` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`1
`
`APOTEX CORP., ) Case IPR2013-00428
` US Patent No. 8,268,299 B2;
` Petitioner, ) Case IPR2013-00429
` US Patent No. 8,323,630 B2
` ) Case IPR2013-00430
` US Patent No. 8,338,941 B2
` v. )
`ALCON RESEARCH, LTD., )
` Patent Owner. )
`
`
`
` DEPOSITION OF MICHAEL J. MILLER, Ph.D.
` Washington, D.C.
` Friday, March 14, 2014
` 9:00 a.m.
`
`Reported by:
`Laurie Bangart, RPR, CRR
`Job No: 33654
`
`ALCON 2002
`Apotex Corp. v. Alcon Research, Ltd.
`Case IPR2013-00428
`
`

`

` EXAMINATION INDEX
` PAGE
`EXAMINATION BY MR. KRINSKY . . . . . . . . . . . 5
`
`4
`
` E X H I B I T S
` (Previously marked, but referred to)
`EXHIBIT DESCRIPTION PAGE
`Exhibit 1001 US Patent No. 8,628,299 B2 . . . . 107
`Exhibit 1002 Declaration of Michael Miller, Ph.D.
` US Patent No. 8,268,941 . . . . . . 162
`Exhibit 1002 Declaration of Michael Miller, Ph.D.
` US Patent No. 8,268,299 . . . . . . 99
`Exhibit 1003 The Xia reference . . . . . . . . . 17
`Exhibit 1004 The Chowhan patent . . . . . . . . 44
`Exhibit 1005 The Gadd reference . . . . . . . . 122
`Exhibit 1006 Travatan label . . . . . . . . . . 90
`
`1
`2
`3
`
`45678
`
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`5
`
` P R O C E E D I N G S
` MICHAEL J. MILLER, Ph.D.,
` having been first duly sworn, testified upon his
` oath as follows:
` EXAMINATION BY COUNSEL FOR DEFENDANT
`BY MR. KRINSKY:
` Q Well, good morning, Dr. Miller.
` A Good morning.
` Q Good to see you again.
` How many marketed ophthalmic pharmaceuticals
`as of 2006 used zinc as a preservative?
` A I don't know how many commercially available
`products used zinc at that time.
` Q Did any?
` A I recall a product by the name of Systane
`that I believe contained zinc, but I don't recall the
`time frame when that was commercialized.
` Q Other than that, are you aware of any?
` A No, I'm not.
` Q Why weren't there more?
` MR. SABHARWAL: Objection. Calls
` for speculation.
` THE WITNESS: I don't know the
` reason why there were not more products with
` zinc.
`
`2 (Pages 2 to 5)
`
` Deposition of
` Michael J. Miller, Ph.D.
`
`Held at the offices of:
` Sterne, Kessler, Goldstein & Fox, PLLC
` 1100 New York Avenue, NW
` Washington, D.C. 20005
` (202)371-2600
`
` Taken pursuant to notice, before
` Laurie Bangart, Registered Professional
` Reporter, Certified Realtime Reporter and
` notary public in and for the District of
` Columbia.
`
`2
`
`3
`
`1
`2
`
`34
`
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A P P E A R A N C E S
`ON BEHALF OF PETITIONER APOTEX CORPORATION:
` Sterne, Kessler, Goldstein & Fox, PLLC
` 1100 New York Avenue, NW
` Washington, D.C. 20005
` By: Keeto Sabharwal, Esq.
` keetos@skgf.com
` R. Wilson Trey Powers, III, Ph.D., Esq.
` tpowers@skgf.com
`
`ON BEHALF OF PATENT OWNER ALCON RESEARCH, LTD.:
` Williams & Connolly, LLP
` 725 Twelfth Street, NW
` Washington, D.C. 20005
` By: David M. Krinsky, Esq.
` dkrinsky@wc.com
` Adam L. Perlman, Esq.
` aperlman@wc.com
`
`ALSO PRESENT:
` Barry J. Copeland, in-house
` counsel for Alcon
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`DAVID FELDMAN WORLDWIDE, INC.
`450 Seventh Avenue - Ste 500, New York, NY 10123 1.800.642.1099
`
`

`

`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`6
`
`8
`
`BY MR. KRINSKY:
` Q Were there concerns in the art about its
`efficacy as a preservative?
` MR. SABHARWAL: Objection. Lacks
` foundation.
` THE WITNESS: Are you asking in an
` ophthalmic formulation?
`BY MR. KRINSKY:
` Q Yes.
` A I don't know if there was any issues or
`concerns associated with zinc in antimicrobial and
`ophthalmic formulations. I just don't have that
`information.
` Q Would a person of ordinary skill in the art
`as of 2006 have had any concerns about the safety of
`using zinc?
` A I don't know if they would.
` Q You don't know one way or another, or you
`don't know of any concerns that they would have had?
` A I know at the time zinc was a known
`antimicrobial agent, but whether there would be
`concerns about its safety in ophthalmic formulations,
`I don't know that.
` Q Well, one of the advantages of using zinc
`that was taught by the Xia reference is that it is not
`
`1
` Xia teaches and use that information during
`2
` routine optimization of an ophthalmic
`3
` formulation to come up with an acceptable and
`4
` an appropriate composition for use in the eye
`5
` that, as is taught in Xia, would provide a
`6
` certain level of antimicrobial activity to
`7
` meet preservative standards.
`8
`BY MR. KRINSKY:
`9
` Q And when you say "routine optimization,"
`10
`what properties would the person of ordinary skill in
`11
`the art have been optimizing for?
`12
` A Well, that would depend on the overall goal
`13
`of what was needed in the ophthalmic formulation,
`14
`which, as taught in Xia, can include optimizing the
`15
`formulation to meet preservative standards.
`16
` Q And does the amount of zinc in the
`17
`formulation affect the ability of the formulation to
`18 meet preservative standards?
`19
` A Levels of zinc in an ophthalmic formulation
`20
`can affect the overall antimicrobial effectiveness,
`21
`and a person of ordinary skill would again look at Xia
`22
`and the ranges that were disclosed and understand that
`23
`these ranges would be appropriate for use in the
`24
`ophthalmic formulation to provide that needed
`25
`antimicrobial activity.
`
`7
`
`9
`
`irritating to the eye, correct?
` A That is correct.
` Q And the person of ordinary skill in the art
`wouldn't have had any reason to avoid using it on the
`grounds that it was irritating to the eye?
` A Based on the teaching of Xia, the person of
`ordinary skill would understand that zinc was not as
`harsh as other agents that were used in ophthalmics at
`the time.
` Q And the person of ordinary skill in the art,
`based on that teaching, would have felt comfortable
`using the concentrations of zinc disclosed in Xia?
` A I believe the person of ordinary skill would
`look at Xia and what was disclosed by Xia and
`understand that an ophthalmic formulation containing
`the ranges of zinc that was taught were acceptable to
`provide a desired level of antimicrobial activity as
`well as safety.
` Q So the person of ordinary skill in the art
`wouldn't have had any reason to avoid using as much
`zinc as Xia teaches?
` MR. SABHARWAL: Objection to form.
` You can answer.
` THE WITNESS: I believe the person
` of ordinary skill would read the ranges that
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` Q I see. If you were to use -- so there's
`some minimum level of zinc that you'd need in order to
`provide adequate antimicrobial activity; is that fair?
` A That's fair to say.
` Q A single molecule of zinc in a droptainer of
`an ophthalmic formulation wouldn't by itself provide
`adequate antimicrobial activity?
` MR. SABHARWAL: Objection to the
` extent it calls for speculation.
` THE WITNESS: Well, Xia does teach
` that zinc has antimicrobial activity, as do
` other prior art, but for zinc to be used in
` an ophthalmic formulation, there are other
` considerations in terms of components that a
` person of ordinary skill would look at in
` order to develop a formula that can actually
` be used in the eye, so there are other
` considerations to put in place.
`BY MR. KRINSKY:
` Q Other considerations besides the level of
`preservative efficacy, you're saying?
` A And again I just want to be clear. We're
`talking about an ophthalmic formulation?
` Q Yes.
` A In addition to components or a component
`3 (Pages 6 to 9)
`
`DAVID FELDMAN WORLDWIDE, INC.
`450 Seventh Avenue - Ste 500, New York, NY 10123 1.800.642.1099
`
`

`

`10
`
`1
`that would provide antimicrobial activity, there can
`2
`be other components in the ophthalmic formulation that
`3
`would be considered to offer a safe and effective
`4
`product that can be used.
`5
` Q That wasn't my question, though, Doctor.
`6 What I'm asking was: In terms of attempting to
`7
`optimize the level of zinc in an ophthalmic
`8
`formulation, one concern would be using enough zinc to
`9
`provide a desired level of antimicrobial activity; is
`10
`that fair?
`11
` A Yes, that's fair.
`12
` Q And your answer suggested that there were
`13
`other considerations besides the level of
`14
`antimicrobial activity that would determine what level
`15
`of zinc to use, and I'm asking what those other
`16
`considerations are, if any.
`17
` A Other considerations could be interactions
`18
`of the zinc with other components in the formula.
`19
` Q Okay, and what would be the concern with
`20
`regard to interactions of zinc and other components in
`21
`the formula?
`22
` A In some cases other components could
`23
`potentiate the antimicrobial effects of zinc, such as
`24
`a borate polyol complex that has been taught in the
`25
`Chowhan reference that I've opined on, or, in the
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`12
`preservative efficacy, are there any parameters that
`the person of ordinary skill would consider relevant
`in attempting to optimize the level of zinc? Is the
`optimization you're referring to an optimization for
`preservative efficacy in the formulation as a whole,
`or is it an optimization of something else in
`addition?
` MR. SABHARWAL: There were like
` three questions there, so I'm going to object
` as compound.
` THE WITNESS: Just for clarity, can
` we break your question apart so that I can
` answer whether we're talking about
` preservative efficacy or some other form or
` attribute of the formulation?
`BY MR. KRINSKY:
` Q Sure. I was trying to ask a clarifying
`question, but I left the original question on the
`table.
` When you speak of optimizing the level of
`zinc in an ophthalmic formulation, are you referring
`to optimization for purposes of preservative efficacy
`or are you referring to optimization of some other
`parameter besides preservative efficacy in addition?
` A If a skilled artisan was looking at the
`
`11
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`opposite direction, to have a negative impact on
`overall antimicrobial activity, such as the presence
`of anions or multivalent metal cations, which I've
`also opined in my declarations.
` Q So the examples you've just given of a
`component that could potentiate antimicrobial activity
`or a component that could interfere with antimicrobial
`activity are both examples, as I understand it, of
`potential interactions between the zinc and another
`ingredient that would affect the preservative efficacy
`of the zinc; is that fair?
` A It's my opinion that a person of ordinary
`skill would understand that this goes beyond just the
`activity of zinc as well. In an ophthalmic formula,
`the antimicrobial activity is represented by the
`holistic effects of the entire formula.
` Q Okay. I think I see why we're talking past
`each other a little bit. I didn't mean to focus on
`the efficacy of the zinc specifically, but what you're
`saying is that these other components could affect the
`preservative efficacy of the formulation as a whole.
` Is that the point you're making?
` A Yes.
` Q Okay, and my question to you is -- where I
`was headed with this line of questioning is: Besides
`
`13
`1
`level of zinc, and one primary goal of formulating was
`2
`to meet a certain preservative effectiveness standard,
`3
`then it is my opinion that one primary goal would be
`4
`to perform that routine optimization for that purpose,
`5
`which would be meeting some standard of preservative
`6
`effectiveness.
`7
` Beyond that, depending on the required
`8
`attributes of the formulation, there may be other
`9
`characteristics of the formula that may need to be
`10
`optimized as well.
`11
` Q And what characteristics of the formula that
`12 may need to be optimized are there that the person of
`13
`ordinary skill in the art would understand relate to
`14
`the level of zinc?
`15
` A Related to the level of zinc, the skilled
`16
`artisan may look at optimizing the formula to be safe
`17
`for use, and stable, as examples.
`18
` Q Are there other examples that you're aware
`19
`of?
`20
` A Another example might be the perceived
`21
`comfort of the formula as it's being used.
`22
` Q And within the -- let me withdraw that.
`23
` Would the person of ordinary skill in the
`24
`art have had a concern with the safety of a level of
`25
`zinc within the ranges disclosed in Xia?
`4 (Pages 10 to 13)
`
`DAVID FELDMAN WORLDWIDE, INC.
`450 Seventh Avenue - Ste 500, New York, NY 10123 1.800.642.1099
`
`

`

`14
`
`16
`
`1
` A To answer your question, I would like to
`2
`have some clarity on what you mean by "safety."
`3
` Q Well, Dr. Miller, it's a consideration that
`4
`you just raised, so I don't know exactly what safety
`5
`considerations you were referring to when you just
`6
`referred to safety, but whatever those are, would
`7
`there have been any safety concern with any of the
`8
`levels of zinc disclosed in Xia?
`9
` A As I sit here, I don't know of specific
`10
`safety concerns associated with the levels of zinc
`11
`that were disclosed in Xia, but a skilled artisan in
`12
`optimizing the formulation would consider safety in
`13
`terms of its use in or on the eye as a consideration
`14
`during that development process.
`15
` Q Would the person of ordinary skill in the
`16
`art, having -- suppose the person of ordinary skill in
`17
`the art had made a formulation according to the
`18
`teachings of Xia that met preservative efficacy
`19
`requirements. Okay? And using a level of zinc to
`20 meet those requirements, according to the teachings of
`21
`Xia, would the person of ordinary skill in the art
`22
`have had any reason to find a way to use less zinc for
`23
`reasons of safety?
`24
` MR. SABHARWAL: Objection. Lacks
`25
` foundation. Calls for speculation.
`
`15
`
`1
` THE WITNESS: Although Xia teaches
`2
` a range of acceptable levels of zinc in order
`3
` to meet preservative standards, the one
`4
` attribute of an ophthalmic formulation by the
`5
` skilled artisan may be to use as low levels
`6
` as possible of components, generally
`7
` speaking, when formulating these types of
`8
` compositions.
`9
`BY MR. KRINSKY:
`10
` Q And that's a general statement about
`11
`whatever components you're using in the formulation?
`12
` A Generally speaking, during the formulation
`13
`of ophthalmics -- and this is aligned with some of the
`14
`teaching in the prior art, such as Xia and Chowhan.
`15 When looking at certain components, such as
`16
`preservatives, agents that will provide an
`17
`antimicrobial effect, generally speaking, it may be
`18
`advantageous to use as low level of an antimicrobial
`19
`agent to avoid potential toxicity or harshness in or
`20
`on the eye.
`21
` Q Would there have been -- would the person of
`22
`ordinary skill in the art have had a particular
`23
`concern in that regard with respect to zinc, or is
`24
`that a general statement about antimicrobial -- about
`25
`excipients with antimicrobial effect in an ophthalmic
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`formulation?
` A I believe the skilled artisan would apply
`this thinking, again based on the teachings of the
`prior art, to limit the amount or concentration of
`preservatives that have been shown to be toxic or
`harsh to the ocular surface in some patients, but also
`it may be extended to certain excipients as well.
` Q I'm not sure I understood your answer.
` Would the person of ordinary skill in the
`art have had a particular concern about the toxicity
`or harshness of zinc?
` A Again, this depends on the level of zinc
`used in the formulation as a whole and whether there
`was any potential for the formulation to exhibit some
`toxic response or some harshness to the eye.
` Q And I don't think that answers my question,
`though.
` Are you aware of any teaching as of 2006
`that zinc posed a greater problem with regard to
`toxicity or harshness than other ingredients that
`could be used to provide antimicrobial activity?
` A And again just for clarity, are we talking
`in an ophthalmic formulation?
` Q Yes, in ophthalmic formulation.
` A I'm not aware of any particular product per
`
`17
`
`se, but I do understand that certain levels or high
`levels of zinc might provide an astringent effect on
`or in that environment.
` Q And at what levels does zinc provide an
`astringent effect in the ophthalmic environment?
` A I do recall prior art that discusses
`astringent effect of zinc. I just don't recall that
`there was a particular concentration of zinc
`associated to provide that response.
` Q Are you aware of zinc being deliberately
`used as an astringent in pharmaceutical products -- or
`in ophthalmic products?
` A I may have seen some reference. I just
`don't recall specifically under what circumstances the
`zinc would be used for that purpose.
` Q Let's look at the Xia reference which has
`been previously marked as Exhibit 1003, Apotex Exhibit
`1003.
` And just for the record, we have an
`agreement, Counsel, that this deposition covers all
`three IPRs, so this is a reference where I believe the
`exhibit number is the same across all three of them.
` MR. SABHARWAL: Yes.
` MR. KRINSKY: I will try to specify
` when I use an exhibit that isn't, but if
`5 (Pages 14 to 17)
`
`DAVID FELDMAN WORLDWIDE, INC.
`450 Seventh Avenue - Ste 500, New York, NY 10123 1.800.642.1099
`
`

`

`18
`
`20
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` there's any doubt, assume that I'm using
` exhibit numbering in the '299, and all of the
` exhibits numbers that I newly use we'll
` consider for all three.
` MR. SABHARWAL: This exhibit,
` Exhibit 1003, I will assume you're using it
` for '299 as well as the others.
` MR. KRINSKY: Well, this is an
` exhibit that Apotex had marked, and I believe
` it gave it the same number in all three.
` MR. SABHARWAL: Correct.
` MR. PERLMAN: Let me just say we
` can also work out a stipulation after to
` clean it up.
` MR. SABHARWAL: Yeah, that's fine.
`BY MR. KRINSKY:
` Q Is this the Xia reference, Doctor?
` A Yes, it is.
` Q And just briefly by way of background, the
`applicant in the Xia reference, I assume Mr. or Dr.
`Xia, worked at Bausch & Lomb, correct?
` A Yes.
` Q You also worked at Bausch & Lomb, didn't
`you?
` A I did.
`
`19
`
` Q Did you know Xia?
` A I did know Xia.
` Q Did you know the other inventors here,
`Salamone and Borazjani?
` A Yes, I did.
` Q And in what context did you know them?
` A Erning Xia, Dr. Xia worked in the
`formulation group, and I worked on product development
`teams with Dr. Xia. Dr. Salamone, as I can recall,
`was in a senior management position in the research
`and development organization and, as part of my
`position, had some interaction with him. And
`Dr. Borazjani was a microbiologist who I believe
`worked in Dr. Salamone's organization.
` Q And did the work that led to this patent
`application relate to a particular product?
` A I don't know that.
` Q Did you -- were you involved in the work
`that is disclosed and claimed in this application?
` A I don't recall having any work associated
`with this application while I was at Bausch & Lomb.
` Q Do you recall having any work associated
`with this application at all?
` A No, I don't.
` Q And were you aware of this work when you
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`were at Bausch & Lomb?
` MR. SABHARWAL: Object to the form
` of the question.
` THE WITNESS: Just for clarity, are
` you asking the work specifically performed
` that supported this application, or work
` associated with components that included this
` application?
`BY MR. KRINSKY:
` Q Well, I'm not sure what you mean by
`"components that included this application," so let's
`answer it either way.
` Were you aware of any, any work specifically
`supporting this application or otherwise associated
`with this application?
` A I was aware of work with components that
`have been disclosed in the application, but I don't
`recall specific work or studies that led to the
`application itself.
` Q And when you say you were aware of work with
`components disclosed in the application, what
`components are you referring to?
` A As an example, the preservative alexidine is
`disclosed in this application, and I recall being
`involved in studies associated with that particular
`
`21
`
`component.
` Q Were you aware of work by Xia or his
`colleagues on the use of zinc in ophthalmic
`formulations?
` A At this time I just can't recall if I was
`exposed to any of the work associated with zinc that
`Xia was working on.
` Q And what was your role at Bausch & Lomb at
`the time?
` A I worked at Bausch & Lomb for over ten
`years, and during that time I was responsible for a
`variety of microbiology, toxicity, sterilization and
`business development groups.
` Q Were you responsible for those various
`groups all at the same time, or did you have a number
`of different positions?
` A I had a number of different positions, and
`it would be easier for me to review in the
`declaration, because I've separated those out.
` Q Sure, and I'm not sure which declaration do
`you have over there. I have copies here.
` A I will work off the '299 declaration.
` Q Okay. Is that a clean unmarked copy of it?
` A Yes, it is.
` Q That, for the record, is Exhibit 1002 from
`6 (Pages 18 to 21)
`
`DAVID FELDMAN WORLDWIDE, INC.
`450 Seventh Avenue - Ste 500, New York, NY 10123 1.800.642.1099
`
`

`

`22
`
`24
`
`1
`the '299 IPR.
`2
` A I am referring to my declaration, starting
`3
`at paragraph 5 on page 4. I started at Bausch & Lomb
`4
`in 1991, and for approximately three years I acted as
`5
`the manager of quality assurance microbiology in one
`6
`of the divisions of Bausch & Lomb.
`7
` I had a laboratory with direct reports,
`8 microbiologists and technicians. And the purpose of
`9
`that lab and my responsibility was to oversee all of
`10
`the microbiology testing that was associated with
`11
`contact lens care solutions, ophthalmic
`12
`pharmaceuticals. And the type of testing was fairly
`13
`broad but included sterility testing, stability
`14
`testing, antimicrobial effectiveness testing.
`15
` During that time I also worked with the
`16 manufacturing groups and the compliance groups in
`17
`ensuring that the labs and the division was following
`18
`good manufacturing practices, and then finally, if the
`19
`FDA would come in and do an audit, either in
`20 manufacturing or the laboratory, I was the point
`21
`person in those areas.
`22
` Q Doctor, I don't mean to cut you off, but I
`23
`don't need you to necessarily review the entirety of
`24
`your testimony here.
`25
` As of the time Xia was working on zinc, what
`23
`was your position at Bausch & Lomb, or had you left
`Bausch & Lomb by then?
` A I had left Bausch & Lomb in 2002. I don't
`know what work Dr. Xia was performing at the time I
`left the company, so it's not possible for me to say
`one way or the other whether I was there and exposed
`to any of that work or not.
` Q So sitting here, you don't know one way or
`another whether you were exposed to any information
`about Xia's work on zinc beyond what's disclosed in
`the application?
` A And as I stated earlier, although there's a
`possibility, while running the laboratories, there
`could have been formulations that came through that
`may have included zinc, I don't recall, but beyond
`that I do not remember having any direct interaction
`with the work that Xia had performed associated with
`the application that we are discussing today.
` Q Okay.
` Xia discloses -- one of the concepts that
`Xia discloses is the idea that zinc can inhibit
`antimicrobial growth in an ophthalmic formulation. Is
`that fair? Excuse me. Can inhibit microbial growth
`in ophthalmic formulations. Is that fair?
` A Yes, that's fair.
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` Q And just for clarity, I've been -- we've
`both been referring to zinc over the course of the
`deposition today. In the context of ophthalmic
`formulation, zinc exists as an ion after some zinc
`compound or salt is dissolved in the formulation,
`correct?
` A Yes.
` Q So when we talk about the antimicrobial
`activity of zinc, we're not talking about elemental
`zinc without any ionization; we're talking about zinc
`ions that are supplied by, for example, zinc chloride?
` A Yes, that's correct.
` Q And one of the embodiments of Xia is the use
`of zinc ions in a formulation as the only
`preservative; is that fair?
` I can direct your attention to the top of
`page 4. The last sentence in the first paragraph on
`page 4 refers to "ophthalmic compositions comprising
`less than a preservative effective amount of a primary
`antimicrobial compound or preferably no primary
`preservative agent."
` Do you see that?
` A I do.
` Q And zinc is not a primary preservative agent
`as Xia uses the term, is it?
`
`25
`
` A That is correct.
` Q What Xia is teaching here is using zinc
`instead of a primary preservative agent?
` A That is correct.
` Q And what Xia teaches is that you can either
`use zinc alone or you can use zinc in combination with
`a smaller amount of a primary preservative agent than
`you'd otherwise use?
` MR. SABHARWAL: Is that a question?
`BY MR. KRINSKY:
` Q Is that correct?
` A Xia does disclose that you can use less than
`a preservative effective amount of a primary
`antimicrobial compound, but Xia also discloses that
`preferably there was no primary preservative agent.
` Q And why is there a preference for not using
`a primary preservative agent in Xia?
` A One reason a person of ordinary skill would
`understand that Xia teaches that it's preferable not
`to use a primary preservative agent would come from
`Xia's disclosure that many preservative agents have a
`tendency to be toxic or be harsh to the eye or
`irritate the ocular tissue.
` Q And by using zinc instead of a primary
`preservative agent, one can thereby minimize the
`7 (Pages 22 to 25)
`
`DAVID FELDMAN WORLDWIDE, INC.
`450 Seventh Avenue - Ste 500, New York, NY 10123 1.800.642.1099
`
`

`

`26
`
`28
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`harshness to the eye or irritation to the ocular
`tissue, correct?
` A That is correct.
` Q And another embodiment of the invention in
`Xia involves the use of a compound called polymer JR,
`correct?
` A Yes.
` Q And would the person of ordinary skill in
`the art have understood Xia to be teaching that
`polymer JR was harsh or irritating to the eye?
` A A person of ordinary skill would understand
`from Xia that polymer JR was less of an irritant than
`what Xia calls "traditional preservatives."
` Q Would the person of ordinary skill in the
`art understand Xia to be teaching that it was
`preferable not to use polymer JR?
` Let me clarify the question.
` Would a person of ordinary skill in the art
`understand Xia to be teaching that it's preferable to
`use zinc alone as compared to using a combination of
`zinc and polymer JR?
` A A skilled artisan would understand Xia is
`teaching that there was preferably no primary
`preservative agent present, and the skilled artisan
`would also understand that Xia teaches that polymer JR
`
`27
`
`is a preservative-enhancing additive, and because this
`polymer JR is not, as I understand or the skilled
`artisan would understand as being identified as a
`primary preservative agent, that Xia is not teaching
`away from using this polymer.
` Q So the person of ordinary skill in the art
`wouldn't understand Xia to be teaching that it's
`preferable to use zinc alone to polymer JR.
` Is that the substance of what you just said?
` A No, that's not what I said.
` The person of ordinary skill would
`understand from reading Xia that this
`preservative-enhancing additive polymer JR can be used
`in the invention disclosed in this application.
`However, polymer JR is not required, and there are
`working examples in Xia where polymer JR is not a
`component.
` Q There are also working examples where
`polymer JR is a component, correct?
` A Yes, correct.
` Q And my question to you is: Does Xia teach
`the person of ordinary skill in the art to use the
`zinc examples in preference to the examples with
`polymer JR?
` A With respect to polymer JR, I don't recall a
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`specific teaching in Xia that suggests to use one over
`the other.
` Q Okay.
` Let's talk a bit about the concentrations
`disclosed in Xia. If we could turn to page 5 of Xia,
`the top of page 5, there's a statement that in an
`embodiment of the formulations, of Xia's formulations,
`"the composition has a minimum of about .001 weight
`percent, about .005 weight percent, about .01 weight
`percent, or about .05 weight percent of a zinc
`compound."
` Do you see that?
` A Yes.
` Q And then it gives maximums as high as 1.0
`weight percent?
` A Yes, I see that.
` Q Does Xia provide any reason to use one of
`these concentrations rather than a different one of
`these concentrations?
` A I don't recall a specific teaching of using
`one concentration over another.
` Q There's certainly no teaching that a
`concentration of, for example, .01 weight percent
`would be unacceptable?
` MR. SABHARWAL: Object to the form
`
`29
`
` of the question.
` THE WITNESS: Are you asking in
` terms of antimicrobial activity or some other
` attribute of the formulation?
`BY MR. KRINSKY:
` Q I'm asking if there's any teaching at all in
`Xia that .01 weight percent of a zinc compound -- and
`for purposes of clarity, we'll say zinc chloride --
`would be suboptimal or any reason not to use that
`concentration.
` MR. SABHARWAL: Same objection.
` THE WITNESS: Well, in this case
` it's going to depend on the use of the .01
` weight percent zinc from zinc chloride in the
` other components in the formulation and what
` the characteristics of the formulation are
` providing to determine if one of those
` characteristics are not being met or, I
` believe as you had stated, was suboptimal in
` performance.
`BY MR. KRINSKY:
` Q Well, let's look at specific examples.
` If we go forward to examples 16, 17 and 18
`in Table 11 of Xia. This is on page 23.
` Earlier you referred to Xia disclosing
`8 (Pages 26 to 29)
`
`DAVID FELDMAN