application. It looked like different amounts
`of Carbopol versus Sepineo were being used, for some reason, and I
`don't know what that is, but it presents to me a question of whether or
`not it is a one-for-one sort of swap, or, you know you can swap it, but
`you have to use different amounts, or what?
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` I don't know what the answer is. Can you shed some light on
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`that?
`
`MR. VARUGHESE: Sure. And to answer that question let
`me go to Slide 19.
`So, this is another case in the Federal Circuit that we've relied
`on -- the Interactive Pictures case -- where the court said, rather than
`focusing on physical or electronic compatibility, the known
`interchangeability test looks at the knowledge of the skilled artisan to
`see whether that artisan would contemplate the interchange as a
`design choice. And what that means is, it doesn't require absolute
`identity for something to be interchangeable.
`Rather, the question is, at the time of invention would the
`POSA view those two components -- those two ingredients -- as a
`design choice. Would he obviously use one or the other, or one over
`the other?
`In terms of percentages -- we turn to Slide 20 -- 23, 23 and
`24. So, Garrett discloses that it's a gelling agent, generally. It
`doesn't talk specifically about Carbopol. It should be about 0.2
`percent to about four percent by weight of the composition.
`Nadau-Fourcade, in talking about hydrophilic gelling agents,
`has a very similar range, 0.01 percent to five percent. And then, the
`other reference from the second ground, Bonacucina -- we turn to
`slide 40, discloses Sepineo specifically should be about 0.5 to five.
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`MR. VARUGHESE: I think the point here is these prior art
`references don't have to tell you exactly which point to go to. Again,
`we're talking about a POSA.
`And I think a POSA seeing these three references that all talk
`about related concepts, gelling agents, hydrophilic gelling agents and
`Sepineo specifically are all teaching a POSA that there's a similar
`range.
`
`There's a similar range within which to operate. And the
`question is prospectively looking at in 2012 based on this art, would a
`POSA have found it obvious one, to use Sepineo instead of Carbopol
`and whether a POSA would have found it obvious to use four percent
`or two to six percent.
`And we think based on these teachings absolutely, especially
`given the experience level of the POSA.
`JUDGE FLAX: So, Garrett teaches us .2 percent to four
`percent generally for a gelling agent?
`MR. VARUGHESE: For gelling agents.
`JUDGE FLAX: And Nadau-Fourcade teaches what?
`MR. VARUGHESE: 0.01 to five percent for hydrophilic
`gelling agents which is what she was dealing with there.
`JUDGE FLAX: 0.001 to 15 percent?
`MR. VARUGHESE: No, sir. It's on Slide 24. It's 0.01 to five
`percent is Nadau-Fourcade.
`JUDGE FLAX: Most preferably. But it's got a larger range
`there as well, Page 11 of Nadau-Fourcade.
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`MR. VARUGHESE: It's got a larger range there. But I think
`the fact that she highlights the most preferred range is going to be
`particularly useful to the POSA. And, Your Honors, I apologize. I
`have demonstratives to hand out.
`I should have said that at the beginning. I don't know if Your
`Honors would like us to hand out hard copies of demonstratives.
`JUDGE FLAX: Sure. You should keep going.
`MR. VARUGHESE: And just to complete that answer, Your
`Honor, under the Federal Circuit's DuPont case these percentages are
`a result effective variable.
`That number one, I think they teach very similar ranges and
`they're all related publications unless there's something critical or
`special by way of teaching away unexpected results, some showing
`that it's not a result effective variable which they've not done here.
`The presumption is that the claimed amounts of Sepineo are
`obvious in view of the teachings of Garrett, Bonacucina and
`Nadau-Fourcade.
`JUDGE FLAX: Well, let's talk about unexpected results.
`MR. VARUGHESE: Yes.
`JUDGE FLAX: Let's talk about the Ostwald ripening which is
`the one that I'm particularly interested in. That's kind of a new one
`here since the institution stage.
`What I see looking at the prosecution history is that the
`declaration by Dr. Warner during the prosecution does discuss particle
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`size to some degree. He's got a paragraph, maybe a paragraph and a
`half about it. Let me pull that up here.
`So, I know that the Patent Owner is arguing that Sepineo is
`providing an unexpected benefit here because when it’s used the
`particles are roughly half the size, let's say, that they are when the
`Carbopol is used. Am I accurately reading the evidence?
`MR. VARUGHESE: I think that's their argument, yes.
`JUDGE FLAX: And so, what I also see is that from, am I also
`right that the only evidence about this is in the Warner declaration in
`the prosecution history?
`MR. VARUGHESE: That's the only evidence regarding the
`particle size issue, that's correct.
`JUDGE FLAX: Upon which their expert gave opinion?
`MR. VARUGHESE: Dr. Osborne gave an opinion, correct.
`JUDGE FLAX: So, my understanding of Ostwald ripening is
`not that of an expert. But what I read in Paragraph 9 of the Warner
`declaration, which seems to be the one that matters on this issue, is
`that you've got different particle sizes.
`The better one was with Sepineo. And it says the data shows
`that recrystallized dapsone particle size is smaller in the Sepineo P600
`formulation as compared to a Carbopol 980 formulation.
`I
`observed, that's Dr. Warner observed, this difference even after six
`months storage under accelerated conditions, 40 degrees Celsius RH,
`75 percent RH thereby showing no significant change in the particle
`size over time.
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`This data suggests that particle size does not change over time
`irrespective of the stabilizer used Carbopol or Sepineo. So, to me this
`presents some ambiguity.
`There seems to be a lot of argument and evidence in this case
`that this Ostwald ripening is something that happens when you have a
`non-dissolved particle in a gel. What this seems to be saying is that
`it's not happening no matter which gelling agent you use.
`Now, perhaps when you started out the size of one was
`different than the other. But neither one changed over six months
`when Dr. Warner seems to have been trying to force a change. Am I
`reading that correctly?
`MR. VARUGHESE: You are. There's another part to it. But
`let me address this. I think what Almirall has done with particle size
`is they have made two unexpected results arguments.
`One, is this focus on Ostwald ripening which I think there's
`some relation to, but different than the particle size itself. So, let's talk
`about Ostwald ripening.
`As Dr. Michniak-Kohn put forward in her testimony, Ostwald
`ripening is this dynamic where particles that are suspended, whether
`in a gel or in a liquid suspension or oil suspension, they could have a
`tendency to sort of agglomerate and clump together.
`But that's a problem that's been known for decades in
`pharmaceutical formulation. And when a formulator or a company
`sets out to develop a gel or suspension
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