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` THE UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________
`COALITION FOR AFFORDABLE DRUGS VIII LLC
`Petitioner
`v.
` THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
`Patent Owner
`_____________________
`Case IPR2015-01836
`U.S. Pat. No. 7,932,268
`Case IPR2015-01835
`U.S. Pat. No. 8,618,135 B2
`________________________
`
` VIDEO DEPOSITION OF THOMAS A. BAILLIE, Ph.D.
`Boston, Massachusetts
`Thursday, August 25, 2016
`
`Reported by: Dana Welch, CSR, RPR, CRR, CBC
`Job No: 111718
`
`TSG Reporting - Worldwide 877-702-9580
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`CFAD Exhibit 1056
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`Page 1
` THE UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________
`COALITION FOR AFFORDABLE DRUGS VIII LLC
`Petitioner
`v.
` THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
`Patent Owner
`_____________________
`Case IPR2015-01836
`U.S. Pat. No. 7,932,268
`Case IPR2015-01835
`U.S. Pat. No. 8,618,135 B2
`________________________
`
` VIDEO DEPOSITION OF THOMAS A. BAILLIE, Ph.D.
`Boston, Massachusetts
`Thursday, August 25, 2016
`
`Reported by: Dana Welch, CSR, RPR, CRR, CBC
`Job No: 111718
`
`TSG Reporting - Worldwide 877-702-9580
`
`CFAD Exhibit 1056
`
`
`
`Page 2
`
` August 25, 2016
` 9:01 a.m.
`
` Video deposition of THOMAS A. BAILLIE,
`Ph.D., held at the offices of GOODWIN PROCTER LLP, 100
`Northern Avenue, Boston, Massachusetts, pursuant to
`Notice, before Dana Welch, a Certified Shorthand
`Reporter, Registered Professional Reporter,
`Certified LiveNote Reporter, a Certified Realtime
`Reporter, and a Notary Public of the Commonwealth
`of Massachusetts.
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`
` A P P E A R A N C E S:
` McNEELY HARE & WAR
` Attorneys for Coalition for Affordable Drugs
` 12 Roszel Road
` Princeton, NJ 08540
` BY: CHRISTOPHER CASIERI, ESQ.
`
`GOODWIN PROCTER
`Attorneys for Trustees of the University
`of Pennsylvania
`100 Northern Avenue
`Boston, MA 02210
`BY: NICHOLAS MITROKOSTAS, ESQ.
` ERIC ROMEO, ESQ.
` CYNTHIA HARDMAN, ESQ.
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` BAILLIE
` P R O C E E D I N G S
` THOMAS A. BAILLIE, Ph.D., sworn
` EXAMINATION
` BY MR. CASIERI:
` Q. Good morning.
` A. Good morning.
` Q. My name is Chris Casieri. We met earlier.
` But just to reintroduce myself, I represent the
` petitioners in this case.
` You've had your deposition taken before?
` A. I have.
` Q. About how many times?
` A. Three times.
` Q. Three times, okay.
` Just a quick review of sort of the ground
` rules in one of these things is I ask questions,
` you answer, and the court reporter takes down your
` answer.
` The court reporter can't really pick up on
` your non-verbal responses, so if you could try and
` make those yeses, yeses, instead of head shakes
` that would be good. And yeahs and nahs don't
` really come through as much in the transcript
` either, so if you could just make an effort to do
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` BAILLIE
` that.
` If you don't understand a question, let me
` know and I'll either rephrase it or try to explain
` it, but otherwise I'm going to assume you
` understand my question. Okay?
` A. Okay.
` Q. And last thing is if you need a break, let
` me know. We generally take breaks about every hour
` or so, but if you need one before then, just let me
` know. I'd ask that you answer the pending question
` before we break, but other than that, just let me
` know. Okay?
` A. Okay.
` Q. You said you had your deposition taken
` three times, I think?
` A. Yes.
` Q. Were those in patent cases; do you know?
` A. They were all in patent cases.
` Q. And were you offering expert testimony in
` those cases?
` A. Yes, I was.
` Q. Do you remember, was a drug involved in
` any of those cases?
` A. Yes. One was Vioxx, the second was
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` Evista, and the third was Exjade.
` Q. Exjade?
` A. E-x-j-a-d-e.
` Q. Do you know if you provided -- did you
` provide a written opinion in those cases?
` A. Yes, I did.
` Q. Did you provide an opinion in those cases
` on behalf of the patent owner or the -- I guess --
` MR. CASIERI: Well, strike that.
` Q. Who did you provide opinions for in those
` cases?
` A. I provided opinions on behalf of the
` patent owners in each of the three cases.
` Q. And were your opinions in each of those
` cases that the patents at issue were valid?
` A. Yes.
` Q. So I'm going to hand to you what's been
` previously marked Penn Exhibit 2024. And this is
` for case IPR2015-01835.
` For now I just want you to -- I guess you
` can flip through it, but my question is going to be
` is that your signature on the back page?
` A. Yes, that is my signature.
` Q. Okay. I'm going to hand to you what's
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` been marked Penn Exhibit 2024 in IPR2015-01836,
` okay?
` MR. CASIERI: Counsel, I don't actually
` even have another one and I don't even have one for
` myself. I'm just trying to move it to the side.
` MR. MITROKOSTAS: I understand. That's
` okay.
` Q. Can you just confirm that that is your
` signature on the back?
` A. It is my signature on the back.
` Q. My question is, are there any substantive
` differences between the opinions in those two
` documents?
` A. There are no substantive differences.
` Q. So today what I'd like to do is stick to
` asking you questions on Exhibit 2024 for case
` IPR2015-01835, okay?
` A. That's fine.
` Q. And what I would ask you is if one of the
` answers that you give me for this Exhibit 01835
` differs for the other declaration, that you would
` point that out to me.
` A. Okay.
` Q. And that way we don't have to go through
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` BAILLIE
` each question twice. Okay?
` A. That's fine.
` Q. Is that fair?
` A. Yes.
` Q. So for now you can put away the second
` declaration if you want to just for convenience
` sake.
` Okay. Let's turn to paragraph 6 of your
` declaration. And if I just refer to Exhibit 2024
` as your declaration, will you understand that I'm
` talking about Exhibit 2024?
` A. Yes.
` Q. Okay. Today I'm going to point to a lot
` of different paragraphs and I'm going to focus on
` specific sections of those paragraphs. So you're
` free to read the entire paragraph when we get
` there. I probably won't read the entire paragraph
` into the record. But if I ask you a question about
` a particular sentence and you need to review the
` whole paragraph, feel free to do so. Okay? And
` again, I'm just trying to make things a little
` simpler here. Okay?
` A. That's fine.
` Q. Now, in paragraph 6 you, I guess, identify
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` the information that you considered in forming your
` opinion; is that fair?
` A. Yes.
` Q. Okay. Now did you consider any other
` information that's not identified in this paragraph
` in forming your opinion?
` MR. MITROKOSTAS: Objection to the form.
` A. I didn't consider any other information in
` the preparation of this declaration.
` Q. Other than your attorneys, did you have
` any discussions or correspondence with anyone in
` forming your opinions expressed in this
` declaration?
` A. No, I did not.
` Q. Are you aware that other individuals
` submitted declarations in these IPRs in support of
` the patent owner?
` A. Yes, I am.
` Q. Did you review any of their declarations?
` A. I reviewed the declarations by
` Dr. Mayersohn and by Dr. Zusman.
` Q. Did you review their deposition
` transcripts of either one of those individuals?
` A. Yes. I have seen the transcripts from
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` BAILLIE
` both of these individuals.
` Q. How about the witnesses for the patent
` owners, Dr. Frank Sacks and any other -- does that
` name sound familiar, Dr. Frank Sacks?
` MR. MITROKOSTAS: Objection to form.
` A. I recognize the names you mentioned, but I
` haven't read their declarations.
` Q. Okay. Did you have a conversation with
` Dr. Frank Sacks after you submitted your
` declaration?
` A. No. I've not spoken to Dr. Sacks.
` Q. Dr. Kimball, you didn't speak with
` Dr. Kimball?
` A. No. I've never spoken to Dr. Kimball.
` Q. Let's move on to your qualifications.
` You have a Ph.D., correct?
` A. Correct.
` Q. In?
` A. I have a Ph.D. in organic chemistry.
` Q. Organic chemistry; okay.
` And then you have a doctor of science in
` chemistry?
` A. That's correct.
` Q. What is a doctor of science?
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` A. Doctor of science degree is a degree more
` frequently awarded in Europe than it is in the
` United States, and it is awarded in recognition of
` contributions to the research field in which you're
` working. It involves the preparation of a thesis
` and an oral defense.
` Q. Does it differ from a Ph.D.?
` A. Yes. It is different from a Ph.D. It is
` based largely on your record of publications.
` Q. Do you have a focus of study in order to
` get a doctor of science?
` MR. MITROKOSTAS: Objection to the form.
` A. The theme of the thesis I submitted was
` applications of stable isotopes in pharmacology,
` toxicology, and clinical research.
` Q. Okay. And what was your -- you had to do
` a thesis, I take it, to get a Ph.D., correct?
` A. Correct.
` Q. What was the title of that, if you
` remember? Or you can just tell me the subject
` matter.
` A. The title, I believe, was "Applications of
` Gas Chromatography, Mass Spectrometry to the
` Analysis of Corticosteroids."
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` Q. Okay. So just to complete this, you do
` not have an M.D., correct?
` A. Correct.
` Q. And you cannot treat patients; is that
` correct?
` A. That's correct.
` Q. Or prescribe medication?
` A. That's correct.
` Q. Let's move ahead to the next paragraph,
` paragraph 10. And I'm just going to skip to the
` last sentence of this paragraph where it says "this
` position also gave me an opportunity to work on
` numerous drug programs relating to
` hypercholesterolemia."
` Do you see that?
` A. Yes, I do.
` Q. If you can tell me, what were the drug
` programs that you were working on?
` A. The major hypercholesterolemia program
` that I was involved with was the statin program at
` Merck, but I also was involved in programs
` associated with the development of the sterol
` uptake inhibitor ezetimibe or Zetia as it was
` ultimately marketed, together with a program that
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` BAILLIE
` was a prostaglandin D receptor antagonist program
` designed to minimize the flushing side effects of
` niacin. In addition, I was involved with the
` so-called CETP inhibitor program, cholesterol ester
` transfer protein inhibitor program, which still is
` ongoing at Merck.
` So these were the various programs that
` dealt with cholesterol-lowering drugs that I was
` personally involved with.
` Q. So when you were involved in them, what
` was -- I guess, take them one at a time, unless
` your role was the same in all of them and you can
` tell me.
` A. The role was basically the same in all
` four of these.
` Q. And what was your role in these projects?
` A. I was responsible for the drug metabolism
` and pharmacokinetics function at Merck worldwide,
` and so members of my department would be involved
` in project teams in all of these different
` programs. And I had responsibility for the PK,
` pharmacokinetics, and drug metabolism support for
` all of these activities.
` And in addition, I was a member of an
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` BAILLIE
` executive review panel that reviewed all candidate
` drugs coming forward for clinical development,
` which, of course, went beyond just the
` cholesterol-lowering programs.
` Q. So what does that really mean?
` MR. CASIERI: I guess, strike all that.
` Q. I'm trying to figure out what you did when
` you say you had responsibility for the PK,
` pharmacokinetics, and drug metabolism support.
` MR. MITROKOSTAS: Objection to the form.
` A. We would -- when I say we, my department
` would be responsible for providing the expertise in
` pharmacokinetics and drug metabolism that was
` necessary for both the preclinical development of
` various drug candidates and also for the clinical
` development programs.
` So for example, in the clinical
` development side, we would be working very closely
` with our colleagues in clinical pharmacology and
` the later stages of clinical research in terms of
` helping them design the initial and late stage
` clinical development protocols and interpreting the
` pharmacokinetic and drug metabolism data that came
` from these trials.
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` BAILLIE
` So I had oversight responsibility for all
` that activity across the company.
` Q. So did you or your group that you were in
` charge of actually design initial and late stage
` clinical development protocols?
` MR. MITROKOSTAS: Objection to the form.
` A. Our department was not solely responsible
` for the development of these protocols, but we
` worked in collaboration with our colleagues in
` clinical pharmacology and clinical research to do
` so.
` Q. How about dosing regimens, did you have
` any responsibility in developing dosing regimens?
` A. Yes. That was part of the collaboration
` that we would have with our clinical pharmacology
` colleagues.
` Q. Would you propose dosing regimens? Like
` what specifically would you do with regard to
` dosing regimens?
` MR. MITROKOSTAS: Objection to the form.
` A. Dosing regimens would derive from an
` understanding of the so-called
` pharmacokinetic/pharmacodynamic relationships,
` PK/PD relationships, and that information obviously
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` BAILLIE
` had a major element of pharmacokinetics. And so it
` was the responsibility of my group to ensure that
` that background information on PK/PD relationships
` developed initially in animals was appropriately
` translated to the design of the clinical trials.
` Q. What steps go into ensuring that the PK/PD
` relationship developed initially in animals is
` appropriately translated to the design of the
` clinical trials?
` MR. MITROKOSTAS: Objection to the form.
` A. Well, an important element is the
` relationship between the dose of the molecule,
` either to animals or to humans, and to the
` resulting exposure, systemic exposure, because
` clearly the pharmacodynamic result is a consequence
` of exposure of the target to the drug itself. So
` one starts by developing these PK/PD relationships
` in animals and ultimately they have to be
` translated to the corresponding situation in
` humans.
` A very important element in that
` translation, of course, is what are the most
` appropriate animals for the human situation.
` That's where metabolism becomes important, because
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` BAILLIE
` you want to select an animal species where the
` metabolism of your candidate drug is going to be
` reflected in the metabolism in humans. And prior
` to a drug candidate being selected for development,
` you can assess that by appropriate in vitro studies
` using liver preparations from the different animals
` and from humans.
` So you can make a cautious extrapolation
` from the animal data to man and you can select the
` most appropriate animal that you think will
` represent the situation in humans. So that's where
` the PK/PD relationship initially developed in
` animals is translated to the human situation.
` Q. So can you tell me, what are all the
` factors --
` MR. CASIERI: Strike that.
` Q. At some point you got animal data,
` correct, and you want to then go to clinical
` trials. To make that transition from animal data
` to clinical trials, what are the steps involved in
` determining how you're going to dose the humans?
` MR. MITROKOSTAS: Objection to the form.
` A. So your question pertains to the
` first-in-human studies?
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` Q. Yeah.
` My question is, if you -- at some point in
` the development of a drug, I assume you're going to
` go from animals to humans, and at some point you're
` going to have to test the drug on humans for the
` first time, correct?
` A. Correct.
` Q. So what I'm trying to understand is what
` steps are involved when you want to make that
` transition from, okay, we have tested it on
` animals, we now want to test it on humans, what
` steps are involved?
` MR. MITROKOSTAS: Objection to the form.
` A. Well, there's quite a large number of
` considerations, as you might imagine, in making
` that very important transition to the so-called
` first-in-human studies. You clearly would want to
` assure yourself during the course of the
` preclinical development that you had, in fact,
` selected appropriate animals for the preclinical
` evaluation of efficacy and of safety, because
` safety considerations are the number one
` consideration when you take a molecule forward into
` a first-in-man study.
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` And so the primary determinant of how you
` would initially dose a human with regard to
` selection of the starting doses is based on safety
` considerations in appropriate animal species. And
` that really requires, then, an understanding of the
` relationship between exposure and effect,
` particularly any effect that would be considered to
` be a toxic effect.
` And there are guidelines that are used
` across the industry, guidelines, in fact, that were
` put out by the Food & Drug Administration that
` provide a roadmap in how you do that. And it's
` based on the so-called no-observed-adverse-effect,
` the NOAEL as it's referred to, in animals.
` And then taking the dose that produces
` that NOAEL and reducing it by an appropriate safety
` factor that is at least ten, usually somewhat more,
` that ultimately gives you a dose that is viewed as
` going to be a safe dose, a human equivalent dose
` divided by a safety factor, is going to be safe for
` administration to humans. So that is the major
` consideration in that translation to
` first-in-human.
` Q. Okay. Let's look at paragraph 11. You
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` BAILLIE
` indicate, "Over the course of my career, the focus
` of my research has been in the field of foreign
` compound metabolism in animals and humans."
` There's more there. But what I wanted to
` ask you was, what is the "field of foreign compound
` metabolism"?
` A. Foreign compound metabolism, the words
` "foreign compound" refer to anything that is
` foreign to life, so that could be a drug; it could
` be an environmental pollutant; it could be really
` any molecule that is not naturally occurring.
` Q. On paragraph 13 you indicate, "Prior to
` and following my career in industry, I have served
` as a consultant to the pharmaceutical industry on
` issues relating to drug metabolism and preclinical
` drug development."
` Do you see that?
` A. Yes, I do.
` Q. Just confirm for me what preclinical drug
` development is.
` A. Preclinical drug development refers to the
` phase of developing new therapeutic agencies that
` is conducted in animal studies.
` Q. And is it correct to say that clinical
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` development is the development phase that refers to
` new therapeutic agencies that is conducted in
` humans?
` MR. MITROKOSTAS: Objection to the form.
` A. Correct.
` Q. In short is human testing, is that --
` A. Clinical drug development would refer to
` testing in human subjects.
` Q. So in your declaration, if you refer to
` preclinical drug development testing or in some
` other capacity, you're referring to animal testing?
` MR. MITROKOSTAS: Objection to the form.
` A. It's correct that terminology
` "preclinical" refers to the animal phase prior to
` human studies.
` Q. And clinical testing throughout your
` declaration would refer to human testing?
` A. That's correct.
` Q. I'm not going to ask you to commit to
` every use of the term "clinical" and "preclinical"
` in every document, but is it fair to say that
` that's a standard terminology used in the
` pharmaceutical industry?
` MR. MITROKOSTAS: Objection to the form.
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` BAILLIE
` A. I think it's generally understood that
` that is what's being referred to.
` Q. So I'm not sure if I quite got the answer
` earlier. But have you ever designed a dosing
` protocol for a clinical trial?
` MR. MITROKOSTAS: Objection to the form.
` A. Not in isolation. But I've worked
` together with my colleagues in clinical
` pharmacology to assist them in developing a dosage
` regimen for human studies.
` Q. Who would typically -- I guess at some
` point if you're developing a clinical protocol, who
` of your colleagues would typically come up with the
` dosing regimen?
` MR. MITROKOSTAS: Objection to the form.
` A. Well, as I said, it would be a team
` effort. It wouldn't be any one individual. It
` would be a result of a conversation between a
` number of us, both in the clinical and non-clinical
` side of the development team. For example, safety
` assessment would be a major player in that
` conversation. The DMPK group, which I oversaw, was
` an important player because they had an
` understanding of the pharmacokinetics in animals
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` BAILLIE
` and its translation to human subjects. So it was a
` team effort.
` Q. And in terms of a dosing regimen, what
` information do you actually get from
` pharmacokinetics in animals?
` MR. MITROKOSTAS: Objection to the form.
` A. Well, the pharmacokinetics has to be
` viewed in the context of, as I mentioned before,
` the PK/PD relationship for a given compound, how
` the kinetics translate to the ultimate effect of
` the molecule. So pharmacokinetics tells you
` something about exposure, systemic exposure to your
` drug from a particular dose. It also has a time
` element which indicates duration of exposure, or
` conversely, rates of elimination of the drug. And
` these are very important considerations in terms of
` the biological effect you're going to see.
` So that PK/PD relationship, if you will,
` in animals really characterizes the pharmacological
` effect of your candidate drug and that is what
` you're then attempting to translate to the human
` situation in your first-in-human clinical trials.
` So the PK/PD data from animals is integral in the
` design of your first-in-human studies.
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` Q. Would you ever look at -- in developing
` this dosing protocol, would you ever look at drugs
` in the same therapeutic class?
` MR. MITROKOSTAS: Objection to the form.
` A. You typically would be aware of what drugs
` from other companies, how they were being dosed in
` the same therapeutic class. But every molecule has
` to be considered on its own merits. You would
` never actually look at competitors' dosing regimens
` as a guide for how you're going to dose your
` compound.
` Q. For example, I think you mentioned you
` worked on statins, right?
` A. I did.
` Q. Were you involved in developing a dosing
` regimen for statins at Merck?
` MR. MITROKOSTAS: Objection to the form.
` A. I was involved in a project that was
` involved in, or that was focused on I should say,
` different salt forms and different formulations of
` simvastatin, which was Merck's major statin
` product, Zocor. And we did some clinical trials on
` some of these new formulations and salt forms that
` involved, of course, identification of appropriate
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` BAILLIE
` doses.
` Q. So when you were working on -- was
` simvastatin a commercially available drug at the
` time?
` A. Yes, it was.
` Q. And you and your group were working on new
` formulations for simvastatin?
` A. That is correct. And particularly, new
` salt forms of simvastatin.
` Q. And ezetimibe, what therapeutic class does
` that belong to?
` A. Therapeutic class is cholesterol-lowering
` agent.
` Q. Was that a commercially available drug at
` the time that you were working on it?
` A. No. But it became an approved product
` during the time that I was at Merck.
` Q. What's the mechanism of action of
` ezetimibe?
` A. Ezetimibe has a very interesting and
` unusual mechanism of action in that it blocks an
` uptake transporter in the gut that is responsible
` for the absorption of sterols from the diet,
` including cholesterol. So basically what ezetimibe
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` BAILLIE
` is doing is it's blocking the uptake of cholesterol
` from ingested foodstuffs.
` Q. And were there other drugs available or
` that you knew of that had that same mechanism of
` action?
` MR. MITROKOSTAS: Objection to the form.
` Q. At the time you were working on it.
` A. Ezetimibe, to my knowledge, was the first
` compound that worked by that particular mechanism
` of action that became an approved therapeutic
` agent.
` Q. So in your role in, I guess, developing
` these dosing regimens, would your group suggest
` specific doses or specific frequencies or would you
` be just providing data?
` MR. MITROKOSTAS: Objection to the form.
` A. The way that the project teams operated at
` Merck, which I believe is representative of the way
` they operate throughout the industry, is that the
` various scientific disciplines that are represented
` on the teams all have a voice in the design of
` studies, whether they be in animals or in humans.
` And so in terms of designing dosing
` regimens, our opinion from DMPK would be weighed as
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` BAILLIE
` heavily as opinions from safety assessment and
` other disciplines. So it really was a joint
` decision. It was a very effective mechanism of
` designing clinical trials, particularly the
` first-in-human studies.
` Q. What kind of opinions would you be sort of
` offering to the group?
` MR. MITROKOSTAS: Objection to the form.
` A. Well, examples of the kind of opinions we
` would offer would be in terms of the frequency of
` dosing that would be necessary. In other words, is
` this particular drug candidate likely to be a
` once-a-day drug or a twice-a-day drug or
` potentially even more frequent? And that dosing
` frequency decision would be, of course, dictated by
` the anticipated pharmacokinetic behavior of the
` compound in humans, which in turn would come from
` the known PK characteristics in animals.
` We would also provide guidance in terms
` of -- together with our colleagues in safety
` assessment -- the starting doses based on our
` understanding of dose exposure relationships.
` Q. Let's take a look at paragraph 61.
` A. Yes, I have that.
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` Q. Okay. You say, although -- first of all,
` you say, "I agree with Dr. Sacks' POSA definition."
` And you'll understand, just to make it easier, if I
` say POSA, you have the abbreviation here, person of
` ordinary skill in the art?
` A. Yes.
` Q. You agree with Dr. Sacks' POSA definition?
` A. I agree with that definition as one of a
` number of definitions of POSA.
` Q. What do you mean that's by a number of --
` "one of a number of definitions"?
` A. Well, I've seen other definitions of POSA
` in connection with these proceedings, one from
` Dr. Zusman, for example, which I felt was perfectly
` acceptable as well.
` Q. So you say, "Although I do not hold an
` M.D. degree, I believe my background, knowledge,
` and experience give me sufficient insight as to the
` perspective of a POSA."
` Do you see that?
` A. Yes.
` Q. Why do you highlight that you do not hold
` an M.D. agree?
` A. Simply because Dr. Sacks' definition in
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` BAILLIE
` the preceding paragraph states that the person of
` ordinary skill in the fields of the patent would
` have an M.D. and several years of experience in
` treating patients.
` I don't have an M.D. degree, but in view
` of my background, knowledge, and experience,
` particularly in the pharmaceutical industry, I
` think I've got a good perspective of what a POSA is
` and the considerations that go into the issues
` being discussed in this patent.
` Q. Would you be able to develop a dosing
` regimen by yourself without access to an M.D.?
` MR. MITROKOSTAS: Objection to the form.
` A. I think that going back to what we were
` discussing previously in terms of the project team
` environment, which is where dosing regimens were
` developed, the membership of that team would not
` absolutely require someone with an M.D. present.
` However, the actual bottom line responsibility for
` any human studies is always associated with an
` individual who is medically trained. So the
` M.D. might not be necessary for the identification
` of a dosing regimen, but ultimately in the conduct
` of a clinical trial, it's a physician who is
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` responsible for the safety of the subjects that are
` enrolled in that trial. So there has to be an
` M.D. that is leading that element of the
` development program legally.
` Q. Why don't we jump ahead to paragraph 80.
` A. I have paragraph 80.
` Q. The subtitle here is "Finding an Optimal
` Dose."
` What is an optimal dose?
` MR. MITROKOSTAS: Objection to the form.
` A. I would consider an optimal dose to be a
` dose that achieves the efficacy objective. So for
` example, in the context of this patent, it would be
` a target degree of cholesterol lowering in the
` subj
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