throbber
UNITED STATES DISTRICT COURT
`DISTRICT OF NEVADA
`BEFORE THE HONORABLE MIRANDA DU, DISTRICT JUDGE
`---o0o---
`
`No. 2:16-cv-02525-MMD-NJK
`January 14, 2020
`Reno, Nevada
`Volume 2
`
`::::::::::::
`
`:
`
`AMARIN PHARMA, INC., and
`AMARIN PHARMACEUTICALS
`IRELAND LIMITED,
`Plaintiffs,
`
`-vs-
`HIKMA PHARMACEUTICALS USA
`INC., et al.,
`Defendants.
`
`TRANSCRIPT OF BENCH TRIAL
`
`APPEARANCES:
`FOR THE PLAINTIFFS:
`
`FOR DEFENDANT HIKMA:
`
`Reported by:
`
`MEAGAN P. KEANE, CHRISTOPHER N.
`SIPES, MICHAEL KENNEDY, JEFFREY
`ELIKAN, JOSEPH KENNEDY, ELAINA M.
`WHITT, BARBARA KURYS, HAN PARK,
`DANIEL J. FARNOLY and ERIC R.
`SONNENSCHEIN
`Attorneys at Law,
`Washington, D.C.
`
`CHARLES B. KLEIN and
`CLAIRE A. FUNDAKOWSKI,
`Attorneys at Law
`Washington, D.C.
`
`Kathyrn M. French, CCR #392, RPR
`Official Reporter
`U.S. District Court
`Reno, Nevada
`
`(Appearances continue on next page.)
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`APPEARANCES CONTINUED:
`
`
`FOR DEFENDANT HIKMA:
`
`FOR DEFENDANT DR.
`REDDY'S LABORATORIES:
`
`
`
`ALISON M. HEYDORN
`Attorney at Law
`Chicago, Illinois
`EIMERIC REIG-PLESSIS
`Attorney at Law
`San Francisco, California
`
`W. WEST ALLEN
`Attorney at Law
`Las Vegas, Nevada
`
`CONSTANCE S. HUTTNER and
`JAMES BARABAS
`Attorneys at Law
`Madison, New Jersey
`MICHAEL D. ROUNDS
`Attorney at Law
`Reno, Nevada
`
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`RENO, NEVADA, TUESDAY, JANUARY 14, 2020, 8:30 A.M.
`---o0o---
`
`THE COURT: Good morning. Please be seated.
`All right. Counsel, did you resolve the issue
`with respect to Mr. Klein's demonstrative exhibits yesterday?
`Is there any objection to the Court attaching them as minutes
`to yesterday's hearing -- yesterday's trial, I mean?
`MS. KEANE: Good morning, Your Honor. Meagan
`
`Keane.
`
`Your Honor, we did have a chance to review the
`demonstrative. In our view, there is an error that's in the
`demonstrative with respect to a couple of patents that are
`actually listed both for the REDUCE-IT indication as well as
`for MARINE. So we don't think the slide is accurate as it's
`depicted.
`
`What we would propose is that we are willing to
`work with defendants' counsel to come up with a compromise
`version that we can agree on and attach that as a
`demonstrative.
`THE COURT: You're referring to DX 2699.
`MS. KEANE: To the summary slide with respect to
`the list of patents, yes, Your Honor.
`THE COURT: And that approach sounds agreeable
`to me. What I was asking, though, is that with the entire set
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`306
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`of exhibits that I admitted into evidence but that Mr. Klein
`had referenced during his cross-examination where he would
`show the exhibit and then highlight certain portions of the
`actual exhibit and reference DDX and then the number. That's
`what I was concerned about.
`MR. SIPES: We apologize, Your Honor. This is
`Christopher Sipes.
`What we thought might make sense, since
`demonstratives usually wouldn't be attached, would be for
`defendants to prepare just a chart that correlates the DDX
`number to the DX number and page. So it would be a simple
`chart, and that would make the record clear without having the
`argumentative parts of the demonstrative in, and we could just
`review that to make sure that it was accurate.
`THE COURT: I think that would address my
`concern. All I want is to make sure that there's notation in
`the record as to whatever the reference is to DDX and then the
`specific slide number.
`MR. SIPES: And the advantage of that, that
`would be a short compact thing that we just would provide the
`reference, Your Honor.
`THE COURT: Mr. Klein?
`MR KLEIN: Your Honor, we can put together that
`chart if you would like, but there was no argument in any of
`the demonstratives. You might be thinking of the opening
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`statement. But it was just call-outs.
`THE COURT: I think the chart serves my purpose.
`All I want is to make sure that -- there were times when I
`thought that you didn't note the actual page of the exhibit
`but you noted the DDX number for certain exhibits that you
`were showing, that it's clear for the record which page of the
`actual exhibit you were referring to.
`So the chart will suffice, and the chart will
`then be attached to yesterday's trial minutes.
`MR KLEIN: Okay. Thank you.
`THE COURT: All right.
`And then on Exhibit 2299, I'm pretty sure that's
`the one that's left that I need to resolve; is that right?
`THE CLERK: Yes.
`THE COURT: That the parties will confer and let
`me know if you are able to reach a resolution.
`MS. KEANE: Okay. Thank you, Your Honor.
`THE COURT: All right. Let's proceed with
`Amarin's next witness.
`MR. M. KENNEDY: Your Honor, this is Michael
`Kennedy for Amarin. Amarin calls Dr. Matthew Budoff.
`THE COURT: Thank you.
`MR. M. KENNEDY: Your Honor, we have some
`demonstratives with this witness as well as a witness binder.
`Permission to approach to distribute the binder, and if Your
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`Honor would like a copy of the slides as well.
`THE COURT: I do not, but I don't want to have
`the same problem with reference to the page number of the
`slides. So if the slide is referenced as an exhibit, then you
`need to reference the actual page number of that exhibit.
`MR. M. KENNEDY: Understood, Your Honor.
`THE COURT: Thank you.
`MATTHEW BUDOFF, M.D.,
`called as a witness on behalf of the Government,
`was sworn and testified as follows:
`THE CLERK: Please be seated.
`State for the record your full name and spell
`both your first name and your last name.
`THE WITNESS: Matthew Budoff; M-a-t-t-h-e-w,
`
`B-u-d-o-f-f.
`
`MR. M. KENNEDY: Good morning, Dr. Budoff.
`THE WITNESS: Good morning.
`DIRECT EXAMINATION
`
`BY MR. M. KENNEDY:
`Are you currently employed?
`Q
`Yes.
`A
`Where are you employed?
`Q
`(Discussion held off the record.)
`
`BY MR. M. KENNEDY:
`Dr. Budoff, where are you employed?
`Q
`I'm employed at the David Geffen School of Medicine at
`A
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`UCLA, formerly known as the UCLA School of Medicine, as well
`as the Lundquist Institute which is a research institute at my
`home institution.
`At a very high level, please describe your job
`Q
`responsibilities in those roles.
`Yes. So my primary responsibility is teaching. I am the
`A
`program director for the Division of Cardiology, which means I
`teach all of the cardiology fellows, those people who are
`doing three years of advanced training in cardiology, on how
`to practice cardiology.
`I also have the opportunity to teach residents,
`medical students, and other clinicians.
`And then, when I'm not teaching, I'm either doing
`clinical work, seeing patients directly, or doing clinical
`research.
`Were you retained as an expert by a party in this case?
`Q
`Yes.
`A
`Which party?
`Q
`Amarin.
`A
`So at a very high level what were you asked to do in this
`Q
`case as an expert?
`Yes, I was asked to opine on the patents and understand
`A
`if there would be infringement in this case if a generic
`version of a product was brought to market.
`Do you specialize in a particular area of medicine?
`Q
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`Yes.
`A
`What area?
`Q
`It's called cardiovascular medicine or commonly known as
`A
`cardiology.
`What is cardiology?
`Q
`Cardiology is the practice of evaluating the heart.
`A
`Do you have a subspecialty within cardiology?
`Q
`Yes, I'm a preventive cardiologist.
`A
`What is a preventive cardiologist?
`Q
`So a preventive cardiologist works to try to prevent
`A
`either the first heart attack in those patients at high risk
`of heart disease, or the second heart attack, what we call
`secondary prevention, in those patients who have already
`suffered a cardiovascular event.
`Are there other subspecialties within cardiology that
`Q
`you're familiar with?
`Yes.
`A
`Such as?
`Q
`There's imaging, there's invasive cardiology, those
`A
`people who spend most of their time putting in stints and
`bypass and other devices, and then there's general cardiology
`as well.
`How long have you characterized yourself as specialist in
`Q
`preventive cardiology?
`About 20 years.
`A
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`How long has the field of cardiology recognized
`Q
`preventive cardiology as a subspecialty?
`It's been about ten years since it was formalized as a
`A
`subspecialty.
`So what did you call yourself before preventive
`Q
`cardiology was formalized as a subspecialty?
`So if there was no check box that said preventive
`A
`cardiologist, then I generally -- I would have to refer to
`myself as a general cardiologist.
`MR. M. KENNEDY: Mr. Brooks, can we have
`Plaintiffs' Exhibit 1161, please.
`BY MR. M. KENNEDY:
`And, Dr. Budoff, you should have this document on your
`Q
`screen as well.
`Yes.
`A
`Do you recognize this document?
`Q
`Yes.
`A
`What is it?
`Q
`It's my curriculum vitae or CV.
`A
`What does your curriculum vitae contain in general?
`Q
`It goes through my education, training, my current work
`A
`and prior work opportunities, and then it lists all of my
`manuscripts and abstracts.
`Does Plaintiffs' Exhibit 1161 accurately summarize your
`Q
`professional and educational background?
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`A
`
`Yes.
`
`MR. M. KENNEDY: Your Honor, we would like to
`admit Plaintiffs' Exhibit 1161 into evidence.
`MR KLEIN: No objection.
`THE COURT: 1161 is admitted.
`(Plaintiffs' Exhibit 1161 received in
`evidence.)
`
`BY MR. M. KENNEDY
`Dr. Budoff, have you worked with us to prepare slides to
`Q
`aid your testimony today?
`Yes.
`A
`Or I should say to illustrate your testimony today?
`Q
`Have you prepared one such slide that summarizes
`your educational qualifications?
`Yes.
`A
`
`MR. M. KENNEDY: Mr. Brooks, if we could have
`
`PDX 2-2.
`BY MR. M. KENNEDY:
`And, Dr. Budoff, is this that slide?
`Q
`Yes.
`A
`Could we focus on the last two items on this slide
`Q
`starting with the internship and residency in internal
`medicine. Could you describe what that involved.
`Yes. So, my internship and residency is three years of
`A
`training to become an internist or a primary care physician.
`So I spent three years at Harbor UCLA Medical Center
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`affiliated with UCLA School of Medicine under that training.
`What does it mean -- what does doing an internship in
`Q
`this context involve?
`So it's basically on-call every third or fourth night,
`A
`taking care of patients in the hospital, seeing patients in
`clinic, just basically learning how to practice general
`medicine.
`I would like to move to the cardiology fellowship at
`Q
`Harbor UCLA Medical Center. What it did that involve?
`So that's another three years of commitment. This is
`A
`just focused on learning how to be a cardiologist, so I'm
`specializing in cardiovascular medicine and learning all of
`the aspects, including imaging and how to treat patients and
`how to do the invasive procedures.
`And so am I correct that starting in 1997 or so you were
`Q
`a full-fledged cardiologist?
`Yes.
`A
`So you testified that you're a professor of medicine.
`Q
`What are your responsibilities in that role?
`So my primary responsibilities as a professor of medicine
`A
`is to teach and do research. There's still an adage of
`publish or perish, so I still publish quite a bit as far as my
`academic career.
`But I spend most of my time teaching, and I'll teach
`everybody from the primary care specialists, family medicine
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`doctors, and internal medicine doctors, the cardiology
`fellows, the interns and residents, and then the medical
`students who are also rotating through different rotations
`with me.
`How long have you been teaching?
`Q
`Oh, I became a -- I started my professorship series in
`A
`1997 so I've been teaching full time since July 1997.
`And am I correct that you teach practicing physicians?
`Q
`Yes.
`A
`Could you go into a little more detail about what you
`Q
`teach them.
`Yeah. So I spend a lot of time -- I get invited to a lot
`A
`of different academic meetings, so I'll present at large scale
`meetings where there will be anywhere from dozens to hundreds
`of practicing physicians, and I will give lectures on --
`usually on things related to lipids or things related to
`cardiovascular imaging to these different groups.
`Do you have an understanding of why people ask you to do
`Q
`these lectures?
`Well, I've been told that I'm fairly clear when I
`A
`lecture, and they find it educational so they invite me back.
`So I usually end up doing these on a regular basis.
`Are you involved in any other physician education
`Q
`activities we haven't already covered?
`Well, I do a lot of publishing, and some of that is in
`A
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`the form of guidelines. So I'll publish medical guidelines
`I'll write on behalf of different societies, different
`guidelines to help educate physicians in the field on how to
`practice cardiology or how to use certain tools in their
`practice.
`What drew you to preventive cardiology?
`Q
`Yeah, so, I mean, the long-standing relationships with
`A
`the patient, the ability to try to help them, enable them to
`prevent a catastrophic event was very rewarding for me, and
`I've enjoyed it in my clinical practice, so I've stayed with
`it over the many years since I started.
`You mentioned you conduct research. What kind of
`Q
`research do you conduct?
`Yeah, so most of my research revolves around looking at
`A
`the effect of different therapies on atherosclerosis, plaque
`build-up in the arteries, to see if drug X improves the
`arteries or if drug Y causes more problems in the arteries.
`I also do a lot of research on clinical trials so
`I'll work with other investigators to perform clinical studies
`to see if a drug has its desired affect, be it anything from
`lowering the blood pressure to improving the cholesterol
`panel, to improving the triglycerides.
`What is an investigator in the context of clinical
`Q
`trials?
`Yeah, so an investigator is the person who is principally
`A
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`responsible for the local site, and the primary investigator
`or the principal investigator is responsible for the overall
`performance of the trial, everything from making sure the
`patients stay in the study and are appropriately treated, to
`ensuring their safety, and then to make sure that we capture
`all of the desired endpoints so that the trial can be
`published and hopefully advance science.
`How long have you -- or how many times have you been a
`Q
`principal investigator at the national level?
`Probably around a dozen or so.
`A
`How many times have you been the principal investigator
`Q
`on a clinical trial at a local site?
`Oh, probably about a hundred times.
`A
`Can you give a few examples of clinical studies you've
`Q
`been involved in recently?
`Yes, I'm currently performing a multicenter trial that
`A
`I'm the overall principal investigator on called EVAPORATE.
`That's actually using the product in question here, Vascepa,
`to look at plaque over time.
`So I'm in charge of all of the sites in the trial
`and the overall performance of the trial, and I recently
`presented some of the interim data at the largest meeting of
`cardiology in the United States called the American Heart
`Association Meeting on a very large scale.
`What do you hope to show in the EVAPORATE trial?
`Q
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`So EVAPORATE is -- the target of EVAPORATE is to
`A
`demonstrate whether Vascepa reduces plaque in the coronary
`arteries as compared to placebo, so to see if some of its
`cardiovascular benefits that we've seen in the REDUCE-IT trial
`actually translate into plaque reduction at the coronary
`level.
`Can you tell us how EVAPORATE is going so far?
`Q
`Yeah. It concludes in February. Hopefully by the end of
`A
`the February we'll have our last patient, last visit.
`So hopefully we'll be -- we plan on presenting this
`at the European Society of Cardiology Meeting in July or
`August which is the largest meeting in the world of
`cardiologists.
`Why do you do so many clinical trials?
`Q
`Well, clinical trials have, I feel, a great purpose. We
`A
`have to remember that about half of what we discover in -- at
`least in fields like cardiology, are based on these clinical
`trials.
`
`These clinical trials show us whether a drug works
`and in whom they work. So, for example, if we just go back to
`the REDUCE-IT trial, it affords us a great opportunity to
`understand that we can reduce cardiovascular events in
`patients who have certain clinical criteria. So participating
`in those studies help us treat patients better.
`You mentioned REDUCE-IT. Did you have a role in the
`Q
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`REDUCE-IT clinical trials?
`Yeah, I was local principal investigator so I was
`A
`responsible for my local site, and then I was a co-author on
`one of the recent papers describing the results in the United
`States population of REDUCE-IT.
`So I think you mentioned earlier that you publish so that
`Q
`you don't perish. Have you prepared a slide that lists some
`of your publications?
`Yes.
`A
`
`MR. M. KENNEDY: Mr. Brooks, can we please have
`
`PDX 2-3.
`BY MR. M. KENNEDY:
`And are these some selected publications from your
`Q
`curriculum vitae, PX 11671?
`Yes.
`A
`Could you tell us a little bit more about number 1103.
`Q
`Is that the paper about REDUCE-IT that you just mentioned?
`Yes. So it's very important to understand how the U.S.
`A
`population behaves in a clinical trial. Sometimes it's a
`little bit different than the overall clinical trials that are
`done with a worldwide influence.
`So Dr. Bhatt and I put together this paper to look
`at the results of the -- of the 3,000 plus patients who were
`United States participants in the trial to see how they
`performed.
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`And if you could tell us a little bit more about 783. Is
`Q
`that also related to EPA?
`Yes. This was a review article. As I was preparing my
`A
`research and preparing for the EVAPORATE trial to see how we
`wanted to perform that study and writing it up, we came across
`a lot of information related to the effects of both EPA and
`DHA on lipoproteins on lipids. So we wrote a little review
`article to help clarify that part of the science.
`Who is the intended audience for these publications that
`Q
`you author?
`Yeah, so, generally, it depends on where we publish it.
`A
`For example, the first publication that we discussed was
`published in Circulation. That's the Journal of the American
`Heart Association, so it generally goes out to all
`cardiologists in the United States and obviously has a bigger
`circulation than just the U.S. It goes around to
`cardiologists in the world. So that paper was more focused on
`getting the word out to cardiology.
`So I would like to ask you a few more questions about
`Q
`your clinical practice. How long have you been seeing
`patients?
`I've been seeing patients since 1990 when I started my
`A
`internship. We had what's called a continuity clinic, and I
`would see patients in my clinic starting in 1990, and I've
`continued since then.
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`How many patients do you see in a typical month?
`Q
`So I see approximately 200 patients in different venues.
`A
`Are there -- do you have different -- do you have
`Q
`different places where you practice?
`Yes, and it depends on my rotations at the time. For
`A
`example, right now I'm supposed to be in the intensive care
`unit, in the cardiac care unit. So tomorrow morning I will be
`rounding in the CCU and taking care of more acute patients.
`I also have a private clinic where I see my own
`patients. And I supervise fellows as well in the cardiology
`clinic where they will see a patient, and then I will go
`discuss the patient with them, go in and discuss the case with
`the patient, and see the patient as -- in a more supervisory
`role.
`Now, in your own practice how do those patients find you?
`Q
`Yeah, I have a pretty typical preventive cardiology
`A
`practice. My practice entails getting referrals from primary
`care physicians.
`So a doctor may see somebody with high
`triglycerides, or may see somebody with very high LDL
`cholesterol, or a bad family history of heart disease and
`refer them directly to me, or I get patients directly from
`word of mouth. Some patients, some of my patients refer me,
`and their colleagues or friends or family members will come to
`see me as well.
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`What are the common medical problems that patients face
`Q
`in your practice?
`Yeah. So my private practice, it's fairly focused on
`A
`preventive cardiology. So, in other words, I try to take
`patients who are high risk and try to work with them on risk
`reduction. So that could be anything from diet and exercise
`to drug therapy, to other types of interventions to help
`prevent them from ever suffering a cardiovascular event.
`Do you see patients with elevated triglyceride levels?
`Q
`Yes.
`A
`How often?
`Q
`Very frequently. Elevated triglyceride levels are part
`A
`of a mixed dyslipidemia, so they're part of -- people come in
`with high cholesterol and high triglycerides, and then I also
`see patients with isolated high triglycerides.
`Do you see patients with severe hypertriglyceridemia?
`Q
`Yes.
`A
`How often?
`Q
`So it's a less common disease. I don't have a lipid
`A
`clinic, I have a general preventive cardiology clinic, but I
`do see patients regularly with severe hypertriglyceridemia.
`Do you see patients with elevated LDL-C levels?
`Q
`Yes.
`A
`How often?
`Q
`So that's most the common disorder that I see and the
`A
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`most common disorder that I treat.
`And, again, those patients with elevated LDL, or bad
`cholesterol, oftentimes have abnormal triglycerides as well.
`So we call that a mixed dyslipidemia.
`Beyond your teaching, research, and clinical obligations,
`Q
`do you engage in other professional activities?
`Yes.
`A
`
`MR. M. KENNEDY: Mr. Brooks, could we please
`have slide PDX 2-4.
`BY MR. M. KENNEDY:
`And can you just briefly explain what you've depicted on
`Q
`this slide.
`Yeah, so these is just some of my recent memberships or,
`A
`rather, affiliations with large organizations, national or
`international organizations, where my expertise was -- I was
`asked to be on the executive committee or be the chair of the
`steering committee for different groups.
`Have you ever received any awards from your peers?
`Q
`Yes.
`A
`
`MR. M. KENNEDY: Mr. Brooks, can we please have
`
`PDX 2-5.
`BY MR. M. KENNEDY:
`Are these some of the awards that you've received that
`Q
`are reflected in your curriculum vitae?
`Yes.
`A
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`323
`
`Could you tell us about one of these awards that may be
`Q
`particularly meaningful to you.
`Yeah, the one that's bolded is, I think, the most
`A
`prestigious is to be named an Endowed Chair.
`That comes with some financial support because
`there's an endowment that supports your position, but, also,
`more importantly, you're recognized among your peers as being
`at the highest level of that field.
`So this is the Endowed Chair of Preventive
`Cardiology that I was awarded in 2015.
`MR. M. KENNEDY: Your Honor, at this time Amarin
`offers Dr. Budoff as an expert in the clinical treatment of
`patients with lipid disorders, including severe
`hypertriglyceridemia, and as an expert in cardiology.
`MR KLEIN: No objection.
`THE COURT: The request to certify Dr. Budoff in
`the clinical treatment of lipid disorders, including severe
`TG, and just preventive cardiology?
`MR. M. KENNEDY: Cardiology in general.
`THE COURT: Cardiology in general. That request
`
`is granted.
`
`MR. M. KENNEDY: Thank you, Your Honor.
`BY MR. M. KENNEDY:
`So, Dr. Budoff, just to orient ourselves, I would like to
`Q
`go over a little bit of scientific background. I know some of
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`this was covered yesterday.
`MR. M. KENNEDY: Mr. Brooks, if we could pull up
`
`slide PDX 2-6.
`BY MR. M. KENNEDY:
`So, Dr. Budoff, what have you shown on this slide?
`Q
`Yeah, so this is a lipoprotein. A lipoprotein -- I know
`A
`Dr. Ketchum touched on this yesterday, but a lipoprotein is a
`kind of a way that we transport both cholesterol and
`triglycerides around the body.
`If they are heavily containing both cholesterol
`and/or triglycerides, the bad lipoproteins, they're designated
`as apolipoprotein B, so you can see that in purple. And you
`can see within the content of that lipoprotein, that bad
`lipoprotein, that has both cholesterol in yellow and
`triglycerides depicted in red.
`What are triglycerides?
`Q
`So triglycerides are basically how we store energy and
`A
`how we then given energy to different organs when needed.
`Are more triglycerides better?
`Q
`Well, up to a point. We need triglycerides, they are an
`A
`energy source, but most commonly, especially in the United
`States, we have excess. We -- we have too many -- we eat too
`many calories, we store that as triglycerides, and
`triglycerides then build-up in the bloodstream which can cause
`plaque build-up, blockages in the arteries that then
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`325
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`subsequently cause heart attacks and death.
`What purpose does cholesterol serve?
`Q
`Cholesterol is very important. It's a precursor for
`A
`vitamins as well as for hormones, so it's a very important
`precursor.
`But, again, in the United States we tend to run an
`excess of cholesterol, and that can, again, start to block up
`the arteries, gets converted into malignant cells that can
`then cause plaque buildup and heart attacks and strokes.
`And what purpose does apolipoprotein B serve?
`Q
`So the apolipoproteins are divided into the good, those
`A
`apo A, and bad lipoproteins, the ones that contain lot of
`cholesterol and triglyceride, are designated apo B.
`So apo B -- I think of B as bad, so apo B is the bad
`lipoprotein that, when in excess, carries around too many
`triglycerides and cholesterol and can cause excess heart
`attacks, strokes, and death.
`MR. M. KENNEDY: Mr. Brooks, can we have
`
`PDX 2-7.
`BY MR. M. KENNEDY:
`Dr. Budoff, what have you shown on this slide?
`Q
`Yeah, so this is just showing the natural -- the natural
`A
`progression of what happens to the lipoproteins in our body.
`When the liver first processes the food and creates
`these very low-density lipoproteins, they are very rich in
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`326
`
`triglycerides. Then, via lipoprotein lipase and other
`enzymes, we deliver some of the triglycerides to organs.
`And the lipoprotein gets smaller and denser, so it
`goes from very low-density to intermediate density. It's now
`a smaller lipoprotein, has less triglycerides and relatively
`more cholesterol, because the cholesterol is still there, and
`then further delivered to LDL cholesterol.
`LDL cholesterol is what we commonly call bad
`cholesterol. This is a cholesterol-rich particle that is most
`associated with heart attacks and strokes and of great concern
`when we think about a patient's cardiovascular risk if they
`have too much LDL cholesterol.
`Again, something we covered a little bit yesterday, but
`Q
`what is hypertriglyceridemia?
`So hypertriglyceridemia is simply hyper, too much,
`A
`triglycerides, and then emia is in the blood. So too many
`triglycerides in the blood, and, again, that's what we call
`atherogenic. It causes atherosclerosis, and it causes
`cardiovascular events.
`And what is severe hypertriglyceridemia, which I may also
`Q
`refert to STG?
`So severe hypertriglyceridemia is a less common disorder.
`A
`It's an extreme state of hypertriglyceridemia mostly caused by
`genetics, so we know it as a chronic condition that is
`lifelong.
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`And when the triglycerides are very high, there are
`different risks as compared to when the triglycerides are only
`moderately elevated.
`Is severe hypertriglyceridemia a condition recognized in
`Q
`medical literature?
`Yes.
`A
`Could you give me example of the type of medical
`Q
`literature in which it's recognized?
`Yes, so it's been discussed in the cholesterol
`A
`guidelines, guidelines that talk about lipids and how to treat
`lipids, for decades.
`Now, you've mentioned guidelines a couple times. What
`Q
`are guidelines in this context?
`So guidelines are very simply the -- to establish the
`A
`medical standard of care. So they instruct clinicians who are
`practicing in the field on the best practices and what they
`should do when encompassing a certain condition.
`Do you use medical guidelines in your own practice?
`Q
`Yes, every day.
`A
`Do you have experience writing guidelines?
`Q
`Yes. I've been involved in probably around 13 or 14
`A
`guidelines, sometimes as the first author, sometimes as a
`member of the writing group.
`MR. M. KENNEDY: Mr. Brooks, could we have
`Plaintiffs' Exhibit 989.
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`And, Your Honor, I believe this is one the
`exhibits that has already been preadmitted in this case.
`BY MR. M. KENNEDY:
`Dr. Budoff, do you recognize this document?
`Q
`Yes.
`A
`What is it?
`Q
`So this is a cholesterol guideline. We commonly refer to
`A
`it as the Adult Treatment Panel III or ATP III report.
`What role does the American Heart Association have in
`Q
`these guidelines? I see that this document has its logo on
`it.
`Yes, so this is -- this is a primary -- they are one the
`A
`primary writers of the guidelines and sponsors of the
`guidelines. They are signed off by many organizations, but
`they are co-led by the American Heart Association and often
`the American College of Cardiology.
`What role does the ATP III guideline play in medical
`Q
`practice?
`Yeah, so this was a very widely used and established
`A
`guideline in the field. It really helped us -- directed
`physicians to be very aggressive with LDL or bad cholesterol
`control, and it also helped define some of the treatments and
`definitions of hypertriglyceridemia.
`MR. M. KENNEDY: Mr. Brooks, could we go to
`page 190 of this exhibit, PX 989. Also t

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