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`UNITED STATES PATENT AND TRADEMARK OFFICE
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
` KOIOS PHARMACEUTICALS LLC,
`Petitioner,
`
`vs.
`Case No. IPR2016-01370
`Patent No. 8,664,231
` MEDAC GESELLSCHAFT FÜR
` KLINISCHE SPEZIALPRAPARATE
` MBH,
`
`Patent Owner.
` --------------------------)
`
`DEPOSITION OF THOMAS ZIZIC, Ph.D.
`New York, New York
`Friday, August 25, 2017
`
`Reported by:
`Shauna Stoltz-Laurie, RPR, CLR
`JOB NO. 19486
`
`TransPerfect Legal Solutions
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`Page 1 of 53
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`KOIOS Exhibit 1039
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`August 25, 2017
`11:33 a.m.
`
` Deposition of THOMAS ZIZIC, Ph.D.
` held at the offices of Ropes & Gray
` LLP, 1211 Avenue of the Americas, New
` York, New York, New York, pursuant to
` Notice, before Shauna Stoltz-Laurie, a
` Certified Realtime Reporter and Notary
` Public of the State of New York.
`
`Page 3
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` A P P E A R A N C E S:
`
` NOROOZI P.C.
` Attorneys for Petitioner
` 1299 Ocean Avenue, Suite 450
` Santa Monica, California 90401
` BY: KAYVAN B. NOROOZI, ESQ.
` Kayvan@noroozipc.com
`
` HALEY & GIULIANO LLP
` Attorneys for Patent Owner
` 75 Broad Street, Suite 1000
` New York, New York 10004
` BY: JAMES F. HALEY, ESQ.
` Haley@hglaw.com
`
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` T H O M A S Z I Z I C , called as a
` witness, having been duly sworn by a Notary
` Public, was examined and testified as
` follows:
` EXAMINATION BY
` MR. NOROOZI:
`Q. Good morning, Dr. Zizic.
`A. Good morning.
`Q.
`Is that how you pronounce it?
`A. Zizic.
`Q. Okay. Thank you.
`And how long did you prepare for
` today's deposition?
`A.
`I met with Mr. Haley yesterday.
`Q. For about how many hours?
`A. Probably about six hours.
`Q. And some more time this morning as
` well?
`A. Not -- I can't say we really
` prepared this morning. I ended up doing a
` little preparation because it was delayed,
` but we didn't really prepare this morning.
`Q. What materials did you review in
` preparation?
`
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`Zizic
`A. Everything --
`MR. HALEY: You can say generally.
` You can say only generally what you
` reviewed, not specifically.
` THE WITNESS: Okay.
`A.
`I basically reviewed all the
` materials that I stated in my report that I
` reviewed.
`Q. Did you review anything new that
` was not discussed or mentioned in your
` declaration?
`A. No.
`Q. Do you understand that in this
` particular deposition setting, because it's a
` deposition related to an inter-parties
` review, you're not permitted to discuss any
` aspects of your testimony or anything related
` to this deposition with counsel during
` breaks?
`A.
`I understand that.
`MR. HALEY: Except, of course,
` attorney-client privilege issues.
` MR. NOROOZI: During breaks, there
` is no communication about the subject
`2 (Pages 2 to 5)
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`Zizic
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` MR. HALEY: Okay.
`Q. All right. Dr. Zizic -- right?
`A. Yes.
`Q. Dr. Zizic, you say in your
` declaration, in tab A at the bottom of page
` 25 if you use the numbering at the bottom of
` your declaration, that you've actively
` practiced rheumatology full time at Johns
` Hopkins until 1985; is that correct?
`A. That is correct.
`Q. Did you continue to practice
` rheumatology full time after 1985?
`A. Yes. Up until 1985, I was on the
` full-time faculty, and all of my income went
` to the university.
` In 1986, I joined Dr. Peter Holt,
` and I presently am still in practice full
` time with him.
`Q. When you say full time, what do you
` mean by that?
`A. Full time.
`Q. Well, in addition to your
` rheumatology practice, you have other
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` professional pursuits, true?
`A. Yes.
`Q. And when you say that you practiced
` rheumatology full time, do you mean that
` you're in your office treating patients five
` days a week, eight hours a day?
`A. No. I'm probably there three days
` a week on average, sometimes ten and 12 hours
` a day.
`In paragraph one of your
`Q.
` declaration, you say that you have treated
` thousands of patients for rheumatoid
` arthritis, right?
`A. Most certainly.
`Q. And are you still actively treating
` patients for rheumatoid arthritis?
`A. Yes.
`Q. How often?
`A. Probably 50 to a hundred patients a
` year.
`Q. And you prescribe them with
` medication?
`A.
`Including Rasuvo, which Medac
` provides us samples.
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`Zizic
` matter of the testimony.
` MR. HALEY: Except attorney-client
` privilege issues.
` MR. NOROOZI: I'm not sure I
` follow what you mean by that. You mean
` that if I ask a question that may
` implicate privilege issues, you --
` MR. HALEY: Right. And then we can
` have a discussion about that to make
` sure that there's a privilege or not
` privilege direction. That's what the
` rules say.
` MR. NOROOZI: Sure. That's fine.
`Q. Let me talk to you about your
` professional background a bit.
` Now, one second. Do you have any
` materials with you yourself today?
`A. No.
`Q. All right. Taken a look at your
` declaration recently?
`A.
`I did.
`Q. Let me give you a copy of your
` declaration that's already been marked as an
` exhibit in this proceeding. Your declaration
`Page 7
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`Zizic
` has been marked as Exhibit 2092.
` MR. HALEY: Counsel, do you have a
` copy for me?
` MR. NOROOZI: I don't. I only
` have one copy of everything. If you
` want, we can take a quick break and
` print one out.
` MR. HALEY: I'll see if I can find
` a copy. (Perusing documents).
`Q. Dr. Zizic, do you know if there is
` a copy of your declaration that you were
` looking at this morning, by any chance, that
` you could give to counsel?
`A.
`I have a marked-up copy.
`MR. NOROOZI: So, Jim --
`MR. HALEY: I thought I brought
` one. Just a second.
` MR. NOROOZI: Okay.
` THE WITNESS: You know what? It's
` on the desk, because you put your phone
` number on the other side of it.
` MR. NOROOZI: Take a quick pause.
` (Mr. Haley left the room, then
` rejoined the proceedings.)
`
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`Zizic
`Q. Right.
`And what about the methotrexate
` product; do you prescribe that as well?
`A. The what?
`Q. There is another methotrexate
` auto-injected product made by a company named
` Antaris, and it is called Otrexup,
`O-T-R-E-X-U-P. Have you heard of that
`product?
`A.
`I have not. They have not called
` on our office.
` Medac calls on our office and
` provides us with samples of all the various
` dosages, depending on where the patient
` graduates to.
`Q. The first time that you heard about
` the Rasuvo product was through a Medac rep?
`A.
`I don't know that for a fact.
`I mean I -- I don't know how I
` heard about Rasuvo first. I know Dr. Schiff,
` and I know Dr. Whitelefter (sic) as well here
` in Boston, and he was a former resident, so I
` know a lot of people that use methotrexate
` all the time.
`
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`Zizic
` I don't know when I first heard
` about Rasuvo.
`Q. How do you know Dr. Schiff?
`A. Professionally, through meetings.
`Q. Have you ever collaborated with
` him?
`I have not.
`A.
`Is he a clinician and researcher
`Q.
` held in high regard in the rheumatology
` community?
`A. You know, I --
`MR. HALEY: Object, form.
`-- I don't know how he's held in
`A.
` the general rheumatology community.
` I know that I disagree with his
` opinion in terms of this case, so --
`Q. With some of his opinions, or all
` of his opinions?
`A. No, some of his opinions, as stated
` in my report.
`Q. Now, in paragraph one, when you
` talk about your experience treating patients
` you mention rheumatoid arthritis but you
` don't mention psoriasis; is that right?
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`Zizic
`A. No, I don't mention psoriasis.
`Q. And have you treated patients with
` psoriasis as part of your practice?
`A. Of course. Psoriatic arthritis,
` some of whom have psoriatic skin disease
` without arthritis, but I certainly do treat
` psoriatic arthritis.
`Q. And is that still an active
` component of the patient population you see?
`A. Yes. Not as prevalent as
` rheumatoid arthritis.
`Q. Do you prescribe methotrexate to
` patients with psoriatic arthritis?
`A. Yes.
`Q. And do those prescriptions differ
` in any way, including with respect to dosage,
` compared to your typical rheumatoid arthritis
` patient?
`A. Not any systematic difference.
`Q. And do you also actively treat
` patients with juvenile rheumatoid arthritis?
`A. Very few. We have a number of
` pediatric rheumatologist at Hopkins. When I
` first started we didn't have any pediatric
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`Zizic
` rheumatologists, so I saw all of them along
` with the rest of the full-time faculty, but
` not now.
`Q. How long has it been since you've
` deferred to other specialists for treating
` juvenile rheumatoid arthritis?
` MR. HALEY: Objection to form.
`A.
`I can't really answer that, because
` some of the patients that I saw when they
` were juveniles are now adults, and I'm still
` taking care of them, so I don't know how to
` answer that quite.
`Q. Well, with respect to new patients,
` how long has it been since you've deferred to
` other specialists for the treatment of JRA?
` MR. HALEY: Objection, form.
`A. Under 16, probably 30 years, 25
` years, somewhere in there.
`Q. And does that mean that you have
` not taken on new juvenile rheumatoid
` arthritis patients in the past 25 to 30
` years?
`A. That's probably fairly accurate. I
` can say that I hadn't (sic) taken on a few
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` because of colleagues who wanted me
` specifically to see the patient, but for the
` most part, that's true.
`Q. Are you familiar with any
` systematic differences in the way that
` methotrexate is a prescribed, including with
` respect to dosage, for patients with juvenile
` rheumatoid arthritis?
`A. Yes.
`Q. What are they?
`A. Well, in general, you're looking at
` milligrams per meter squared to be able to
` compensate for the difference in size and
` therefore the dosage that you administer. So
` until they get to more than 75 pounds or more
` than 16 years of age, you generally are doing
` it milligrams per meters squared rather than
` the way we treat adults.
`Q. Does that approach result in -- on
` average higher dosages being given to
` patients with JRA than patients with
` rheumatoid arthritis?
`A.
`I don't know that I can say that
` directly. I mean because you're going up to
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`Zizic
` a maximum. You still start at a lower dose
` for JRA, and work up, you don't go up to the
` maximum, ten milligrams or 15 milligrams per
` metered squared. So I can't answer that.
`Q. Now, before July of 2006 --
`MR. NOROOZI: Withdrawn.
`Q. Have you ever personally
` administered methotrexate to a person?
`A. You mean me given the injection?
`Q. Yes.
`A. No.
`Generally a nurse does that.
`Q. Have you ever personally formulated
` a methotrexate solution for injection?
`A. No.
`Q. Have you prescribed methotrexate
` for injection to your patients?
`A. Of course, yes.
`Q. And you've done that with
` specificity as to the administration format,
` true?
`A. Dose and administration format.
`Q. Before July 26, did you prescribe
` the administration of methotrexate for the
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`Zizic
` treatment of inflammatory autoimmune diseases
` in intramuscular administration form?
`A. Yes.
`Q. Before July 26, did you prescribe
` the administration of methotrexate for the
` treatment of inflammatory autoimmune disease
` in subcutaneous forms?
`A.
`I have.
`Q. Regularly?
`A. Regularly.
`Q. And was there a point in time when
` you switched from prescribing the
` intramuscular form to the subcutaneous, or
` did you consistently prescribe both around
` the same time period?
` MR. HALEY: Objection, form.
`A.
`I think there was a gradual trend
` for more subcutaneous than intramuscular over
` that period of time before and more so even
` presently, particularly since Rasuvo has been
` present. But there are variables at which
` one you're going to prescribe, sometimes the
` patient doesn't want to give themselves sub-Q
` injections, so they come in to the clinic and
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`Zizic
` get an IM injection, or sub-Q.
`Q. Now, prior to July 26 did you
` prescribe methotrexate to patients for the
` treatment of inflammatory autoimmune diseases
` in subcutaneous form in a self-administrable
` syringe or some other type of injection
` device?
`A.
`I don't remember using an injection
` device prior.
`Q. Well, let me be specific, because
` when I said injection device I mean any type
` of -- any type of injection, including a
` prefilled syringe. Do you follow me on that?
`A.
`I do.
`Q. And even a vial and syringe, where
` the patient draws their own methotrexate.
` Are you with me on that?
`A.
`I'm with you.
`Q. All right. Now, prior to July 2006
` did you ever prescribe methotrexate for
` treating inflammatory autoimmune diseases to
` be administered subcutaneously to patients in
` a form where the patient would administer
` their own methotrexate?
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`Zizic
`A. Yes.
`Q.
`In what formats, in what sort of
` injection approaches?
`A. Subcutaneous.
`Q. And using what type of device, a
` prefilled syringe, or a vial and syringe and
` draw method? How would you describe it?
`A. Prime --
`MR. HALEY: Objection, form.
`THE WITNESS: I'm sorry.
`MR. HALEY: Objection, form.
`-- primarily vial and syringe.
`A.
`Q. Why would you make such a
` prescription?
`A. Well, there were 25 milligram per
` cc's in two-cc vials, there were ten
` milligram per cc, and there were 25 milligram
` ten -- in ten-cc vials so that patients at
` home could administer the weekly injection
` until the next clinic visit, and so it was --
` they have a preservative for sub-Q, and so it
` was meant for that.
`Q. Well, would you prescribe
` self-administration because of the
`
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`Zizic
` convenience benefits to the patient?
`A. Well, more than convenience.
` There's several aspects to it.
` One was the fact that it's
` generally less painful than the IM injection
` because methotrexate is irritating.
` And it was also more convenient for
` them in terms of not having to come in to the
` clinic.
` And less costly to the healthcare
` system: They didn't have a nurse visit every
` week. They didn't have to worry about
` transportation costs or taking off time from
` work or whatever.
`Q. When you would prescribe
` methotrexate prior to July 26 would you
` simply prescribe concentration amounts that
` were available on the market as FDA-approved
` products?
`A. Yes.
`Q. Did you ever prescribe, prior to
` July 2006, a methotrexate solution that would
` have required reconstitution?
`A. No. I didn't use any compounding
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`Zizic
` or -- with my patients. It wasn't necessary.
`Q. Regardless of dosage format,
` whether intramuscular or subcutaneous or
` anything else, you never asked anybody to
` formulate a methotrexate solution for one of
` your patients in a concentration that was
` above 25 milligrams per milliliter?
`A.
`I did not.
`Q. Did you ever ask anybody in your
` entire career to formulate methotrexate in
` any concentration for any of your patients?
`A. No.
`It was available so that you could
` give them what they needed.
`Q. Meaning that you prescribed
` methotrexate in already-constituted liquid
` vials or some other approach where the
` solution was already prepared?
`A. Yes.
`Q. And the solution came prepared in
` the product itself?
`A. Correct.
`Q. Are you aware of any physicians or
` other colleagues, including pharmacists
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`Zizic
` pharmacologists that you've worked with in
` your career, who have reconstituted
` methotrexate?
`A. Early on in my career, in terms of
` chemotherapy for leukemia or osteosarcoma,
` but not for rheumatic diseases.
`Q.
`It's true that once the
` methotrexate solution arrives already
` constituted, its concentration cannot be
` increased, it can only be decreased, right?
`A. That is correct.
`Q. However, when the methotrexate
` comes in powder form, lyophilized for
` reconstitution, its concentration can be
` selected within a wide range depending on how
` much liquid you use to reconstitute it,
` right?
`A. That is correct.
`Q.
`In your declaration, you talk about
` toxicity risks potentially associated with
` cytotoxic drugs, correct?
`A. Correct.
`Q.
`In your declaration, you don't cite
` to any study or article from prior to July
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` 2006 that shows that concentrations of
` methotrexate above 25 milligrams per
` milliliter administered either
` intramuscularly or subcutaneously cause
` toxicity, true?
`A.
`I'm not aware of it being given in
` concentrations above that.
`Q. Well, before we get there, I just
` want to get a direct answer to my question so
` I understand what's in your declaration. Is
` that fair?
`A. That's fair.
`Q. All right. In your declaration,
` you don't cite to any studies that show that
` administering methotrexate in concentrations
` above 25 milligrams per milliliter either
` intramuscularly or subcutaneously causes
` toxicity to the patient, true?
`A.
`I am not aware of any studies that
` were done on concentrations above 25
` milligrams of methotrexate per cc given
` intramuscularly or subcutaneously, period, so
` there's no articles I can cite to you,
` because to my knowledge, they don't exist.
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`Zizic
`Q. Now, when you say 25 milligrams per
` cc you mean 25 milligrams per milliliter. Is
` that the same thing?
`A. Cc's and milliliters are the same
` thing, yes.
`Q. You're not aware of such studies,
` right?
`A. No, it's not true. I have it in my
` declaration.
`Q. Okay. So I'm sorry, if I could
` make sure you answer the question in a way
` that's clear.
` (Technical failure interruption,
` and a brief recess was taken.)
`Q. All right, Dr. Zizic, we were
` discussing whether you have cited to any
` studies in your declaration that show that
` either intramuscular or subcutaneous
` administration of methotrexate in any
` particular concentration, because of its
` concentration, not dosage, causes toxicity in
` parents. Do you recall that question?
`A. You stated it a little differently
` that time.
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`Zizic
`Q. And what's the difference in this
` articulation compared to last time?
`A. Well, you're stating now to citing
` papers that state because of concentration
` and not its dosage.
` But be that as it may, I'm
` understanding your question.
`Q. And you also understand that my
` question is specific to the paper being
` directed specifically to methotrexate and
` only two dosage formats, either intramuscular
` and subcutaneous, right?
`A. Yes.
`Q. And with that understanding, is it
` your opinion that you have such studies in
` your declaration cited?
`A. Yes.
`Q. Could you direct me to where?
`A. On page eight, the Gaze paper, Case
` 13, noting "Infusion of methotrexate 100
` milligrams with resulting sloughing."
`Q. "Infusion of methotrexate 100
` milligrams" refers to the dosage of
` methotrexate, correct?
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`Zizic
`It refers to the dosage, the
`A.
` amount, yes.
`Q. And so where on page eight in your
` discussion of Gaze do you show that Gaze
` talks about concentration of methotrexate
` causing toxicity?
`A. Well, that's not in the
` declaration.
`If you'd like to look at the paper,
` I can explain to you what it is saying.
`Q. Well, but as a starting point your
` declaration's discussion of Gaze, which is
` Exhibit 2095 and which is discussed here on
` page eight of your declaration, does not
` itself show a reference to Gaze that
` discusses concentration of methotrexate
` creating toxicity in parents, right?
`A.
`I don't agree with that.
`Q. Okay. So you have only the top
` half of page eight is talking about Gaze,
` right?
`A. Correct.
`Q. And there are two quotes from Gaze
` in the top half of page eight, right?
`7 (Pages 22 to 25)
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`Zizic
`A. Correct.
`Q. The first quote is not specifically
` discussing methotrexate at all, right?
`A.
`(Reading) Well, methotrexate is a
` chemotherapeutic agent, so I don't know if I
` can agree it's not discussing it. It doesn't
` mention it specifically, but it is in the
` class of chemotherapeutic agents that he's
` talking about.
`Q. Well, and my question was the first
` quote from Gaze is not specifically
` discussing methotrexate, and you agree with
` that, right?
`A.
`It is not specifically mentioning
` methotrexate, which is a chemotherapeutic
` agent, however.
`Q. All right. Now, the second quote
` from Gaze is only talking about a dosage
` amount of methotrexate, not a concentration,
` right?
`A. Not as in here, not in here, that's
` correct.
`Q. All right. Now, do you recall,
` from the Gaze paper, what was the
`
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`Zizic
` concentration of methotrexate associated with
` that 100 milligram dosage?
`A.
`I do recall.
`Q. And what was it?
`A.
`It was 100 milligrams in one liter.
`Q. And so what does that come out to
` in milligrams per milliliter?
`A.
`It would come out to be one-tenth
` of a milligram per milliliter in the entire
` solution.
`Q. And so the Gaze paper is talking
` about toxicity of methotrexate associated
` with a concentration of -- what was the
` amount?
`A.
`.1 milligram per milliliter.
`Q. Okay. And so that is one-250th the
` concentration of what you referred to in your
` declaration as a standard 25 milligram per
` milliliter concentration of methotrexate that
` you were familiar with, right?
`A. No.
`Q. The Gaze paper was discussing a
` concentration of methotrexate of .1
` milligrams per milliliter?
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`Zizic
`A. Correct.
`Q. And so if it were one milligram per
` milliliter, that would be a 25th of the
` standard concentration that you were familiar
` with, right?
`A. Right.
`But I don't think that you could
` look of extravasation in the soft tissues,
` where several hundred cc's could be present
` in the soft tissue that is also there for a
` prolonged period because it has to be
` absorbed through the capillaries, and it may
` even get trapped in some of the fascial
` planes. So you may have exposure for an
` extreme amount of time. So you can't -- you
` can't equate 25 cc's -- 25 milligrams per cc
` that you inject under the skin or
` intramuscularly, where it's going to be
` absorbed reasonably quickly, compared to
` hundreds of cc's that can get out of the
` extravasation into the soft tissue and be
` there for a prolonged period. So it's not an
` equatable -- it's not apples and apples. So
` I'm just -- you know, your example, your
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`Zizic
` strict milligrams per cc, doesn't apply here.
`Q. So I think I understand you, and I
` just want to make sure that we're on the same
` page.
` MR. NOROOZI: Withdrawn.
`Q. There's a concentration of the
` methotrexate solution which is denoted in
` milligrams per milliliter, such as 25
` milligrams per milliliter. You're familiar
` with that, right?
`A. Of course I am, yes.
`Q. And there's another concept, which
` is a concentration of methotrexate that is
` either in the patient's tissue or in the
` patient's blood after administration. You're
` familiar with that, too, right?
`A.
`I am.
`Q. Those are two different concepts,
` right?
`A. They are not two different
` concepts. They are two different amounts
` that are -- the tissue's being exposed to.
`Q. Well, if we have a one-gram dose of
` methotrexate administered to a patient,
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` whether it's administered in 25 milligrams
` per milliliter or ten milligrams per
` milliliter will not affect the concentration
` of methotrexate that is the patient's blood
` plasma or in their tissue, right?
`A. No, that is wrong.
`Q. "That is" --
`A.
`-- wrong.
`Q. Okay. So you're saying that if you
` apply the same dosage of methotrexate, the
` same dosage amount, one gram, if you apply
` that in a higher or lower concentration, that
` will impact the concentration of methotrexate
` that is in the patient's blood?
`A.
`It depends upon the rate of
` administration. It depends upon whether
` there are third spaces, such as pleural
` effusions, peritoneal, effusions where
` methotrexate going to get in and clear much
` more slowly. It depends upon the kidney
` function, renal clearance. So it depends how
` quickly you put in that thousand milligrams.
` If you put it in, as your example
` intends, in ten-milligram increments or a
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`Zizic
` hundred-milligram increments, you could have
` a very significant difference in the plasma
` concentration that the cells are exposed to,
` based on the metabolism, the excretion --
`Q. Okay.
`A.
`-- and other factors, such as third
` spaces.
`Q. So I think my example may not have
` been clear. I think maybe there's a
` misunderstanding on my question. I'll try to
` clear it up.
` Let's assume an experiment. Are
` you with me so far?
`A. Yes.
`Q. And in this experiment, we're going
` to keep every variable constant except one.
` Are you with me there?
`A. Sure.
`Q. That's a good way to do
` experiments, right?
`A.
`If you can.
`Q. Now, when I said every variable
` constant I mean the same kidney -- right? --
` and the same rate at which the drug is
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`Zizic
` administered, and the same administration
` format, and every other relevant factor the
` same except for one factor, which is the
` concentration of the methotrexate in
` milligrams per milliliter. Are you with me
` so far?
`A. Okay.
`Q. Now, in scenario A, we have ten
` milligrams of methotrexate that's being
` administered at a concentration of ten
` milligrams per milliliter. Are you with me
` there?
`I am.
`A.
`Q. And so we know that that is going
` to be one milliliter of methotrexate, right?
`A. Correct.
`Q. All right. Now --
`MR. HALEY: Objection, form.
`Q. Okay. In scenario B, we're going
` to still administer ten milligrams of
` methotrexate. Are you with me there?
`A. Um-hm.
`Q. Except we're going to do it in 25
` milligram per milliliter concentration. Are
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` you with me there?
`A. Okay.
`Q. Now, nothing else is different
` between scenario A and scenario B in terms of
` the patient, the administration format, the
` amount of time it's administered and so
` forth. Are you with me on that?
`A.
`I am.
`Q.
`Is it your testimony that the
` concentration of methotrexate that will be in
` the patient's blood in scenario A will be any
` different than the concentration that will be
` in their blood in scenario B?
`A. Assuming you're giving .4
` milliliters in scenario B, is that the
` assumption I'm supposed to make?
`Q. The .4 milliliters will be the
` consequence of the fact that you're giving
` ten milligrams at 25 milligrams per
` milliliter, right?
`A. Correct.
`Q. Okay.
`A. You didn't tell me how much you're
` going to put in, though. How much are you
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`Zizic
` putting in in scenario B?
`Q. Well, it's ten milligrams --
`A. Right.
`Q.
`-- at 25 milligrams per
` milliliter --
`A. Right.
`Q.
`-- which, as you said, is .4
` milliliters, right?
`A. Yes.
`Q. And so we're putting in the same
` dosage of methotrexate in two different
` concentrations, resulting in scenario A
` having a one-milliliter injection of ten
` milligrams of methotrexate, and scenario B
` having a .4-milliliter injection of ten
` milligrams methotrexate, correct?
`A. Correct.
`And this is administered
` intravenously; is that what you're saying?
`Q. Let's assume it's administered
` subcutaneously. Will there be any
` difference, in your view, in the
` concentration of methotrexate that is in the
` patient's blood between scenario A and
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`Zizic
` scenario B?
`A. There may or may not be.
`Q. You can't say one way or another?
`A. Well, it would either be the same
` or slightly less in the .4/25 milligrams per
` cc, because you may cause some irritation and
` spasm of the pre-capillary arterials in the
` area, so you may have a little bit of delay
` in absorption in scenario B as compared to
` scenario A, but that would be the variable
` that you're not able to control for, because
` you've got a different concentration, two and
` a half times stronger, that the