Trials@uspto.gov
`571-272-7822
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`Paper # 36
`Entered: July 12, 2023
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`EYENOVIA, INC.,
`Petitioner
`v.
`SYNDEXIS, INC.,
`Patent Owner.
`__________
`
`IPR2022-00384 (Patent 10,842,787 B2)
`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
`____________
`
`Record of Oral Hearing
`Held: April 14, 2023
`__________
`
`Before ERICA A. FRANKLIN, SUSAN L. MITCHELL, and
`JAMIE T. WISZ, Administrative Patent Judges.
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`571-272-7822
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`
`
`
`
`Paper # 36
`Entered: July 12, 2023
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`EYENOVIA, INC.,
`Petitioner
`v.
`SYNDEXIS, INC.,
`Patent Owner.
`__________
`
`IPR2022-00384 (Patent 10,842,787 B2)
`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
`____________
`
`Record of Oral Hearing
`Held: April 14, 2023
`__________
`
`Before ERICA A. FRANKLIN, SUSAN L. MITCHELL, and
`JAMIE T. WISZ, Administrative Patent Judges.
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`IPR2022-00384 (Patent 10,842,787 B2)
`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`
`
`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER:
`
`THOMAS H. WINTNER, ESQ
`PETER J. CUOMO, ESQ.
`of: Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
`One Financial Center
`Boston, Massachusetts 02111
`(617) 348-1625 (Wintner)
`(617) 348-1854 (Cuomo)
`twinter@mintz.com
`pjcuomo@mintz.com
`
`
`
`
`ON BEHALF OF THE PATENT OWNER:
`
`JAD A. MILLS, ESQ.
`MICHAEL ROSATI, ESQ.
`of: Wilson Sosini Goodrich & Rosati
`701 Fifth Avenue
`Suite 5100
`Seattle, WA 98104-7036
`(206) 883-2529 (Rosati)
`(206) 883-2554 (Mills)
`mrosato@wsgr.com
`jmills@wsgr.com
`
`
`
`The above-entitled matter came on for hearing Friday,
`
`April 14, 2023, commencing at 10:00 a.m., at the U.S. Patent and Trademark
`Office, 600 Dulany Street, Alexandria, Virginia.
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`IPR2022-00384 (Patent 10,842,787 B2)
`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`
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`P-R-O-C-E-E-D-I-N-G-S
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`10:01 a.m.
`JUDGE MITCHELL: So good morning, everyone. We have a final
`hearing this morning in three cases, IPR2022-00384, IPR2022-00414, and
`IPR2022-00415. I am Judge Mitchell and seated to my left is Judge Wisz.
`And with us by video conference is Judge Franklin. I would like to
`get appearances for the parties on the record so let me start with Petitioner.
`MR. WINTNER: Good morning, Your Honor. Tom Wintner from
`Mintz, Levin in Boston and with me today is Peter Cuomo also from Mintz,
`Levin.
`
`MR. CUOMO: Good morning, Your Honor.
`JUDGE MITCHELL: Thank you, good morning. And who do we
`have for Patent Owner?
`MR. MILLS: Good morning, Jad Mills from Wilson Sosini on
`behalf of the Patent Owner, Syndexis. With me is lead counsel, Mike
`Rosati.
`
`JUDGE FRANKLIN: Great, welcome. Thank you. So as set forth
`in our oral hearing order, each side has 60 minutes to present its case for the
`three IPRs. My colleagues and I will do our best certainly to keep track of
`time up here. And you will see hopefully we've got, yes, so you shouldn't
`have to be tracked by yourself.
`The Petitioner will present its arguments first as it bears the burden
`of showing unpatentability of the challenged claims. Petitioner, at this point,
`would you like to reserve time for rebuttal?
`MR. WINTNER: Ten minutes, please, Judge Mitchell.
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`IPR2022-00384 (Patent 10,842,787 B2)
`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`JUDGE MITCHELL: Thank you. And Patent Owner, you will have
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`the last word if you wish. Would you like to reserve some time?
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`MR. MILLS: Yes, 15 minutes, please.
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`JUDGE MITCHELL: Thank you. So, to assist Judge Franklin in
`following along with your argument, and for the clarity of the record, it's
`very important that if you refer to an exhibit you state the exhibit and the
`page number to which you are referring, and when you're referring to a
`demonstrative that you state the slide number. Also, if there's any argument
`that's particular to one case or another, just make that clear on the record so
`when we go back we're very sure of what you're talking about.
`
`We did want to note that demonstratives are not evidence and will
`not be considered as such. They're used just for the benefit of those of us in
`the room to follow and for the benefit of the transcript that will become a
`part of the public record.
`
`The Panel will distinguish evidence in the record from argument
`appearing in any demonstrative exhibits and all arguments must be
`supported by evidence already of record and relied upon in the briefing. The
`panel will not consider arguments or evidence appearing only in
`demonstrative exhibits.
`
`So, that being said, we did note that our oral hearing order asked the
`demonstratives be mailed to the Board at least emailed to the Board at least
`two days, business days prior to the day of hearing. So we did certainly
`receive your demonstratives and we have them, but I know we received
`them in sort of a couple of different ways. But I just wanted to note that we
`just wanted them sent by email and not made part of the record. I know
`you're dealing with Panels that may handle it differently, so trying to follow
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`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`what's going on may be tough, but just a reminder to make sure you read that
`Oral Hearing Order and to abide by that.
`
`So, with that being said, Petitioner, let me get the clock set and you
`can begin when you're ready.
`MR. WINTNER: All right, let me just make sure this clicker is still
`working. I think it is. Okay. So we got that. Okay.
`So, Judge Mitchell, Judge Wisz, Judge Franklin, good morning.
`Again, my name is Tom Wintner from Mintz Levin. Thank you for your
`time today. I'll be speaking on behalf of the Petitioner in these three cases,
`Eyenovia, Inc. And I believe there are hard copies of the demonstratives in
`front of you if you need them.
`JUDGE MITCHELL: Oh, we got that.
`MR. WINTNER: Although I will also be flipping through the slide
`presentation electronically.
`As Judge Mitchell stated, there are three IPRs that we'll be talking
`about today relating to three Syndexis patents, which I will refer to as the
`'787, the '145 and the '557 patents. They share a common specification.
`And the claim structure as you've seen in our papers is quite similar. So, for
`the most part, I'm going to be talking about the '787 patent, and then we'll
`shift to the '145 and the '557 patents a little bit later on.
`But, obviously, where there's a specific slide directed to a specific
`patent, I will do that. And now we're on to Demonstrative Slide 2. This is
`simply showing the three, the face of the three patents. The '787 and '557
`patents are very, very similar in claim structure.
`One is a composition of matter claim set. The other is directed to
`methods of treatment using that composition of matter. The '145 patent is
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`IPR2022-00384 (Patent 10,842,787 B2)
`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`directed to kits comprising a pharmaceutical composition identical to that in
`the '787 and '557 patents, along with instructions of use.
`And for today's presentation, I'm going to provide enough reference
`for four units. The first unit is going to be a little bit of background about
`the science and technology that relates to these particular patents.
`The second will be to discuss the key pieces of art that we rely on
`for our three grounds for two of the cases and our two grounds for the '145
`case. The third set will be a little bit of a claim by claim analysis focusing
`on the '787 patent.
`And then the final section will be a discussion of the '557 and '145
`patents, which should go relatively quickly because a lot of those claim
`elements are different -- or, excuse me, are the same. Now we'll move on to
`Demonstrative Slide 3.
`So, first, a little bit of background about atropine which is the active
`ingredient that is claimed in all of these patents as one reference. This
`Exhibit 1008 describes atropine. It is the oldest and most effective
`pharmacological treatment to inhibit the development of myopia or
`nearsightedness.
`Atropine comes from the night shade family of plants. It's been
`known since the mid-1800s and interestingly enough it's stability, I'm not
`quite sure why, but its stability has been studied for a long, long time going
`back to the 1800s, but certainly into the '50s and '60s through some
`references that we will discuss.
`Structurally, as shown on Slide 3, in the red part of the molecule, it
`is a carboxylic ester, so a carboxylic group connected to an oxygen. And
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`IPR2022-00384 (Patent 10,842,787 B2)
`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`therefore degrades in ways that are known to chemists and have been known
`for hundreds of years.
`And this one shown here is the classic base catalyzed hydrolysis so
`you take hydroxyl ion, it will attack that ester group, it will cleave it and it
`will yield tropine and tropic acid. You can also do this via an acid catalyzed
`mechanism at low pH.
`But this has been known and there is no suggestion anywhere in the
`'787 patent, in the specification in the file history that atropine behaves any
`differently in terms of this kind of base catalytic hydrolysis than any other
`carboxylic ester drug that formulators have studied.
`Now, there were studies done in the '50s and '60s particular to
`atropine. One was done by Kondritzer, that's Exhibit 1005. We're on
`Demonstrative Slide 4 and also on Lund. That's Exhibit 1007 which was
`sort of a follow-on study about a decade later.
`What's shown on this slide is Table 3 plucked out of Kondritzer
`which is at Page 4 of Exhibit 1005. And I think what's in both Kondritzer
`and Lund did two things. First they did theoretical studies, where we can we
`predict using physical chemistry, physical organic chemistry, equations for
`the stability of atropine.
`And then they also confirmed whether those predictions comported
`with reality when they did empirical studies and for the most part they found
`that was the case. What's interesting about Table III is it shows you
`precisely where persons of ordinary skill in the art would have been
`interested in looking at atropine specifically between pHs 2 that's on the far
`right and 7.
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`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`For this kind of a carboxylic acid, it would have been carboxylic
`ester, excuse me, it would have been known to be stable, relatively stable in
`the acidic range. So, i.e., below pH 7. The minute you get above pH 7, you
`have a lot of hydroxyl ion concentration and you get very, very rapid
`degradation.
`So really the framework that Kondritzer was using to study shows
`the person of ordinary skill in the art where you would normally want to be
`formulating atropine somewhere in that 2 to 7 range.
`And of course, it provides specifics with respect to where it is most
`stable. Kondritzer predicted and actually showed empirically that the range
`of pH 3 to 5 was particularly stable and Lund, Exhibit 1007, did similar
`studies, came up with similar results.
`Lund was looking at an additional degradation product due to
`dehydration. So now moving on to Slide 5, another component of the
`background technology is the use of atropine for treatment of various
`diseases. In this case, we're talking about myopia.
`Prior to the priority date of these patents which is April of 2015, so
`that's sort of the key date here, 1 percent and 0.5 percent solutions of
`atropine have been used to either treat myopia or inhibit the progression of
`myopia.
`That was well known and by 1 percent or 0.5 we're talking weight
`percentages. The problem with those formulations is that while they were
`effective, they also caused some side effects and they're shown here for the
`photophobia, cycloplegia, mydriasis and well prior to 2015 several different
`groups including the Chia group which we'll be discussing a little bit more in
`detail later looked at lower dose formulations.
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`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`So they specifically look at .05, .025 percent and then Chia actually
`went all the way down to .01 percent which is within the claimed range for
`the challenged patents here to see whether if that dose was reduced, they
`could still achieve clinical effectiveness while reducing side effects.
`So the use of the low-dose atropine at least as low dose is claimed in
`these patents was also known prior to 2015. I now want to talk a little bit
`about the issue of buffers which has come up in all of the papers and it is
`certainly an element of the claims.
`The, you know, there's sort to two key issues with respect to the
`buffers. You know, one issue is sort of what is a buffer? I don't actually
`think that's terribly disputed between the parties, but then some of the key
`questions are would a person of ordinary skill in the art have been motivated
`to use a buffer either with atropine generally or with an ophthalmic
`formulation using atropine?
`And one of the key teachings with respect to the motivation to use a
`buffer in any ophthalmic solution comes from Remington which both
`experts in this case agree is the formulator's Bible that's, Remington's
`Pharmaceutical Sciences which is Exhibit --
`JUDGE FRANKLIN: Counsel?
`MR. WINTNER: Yes.
`JUDGE FRANKLIN: I don't or I'm actually sorry to interrupt you
`there because I want to hear your next statement, but you mentioned that
`there is really no dispute about what is a buffer and theoretically that may be
`true. But we definitely have issues of, when is a compound a buffer? So I
`want to make sure you plan to address that issue too.
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`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`MR. WINTNER: Fair question, Judge Franklin. I, by saying I
`think, I don't think there's a dispute that both experts say that a buffer sort of
`the quintessential definition of a buffer is something that is able in some
`way, shape or form to maintain a pH or a pH range.
`But you're correct that there may be a dispute as to when is a buffer
`effective? And I think that is something that certainly comes up in Patent
`Owner's papers. And that's an issue that I will address later on in the
`presentation.
`JUDGE FRANKLIN: Thank you.
`MR. WINTNER: So, now we're looking at -- again, this is Slide 6,
`Exhibit 1019, an excerpt from Remington. So this excerpt from Remington
`comes from a specific section in Remington. It's dedicated to ophthalmic
`formulations.
`And Remington makes it clear that the formulator needs to look at a
`variety of different things including sterility, clarity, buffer, buffer capacity,
`pH tonicity, et cetera. So all of these things need to be taken into account by
`the formulator.
`And Remington sets forth sort of for ophthalmic solutions, two very
`important things. It basically says you need to balance the proper pH and
`the buffer and the buffer capacity with patient comfort in the eye.
`Remington starts by saying you need to make sure you have a stable
`composition. If you don't have a stable composition, it doesn't matter
`whether it's comfortable or not comfortable. You're not going to have
`anything that you can give to the patient and be clinically effective.
`But it does say that because the physiological pH of the eye is 7.4.
`You want to be as close as possible to that as you can be. Or, if you're going
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`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`to be formulating at a lower pH or a higher pH as you often have to do and
`Remington, on Page 54 points out that a large, large swath of drugs are just
`like atropine, they are salts of weak bases.
`You may recall that atropine has that little nitrogen group on it so it's
`a weak base. They are all going to be stable only in acidic formulations and
`so what you're trying to balance in the formulation is can I get this thing
`stable, but can I do it in a way where I am minimizing my buffer capacity
`such that when I put it into the eye, the volume of the fluid in the eye can
`overcome that buffer and the patient doesn't experience too much stinging in
`the eye?
`So in a sense, it's sort of a dual motivation. You obviously --every
`formulator knows you need to have your drug be stable. If it's not stable,
`you're not going to be able to administer it, but you're also trying to
`minimize patient discomfort and by doing that you're either going to try to
`keep the pH closer to 7.4 or use a minimal or a low-capacity buffer.
`That's the language that's used in Remington so that buffer can be
`overcome when it's put into the eye.
`JUDGE MITCHELL: So, can I ask you a quick question?
`MR. WINTNER: Sure.
`JUDGE MITCHELL: So, suppose I’m now looking to make a
`formulation, is it only going to look at the buffer to maintain a pH for
`stability. Are they only looking at a buffer for stability of the formulation?
`Or another consideration?
`MR. WINTNER: Generally speaking, that's the primary purpose. If
`you look at Remington and other references that talk about buffers. The,
`because a buffer sort of by definition is going to be maintaining a pH or a
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`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`pH range, the reason you would normally be adding it would be is if it went
`a little bit lower or a little bit higher.
`That would cause some sort of a stability either in the active
`ingredient itself or in some other piece of the formulation that might cause it
`to precipitate out or something like that. So if we go to the next slide, this
`slide sort of addresses the reasonable expectation of success prong.
`There is certainly a motivation to use buffers with ophthalmic
`formulations. The question is, if you were to actually make one of these,
`could you do it and would you have a reasonable expectation of success in
`doing so?
`And this is Slide 7 which is an excerpt from Dr. Laskar's deposition.
` He's the expert on behalf of the Patent Owner Syndexis. And he said that
`and this is at Exhibit 1078, Pages 143 to 144, a POSA would be able to
`prepare a buffer of pHs within that range of 4.8 to 6.4.
`So there's no -- there doesn't appear at least to me to be any dispute
`amongst the experts that to formulate any buffer at any pH range, but
`certainly the pH range that's claimed in these patents which is about 4.8 to
`about 6.4 would be routine experimentation, routine work for the formulator
`whether you were using a citric buffer, an acidic buffer, a phosphate buffer
`all sorts of different components, the formulator would know how to create
`those sorts of solution pH ranges.
`If we flip to Slide 8, I think what's interesting about this case is if
`you look at the prosecution record and you look at the specification while
`there's a lot of emphasis on buffer in this IPR, there's actually very little
`discussion of buffer, buffer capacity, anything like that in the prosecution
`history.
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`IPR2022-00384 (Patent 10,842,787 B2)
`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`What is emphasized is actually pH and the criticality or the
`unexpectedness or the alleged unexpectedness of this pH range of 4.8 to 6.4.
` I'm paraphrasing, but essentially the way in which this patent was granted
`was by convincing the examiner that it wouldn't have been expected.
`And it certainly wasn't present in the primary references that were
`raised by the examiner that atropine would be stable at this pH range of 4.8
`to 6.4. There is no discussion in the file history, there is essentially no data
`whatsoever in the '787 patent specification that talks about the criticality of
`the buffer.
`For example, I'm not aware of any experiment that's outlined in the
`'787 patent. It compares a formulation with a buffer to one without a buffer.
` So everything that the patentee or the applicant talked about during
`prosecution related to this pH range.
`And what we do know is that pH range, this is now Slide 9, 4.8 to
`6.4 was in fact, well known in the prior art as a pH range at which atropine
`either was known to be stable or would have been expected to be stable.
`At least as a matter of overlapping ranges. Kondritzer which was
`not before the examiner indicated that pH 3 to 5 would be very good. Lund
`which was cited in an IDS, but was not discussed pH 2 to 5.4 and the Akorn
`reference which is Exhibit 1004, shows in an FDA approved formulation a
`pH of 3.5 to 6 for an atropine ophthalmic product.
`There's a quote from Kondritzer on this slide referring to prior
`studies before Kondritzer, stability is claimed for 0.1 sterilized atropine
`sulfate solutions in storage if the pH is kept in the range 2.8 to 6.
`So again, every POSA looking at atropine would know based on
`Kondritzer and other studies that this range of 4.8 to 6.4 was not, in fact, an
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`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`unexpected range if you wanted to keep your atropine stable. This is now
`Slide 10.
`All of the claims, and first I want to point out a mistake on this slide,
`Your Honors. I apologize. This lays out Claim 1 from each of the three
`patents. The right-hand box is actually the '787 patent claim and the box on
`the left-hand side of the bottom, the kit is actually the '145 patent.
`So the labeling of those two boxes is swapped. But the point here is
`that all Claim 1 which is the primary independent claim of all of the patents
`doesn't say anything in particular about the buffer. It doesn't say how
`effective it needs to be.
`It doesn't say what composition it will have. It doesn't say how
`many, you know, grams it should have. It just says a buffering agent or a
`buffer. And then the dependent claims and this, I'll focus on Claims 6 and 7
`of the ’787 patent, but they're similar claims in the other two patents, list
`first a laundry list of our accused group of well-known buffering agents for a
`phosphate citrate acetate carbonate, et cetera.
`And then Claim 7 is actually even more specific wherein the
`buffering agent comprises sodium dihydrogen phosphate, disodium
`hydrogen phosphate or a combination thereof. That phosphate buffer pair as
`I will refer to it, is a very commonly known buffer pair involving two
`different species of phosphate salts. Okay, so now we're going to get into
`the prior art and the --
`JUDGE FRANKLIN: And before you do, --
`MR. WINTNER: Yes, Your Honor.
`JUDGE FRANKLIN: I'm going to interrupt again. I think you put
`those claims up in your Slide 11. This might be a good time to address an
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`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`argument that we see coming from Patent Owner in terms of what Claim 7
`of the '787 patent means when it says the buffering agent comprises.
`MR. WINTNER: So if I understand the argument that Patent Owner
`has made and I think Patent Owner's expert also made, essentially what
`we've said is well one of the arguments that the expert makes and we'll get to
`this soon, but I can talk about it right now is that Akorn which includes very
`clearly the same exact two phosphate salts that are listed here that a POSA
`looking at a Akorn wouldn't think that those were actually operating as a
`buffer.
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`And they wouldn't think that because the pH range specified in
`Akorn is 3.5 to 6 which is below the effective buffering range of the
`phosphate buffer. And the point that, the only real point that we're trying to
`make, there's several reasons why we challenge that in rebuttal evidence.
`And I'll go through some of that, but one of them is actually a legal
`reason which is if, in fact, Claim 1 which and again we're looking at Claim 1
`of the 787 Patent on Slide 10. It needs to have a buffering agent to provide a
`pH from about 4.8 to about 6.4 and then Claim 7 which depends from Claim
`1 says that buffering agent comprises this phosphate salt pair, one would
`think that the phosphate salt pair can, either in whole or in part if you want
`to use the comprising language, be contributing to that pH range of 4.8 to
`6.4.
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`Otherwise, there's no way that the full scope of Claim 1 would be
`enabled. So if even though I understand the comprising argument which I
`think is that well maybe it's not actually the phosphate that's doing the
`buffering, maybe you're throwing something else in there.
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`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`To me that's a little bit of a fake because first of all it doesn't explain
`what that other thing might be. Second, Claim 7 is very clear about what the
`primary buffering agent is supposed to be. And third, at a minimum, that
`phosphate buffering pair must be contributing in some way, shape or form to
`the maintenance of that claimed pH range.
`Otherwise, those claims would not be enabled. Does that address
`your question, Judge Franklin?
`JUDGE FRANKLIN: It does, thank you.
`MR. WINTNER: Okay. So I'm not going to run through the
`Instituted Grounds. These are, this is Slide 12. These are outlined in the
`Petition. They're quite similar for each of the patents with the exception of
`the ’145 Patent where there's one less ground because the claims are a little
`bit different.
`But I want to talk briefly about the primary references. Chia Exhibit
`1003, this was a 2011 study published in the Journal of Ophthalmology. It
`was not cited or considered during prosecution. And really, this was the first
`study to show that you could use the low-dose atropine .01 percent which is
`precisely in the range that's claimed in the '787 patent.
`And you could not only get efficacious results, i.e., you could help
`to treat myopia or stem the progression of myopia, but you also could reduce
`side effects. Second reference is Exhibit 1004. That's Akorn. This is an
`FDA approved atropine formulation.
`It was publicly available before the priority date. It also was not
`cited or considered during prosecution. And it includes several of the
`ingredients that are claimed in the challenged patents and, of course, it has
`expressly listed dibasic sodium phosphate and monobasic sodium phosphate.
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`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`And it includes a pH of 3.5 to 6 which actually aligns with the USP,
`the United States Pharmacopoeia Monograph, for atropine sulfate of 3.5 to
`6. So at a minimum a POSA looking at this would understand that is a range
`at which I ought to be able to stably formulate atropine because it's in an
`FDA approved substance that presumably is still around for a while.
`Third primary reference is Wu. This is a patent application. We're
`now onto Slide 15. Wu was Exhibit 1006. This was also not cited or
`considered during prosecution, also publicly available before the priority
`date.
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`Wu is interesting in the sense that while it has a broad specification
`with respect to some different compounds, it certainly is directed to atropine
`and it has claims that are specifically directed not to just a combination of
`atropine and other things, but solely to atropine for the treatment of myopia.
`In the low doses that fit within the ranges of the challenged patents,
`it also indicates that a pH range of 4.5 to 8 can be used and it has sort of a
`generic disclosure. In paragraph 40 it talks about how buffers, preservatives
`and other excipients can be included with this ophthalmic composition.
`We're already talked about Kondritzer. This was also not cited or
`considered during prosecution. Lund, this is now Slide 17. Lund is Exhibit
`1007. Lund is a follow on from Kondritzer. I'm not going to say a lot about
`it.
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`It was cited, but never considered substantively during prosecution
`and also talks about the acidic pH stability range for atropine. Last slide
`before I get to the claim-by-claim analysis is the level of ordinary skill in the
`art.
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`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`Petitioner set this forth in the petition. It was also set forth in Dr.
`Byrn's declaration in support of the petition and shown here on Slide 18. I
`am not, I know there is, has been some challenge to this. What's a little bit
`curious is that I'm not aware that either Petitioner's, excuse me, Patent
`Owner's expert or the Patent Owner response or any other papers actually
`provides an alternative explanation for this.
`My understanding is that the argument is this should potentially be a
`narrower definition that was more directed to ophthalmic formulations. First
`of all, they haven't presented what that would be.
`Second of all, given the breadth of these claims, that doesn't seem to
`be necessary. And third, even if there were a narrower definition, Dr. Byrn
`would need that definition. He testified that he's worked since 2007 with a
`Purdue University program in Africa where he taught ophthalmic
`formulations in Africa.
`He has worked or done consulting work for Alcon which is a well-
`known company that works in the eye space. So even if that were the
`definition and we've never been presented with what the alternative should
`be, he would meet that. Let's touch, let's move to the challenge claims.
`JUDGE MITCHELL: Can I ask one quick question?
`MR. WINTNER: Yes.
`JUDGE MITCHELL: Just to make sure I understand. So of all the
`references, only Alcorn has -- or Akorn, sorry, has a specific formulation
`with buffers. The other references say you can use buffers, but don't give us
`any particular formulations of ophthalmic solutions that have a buffer.
`MR. WINTNER: Certainly of all of the references, Judge Mitchell,
`that I'm aware of that are cited in our grounds, that is correct. There is, you
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`IPR2022-00414 (Patent 10,940,145 B2)
`IPR2022-00415 (Patent 10,888,557 B2)
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`know, one of the background references Remington itself actually, and I'll
`show this on a slide, does have a sort of stock solution of atropine because I
`guess it was commonly studied that includes the phosphate buffers.
`But of the ones that we cite in
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