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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`ARGENTUM PHARMACEUTICALS, LLC,
`Petitioner,
`
`v.
`
`ALCON RESEARCH LTD.,
`Patent Owner.
`____________
`
`Case IPR2017-01053
`Patent 8,268,299 B2
`____________
`
`Record of Oral Hearing
`Held: June 14, 2018
`____________
`
`
`
`
`Before GRACE KARAFFA OBERMANN, SUSAN L. C. MITCHELL, and
`CHRISTOPHER M. KAISER, Administrative Patent Judges.
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`Case IPR2017-01053
`Patent 8,268,299 B2
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`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER:
`
`
`MICHAEL R. HOUSTON, Ph.D., ESQUIRE
`Foley & Lardner, LLP
`321 North Clark Street
`Suite 2800
`Chicago, IL 60654
`
`
`
`ON BEHALF OF THE PATENT OWNER:
`
`
`ALEXANDER S. ZOLAN, ESQUIRE
`DAVID M. KRINSKY, ESQUIRE
`Williams & Connolly, LLP
`725 12th Street, N.W.
`Washington, D.C. 20005
`
`
`
`
`
`The above-entitled matter came on for hearing on Thursday, June 14,
`2018, commencing at 10 a.m., at the U.S. Patent and Trademark Office, 600
`Dulany Street, Alexandria, Virginia 22314.
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`Patent 8,268,299 B2
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`P R O C E E D I N G S
`- - - - -
`JUDGE OBERMANN: Good morning. Please be seated. We're on
`the record. If you just give us a minute. All of the judges have basically
`every exhibit as well as every brief on our computers so if you see us
`looking down and reading or typing it doesn't mean we're shopping on
`Amazon and it doesn't mean we're emailing our friends. We're actually
`paying attention to what you're doing and we're pulling up stuff here that's
`related to your case and taking notes right online. So let me just get my
`computer started so that we can get going here.
`Okay. This is a final hearing in IPR2017-01053 Argentum
`Pharmaceuticals v. Alcon Research Ltd. The challenged patent is U.S.
`patent 8,268,299. I'm Judge Obermann and to my right is Judge Mitchell.
`We have appearing today remotely from Colorado Judge Christopher Kaiser,
`so because we do have Judge Kaiser appearing remotely I want to remind
`counsel that if you're referring to an exhibit he might not necessarily be able
`to see your demonstratives so please give him the slide number and he can
`pull it up on his computer and follow along.
`Let's start with introductions. Who do we have for Petitioner, today?
`MR. HOUSTON: Good morning, Your Honor. Michael Houston,
`counsel for Petitioner Argentum. I'll be arguing and I have with me Mr.
`Tyler Liu from Petitioner, Argentum.
`JUDGE OBERMANN: Thank you very much, but Mr. Houston
`you'll be doing the entire presentation?
`MR. HOUSTON: Yes, yes, Your Honor.
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`JUDGE OBERMANN: Great. And who do we have for Patent
`Owner?
`MR. ZOLAN: Good morning, Your Honor. Alexander Zolan on
`behalf of the Patent Owner. With me is David Krinsky, lead counsel, and
`also Drew Holmes from Novartis, the Patent Owner's parent company.
`JUDGE OBERMANN: Great. And who will be presenting
`arguments?
`MR. ZOLAN: I'll be presenting.
`JUDGE OBERMANN: Okay. And you're Mr. Zolan?
`MR. ZOLAN: That's right.
`JUDGE OBERMANN: Okay. I see you on the list. Great. Each
`party has 45 minutes to present their case. That was in the Hearing Order.
`Petitioner will go first and you may reserve rebuttal time if you'd like, and
`then Patent Owner you can present your case and your case should also
`include any argument you might have on secondary considerations, and I
`will allow you if you'd like to reserve a small bit of time to do a final
`presentation, basically to sur-reply but only on the issue of secondary
`considerations since you bear the burden on that. I'm very appreciative that
`neither party filed any objections to the demonstratives. Thank you very
`much, and I'll just remind you that the demonstratives are not evidence, that
`they're simply a tool for us so that we can see all the evidence that's already
`in the record, sort of synthesized. So I thank you for that.
`Along those lines I'll ask that you don't object during each other's
`presentation. There's no issue of confidential information here. That's the
`only reason I would expect to hear opposing counsel interrupt their friend
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`during their presentation is if there was a disclosure of confidential
`information. I don't think that's an issue here. We are open to the public,
`and I'm going to start the clock ticking when Mr. Houston wants to begin his
`presentation. First of all, I should ask would you like to reserve some time?
`MR. HOUSTON: Yes, Your Honor. I'd like reserve 20 minutes.
`JUDGE OBERMANN: Twenty minutes? I'm going to put 25
`minutes on the clock.
`MR. HOUSTON: And, Your Honor, would it be helpful to the panel
`and the court reporter to have hard copies of the demonstrative slides?
`JUDGE OBERMANN: I'd kind of like that, yes.
`MR. HOUSTON: Okay. I'll ask my co-counsel to approach, if that's
`
`okay.
`
`JUDGE OBERMANN: Sure, thank you. Okay, great. Okay, Mr.
`Houston, when you're ready I'll set your clock ticking.
`MR. HOUSTON: Good morning. May it please the Court. Your
`Honors, as I mentioned before I'm Mike Houston. I'll be speaking on behalf
`of Petitioner, Argentum, this morning in these proceedings.
`I have some demonstrative slides to guide my remarks this morning as
`you're well aware. Slide 2 of the demonstrative really just summarizes the
`filings that have been occurred in the proceedings so far, the filings that have
`occurred and haven't occurred.
`Slide 3 just shows the grounds that were instituted on in the Institution
`decision. Thankfully, in this case that included all grounds and all claims
`that were raised in the petition so they don't have an SAS Institute issue to
`deal with in this proceeding.
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`Going forward, and slide 4 starts out with claim 1 of the 299 patent
`which I'm sure the panel is quite familiar with at this point as it encompasses
`most of the disputes that are at issue between the parties in the proceeding.
`Claim 1 calls for a self-preserve ophthalmic composition containing zinc in a
`specified concentration range. It also calls for certain concentration ranges
`of borates and polyols and anions in the composition and finally the claim
`requires that the composition has to satisfy the USP 27 preservative efficacy
`standard, which is just a test by which we measure whether or not a given
`composition is able to prevent the proliferation of certain key microbes both
`bacteria and fungi across certain time intervals that are measured between 14
`and 28 days in that test.
`Now whether we're look at claim 1 or any of the other claims in the
`299 patent, a key point for the obviousness analysis in this proceeding is that
`none of the claims call for any ingredients that were not already well known
`in the art for use in ophthalmic compositions. There's no new ingredients
`here. Nor do the claims specify any concentration ranges for the ingredients
`that were also not encompassed by the prior art. So, and then lastly but just
`as important, is that none of those components are described as performing
`any function in the composition that was also not already identified in the
`prior art.
`JUDGE OBERMANN: I do have one question, I don't want to
`interrupt you too much, but --
`MR. HOUSTON: Sure.
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`JUDGE OBERMANN: -- is there anything in the prior -- is there any
`composition in the prior art where the borate and polyol component was
`added to boost zinc in particular?
`MR. HOUSTON: I don't believe there's that express teaching in the
`art. Had there been, I believe we might be here talking about anticipation as
`opposed to obviousness, Your Honor. What there are in the record, and I'm
`going to get to in my remarks, is there are compositions like in Xia that have
`zinc, that have borate, that have polyol, so they were there. But I think your
`question was --
`JUDGE OBERMANN: But don't they have other things going on as
`well? I'm wondering if there's any suggestion in the art that that borate
`polyol component would boost zinc, and I want to know specifically if you
`don't have that showing what you're relying on as a reason to add that
`complex to zinc for any reason --
`MR. HOUSTON: Sure.
`JUDGE OBERMANN: -- in a composition that also has all these
`other things going on?
`MR. HOUSTON: So I'd like to make a few points to address your
`question, Your Honor, and I'll start with the fact -- let's not lose sight of the
`fact -- that first of all Xia which teaches zinc --
`JUDGE OBERMANN: That's the X-I-A reference?
`MR. HOUSTON: Yes.
`JUDGE OBERMANN: Okay.
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`MR. HOUSTON: X-I-A, yes, Your Honor. I pronounce it Jaw
`(phonetic), I'm not sure if that's -- but when we were working with Mr. Xia
`and he seemed to agree that was close enough.
`JUDGE OBERMANN: Okay.
`MR. HOUSTON: So I'll start, if you don't mind, with the Xia
`reference which teaches zinc. But -- sure, Your Honor.
`JUDGE OBERMANN: I just wondered, it wasn't real clear to me
`from your brief and I don't know that you have to do it this way, but are you
`starting with the composition that's in Schneider and then modifying it in
`view of Xia? Is that what you're doing?
`MR. HOUSTON: I think that makes the most sense, Your Honor,
`because what Xia says is hey, there are all these ophthalmic compositions
`out there that use the traditional preservants like benzyl chromium chloride
`and Xia says those are known to be harsh preservatives, it would be great to
`avoid those if you can or minimize them if you can, and it teaches a way to
`do that and it specifically describes doing that for ophthalmic compositions -
`-
`
`JUDGE OBERMANN: What is it missing?
`MR. HOUSTON: -- and ones that treat glaucoma -- I'm sorry?
`JUDGE OBERMANN: What is it missing, Xia?
`MR. HOUSTON: Well, actually it --
`JUDGE OBERMANN: (Indiscernible.)
`MR. HOUSTON: Oh, what is Xia missing? Well Xia doesn't have
`some of the more specific compositions or the active ingredients.
`JUDGE OBERMANN: Does it have the complex?
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`MR. HOUSTON: It does, Your Honor, because what we have
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`is we have the borate in there and it teaches that you can have polyols in
`there. It teaches mannitol for tonicity adjustment for example.
`
`JUDGE OBERMANN: Do we have any reference that
`discloses the propylene glycol sorbitol complex with zinc?
`
`MR. HOUSTON: Well, that's what I'd like to get to, Your
`Honor. If you're asking does it teach it that way --
`
`JUDGE OBERMANN: Just those two things together. Do we
`have a reference that has those two?
`MR. HOUSTON: Xia. Xia teaches that you propylene glycol as --
`JUDGE OBERMANN: Does it really teach the combination of
`putting the particular complex that's in claim 1, the propylene glycol sorbitol
`mix, with zinc?
`
`MR. HOUSTON: So the one thing Xia doesn't expressly teach
`is sorbitol. It teaches that you can use polyols and glycols and mannitols,
`that class of compounds to hep adjust tonicity and certainly sorbitol falls
`within that list. It wasn't expressly listed but it teaches that you can do that.
`It expressly teaches propylene glycol. It expressly teaches boric acid and we
`know, even Dr. Majundar, our (indiscernible) expert admits that when
`they're present, when the borate and the polyols are present, they will form
`complexes.
`Now, the Xia reference itself doesn't acknowledge that complex
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`formation but that is occurring in the Xia solutions, Your Honor, and
`similarly to Schneider, Schneider has mannitol and it as boric acid as well.
`Complexes are forming there. It wasn't until Chowhan came along that
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`Chowhan said ah, you know all these polyols and these borates that you're
`using in your ophthalmic compositions, well it turns out if you're just careful
`in the way you adjust the concentrations and what you have in there, you can
`actually optimize that and get good preservative efficacy from the things you
`already have in your compositions.
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`JUDGE OBERMAN: Yes. But what were the antimicrobial
`elements in that reference?
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`MR. HOUSTON: In Xia?
`
`JUDGE OBERMANN: No.
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`MR. HOUSTON: In Schneider?
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`JUDGE OBERMANN: No.
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`MR. HOUSTON: Oh, sorry. In Chowhan?
`
`JUDGE OBERMANN: Yes.
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`MR. HOUSTON: Okay. So Chowhan is basically teaching
`that that concept of borates combining with polyols to form preservative
`efficacy, that works with whatever compositions you want to use.
`
`JUDGE OBERMANN: Well, I'm not buying that because it
`sounds like zinc at very low concentrations is very different from some of
`these other things. You had BAK in there, you had EDTA in there, you had
`all different kinds of things in there. Where is the suggestion that you could
`lower zinc to a level lower than any of the examples that are in Xia and
`boost it by adding the specific complex?
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`MR. HOUSTON: And so I think that the answer to your
`question comes right out of the references. Xia teaches that, under its two
`embodiments whether it's zinc along or zinc plus another preservative, it
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`says you have a preservative effective amount of zinc and it tells us the
`range of zinc that's useful for that and the range that it expressly teaches
`goes down to --
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`JUDGE OBERMANN: I know. But your friends point out that
`the lowest example, example 18, and that one uses zinc at a higher
`concentration.
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`MR. HOUSTON: Well, it is higher although only slightly
`higher, right? It's .48 millimolar and the claimed range here is .4. So it's
`very close already, Your Honor, and we know that it is absolutely error to
`focus on a prior art reference express working examples or preferred
`embodiments to the exclusion of the other teaching.
`
`JUDGE OBERMANN: I'm not trying to (indiscernible), I'm
`trying to see a suggestion --
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`MR. HOUSTON: Okay.
`
`JUDGE OBERMANN: -- where somebody at the time of this
`invention would have looked at these references together and said you know
`what? I can use zinc and I can take out all this other stuff and I can add a
`complex and I'm going to pick, for some reason, propylene glycol and
`sorbitol to make that complex and it's going to boost my very low
`concentration of zinc. I hope that you're going to get to this because if
`you're telling me that your starting with the composition in Schneider, I
`would like you to detail to me in the mind of the artisan what changes have
`to be made, what steps and what reasons to get to what I'm looking at in
`claim 1.
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`MR. HOUSTON: Sure, Your Honor. So like I said,
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`Schneider's the conventional ophthalmic composition for treating glaucoma.
`It has the active ingredient travoprost but it uses benzyl chromium chloride
`and that's on slide 8.
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`JUDGE OBERMANN: And that's what we want completely
`out of ours, right?
`
`MR. HOUSTON: Yes. And so Xia comes along and says, in
`fact the whole art kind of recognized that there's a problem with benzyl
`chromium chloride. It's not ideal, you have to have it because you have to
`have preservative efficacy but the art recognizes that especially a lot of in
`vitro tests show that it looks like it causes problems. It's toxic.
`
`JUDGE OBERMANN: So there's our reason that we want to
`get rid of it?
`
`MR. HOUSTON: So there's our reason to move away from
`benzyl chromium chloride, the conventional preservative that was used in
`Schneider which is what's in the Travatan commercial product that was first
`marketed by Alcon. Okay, so that's formulation A from example 2 of
`Schneider, Exhibit 1007 that we're showing here on slide 8.
`
`And so we have Xia come along and say ah, we have
`recognized this problem with the conventional preservatives. I mean they're
`right here on slide 7 in the middle box. It's recognizing that these traditional
`preservatives are problematic and it says that, hey, the way to solve that, get
`rid of that conventional preservative and use zinc instead and use it in a
`preservative effective amount which Xia defines as an amount of zinc that is
`sufficient to meet the preservative efficacy test.
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`JUDGE OBERMANN: Without any of these other things in it?
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`MR. HOUSTON: Absolutely. That's the way -- if you look at
`
`Xia -- that's the way it defines that. It's enough zinc to meet the preservative
`efficacy test. But Xia goes further. Xia says well, there's sort of two ways
`to do this. You can use just the zinc or you can use the zinc along with a
`second preservative that is not there in an amount that would pass
`preservative efficacy by itself. So Xia says a less than preservative effective
`amount of your second preservative. So that's the express teaching to make
`the first step to go from Schneider that uses benzyl chromium chloride to go
`and do something that has zinc instead as a replacement.
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`JUDGE OBERMANN: And can you tell me where exactly -- I
`really am meaning this genuinely -- where in Xia is the teaching that you're
`going to go really low and not include any of the other things?
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`MR. HOUSTON: Well, it's just in that -- like I said -- Xia
`teaches that what it's focused on, and this is in the Summary of the Invention
`of Xia which we can pull up perhaps, Tyler, Xia's Exhibit 1003, Summary of
`the Invention I believe is on page 4 of the reference. So the present
`invention is a directed composition with a preservative effective amount of
`zinc and has a less than preservative effective amount of another
`preservative agent, and then -- I can't remember, it's just the top of the next
`page -- it tells you what zinc concentrations, I believe it's the top, I'm sorry.
`Tyler keep going, maybe it's the next page. Right there. So then it says,
`here are the zinc concentrations that work for this invention.
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`JUDGE OBERMANN: Okay. I understand it, I've read the
`reference.
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`MR. HOUSTON: Okay.
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`JUDGE OBERMANN: What I need to know, first of all, that
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`general disclosure. Your friend is arguing that that could mean, you know,
`low doses when you have it combined with something else.
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`MR. HOUSTON: Okay.
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`JUDGE OBERMANN: So I think to be fair we need to look at
`the examples. Am I correct, are there any examples in there where zinc is
`the only preservative and you would hit the amount that you need?
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`MR. HOUSTON: Okay. So if I could I just want to make clear
`that I don't agree that you have to look at Xia's examples and I think it's error
`to only look at only Xia's examples. But that's fine.
`
`JUDGE OBERMANN: Well, I'm looking at this and I'm --
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`MR. HOUSTON: Okay.
`
`JUDGE OBERMANN: -- and I'm an ordinary artisan and I
`don't have the benefit of the roadmap of the patented issue and I'm looking at
`this and I'm saying okay, I'm being told I can use zinc alone or I can use zinc
`with some other --
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`MR. HOUSTON: Something else.
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`JUDGE OBERMANN: And then I'm looking at this general
`disclosure that I can go low, I can go high, and then I'm looking at the
`examples and I say, oh, when I go low I've got something -- I don't know. I
`need to see something that's going to tell me that I can go as low as that
`general disclosure and that will be effective --
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`MR. HOUSTON: Okay.
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`JUDGE OBERMANN: -- without the other stuff which is
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`what, a JP thing or --
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`MR. HOUSTON: Well, the polymer JR is an example of
`another preservative agent that can be added to zinc, but as I've mentioned
`before so example 18 gets us to .48 millimolar zinc. Zinc along passes
`preservative efficacy. So we're very close right there.
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`JUDGE OBERMANN: So are you arguing that someone -- it's
`not a result effective variable at that point, is it?
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`MR. HOUSTON: Zinc?
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`JUDGE OBERMANN: Well --
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`MR. HOUSTON: Zinc concentration?
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`JUDGE OBERMANN: -- you're relying on the .48 and you're
`saying it's close enough. Don't you have to do something to get it into the
`range of the claim?
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`MR. HOUSTON: Well, so zinc concentration is certainly a
`result effective variable. It's known that the concentration of zinc affects
`preservative efficacy.
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`JUDGE OBERMANN: But with all this other stuff going on.
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`MR. HOUSTON: I'm not sure what other stuff you're referring
`to, Your Honor. We've taken the conventional preservative out, replaced it
`with zinc,
`JUDGE OBERMANN: You've also go to take out EDTA.
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`MR. HOUSTON: Sure.
`
`MR. HOUSTON: You've to manipulate the anionic content. You've
`got to get this complex in there to boost it.
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`MR. HOUSTON: Tyler, if we could go back to slide 8 which is
`Schneider's formulation and let me see if I can walk us through those
`changes. So in the original Travatan composition --
`JUDGE OBERMANN: What slide number is that, 8?
`MR. HOUSTON: Slide 8, Your Honor, yes. So in that case, and this
`is in our papers by the way, in order to get from there to Xia you're going to
`take out the benzyl chromium chloride and replace it with zinc and Xia
`teaches us -- you mentioned about EDTA, Your Honor -- Xia teaches us
`that, yes, can you have EDTA in your solution? Sure you can but if you do
`you're just going to have that much more zinc to offset the EDTA.
`So Xia teaches us that while you can have EDTA there, if you have
`some other reason that you want it, that it's going to just degrade the
`efficiency of zinc so you're going to have to use more zinc.
`JUDGE OBERMANN: So does Xia actually take it out?
`MR. HOUSTON: Oh, absolutely. Xia has many examples without
`EDTA. That's shown here on slide 14, Your Honor.
`JUDGE OBERMANN: One of the other things that jumped out at me
`is you're changing the complex in Schneider because they have a borate and
`a polyol but it doesn't have the sorbitol or the propylene glycol; is that
`correct?
`MR. HOUSTON: Yes.
`JUDGE OBERMANN: But then you're relying on the concentration
`that's disclosed. Is there any reason that we would use the same
`concentration once we've changed everything?
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`MR. HOUSTON: Well when you say would you change everything, I
`think that's exactly where the teachings from Chowhan come in. Chowhan
`says hey, remember those borates and polyols that you used in your
`ophthalmic composition, look what we discovered? We discovered that if
`you pick certain ones and you use them in specific concentration ranges you
`actually get, No. 1) a preservative effect from the borate polyol complexes
`and you get a boost to what your other preservative agent is in your solution.
`JUDGE OBERMANN: (Indiscernible) talk about. So, but you're
`relying on the percentage of what's disclosed in Schneider and not in
`Chowhan, right?
`MR. HOUSTON: I think we pointed out that Schneider already uses,
`for example, boric acid that's within the claimed range but I don't think we're
`relying on Schneider to teach the claimed boric polyol concentrations.
`JUDGE OBERMANN: Oh, you're not.
`MR. HOUSTON: And in fact, I mean I will admit that the polyol in
`Schneider isn't within the claimed range and it's not even the same polyol,
`it's a mannitol versus sorbitol. Now the 299 patent specification makes clear
`that mannitol is really part of the invention as well, but that doesn't end up in
`the claims that are at issue here.
`JUDGE OBERMANN: Okay.
`MR. HOUSTON: And so --
`JUDGE OBERMANN: I must have misread your petition because I
`thought that you were relying on Schneider for the concentration of that
`complex.
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`MR. HOUSTON: No, Your Honor. That comes directly out of
`Chowhan. Chowhan is the seminal teaching that says here's what you do to
`your borates and your polyols to get this nice bump in preservative efficacy.
`JUDGE OBERMANN: Oh, I see. I didn't see that, because on page
`15 of your brief you say Schneider included EDTA, tromethamine, and
`borate polyol system or the polyol mannitol boric acid in the borate polyol
`system falls within the claimed range?
`MR. HOUSTON: Your Honor, you were reading from page 15 of the
`petition?
`JUDGE OBERMANN: I am. Where do you get the .3 weight percent
`for a boric acid in claim 1?
`MR. HOUSTON: I believe that comes -- well, one place it comes
`from is right out of Schneider. That's the concentration Schneider reports
`using.
`JUDGE OBERMANN: But you say that's a claimed range. I'm not
`seeing a claimed range for boric acid in 1.
`MR. HOUSTON: Well it's the borate, Your Honor. The borate is
`called for between .12 weight percent.
`JUDGE OBERMANN: Oh, I see. Okay. So you're saying that
`somebody would keep the borate concentration the same and then switch out
`the mannitol, add these two other things?
`MR. HOUSTON: Your Honor, I think that's getting a bit specific.
`What we're saying is that a POSA is going to be charged with knowing the
`teachings of Chowhan, so they're going to do what Chowhan says.
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`JUDGE OBERMANN: Well, it's pretty specific in the claim and I
`think you have to show that somebody would have been led to this particular
`composition.
`MR. HOUSTON: Well, Your Honor, I mean just look. The claim
`calls for .12 weight percent borate, for example. That's over an order of
`magnitude range. It calls for a range of the borate polyol complex that's
`actually even wider than the preferred range that's taught in Chowhan. So
`what we're saying is a POSA is going to be aware of Chowhan and Chowhan
`teaches you how to adjust what's the components that are already commonly
`used in the ophthalmic compositions.
`JUDGE OBERMANN: But not with zinc.
`MR. HOUSTON: I'm sorry?
`JUDGE OBERMANN: But not with zinc.
`MR. HOUSTON: Oh, well it teaches that it's to be used with another
`preservative. It says it presents its own preservative efficacy, the complexes
`themselves, and it boosts the preservative efficacy of the preservative you
`already have there. It's not designed to be used by itself, Your Honor, and so
`it's a teaching that says it does two things. It gives its own preserved
`efficacy effect and it helps the preservative that you already have there,
`whatever that is.
`JUDGE OBERMANN: Does it describe, because it does say it
`increases the antimicrobial efficacy of other antimicrobial agents. So does
`Chowhan list other antimicrobial agents or give any examples?
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`MR. HOUSTON: Oh, gosh, Your Honor. That is something I just
`don't have memorized. I can take a look at that maybe while Patent Owner
`is speaking --
`JUDGE OBERMANN: Sure.
`MR. HOUSTON: -- and see if I can answer that in rebuttal.
`JUDGE OBERMANN: Sure.
`MR. HOUSTON: To be fair I don't think it expressly lists zinc. I
`think it's a more general teaching. It's a teaching that Alcon came up with
`some 20 years ago, where they said aha, we found out that the borates and
`the polyols that are in all these ophthalmic compositions they can be
`optimized to give this nice effect, and so it's a general teaching. It doesn't
`have to be limited to just zinc. It's telling the POSA that you're going to get
`this effect when you tweak your borates and your polyols, as Chowhan
`teaches.
`JUDGE OBERMANN: But is there more discussion in Chowhan that
`really tells me hey, pretty much any antimicrobial agent that you use in these
`solutions would be boosted by that complex?
`MR. HOUSTON: Tyler, if we could pick up slide 9? If we could go
`to demonstrative slide 9? And I think, Your Honor, this also helps kind of
`meld the teachings of Xia and Chowhan because Chowhan also recognizes,
`which is shown on slide 9 at the top box, yes, benzyl chromium chloride is
`the traditional preservative, it works great. But it's harsh, it's toxic, it's not
`one we want to use. So Chowhan is saying here's another way to get around
`benzyl chromium chloride. Optimize your borate polyols for use with
`another preservative and get away from these harsh effects of benzyl
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`chromium chloride which is the same exact motive that a POSA was
`pursuing in trying to implement Xia to begin with. So they have harmonious
`--
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`JUDGE OBERMANN: Along those lines, your friend argues on page
`21 of the response that while a POSA would understand the challenge
`effective to augment antifungal activity, a POSA would in challenge would
`not have expected that the borate polyol complexes would restore the
`antibacterial activity. What's your response to that?
`MR. HOUSTON: Yes, Your Honor. So we have slide 16 on that. In
`brief, what I would say is the following. So first of all, Chowhan describes
`the borate polyol complexes as having antimicrobial properties. Every
`expert in this case agrees that antimicrobial is a term of art that covers both
`bacteria and fungi. So when it says it has antimicrobial properties that's not
`limited to fungus, it covers both bacteria and fungus.
`Now what Patent Owner points to are the examples in Chowhan
`where, in its case, the examples that it shows were using the borate polyol
`complexes with BAK and what happens is BAK is so effective at killing
`your bacteria, you basically reach the limit of bacteria killing that you can
`get. You just can't get any more bacteria killing because you have around
`100,000 bacteria per mil in your starting solution, and so getting the 5 order
`log reduction, that's the most you can get. There's no more bacteria to kill.
`So you've kind of maxed out your sensitivity of that test, and so of course
`when you add your borate polyol complex to that, you're not going to see
`any additional bacteria killing because there are no more bacteria to kill.
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`So they're trying to rely on this example to say aha, it doesn't show
`any increased bacteria killing that the complex doesn't. But that's a faulty
`premise of the test. The test is already saturated and, Your Honor, that
`concept -- and this is cited in our brief -- it was recognized by Dr. Zhanel.
`He admitted that you've got a finite amount of bacteria in there and when
`you get to about a 5 log reduction, which is what you see with BAK, you
`can't get any more. I mean there's decimal point bumps here and there that I
`think are really just background noise, I don't think those are significant.
`JUD
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