` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
` ARGENTUM PHARMACEUTICALS LLC )
` )
` Petitioner, )
` )
` vs. ) No. IPR2017-01053
` )
` ALCON RESEARCH, LTD., )
` )
` Patent owner. )
`
` DEPOSITION OF ERNING XIZ, Ph.D.
` May 11, 2018
` Chicago, Illinois 60654
` 9:00 a.m.
`
`REPORTED BY:
`JO ANN LOSOYA
`
`1
`2
`
`345
`
`6
`
`7
`
`8
`
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`
`22
`23
`24
`25
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`ALCON 2166
`Argentum Pharm. LLC v. Alcon Research, Ltd.
`Case IPR2017-01053
`
`
`
`Page 2
`
`PRESENT:
` Appeared on behalf of Defendants.
` FOLEY & LARDNER
` 321 North Clark Street, Suite 2800
` Chicago, Illinois 60654
` (312) 832-4378
` BY: MICHAEL R. HOUSTON, ESQ.
` mhouston@foley.com
`
` Appeared on behalf of the patent owner.
` WILLIAMS & CONNOLLY
` 725 Twelfth Street NW
` Washington, DC 20005
` (202) 434-5097
` BY: ALEXANDER S. ZOLAN, ESQ.
` azolan@wc.com
` DAVID M. KRINSKY, ESQ.
` dkrinsky@wc.com
`
`REPORTED BY: JO ANN LOSOYA
`LICENSE #: 084-002437
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 3
`
` EXAMINATION
` Witness Page Line
` ERNING XIZ, Ph.D.
` By Mr. Zolan 4 7
` By Mr. Houston 107 21
`
` ***************
` E X H I B I T S
`EXHIBIT DESCRIPTION PAGE
`EXHIBIT 1093 Declaration 5
`EXHIBIT 2122 Winslow article 16
`EXHIBIT 1002 Original declaration 20
`EXHIBIT 1007 Schneider reference 58
`EXHIBIT 1003 Xia patent 72
`EXHIBIT 104 Chowhan reference 76
`EXHIBIT 2121 Deposition transcript 85
`EXHIBIT 1042 Systane Free 94
`EXHIBIT 1110 Systane Free screenshot 95
`EXHIBIT 1111 Systane Free screenshot 95
`EXHIBIT 1041 Systane Free screenshot 127
`
`1
`2
`3
`4
`5
`
`67
`
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 4
` (Witness sworn at 9:04 a.m.)
` WHEREUPON:
` ERNING XIZ, Ph.D.,
` called as a witness herein, having been first duly
` sworn, was examined and testified as follows:
` E X A M I N A T I O N
` BY MR. ZOLAN:
` Q. Good morning, Dr. Xia.
` A. Good morning.
` Q. It's good to see you again.
` A. Same here.
` Q. How does your own experience inform your
` opinions about how the POSA would understand prior
` art?
` MR. HOUSTON: Objection, form.
` THE WITNESS: Can you repeat that?
` BY MR. ZOLAN:
` Q. Yeah. How does your own experience
` inform your opinions about how the POSA would
` understand prior art?
` MR. HOUSTON: Same objection.
` BY THE WITNESS:
` A. You're talking about how the POSA
` understands the prior art?
` Q. Well, what I'm asking is how does your
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 5
` experience, you, as Dr. Xia, who is the expert
` witness in this case, how does your personal
` experience inform your opinions about how the person
` of ordinary skill would understand prior art?
` A. By definition, the prior art, the date of
` the publications should be preceding the publication
` filing date of the patent's applications. So
` everything, every single publications before that
` date can be considered as prior art.
` Q. Okay. I guess I'm not asking what makes
` something prior art. What I'm asking is when you
` are reading a reference and you are opining about
` how that reference would inform the person of
` ordinary skill, how does your personal experience
` inform those opinions?
` A. My base is based on the related
` information from prior arts, not just everything I
` read. If I read reference involves zinc, for
` example, does not mean I will use that publications.
` Q. Let me make it a little more concrete.
` I'm going to hand you what has been marked as
` Exhibit 1093.
` (Deposition Exhibit 1093 was
` marked for identification.)
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 6
`
` BY MR. ZOLAN:
` Q. Dr. Xia, do you recognize Exhibit 1093 as
` the second expert declaration that you submitted in
` this case?
` A. Yes.
` Q. Can you turn to Paragraph 8, please.
` A. Yes.
` Q. Now, on Page 6, so the second part of
` Paragraph 8, the last sentence there says: "These
` precepts comport with my own experience of how a
` POSA would understand prior art patents and other
` references pertinent to ophthalmic formulation."
` Did I read that right?
` A. Yes.
` Q. What I'm asking is what do you mean how
` the precepts comport with your own experience of how
` a POSA would understand prior art patents?
` A. I believe I mean that the information
` that I read from related reference of publications
` has to be closely related to the formulations I
` develop.
` Q. I'm not sure that answered my question.
` When you're opining on the issues in this case, are
` you considering how you would have gone about
` thinking through the issues, or are you thinking
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 7
` about how a person of ordinary skill would go about
` thinking through the issues, or is there no
` difference between those two?
` A. When I approach issues like this, of
` course, I would base it on my experience and the
` knowledges and sometimes I will start searching for
` related publications, not necessarily on the
` positive side. I probably would look at it on the
` negative publication as well.
` Q. Well, a little earlier in Paragraph 8,
` you say that a person of ordinary skill is presumed
` aware of all pertinent art and is a person of
` ordinary creativity.
` Do you see that?
` A. Yes.
` Q. What does "ordinary creativity" mean?
` A. To me, it means not just focused on the
` examples. You have to be analytical and try to
` learn from examples, especially from bad examples,
` without the limit the creations. So you have to be
` very creative. You have to be thinking outside the
` box.
` Q. What I'm trying to understand is, would
` you call yourself a person of ordinary creativity?
` A. Do I call myself a person with ordinary
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 8
`
` creativity?
` Q. Yeah.
` A. Yes.
` Q. Are you -- so, and this is what I was
` trying to get at earlier.
` Do you consider when you're coming up
` with your opinions in this case that the ideas and
` solutions to problems and ways that you think
` outside the box are the ways that the person of
` ordinary skill in the art would be thinking?
` A. If we using the same definition for POSA,
` I assuming a POSA should have -- should be that
` person with ordinary creativities.
` When I was reading some declarations
` from Alcon's experts, by qualifications, we're very
` similar. But when I read the description about
` practice, sometimes I see difference, I see huge
` difference.
` Q. Is the person of ordinary skill in the
` art -- you mentioned thinking outside the box. Is
` the person of ordinary skill in the art trying to
` innovate?
` A. Most of the time, it involves
` innovations.
` Q. Well, do you mean by that that most of
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 9
` the time patents involve innovations, or do you mean
` most of the time the person of ordinary skill in the
` art is trying to innovate?
` MR. HOUSTON: Objection, form.
` THE WITNESS: Can you repeat your
` question for me?
` BY MR. ZOLAN:
` Q. Yes. So I asked you the question -- you
` mentioned the person of ordinary skill as thinking
` outside the box, and I'm asking whether that means
` if the person of ordinary skill is trying to
` innovate, and I think the answer you gave was most
` of the time, it involves innovations. And I just
` didn't understand whether your answer meant these
` patent cases involve innovations or whether you were
` saying yes, the person of ordinary skill in the art
` tries to innovate? That's my question.
` A. My own experience, most of the practice
` in the company when I was working for Bausch and
` Lomb, it is based on the innovation approaches to
` make a better product to solve the problem
` associated with all the products.
` That's the innovations. That did not
` create anything. The majority of time, the results
` is dependent on the additive results. It's not
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 10
`
` dependent on the synergistic results.
` So that's why I say, differentiate
` innovations from the inventions, but what we're
` working on most of the time in the company is to
` make next generation products. It's based on
` something and make it better. That's what I'm
` saying, most of times, innovations.
` Q. So, your opinions about the person of
` ordinary skill in the art who you say would have
` ordinary creativity --
` A. Yes.
` Q. -- you have already said that that person
` thinks outside the box, right?
` A. Yes.
` Q. And what I'm asking is when that person
` is thinking outside the box, are they trying to
` innovate, are they trying to invent something?
` MR. HOUSTON: Objection, form.
` THE WITNESS: Can you give me your
` definition of inventions?
` BY MR. ZOLAN:
` Q. Are they trying to come up with something
` that's patentable?
` A. In my personal experience, patentability
` is value-added for products. It is not necessary to
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 11
` have a patent to protect the products. It's not
` easy to create something nobody knows before.
` That's what I'm talking about. I cannot say 10
` percent of my activity involves the creations and
` 90 percent is innovations. There's no clearcut. To
` me, invention involves unexpected results.
` Q. So, I began this whole line of
` questioning by asking you about your experience --
` A. Sure, it's a good discussion.
` Q. -- and how it informs the person of
` ordinary skill in the art, right. And what I want
` to know -- the question I'm asking has to do with
` the person of ordinary skill in the art and not
` necessarily you in your experience with Bausch and
` Lomb. You understand the person of ordinary skill
` in the art is a, you know, a legal construction --
` A. Yes.
` Q. -- in this cases. So, that hypothetical
` person of ordinary skill in the art, is that
` hypothetical person of ordinary skill in the art
` trying to innovate?
` MR. HOUSTON: Objection, form.
` BY THE WITNESS:
` A. I think this person probably should
` involve two things, both innovations and 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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 12
` creations. Again, majority of time, when POSA goes
` to lab, he must design certain experiments in a
` certain way and hopefully he can expect certain
` results. That's typical daily practice for a POSA.
` Q. Is that person of ordinary skill in the
` art motivated by a desire to innovate, create
` something new, invent something that's patentable?
` A. Your question is is there motivation for
` POSA to invent some things?
` Q. Yeah.
` A. Yes.
` Q. You criticize Dr. Zhanel for relying on
` an article by Winslow, right?
` A. I try not criticize. I say I disagree.
` I disagree with his approach.
` Q. Fair enough. Well, let me start
` somewhere else.
` What is a micronutrient?
` A. Sorry. I didn't hear.
` Q. What is a micronutrient?
` A. Micronutrient, I'm not expert of
` microbiologist, but my understanding, minimal
` understanding is something in the medium or in the
` preparations can be used as a source of food.
` Q. It's something that a microorganism needs
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 13
`
` to live?
` A. Most of time, it needs for live but
` certain times, it's for survive.
` Q. So I'm not sure I see the difference
` there. But let me make sure I understand what
` you're saying. You're saying most of the time it
` needs -- Strike that.
` You're saying most of the time a
` micronutrient -- Strike that.
` You're saying most of the time a
` microorganism needs a micronutrient to live, but
` certain times, it needs a micronutrient to survive.
` What's the difference between needing something to
` live and needing something to survive?
` A. Because certain preparations that will
` provide food for microorganisms does not have
` everything a microorganism needs to live. So they
` just use whatever they have in the medium to keep
` themselves survive, you know.
` Q. I see. Are you distinguishing something
` that a microorganism needs in order to grow and sort
` of reproduce?
` A. Yes.
` Q. That's the distinction you're making?
` A. Hm-hmm.
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 14
`
` Q. I see. Okay. So zinc is a
` micronutrient, right?
` MR. HOUSTON: Objection, form.
` BY THE WITNESS:
` A. Zinc at the low concentration can be
` micronutrient.
` Q. So, the complete lack of zinc in a
` solution causes microorganisms in that solution to
` die because they don't have the zinc they need to
` survive; is that fair?
` A. Again, I'm not a microbiologist. I have
` to say you have to be specific. I have a feeling
` that some microorganism does not need zinc or
` magnesium or other metals to survive. So that's why
` I cannot agree with you 100 percent here.
` Q. Okay. What if we limit it to the three
` bacteria that are used as part of the preservative
` efficacy tests. So considering those three
` bacteria, if they are placed in a solution that
` contains absolutely no zinc at all, those bacteria
` won't survive, right?
` MR. HOUSTON: Objection, beyond the
` scope.
` BY THE WITNESS:
` A. I don't know that it does. I do not want
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 15
`
` to speculate.
` Q. You do know that at a certain point at
` some low concentration of zinc in a solution, the
` zinc will serve as a foodstuff for those three
` strains of bacteria; is that fair?
` MR. HOUSTON: Objection, form; objection,
` beyond the scope.
` THE WITNESS: Can you repeat your
` question?
` BY MR. ZOLAN:
` Q. At certain low concentrations of zinc in
` a solution, the zinc serves as a foodstuff for the
` three bacterial strains we're now talking about?
` MR. HOUSTON: Objection, form; objection,
` beyond the scope.
` BY MR. ZOLAN:
` Q. Is that fair?
` A. It's not fair because do you have other
` food source in the system?
` Q. Are you saying that at certain low
` concentrations of zinc, e-coli will choose to eat
` some other micronutrient and not zinc; is that your
` testimony?
` MR. HOUSTON: Objection, beyond the
` scope.
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 16
`
` BY THE WITNESS:
` A. Yeah, I don't know the biology of this
` the question. I will not speculate.
` MR. ZOLAN: Off the record.
` (Whereupon, a break in the
` proceedings was taken.)
` (Deposition Exhibit 2122 was
` marked for identification.)
` BY MR. ZOLAN:
` Q. Dr. Xia, I'm handing you a copy of
` Exhibit 2122. And is Exhibit 2122 a copy of the
` Winslow article that Dr. Zhanel relies upon for his
` opinions in this case?
` A. Yes.
` Q. If you could go to table 2, which is on
` Page 54, and the text underneath table 2, I'm
` looking at the second sentence in that paragraph
` underneath table 2, which says: "As the
` concentration of salt increases from a minimum,
` there is first an increasing stimulation of
` development (as measured by the count after
` 48 hours). As the salt is further increased, the
` numbers fall off again. This we have called the
` zone of decreasing stimulation. Finally, as the
` salt content becomes even higher, we enter a zone of
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 17
` toxicity in which the number of bacteria is below
` that of the control -- reaching a condition of
` sterility with the highest salt concentrations.
` This is the zone of toxicity."
` Do you see that?
` A. Yes.
` Q. Did I read that right?
` A. Yes.
` Q. And in table 2, there's a column that
` had -- the heading of one of the columns is zinc
` chloride; is that right?
` A. Yes.
` Q. And there's numbers beneath that heading,
` right?
` A. Yes.
` Q. And those numbers are the percentages of
` the e-coli bacteria that is present in solution
` after -- between 44 and 48 hours; is that right?
` A. You mean, the calculation is best on the
` number of bacteria they put at zero time.
` Q. So at zero time, there's a certain amount
` of bacteria inoculated into the solution, right?
` A. That's 100 percent.
` Q. Right. And then at 44 to 48 hours later,
` the percentage of that population of bacteria is
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 18
` measured, and the number in the column headed by
` zinc chloride is the percentage of the originally
` inoculated bacteria population that is now present
` in the solution; is that right?
` A. I just try to verify -- make sure before
` I say yes, that's a 200 -- 208 means the population
` doubled. Close enough, right.
` Q. That's your understanding?
` A. Yeah.
` Q. Yeah.
` A. To make sure we have same understanding.
` Now, I can answer your question. Okay.
` Q. So, does that mean the answer to my
` question is yes, that the numbers beneath zinc
` chloride in that column represent the percentage as
` compared to the original population of bacteria that
` is present in the solution after between 44 and
` 48 hours; is that right?
` A. Yes.
` Q. And the numbers in that column illustrate
` what is described in the text below table 2 that we
` just read; is that fair?
` A. It's fair.
` Q. So, looking at the zinc chloride column
` and the molality column all the way to the left of
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 19
` table 2, at a molality of 0.001, which is equivalent
` to 1 millimolar; is that right?
` A. Equals to 1 millimolar, yes.
` Q. At a molality of .001, or 1 millimolar,
` all of the e-coli were killed after 44 to 48 hours;
` is that right?
` A. From the table 2, yes.
` Q. That's because the population -- Strike
` that.
` That's because the concentration of
` zinc in that solution reached a level of toxicity
` that prevented the growth and actually killed the
` bacteria; is that right?
` A. Under these conditions, yes.
` Q. And at a molality of 0.005, 57 percent of
` the e-coli remained after 44 to 48 hours; is that
` right?
` A. Okay. Let me take a quick look at their
` procedures.
` Yes.
` Q. That concentration 0.005 is equivalent to
` .5 millimolar, right?
` A. Yes.
` Q. And the .5 millimolar zinc chloride or
` zinc ions is equivalent to .007 percent weight by
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 20
`
` volume; is that right?
` A. Sorry.
` Q. Have you done the calculation?
` A. I can do calculation quickly if you want
` me to do.
` Q. Yeah. You could verify that. Because I
` do want to be on the same page about what -- I want
` to convert the millimolar concentration to percent
` weight by volume.
` A. Molecular weight of zinc chloride is,
` what, 61.38. That's what I remember.
` (Deposition Exhibit 1002 was
` marked for identification.)
` BY MR. ZOLAN:
` Q. I'm going to hand you Exhibit 1002, which
` is your original declaration in this case; is that
` right?
` A. Yep.
` Page 12 has a concentration similar
` to this concentration, .005 percent, equals 2.04
` millimolar, or the other way around. Let's see.
` You want me to...okay, I can grab my phone and I can
` calculate easily.
` Q. Yes.
` MR. HOUSTON: I can provide Dr. Xia with
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 21
`
` a phone calculator, if that's all you need.
` BY THE WITNESS:
` A. But I need to look up the molecular
` weight of zinc chloride. I think it is 61.38. I
` could be wrong.
` Q. You refer to it in your declaration, I
` believe.
` A. It's 136.28. Zinc is 61, but the whole
` thing is 136.286.
` MR. HOUSTON: Could you repeat the number
` you came up for the molecular weight of zinc?
` THE WITNESS: 136.286.
` BY MR. ZOLAN:
` Q. Dr. Xia, in Paragraph 50 of Exhibit 1002
` in your first declaration in this case, Paragraph 50
` on Page 33. In this paragraph, you describe how to
` do this conversion, right?
` A. Yeah.
` Q. And you describe the molar mass of zinc
` chloride at 136 grams per mol, right?
` A. Yes.
` Q. That's the number you just verified,
` right?
` A. Just verified, right. Yeah.
` Q. The answer I'm looking for is 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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 22
` conversion from 0.005 molality of zinc chloride into
` a concentration in percent weight volume. I can
` represent to you that that is 0.007 percent, but I
` want you to agree with me about that. So if you
` need to do the calculation, please do.
` A. Your calculation is zero point --
` Q. 007 percent weight volume.
` A. Let me try to follow your calculation.
` You have 0.5 mol.
` Q. 0.5 millimolar. So I'm looking at the
` molality column --
` A. Yeah, 0.005.
` Q. Right.
` A. That's mol.
` Q. Right. Which is equivalent to 0.5
` millimolar, and converting that to percent weight
` volume.
` A. So that's -- now, if we use .5 times 136,
` you got 68 milligrams. That's not grams. That's
` milligrams because you're using millimolars. That's
` in the one liters. In 100 percent, you divide it by
` 10, that is 6.8 milligrams per 100 milliliters.
` Now, you divide by 1,000, divide -- I'm getting
` myself confused. 0.0068. Yep, okay.
` Q. And because for reasons of -- significant
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 23
`
` digits reasons, it's .007?
` A. Yeah. Round up.
` Q. Okay. We now agree, don't we, that
` what's represented in the table 2 in the row that is
` .0005 molality of zinc chloride after 44 to
` 48 hours -- Strike that.
` We now agree that that .0005 molality
` of zinc chloride is equivalent to .007 percent
` weight volume?
` A. Yes.
` Q. And that concentration of zinc ions when
` added to solution under the conditions in Winslow
` led to a decrease in the e-coli population by about
` 43 percent over the course of 44 to 48 hours, right?
` A. Yes.
` Q. One-half of that concentration of zinc
` ions is represented by .0025 molality, right, that's
` the next row down?
` A. Okay. Yes.
` Q. Doing the same conversion is now a lot
` easier because all we need to do is cut it in half.
` That concentration, .0025 molality, is equivalent to
` .0034 percent weight volume of zinc chloride?
` A. Yes.
` Q. Is that right?
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 24
` Okay. And the percentage of e-coli
` that's in the solution when .0034 percent weight
` volume concentration was placed in it times zero,
` after 44 to 48 hours, the percentage of e-coli in
` that solution has increased to be 135 percent of the
` original inoculation; is that right?
` A. That's right.
` Q. And this is illustrating what Winslow
` described below, which is that at higher --
` relatively higher concentrations of zinc ions, those
` zinc ions are toxic to e-coli; is that right?
` A. From his publication, yes.
` Q. And as that concentration of zinc ions
` goes down, at some point, the zinc ions will
` actually promote the growth of e-coli; is that fair?
` MR. HOUSTON: Objection, form.
` BY THE WITNESS:
` A. I cannot agree with you because I do not
` see control here with other zinc. I don't see
` control here. He should have a sample -- he should
` have data from zero percent of zinc with same number
` of bacteria after 44 or 48 hours at 37 degrees. So,
` what is that reading then compared to this readings
` with/without the zinc so I can probably say yes or
` no.
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 25
` Q. So, underneath table 2, there's a heading
` that says: "Survival of bacteria in salt solutions
` of various strengths as compared with salt-free
` control percent."
` What do you understand that to mean?
` A. Yeah. That's probably their controls,
` yeah. So you have -- for each data point, they have
` one controls. So I hope that they have calculation
` here. They didn't show the number of the controls
` but they just -- okay.
` Q. Can you answer my question now?
` A. Your question, repeat it again.
` Q. Yeah, as the concentration of zinc ions
` goes down from the toxic concentration, at some
` point, the zinc ions will actually promote the
` growth of e-coli; is that right?
` MR. HOUSTON: Objection, form.
` BY THE WITNESS:
` A. From the data here, present here at
` certain concentrations, the e-coli is in a better
` environment to grow. I do not believe that promote
` growth of e-coli.
` Q. Well, after 44 to 48 hours, there are
` more e-coli present in the solution that began with
` .00025 molality zinc chloride than in the salt-free
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 26
`
` control, right?
` A. Compared to zinc-free controls, right.
` In zinc-free, yes. Yes.
` Q. Okay. In this paper, Winslow is
` illustrating under the conditions in the Winslow
` paper, this -- the phenomenon that there's a -- that
` a concentration of zinc ions will be toxic to an
` organism, it will then become a foodstuff to an
` organism at lower concentrations, and in even lower
` concentrations, it again inhibits the growth of an
` organism.
` Is that a fair summary of what the
` Winslow paper is describing?
` A. If you use Dolloff, D-O-L-L-O-F-F,
` mediums for this experiment, whatever you just
` summarized is right.
` Q. Do you have any reason to think that that
` general phenomenon would be different if the
` experiment had been conducted using Tryptic Soy
` Agar?
` MR. HOUSTON: Objection, beyond the
` scope.
` BY THE WITNESS:
` A. I don't know what was that you're
` talking. That's the medium for --
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 27
` Q. Well, that's a medium you identify as an
` acceptable media for bacteria in your expert
` declaration in Paragraph 14, but if the experiment
` were done under the same solution that one would use
` to carry out the standard preservative efficacy
` tests, do you have any reason to think that the
` general phenomena I described and that the Winslow
` paper describes would be any different?
` A. Yes.
` Q. How would it be different?
` A. You're talking about 44 hours to
` 48 hours?
` Q. Yes.
` A. Because the regular USP PET test that
` does not have -- majority of solution in a test tube
` is the products. Now, you inoculate 10 times 5 or 6
` population of bacteria. Bacteria were originally
` cultured in the mediums, certain medium, to make
` sure they grow. They are heavy. But when you do a
` PET test, you just take -- again, I'm not a
` microbiologist -- but you take this much of
` bacteria, put inside your test tube of ophthalmic
` solutions, which is not medium. It's products. So
` you provide no -- majority of them, there's no
` source of food there. So, that's a huge difference.
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 28
` And in 48 hours, things can change because without
` food source.
` MR. ZOLAN: Let's take a quick break.
` (Whereupon, a break in the
` proceedings was taken.)
` BY MR. ZOLAN:
` Q. Dr. Xia, a minute ago I asked you about
` generally what the Winslow paper is describing, the
` general phenomenon, and you agreed, although you --
` as a caveat, I think, in your answer agreeing, you
` said if you use a Dolloff medium for this
` experiment, I agree. I'm wondering whether you have
` any reason to believe that this general phenomenon
` is not replicable outside of a Dolloff medium?
` MR. HOUSTON: Objection, form; objection,
` beyond the scope.
` BY THE WITNESS:
` A. I don't know that.
` Q. By "I don't know that," do you mean you
` don't have any reason to believe that the general
` phenomenon is not replicable outside the Dolloff
` medium?
` MR. HOUSTON: Objection, beyond the
` scope.
`
`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
`
`800-642-1099
`
`David Feldman Worldwide
`A Veritext Company
`
`www.veritext.com
`
`
`
`Page 29
`
` BY THE WITNESS:
` A. I don't know the results, yeah. It
` really depends on what kind of medium you use. You
` can replicate the results by using very similar
` mediums, right, but what's in my mind for
` preservative efficacy test that you tried not using
` mediums, you're using a product, and your product
` should not have source of food which may attract
` bacteria or fungi. Get your product contaminated.
` So that's a huge difference between this test and
` the test I am focused on.