trials@uspto.gov
`571-272-7822
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`IPR2015-01205, Paper No. 36
`September 27, 2016
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`AKORN, INC.,
`Petitioner,
`
`v.
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`SENJU PHARMACEUTICAL CO., LTD, MITSUBISHI
`CHEMICAL CORPORATION,
`Patent Owner.
`____________
`
`Case IPR2015-01205
`Patent 6,114,319
`____________
`
`Held: September 7, 2016
`____________
`
`
`
`BEFORE: DEBORAH KATZ, JACQUELINE WRIGHT
`BONILLA, and GRACE KARAFFA OBERMANN,
`Administrative Patent Judges.
`
`
`
`The above-entitled matter came on for hearing on Wednesday,
`September 7, 2016, commencing at 10:03 a.m., at the U.S. Patent
`and Trademark Office, 600 Dulany Street, Alexandria, Virginia.
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`571-272-7822
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`IPR2015-01205, Paper No. 36
`September 27, 2016
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`AKORN, INC.,
`Petitioner,
`
`v.
`
`SENJU PHARMACEUTICAL CO., LTD, MITSUBISHI
`CHEMICAL CORPORATION,
`Patent Owner.
`____________
`
`Case IPR2015-01205
`Patent 6,114,319
`____________
`
`Held: September 7, 2016
`____________
`
`
`
`BEFORE: DEBORAH KATZ, JACQUELINE WRIGHT
`BONILLA, and GRACE KARAFFA OBERMANN,
`Administrative Patent Judges.
`
`
`
`The above-entitled matter came on for hearing on Wednesday,
`September 7, 2016, commencing at 10:03 a.m., at the U.S. Patent
`and Trademark Office, 600 Dulany Street, Alexandria, Virginia.
`
`
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`Case IPR2015-01205
`Patent 6,114,319
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`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER:
`
`
`ELDORA LYNN ELLISON, Ph.D., ESQUIRE
`CHANDRIKA VIRA, ESQUIRE
`SANA F. HUSSAIN, ESQUIRE
`Sterne, Kessler, Goldstein & Fox, PLLC
`1100 New York Avenue, N.W.
`Washington, D.C. 20005
`
`ON BEHALF OF PATENT OWNER:
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`
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`JOHN KAPPOS, ESQUIRE
`FILKO PRUGO, ESQUIRE
`O'Melveny & Myers, LLP
`610 Newport Center Drive
`Seventeenth Floor
`Newport Beach, California 92660
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`Case IPR2015-01205
`Patent 6,114,319
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`P R O C E E D I N G S
`- - - - -
`JUDGE KATZ: Okay. I think we'll get started. Good
`morning. This is an oral argument for inter partes review number
`2015-01205. The petitioner is Akorn, Inc., and patent owners are
`Senju Pharmaceutical Company Limited and Mitsubishi
`Chemical Corporation. I am Judge Katz. Judge Bonilla is on my
`right and Judge Obermann is on my left.
`And before we get started, I would like to point out a
`few housekeeping things. The hearing is open to the public, and
`a full transcript of it will become part of the public record, just so
`you know. Each party has been accorded 45 minutes in total to
`present their arguments. Petitioner will go first followed by the
`patent owner. There is no motion to amend in this case. So the
`petitioner carries the burden and may reserve rebuttal time.
`Counsel should not interrupt the other side when
`making objections. And if you have objections, you can discuss
`them during your argument but not -- please don't interrupt the
`other side.
`When you refer to an exhibit when you are presenting
`your argument, please indicate that in numbers, either the slide
`number, the exhibit number, the page number, the line number,
`whatever you are referring to so that the record is complete
`because the transcript will obviously only have what you say. So
`please don't just gesture.
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`So now if counsel for petitioner, if you could introduce
`yourself and those with you, please.
`MS. ELLISON: Good morning, Your Honor. I'm
`Eldora Ellison from Sterne, Kessler, Goldstein & Fox. I have
`with me my backup counsel, Chandrika Vira and Sana Hussain.
`JUDGE KATZ: Thank you. And for patent owners,
`please introduce yourself.
`MR. KAPPOS: Good morning, Your Honors. I'm John
`Kappos from O'Melveny & Myers, and I represent Senju
`Pharmaceuticals, Mitsubishi Chemical and Alcon, the licensee
`under the '319 patent. And I'm joined today by my partner, Filko
`Prugo and Barry Copeland from the legal department at Alcon.
`JUDGE KATZ: Thank you. So petitioner, would you
`like to reserve time?
`MS. ELLISON: Yes, Your Honor. I would like to
`reserve ten minutes for rebuttal.
`JUDGE KATZ: So I will set this at 35 minutes and
`note that you have ten minutes. Whenever you are ready, I'll start
`the clock when you let me know.
`MS. ELLISON: May it please the Board, I would also
`like to split the argument with my backup counsel, Chandrika
`Vira, if you don't mind. I will address the prima facie case and
`I'll spend about 25 minutes doing that, and she will address
`objective indicia and spend about ten minutes. And that will
`leave us ten minutes for rebuttal.
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`
`So we, of course, have prepared demonstratives. If you
`would like paper copies, we have those available to you and can
`give them to you if you would like to have paper copies.
`JUDGE KATZ: Sure.
`MS. ELLISON: Yes, if we may approach the bench.
`So we have provided on slide 2 an overview of our arguments
`which is that all of the challenged claims would have been
`unpatentable for obviousness over a combination the '848 patent,
`which is also known as Kimura, and the Ding reference. Ding
`discloses emulsions and the '848 patent discloses suspensions of
`difluprednate, difluprednate being the active ingredient here. We
`also will address Senju's objective indicia arguments.
`Turning to slide 3, we've set forth the independent
`claims. There are two of them, claims 1 and 18. Our opponents
`have not made any separate arguments regarding patentability of
`any of the dependent claims. So all of the dependent claims fall
`together with these independent claims. Claim 18 is more narrow
`in scope than claim 1 and thus falls within claim 1. So most of
`the arguments have been directed specifically to claim 18 since
`that will of course also address claim 1.
`What you see is a claim composition. And it's
`important to remember that the claims are directed to
`compositions because many of our opponent's arguments pretty
`much act like these claims are method claims, but they are not.
`They are composition claims directed to a difluprednate emulsion
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`in the form of an eye drop, nasal drop or ear drop. And the
`emulsion, the composition comprises difluprednate, castor oil,
`water and polyoxyethylene 20 sorbitan monooleate. Those last
`three ingredients are important for making the emulsion. The
`polyoxyethylene 20 sorbitan monooleate is also known as
`polysorbate 80. And so you'll see many references to polysorbate
`80.
`
`We submit that the '848 patent discloses a difluprednate
`emulsion and thus it discloses the difluprednate -- excuse me, a
`difluprednate suspension and thus it provides the difluprednate
`that we use in combination with the Ding reference to render the
`claims obvious. The Ding reference relates to an emulsion that's
`used for formulating poorly water soluble drugs such steroids.
`And difluprednate is a poorly water soluble drug. There's no
`dispute about that in the record.
`So let's first take a quick look at the state of the art. Of
`course we view this through the lens of the person of ordinary
`skill in the art. And both parties agree that a person of ordinary
`skill in the art here is highly educated, a Ph.D. in an area like
`pharmacy or ophthalmics, drug development and drug delivery.
`We have provided for your review a quick timeline
`summarizing the state of the art leading up to the earliest possible
`prior to date of May of 1997. And what's important to note here
`is that difluprednate had already been proposed as a potent
`antiinflammatory or antiallergic agent for use even in an
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`ophthalmic formulation. So back in the 1970s, it had been
`proposed for use in an ophthalmic ointment, although we all can
`recognize that the problems with ointments are that they blur your
`vision. So they have their own set of drawbacks.
`Even Senju's own reference, the Takeda reference,
`recognizes that difluprednate was described as being closest to an
`ideal corticosteroid. And by the mid 1990s, in the Kimura
`reference difluprednate had been proposed as an ophthalmic
`suspension.
`At the same time or leading up to the filing date also,
`there was the development of ophthalmic emulsions. And we've
`outlined a lot of those on the right-hand side of the slide. So what
`you see is by the 1990s, the interest in emulsions as ophthalmic
`formulations for poorly water soluble drugs had been renewed
`particularly with the development of submicron emulsions
`because they were found to provide even increased comfort.
`And you can see there are many examples of poorly
`water soluble drugs that had been formulated as ophthalmic
`emulsions prior to the filing date, including steroids, and
`including the Ding reference notes that describes the use of an
`emulsion to formulate prednisolone acetate. Prednisolone acetate
`is a steroid that is the precursor difluprednate. Difluprednate is a
`derivative of prednisolone acetate. So the prior art was very, very
`close to the claimed invention.
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`So as I mentioned, and I'm turning now to slide 8,
`steroids were known to be poorly water soluble, meaning they
`can't readily be dissolved in water or aqueous liquids. And so
`formulators looked for other ways of formulating difluprednate.
`One way that had been used and as described in the Kimura
`reference is to use a suspension. But a suspension is a solid
`particle that's dispersed in a liquid. So basically little particles,
`crystals, I say rocks, in your eyes that are suspended in liquid and
`administered to the eyes. But those --
`JUDGE BONILLA: Are suspensions by definition here
`aqueous suspensions? Is that how you distinguish it from
`emulsion?
`MS. ELLISON: No. We distinguish suspensions from
`emulsions in that suspensions are solid particles in liquids,
`typically in aqueous liquid, because you don't want to have a bad
`solvent in your eye. Whereas, a suspension is an oil-water
`mixture where a poorly water soluble drug like difluprednate is
`actually dissolved in the oil phase of that --
`JUDGE KATZ: Is an emulsion?
`JUDGE BONILLA: You said suspension.
`MS. ELLISON: I'm sorry, an emulsion is an oil and
`water mixture where the poorly water soluble drug like
`difluprednate is dissolved in the oil phase --
`JUDGE BONILLA: So it's never in a solid state in the
`emulsion --
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`MS. ELLISON: That's exactly the point, is to get the
`drug out of a solid state and to dissolve it in the oil phase. These
`are lipophilic drugs as even Senju's expert has acknowledge,
`meaning they are fat loving. They like the oil. So you can
`dissolve the active in the oil part of the oil and water phase of the
`oil and water emulsion.
`So suspensions were known to have drawbacks. They
`were better than, of course, trying to formulate a poorly water
`soluble drug in aqueous liquid. But even with suspensions there
`were drawbacks. And one of those drawbacks was ocular
`irritation. And one of the reasons for the ocular irritation is
`because the suspension has solid particles in it. And if those
`particles are too the large, patients will feel the discomfort of
`having that drug in their eye and so they end up blinking and
`tearing and wiping the drug away. And this leads to low
`bioavailability because the drug is not sufficiently present in the
`eye long enough to be absorbed, to dissolve and then be absorbed
`into the eye.
`Another problem that was well known with suspensions
`is that they tend to, the particles in the suspensions tend to settle
`and agglomerate at the bottom of the vial during storage. This
`leads to agglomeration of the particles and caking of the particles.
`So the best solution that the field had come up with is to instruct
`patients to shake vigorously, maybe 40 times. But even one of
`the references in the record here demonstrates that patients had
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`poor compliance with these requirements for shaking. In one
`study, about half of the patients didn't even shake the bottle at all,
`let alone shake it well enough to adequately redisperse the
`particles. But even upon redispersion, one doesn't necessarily get
`the small particles again. You can still have caking and
`agglomeration.
`And the other problem with this is it leads inconsistent
`dosage. These were all problems that were well recognized in the
`art, drawbacks of suspensions. You get an inconsistent dosage
`from drop to drop or treatment to treatment because of the natural
`tendency of particles to settle in suspensions.
`Emulsions, on the other hand, were recognized as being
`well suited for using with poorly water soluble drugs. As we
`show here in the Hollingsbee reference, this is on slide 9, the drug
`will be dissolved in the oils. This is addressing your question,
`Judge Bonilla.
`And the Ding reference in particular demonstrates the
`formation of an emulsion for use with a poorly water soluble drug
`where the emulsion can be provided with a high comfort level
`and low irritation potential. So this illustrates one of the
`advantages of using an emulsion over the suspension
`formulations that had been known.
`Additionally, as the Kassem reference points out, the
`bioavailability with emulsions can be more than doubled. It can
`be increased because you would have longer residence time of the
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`emulsion on the eye as compared with other formulations.
`Solutions were known to move out of the eye quickly.
`Suspensions were known to have their irritation problems causing
`patients to blink and tear up and again move the drug out of the
`eye before it's absorbed.
`JUDGE BONILLA: Now, patent owner comes forward
`with some references that indicate that the types of things you use
`in an emulsion such as surfactants would actually increase
`irritation. How do you respond to that?
`MS. ELLISON: We respond to that in a couple of
`ways. First and foremost, the Ding reference, which is the key
`reference upon which we rely, demonstrates high comfort level
`and low irritation potential. That's a quote straight from Ding.
`So their theories about concerns with emulsions did not exist with
`Ding's emulsion.
`Secondly, with respect to surfactants -- and I can skip to
`the slide on that. Slide 27, I believe. So with respect to
`surfactants, the evidence that our opponents rely upon -- actually,
`I'll go back to this one. With respect to surfactants, we've put in
`quite a bit of evidence demonstrating that polysorbate 80, the
`particular surfactant that's used here in formulating this case of
`obviousness and that's encompassed by the claims, this was
`known to be a nonirritating, nonionic surfactant. And the
`nonionic surfactants were known not to be irritating in contrast to
`anionic surfactants or cationic surfactants. Our opponents also at
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`one point, point to cosurfactants, but nonionic surfactants don't
`require cosurfactants. So cosurfactants may have had some
`irritation concerns, but they are not needed here. Anionic or
`cationic surfactants are what's described in the references upon
`which our opponents rely. But polysorbate 80 was a nonionic
`surfactant, and the nonionic surfactants were known to be mild
`and not irritating.
`Our opponents point to the van Pinxteren reference as
`part of making their arguments, but the van Pinxteren reference
`really is not applicable here because in van Pinxteren the
`polysorbate 80 was administered intraarterially, not topically.
`Whereas, the claimed invention here and the art we are relying on
`relates to topical administration, eye drops. Not intraarterial
`administration.
`JUDGE BONILLA: But it still raised pressure in the
`eye; is that correct? It's just that the administration was different?
`MS. ELLISON: The form of administration was
`different, and I don't believe there is any evidence that the amount
`of polysorbate 80 was an amount that's necessarily used here. Of
`course, these claims have no limitations on the amount of really
`any component and the claims are quite broad in that regard.
`Additionally, other references relating to emulsions
`which use surfactants like Aviv, Kassem and Hollingsbee, all
`used relatively high percentages of surfactant. Higher than what
`Ding used. So Ding used up to, I think, 1 percent surfactant.
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`Aviv used up to 5 percent and Kassem used some totaling up to
`3-1/2 percent or Hollingsbee 2-1/2 percent, and they did not
`experience any IOP concerns. So these concerns that our
`opponent points to are generalized concerns that do not relate
`specifically to the references we rely upon, namely Ding, and do
`not specifically relate to polysorbate 80 when it's administered
`topically in a small amount. Only microliters of these are
`administered to patients when they are used as eye drops.
`So I'll go back to, I think I was here at slide 9. I want to
`note that our opponents have in a number of places, and it's just
`one example in dealing with the Bar-Ilan reference, they have, in
`our view, mischaracterized the art. And we've laid this out on
`slides 10, which we're looking at now, and I'll show you slide 11
`as well. For example, they point to the Bar-Ilan reference in an
`effort to say that there is a general reluctance in the field to
`develop emulsions. But if you dig into Bar-Ilan and look at what
`Bar-Ilan bases that comment on, Bar-Ilan bases that comment on
`references from the late 1980s.
`But importantly, Bar-Ilan goes on to say that interest in
`emulsions was renewed with the development of submicron
`emulsions. Our opponents conveniently ignore this fact, that the
`field actually developed over time and emulsions were of newer
`interest beginning in the mid '90s, particularly with the use of
`nonionic surfactants as they were recognized as being
`nonirritating, as the Bar-Ilan reference points out. You can see in
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`making these statements, Bar-Ilan points to more recent
`references, those from the mid '90s, including a PCT publication
`that corresponds to the very Aviv reference that we've used in the
`case. And so what Bar-Ilan, when you look at it in its entirety,
`what Bar-Ilan teaches is that there was actually an increased
`interest in emulsions that was continuing to develop in the art,
`particularly with improvements over what had previously been
`shown.
`
`So turning now to slide 13, we've just summarized our
`arguments regarding reasons to combine, which is that prior art
`suspensions had known drawbacks. The '848 patent, while it
`provides a suspension of difluprednate, those the drawbacks still
`existed. The '848 suspension did not solve those drawbacks.
`Whereas, Ding taught that emulsions could be formulated with
`poorly water soluble drugs, including prednisolone acetate from
`which difluprednate is a derivative. And these emulsions could
`be formulated with high comfort levels and low irritation
`potentials. So this really addresses a lot of the drawbacks that
`have existed with suspensions.
`So slide 14, again, just kind of summarizes our
`argument. Slide 15 teaches that difluprednate was useful for
`treating a variety of antiinflammatory, antiallergic conditions.
`And this is based on the teachings in the '848 patent.
`What I would like to note here is there's been some
`discussion in the case about target tissues. Well, as I noted
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`earlier, these claims are composition claims that don't specify any
`target tissue. But in any event, the '848 patent on which we rely
`says that difluprednate can be used to treat all the same target
`tissues that the '319 patent purports to treat as well.
`And these are not just interior to the eye. These are also
`surface eye tissues. So for instance, conjunctivitis, all the forms
`of conjunctivitis treat the inflammation of the conjunctiva, of
`course. That's the condition that would be treated, would be
`inflammation of the conjunctiva which is external. Blepharitis is
`inflammation of the eyelids. So again, external. And uveitis is
`interior to the eye, but as you can see, difluprednate was already
`recognized as being treated for all of these various types of eye
`conditions.
`JUDGE KATZ: So on Ding, it seems to be directed
`towards targeting the lacrimal gland; is that correct?
`MS. ELLISON: That's what our opponents have
`argued, but that is not correct, Your Honor. And I'll jump right to
`that. So let's look at slide 22. So our opponents have argued that
`Ding is specific to the lacrimal glands, but the evidence shows
`otherwise. Here is a quote from Ding itself, which Ding explains
`that the emulsions were also effective in delivery of cyclosporin
`A to the tissues of interest, lacrimal gland, cornea and
`conjunctiva. So again, the very same tissues that we just
`mentioned.
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`
`And there's been a lot of discussion in the record about
`Figures 1 and 4 of Ding. And I'll note a couple of things about
`them.
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`JUDGE KATZ: Yeah, if you could walk through what
`the X axis, what those -- the different formulations are and where
`they come from in Ding. I was confused.
`MS. ELLISON: Sure. I might need my glasses for that
`one. Just one second. So what Figures 1 and 4 of Ding show is
`that Ding tried various formulations of cyclosporin A and
`ultimately concluded, as we show at the top of the slide, that the
`emulsions were effective in delivering cyclosporin A to various
`tissues, including the cornea and the conjunctiva. There's another
`place in Ding, this is at page 11 where Ding points out that
`therapeutic levels of the drug were delivered to all these various
`tissues.
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`So regarding Figures 1 and 4, one thing to note is that
`the Y axes on these figures are not the same. So you can't just
`compare them side by side because the Y axes differ. As you can
`see, in the lacrimal glands it goes up to only about 60 nanogram
`equivalents per gram. Whereas, for instance, in the conjunctiva,
`the Y axis goes up to about 4,000.
`JUDGE BONILLA: Should we be concerned that this
`indicates using something other than castor oil?
`MS. ELLISON: I'm sorry, Your Honor, should we be
`concerned that what?
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`JUDGE BONILLA: That it teaches using something
`other than castor oil? There's lots of things listed there.
`MS. ELLISON: There are lots of things listed here and
`there are a number of formulations that were tested, but what
`Ding, when you read the reference in its entirety, teaches is that
`the emulsion formulation, the caspem, the one that we have
`outlined with the red boxes, is the formulation that Ding proposes
`for use in treating ocular conditions.
`JUDGE KATZ: So if you could point me to where that
`is in Ding? I was having trouble finding out what caspem is
`compared to castor oil and compared to --
`MS. ELLISON: Yes, Your Honor. So page 16 of Ding,
`Table A outlines the various formulations or excuse me, the
`components of the various formulations. I'm sorry, it's page 15 at
`the bottom, page 13 at the top. So original page number 13 in
`Ding outlines the various formulations. So what you see is Ding
`tried castor oil. That was at 99.8 percent castor oil. That's the
`first set of boxes in each figure.
`JUDGE KATZ: We are on page, you said, Table A?
`MS. ELLISON: Table A.
`JUDGE KATZ: So castor oil is the first?
`MS. ELLISON: Castor oil is the first one. And you see
`that's an extraordinary high level of castor oil. 99.8 percent of the
`formulation was castor oil.
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`JUDGE KATZ: So that's only castor oil? Not
`surfactant?
`JUDGE BONILLA: So is caspem the second one?
`MS. ELLISON: Caspem is the second one, correct.
`JUDGE OBERMANN: When you say the second one,
`you are talking about cyclodextrin?
`JUDGE BONILLA: The second column.
`JUDGE KATZ: So when it says castor oil, that's not an
`emulsion of castor oil. It's just castor oil by itself?
`MS. ELLISON: Right. That's the drug dissolved in
`castor oil. Whereas, caspem is the castor-oil-in-water emulsion
`that's shown in the second column of reagents in Table A.
`JUDGE OBERMANN: That's not disputed at all that
`caspem is castor oil and water?
`MS. ELLISON: Correct, there's been no dispute about
`that in the case.
`JUDGE KATZ: Then how does that differ from the
`other? So then I assume we just march along that aqueous --
`MS. ELLISON: The next -- the next one is an aqueous
`solution. But note that that aqueous solution contains
`cyclodextrin used as a solubilizer and permeation enhancer. It
`uses it at 14 percent, which is an extraordinarily high amount of
`cyclodextrin. Too much cyclodextrin will irritate the eye. And
`even Senju's expert, Dr. Majumdar, testified that he's only ever
`used it up to 5 percent.
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`JUDGE KATZ: I'm just trying to match up when it
`says cyclodextrin, the third sort of group of bars in Figures 1
`through 4, that's referring to the third column in Table A?
`MS. ELLISON: Yes, Your Honor.
`JUDGE KATZ: And the forth group of bars is the
`fourth column and so on?
`MS. ELLISON: Correct, Your Honor.
`JUDGE KATZ: Okay. Thank you. So actually, let me
`ask you then which ones -- only the second column of Table A is
`an emulsion?
`MS. ELLISON: Miglyol is also an emulsion, but that's
`an emulsion with different types of oil. So caspem is the only
`emulsion with a castor oil -- it's the only castor oil and water
`emulsion.
`JUDGE KATZ: So then we should be comparing, as
`you noted in your slide 21, caspem to all the other -- we are
`comparing caspem to the other formulations?
`MS. ELLISON: I think you can compare caspem to the
`other formulations, but I think the important thing to understand
`is that even if caspem is not the highest under all circumstances at
`all time points, what's still clear from Ding's teachings is that
`caspem or Ding's emulsion, as we call it, is useful and delivers
`therapeutically effective amounts of drug to all the tissues of
`interest. Not just to the lacrimal gland, but to all the tissues of
`interest. And Ding states that very clearly. It's shown very
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`clearly here on slide 21. It's also shown quite clearly on page 11
`of Ding.
`JUDGE BONILLA: Remind us how cyclosporin A
`relates to the issues in the claims.
`MS. ELLISON: Cyclosporin A is also used for treating
`inflammatory conditions. It's not a steroid. It's a slightly
`different drug. But the Ding reference also makes it clear that
`Ding's emulsions can be used with steroids which Ding notes are
`poorly water soluble. In particular, the Ding reference states that
`its emulsions can be used with prednisolone acetate. The steroid
`that's at issue, difluprednate, it's a derivative of prednisolone
`acetate. So Ding nearly anticipates the claims and there's just the
`swath from prednisolone acetate to difluprednate.
`JUDGE BONILLA: Is cyclosporin A also water
`insoluble?
`MS. ELLISON: Cyclosporin A is also poorly water
`soluble. This is the attraction of emulsions, is that they can be
`used to formulate drugs that are poorly soluble in water. You
`can't just dissolve these in water and expect that you can have a
`useful eye drop. So in the past, while some people have used
`suspensions for ointments to try to deal with this problem, from
`the beginning in at least the '80s and certainly with renewed
`interest beginning in the mid '90s, persons of skill in the art
`addressed this problem of poorly water soluble drugs by using
`emulsions.
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`JUDGE KATZ: So if we go back to Figures 1
`through 4, is the oil, the castor oil alone, is that sort of a control?
`I mean, what I'm sort of getting at is when you say that -- and I
`see that Ding state that it's effective in delivery, but then if we
`look at the data, is there some sort of threshold where something
`is called effective or not or is everything effective in Figures 1
`through 4?
`MS. ELLISON: Well, Ding has stated -- if you turn to
`page 11, Ding has stated that therapeutically effective levels were
`obtained with all of these drugs. And just one second -- excuse
`me. Ding has stated that therapeutically effective levels were
`obtained with its emulsion in all of the tissues of interest. So
`that's at page 11 at the top --
`JUDGE KATZ: Right, and that's a statement, which I
`understand that there's that statement. But then if we look at
`Figures 1 through 4, I guess what I'm asking is, is there a control
`to show that something is effective versus not effective that we
`can see from Figure 4?
`MS. ELLISON: With all due respect, I would consider
`the castor oils to be -- castor oils were known as a formulation, as
`one way and a sort of old fashioned way of delivering drug. I
`don't think there's a negative control on these slides. And there's
`no evidence in the record about some minimal threshold of drug
`that needs to be delivered to any of these tissues for it to be
`effective beyond the fact of what Ding plainly states is that Ding
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`viewed its drug as providing effective amounts or viewed its
`formulations providing effective amounts of these drugs. But you
`can imagine that the amount of drug that's needed in any situation
`may vary depending on the particular disease or condition that's
`being treated.
`But again, I'll note these are composition claims. These
`are composition claims that have no limitation in them with
`respect to the amount of active, with respect to the amount of
`castor oil, with respect to the amount of surfactant. They just
`have the ingredients in them. While there are some dependent
`claims that specify particular ratios, as I noted, our opponents
`have not made any separate patentability arguments for any of the
`dependent claims. So they all fall together with the broad claims.
`I am running short on time. Let me just take one minute
`to address reasonable expectation of success. Again, we rely and
`point to lots of teachings in the art, but in particular, we note that
`with Ding, Ding taught success with prednisolone acetate and has
`low irritation potential and high comfort levels.
`I think with that, I'm going to turn this over to Ms. Vira
`so that she can address objective indicia with the time we have
`left.
`
`MS. VIRA: Good morning, Your Honors. Senju has
`put forward four objective indicia that it claims supports the
`patentability of its claims. However, I will be presenting
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`evidence that no
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