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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 IPR2015-01835 & IPR2015-01836
` U.S. Pat. No. 7,932,268
`
` ________________________
`
` VIDEOTAPED DEPOSITION
` OF
` S. DAVID KIMBALL, PH.D.
` New York, New York
` Monday, July 11, 2016
`
`Reported by:
`ANNETTE ARLEQUIN, CCR, RPR, CRR, CLR
`JOB NO. 109962
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`PENN EX. 2304
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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 IPR2015-01835 & IPR2015-01836
` U.S. Pat. No. 7,932,268
`
` ________________________
`
` VIDEOTAPED DEPOSITION
` OF
` S. DAVID KIMBALL, PH.D.
` New York, New York
` Monday, July 11, 2016
`
`Reported by:
`ANNETTE ARLEQUIN, CCR, RPR, CRR, CLR
`JOB NO. 109962
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` July 11, 2016
` 9:03 a.m.
`
` Videotaped deposition of S. DAVID
`KIMBALL, Ph.D., held at the offices of
`GOODWIN PROCTER, 620 Eighth Avenue, New
`York, New York, pursuant to Notice, before
`Annette Arlequin, a Certified Court
`Reporter, a Registered Professional
`Reporter, a Certified LiveNote Reporter, a
`Certified Realtime Reporter, and a Notary
`Public of the State of New York.
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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, New Jersey 08540
` BY: CHRISTOPHER CASIERI, ESQ.
` - and -
` GONSALVES LAW FIRM
` Attorneys for Coalition for Affordable Drugs
` 2216 Beacon Lane
` Falls Church, Virginia 22043
` BY: GREGORY GONSALVES, ESQ.
`
` GOODWIN PROCTER
` Attorneys for Trustees of the University
` of Pennsylvania
` 901 New York Avenue, NW
` Washington, DC 20001
` BY: WILLIAM JAMES, ESQ.
` ERIC ROMEO, ESQ.
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` S. David Kimball, Ph.D.
`S. D A V I D K I M B A L L, P.h.D., called as
` a witness, having been duly sworn by a
` Notary Public, was examined and testified
` as follows:
`EXAMINATION BY
`MR. CASIERI:
` Q. Good morning.
` A. Good morning.
` Q. My name is Chris Casieri. I
`represent the petitioner in these two
`proceedings.
` Can you just state your name for the
`record?
` A. Yes. David Kimball.
` Q. And you're aware that you are here
`for two different proceedings, correct?
` A. That's correct.
` Q. And you submitted -- we'll get to
`that. A couple ground rules.
` You've had your deposition taken
`before, correct?
` A. Yes, but mostly for personnel
`matters.
` Q. Okay. Just by way of reminder, I'm
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`going to ask you questions and you'll give
`answers.
` The court reporter will take down the
`answers. She can only take down your verbal
`responses so if you could try and keep your
`responses to verbal instead of shaking your head
`or yeahs and nahs. We appreciate that.
` And then if my questions, if you
`don't understand a question, just ask me, let me
`know and I'll try and clarify the question and
`rephrase it, okay?
` A. Yes, I understand.
` Q. I'm going to hand you what's been
`marked Penn Exhibit 2025.
` A. Okay. Thank you.
` Q. And if you can just turn to the back
`of that and just confirm that that's your
`signature.
` A. Yes, that is my signature.
` Q. Page 72?
` A. Yes.
` Q. I'm going to hand you a second
`document titled "Declaration of Dr. S. David
`Kimball, Ph.D.," Penn Exhibit 2025 and the IPR
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` S. David Kimball, Ph.D.
`or the case number is IPR 2015-01836.
` Can you take a look at that?
` MR. CASIERI: Sorry. I didn't bring
` an extra one.
` A. That is also my signature.
` Q. Okay. Can you confirm that these --
`strike that.
` Do those two declarations, are they
`substantively the same?
` A. Yes, the substance is the same.
` Q. Can you just generally describe what
`the difference between the two declarations is?
` A. The difference is in relating to the
`two different patents, the '268 and the '135.
` Q. But the -- is there any significant
`difference in the opinions expressed in the one
`as compared to the other?
` A. No. My opinions with respect to the
`patents is the same regardless of whether it's
`'135 or '268.
` Q. Okay. What I'd like to do is just
`put the 1836 declaration, just put that to the
`side.
` A. Um-hmm. Okay.
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` Q. I'd like to use the other one for the
`purposes of today and I know it's difficult to
`do, but to the extent the answer you give on
`today differs between the two, if you can just
`let me know.
` A. Yeah, I will inform you if there's
`any difference.
` Q. Okay.
` MR. CASIERI: Did you want to see it?
` MR. JAMES: See what? Sorry.
` MR. CASIERI: This is the second
` declaration.
` MR. JAMES: No, that's okay. Thank
` you.
` If you ask questions about it, then
` I'll want to see it.
` MR. CASIERI: All right.
` MR. JAMES: Otherwise...
`BY MR. CASIERI:
` Q. So we are just going to focus for now
`on Penn Exhibit 2025.
` That's for case 2015-1835, correct?
` A. Yes.
` Q. So I'll ask you to turn to paragraph
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`6, which is on page 3.
` A. Okay.
` Q. In paragraph 6 you identify materials
`considered in forming your opinion?
` A. They should be in the exhibit. In
`2033, is that the question?
` Q. No, I was just generally saying is
`this what you're identifying in this paragraph
`the materials that you --
` A. Yes, that's what's written.
` Q. Did you consider any other
`information that's not identified in this
`paragraph?
` A. My 35 years of experience has formed
`my opinions as well.
` Q. Did you have any discussions or
`correspondence with anyone other than your
`attorneys in forming your opinions expressed in
`the declaration?
` A. No.
` Q. Okay. Did you have any discussions
`or correspondence with any of the other
`witnesses that submitted declarations in these
`IPRs?
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` A. No.
` Q. Do you know who the other witnesses
`that submitted declarations are?
` A. On the Penn side or the --
` Q. Either. First let's start with the
`Penn side.
` A. I know their names and I know, Dick
`Gregg obviously I know from my past work at
`Bristol-Myers. He was heading up the metabolic
`disease research.
` Q. Do you know Dr. Rader?
` A. I do not know Dr. Rader.
` Q. But you did not have a discussion
`with Richard Gregg?
` A. Yeah. Well, yeah. He goes by Dick,
`but yeah.
` Q. Gregg.
` A. No, I did not.
` Q. Did you review his -- you didn't
`review his declaration?
` A. I did not. I have not seen his
`declaration.
` Q. In preparation for today's
`deposition, did you see his declaration?
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` A. No, I have not seen his declaration.
` Q. Okay. Why don't we turn to, I
`believe it's the next section, "Qualifications."
` A. Um-hmm.
` Q. So do you have an M.D.?
` A. I do not have an M.D.
` Q. Just so the record is clear, an M.D.
`is a medical doctor?
` A. That's correct. I have a Ph.D., not
`an M.D.
` Q. You did not go to medical school?
` A. I did not go to medical school.
` Q. You cannot prescribe medications of
`any kind?
` A. That is correct, I would not want to.
`I cannot.
` Q. Understood.
` You have not treated any patients,
`correct?
` A. I am not a practicing physician. I
`can't directly treat patients.
` Q. And I guess it's fair to say you have
`not treated patients with lipid disorders.
` A. I have not prescribed drugs to treat
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`patients for lipid disorders.
` Q. Okay. Can you turn to paragraph 10.
` A. Um-hmm.
` Q. Okay. So you indicate here that,
`"Lomitapide was developed at BMS during my time
`there."
` Do you see that?
` A. I do.
` Q. BMS is Bristol-Myers Squibb?
` A. Bristol-Myers Squibb, correct.
` Q. And then you indicate, "Although I
`did not formally work on the MTP inhibitor
`program at BMS, I was well acquainted with both
`the people and the underlying science involved
`in that program."
` Did I read that right?
` A. You did, yes.
` Q. Okay. So you say you didn't formally
`work on the MTP inhibitor program.
` Did you have any role in that MTP
`inhibitor program while you were at BMS?
` MR. JAMES: Objection to the form.
` A. I didn't -- I wasn't leading the MTP
`program. I was in leadership in medicinal
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`chemistry, so obviously I would have heard
`reports about it and we would have discussed all
`of the programs at Bristol-Myers over time, so
`we were aware.
` Q. I'm not sure I understand.
` Did you have any duties and
`responsibilities with regard to the MTP program?
` A. I had no specific duties or
`responsibilities.
` Q. What do you mean you say you were
`acquainted with the underlying science involved
`in that program?
` A. We would have -- there would be
`discussions fairly frequently, seminars,
`discussions about the science going on across
`the programs, presentations of all the drug
`discovery and development that was going on. So
`I was clearly aware of what was going on. This
`was a high level, very cutting edge program.
` Q. I guess did you have any input in the
`direction that that program was going to go?
` A. No. That was not my role.
` Q. Okay. At that time, what was your
`position at BMS?
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` A. I was the research group leader at
`that time in cardiovascular disease and
`antihypertensives, antithrombotics and
`anticoagulants over that period of time.
` Q. And then there would be someone else
`who was -- had a similar role who was in charge
`of the MTP inhibitor program?
` A. Yes. That would have been Scott
`Biller and Jeff Robl.
` Q. So in forming the opinions that you
`express in your declaration, did you rely on any
`of those recollections of the BMS MTP inhibitor
`program?
` A. No, I did not.
` Q. Did you know Peter Ringrose?
` A. Yes, but not well. He was the head
`of research.
` Q. Did you report to him?
` A. No, I did not. My supervisor
`reported directly to him.
` Q. So just to summarize -- strike that.
` Did you discuss BMS's decision at all
`to discontinue the development of lomitapide?
` A. I did not. That would be on the
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`development team. I was not on the development
`team for MTP.
` Q. So informally were you ever consulted
`about the decision to discontinue lomitapide?
` A. No. This was -- this is a discussion
`that's held on the development team and if I had
`been the leader of the MTP program, I would have
`been on the team, but I was not.
` Q. So just -- this next question doesn't
`apply just to BMS. This applies to you,
`experiences generally.
` Were you ever involved in the
`development of a drug for treating
`hyperlipoidemia?
` MR. JAMES: Objection to form.
` You can answer.
` A. Yes, at Lexicon I was.
` Q. Okay. What drug was that?
` A. The drug never got past preclinical
`development.
` Q. When were you at Lexicon?
` A. I was at Lexicon from 2001 to 2007.
` Q. What was therapeutic class of that
`drug?
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` A. That was an anti-atherosclerosis drug
`and we had a number of targets. We at that
`point had more knockout animals than the rest of
`the world combined. We had a number of targets
`for arthrosclerosis, metabolic syndrome and
`diabetes which we pursued.
` Q. Does that class work by lowering
`cholesterol?
` MR. JAMES: Objection to form.
` A. The class works by lowering lipids.
` Q. You said that never got past
`preclinical development.
` Can you explain what preclinical
`development is?
` A. Preclinical development is everything
`that occurs before a compound is approved to go
`into clinical trials, so everything up to the
`investigational new drug filing.
` Q. Clinical trials is human trials?
` A. Human trials, that's right.
` Q. So preclinical trials involves animal
`testing?
` A. Um-hmm. Everything from the
`discovery of a lead molecule, optimizing lead
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`molecule, working to optimize its
`pharmacokinetics, pharmacodynamics, toxicology,
`its safety profile in animals and running
`through the preclinical submission for
`investigative new drug. All of that's required
`to go into demand.
` Q. And how far within the preclinical
`development did you get with any of your drugs
`at Lexicon?
` A. At Lexicon we put 10 molecules into
`IND, into clinical trials. All of those came
`out of the team I was leading in Princeton.
`They were all small molecule therapeutics.
` Q. Okay. Actually I don't think you
`ever told me the name of the drug that was for
`treating atherosclerosis and you don't have to
`tell me it.
` A. Well, it never got a name because it
`never got to the point where we were going to
`submit.
` Q. Okay.
` A. So it was in preclinical development.
` Q. So how far did it get before you
`discontinued?
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` A. In animal testing.
` Q. Did you ever work on any other drugs
`that were designed to treat lipid disorders or
`high cholesterol?
` A. No. Those were the primary targets
`at Bristol-Myers. Excuse me, at Lexicon
`Pharmaceuticals.
` Q. Do you have any publications or
`patents related to MTP inhibitors?
` A. Related to MTP inhibitors
`specifically, no.
` Q. Let's skip to paragraph 63.
` A. Sixty-three?
` Q. Yes.
` A. Okay.
` Q. In paragraph 63 you essentially agree
`with Dr. Frank Sacks' proposed definition for a
`person of ordinary skill in the art, correct?
` A. Yes.
` Q. Now if you turn to paragraph 64,
`that's where you agree with Dr. Sacks' person of
`ordinary skill in the art definition.
` And then you say, "Although, I do not
`hold an M.D. degree, I believe my background,
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`knowledge and experience gives me sufficient
`insight as to the perspective of a person of
`ordinary skill in the art."
` Do you see that?
` A. Yes, I do.
` Q. Do you consider yourself a person of
`ordinary skill in the art?
` A. So POSA, the POSA in the context of
`drug development is a team and it's a team
`that's comprised of basic scientists; chemistry,
`pharmacology, toxicology, all the way through
`the medical doctor. The M.D. of course has to
`sign off and has the responsibility and the
`liability for actually putting a drug into human
`trials, but it's a composite and everyone works
`together on that team and informs each other.
` Q. And do you consider yourself a piece
`or a member of that team?
` A. Yes. I have been -- since the late
`'80s I've been on clinical development teams and
`drug development teams.
` Q. So the person of ordinary skill in
`the art in this instance is not a single person,
`but a group of people?
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` A. It necessarily must be.
` Q. And so no one person would have all
`the knowledge of this team of people involved in
`a drug development?
` MR. JAMES: Objection to the form.
` A. No individual person would
`necessarily have it by themselves. They would
`consult and they would obtain input from other
`experts.
` Q. Let's skip ahead to paragraph 69.
` A. Yes.
` Q. Okay. So you -- strike that.
` Where you testified that you did not
`read the declaration of Dr. Richard Gregg,
`correct?
` A. That's correct.
` Q. And you did not read the declaration
`of Dr. Rader?
` A. I did not.
` Q. Do you feel you have any proprietary
`information that a person of ordinary skill in
`the art would not have due to your employment at
`BMS?
` A. No.
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` MR. JAMES: Sorry. I just want to
` make sure I understand your question.
` You're asking about proprietary
` information about this subject matter.
` That was a very broad question.
`BY MR. CASIERI:
` Q. Yes, with regard to the two
`patents-at-issue in these two IPRs.
` A. I do not have and never have had
`proprietary information on the program.
` Q. We can turn to paragraph 73.
` A. Okay. I'm there.
` Q. And the heading is "The chemical
`structure of a drug molecule determines its
`biological performance."
` Did I read that right?
` A. You did.
` Q. Can one skilled in the art determine
`the biological performance based solely on the
`chemical structure?
` A. That's not what this says. That's a
`misreading of it.
` It says that the function is defined,
`is determined by the performance, not that you
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`can necessarily draw a structure and know what
`it will do.
` Q. Right. I didn't, I didn't read it, I
`just asked you a question.
` So --
` A. Well, that's the answer.
` MR. JAMES: Maybe you could ask the
` question again.
`BY MR. CASIERI:
` Q. My question is, can one skilled in
`the art determine the biological performance
`based solely on the chemical structure?
` A. One can, based on experience and
`given data, one can guess, but one can never
`know without doing the experiment.
` Q. All right. Let's turn to paragraph
`77.
` (Witness complies.)
` Q. So every drug has its own unique
`chemical structure, correct?
` A. That's correct.
` Q. Now you indicate in here that, "A
`POSA would generally not expect drugs with very
`different chemical structures to be able to be
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`dosed effectively using the same regimen."
` Do you see that?
` It's actually at the end of the
`paragraph.
` A. All right. Okay. Where it says, "A
`POSA would generally not expect drugs with very
`different chemical structures to be able to be
`dosed effectively using the same regimen." Yes.
` Q. Okay. So would you expect a POSA to
`be able to determine what a very different
`chemical structure is compared to just a
`different chemical structure?
` MR. JAMES: Objection to the form.
` A. The difference in chemical -- a
`significant difference in chemical structure can
`be quite small. Could a stereoisomer, left
`hand, right hand. Could be a methyl group. But
`a POSA would absolutely understand that any
`change in structure can impact pharmacokinetics
`and subsequently pharmacodynamics.
` Q. But a POSA can tell by simply looking
`at a structure which one is going to have a big
`impact in the change and which one won't?
` A. There obviously are classes of drugs
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`or classes of structures that where there's data
`and it's known what the liabilities could be,
`but you can never know without doing the
`experiment.
` Q. Okay. And when you say a POSA in
`this context, would you be necessarily be
`referring to an M.D. or someone else on the team
`that you referred to earlier?
` A. I am always, unless I specify
`otherwise, I'm referring to POSA as the team,
`and there are different expertise and different
`insights will come from different people within
`that team.
` Q. Okay. So specifically for this
`question, would you expect an M.D. to understand
`the difference?
` A. Yes, an M.D. would absolutely
`understand the significance of the change.
`There might be a chemist that would point it out
`or a pharmacologist. It could be anyone in the
`team.
` Q. But I'm asking, would the M.D. be
`able to point it out?
` A. Yes.
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` Q. Let's look at the next paragraph.
` A. Paragraph 78?
` Q. Yes.
` This paragraph concerns, can we call
`it the CURVES clinical trial?
` A. Yes.
` Q. The CURVES clinical trial is a study
`of statins; is that right?
` A. That's correct. It's comparing
`different statins and their efficacy.
` Q. And you identify a number of
`different -- the structure of a number of
`different statins in Figure 1 on page 29?
` A. Yes.
` Q. Are these the same structural class
`as lomitapide?
` A. No, they're not.
` Q. Are the statins in Figure 1 in the
`same therapeutic class as lomitapide?
` A. The statins identified are
`cholesterol-lowering drugs.
` Q. Do you have an understanding as to
`what therapeutic classes?
` A. I'm not sure I understand the
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`question.
` Q. I'm just trying to make sure we're
`talking about the same thing. I know you know
`what a therapeutic class is. I'm just asking
`you for what your definition is.
` A. It could be very broad. In the case
`that I just cited, cholesterol-lowering which
`many different mechanisms of action effect, but
`when you get to specific mechanisms of action,
`there are a lot of details and changes in the
`biological.
` So you may refer to statins as a
`class and MPT inhibitors as a class or you may
`refer to all of the cholesterol-lowering agents
`more generically.
` Q. Okay. So do the statins have the
`same mechanism of action for
`cholesterol-lowering as MTP inhibitors have?
` A. No, they do not.
` Q. What is the mechanism of action of
`statins?
` A. They inhibit an enzyme called HMG-CoA
`reductase.
` Q. And MTP inhibitors, what is the
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` S. David Kimball, Ph.D.
`mechanism of action there?
` A. They inhibit the packaging of lipids
`into lipoprotein packets, packages of lipo
`proteins.
` Q. And so from a treatment standpoint,
`you can consider them the same therapeutic class
`or not?
` A. They both lower cholesterol. They're
`both differently effective in treating lipid
`disorders. They're not the same.
` Q. But they do it in a different way?
` A. They do it in a different way and
`there are different details in terms of the
`impact on therapeutic efficacy.
` Q. What do you mean "there are different
`details in terms of the impact on therapeutic
`efficacy"?
` A. They don't have the same mechanism of
`action.
` Q. Okay. If we look at Figure 1, in
`your opinion, a POSA would be able to tell which
`structures have very different chemical
`structures and which ones don't?
` A. From Figure 1?
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` S. David Kimball, Ph.D.
` Q. Yes.
` A. Yes.
` Q. If you turn to paragraph 80, I think
`you identify which ones that you consider to be
`fairly similar structures; is that right?
` A. Yes. At a higher level, the top
`three are similar and the bottom two are
`similar.
` Q. And at the higher level, you consider
`simvastatin, lovastatin and pravastatin have
`fairly similar structures; is that correct?
` A. Yes.
` Q. And then atorvastatin and fluvastatin
`you consider to have fairly similar structures?
` A. To each other.
` Q. To each other.
` But you wouldn't consider the --
`strike that.
` Do the compounds on the top,
`simvastatin, lovastatin and pravastatin, have a
`fairly similar structure to the ones on the
`bottom?
` A. There are key structural components
`that drive their efficacy against this target,
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` S. David Kimball, Ph.D.
`against the HMG-CoA reductase.
` Q. I guess what I'm asking is -- all
`right. Let's look at paragraph 80.
` You say, "One of the more interesting
`results of this study is the significant
`differences in biological performance between
`drugs with fairly similar structures."
` And then example, fluvastatin versus
`atorvastatin and then simvastatin versus
`pravastatin versus lovastatin, right?
` A. Yes.
` Q. And so I guess I thought you're
`implying that fluvastatin and atorvastatin have
`not fairly similar structures with simvastatin,
`pravastatin and lovastatin.
` MR. JAMES: Objection to the form.
` Mischaracterizes the document.
` A. The three top ones are very closely
`related and differ by a very small amount.
` The two on the bottom are more
`similar to each other than to the three on the
`top.
` Q. Okay. So are the three on the top
`similar to the three on the bottom in terms of
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`structure?
` A. In terms of the critical structure,
`yes, there's a piece on all of them that gives
`them the ability to inhibit HMG-CoA reductase.
` Q. So how are you differentiating the
`three on the top from the two on the bottom, if
`at all?
` A. Well, as a chemist, as a medicinal
`chemist and as anyone who is in the drug
`development business would see, there are two
`rings, two six-membered rings on the top ones
`that are south, east and northwest, their
`orientation. Those rings are common to
`simvastatin, lovastatin, pravastatin. Those
`actually came from a fungal lead when the
`initial discovery of these class of compounds.
` Atorvastatin and fluvastatin have
`rings. There is a central ring which is about
`five members. It's a five-sided ring with a
`nitrogen in the middle. It's called a pyrrole
`and those are very similar. That's not
`something that came from a natural product.
` Q. And because of that, you would expect
`the three on the top and the two on the bottom
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`to have different biological performance?
` A. The point of the paragraph 80 is that
`even tiny differences, even between the three on
`the top or the two on the bottom, drive very
`different pharmacokinetics and pharmacodynamics
`in vivo as proven by the graph.
` Q. Is that what you mean when you say
`"biological performance"?
` A. Yes. Efficacy is what I meant by
`that, yes.
` Q. So they all -- but they all have the
`same mechanism of action, correct?
` A. That's correct. They all work
`through the same mechanism but have very
`different efficacy in vivo in humans.
` Q. So would a person of -- a POSA expect
`drugs with similar chemical structures to be
`able to be dosed effectively using the same
`regimen?
` A. No. A POSA would never make that
`assumption, cutting and pasting the drug
`protocol from one compound to another.
` Q. So if they can't rely on a structure
`to determine a dosing regimen, then how would a
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`POSA ever be able to find an effective dosing
`regimen?
` A. An effective dosing regimen is found
`empirically through animal studies and safety
`studies and then translated carefully into human
`trials.
` Q. So you can never look at another drug
`in a therapeutic class as a starting point for a
`dosing regimen?
` A. You cannot translate a human dosing
`regimen from one molecule to another, even if it
`differs only by one carbon atom.
` Q. You might have answered my question.
`I just want to make sure I'm understanding
`because I was asking you, could you look at a
`drug in a therapeutic class with the same
`mechanism of action as a starting point for
`developing a dosing regimen for another drug in
`that same therapeutic class with the same
`mechanism of action?
` A. Only in a preclinical setting would
`you do that. You can't dose humans without
`knowing that it's safe.
` Q. So in developing a dosing regimen,
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`you would look at the preclinical animal testing
`that took place?
` A. Absolutely. The FDA would require
`that you do that.
` Q. How is it that you would determine
`where to start in preclinical with a new drug?
` A. Without being too specific, because
`this is outside of my part of the POSA, my
`expertise, but you would look at the safety
`profile in vivo in animals and you would
`administer starting with a much lower dose in
`humans and slowly work your way up until you
`understood that you had a safe and effective
`window for dosing.
` Q. You said this is outside of your part
`of the POSA.
` What exactly is your part of POSA?
` A. In saying that, I'm referr
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