`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`Page 1
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`)
`
`) )
`
` ARGENTUM
` PHARMACEUTICALS LLC,
`
`) )
`
`Petitioner,
`
`vs.
`
` Inter Partes
`) Review No.
`) IPR2017-01053
` ALCON RESEARCH, LTD., )
`)
`Patent Owner. )
`
`The deposition of GEORGE G. ZHANEL, Ph.D.,
` called by the Petitioner for examination, pursuant
` to stipulation, and pursuant to the applicable
` rules, taken before Sandra L. Rocca, CSR, CRR, at
` 321 North Clark Street, Chicago, Illinois, on the
` 10th of April, 2018, at the hour of 11:57 a.m.
`
`www.veritext.com
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`Veritext Legal Solutions
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`Exhibit 1048
`ARGENTUM
`IPR2017-01053
`888-391-3376
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`Page 2
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` A P P E A R A N C E S :
`
` F O L E Y & L A R D N E R
` B y : M R . M I C H A E L R . H O U S T O N , P h . D .
` 3 2 1 N o r t h C l a r k S t r e e t , S u i t e 2 8 0 0
` C h i c a g o , I l l i n o i s 6 0 6 5 4 - 5 3 1 3
` 3 1 2 . 8 3 2 . 4 3 7 8
` m h o u s t o n @ f o l e y . c o m
` a p p e a r e d o n b e h a l f o f t h e
` P e t i t i o n e r ;
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` W I L L I A M S & C O N N O L L Y , L L P
` B y : M R . A L E X A N D E R S . Z O L A N
` M R . A D A M L . P E R L M A N
` 7 2 5 1 2 t h S t r e e t , N W
` W a s h i n g t o n , D . C . 2 0 0 0 5 - 5 9 0 1
` 2 0 2 . 4 3 4 . 5 2 0 8
` a z o l a n @ w c . c o m
` a p e r l m a n @ w c . c o m
` a p p e a r e d o n b e h a l f o f t h e
` P a t e n t O w n e r .
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`Page 3
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` I N D E X
`
` WITNESS PAGE
`
` GEORGE G. ZHANEL, Ph.D.
`
` EXAMINED BY
`
` Mr. Houston 4
`
` EXHIBITS
`
` NUMBER PRESENTED
`
` Exhibit 1001 U.S. Pat. No. 8,268,299 29
`
` Exhibit 1003 WO 2005/097067 A1 26
`
` Exhibit 1004 U.S. Pat. No. 6,143,799 60
`
` Exhibit 1007 U.S. Pat. No. 6,011,062 63
`
` Exhibit 2025 ALCON 2025
`
` Zhanel declaration 5
`
` Exhibit 2123 T.J. McCarthy article 110
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` GEORGE G. ZHANEL, Ph.D.,
`
` having been first duly sworn, was examined and
`
` testified as follows:
`
` CROSS EXAMINATION
`
` BY MR. HOUSTON:
`
` Q Good afternoon, sir. Could you start just
`
` by stating your full name for the record?
`
` A My name is George Zhanel.
`
` Q And Dr. Zhanel, is that right?
`
` A Dr. Zhanel.
`
` Q Dr. Zhanel, have you sat for a deposition
`
` previously?
`
` A Yes.
`
` Q About how many times have you been deposed?
`
` A Approximately ten times.
`
` Q Okay. So you're reasonably familiar with
`
` the procedure here where I'm going to ask you a
`
` series of questions and you're going to try to
`
` answer those questions to the best of your ability
`
` while the court reporter sitting here beside us will
`
` try record the things we say and the questions I ask
`
` and the answers you give.
`
` A Yes.
`
` Q Given your familiarity with it, then I'll
`
` skip some of the other preliminaries and I'll just
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` ask that if there's a point at any time today that I
`
` ask you a question that you don't understand or need
`
` clarification on, please just ask me for
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`Page 5
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` clarification if you need it.
`
` A Thank you.
`
` Q Fair enough? Okay.
`
` (Document marked previously as
`
` Exhibit 2025 was presented.)
`
` Q I'll start by handing you, sir, an exhibit
`
` that's been marked Exhibit Alcon 2025 which I
`
` believe you'll recognize as a copy of the
`
` declaration that you submitted in this proceeding.
`
` Is that right?
`
` A Yes.
`
` Q I'll ask you to turn to paragraph 10 of your
`
` declaration to start with. It's on page 5.
`
` A Yes.
`
` Q And there on paragraph 10 you have listed a
`
` number of companies that you have provided some
`
` services for. I don't know if the right way to
`
` characterize that is consultant services or some
`
` other services for these companies. Do you see that
`
` there?
`
` A Yes.
`
` Q At the outset I wanted to clarify, I don't
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` see Alcon on that list. Is that correct?
`
` A Yes.
`
` Q So aside from this proceeding, have you
`
` previously done any work for Alcon?
`
` A I have not been a consultant regarding
`
` research matters and innovative research projects
`
` with Alcon.
`
` Q What about any other type of consultancy
`
` work for Alcon, again besides this proceeding?
`
` A The only consultancies that I've done
`
` regarding Alcon are this litigation. The
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` consultancies that are on page 10, these are
`
` research related matters where people are asking my
`
` opinion typically about innovative new molecules.
`
` Q Just so I'm clear, when you said the work
`
` you did for Alcon -- I'm sorry, I'm not sure exactly
`
` how you worded it -- was related to litigation, is
`
` the work you've done for Alcon just this proceeding
`
` or have you done other work for Alcon related to
`
` litigation matters?
`
` A I have been previously involved in other
`
` litigation regarding Alcon.
`
` Q About how many other litigations have you
`
` been involved with for Alcon?
`
` A I can't recall precisely. I remember a case
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` regarding an eye drop called Vigamox, which has an
`
` antimicrobial in it; a separate proceeding on
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` Travatan Z. That's what I recall. Travatan Z
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` related and Vigamox, which is moxifloxacin related.
`
` Q What's the antimicrobial that you referred
`
` to in Vigamox?
`
` A Moxifloxacin. It's a fluoroquinolone.
`
` Q And then what about Novartis? Again I don't
`
` see Novartis listed on this list of companies here
`
` in paragraph 10. So is it safe to assume that you
`
` haven't done any research related consultations with
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` Novartis or Novartis entities?
`
` A That's correct.
`
` Q What about litigation work for Novartis or
`
` its various entities?
`
` A Not that I'm aware of or recall.
`
` Q Among the companies that are listed here in
`
` paragraph 10, are any of these companies working on
`
` ophthalmic solutions? Or maybe a better way to put
`
` that, rather than put you on spot there, is was any
`
` of your work for these companies related to
`
` ophthalmic solutions?
`
` A Yes.
`
` Q Can you describe which ones those would be
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` for?
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` A I'll describe it in two ways. One, for
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` example, is a company called Bayer or Bayer. They
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` are the innovators of the drug moxifloxacin, the
`
` fluoroquinolone, and they worked, I believe, in
`
` partnership with Alcon regarding the moxifloxacin
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` eye drops.
`
` Other companies on this list I have
`
` consulted for, they're making novel antimicrobials
`
` or agents with antimicrobial activity and they are
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` asking my advice in part regarding potential
`
` indications for these molecules which would include
`
` ophthalmic uses.
`
` Q Is the list of such companies short enough
`
` that you could identify those for me?
`
` A I'll say more than half of these companies,
`
` likely two-thirds, they're making a molecule and
`
` they are asking my opinion to look at all the
`
` properties of the molecule and guide them about any
`
` potential uses for any type of infection. So
`
` whether I'm consulting for Abbott or Achaogen or
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` Astellas, Bayer, GlaxoSmithKline, Ortho McNeil,
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` Merck, Paratek, Pfizer, they are asking my opinions
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` regarding any and all indications, so I don't want
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` to limit to exclude any of them.
`
` Q Okay. With respect to your consultancy work
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` for these companies, has it ever gotten down to the
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` level of where you are recommending or discussing
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` specific ophthalmic formulations as opposed to I
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` think the way you just described, at least that
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` aspect of your work, was identifying applications
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` for some of the novel antimicrobials they're working
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` on?
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` Have you ever gotten to the level of
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` consulting as to specific ophthalmic formulations?
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` A Yes. We're talking about does this agent
`
` have the potential to be used for ophthalmic
`
` infections, what would be the advantages, what would
`
` be the disadvantages compared to the comparators;
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` types of formulations, ointments, drops, potential
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` intraocular injections. Yes, we're talking about
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` formulations.
`
` Q What about consulting as to specific
`
` formulations that would be desirable for
`
` aqueous-based ophthalmic eye drop solutions?
`
` A Yes, we are talking about aqueous-based
`
` ophthalmic compositions of active -- that include
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` active ingredients in them.
`
` Q So limited to that topic, have one or more
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` of your consulting activities -- did one or more of
`
` your consulting activities occur prior to
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` September 2006?
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` A Yes, many of these -- I've been consulting
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` for many of these companies for the last 25, close
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` to 30 years.
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` Q As part of this consulting work prior to
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` 2006, have you ever provided guidance to one of
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` these companies, or anyone else really, with respect
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` to developing an ophthalmic eye drop formulation
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` that's specifically designed to not use a
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` conventional preservative such as benzalkonium
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` chloride, which if you don't mind, maybe if we
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` could, can we abbreviate that as "BAK" today?
`
` A Yes.
`
` Q So have you ever consulted for the specific
`
` purpose of avoiding the use of BAK in an ophthalmic
`
` suspension formulation -- I'm sorry, not ophthalmic
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` suspension -- ophthalmic eye drop formulation?
`
` A Yes.
`
` Q Can you give me an example of that?
`
` A Yes. BAK is a very commonly used,
`
` traditional, conventional primary preservative, but
`
` ophthalmic compositions can also be self-preserved
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` with an antimicrobial in them. For example, the
`
` moxifloxacin eye drops, they do not have a
`
` traditional preservative. They are self-preserved
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` because the fluoroquinolone, the antimicrobial
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` provides the preservative activity.
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` Q So in that case, what would be the purpose
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` of avoiding BAK or the use of BAK in such a
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` formulation?
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` MR. ZOLAN: Objection to form, vague.
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` THE WITNESS: In that particular
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` formulation, a person of ordinary skill would see
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` having both the antimicrobial moxifloxacin and the
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` BAK as being redundant and an unnecessary use of
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` BAK.
`
` Q Would you agree with me that as of September
`
` 2006, a POSA -- and if you don't mind I'll use POSA
`
` in the same way you've used it in your
`
` declaration -- that a POSA would have appreciated a
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` desirability of avoiding the use of BAK, if
`
` possible, in an ophthalmic eye drop formulation?
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` A A POSA was aware in 2006 that BAK was a very
`
` commonly used preservative. But for an eye drop
`
` that would be used in a chronic fashion, a person of
`
` ordinary skill would see the advantage of not having
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` BAK and potentially preserving using other
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` preservatives.
`
` Q I'm going to try to not get into what might
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` be proprietary details of this moxifloxacin
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` formulation that you've been discussing, but I'm
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` going to try to ask some general questions and you
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` can let me know if we get into a sensitive area.
`
` In the formulation that you consulted for
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` regarding the inclusion of moxifloxacin and not
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` including BAK -- first of all, let me just make sure
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` I'm clear. That was something that occurred before
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` September of 2006, is that right?
`
` A I can't recall the exact year. It would
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` have been -- I can't recall the exact year.
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` Q Well then, let me back up. Is there an
`
` instance where you consulted with one of these
`
` companies regarding a BAK-free ophthalmic eye drop
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` formulation that you know for certain was before
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` September of 2006?
`
` A Yes.
`
` Q Okay. Can you give me an example of that?
`
` A There are other fluoroquinolones, for
`
` example, levofloxacin and ofloxacin, that also have
`
` been formulated into eye drops. These are also
`
` self-preserved eye drops that do not have BAK in
`
` them.
`
` Q Do those compositions have -- the
`
` formulations you're aware of, do they contain boric
`
` acid or a borate?
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` A I can't recall.
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` Q What about a polyol, do you recall if they
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` contain a polyol?
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` A I can't recall.
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` Q What about zinc, do any of the ones you've
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` consulted on prior to 2006 contain zinc?
`
` A No.
`
` Q Did the formulations -- did the BAK-free
`
` formulations that you've consulted on prior to
`
` September of 2006 contain any additional
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` preservative agents besides the fluoroquinolones
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` that you've mentioned?
`
` A Not that I recall.
`
` Q So those were all instances of, to the best
`
` of your recollection, a single preservative agent?
`
` A Correct.
`
` Q Prior to September of 2006, do you ever
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` recall consulting with anybody or working on a
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` project that involved multiple preservative agents
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` where none of the preservative agents are one of the
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` conventional ones such as BAK?
`
` A Could you repeat that question for me one
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` more time?
`
` Q Sure. Let me see if I can remember it.
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` (Record read as requested.)
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` THE WITNESS: I can't recall.
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` Q Do you recall any formulations you worked on
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` prior to 2006 that involved a borate or boric acid?
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` A I can't recall a specific formulation, but
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` I'm certain the answer to that is yes because boric
`
` acid is a very commonly used buffer in ophthalmic
`
` compositions, so it wouldn't surprise me if the
`
` answer to that question is yes.
`
` Q Do you have any specific recollection of
`
` those compositions that you expect would contain
`
` boric acid or a borate of those also containing a
`
` polyol?
`
` Maybe I could interrupt your thinking for a
`
` second, Dr. Zhanel, because I realize -- at least I
`
` don't want there to be an ambiguity about what I
`
` mean by polyol. So I guess for purposes today, I
`
` know you've used it a number of times in your
`
` declaration, I suspect the best thing to do is to
`
` use the description of polyol that's used in the
`
` '299 patent, the patent at issue here.
`
` A Yes.
`
` Q But if you have a different understanding,
`
` please let me know.
`
` A I have the same understanding.
`
` Q Okay, thank you. So with that then, do you
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` recall ever working on a formulation prior to
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` September of 2006 that would have contained boric
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` acid or a borate and a polyol?
`
` A I do not recall working on such a
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` formulation or consulting on such a formulation
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` prior to 2006.
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` Q Is the answer the same as to formulations
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` that would contain zinc?
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` A So I've been teaching, learning, discussing,
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` was trained regarding zinc back starting in the
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` '80s, so I've had a lot of opinions on zinc. And if
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` your question is has anyone asked my opinion
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` regarding using zinc, boric acid and a polyol before
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` 2006 together, I can't recall that.
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` Q Okay. And so I'm glad you asked because
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` that will allow me to clarify. I just wanted to
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` know if you've done any consulting on an ophthalmic
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` eye drop solution prior to September 2006 that would
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` contain zinc? I'll leave the boric acid polyol
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` piece out of it is my point.
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` MR. ZOLAN: Objection to form, asked and
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` answered.
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` THE WITNESS: I have consulted for companies
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` and given my opinion regarding the usage of zinc as
`
` an antimicrobial agent for a variety of settings
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` which would include aspects of ocular infections.
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` Q If it's not too voluminous, could you
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` describe or summarize what -- again I want to make
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` sure that we're limited to prior to September 2006.
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` Would you summarize what your opinions were
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` regarding the usage of zinc in the context of -- I'm
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` sorry, what did you say, ocular --
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` A Ocular infections.
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` Q Ocular infections, okay.
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` A In brief, this teaching is that zinc, like
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` many trace metals, is an essential element in the
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` human body, but also an essential micronutrient for
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` organisms.
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` However, as you increase the dose of zinc,
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` you get to a point where zinc displays a
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` dose-dependent inhibition of microorganisms and if
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` you use a high enough concentration, you actually
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` kill microorganisms. I've also been asked about my
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` opinions regarding zinc safety regarding human
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` tissues, including ocular tissues and as well have
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` been asked about my opinion about using zinc with
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` traditional preservatives.
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` Q So the last part, the part about using zinc
`
` with traditional preservatives, when were you asked
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` about that? About when?
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` A Back as early as the late '80s, early '90s.
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` Q And this would have been in the context of
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` ocular infections or treating ocular infections?
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` A This would have been in the context of
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` preventing and treating infections, for example, on
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` the skin, but it could also be in the eye.
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` Q Well, I do want to be a bit more specific.
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` I think you said you had given opinions regarding
`
` the usage of zinc in the context of ocular
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` infections. So I just want to be clear, you have
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` consulted or opined as to the usage of zinc in the
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` context of ophthalmic eye drop formulations, is that
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` fair to say?
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` A Yes, people are asking my opinion about
`
` zinc's biological properties in the context of
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` treating and preventing ocular infections.
`
` Q And so then what is your opinion? What have
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` you told these companies that ask you your opinion
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` about zinc in treating or preventing ocular
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` infections, prior to 2006?
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` MR. ZOLAN: Objection to form, vague.
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` THE WITNESS: It would depend on the exact
`
` and precise question they are asking me, but a
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` significant aspect of what I would say would be that
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` zinc is a safe agent regarding ocular formulations.
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` It can be used at relatively high doses,
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` 0.25 percent, 0.5 percent, even 1 percent, perhaps
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` even higher, can be used at high concentrations and
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` it's a safe agent.
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` I've been advising them that this is a
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` dose-dependent inhibitor of organism growth and has
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` the capability of actually killing organisms at high
`
` enough concentrations. Those are the major things
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` that I've been telling them. And a word of caution.
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` I've also been saying that zinc is -- this is not a
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` traditional preservative. It has no track record
`
` being used alone. So realize that this is different
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` than a BAK where a low concentration of BAK may
`
` simply not inhibit all the organisms or it may fail
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` preservative efficacy, but a low concentration of
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` zinc can actually stimulate bacterial growth because
`
` it's an essential micronutrient.
`
` Q In the context of those consultations, have
`
` you provide any context -- any suggestion as to the
`
` concentration of zinc at which it -- I don't want to
`
` put words in your mouth -- but in which it kind of
`
` crosses over from being an inhibitor to being a
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` promoter or a nutrient for microbes?
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` A Yes, I'm aware you're asking me, not a POSA,
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` you're asking me, I'm -- this is all I do for a
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` living. So I'm aware of the literature and I would
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` have been aware of the literature regarding zinc's
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` dose-dependent antimicrobial activity and that was
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` well-described at which concentrations it would act
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` as a nutrient, at which concentrations it would
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` inhibit growth, at which concentrations it would
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` kill organisms, at which concentrations it may cause
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` toxicity to the eye.
`
` Q Okay. So prior to September of 2006, what
`
` is the range of concentrations for zinc that you
`
` would -- that you would recommend would be good for
`
` inhibiting bacterial growth as opposed to that would
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` promote bacterial growth?
`
` A So if I was asked, prior to 2006 if zinc was
`
` to be used as the sole preservative without any
`
` traditional preservative, so no assistance of BAK or
`
` Polyquad or chlorhexidine or another traditional
`
` preservative, if zinc was being used alone, the
`
` prior art teachings were that if you're using low
`
` concentrations in the range of 0.07, 0.1, 0.2
`
` millimolar, perhaps even up to 0.3 or stimulating
`
` bacterial growth, there was data that 0.5 millimolar
`
` of zinc could inhibit growth that subsequently led
`
` to rapid bacterial adaptation and resistance and
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` that concentrations of 1 millimolar or higher could
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` inhibit growth and actually kill organisms.
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` Q What about the context -- now you prefaced
`
` that answer by making clear you were talking about
`
` zinc as the sole preservative. What about the
`
` context in which zinc was not the sole preservative?
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` What concentrations would you have suggested under
`
` those circumstances might be used -- might zinc be
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` used as a preservative?
`
` A So if you have a formulation that would have
`
` a traditional preservative such as BAK, I would or a
`
` POSA would have an expectation that at the typical
`
` concentrations of BAK used, for example,
`
` 0.015 percent, that the BAK would be the heavy
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` hitter in terms of the preservative efficacy. This
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` agent would have broad spectrum antimicrobial
`
` activity and would be killing these organisms. And
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` so if you were adding zinc, you would not really be
`
` depending on zinc for the preservative efficacy
`
` because the traditional preservative would do the
`
` job.
`
` Q Okay. So then what does that mean that in
`
` those instances, you wouldn't really suggest any
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` particular limits on the amount of zinc, high or
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` low?
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` A It would depend on the specific question
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` that I was asked. If I was asked in an ophthalmic
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` composition that had a traditional preservative such
`
` as BAK, at the typical concentrations used, if I
`
` wanted to add zinc to provide additional
`
` antimicrobial activity to provide assurance of
`
` sterility in that eye drop, I would recommend
`
` concentrations of 0.025, 0.05, 0.1 because the
`
` literature show that these concentrations
`
` demonstrated antimicrobial activity and were safe to
`
` use in an eye drop.
`
` Q I apologize if I'm asking a silly question
`
` here, but in that context, the context where you
`
` have the traditional preservative and you're adding
`
` zinc to provide this additional assurance of
`
` preservative efficacy let's call it, if that's okay,
`
` you just listed off some lower concentration ranges
`
` 0.25, 0.05, 0.1 -- by the way, I assume we're
`
` talking about millimolar of zinc at those numbers?
`
` That's what that's referring to?
`
` A The most current numbers I gave you
`
` 0.025 percent, 0.05 percent, 0.1 percent. I wasn't
`
` referring to millimolar. I apologize. Those were
`
` percentages.
`
` Q Oh. Well okay. So it seems like if I
`
` recall correctly, in the previous answer when you
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` were discussing zinc as the sole preservative, I
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` think you gave me millimolar numbers?
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` A That's correct. I did do that.
`
` Q Just to stay consistent for this latter
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` situation where it's the BAK plus zinc, can you tell
`
` me what levels you're talking about in millimolar?
`
` A Yes. 0.025 percent.
`
` Q Let me just stop you one second. It looks
`
` like you're looking at your declaration. Can you
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` just tell me the page or paragraph number?
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` A I'm looking at my declaration, paragraph 41
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` on page 24.
`
` Q Okay, thank you. I'm sorry. Please
`
` continue.
`
` A Answering your question, zinc at a
`
` concentration of 0.025 percent is equal to
`
` 1.8 millimolar. Zinc at a concentration of 0.050
`
` weight percent is equal to 3.7 millimolar. And I
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` talked about even going higher to 0.1 weight percent
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` which would be 7.4 millimolar.
`
` Q Now, zinc by itself -- you said you would
`
` not recommend zinc as the sole preservative by
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` itself at those concentration levels, correct?
`
` A I'm sorry. Which concentrations?
`
` Q The ones we just referred to, let's call it
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` 1.8 to 3.7 millimolar.
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` A So prior to 2006, if someone was asking my
`
` advice about using zinc as the sole preservative in
`
` an ocular formulation, I would have said, don't.
`
` Why would you. There are traditional preservatives
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` that are there that are proven, tested, on the
`
` market. We know their efficacy. We know their
`
` toxicity. Zinc is an unproven, nontraditional
`
` preservative.
`
` Q Okay. I appreciate that, Dr. Zhanel. But I
`
` do want to go back to what I wrote in my notes which
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` is -- and you can again correct me if I'm wrong, but
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` what I had written down was in the context of zinc
`
` being used as a sole preservative, you recited some
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` concentration ranges to me and you said that
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` starting at around 0.5 millimolar is when you would
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` see inhibition of microbes, and at 1 millimolar or
`
` greater, you would see inhibition and actual killing
`
` of microbes. Did I record that correctly?
`
` A Numerically I think your recordings are
`
` accurate, but I think that's not my answer. My
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` answer -- you asked me two separate questions.
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` Question one was regarding antimicrobial activity of
`
` zinc. And I was purely answering that question in
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` terms of antimicrobial activity of zinc, it was
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` well-known in the literature prior to 2006 that zinc
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` was a dose-dependent inhibiter of organisms. And if
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` you use zinc alone, if you were using concentrations
`
` in millimolar of 0.07, 0.1, 0.2, even 0.3, that
`
` these concentrations were described as stimulating
`
` the growth of organisms.
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` Concentrations of approximately
`
` 0.5 millimolar of zinc alone were described as
`
` inhibiting organisms, but then allowing adaptation
`
` and organisms to regrow, presumably developing
`
` resistance or tolerance to zinc. And there were
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` data described using zinc alone at 1 millimolar
`
` where you would get organism killing. Those are the
`
` concentrations that I was using to answer using zinc
`
` alone to inhibit organisms.
`
` Q Okay. So then let me go to what I think --
`
` at least I had intended to be the next question
`
` which was in the context where you're using zinc, in
`
` addition to the traditional preservative, so zinc to
`
` provide this additional assurance of microbial
`
` control or preservative efficacy, there I asked you
`
` what concentration of zinc levels you would have
`
` recommended and I think the lowest number you
`
` started with was 0.025 percent which we established
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` equates to 1.8 millimolar. Am I correct so far?
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` A In part correct. My answer to that question
`
` was myself or a person of ordinary skill, if they
`
` were asked a question saying if I have an eye drop
`
` that has a traditional preservative in it such as
`
` BAK at the conventionally used concentrations, for
`
` example, 0.015 percent --
`
` Q Of BAK?
`
` A -- of BAK, do I need to add zinc. And my
`
` opinion would be you don't need to. You have a
`
` traditional preservative and I would have an
`
` expectation that that traditional preservative would
`
` pass PET testing and provide antimicrobial activity.
`
` But if you are forcing me to recommend a
`
` concentration of zinc to add to that traditional
`
` preservative BAK, then I would say, okay, I would
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` start at concentrations of 0.025, 0.05 percent of
`
` zinc. And my rationale would be I know that these
`
` concentrations inhibit organisms and I know that
`
` they are safe to the eye.
`
` Q I think as part of your earlier -- one of
`
` your earlier responses you indicated that you were
`
` -- at that time you were aware of the literature in
`
` this area, is that right?
`
` A Yes.
`
` Q When's the first time you recall becoming
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` aware of the '299 patent or its -- or the
`
` application that led to the '299 patent?
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` A I can't recall when I would have first read
`
` the '299 patent, but it would have been at the time
`
` that I was involved in this litigation.
`
` Q Well, just to clarify, to help you out I
`
` think you said you were involved with -- before this
`
` proceeding, you were involved with another
`
` proceeding involving Travatan Z. Would that likely
`
` have been the first time you saw it? Is that what
`
` you're referring to as opposed to this proceeding
`
` here?
`
` A I can't recall the first time I saw the '299
`
` patent, but it would have been when I was involved
`
` in Travatan Z litigation.
`
` Q What about -- just for ease of reference,
`
` I'll hand you what