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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`
`MICRO LABS LIMITED AND
`MICRO LABS USA INC.,
`Petitioners,
`
`v.
`
`SANTEN PHARMACEUTICALS CO., LTD., AND
`ASAHI GLASS CO., LTD.,
`Patent Owners.
`____________
`
`Case IPR2017-01434
`Patent 5,886,035
`____________
`
`Record of Oral Hearing
`Held: September 6, 2018
`
`
`
`
`Before JO-ANNE M. KOKOSKI, CHRISTOPHER G. PAULRAJ, and
`DEBRA L. DENNETT, Administrative Patent Judges.
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`Case IPR2017-01434
`Patent 5,886,035
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`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER:
`
`
`CEDRIC C.Y. TAN, ESQ.
`ALTON L. HARE, ESQ.
`SOPHIA WEI, ESQ.
`KEETO SABHARWAL, ESQ.
`Pillsbury Winthrop Shaw Pittman
`1300 Seventeenth Street, N.W.
`Washington, D.C. 20036
`
`
`ON BEHALF OF THE PATENT OWNER:
`
`
`ARLENE L. CHOW, ESQ.
`ERNEST YAKOB, Ph.D.
`TAKASHI OKUDA, ESQ.
`Hogan Lovells US LLP
`875 Third Avenue
`New York, NY 10022
`
`
`
`
`The above-entitled matter came on for hearing on Thursday,
`
`September 6, 2018, commencing at 1:00 p.m., at the U.S. Patent and
`Trademark Office, 600 Dulany Street, Alexandria, Virginia.
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`Case IPR2017-01434
`Patent 5,886,035
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`P R O C E E D I N G S
`- - - - -
`JUDGE KOKOSKI: Good afternoon. Today we will hear
`argument in Case Number IPR2017-01434, concerning U.S. Patent Number
`5,886,035. I'm Judge Kokoski, and Judge Paulraj is here with me, and Judge
`Dennett is joining us remotely.
`Let's start with appearances beginning with Petitioner.
`MR. TAN: Good afternoon, Your Honor. My name is Cedric Tan
`for Petitioners. With me is Keeti Sabharwal, Sophia Wei, and Alton L.
`Hare, all with the law firm Pillsbury.
`JUDGE KOKOSKI: Thank you.
`MS. CHOW: Good afternoon, Your Honor. My name is Arlene
`Chow. I'm with the law firm Hogan Lovells on behalf of Patent Owner.
`Also with me is Ernest Yakob, Takashi Okuda, as well as representatives
`from Akorn, Asahi Glass, and Santen Pharmaceutical.
`JUDGE KOKOSKI: Thank you. Welcome.
`I do want to remind the parties that Judge Dennett cannot see
`anything that you put up on the screen, but she does have a copy of the
`demonstrative exhibits that you provided to us. So during your argument,
`just make sure that you state what slide or page number you're on so that she
`can follow along.
`Speaking of the demonstratives, we did receive objections from
`both parties with respect to the demonstrative exhibits. We've reviewed all
`those objections, and we're going to overrule them. We do note that both
`parties raised a number of objections alleging that there are new arguments
`in the slides, and while we're not going to limit the use of the slides by either
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`party, we may ask you questions about where support is for arguments that
`you make in the slides, where we can find that support in the papers.
`You are also free to argue during your own argument time that the
`other party is making new arguments here, but please don't interrupt during
`the other party's argument time. We're aware of your concerns with the
`demonstratives, and we can deal with that when we're looking at the record,
`at the close of all of the evidence.
`So consistent with our hearing order, each party has 60 minutes to
`present their arguments. Petitioner will proceed first and may reserve
`rebuttal time. How much time would you like to reserve, if any?
`MR. TAN: I would like to reserve -- I would like to split it
`half/half.
`JUDGE KOKOSKI: Okay. You can begin when you're ready.
`MR. TAN: Good afternoon again. This is Cedric Tan for the
`Petitioners. May it please the Board, I would like to start off by referring to
`paper 11, the Board's institution decision. It is -- in its institution decision,
`the Board found that the Petitioners have demonstrated a reasonable
`likelihood on prevailing on its challenge of claims 1 to 14 of the '035 patent,
`but a genuine issue of material fact existed as to whether Compound C
`would have been selected as a lead compound due to conflicting expert
`testimony. The Board indicated in its decision that the parties will have the
`opportunity to develop the record for trial. Now here we are, nine months
`later, with a more fully developed record, with additional expert evidence
`coming primarily from two of the main experts in this case, Dr. deLong for
`Petitioners and Dr. Macdonald for Patent Owners, but from the time that
`Patent Owners filed their preliminary response until today, they and their
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`experts, in particular Dr. Macdonald, have been and continue to be flat
`wrong when they assert that
`Klimko explicitly teaches away from further development of Compound C
`due to an unacceptably -- unacceptable therapeutic profile due to the side
`effects of hyperemia and an initial increase in IOP for Compound C, and in
`their -- and their experts are wrong, and we will address that, but first I
`wanted to note very up front that nowhere, nowhere do Patent Owners
`challenge the undisputed and clear structural similarity between their
`claimed compound, Tafluprost, and the lead compound, Compound C, from
`Klimko.
`Can we go to slide 4, please. Tafluprost differs from the lead
`compound from Klimko, Compound C, only slightly, in that it has two
`fluorine substituents at the C-15 carbon, whereas Compound C has a
`hydroxyl group. In view of the minor differences, the Board's institution
`decision focused on the issue of selection of the lead compound, Compound
`C, and were persuaded to institute based on the current record then. The
`Board instituted on two grounds.
`Let's go to slide 5. Ground one over Klimko, Kishi, and Ueno, and
`ground two over Klimko, Kishi, Bezuglov 1982 and/or Bezuglov 1986 and
`Ueno. Now, I want to touch upon the references very quickly just for
`background purposes.
`Let's go to slide 6. Klimko, which is Exhibit 1003, discloses to a
`person of ordinary skill in the art Compound C, a lead compound that would
`be a natural choice for further development and as a compound for treatment
`of elevated IOP or glaucoma.
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`Can we go to slide 12, please. Kishi, Exhibit 1005, discloses to a
`person of ordinary skill in the art that PG2-alphas, like Compound C, used to
`treat glaucoma and elevated IOP can be modified to remove the hydroxyl
`group from the C-15 position, so that side effects such as hyperemia, which
`is redness of the eye, or initial increase in IOP are eliminated. Kishi also
`discloses that removal of the hydroxyl group at the C-15 position, such as in
`Compound C, protects PG2-alphas from metabolic degradation.
`Can we go to slide 15, please. Ueno, Exhibit 1029, references
`Kishi and its teaching of the removal of the C-15 hydroxyl group and
`specifically discloses difluorination at the C-15 to treat inflammatory
`conditions of the eye, such as conjunctivitis, and conjunctivitis and
`hyperemia are related.
`Now, let's go to slide 17. Now, Bezuglov 1982 and Bezuglov
`1986, which is a related reference, in ground two, teach that substitution at
`the C-15 position of the 15 hydroxyl group with fluorine of a PG2-alpha
`improves stability and maintains activity of PG2-alphas, in part, by
`protecting the fluorinated prostaglandin analog from enzymatic metabolic
`degradation.
`Can we go to slide 17, please. This is Bezuglov. Now, Bezuglov
`specifically teaches that fluorinated prostaglandin analogs at the C-15
`position, when they are fluorinated, did not use the activity characteristics of
`prostaglandins.
`Slide 18, please. Bezuglov 1986 teaches that fluorine resembles
`oxygen and, thus, a natural choice for substitution at the C-15 hydroxyl
`while increasing metabolic stability.
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`So I wanted to turn back now to something that I touched upon
`earlier, and that is regarding the main experts in this case, a focal point here,
`because the Board indicated that there was conflicting expert testimony.
`Both sides' main experts are in the area of medicinal and synthetic organic
`chemistry, but that's where their similarities end. Unlike Dr. deLong, who is
`Petitioner's expert, Dr. Macdonald, who is Patent Owners' expert, is not an
`expert in the relevant field of the '035 patent.
`This is slide 67. In spite of his alleged 30 years of experience as a
`technical consultant, none of his over 200 scientific publications or more
`than 50 patents are in the area of prostaglandin analogs. None are in the
`development of medicinal compounds to treat glaucoma or ocular
`hypertension. Instead, Dr. Macdonald's admitted expertise is the medicinal
`chemistry and molecular pharmacology of lipid signaling systems.
`Petitioner's expert, Dr. deLong, is different. He is vice president of
`Aerie Pharmaceuticals, a publicly traded company focused on discovery,
`development, and commercialization of drugs for treatment of patients with
`glaucoma and other eye disease. He's an inventor, an inventor of Rhopressa,
`for the treatment of elevated IOP and glaucoma, and has decades of
`experience in researching and developing compounds for treatment of a
`glaucoma or ocular hypertension, inclusive of prostaglandin analogs. He has
`also many scientific publications and patents and patent applications in this
`area.
`
`He has the right experience, and I want the Board to remember
`this, because when Patent Owners' counsel gets up and seeks to rely on their
`expert, Dr. Macdonald, the question that needs to be asked is, who is the
`more credible expert in view of their actual experience, because
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`Dr. Macdonald got it wrong when he said there was an initial increase of an
`IOP for Compound C, Petitioner's lead compound, based on the data
`reported in Klimko.
`I quote Dr. Macdonald: "As explained above, the data of Table 4
`in Figure 2 conveys that there is an unacceptable initial increase in IOP after
`administration of the fifth dose." This is 90 of Exhibit 2001 of Macdonald's
`declaration.
`First, initial -- an initial increase in IOP means after the first dose,
`the initial dose. Klimko does not report in Table 4 or Figure 4 -- and let's go
`to slide 8 -- any IOP immediately after the first dose. It reports percent IOP
`reduction after the fourth dose and after the fifth dose. As you can see there
`in the yellow, the first reported time point is 16 hours after the fourth dose,
`and then thereafter, two hours after the fifth dose, and then thereafter, four
`hours after the fifth dose, and then six hours after the fifth dose. So initial
`increase in IOP refers to the first initial increase, the first dose of a
`compound, and that is not what is reported in Klimko.
`As Dr. deLong indicated, Table 4 here, which is in this slide, was
`designed to skip measurements of an initial increase in IOP since it measures
`IOP after the fourth dose, not the first dose. So data in Klimko is not even
`relevant to and cannot be tied to an initial increase in IOP, but even we put
`aside that, the data in Table 4 is after the fourth and the fifth dose. There is
`no increase, no increase in IOP anywhere reported in Klimko.
`Let's look at this date in Table 4, which is slide 8. As I said, Table
`4 reports percent IOP reduction in lasered cynomolgus monkeys
`administered for compounds A through E, inclusive of Compound C, the
`lead compound. So first, in measured baseline is reported on this table for
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`all of the compounds, that's compounds A through E. This is a baseline.
`This is a measurement of IOP prior to the administration of any of the
`compounds.
`With respect to Compound C, which is the highlighted yellow
`portion, you see that the baseline IOP is reported at 38.2 millimeters of
`mercury. Following that, for the sixth hour after the fourth dose to the
`second hour after fifth dose, fourth hour after fifth dose, sixth hour after fifth
`dose, there is a percentage reported. This represents the percentage below
`baseline of IOP reduction. So what you see is, for sixth after the fourth
`dose, 30.2 percent reduction below the baseline or 38.2 millimeters, and then
`thereafter, 25.3 percent, thereafter 23.6 percent, and thereafter 28.9 percent.
`So IOP reported in Table 4 for Compound C has never, ever increased above
`baseline, because it is always reported as a percentage below baseline. It is
`reducing baseline IOP below 38.2 millimeters.
`Now, this data here can also be viewed on slide 37, which is a
`replot of Klimko's data. Here, on this slide, the X axis shows IOP of the
`experimental eye minus the IOP of the baseline measurement. Here there's
`nothing above the zero on the X axis because there is no increase in IOP
`above baseline. As you can see, none of the compounds, inclusive of
`Compound C, even approach or go beyond or above the zero axis on this
`figure.
`
`So why are we here? Does initial increase in IOP matter for
`Compound C? No, not really. We only address initial increase in IOP
`because patient -- because Patent Owners have erroneously relied on it, even
`though there is no evidence of Compound C having such a side effect in
`Klimko's data. It's a red herring. And even if there's initial increase in IOP,
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`it could be readily resolved, and that is by lowering the dose of the
`compound to lower side effects such as an initial increase in IOP.
`Let's go to slide 33 to see that.
`JUDGE KOKOSKI: Before you move --
`MR. TAN: Certainly.
`JUDGE KOKOSKI: -- I have a question about that slide 37, the
`chart that you just had up. Is there any significance or are we to take any
`significance away from the fact that the IOP reduction does increase with
`time before -- you know, between -- at dose -- I guess at 2 and at 4, and then
`it goes down at 6? So we are seeing -- I know it's not above baseline, but it's
`still an increase from that original dosage. So is that significant in any way?
`MR. TAN: That is not significant with respect to the definition of
`initial increase in IOP. An initial increase in IOP is a concern because there
`is an increase in IOP above your normal predose IOP level. That is a
`concern, because by giving you the drug, your IOP has gone above what
`you've tried to reduce it from, but in this case, because your IOP is being
`reduced and is below your baseline IOP, then there is no concern from a --
`from a medical standpoint.
`JUDGE KOKOSKI: So the fact that -- that C does demonstrate
`that later increase and then decrease, that wouldn't be something that would
`dissuade someone from further research with Compound C? Because the
`other compounds, you know, appear to kind of go down and then go up. So,
`you know, I understand that, but is there anything that would dissuade them
`because of that?
`MR. TAN: No, and you point something out that is very evident
`from this particular figure and from other figures, is that Compound C has a
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`different curve from the other compounds, and that is something that you
`actually really want to see, because what you're actually seeing is not a
`reduction in efficacy of Compound C when you have a decrease in
`percentage IOP reduction. All it means is that at that point in time, the
`concentration of Compound C is at its lowest level. It's at its trough, and the
`slow metabolism of Compound C results in later it taking more of an effect,
`and that's why you see an increasing percent IOP reduction later on from
`four hours to the six-hour point -- time point. And that's really what you
`want to see with respect to a drug that you would want to dose once a day, a
`slow metabolism and effective once a day.
`So Kishi, one of the prior references referred to before -- and let's
`take a look at slide 12, please -- specifically teaches the removal of the
`hydroxyl at the C-15 position of PGF2-alpha prostaglandins, not only
`limited to hyperemia, but also, and you can see it right here in the
`highlighted language, any initial increase in IOP.
`So I wanted to step back now. What is this case about? This is a
`lead compound obviousness case; that is, the claimed compound is obvious
`in view of the lead compound that has been selected and modified. Every
`lead compound obviousness analysis considers the target molecule, that is,
`the claimed molecule. The analysis cannot be done in a vacuum. It would
`be a fallacy to say otherwise.
`The case law looks at a prima facie case of obviousness is
`established by identifying a compound in the prior art with structural
`similarity as the claimed compound when there is motivation for a person of
`ordinary skill in the art to select the lead compound as the natural choice to
`further develop and modify and when there's motivation to modify that
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`compound with a reasonable expectation of success in a manner taught by
`the prior art, such that the natural result would be the molecule that is being
`claimed.
`So where do we begin here? Let's look at the claims of the patent.
`There are two independent claims. Let's look at slide 2. The claims of the
`'035 patent are directed to both the genus of PGF2 alpha prostaglandin
`analogs, and medicines containing these analogs, inclusive of Tafluprost.
`Now, the other independent claim, let's take a look at that on slide 3, is
`independent claim 12. This claim is directed to three named compounds and
`their alkyl esters or salts. So the isopropyl ester of the very first compound,
`which is in green, that is Tafluprost. That is
`16-phenoxy,15-deoxy,15,15-difluoro,17,18,19,20-tetranorprostaglandin
`F2-alpha.
`Let's go to slide 6. So why would a person of ordinary skill in the
`art have chosen Compound C as a lead compound for further development
`and modification? Well, selection of a lead compound is not done in a
`vacuum, not done concerning only one prior reference. It's done concerning
`the prior art as a whole. So what does the prior art tell us about Compound
`C? Compound C has longer lasting IOP-reducing efficacy. It has superior
`IOP-reducing effectiveness relative to its commercially available drug,
`latanoprost, which it was compared to in Table 4, which is the gold standard
`or was the gold standard for treatment of elevated IOP, and that is compound
`E in Klimko. And any potential side effects can be reduced or eliminated by
`further modification, modification, as I indicated before, as taught by Kishi,
`removal of the C-15 hydroxyl group would eliminate side effects such as
`hyperemia and an initial increase in IOP.
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`Let's go to slide 8. Now, this is a table that we have gone through
`it before. You know, as you can see from this table, at the 16th hour after
`the fourth dose, that represents the greatest elapsed time after administration
`of any dose. So Compound C at that point, 16 hours after administration of
`dose, even though it's the fourth dose, has the greatest IOP reduction shown
`at 30.2 percent. This means that it's long lasting and has superior
`IOP-reducing efficacy that is going on even 16 hours after the dose. But the
`long lasting -- the longer lasting efficacy of Compound C is better illustrated
`in graphical representation, Figure 2 of Klimko, which is slide 9 here.
`JUDGE DENNETT: Can you repeat the slide number?
`MR. TAN: Certainly. It is slide 9, Your Honor.
`JUDGE DENNETT: Oh, okay. Thanks.
`MR. TAN: In this slide, Compound C's attributes over the other
`compounds can clearly be seen, and as I indicated before in answer to Your
`Honor's questions, its curve in Figure 2 is different and advantageously so as
`can be seen here. Compound C is the one with the red arrow. As can be
`seen 16 hours after the fourth dose, it has the greatest reduction in IOP, but
`what you see here is that the curve is such that there is increasing percent
`reduction in IOP going from the fourth hour to the sixth hour after the fifth
`dose. All of the other compounds have a reverse sort of curve, wherein the
`percent IOP reduction is peaking much earlier --
`JUDGE PAULRAJ: Counsel?
`MR. TAN: Certainly.
`JUDGE PAULRAJ: So in this curve, you have labeled the
`latanoprost, that's compound E in Klimko, but that -- as you said, that seems
`to be -- that seems to have the least IOP-lowering activity. It's -- you know,
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`the -- but you said that was the gold standard. Can you explain why that
`would be the gold standard?
`MR. TAN: Latanoprost at that point in time was the only
`commercially available product that was a prostaglandin analog that was
`being compared in this trial to compounds A through D.
`JUDGE PAULRAJ: Was that the only commercially available
`product in this area?
`MR. TAN: There was another commercially available product that
`was isopropyl unoprostone.
`JUDGE PAULRAJ: And when was latanoprost approved?
`MR. TAN: Latanoprost was approved I believe in June 1994. I'm
`sorry, I'm -- let me correct myself. It was 1996.
`JUDGE PAULRAJ: Thank you.
`MR. TAN: So one of the things that we've heard from Patent
`Owners in this case in the record is how Compound C has much more
`hyperemia and that the person of ordinary skill would have been dissuaded
`from selecting this compound because of it. Well, what is hyperemia?
`Well, hyperemia is redness of the eyes, the same type of redness that you
`would see in my eyes right now because I'm wearing contact lenses. It's not
`toxicity. It doesn't result in blindness the way that glaucoma would if left
`untreated. It's simply a cosmetic issue that can be addressed.
`Well, let's go to slide 12. Kishi teaches us that removal of 16 -- of
`the C-15 hydroxyl of PGF2-alpha improves stability and eliminates side
`effects. Well, what side effects? As I've indicated before, it expressly says
`side effects such as hyperemia or conjunctiva, initial increase in intraocular
`pressure.
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`Let's go to slide 13. So Kishi also teaches that removing a
`hydroxyl group and replacing it with a hydrogen results in some -- some loss
`of IOP-reducing activity. This is seen in Table 1. The compound referred to
`as "C" here, it's not Compound C of Klimko. It's just -- it's referred to as
`"C," and it's a compound that has a hydroxyl group still at the C-15, which
`means it hasn't been removed, but it results in more of a difference in
`increasing IOP. It results in a decrease of 5.8 millimeters, more so than
`compound A, wherein the hydroxyl group at the C-15 has been replaced. So
`this means to a person of ordinary skill in the art, based on this data here in
`Kishi, that the hydroxyl group needs to be replaced with a proper surrogate
`that would be -- offset of the potential -- just some of the potential loss of
`IOP-reducing activity.
`Well, Ueno -- let's go to slide 15 -- teaches that that surrogate that
`can replace that C-15 hydroxyl group, that surrogate can be fluorine through
`a difluorination at the C-15 position. Ueno teaches that PGF2-alpha can be
`used to treat inflammatory diseases such as conjunctivitis, as I said, that's
`related to hyperemia --
`JUDGE KOKOSKI: How exactly is that related to hyperemia?
`MR. TAN: Conjunctivitis is something that affects the eye, and it
`is a -- sort of a redness related to hyperemia. Hyperemia, at its basic, just
`means redness, and so that's how they're related. They are both eye --
`symptoms of the eye, a redness that you will see.
`JUDGE DENNETT: So do you think that the -- wouldn't
`conjunctivitis indicate an inflammation of the eye? Is that right?
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`MR. TAN: Conjunctivitis is -- yes. Yes, Your Honor.
`Conjunctivitis has additional inflammation of the eye, but it also has the
`redness.
`JUDGE DENNETT: Okay, thanks.
`MR. TAN: If we can go to slide 14. Ueno specifically references
`Kishi's teaching of removing the C-15 hydroxyl group and specifically
`teaches difluorination at the C-15 position. Ueno, contrary to what Patent
`Owners will probably argue, is a researcher and inventor that is well
`recognized in the prostaglandin and anti-glaucoma field. He's recognized as
`somebody who does research there. His name is synonymous with
`anti-glaucoma and reduction of elevated IOP.
`But separate from Ueno, there are additional motivations for a
`person of ordinary skill in the art to make a difluorination substitution as
`taught by Ueno.
`Let's go to slide 16. Difluorination at the C-15 position avoids a
`stereogenic center at the C-15 position, and this simplifies the manufacturing
`process and regulatory process. Removing the stereogenic center of what's
`making the isomer that would either need to be eliminated or characterized
`as an impurity as you go through the regulatory process of developing a
`commercial product. This ends ground one.
`Ground two is different in that ground two adds two related
`publications I touched upon very briefly at the beginning of my argument,
`and both of those teach fluorine substitution at the C-15 position.
`Let's go to slide 17. Bezuglov 1982, the additional reference,
`teaches that substitution of the C-15 hydroxyl group with fluorine extends
`the activity characteristic of PGF2 analogs by protecting the prostaglandin
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`from enzymatic degradation by 15-fluoro-deoxyprostaglandin
`dehydrogenase. Bezuglov 1982 specifically teaches that fluorinated C-15
`PGF2-alphas did not lose the activity characteristic of prostaglandins and, as
`suspected, had prolonged activity compared to natural prostaglandins.
`Prolonged activity is really what you want to see when you're looking to
`develop a product for treatment of elevated IOP, because you would want
`the potential for once-a-day dosing.
`Let's take a look at slide 18. Bezuglov 1986 teaches increased
`selectivity and stability for prostaglandin analogs by fluorination at the C-15
`position, to replace a C-15 hydroxyl and protect the molecule from
`enzymatic degradation. This leads to long action, as I indicated before.
`Let's go to slide 19. So Bezuglov 1982 and 1986 motivates a
`person of ordinary skill in the art to replace hydroxyl at the C-15 position. It
`enhances and prolongs IOP, reducing activity of the lead compound, and
`restoring, at a minimum, any reduction in IOP that would have resulted
`potentially from removal of the hydroxyl group. So it is a substitution of the
`hydroxyl with a fluorine. So fluorine and oxygen are close proximally on
`the periodic table, and they share many similarities, has high
`electronegativity like oxygen, has a hydrogen bond acceptor capability and
`is a known substitution in prostaglandin derivatives.
`Let's go to slide 16. So when we were talking earlier, this slide 16
`shows you why you would want to avoid the stereogenic center and do
`difluorination, because when you do monofluorination, as I indicated before,
`you would have to characterize impurities with respect to the product. You
`would have to go through additional steps in the regulatory process, whereas
`if you do a difluorination, there would be no isomer that you would have to
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`deal with, no impurity that you would have to deal with potentially, and it is
`much easier to manufacture.
`So let's go to slide 20. So in combination with Ueno, Bezuglov
`1982 and 1986, they made clear the benefits of fluorination and special
`difluorination at the C-15 position to substitute for the hydroxyl group. So
`I'd like to sum up by noting that Patent Owners are wrong when they assert
`that Compound C would not have been a natural choice for further
`modification as a lead compound to develop a drug for treatment of
`glaucoma and elevated hyperemia, because hyperemia and initial increase in
`IOP are side effects that can be taken care of by removal of the C-15
`hydroxyl group, but even before we even get to that point with respect to the
`initial increase in IOP, there is no initial increase in IOP. Klimko doesn't
`report any data that relates to an initial, which means after the first dose,
`showing an increase in IOP, nor even an increase in IOP. So Tafluprost, the
`claimed compound, is obvious in view of the clear teachings of the art,
`Klimko, Kishi, and Ueno, and also Bezuglov 1982 and 1986, as in ground
`two, if you need to refer to them as well, too.
`Thank you, Your Honors. Do you have any questions?
`JUDGE PAULRAJ: None from me at this time.
`JUDGE KOKOSKI: No. Thank you.
`Judge Dennett, we are getting a little bit of feedback in the hearing
`room. Could you mute your mic when you're not speaking?
`JUDGE DENNETT: Yes, I will.
`JUDGE KOKOSKI: Thank you very much.
`JUDGE DENNET: Sorry about that.
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`JUDGE KOKOSKI: Patent Owner, you have 60 minutes. You
`can start when you're ready.
`MS. CHOW: And, Your Honor, if I may ask, would it be possible
`for me to reserve some time for surrebuttal, ten minutes of my time? Is that
`possible?
`MR. TAN: Your Honor, if I may object, they are Patent Owners.
`They don't get the last word, Your Honor. So no rebuttal time should be
`reserved for them.
`MS. CHOW: There is -- there are these new PTAB rules, Your
`Honor, and that is what I'm relying on. We have seen an indication that now
`that surrebuttal time would be permitted.
`JUDGE KOKOSKI: You are referring to the trial practice guide
`updates.
`MS. CHOW: Yes.
`JUDGE KOKOSKI: Just give us a minute.
`(Pause in the proceedings.)
`MR. TAN: Your Honor, if I may just interject, my understanding
`is that it only applies when you have motion to amend claims, and that's not
`the situation here.
`JUDGE KOKOSKI: We understand that, but I think just in light
`of the changes in kind of how things are in flux right now, we are going to
`go ahead and give you -- let you reserve the ten minutes --
`MS. CHOW: Thank you, Your Honor.
`JUDGE KOKOSKI: -- in this case. So I'll go ahead and take that
`off your clock now.
`MS. CHOW: Thank you very much, if I may proceed?
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`If it please the Board, slide 2, please Takashi. I would first like to
`just set the stage as to the fact that Tafluprost is a unique molecule with three
`critical differences from prior art marketed compounds. Here, we have
`Tafluprost as well as an unoprostone. There are two Fs at the 15 position,
`phenoxy at the 16 position, as well as a C13/C14 double-bond.
`Next slide, slide 3. Now, I'd like to stress that this is an
`unpredictable art.
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