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UNITED STATES DISTRICT COURT

FOR THE DISTRICT OF NEW JERSEY

__________________________________

HELSINN HEALTHCARE, S.A. and

ROCHE PALO ALTO, LLC,

Plaintiffs,

-vsDR. REDDY'S LABORATORIES, LTD.,

DR. REDDY'S LABORATORIES, INC.,

TEVA PHARMACEUTICALS USA, INC.,

and TEVA PHARMACEUTICAL

INDUSTRIES, LTD.

Defendants.

CIVIL ACTION NUMBER:

11-3962

TRIAL

__________________________________

Clarkson S. Fisher United States Courthouse

402 East State Street

Trenton, New Jersey 08608

June 4, 2015

B E F O R E: THE HONORABLE MARY L. COOPER

UNITED STATES DISTRICT JUDGE

Certified as True and Correct as required by Title 28, U.S.C.,

Section 753

/S/ Regina A. Berenato-Tell, CCR, CRR, RMR, RPR

/S/ Carol Farrell, CCR, CRR, RMR, CCP, RPR, RSA

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A P P E A R A N C E S:

PAUL HASTINGS

BY: JOSEPH O'MALLEY, ESQUIRE

ISAAC S. ASHKENAZI, ESQUIRE

ANGELA NI, ESQUIRE

SAUL EWING

BY: CHARLES M. LIZZA, ESQUIRE

Attorneys for the Plaintiffs

BUDD LARNER

BY: STUART D. SENDER, ESQUIRE

ANDREW ALLEN, ESQUIRE

Attorneys for the Defendant, Dr. Reddy's Laboratories

WINSTON & STRAWN

BY: JOVIAL WONG, ESQUIRE

GEORGE LOMBARDI, ESQUIRE

JULIA MANO JOHNSON, ESQUIRE

BRENDAN F. BARKER, ESQUIRE

LITE DePALMA, GREENBERG, LLC

BY: MAYRA V. TARANTINO, ESQUIRE

Attorneys for the Defendant, Teva

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I N D E X

WITNESS VOIR DIRECT CROSS REDIRECT RECROSS

DIRE

JOHN P. FRUEHAUF

By Mr. Wong 4 14 183

By Mr. O'Malley 107 204

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(In open court. June 4, 2015, 9:30 a.m.)

THE COURT: Good morning, everyone. Okay. Are we

ready to go to work today? Would you like to call your next

witness?

MR. WONG: Yes. Good morning, Your Honor. My name

is Jovial Wong. I represent the Teva defendants. Good to see

you again.

As our first witness defendants call Dr. John Freuhauf.

He will be discussing more about the efficacy of palonosetron.

(Whereupon, JOHN FRUEHAUF, witness for the

defendants, sworn.)

THE DEPUTY CLERK: Please state and spell your full

name for the record.

THE WITNESS: John P. Fruehauf, F-R-U-E-H-A-U-F.

VOIR DIRE EXAMINATION BY MR. WONG:

Q. Good morning, Dr. Fruehauf.

A. Good morning.

Q. Dr. Fruehauf, have you been asked to provide expert

opinions in this case?

A. Yes, I have.

Q. And, in general, what do your opinions relate to?

A. They relate to the clinical development of palonosetron.

Q. Okay. Let's do a little background first, Dr. Fruehauf.

Where are you currently employed?

A. University of California Irvine.

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Q. And what is your current position at the University of

California Irvine?

A. I'm a professor of clinical medicine and the director of

clinical pharmacology and developmental therapeutics.

Q. And is there a particular cancer center that you work at

at UC, Irvine?

A. I work at the Chao Family Comprehensive Cancer Center.

Q. And what is a comprehensive cancer center?

A. It is a cancer center -- there are 43 comprehensive

cancer centers in the United States, and this is one of those.

They're designated by the National Cancer Institute, and they

have to have the complete array of services from basic

research to clinical trials development to qualify.

Q. How long have you been at UC, Irvine?

A. Since 1993.

Q. Can you briefly describe your educational history?

A. I went to college at UC Santa Barbara where I got a

bachelor's degree in psychology and a bachelor's degree in

cellular and organismal biology. And then I proceeded to

medical school and did an M.D./Ph.D. program at Rush

University in Chicago, and my Ph.D. was in pharmacology.

Q. What is pharmacology?

A. Pharmacology is the study of how drugs work.

Q. Okay. After you got your medical degree in 1985 what did

you do?

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THE COURT: Just a second. The Ph.D. was in what?

THE WITNESS: Pharmacology.

THE COURT: Okay. And the M.D. was an M.D.?

THE WITNESS: Yes, ma'am.

THE COURT: Then you went on to specialize in your

medical training?

THE WITNESS: Yes. Then I did my residency at UC,

Irvine, and then I went to do my fellowship. After two years

of residency I was in the scientists' training track, so I did

four years of medical oncology at the National Cancer

Institute in Bethesda and then one more year in biotechnology

there.

BY MR. WONG:

Q. Okay. While at the National Cancer Institute, did you

participate in clinical trials?

A. Yes, I did. In fact, every patient who we saw at the

cancer center had to be on a clinical trial.

Q. After your time at the National Cancer Institute what did

you do?

A. Then I went to OncoTech, a biotechnology company.

Q. What was the focus of your work at OncoTech?

A. OncoTech was a company that -- the tumor from the patient

would be sent to the laboratory, and we would study the

effects of different chemotherapy agents that might be

selected for that patient's tumor type. And we looked at the

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impact of the drugs on the tumors growing in a test tube, so

to speak, and then based on the results we could advise the

clinician about, you know, which drug would be less likely or

more likely to be effective for that patient.

Q. Okay. Did your work at OncoTech include drug product

development?

A. Yes, it did. So, if there were residual tumor cells

after performing the primary testing, then we worked with

pharmaceutical companies to study their developmental

compounds in a preclinical setting against the human tumors,

which we felt was more representative than the typical cell

lines that most companies would utilize.

Q. Okay. How long were you at OncoTech?

A. Until 2006.

Q. And where did you go after OncoTech?

A. I was working at both UC, Irvine -- as a medical

oncologist -- and OncoTech, but I was part-time at the

university until 2006, and then I went full-time at that year.

Q. Okay. Now, while at UC, Irvine, what has been the focus

of your research?

A. Basically clinical trials, you know, to translate ideas

from the laboratory into the clinic, writing clinical trials,

carrying them out.

Q. Okay. What does the term or principle "bench-to-bedside"

mean?

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A. So, bench-to-bedside is really how we were trained at the

NCI.

So you would go into the laboratory, do experiments

with cell lines and drugs and then come up with maybe a new

combination of treatments that you could then go and write a

clinical trial and give it to the patients to see if it works

better than what was there before.

Q. Okay. And what types of clinical trials do you carry out

now?

A. I carry out various clinical trials in different

diseases: Melanoma, urological oncology, kidney cancer,

bladder cancer.

Q. Do you have experience carrying out all phases of

clinical trials?

A. Yes. As director of developmental therapeutics, I'm

involved in Phase I, Phase II, and Phase III trials.

THE COURT: What is Phase I, Doctor?

THE WITNESS: Phase I?

THE COURT: To you. You know, I hear what it is from

lawyers and that kind of thing, but what does Phase I consist

of in your experience?

THE WITNESS: Well, in my experience it is the first

time you -- usually there's the first-in-man Phase I.

First-in-man. So, the first time you actually take a drug and

give it to a human being before it has been given to animals

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and put on cells, and this is the first time you're giving it

to a person, so it is a safety question.

THE COURT: So, this is healthy volunteers?

THE WITNESS: In the perspective of the situation at

hand that would be healthy volunteers.

THE COURT: Okay. Fine. Thank you.

BY MR. WONG:

Q. How many clinical trials are you currently involved with?

A. Seven or eight trials right now.

Q. And does your work at UC, Irvine also include preclinical

trial work?

A. Yes. So, I mean, we -- you know, based on my prior

laboratory experience at OncoTech I have continued to do the

work of sort of correlating what happens in the test tube with

what happens in people and trying to figure out are there

markers we can study on the patient's tumor, like is there a

mutation that would predict the drug will or won't work for

that patient.

THE COURT: Do you have test tube laboratories in

your --

THE WITNESS: Yes. I train Ph.D. students, so I have

a regular, you know, bench laboratory where we grow the cells

and tissue culture, and we add the drugs, and flow cytometry

and HPLC and stuff like that.

BY MR. WONG:

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Q. Getting back to your clinical practice in humans, how

busy is your clinical practice?

A. I have three days a week that I see patients, and then

there's a month every year that I'm in the inpatient service

taking care of all the cancer patients in the hospital.

THE COURT: How do you do both, this kind of heavy

research that you're doing, clinical trials and preclinical

lab work, and also follow patient charts?

THE WITNESS: So, it is all about protected time.

You know, you have to have some protected time to be able to

go to the lab and talk to your post doc or graduate students

about their experiments and review their data. You go to the

clinic and, so, I have a really good nurse, and I have a good

post doc, and those people help me tremendously in managing

things on a daily level. So I become more of a supervisor.

But the patient care takes the most time.

BY MR. WONG:

Q. Over in your entire career, about how many cancer

patients do you think you have treated?

A. Oh, you know, more than 1,000.

Q. Now, as part of your clinical oncology practice do you

have experience with supportive care of your patients?

A. Yes. At the time I trained at the National Cancer

Institute there wasn't really a palliative care specialty yet,

which does do supportive care today, and, so, we were trained

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to support the patient with pain medications, antinausea

medications, antidiarrheal medications just to really support

the whole patient.

So, I grew up out of that experience, and, so, to this

day I'm trying to manage the quality of life for the patient

concomitantly with the intervention for their -- to treat

their cancer.

Q. Okay. Can you explain your experience with antiemetics?

A. Unfortunately today we still use chemotherapy for the

vast majority of cancer patients. And, so, as a result we

need to be giving medications that will suppress nausea and

vomiting.

And as research into the mechanisms of what causes this

process in people, drugs have been developed that attack the

different sort of pathways that stimulate nausea and vomiting.

So, today we sort of use an amalgam of agents that will

attack different pathways so you're simultaneously suppressing

the impulse to throw up and to feel sick.

So, there would be Marinol, for instance, for

cannabinoid receptors; NK-1 -- Emend is an NK-1 receptor

inhibitor; the 5-HT receptor inhibitors, such as palonosetron

and Compazine. I give Compazine frequently, which is a

dopamine receptor suppressor.

So, it is really combining drugs that work on different

pieces of the process of nausea.

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Q. Okay.

THE COURT: And these receptors are not just in the

brain, right?

THE WITNESS: No. There's the gut process, which is

where serotonin signaling starts in the body. It is all built

on the concept of an evolution you don't want to eat poison.

So when your gut senses a poison, your body wants to extrude

it, so it sends a signal to the brain stem to throw up,

basically.

BY MR. WONG:

Q. And in addition to your research at UC, Irvine do you

also teach?

A. Yes. I teach an undergraduate class every fall, so it is

coming up, and it is about 250 undergraduate students that are

upper division. And I'm teaching --

THE COURT: These are not medical students?

THE WITNESS: No. This is undergraduates, and they

are pharmaceutical sciences majors, and they're mostly

prepharmacy, but there are subsets that are premed and

preindustry. And I teach the fundamentals of drug

development, the clinical phases of drug development, concepts

of how does the membrane and the receptor work for drugs.

Basic concepts that would help them in the future.

BY MR. WONG:

Q. Aside from undergrads, do you teach any other students?

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A. Yes. So, I teach, of course, medical students,

residents, and fellows. And next month I'll be giving a core

lecture to the new fellows that are just starting on melanoma

and how we approach melanoma. So, you know, I enjoy teaching.

Q. Okay. Do you teach your students about clinical trials?

A. Yes. So, the undergrad class, that's a big component of

it, because so much of what you do as a pharmacist is you're,

you know, giving drugs, and you need to know, sort of, how do

we come up with these package inserts and how -- what does the

drug have to go through to finally be accepted?

Q. Okay. Outside of UC, Irvine are you involved with any

professional organizations in your field?

A. Yes. I'm a member of the American Society of Clinical

Oncology, the American Association of Cancer Research, which

are the two big meetings for sort of the bench and bedside

presentations on results, and, you know, some local

organizations.

Q. Okay. Have you also published papers in the field of

oncology?

A. I have about 80 peer-reviewed publications.

Q. Okay. Are you yourself also a peer-reviewer on relevant

journals?

A. Yes. I peer review articles. I got a text message this

morning about I'm late on reviewing a manuscript, so I review

for Cancer Research, Clinical Cancer Research, you know,

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various cancer journals.

Q. Okay. Have you ever served as an expert witness in a

patent trial?

A. Yes, I have.

Q. How many?

A. In one trial.

Q. And in that trial, generally speaking, what was the

expertise that you were offering?

A. It was about the preclinical and clinical development of

pemetrexed.

MR. WONG: Your Honor, defendants tender Dr. Fruehauf

as an expert in the clinical sciences and pharmacology with a

focus on oncology and supportive care.

MR. O'MALLEY: No objection.

THE COURT: Admitted.

MR. WONG: Thank you.

DIRECT EXAMINATION BY MR. WONG:

Q. Okay. Dr. Fruehauf, let's get right to your opinions.

In forming your opinions in this case have you reviewed

the '219 patent?

A. Yes, I have.

Q. And have you reviewed the asserted claims of the '219

patent?

A. Yes, I have.

Q. Let's see the '219 patent. It is DTX-0268. Let's go

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right to the claims on Page 11.

And, Dr. Fruehauf, in your opinion what is the subject

matter of the '219 patent?

A. I think the subject matter of this patent is related to a

formulation that maintains stability for 24 months of the

compound, the active pharmaceutical ingredient, palonosetron.

Q. Okay. In your opinion who would a person of ordinary

skill in the art be with respect to the '219 patent?

A. A formulator.

Q. Are you a formulator?

A. No. No, sir.

Q. What is your training in?

A. I'm a medical oncologist and a pharmacologist.

Q. Okay. So, how is that relevant to a POSA -- can I use

the term "POSA" for a person of ordinary skill in the art?

A. Yes.

Q. How is your training relevant to a POSA for the '219

patent?

A. Well, my expertise would be applied more to the

administration to a human to reduce the likelihood of cancer

chemotherapy-induced nausea and vomiting. Cancer

chemotherapy-induced nausea and vomiting. And I'm trying to

stick with mainly what's in the text there, but I do

paraphrase, and I apologize.

THE COURT: Maybe if you slow down just a little bit.

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We have plenty of time.

THE WITNESS: Yes, ma'am.

BY MR. WONG:

Q. If we call that "CINV" is that okay?

A. Yes, sir.

Q. Okay. So, with respect to this part of the claim, what

type of expertise are you offering for the '219 patent?

A. The clinical development component where how did they

come to this conclusion that the drug is effective at reducing

the risk of nausea and vomiting, and this is -- really the key

is to reduce the likelihood of cancer chemotherapy-induced

nausea, and that stems from the clinical trial data.

Q. Okay. Do you have preclinical and clinical expertise?

A. Yes, sir.

Q. Okay. Have you prepared a demonstrative to explain the

various types of clinical trials?

A. Yes, I have.

Q. Okay. Let's have Fruehauf 2. Can you walk the Court

through this general paradigm of preclinical and clinical

trial processes?

A. So, this is an overview.

THE COURT: Just a second. Give me a moment. I'll

be right with you. Okay. So, you have s demonstrative here.

Go right ahead.

THE WITNESS: So, this is an overview of the

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preclinical -- so that's before it gets to people -- and the

clinical trial process. And, basically, this is what I

discuss with my undergraduate students, but there's a

preclinical phase. Somebody conceives of a drug or, you know,

let's say a drug that would have an intended purpose to

improve people's outcomes.

So, they have to test it in animals to show that it is

safe in animals, and they'll have animal models that would be

reproducing the human state that they're trying to mitigate.

So, for instance, they could use ferrets and give them

high doses of chemotherapy like Cisplatin, and the ferrets

would vomit. And they can then give the ferret the drug that

they're developing that's supposed to suppress vomiting and

show that at a certain dose for that animal, where the drug

reaches a certain concentration in the animal's blood, it

effectively suppresses the nausea.

So, that's the test of effective, and coming up with

the dose in animals that's so critical to, you know, going to

the FDA with this information of safety and efficacy to ask if

we can give this to people. And the safety part is basically

giving higher and higher doses of the drug to animals over an

extended period of time and then sacrificing the animals and

looking at all their organs through the microscope and

checking their biology, their kidneys still function, is their

liver fine, and so on and so forth.

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And, so, if you can find that at the doses needed to be

effective in the animal model that it doesn't cause toxicity

in the animal, then you go to the FDA and you file an

Investigational New Drug Application. And that's this

interface right here.

And when you go to the FDA with this information and

you say, This is my plan in Phase I, I'm starting at a much

lower dose than was found to be safe in the animal. I want to

give a group of healthy volunteers this drug, and I'm going to

give increasing amounts of the drug to make sure that as I go

up and up and up in the doses that are given to people that I

can cover the dose that I can, you know, predict was working

in the animals.

So, I'll give a model dose that worked in animals to

people in Phase I and find out if that's safe.

THE COURT: So, these folks are not suffering from

nausea?

THE WITNESS: No, ma'am.

THE COURT: You're just checking for safety?

THE WITNESS: Yes. And when I was a medical student

I would go in and work with the Phase I studies. These are

usually younger people who are getting paid to come in for

three days, and we give them the medicine, and we check their

blood pressure and draw their blood and check their blood

levels just to prove that in a normal human being there's no

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unexpected adverse event.

And, so, once we have gone up through this range of

doses, and we have determined that it is not toxic and, also,

that we have confirmed that we can give a dose in humans that

are normal without an illness that matches the dose that was

effective in animals, then we take these two pieces of

information, we go back to the FDA and we say, Okay, we would

now like to now prove that the drug is effective for the

intended purpose on a group of patients, and that is the Phase

II goal.

So, in Phase II of the trials we are determining if the

dose we found is safe and is similar to the dose that was

effective in animals will now be effective in humans.

And, you know, these study designs tend to be unblinded

usually, and we would just give the drug to the people who are

let's say cancer patients that are going to get chemotherapy

that's highly nausea-provoking or highly emetogenic and see if

the drug would prevent that nausea.

And if we have success here, in other words we have

defined an effective dose in Phase II, then we go and ask the

FDA, Do you agree that we have defined the effective dose,

and, if so, can we take this into a larger Phase III trial

where we can confirm in a larger group of people and do more

safety analysis, and critically here in Phase III, compare the

new drug with what's already out there that it would be

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equivalent or better than the existing therapies.

Then if these Phase III studies are effective -- it

might just be one, two or three, it is not critical how many,

but if your Phase III study is effective, then you go and ask

for your New Drug Application approval so that you can

commercialize the agent.

MR. WONG: Okay.

THE COURT: And you can select a couple of two or

three different dosage levels to put into your Phase II or

Phase III trials, right?

THE WITNESS: Absolutely. And I think that, you

know, certainly in this case that's what was done.

BY MR. WONG:

Q. Okay. Now, Dr. Fruehauf, is this how drugs are currently

tested for safety and efficacy?

A. Yes. This is the current process, and it goes back to

the sixties when there was realization of the need for a sort

of codified process that everyone could follow where, you

know, these safety signals would be identified early and then

that if you thought it was really working you could really

prove that on a statistical basis.

Q. Okay. Now, who is carrying out these types of

preclinical and clinical studies?

A. So, the preclinical studies would be done, you know, by

scientists, pharmacologists, you know, Ph.D.s, and then --

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THE COURT: Ph.D.s in what?

THE WITNESS: Pharmacology, cell biology, physiology.

So, the preclinical work is mainly done by that level

of person, and then when you go into people, of course, now

we're talking about patients or even healthy volunteers, but

if you're giving a drug to a person, you have to be a

physician.

THE COURT: Yes.

THE WITNESS: So, that's where we start as clinicians

in Phase I.

BY MR. WONG:

Q. Okay. By 2002 how would you characterize the practice of

conducting these clinical trials?

A. Very routine.

Q. Okay. Now, going back to Phase II just to follow up on a

couple of issues --

THE COURT: Do you design clinical trials? I know

that you supervise them, right?

THE WITNESS: No, I have two INDs right now for two

different clinical trials that I'm carrying out for melanoma.

So, I have gone through this with the FDA.

THE COURT: The IND is where you go to get permission

for Phase I research?

THE WITNESS: Well, actually, so the IND itself

carries through all the way until you're done with Phase III.

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So you're making sort of amendments to your Investigational

New Drug Application as you go forward.

BY MR. WONG:

Q. Okay. Were you in court on Tuesday to hear opening

statements?

A. Yes, sir.

Q. Did you hear the term "minimum effective dose"?

A. Yes, I did.

Q. What is the minimum effective dose?

A. That would be the dose that has the sort of optimal

effect for the intended purpose, such as, let's say,

suppressing nausea, but is the least amount of drug because

the more concentration you have in the blood, the more likely

it is that the drug will bind to other places besides the

intended target and give you side effects.

So, you want to avoid side effects as much as possible,

so you want the minimum amount of drug that would have the

intended effect.

Q. Okay. And in the clinical trials what does it mean that

a trial is "randomized"?

A. So, randomized trials are trials where, you know, let's

say there's different arms on a study. You know, for

instance, the comparator study here, we have one arm that

would be a standard drug that's already approved. Now we have

the new drug.

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So, you might just have a two-arm study; one for the

comparator, one for the new drug, which how do you know what

the patient is going to get? You flip a coin or you use a

random number generator. And then that patient would be

randomly assigned to one of those two treatment arms. And

that could go for four arms or three arms, it doesn't matter,

but the simple thing would be you flip a coin. If it is three

arms, you have a three-sided dice you throw in a sense, and it

is just randomly picking.

So, this is to avoid bias. This is to avoid the

physician sort of he wants the drug to work, let's say, or

she, and, so, the doctor could subconsciously even put the

better patient into a given arm. So, this is to avoid bias.

Q. Okay. What --

THE COURT: And if you have got -- you call it an

"arm," which would be one substance being tested; another arm

would be another substance being tested --

THE WITNESS: Yes, ma'am.

THE COURT: -- and this is probably blinded, so the

doctor doesn't know which the doctor is administering, right?

THE WITNESS: Yes. The double-blinded --

THE COURT: We'll get there. I'm just -- arm, "arm"

is your term for a given drug that's going to be administered.

THE WITNESS: Or a drug at a given dose.

THE COURT: Okay. Yes. But in randomizing you want

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to distribute your population, so you get about as many people

in each arm.

THE WITNESS: Balanced.

THE COURT: Right? Okay.

BY MR. WONG:

Q. Okay. Your Honor, you mentioned "blinded."

Dr. Fruehauf, what does it mean when a trial is

"blinded"?

A. So, the blinding would be, again, trying to avoid bias.

And you don't want people to know, you know, what the patient

is getting until after things are done so, there's not bias.

And, so, let's say you've got two drugs in a comparator

study. One drug is given in a bag of 50 milliliters of

solution through an I.V. The other drug is given as a quick

bolus.

Now, obviously, how could you not let the person know

if you just gave one or the other? So everybody gets the

same. They'll get a placebo, let's say, in the bag and the

active ingredient in the injection so that way nobody knows

what that patient really got. And the blinding is there's a

place where they put the drugs together with a number on it,

and then they'll ship it based on the arm the patient is on,

and only the people -- nobody really knows what they're

getting.

Q. Okay.

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THE COURT: And double-blind?

THE WITNESS: So, the patient doesn't know and the

doctor doesn't know and the company doesn't know.

BY MR. WONG:

Q. Okay. Just a little more glossary terms. In clinical

trials, what does the term "first patient in date" mean?

A. So, you know, let's say you've got your IND and you're in

Phase II and -- or you're in Phase III, and you have a

protocol. So, the protocol has to go through a review by a

review board, be approved, and once it's approved, the patient

can be accrued to the study. They have to sign a consent.

THE COURT: Accrued?

THE WITNESS: Accrual is adding people into the

study.

THE COURT: Fine. We just want to make sure that's

the word you used.

THE WITNESS: Yes, ma'am. Thank you. I know it's

like, to me, too much second nature.

So, "accrual" is a term just to put somebody into a

trial, and once they have signed a consent, they can be

randomized. And once they're treated, that's the first person

on, so to speak.

Now, you can really consider once they sign the consent

you intend to treat them, and that's -- they're the first

person on.

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BY MR. WONG:

Q. And then on the other side, what does the term "last

patient out date" mean?

A. So, that would be, you know, in the statistical design of

the trial, you've made assumptions about what will happen,

what the differences might be, and you have a number of

patients that you think are required to be able to show what

you want the study to show.

And, so, you have a target of end number of patients to

be put on the study, and when you've reached that target,

that's your last patient, you've met your accrual goal and

that's the last patient on. And when they're last patient out

is they got the drug, the effect of the drug was measured, and

now they're done.

Q. As of the last patient out date in a clinical trial, what

does the data look like?

A. So, in a blinded trial, the last patient out, you have

all the data and all the results in your spreadsheet. You

just don't know which patient got what drug.

Q. Okay. Is the data unblinded at some point?

A. So, once the last patient's out, there's sort of, you

know, the term used in the pharmaceutical -- by companies is

"cleaning" the data, so they have people that go and make sure

all the data is correct, there aren't mistakes of, you know,

this number should have been in this box or that box and so

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on.

So, they clean the data. And once it is cleaned, they

lock the data.

Now, once you lock the data for the FDA, you can no

longer change any of the data. That's it. It's fixed.

So, once the data is locked and can no longer be

touched, then you can unblind the data, and now you'll know

who got what and you can, you know, determine if the drug was

effective or not.

Q. Okay. After the data is unblinded, can the data change

at all?

A. No. It's been locked, so you can't change the data in

any way.

Q. And in your experience in clinical trials, is the

unblinding date important to investigators and sponsors of a

clinical trial?

A. Absolutely. I mean, they've made an investment of

millions of dollars. They want to help people. They want a

compound that will do that. They want to know did this study

show that the drug works. The physicians want to know.

Everybody who participated wants to know.

Q. And when is the first analysis of the unblinded data

typically done?

A. As soon as the unblinding is done then, you know, the

clock is ticking. You want to get your results analyzed so

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that you can put together your NDA application if it's a Phase

III study, or if it's the Phase II result, you want to go

right away into Phase III.

THE COURT: So, but it's not just the -- you push a

button on a computer and out comes the analysis, not quite?

THE WITNESS: It's pretty close to that. I mean, you

have in the -- the clinical research -- the clinical --

there's usually a company that's working for the drug company

that handles the statistics, and they have the database. So,

the database is set up to actually just be the input into the

statistical analysis program.

And I've run these programs. I mean, it's not that

complicated. So, it could take a couple of days to do an

analysis once the data is unblinded.

BY MR. WONG:

Q. Okay. Is the initial statistical analysis of the

efficacy data that is conducted -- that is conducted, the

initial analysis, is that analysis reliable?

A. Well, the data never changed, and it's all preordained

because when you go to the FDA and you say, I want to run a

Phase III trial, for instance, you have to tell them what

analysis you will do at the end, how you will do that

analysis.

So, you have to follow what you already said you were

going to do years earlier. So, that is it. That first

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analysis is the result of the study based on the preordained

process of analysis.

THE COURT: Then why do you call it the first

analysis? Can you go back and troubleshoot it?

THE WITNESS: You can't really change the data.

Now, what can happen, you know, I've been involved

where, you know, we have the primary result and we have the

analysis, but we notice something, let's say. We noticed

that, gee, it seemed like people that had high blood pressure

did better. So we can do what's called an ad hoc analysis of

data, but that doesn't change the data. It's just another way

of looking at the same data.

THE COURT: And saying, oh, and we also learned this

in addition.

THE WITNESS: Correct. But for regulatory purposes,

that wasn't preplanned, and so it isn't assigned the same

degree of credibility.

MR. WONG: Okay. Thank you, Doctor.

THE COURT: And the analysis is not likely -- you

know how if you do -- if you tell somebody to do a numerical

computation of some sort and they do it and they bring it to

you and you pick it up and you say this doesn't look right,

then you find out that they made some mistake in the middle.

THE WITNESS: So, that you have avoided in the data

cleaning step because this is so regulated.

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THE COURT: Regimented.

THE WITNESS: It's regimented. I mean, there's not

room. I mean, I wouldn't say that mistakes are impossible,

but there's a tremendous effort with lots of people who work

through weekends and nights when this data is being cleaned to

get to the result. There's tremendous stress on those people

to get it right because if they don't get it right, they get

their hand slapped by the FDA.

And, in fact, the FDA has stated that the way

pharmaceutical companies do research is far superior to how,

let's say, you know, a cancer center would do research because

it's so regimented and refined as a process that's become so

routine.

BY MR. WONG:

Q. Okay. Thank you, Dr. Fruehauf. Let's get back to your

opinions in this case.

A. Yes, sir.

Q. As of the January 30th, 2002 date, was it known that

administering palonosetron to humans reduces the likelihood of

CINV?

MR. O'MALLEY: Objection; vague.

Known by whom?

Objection; vague. Objection as to form.

THE COURT: Can you rephrase?

MR. WONG: Sure.

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BY MR. WONG:

Q. With respect to a person of ordinary skills in the

clinical sciences, would that person know as of January 30th,

2002, that palonosetron administered to a human reduces the

likelihood of CINV?

A. Yes.

Q. Okay. Have you reviewed the documents in this case that

support your opinions?

A. Yes, I have.

Q. Have you prepared a summary of those documents?

A. Yes, I have.

Q. Let's go to Fruehauf 3.

Dr. Fruehauf, what were the key documents that showed

that palonosetron reduced the likelihood of CINV by the

critical date?

THE COURT: Counsel, before you allow the doctor to

answer your question, are you asking him for documents that

would be available to this hypothetical skilled artisan?

MR. WONG: That's right.

THE COURT: So, these are public by legal definition?

MR. WONG: Well, for the on-sale bar, it can be

private documents, confidential documents, or public

documents.

THE COURT: But available to the hypothetical skilled

artisan --

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MR. WONG: Available --

THE COURT: -- I would think?

MR. WONG: Well, let me ask the doctor this.

BY MR. WONG:

Q. In your analysis of the question of whether a person

would know if the palonosetron would work, what kind of

documents did you review?

A. I reviewed the Phase II study results from the Syntex

trial that was concluded in 1995.

THE COURT: And is that publicly available in 1995,

Doctor?

THE WITNESS: No.

MR. WONG: I can ask.

BY MR. WONG:

Q. For your opinions herein today, did you review both

public and private, confidential documents?

A. Yes, I did.

Q. Did you rely on both public and private, confidential

documents in forming your opinions?

A. Yes, I did.

THE COURT: All right. You may proceed, but I want

the distinction to be observed, if you would, please.

Is that your basis, Mr. O'Malley?

MR. O'MALLEY: Yes. He said, as you noted, quite

clearly that this would be what a POSA knew. POSAs don't know

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our clinical -- our confidential clinical documents. There's

no foundation for this slide.

THE COURT: Okay. So, we'll keep this distinction

going, and you can ask your questions, Mr. Wong.

MR. WONG: Thank you.

BY MR. WONG:

Q. So out of the documents that you relied on, what were the

key documents that formed your opinion?

A. So, I looked at the Syntex Phase II trial, 2330. That

was the first study of palonosetron in people that were sick.

And I looked at a meeting minutes that Helsinn had, where when

Helsinn licensed from Roche who had acquired Syntex, Helsinn

had a meeting with the Syntex folks to learn, well, what did

we in-license? What's the science that we have now that we've

in-licensed this? So, that meeting was in 1998.

And then after their review of this, they sent a letter

to the FDA explaining their intentions for a clinical

development program. That was November 1999. And then they

began their Phase III studies and put out a press release to

the effect that we are now carrying out a clinical trial based

on results from the Phase II study. We've moved into Phase

III.

And I reviewed the Phase III trials. I reviewed the

reports for the trials and also a declaration by Cantoreggi

who stated, you know, that they knew that the drug was

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effective at a certain time.

MR. WONG: Okay. Let's go right to the first

document. Can we have the Syntex Phase II trials, DTX-0227.

Let's go to Page 5 of the study.

BY MR. WONG:

Q. Dr. Fruehauf, do you recognize this document, DTX-0227?

A. Yes, sir. So, this is the final report on the 2330

clinical trial, which is the dose ranging, efficacy, safety,

and pharmacokinetic study of single-intravenous doses of

RS-25259, which is palonosetron, for prevention of nausea and

vomiting in chemotherapy-naive cancer patients receiving

highly emetogenic chemotherapy.

Q. Dr. Fruehauf, were you in court on Tuesday to hear Dr.

Calderari's testimony on this document?

A. Yes, I was.

MR. O'MALLEY: And I'll just object until they lay

the foundation that your Honor requested as to whether or not

the POSA would have had this, since the overarching opinion is

that a POSA would have known X.

THE COURT: Okay. Mr. Wong, can you -- is this

available to a POSA?

BY MR. WONG:

Q. Would this document have been available to a POSA? Was

this document publicly available as of 1995?

A. I don't believe so.

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Q. If you saw this document in 1995, would you understand

that, and reviewing the data, would you understand that

palonosetron was effective to reduce CINV?

MR. O'MALLEY: Objection. Calls for speculation.

THE COURT: Sustained.

You can ask him what this document tells him now.

That's fine.

MR. WONG: That's fine.

So let's go to Page 14. Let's go right to results or

the study synopsis, and let's go to objections down low. The

objectives below.

BY MR. WONG:

Q. Dr. Fruehauf, what was a primary -- what was a primary

objective of this Phase II study? Looking at this document

today, what was the primary objective of the Phase II study?

A. It was, basically, to determine whether palonosetron,

over a dose range of 1-90 micrograms per kilogram, given to

patients who were treated with highly emetogenic chemotherapy

would reduce the likelihood of chemotherapy-related nausea.

Q. Okay. In carrying out the primary objective of this

study, would it include a determination of whether

palonosetron reduces the likelihood of CINV when administered

to humans?

A. Yes.

MR. WONG: Let's go to the methodology section.

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Right below.

BY MR. WONG:

Q. Dr. Fruehauf, how would you characterize this Phase II

Study 2330?

A. This is a very strong Phase II study because it was

randomized and double-blinded in multicenter, so in

multicenter trials, you have a variety of people

participating, which decreases bias.

And then it was this dose-ranging efficacy study, so

they wanted to know what dose is working to suppress nausea.

So it was a very strong design for a Phase II trial.

THE COURT: You said not all Phase II trials are even

blinded at all.

THE WITNESS: Correct.

THE COURT: This was?

THE WITNESS: Yes.

MR. WONG: Okay. Let's go to the next section, the

number of subjects section.

BY MR. WONG:

Q. Dr. Fruehauf, how many patients in total were involved in

this Phase II Study, 2330?

A. There were 161 patients, more males than females, and

then there were 13 patients who were excluded from the

efficacy analysis for various reasons, which, you know, we

won't go into, but -- and, so, it was 161 patients with 13

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excluded.

Q. And how many patients actually got the 0.25 milligram

dose of palonosetron?

A. There were -- which is the equivalent of

3-micrograms-per-kilogram dose. Of 3 micrograms per

kilogram, .25 was the equivalent to 3 micrograms per kilogram,

and there were 24 patients who received that dose.

Q. So, did the study design of this Phase II study allow the

determination of whether palonosetron administered at

0.25 milligrams reduces the likelihood of CINV when it was

administered to a human?

A. Yes.

MR. WONG: Let's go to summary and conclusion section

on Page 15.

BY MR. WONG:

Q. Right here in the first sentence, what was Syntex's

conclusion on this Study 2330?

A. They concluded that all four doses, and they're talking

about 3, 10, 30 and 90, they didn't -- .3 to 1 was a low dose

that wasn't expected to have the full effect, but it did have

some effect because no drug would have lead to, you know, zero

control of nausea and vomiting.

So, they found that 3, 10, 30 and 90, let's take the

percent complete control going across, those were equivalent

and effective. All four doses were approximately equally

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effective as compared with the combined results from a cohort

of the .3 to 1 micrograms per kilogram.

Q. And what do they state in the first sentence?

A. They state that palonosetron was administered as a single

bolus intravenous injection of these doses 30 minutes prior to

chemotherapy.

Q. So, let's focus in on the --

THE COURT: And that they were looking at suppressing

CINV for 24 hours after the chemotherapy.

THE WITNESS: Yes, ma'am. So, the endpoints here

were complete control at 24 hours, which means, by definition

in the study, that they didn't throw up and they didn't feel

nauseated. They didn't need a medicine to help them after

they got the first medicine.

And then this is a second endpoint, complete response,

where the numbers were a little lower because that would be

those patients might have needed some rescue medicine, and

then the median time --

THE COURT: What's the difference between complete

control at 24 hours and complete response at 24 hours, can you

tell us?

THE WITNESS: Yeah, this is really the difference

between who needed a rescue medication, and the percentage of

people -- like this is a lower number for complete response

because they might have felt nauseated. They didn't throw up,

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but they might have felt nauseated. They filled out a

questionnaire --

THE COURT: Yes.

THE WITNESS: -- about how they felt over the 24-hour

period --

THE COURT: Yes.

THE WITNESS: -- and they used that questionnaire to

assess the benefit of the drug for its intended effect.

THE COURT: And that last row says, "median time in

hours to failure defined as first emetic episode or rescue

drug."

THE WITNESS: Yes. So that is, you know, basically,

they got the medicine, they got the chemotherapy, and how long

did the medicine work for? When did it wear off?

So when it wore off, that means you're starting to feel

sick. And that's the delayed emesis. And, so, let's say for

the .25 or the 3-micrograms-per-kilogram, that time to failure

was 22.7 hours, compared to, let's say, 19 for 10, greater

than 24 for 30, and 21.8 for 90. We can see these numbers are

all pretty consistent, but these numbers are lower, so there's

sort of a --

THE COURT: In other words, the dosage beginning with

3 and going up was pretty consistent. It's just the dosage

below 3 that fell off.

THE WITNESS: So, you know, what we understand about

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palonosetron is it was very potent. And, you know, you're

binding to a receptor, and if you -- if you have enough drug

to bind to all the receptors and they're all blocked at a

certain dose, giving more drug won't have any more benefit.

THE COURT: Doctor, we're talking about this H --

THE WITNESS: 5-HT.

THE COURT: -- 5-HT3 receptor. That's not the only

receptor that sends signals of nausea to the brain, is it?

THE WITNESS: No. As I was explaining earlier from

my practice, I will combine drugs that will work on different

receptors because here there's only a 50 percent control.

THE COURT: Even at best --

THE WITNESS: Even at best.

THE COURT: -- with palonosetron.

THE WITNESS: With one drug. So, if you give a

second drug and a third drug, now you're going to improve your

control rate to some degree; but, of course, as you add more

drugs, you're getting into more side effects.

THE COURT: But the other drugs would target other

receptors theoretically.

THE WITNESS: Correct.

THE COURT: Thank you.

THE WITNESS: So, here we have a saturation of the

receptors, and as you go higher, you don't really see any

change after that.

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BY MR. WONG:

Q. Let's just focus on the 0.25 milligram data that's under

3-microgram-per-kilogram. What do the data, 46 percent,

39 percent and 22.7 hours, based on those data what can you

conclude about whether 0.25 milligrams of palonosetron reduced

the likelihood of CINV in patients who got this dose?

A. It's very clear that it effectively reduced the risk. I

mean, if there was zero here, from my clinical experience if

you don't give any premedication to someone who's getting

highly emetogenic chemotherapy, 90 percent of them are going

to throw up.

THE COURT: Because that's nature's way --

THE WITNESS: That's nature's way.

THE COURT: -- is that right?

THE WITNESS: They get a poison, they want to throw

up. So, you have to have something in there to suppress that

natural reaction to the poison that we're putting in their

veins.

And, so, this was partially effective, and then this

was the maximal effect, I think, in this Phase II trial.

THE COURT: You're referring to the Column 3.

THE WITNESS: Yes.

THE COURT: The column under the Dosage 3.

THE WITNESS: Right. So this is -- these percentages

of control are similar as they stated, all four doses were

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approximately equally effective. So these are all kind of the

same. So this would be the minimal effective dose in this

particular set of doses.

THE COURT: Referring to the column under 3.

THE WITNESS: Yes, ma'am.

THE COURT: When you use a pointer, the record, the

cold page of the record, doesn't know which column, so I'm

just filling that in for you. You don't have to worry about

it.

THE WITNESS: Understood. Thank you. I'll try

and --

MR. WONG: Thank you, your Honor.

Okay. Let's go back to the timeline, Fruehauf 3.

THE COURT: Okay.

MR. WONG: Unless you have any other questions.

THE COURT: I wonder, could we take a recess now?

Would that be all right?

THE COURT: Back in session.

MR. WONG: Thank you, Your Honor.

BY MR. WONG:

Q. I think we left off on Fruehauf 3, the timeline.

Dr. Fruehauf, just wrapping up on the Syntex Phase III Study

2330. What is the date of the study report, Study 2330? What

is the date of the study report?

A. The date of the study report was July, 1995.

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Q. Now, if a person of skill in the clinical sciences were

to see the data in the Syntex study, on or about 1995, would

he or she come to the same conclusions that we just discussed?

MR. O'MALLEY: Objection, Your Honor. No foundation.

We've already received testimony that that POSA could not have

seen it.

MR. WONG: Your Honor, my question is just if that

person were to see this document.

THE COURT: I'll permit it. Experts can be asked

hypotheticals. I agree with you that there's not a fact upon

which they could base this hypothetical, but I'll permit the

question.

MR. LOMBARDI: Your Honor, at some -- maybe not now,

but at some point it might be helpful to address the role of

POSA in the ready-for-patenting analysis because it's

different than the prior art and there's not a requirement

that a person of skill in the art have seen the public data.

THE COURT: Okay. Let's defer that. Don't want to

argue it now.

MR. WONG: Thank you.

THE COURT: Go ahead and make your record, Mr. Wong.

MR. WONG: Okay.

BY MR. WONG:

Q. The answer to my question was? Let me read the question

again.

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If a person of skill in the art in the clinical

sciences were to see the Syntex data as of 1995, would he or

she come to the same conclusions that we just discussed?

A. Yes, I think it would be clear that the drug at the .25

milligram dose reduced the likelihood of nausea and vomiting.

Q. Okay. Let's move on.

What is the next document you considered in forming

your opinions?

A. The July, 1998 Helsinn meeting minutes.

Q. And what is important about this document, this meeting

minutes from July, 1998?

A. Well, this is really where Helsinn was taking the reins

of the development process. And they needed to assess what

they had, and this is really their interpretation of what the

drug had done so far.

Q. Okay. Let's go to DTX-0015.

Okay. Let's orient ourselves. Is this the Helsinn

meeting minutes that you relied on?

A. Yes, it is.

Q. Okay. And what is the title here of this document?

A. This is Helsinn Palonosetron Team Meetings,

palonosetron --

THE COURT: These are all internal people?

THE WITNESS: So, these were -- yes, these were

people from Syntex. There were some Syntex people --

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THE COURT: Okay.

THE WITNESS: -- and then there were -- no, they

weren't all inside people. And then there were Helsinn

people, and then there was an outside expert that was invited

to the meeting.

THE COURT: They were paid to come by somebody?

THE WITNESS: I don't know. Probably.

THE COURT: Okay.

BY MR. WONG:

Q. Where were these meetings held?

A. In Palo Alto, California.

Q. And when did these meetings take place?

A. In July of 1998.

Q. Let's take a look, let's enlarge it and see who attended

these meetings. So when you say outside consultants, what

outside consultants attended the meeting?

A. A Dr. David Gandara from UC Davis.

Q. Do you know Dr. Gandara?

A. Yes, I do.

Q. Who is Dr. Gandara?

A. Dr. Gandara is a medical oncologist who has published

widely on antiemetic chemotherapy trials, on chemotherapy for

lung cancer. He's published more than 100 papers. His papers

have been cited by more than -- each paper, might be a

thousand people have cited his paper. So he's very well

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respected in the oncology community.

Q. Now, based on your review of these meeting minutes, what

was the purpose of these meetings?

A. The purpose of the meeting, as I stated, was to

understand on the -- from the perspective of Helsinn, what did

Syntex do, what were their data, and how could we go forward

in the regulatory process.

Q. Okay. Let's go to Page 8. This is DSC, Page 8. What

does this -- if you blow it up a little bit more.

What does this portion of the -- in general, what does

this portion of the meeting minutes disclose?

A. So, this discloses the doses that I'm pointing out here

under the overview, where it states, "The following drug doses

and concentrations are proposed for the CINV and PONV trials."

So the chemotherapy-induced nausea and vomiting and

postoperative nausea and vomiting trials.

And then below that, they have the CINV table, where

they list a dose of drug that would be put in the 5 milliliter

volume, with the concentration listed next to the dose, and

the dose chosen for CINV was .25 -- or doses, .25, .75 and 2.

Q. What were these -- on what data were these doses chosen?

Based on what data were these doses chosen?

A. The discussion at the meeting was about the Phase II

trial, and based on the Phase II trial results, as we

described, you're trying to identify in Phase II the minimally

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effective dose, and so they've taken that Phase II trial

result and now they're proposing to take these doses forward

into Phase III.

Q. Were all three doses actually studied in Helsinn's Phase

III trials?

A. No, they reduced it down to .25 and .75, just those two.

Q. And just to be clear, as shown in this table for CINV,

what was the concentration of the formulation where the dose

was 0.25 milligrams?

A. The concentration was 0.05 milligrams per milliliter.

Q. And was the design of the Phase III clinical trials also

discussed at these team meetings?

A. To some degree, yes.

Q. Let's go to Page 10. And let's -- first two paragraphs.

This is DTX, Page 10, first two paragraphs. So under CINE

study designs, what does Helsinn say about the Phase II

studies?

THE COURT: We've already established that CINE is

synonymous with CINV.

MR. WONG: Correct, Your Honor.

THE COURT: Do you see it that way, Doctor?

THE WITNESS: Yes, ma'am.

THE COURT: Okay.

THE WITNESS: Emesis or vomiting --

THE COURT: All right.

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THE WITNESS: -- are equivalent.

BY MR. WONG:

Q. So let me repeat the question.

What does Helsinn say here about Phase II studies?

A. It says that, you know, that they don't want to use a low

dose because that wouldn't be ethical because it wouldn't have

as much control, so they're proposing to test the effective

doses seen in Phase II, and as we've stated, these were

equivalent, according to the conclusion from the Phase II

study. So we're going to take these equivalent doses in a

sense and compare them to ondansetron at 32 milligrams which

at that time was the standard dose for ondansetron to prevent

chemotherapy-induced nausea and emesis.

THE COURT: Just saying this, ondansetron, 32

milligrams, compared to a quarter milligram or three-quarter

milligram of palonosetron.

THE WITNESS: Yes, ma'am. And this is because the --

we use the term "potency," and so the mechanism of the drug is

completely different. It doesn't compete with serotonin. So

they have a receptor, serotonin would come and bind to the

receptor. You can try and block that. Now you've got to have

more of your drug than there are serotonin molecules to keep

it from binding and signalling nausea.

But what palonosetron does is it binds a different

place, and the receptor goes off the surface of the cell. And

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you don't have to compete with serotonin anymore because

you've down-regulated the receptor completely. So this was a,

you know, second-generation drug.

BY MR. WONG:

Q. Okay.

THE COURT: Palonosetron?

THE WITNESS: Yes, ma'am. Palonosetron was a

second-generation 5-HT inhibitor.

BY MR. WONG:

Q. Just for the record, these -- these weighted doses of 3,

10 and 30 micrograms per kilogram, what do they equal when you

turn them into fixed doses?

A. .25, .75, and 2 milligrams.

Q. And what was the injection volume that Helsinn selected

for these doses?

A. The volume is planned to be 5 milliliters.

Q. If a person of skill in the clinical sciences were to see

this information, how would he or she interpret the

information?

A. That Helsinn interpreted the Phase II trial results to

indicate that the .25 milligram dose was the minimal effective

dose, and they were going to take that with a couple of other

doses that were higher into the Phase III study.

MR. WONG: Let's go to Page 12. If you could blow up

the top section.

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BY MR. WONG:

Q. What is the title of this section of the meeting minutes?

A. This is entitled "Gandara Meeting."

Q. And with respect to the section, dose selection, what

does it state regarding Dr. Gandara?

A. So, after meeting with Dr. Gandara and his review of the

data, it states that the dose selection, and then we'll just

quote what it says, "Gandara recommended that, despite the

unusual result in 2332," which was an oral trial, not an I.V.

trial, that the 3 microgram per kilogram was most likely the

correct dose for chemotherapy-induced nausea and vomiting.

Q. Do you agree with Dr. Gandara's recommendation here?

A. Yes, I do.

Q. And why is that?

A. Because I think it's clear from the trial that the .25

milligram dose was the inflexion point, and after that you've

saturated the receptors and that that's the minimally

effective dose and you want to avoid higher doses because, as

you go up on doses, you're more likely to get side effects.

So Dr. Gandara came to the same conclusion that I have, and

he's recommending that he thinks that the 3 microgram per

kilogram dose was most likely the correct dose for CINV.

THE COURT: For intravenous administration?

THE WITNESS: Yes, ma'am, for intravenous

administration. Not for oral administration.

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BY MR. WONG:

Q. Let's go back to the timeline, Fruehauf 3. Dr. Fruehauf,

what is the next document that you considered after the July,

1998 meeting minutes?

A. I considered the 1999 Helsinn letter to the FDA.

Q. Were you in court when Dr. Calderari testified about this

document?

A. Yes, sir.

Q. Okay. Let's go to the document DTX-0293. Just to remind

the Court, what is this document, DTX-0293?

A. So, as we heard from Dr. Calderari, Helsinn could not

directly communicate with the FDA because they did not have a

subsidiary in the United States. So they had to hire a

consulting firm to communicate on their behalf to the FDA. So

the Austin, Texas, August Consulting Company was hired by

Helsinn. And this is a letter to the Center for Drug

Evaluation and Research at the FDA, where they are providing

now on their INDs -- so they have licensed-in this IND which

was already filed by Syntex, and they're amending it to go to

the next step. Their proposal is now to go to three new Phase

III protocols, PALO-99-03, PALO-99-04 and PALO-99-05.

Q. Did they actually attach the protocols to this letter?

A. Yes, sir.

MR. O'MALLEY: I'm sorry. I hate to interrupt. But,

again, the foundational question we've been requesting as to

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all these documents and the Court has has not been

established.

THE COURT: I think that's fine for you to note your

objection when each document comes up, but we'll keep going.

MR. WONG: Let me repeat my question.

BY MR. WONG:

Q. Were the Phase III protocols, the proposed protocols,

attached with this letter?

A. Yes, sir.

Q. Okay. Let's take a look at the protocols. Let's go to

Page 21.

What is disclosed here?

A. So this is the 99-03 protocol which was basically

addressing the question of single I.V. doses of palonosetron

at the .25 and the .75. Now, they've, you know, just chosen

these two, lower doses, versus ondansetron at a 32 milligram

dose, in the prevention of moderately emetogenic

chemotherapy-induced nausea and vomiting.

Q. Okay. And what is the date of this proposed protocol?

A. November 15th, 1999.

Q. Let's go to Page 34 in this document. And this is into

the 99-03 proposed protocol. What is shown here at the bottom

of Page 34?

A. So, what is shown here is, you know, they have to have

the justification for the FDA on dose selection. They have to

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provide the data to the FDA for their protocol, and any

investigator -- I mean, when I review protocols and I'm on our

investigation, you know, IRB, Investigation Review Board, and

I review maybe half of all the protocols that come through.

And I want to know, well, should we open the study here, did

the drug work? Has it been effective? I mean, could we

expect a good result for our patients and our institution?

And so in the protocol, you need to be showing what the

drugs did and why you picked, you know, this dose, for

instance. And so they're just reiterating what we've already

reviewed which was the Phase II data, to support their dose

selection for the .25 milligram dose by giving the data from

the Phase II study.

Q. And what does Helsinn say about this data on the next

page?

THE COURT: Just a second. Doctor, the data in the

table is the same as we saw.

THE WITNESS: Identical.

THE COURT: Right. The first column, the labels that

they use are a little different.

THE WITNESS: Here, it's percent with CR, so complete

response.

THE COURT: Complete response.

THE WITNESS: And then CC was the complete control,

and then here was the time to failure where we saw, you know,

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the -- that number of hours it took before people actually got

sick.

THE COURT: And what does this p-value refer to?

THE WITNESS: So the p-value is the probability that

the result seen could have occurred by chance alone, and in a

smaller trial like this where there's small numbers of people

per arm, you know, you're really looking more for the trend

or, as Dr. Calderari said, the signal. And so the probability

that 46 percent control occurred by chance is one chance in 10

that that occurred by a random event.

THE COURT: Okay.

THE WITNESS: And then this one says that there is

one chance in a hundred that this time to failure occurred,

you know, as a -- is a mistake.

THE COURT: So that's just a statistical explanation?

THE WITNESS: It's a statistical explanation, and the

way I, you know, look at these data is that since these were

pretty much equivalent, you can kind of combine all this and

be -- you know, it's very clear that the drug reduced nausea

and vomiting, and you could look at this number and say, gee,

there was this statistically significant, even with these

small numbers, delay in time to failure for the .25 dose.

BY MR. WONG:

Q. Okay. So let's go to the next page, and what does

Helsinn say about this Phase II data on the next page? Let's

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blow up the first paragraph.

A. So, you know, as part of their protocol proposal to the

FDA, again, they have to give the rationale for the dose

selection. And so, they're saying that data from this Phase

II study clearly demonstrate that the 3 microgram per kilogram

dose or the .25 milligram dose of palonosetron is the minimal

effective dose in preventing chemotherapy-induced nausea and

vomiting.

Q. Okay. And do you agree with this statement to the FDA?

A. Yes, I do.

Q. Okay. Now, are you surprised that Helsinn is making this

statement in this proposed protocol for its Phase III trial?

A. No, as I said, they need to have a statement about what

the result was from Phase II. So Phase II, as we've said

earlier, the goal is to find the minimally effective dose. So

they're making the statement here that they did do that, they

were successful in their Phase II trial, and that the

minimally effective dose is the .25 milligram dose.

THE COURT: So they're building on their Phase II

work?

THE WITNESS: Yes, ma'am.

BY MR. WONG:

Q. If a person of skill in the art in the clinical sciences

were to see this statement to FDA, would they interpret the

statement the same way?

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A. They would interpret this statement as to indicate that

the Phase II study showed that the .25 milligram dose could

reduce the risk of nausea and vomiting.

Q. Let's go back to the timeline, Fruehauf 3.

Dr. Fruehauf, what is the next document that you

considered in forming your opinions?

A. The Helsinn press release.

Q. Let's go to DTX-1227. The Court has seen this document,

but let's just orient the Court.

Were you in court when Dr. Calderari testified about

this document?

A. Yes, sir.

Q. Is this the Helsinn press release that you're referring

to?

A. Yes, it is.

Q. What is the date of this press release?

A. September, 2000.

Q. Was this press release public, made public as of

September, 2000?

A. Yes, it was.

Q. Let's go to the third paragraph.

In the third paragraph, what does the public press

release state about Helsinn's Phase II trials?

A. The public press release states, "The Phase II trials

demonstrated the efficacy of palonosetron in the prevention of

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emesis with no significant side effects."

Q. Okay. If you read this press release as of September,

2000, what would you understand about this disclosure?

A. I would understand that, you know, they were pleased with

their results. They had accomplished what they wanted to in

terms of they licensed the drug that had a successful Phase II

trial as an underpinning of its further development and that

palonosetron did reduce the risk of nausea and vomiting.

Q. Would a person of skill in the art in the clinical

sciences understand that Helsinn knew that palonosetron

reduced the likelihood of emesis?

A. Yes.

Q. Is it unusual for a company to issue a press release

about their clinical trials?

MR. O'MALLEY: Objection, foundation.

THE COURT: I'll permit it.

BY MR. WONG:

Q. Based on your experience.

THE COURT: You read the public literature?

THE WITNESS: Yes, ma'am.

THE COURT: And a lot of other literature?

THE WITNESS: Yes, ma'am. I get --

THE COURT: Technical literature, you read also?

THE WITNESS: Yes, ma'am.

But I'll get e-mails, you know, like this not

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infrequently from clearinghouses that follow the press

releases and then they send them to us so that we have -- are

kept abreast of where drugs are in development because, of

course, we're waiting for the next new thing for our patients.

And so -- and as the, you know, chief scientific

officer Oncotech for -- for 14 years, we put out press

releases, and we wanted to know -- you know, we wanted to let

our clients know what we were doing and that we weren't just

standing still, that we were making progress as a business.

So I think that this is an example of a company that wants

people to know that they are moving forward.

BY MR. WONG:

Q. For the record, this press release was issued by who?

A. Helsinn.

Q. Would a person of ordinary skill in the clinical sciences

view the statements in this Helsinn press release differently

had it been issued by a larger pharmaceutical company?

A. No, sir.

Q. And you actually reviewed the Phase III clinical trial

reports?

A. Yes, sir.

Q. Okay. How many were there?

A. Three.

Q. Okay. And what were they called?

A. 99-03, to use shorthand, 99-04 and 99-05.

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Q. And, in general, what were the differences between the

three Phase III study reports that Helsinn conducted?

THE COURT: That's in the record. We can move on.

MR. WONG: That's fine. Thank you, Your Honor.

BY MR. WONG:

Q. Let's look at the first study report, PALO-99-03,

DTX-0288, and let's go to Page 3. Dr. Fruehauf -- you can

blow up the entire -- thank you.

Dr. Fruehauf --

A. Yes, sir.

Q. -- do you recognize this document?

A. Yes, I do.

Q. Is this the final study report for 99-03?

A. Yes, it is.

Q. When was the study started?

A. The study was initiated with the first patient in in

August 1st, 2000.

Q. And when was the study completed?

A. The last patient out was October 2nd, 2001.

Q. And when was the study report written?

A. This report was written July 19, 2002.

Q. Does the study report describe the batches -- does the

study report describe the batches used in the clinical trial

PALO-99-03?

A. Yes, it does.

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Q. Let's look at Page 7; let's go to the bottom section.

Dr. Fruehauf, what doses of palonosetron were

administered in the 99-03 study?

A. You know, as we have stated previously, .25 and .75

milligrams of palonosetron.

Q. And for the .25 milligram dose, what were the batch

numbers?

A. The batch number -- the batch number for the .25

milligram dose was 1737321 and HPA003.

Q. Okay. Does the study report provide the final efficacy

analysis results?

A. Yes, sir.

Q. Let's go to Page 9 and under the summary section,

efficacy results. Let's look at Table 1. What does Table 1

report?

A. Table 1 reports that patients with a complete response

rate during the first 24 hours after chemotherapy, which is

the same endpoint as we looked at for the Phase II trial, and

it shows that the -- for the zero- to 24-hour time period,

that in this case, palonosetron at .25 had an 81 percent

complete response rate.

Now, just -- this number is about double, you know,

almost the prior number we looked at, and that's because this

study looked at moderately emetogenic chemotherapy, whereas

the Phase II study was done for highly emetogenic

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chemotherapy. So we would expect a higher number in this

trial than in the Phase II trial.

Q. Does the data in Table 1 show that 0.25 milligrams of

palonosetron reduces the likelihood of CINV when given to a

human?

A. Yes, it does.

THE COURT: The likelihood --

MR. WONG -- of CINV.

THE COURT: Reduces it, yes.

MR. WONG: Right.

BY MR. WONG:

Q. Okay. And does the study report provide a plan for how

the data was analyzed?

A. Yes, it does.

Q. Let's go to Page 56 of DTX-0288, in the bottom portion

under 5.8.1. Dr. Fruehauf, how was the data analysis

performed?

A. Well, the data analysis was performed according to the

preplanned protocol. So before anybody went on this study, it

was determined that this is what they would do. And then now

the study is done and this is what they did, and they --

Q. How -- go ahead.

A. And they used a SAS software program which is a

statistical analysis package. I used that in graduate school.

I use a little more modern ones today, but the SAS company was

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the most common and widely accepted statistical package for

running analysis, statistical analysis for clinical trials.

Q. Does the analysis plan indicate when the data was closed?

A. It states that the database was closed or locked on 19

December, 2001.

Q. Does the statistical plan indicate when the database was

unblinded?

A. It was unblinded on January 2nd, 2002.

Q. Did you review any initial analysis of the unblinded data

from PALO-99-03?

A. Yes.

Q. And when was the initial analysis performed?

A. January 7th, 2002.

Q. Are you surprised that within a week of the unblinding

dates, preliminary analysis of the data was performed?

A. No. As we discussed earlier, people want to know the

answer. You know, if it's Christmas day and Christmas morning

and you're eight years old and you're looking down under the

tree, there's a package for you, you're not going to just sit

there. You're going to run over there and open it. This was

their first chance to see what were the results of this trial

they've worked so hard to carry out.

Q. Analyzing the unblinded data?

A. Analyzing the unblinded data.

Q. Let's go to DTX-0264. Dr. Fruehauf, do you recognize

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this document?

A. Yes, I do.

Q. What is this document?

A. This is a document, again, August Consulting,

representing Helsinn to -- it's a letter to the FDA, and it's

a request for pre-NDA meeting, and that really means that they

are putting their regulatory package submission in for

licensure for the new drug application, and they're going to

come in with their data to support that licensure.

Q. Okay. And what is the date of this letter?

A. The date of this letter is February 7th, 2002.

Q. Did you rely on this document in forming your opinions in

this case?

A. Yes, sir.

Q. Was there anything attached to the letter?

A. Yes, there was.

Q. Okay. Let's go to Appendix 1, starting on Page 9. And

if we can blow up the entire page on Page 9.

So, what was attached to the letter?

A. So, what we have here is the analysis of the unblinded

data from the SAS output. And if we could blow up the bottom

of the page here, down here, we can see it says, SAS, analysis

tables, printed, 7 January, 2002. So this would be that SAS

output, and then it further states that this is confidential

property of Helsinn Healthcare S.A.

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Q. And what -- based on your experience, what does that

indicate to you?

A. That indicates to me that these data were available for

Helsinn's review on January 7th, 2002.

Q. In your experience, would you have expected that people

at Helsinn would have seen this document on or about January

7th, 2002?

A. In my experience, they would want to see it as soon as

possible, yes.

Q. All right. Let's look at the data on Page 9. So let's

just take the first row. That starts zero to 24 hours. What

does the data look like for the 0.25 milligram dose?

A. The data for the .25 milligram dose in the first column,

under treatment group, shows an 81 percent control, complete

control -- complete response, not complete control, excuse

me -- complete response, 81 percent complete response during

the zero- to 24-hour period.

Q. Okay. If you saw this data on January 7th, 2002, what

would you know about the efficacy of 0.25 milligrams of

palonosetron to reduce the likelihood of CINV?

A. You would know that it did reduce the likelihood of

chemotherapy-induced nausea and vomiting.

Q. And what does the 81 percent indicate again?

A. That 81 percent of the patients did not have nausea or

vomiting during the first 24 hours -- pardon me?

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Q. Go ahead.

A. -- did not have nausea and vomiting in the first 24 hours

after receiving that dose of palonosetron, 30 minutes prior to

their chemotherapy.

Q. Have you compared this initial analysis of the data here

to the analysis of data that was included in the final study

report of PALO-99-03?

A. Yes, I have.

Q. Let's go to Fruehauf 4. Dr. Fruehauf, what is shown on

the top portion of this document?

A. So the top portion of the slide is the SAS output table

from the January 7, 2002, SAS run, you know, analyzing the

data, the unblinded data.

Q. And what is shown on the bottom here, Fruehauf 4?

A. And this was the final report which of course, has the

identical results.

Q. Is it surprising that the identical results in the final

report are identical to the preliminary analysis?

A. They have to be because this was the, you know,

pre-stipulated result of the unblinded data which had been

locked so it can't change.

THE COURT: When was it locked?

THE WITNESS: It was locked before it was unblinded.

BY MR. WONG:

Q. All right. Let's go to Fruehauf 3 again, the timeline.

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And what was the date of the preliminary analysis?

A. January 7th, 2002, which occurred before the critical

date.

Q. How does that inform your opinion overall?

A. That, you know, we have a clear understanding from a

Phase II study that .25 was the minimal effective dose that

was carried forward into Phase III, and in the Phase III

trial, that .25 milligram dose was very effective at reducing

the likelihood of chemotherapy-induced nausea and vomiting in

a prospective randomized trial.

Q. Have you reviewed the other Phase III --

THE COURT: Why do you call it "prospective"? You

used the word.

THE WITNESS: Yes, ma'am. Prospective is you plan it

in advance, and you do what you plan to do, and you can't

change what you plan to do.

BY MR. WONG:

Q. Have you reviewed the other Phase III reports in forming

your opinions?

A. Yes, I have.

Q. Those would be 99-04 and 99-05?

A. Yes, sir.

Q. I don't want to go through all of them, but for the

record, let's just look at DTX-0289 very quickly. Let's go to

Page 2. Dr. Fruehauf, is this the study report for

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PALO-99-04?

A. Yes, sir.

Q. What was the start date of the study?

A. May 3rd, 2000.

Q. What was the finish date of the study?

A. December 27th, 2001.

Q. When was the study report written?

A. July 19, 2002.

Q. Okay. Let's go to DTX-0290, Page 2. Dr. Fruehauf, do

you recognize this document?

A. Yes, I do.

Q. What is this document?

A. This is the PALO-99-05 clinical trial.

Q. When was the 99-05 clinical trial started?

A. First patient in was July 6, 2000.

Q. When was the last-patient-out date?

A. Last patient out was December 31, 2001.

Q. What was the date of the report?

A. The date of the report was August 2nd, 2002.

Q. Okay. Let's go back to the timeline, Fruehauf 3.

Dr. Fruehauf, have you reviewed any documents that --

from Helsinn to the Patent Office that were helpful in forming

your opinions?

A. Yes, I did.

Q. Okay. Let's see DTX-0287, Page 0413. Dr. Fruehauf, is

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this the document from Helsinn to the Patent Office that you

were referring to?

A. Yes, it is.

Q. Let's start at the top. This declaration was submitted

for what patent application number?

A. Patent Application Serial Number 11/129,839.

Q. And what was the title of the patent application?

A. The title was "Palonosetron for the treatment of

chemotherapy-induced emesis."

Q. Was this application for one of the asserted patents in

this case?

A. No.

Q. So why is it relevant to your opinions in this case?

A. Because this patent application states the date that the

declarants say they knew that palonosetron was effective at

reducing the risk of nausea and vomiting and that they knew

that the .25 milligram dose could do that.

Q. Okay. Let's go to Paragraph 4. And who are the people

that -- who are the declarants of this declaration?

A. Riccardo Braglia, Sergio Cantoreggi, and Enrico Braglia.

Q. Let's go to Paragraph 9. Do these paragraphs describe

the role of each of the declarants?

A. Yes, it states here that Enrico Braglia and Riccardo

Braglia worked with Dr. Macciocchi as he developed the

clinical protocol of PALO-99-03, and they participated with

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Dr. Macciocchi in the design --

THE COURT: In the decision.

THE WITNESS: -- in the decision -- thank you,

ma'am -- in the decision to study palonosetron for the

treatment of acute and delayed-onset CINV and worked with him

to fund and implement PALO-99-03.

BY MR. WONG:

Q. Okay. Let's see Paragraph 10 below. What does Paragraph

10 state, Dr. Fruehauf?

A. It states that Sergio Cantoreggi also worked extensively

with PALO-99-03, was familiar with the work reported in

PALO-99-03.

Q. Did the declarants sign this declaration?

A. Yes, they did.

Q. Let's go to the last page, 416. On what date did each of

the three declarants sign this declaration?

A. August 23rd, 2010.

Q. Let's go back to the front, Paragraphs 2 and 3.

Dr. Fruehauf, please read what is stated here in these

paragraphs.

A. Paragraph 2 states, "We submit this declaration to

establish that Alberto Macciocchi, Enrico Braglia, and

Riccardo Braglia had conceived the invention defined by claim

1 of this application, and reduced it to practice, before

November 16, 2001, the date that Dr. Piraccini published

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abstract Number 5169 in Blood, Volume 98, Number 11, Part 2."

Q. Paragraph 3 as well?

A. Paragraph 3 states that "In particular, we submit this

declaration to establish that Alberto Macciocchi, Enrico

Braglia and Riccardo Braglia had conceived the idea to use

palonosetron for the treatment of acute and delayed-onset

CINV, and had conducted clinical trials in humans to test this

idea, at least as early as October 2nd, 2001."

Q. Okay. Let's go to Paragraph 6 and 7. I apologize for

jumping around. What do the declarants attach to this

declaration?

A. They attach the clinical study report for PALO-99-03, and

they state that, "As can be seen from Page 1 of Exhibit A,

Helsinn initiated PALO-99-03 on August 1, 2000, and completed

the study on October 2, 2001."

Q. Was Exhibit A the same PALO-99-03 report that we just

reviewed?

A. Yes, sir.

Q. Let's go down to Paragraph 11. Let's look at the claim

that was pending, and Paragraph 12, as well.

Dr. Fruehauf, what was the claim that was pending at

the time of this declaration?

A. This claim states that "A method of treating chemotherapy

or radiotherapy-induced acute and delayed emesis in an adult

human for five days after an emesis-inducing chemotherapy or

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radiotherapy event, comprising administering to said human a

single dose of a treatment-effective amount of about 0.25

milligrams of palonosetron in the form of palonosetron

hydrochloride prior to said emesis-inducing event, without

administering any further palonosetron during said five-day

period."

Q. And what do the declarants state in Paragraph 12?

A. And in Paragraph 12, they state that "Exhibit A proves

that we had conceived each of the features of this method, and

tested the method in humans, before October 2nd, 2001."

Q. What -- how are these paragraphs significant to you

forming your opinions in this case?

A. Because it indicates that they're saying that they knew

the result, they knew that .25 milligrams was effective to

reduce the risk of chemotherapy-induced nausea and vomiting,

by October 2nd, 2001.

Q. Let's go to Paragraph 17 and 18. What is described here

in Paragraph 17 and 18 of the declaration?

A. This is further supporting their contention, "Thus, we

had conceived the idea to use .25 milligram palonosetron for

the treatment of acute and delayed-onset CINV, as described in

claim 1, at least as early as August 1, 2001," which is the

date that PALO-99-03 began.

And, "Mostly importantly, we had successfully tested

the method in human patients, and we had done so before

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October 2nd, 2001 (the date the study was completed)."

Q. Dr. Fruehauf, in your experience, what does it mean when

someone says, "We have successfully tested the method in human

patients, and we had done so before October 2nd, 2001 (the

date the study was completed)"?

A. In my experience, that would mean that they had some

understanding of the result from the study and that it was

successful.

Q. Okay. Now, as of --

THE COURT: Just a second. They did get the results

of the study but not on October 2nd, right?

THE WITNESS: So they would have --

THE COURT: So what date are you relating to -- so

what date are you relating to your answer here?

THE WITNESS: So this is --

THE COURT: Your answer was that in your experience,

this sentence would mean that these inventors had some

understanding of the result from the study and that it was

successful. But your answer didn't give a date.

THE WITNESS: Before October 2nd, 2001.

BY MR. WONG:

Q. Okay. I can follow up with that. So as of October 2nd,

2001, the last patient out date, the data was still blinded.

Isn't that right?

A. Yes, sir.

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Q. Okay. How could investigators come to the conclusion --

come to any conclusion on the study results when the data is

still blinded?

A. So the data is constantly being reviewed, but it's always

blinded. And in the protocol, it's stated that there were --

there was an ethics committee that was reviewing the data and

constantly analyzing what was happening, so you can know the

blinded data, you can know the percentage of all the patients

who had control of nausea and vomiting, but you wouldn't know

what treatment they were getting.

Q. Okay. Have you prepared some slides to explain this to

the Court?

A. Yes, I have.

Q. Okay. Let's go to --

THE COURT: The ethics committee includes Helsinn

representatives?

THE WITNESS: Usually they're independent, and

Helsinn had hired a German company to be the clinical research

coordinator, and I think they picked an ethics committee. And

it was stated in the protocol that there was this ethics

committee, and they were receiving updates continuously. In

the United States, we call it a Data Safety Monitoring Board.

And we require, you know, I am first since I'm the chairman of

our Data Safety Monitoring Board at UC Irvine. So we're

always looking at any bad things that are happening to make a

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decision, should we stop that study. I mean, if people are

getting really sick and there's not that much benefit, we

should stop it.

BY MR. WONG:

Q. Okay.

THE COURT: But -- wait a minute.

Your -- that ethics board, ethics committee, are they

working in secret, or are they allowed to tell the proponent

of the study how it's going, if no adverse decisions have to

be made?

THE WITNESS: So, in my experience in the United

States, the pharma company will get a letter from the Data

Safety Monitoring Board. The Data Safety Monitoring Board

works in secret. It's confidential. They can actually see

unblinded data, because they can monitor if the drug is

hurting people.

THE COURT: Right.

THE WITNESS: And -- but what we see in our protocols

is updates, where the DSMB sends a letter saying, we reviewed

the safety, we agree the study can proceed. So they're not

revealing anything other than there wasn't futility, because

there is sometimes a futility that's reached where you're

never going to prove the drug works.

That was not in this protocol. There was not a

futility boundary described. But that is the concept that, if

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the drug is hurting people and it's never going to be shown to

be effective, we should just turn it off. So that's one of

the things that Data Safety Monitoring Boards review.

THE COURT: Well, you said two things. You said if

it's hurting people, we definitely need to shut down this

study, right?

THE WITNESS: Yes.

THE COURT: Then you said futility, it is not

working, this thing, we can see from these early results of

the Phase III that nothing's happening to help these patients.

THE WITNESS: That would be the ethical --

THE COURT: That would be futility?

THE WITNESS: Yes. That's the ethical principle that

if it turned out that, you know, it wasn't working and people

were throwing up 90 percent of the time --

THE COURT: No point in putting more of this into

them?

THE WITNESS: Yes, ma'am.

THE COURT: Right?

THE WITNESS: Yes, ma'am.

THE COURT: Or putting more of it into more people?

THE WITNESS: Correct.

THE COURT: So even futility is reported back to the

proponent of this study --

THE WITNESS: Well, they don't --

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THE COURT: -- sometimes?

THE WITNESS: Yeah. If it was -- but, you know,

usually what you're seeing is, because it's all so routine,

everything has pretty much been worked out carefully, you just

get a letter back saying, we reviewed the study and everything

looks good and continue.

MR. WONG: Let me ask a --

THE COURT: Steady as you go, in other words?

THE WITNESS: Yes, ma'am.

BY MR. WONG:

Q. Let me ask this question: As of October 2nd, 2001, the

last patient out date, was blinded data available?

A. Yes.

Q. And could any analysis be performed on that blinded data

as of October 2nd, 2001?

A. In my experience, yes.

Q. Could that analysis give any indication as to whether or

not the drug was working?

A. Broadly, yes.

Q. Okay. Can you explain to the judge how that can be?

Have you prepared some slides?

A. Yes, sir.

Q. Let's go to Fruehauf 5. Okay. What is here in Fruehauf

5?

A. So these are the unblinded data, where we've already

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locked the database and we know who got what.

Q. And what can you -- what would the blinded data look

like?

A. So you wouldn't know that 81, 73. You'd only know if you

added all these up and averaged it, that would be the overall

population control rate. And you could compare that, for

instance, to a historical rate for, let's say, ondansetron.

Q. Okay. And let's go to the next slide. And when you

compare the collected data for all three arms to the

historical control rate, what are the outcomes that could --

that could proceed?

A. There is three possible outcomes. So here would be a

historical comparator like ondansetron that has an expected

control rate, and then the blinded data which would include

the comparator so it would include the two doses of

palonosetron in the comparator. But it would be averaged, and

if that average is low, that means the two drugs, in addition,

were pulling down the benefit rate because they weren't

working so the average is actually less. So the new drug was

less effective than the comparator drug.

Q. What would the second outcome be?

A. The second would be where, in the next slide, we can see

that the blue bar is the same height as the red bar, and it's

equally effective. So when we average everything out, the

comparator drug and the new drug, let's say, were equivalent

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in average to the historical comparator drug.

Q. And what is the third outcome that could happen?

A. And the third one would be where the new drugs are

actually a little better than the comparator, and in the next

slide, what we'll see is that the blue bar is higher because

we're averaging the higher control rate from the new drugs

with the comparator, and that gives us an advantage over just

the comparator by itself.

Q. All right. As of October 2nd, 2001, the last patient out

date, if you did this type of analysis on the blinded data

from PALO-99-03, did you prepare a slide to show what that

would look like?

A. Yes, sir.

Q. Let's go to the next slide.

Can you explain to the Court what the results would be,

what is shown?

A. So, in the protocol, they had actually explained on Page

64 that they had analyzed 7,000 patients who had been treated

with antiemetic therapy and come up with a equation, a

calculation, they could predict what a given patient, given a

certain kind of chemotherapy, low, moderate or highly

emetogenic, what ondansetron would do in terms of control rate

in that setting. And they used a 70 percent historical

efficacy control rate for ondansetron. And they needed to do

that to sort of get a sense of how many people do we need to

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know that the new drug is going to be as good or better than

ondansetron.

And if you average together these numbers which

would -- what would be happening in a blinded setting, the

blinded data is 74.4 percent compared to 70 percent, so, in my

experience, you could reach a conclusion that the

palonosetron .25 and .75 were reducing the risk of nausea and

vomiting and maybe even a little more than the historical

control.

THE COURT: Because they were pushing the

ondansetron-only ratio up?

THE WITNESS: Correct.

THE COURT: They were exceeding the ondansetron-only

ratio?

THE WITNESS: Yes, ma'am.

MR. WONG: Thank you.

BY MR. WONG:

Q. Now, how does that inform your opinions on the statements

made in the Cantoreggi declaration?

A. This supports Cantoreggi's statement.

Q. Thank you.

Let's talk a little bit about the --

THE COURT: Just curiosity. The last patient out is

what, October 2001, in the 03 study?

THE WITNESS: Yes, October 2nd, 2001.

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THE COURT: Right. So all that blind data is there.

It hasn't gone through the cleanup, the quality control?

THE WITNESS: That's correct.

THE COURT: And it certainly hasn't been locked --

THE WITNESS: Yes, ma'am.

THE COURT: -- and then unblinded.

If I'm Helsinn and I wanted to take a peek as of

October 3rd, 2001, just to the 99-03 results, can I do that?

THE WITNESS: This is the only thing you can do.

THE COURT: But I can do that much?

THE WITNESS: Yes.

THE COURT: What you've described here.

THE WITNESS: Because it's blinded so you're not

compromising the data. The last patient's out. You're not

going to change anything.

THE COURT: But you're allowed to see it?

THE WITNESS: Yes.

THE COURT: These gross figures?

THE WITNESS: Yes.

THE COURT: Gross blinded, not cleaned-up figures?

THE WITNESS: In my experience, that's true.

THE COURT: Okay.

MR. WONG: Thank you, Your Honor.

BY MR. WONG:

Q. Let's shift subjects.

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THE COURT: I thought possibly, for example, the

consulting firm who does the -- for example, you're doing the

Phase III clinical trial, Doctor, in your hospital, and you're

doing it for a pharma company. Well, you know, what are they

allowed to see of what you've got and when?

THE WITNESS: So, the CRO has the data.

THE COURT: CRO is the contract research

organization.

THE WITNESS: Yes, ma'am. That's what they'd hired

that, the German company, I can't remember their name, to

collect the data, implement the study, collect the data. So

they had the data. And they could ask for an analysis of

blinded data because that's not precluded by the FDA.

THE COURT: Just a minute. You use the word "they."

Are we talking about the German CRO company or Helsinn, the

customer?

THE WITNESS: Helsinn could ask the German company to

take a -- you know, do an analysis of the overall data. It's

not compromised, it's not unblinded, and the study is done.

THE COURT: Okay.

BY MR. WONG:

Q. And just for the record, could -- as of October 2nd,

2001, could a person of ordinary skill in the clinical

sciences also conduct that same analysis on the blinded data?

A. Yes.

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THE COURT: If they could get ahold of the data?

THE WITNESS: Yes, ma'am.

BY MR. WONG:

Q. Let's talk about the formulations that were actually used

in Phase II and Phase III trials. Have you performed a

comparison of the formulations?

A. Yes.

Q. Let's go to Fruehauf 10. Let's walk through this. What

is listed on the left side of the slide?

A. This is the Phase II formulation for the Phase II trial,

and this is the Phase III formulation for the Phase III trial.

Q. Okay. And what is the active ingredient in each of the

formulations?

A. The active pharmaceutical ingredient is identical,

palonosetron .25 milligrams.

Q. And based on your review of the documents, was 0.25

milligrams of palonosetron administered in the formulations

for both the Phase II study and the Phase III study?

A. Yes.

Q. What -- let's stick with the Phase II formulation. What

are the other components of the Phase II formulations?

A. These are inactive excipients that are just there to

support, as we heard from testimony on Tuesday, just to

maintain the tonicity, a buffer, water, they're inactive.

They have no effect on the intended use.

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Palonosetron is the active ingredient. Once injected

into a person, only palonosetron is going to mediate an effect

to suppress nausea and vomiting. And these other things are

just safe and they just get diluted in the blood.

Q. To be clear, do the inactive excipients, sodium

chloride -- inactive excipients, sodium chloride, dibasic

sodium phosphate, monobasic sodium phosphate --

THE COURT: Counsel, please. Slow down.

MR. WONG: -- water for injection. Thank you, Your

Honor.

BY MR. WONG:

Q. -- water for injection, and NaOH solution, do they affect

the efficacy of the 0.25 milligram dose of palonosetron?

MR. O'MALLEY: Objection, Your Honor. He said he has

no expertise in formulation.

THE COURT: Does it go beyond his report?

MR. WONG: This is right in his report, and if I can

lay a foundation.

THE COURT: Okay. Let's see.

BY MR. WONG:

Q. Dr. Fruehauf, are you a pharmacologist?

A. Yes, my Ph.D. is in pharmacology.

Q. Does a pharmacologist -- would a pharmacologist study the

effects of the drug formulation when it's administered into

the body?

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A. Yes. And, as a clinician, I want to know when I give the

drug to someone that the things that are in that vial aren't

going to do anything to interfere with the drug I'm giving to

the patient. So, as a pharmacologist, I understand why

they're there and what they're doing. As a clinician, I know

they're not interfering with the intended effect of the drug.

Q. And what happens when the Phase II formulation is

actually injected into the patient and into the blood?

A. It's the active ingredient by itself that's mediating the

reduction in risk of nausea and vomiting.

THE COURT: Why do you use the word "mediating"?

THE WITNESS: It's a pharmacology term.

THE COURT: For --

THE WITNESS: It's just -- I'm sorry. You know, it

carries out the effect or it carries out the activity or it

carries the -- it is -- it's the business end. Without that,

that's where the rubber meets the road. The other stuff is

not on the road. Only palonosetron is carrying the car down

the road.

BY MR. WONG:

Q. And would that be the same for the Phase III formulation?

A. Yes, sir.

Q. Do the inactive excipients listed in the Phase III

formulation impact the efficacy of the 0.25 milligram dose of

palonosetron when it is administered to the patient?

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A. No, they do not.

Q. If a person of ordinary skill in the clinical sciences

understood that the Phase II formulation with 0.25 milligrams

was effective for CINV, would that same person -- what would

they understand about the Phase III formulation with that same

0.25 milligram amount?

A. They would expect it to behave in an identical fashion.

Q. Let's go to Fruehauf 11. Let's go back to the '219

patent.

THE COURT: May I just ask a quick question about

this? I don't want to know much about pH. But pH buffering

is something that the formulator always has to keep in mind

and has -- somehow this is -- this multidisciplinary

formulation process has to arrive at an appropriate pH --

THE WITNESS: Yes, ma'am.

THE COURT: -- for the formula that's involved.

THE WITNESS: Yes, ma'am.

THE COURT: Right? And then it's supposed to stay at

that pH while it's in the bottle?

THE WITNESS: Yes, ma'am.

THE COURT: But once it's injected into the body, the

body's pH --

THE WITNESS: Yes.

THE COURT: -- affects that, and we don't think about

it anymore, for purposes of the problems we're talking about

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here.

THE WITNESS: Yes, ma'am.

THE COURT: But the pH in the bottle is important to

the formulation?

THE WITNESS: It's more important to the injection

process, because when it goes into the vein, it's now going to

immediately interact with the cells of the vein.

THE COURT: And the blood inside the vein.

THE WITNESS: And the blood inside the vein. But the

vein cells, the endothelial cells that make up the vein,

they'll react with the excipients, and if the overall pH is

acidic or basic, it would irritate. It wouldn't be balanced

with the cells and the blood.

So you're trying to give a neutral -- the pH in the

body is 7.4. So you're trying to design a solution that would

be 7.4, so when you inject it into the body, it won't irritate

the vein because that would be bad. And, you know, we -- and

then what happens if it leaked out when it was being injected?

Then it's in the tissue. And that can cause an extravasation

is the term for -- extravasation is when things leak out, and

that's a problem.

So you're trying to really have a balanced pH, balanced

pH means around 7.4, so that when it goes into the body, it

won't irritate.

THE COURT: Well, 5 is nowhere near 7.4, is it?

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THE WITNESS: Well, if we go back, I guess we could

look at the formulation. So these --

THE COURT: Phase III is at 5.

THE WITNESS: Right.

THE COURT: Looks like Phase II --

THE WITNESS: This was 7.4. And then they're adding

a sodium hydroxide which is basic and a hydrochloride to reach

a pH of 5.

THE COURT: Excuse me just a minute, Doctor. Is the

Phase II just saline?

THE WITNESS: No. It included a buffer, so the

disodium -- dibasic sodium phosphate and monobasic sodium

phosphate are buffers, in water, and then there was a --

THE COURT: So buffers to address pH?

THE WITNESS: Yes. And then the sodium hydroxide,

hydrochloride are based in acid to give you a final pH of 7.4.

Here --

THE COURT: So it was palonosetron, buffered for the

pH to match the body's pH, and some saline water.

THE WITNESS: Yes.

THE COURT: Is that what it was in --

THE WITNESS: Yes, ma'am.

THE COURT: -- Phase II?

THE WITNESS: Yes, ma'am.

THE COURT: So then we go to Phase III, and there are

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some stabilizers in there, I'm told.

THE WITNESS: Yes. The --

THE COURT: Okay. We won't get to that right now.

THE WITNESS: Right.

THE COURT: But my only question is, we're getting

buffering down to 5.0 --

THE WITNESS: They're bringing the pH --

THE COURT: -- give or take a little bit.

THE WITNESS: Yeah. They're bringing it to 5, which

is somewhat basic, but when it reaches the blood, because that

isn't like acid, it's not like hydrochloric acid, and it's

buffered, it will immediately go to the body pH.

THE COURT: So 5.0 is okay for an intravenous --

THE WITNESS: Yes, it can be.

THE COURT: -- formulation of this? All right.

THE WITNESS: It can be, depending on all the other

things that are there.

THE COURT: All right. Thank you.

MR. WONG: Thank you, Your Honor.

BY MR. WONG:

Q. Let's go to Fruehauf 11, and let's go back to the claims.

THE COURT: It was apropos of when you put this

formula -- Phase III formulated I.V. vial product into the

body, does it have any effect that's different in terms of

therapeutic effect from what was injected into the body in

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Phase II? And my question was, well, does the buffering

change the therapeutic effect at all, I guess?

THE WITNESS: And the purpose for this testimony is

to say that, no, it has no impact on the active ingredient.

But it's very important for other purposes.

THE COURT: Okay.

MR. WONG: Thank you, Your Honor.

BY MR. WONG:

Q. So let's go back to Claim 1 of the '219 patent and this

clinical part of the claim that you opined on.

Dr. Fruehauf, considering all of the evidence we

reviewed today, what is your opinion as to whether it was

known prior to the critical date of January 30th, 2002,

whether 0.25 milligrams was -- of palonosetron was -- could

reduce the likelihood of CINV?

A. I think it would be clear to a person of skill in the

clinical arts, based on the Syntex Phase II study, based on

unblinded data analysis of PALO-99-03 where that output was

January 7th and Cantoreggi's declaration that would

potentially rely on blinded data, that it was clear that

the .25 milligram dose reduced the likelihood of

chemotherapy-induced nausea and vomiting.

Q. Thank you. We're almost done. Let's go back --

THE COURT: Before we get to the next whatever, line

of questioning, I'd like to see counsel at the side for a

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Direct - Fruehauf

United States District Court

Trenton, New Jersey

90

moment on the record.

(The following occurred at sidebar.)

THE COURT: I don't have any earthshaking

pronouncement at all, but the doctor's most recent answer was,

it would be clear to a person skilled in the clinical arts

that this dosage of the drug would be effective before the

critical date.

Now, he started out his testimony saying, well, a POSA

for this drug would be a formulator, not a clinical guy. And

now the question is being asked as if the POSA is a clinical

guy. And so I'm wondering whether -- I'm not saying that

either the pending question or answer was improper. I'm just

wondering whether at some point, if I'm being asked to define

the POSA for purposes of this overall patent dispute, that the

POSA for formulating the excipients that go into the drug

might be a different POSA from a POSA evaluating the efficacy,

potential efficacy of the active pharmaceutical ingredient in

the formulation. And I leave that for you to think about.

MR. LOMBARDI: Just as a preview, Your Honor, we

won't discuss it here, but this is something that has been

played out through the case and through the definition of

POSA, and the way the parties have dealt with the issue, and

we can describe that for you now or just let things develop,

but you're hitting on a point that is accurate and there is

explanation for how this works.

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Direct - Fruehauf

United States District Court

Trenton, New Jersey

91

THE COURT: I'm taking a dim view of what you're

telling me because in the trial briefs, I think one side or

the other said, well, they say POSA is this, and we don't

think that that's right, but it won't change the result in

this case, so let's move on.

Well, sometimes, the definition of POSA does change the

result in the case. And I just don't want to be blind-sided

way down the road and have some of this testimony -- some of

this testimony elicited by one or both sides, useless to me.

MR. WONG: If I can just add, I don't think there's

any disagreement between the parties that the POSA does

consult with others skilled in art, the POSA

formulator, with others skilled in the art, including those --

including those in the clinical sciences.

THE COURT: A POSA does consult with others of skill

in the art -

MR. WONG: -- including those in clinical sciences.

I don't think the parties dispute that.

MR. O'MALLEY: There is a dramatic disagreement among

the parties regarding the POSA.

THE COURT: Okay, wait. We can't air this now. But

before we let go of this witness or maybe even before we do

cross, we are going to have to air it. So let's get through

the direct, and then we'll have this discussion as best we

can. And we won't have our experts in the room.

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Direct - Fruehauf

United States District Court

Trenton, New Jersey

92

MR. WONG: Okay.

THE COURT: And then I'll see where we go from here.

MR. WONG: Thank you. Five more minutes, at most.

THE COURT: No, no hurry. I'm glad that we at least

are focused now.

MR. WONG: Thank you, Your Honor.

(Sidebar concluded.)

BY MR. WONG:

Q. Thank you.

Let's go back to the '219 patent, Page 1. Now,

Dr. Fruehauf, do you have an understanding that plaintiffs'

experts disagree with your opinion as to when it was known

that palonosetron would reduce the likelihood of CINV?

A. Yes, I do.

Q. And what is your understanding of what plaintiffs'

experts say?

A. Dr. Saab, who is a plaintiffs' expert, has said that he

believes that you need two prospective randomized blinded

trials.

THE COURT: Can you raise your voice just a little

bit? Yeah, good.

THE WITNESS: Dr. Saab has stated that you would need

two prospective randomized trials such as the Phase III trial

here, two of those, to know that the dose reduced the

likelihood of nausea and vomiting.

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Direct - Fruehauf

United States District Court

Trenton, New Jersey

93

THE COURT: The .25 dose?

THE WITNESS: The .25 dose reduced the risk or

likelihood of nausea and vomiting from chemotherapy.

BY MR. WONG:

Q. And what is your opinion as to the standard Dr. Saab is

applying to this inquiry?

A. I disagree because I think that one -- the FDA criteria

and the Patent Office criteria are two different things. And

I think a person of skill in the clinical sciences looks at

these data and says, gosh, even just the Phase II study tells

me that the .25 dose reduces the risk of nausea and vomiting,

and then it's confirmed in the Phase III study that's

prospective blind -- double-blinded and randomized. And, I

mean, on the strength of those two studies alone, I think that

it's clear that the .25 dose was effective at reducing the

likelihood of cancer chemotherapy-induced nausea and vomiting.

Q. Thank you.

Now, when was the data from all three clinical reports,

all three clinical trials, when was that data completed and

fully analyzed?

A. Sometime around August of 2002.

Q. And when was the '219 patent filed?

A. I believe it was January 30, 2003.

Q. So at the time Helsinn filed the patent, did Helsinn have

the multiple Phase III clinical trial data that Dr. Saab is

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Direct - Fruehauf

United States District Court

Trenton, New Jersey

94

requiring?

A. Yes, they would have had the knowledge of all three Phase

III studies, 99-03, 99-04, and 99-05.

THE COURT: As of January 30, 2003, when they file

their patent application, is that what you understand, the

question?

THE WITNESS: Before that time, in the summer before

that -- in the summer of 2002, they knew that from those three

trials. Then they filed January 30, 2003.

BY MR. WONG:

Q. Have you reviewed the patent specification for the '219

patent?

A. Yes, I have.

Q. Does the patent specification include any of the

completed and fully analyzed clinical trial data from PALO-03,

PALO-04 or PALO-05?

A. No, it does not.

Q. Does the patent specification include any Phase I or

Phase II clinical trial data?

A. No, it does not.

Q. Does the patent specification include any preclinical

data?

A. No, it does not.

Q. Thank you, Dr. Fruehauf. No more questions.

THE COURT: So, at this point, you may step down.

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Direct - Fruehauf

United States District Court

Trenton, New Jersey

95

We're not finished with your testimony, but we're going to

take a recess now, and I'll have a discussion with the lawyers

before you're called back to the stand.

THE WITNESS: Okay. Yes, ma'am.

THE COURT: Okay. Thank you. Watch your step,

please.

(Witness left the stand.)

THE COURT: Can I see you back at the side, counsel,

on the record.

(The following occurred at sidebar.)

THE COURT: It's 10 of 12, and it's time for a

recess. It's time for us to get some food in us, even though

it's not like 12:30 or 1 yet. Off the record.

(Discussion held off the record.)

THE COURT: We are going to take a recess now. But

when we come back after the recess, I think we need to have

some oral argument directed to the issues, whatever they are,

concerning the definition of the POSA. As I suggested, that

there might be a problem that we need to address, at least

preliminarily now, before we continue with the testimony of

this first expert. Okay?

MR. WONG: Okay.

THE COURT: So I would like to see you back at --

could we make it 1:00? Take a little extra long lunch? Will

that work?

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Colloquy

United States District Court

Trenton, New Jersey

96

RESPONSE: Yeah.

THE COURT: Okay. This won't be final argument, but

I just need to know where we're going with this. Thank you.

(Sidebar concluded.)

(Luncheon recess taken.)

THE COURT: Fine. Let's have whatever discussion

necessary before we proceed with the testimony, and if it is

appropriate, I think we should exclude our witnesses.

MR. O'MALLEY: We have done so, your Honor.

THE COURT: Okay.

MR. LOMBARDI: Both sides, your Honor.

Your Honor, I'll just start. I understood your

question was on the definition of the person of ordinary skill

in the art, and I don't think that there's really much of a

dispute among the parties.

I'll give you kind of the general statement, and then

I'll come back and show you specifics, but to give you the

general idea, incorporated into both parties' definition of

the person of ordinary skill in the art here is the idea that

it is a person who is part of a team that -- that works for

the formulation of a pharmaceutical compound.

And incorporated into both parties' definition is the

idea that this person would collaborate with others of

different expertises. And, so, the way both parties have

approached this is that a person of ordinary skill in the art

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Colloquy

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Trenton, New Jersey

97

is, in our case, we say a formulator who would have access to

people in other areas, for instance, clinicians -- excuse me;

I apologize, your Honor -- clinicians like Dr. Fruehauf to get

information and to inform them in their evaluation of what has

gone on.

And, so, that is what you see in the briefs.

DJ, if you could...

This is from our trial brief. Under level of ordinary

skill in the art, Page 20. And we note that the

patents-in-suit relate to the field of intravenous

formulations of 5-HT3 receptor antagonists, which your Honor

has heard a lot about. "A POSA in that field is a formulator

with a Ph.D. in pharmaceutical sciences, pharmaceutical

chemistry, or a similar field involving pharmaceutical

formulations."

And then this is the collaboration language: "The POSA

would collaborate with persons of ordinary skill in the

clinical sciences, for example, Ph.D. pharmacologists or

practicing medical doctors with respect to issues regarding

clinical safety and dose." So, there's the concept of the

clinician, and that's the role that Dr. Fruehauf, obviously,

is playing here.

Now, plaintiffs, it is a slightly different definition,

but in this respect I believe is essentially identical. I'll

show you this is from plaintiffs' trial brief in the section

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Colloquy

United States District Court

Trenton, New Jersey

98

under obviousness, but this is where they talk about the

definition of POSA.

THE COURT: Page what?

MR. LOMBARDI: It is Page 11. And, obviously, your

Honor, the definition of POSA is the same for the entire case.

It is the same for a patent. You have one POSA is the

appropriate definition for POSA for that patent, and whatever

issue comes up, the definition of a POSA stays the same.

If you had two dramatically different patents involving

different expertise, you could have different POSAs, but for

our case, there's just one POSA. And here's what they say the

definition should be: "A person actively involved in the

development of pharmaceutical products which involves a number

of disciplines and requires collaborative teamwork amongst

persons with relevant" expertise --

THE COURT: Experience.

MR. LOMBARDI: I'm sorry. -- "experience in

designing and developing pharmaceutical drug product

formulations that meet all regulatory requirements. As such,

a POSA could have a degree in chemistry, pharmaceutical

chemistry, pharmacy, medicine, clinical pharmacology, or

another pharmaceutical science-related field and experience in

designing, developing, evaluating, and/or testing

pharmaceutical formulations." And then they talk about our

definition.

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Colloquy

United States District Court

Trenton, New Jersey

99

Defendants' definition is similar, but it's limited to

a formulator that collaborates with such medical

professionals. Because the asserted claims are directed to,

inter alia, treating emesis, however, a composite POSA

definition that includes clinical expertise is appropriate to

resolve the parties' obviousness dispute.

So, both parties talk about this idea that it's a team

in which -- and as you see, we have different definitions

about who the precise individual would be, but that individual

would have access to others that were part of the team and

would rely on others' expertise in their areas of expertise.

So, that's what -- that's what the definition of POSA

is for purposes of this case, your Honor.

THE COURT: Would you excuse me? I'll be right back.

MR. LOMBARDI: Yes.

THE COURT: Right back.

(Brief recess.)

THE COURT: Okay. I'm looking at the one opinion,

the one substantive opinion that we have filed in this case,

which, as you know, had to do with the preamble language and

whether it was limiting or not, and I didn't have to get into

what a POSA was in that opinion.

But in the related case, you call it 502 -- 505(b)(2)

case, Docket Number 12-2867 at Pages -- internal Pages 21 to

23 we picked up a POSA definition that defendants' expert Dr.

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Colloquy

United States District Court

Trenton, New Jersey

100

Kibbe had supplied, and we had understood there was no dispute

about it at that time.

So, with that, I'll hear from you, Mr. O'Malley.

MR. O'MALLEY: Sure.

Going to the claim construction decision you just cited

to, our position was that the POSA dispute had no effect on

your claim construction decision, and that's as far as we went

on that and, truly, it didn't.

In this case, it's teed up, and while it may read

similarly in some fashion, there's a meaningful difference

between the two definitions.

As Mr. Lombardi indicated, our person of ordinary skill

is a person actively involved in the development of a

pharmaceutical product, which involves a number of

disciplines, including clinicians. Their definition is a

pharmaceutical formulator.

Now, that person works with persons in other

disciplines, but I'm not aware of any decision that supported

the invalidity of a patent based on how a work colleague would

have interpreted the prior art to a POSA. And that's

essentially the proofs you're going to be getting here.

That's the proofs you got this morning.

Dr. Fruehauf doesn't claim to be a formulator, and he

didn't interpret anything from the perspective of their POSA.

Now, what is this all about? It goes back to framing

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Colloquy

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Trenton, New Jersey

101

the obviousness question. If you believe -- and you have

already ruled, so it's curious that our opponent seems to

still be in denial -- but if you acknowledge that this

invention is about the treatment of emesis, which you've ruled

is a meaningful claim limitation, then framing the obviousness

question goes back to what would a POSA, including this

clinician looking for a better treatment for emesis, where

would he have started?

And if -- they have a problem with that because of all

the facts we've alluded to in our opening, the NK-1s coming on

the scene, et cetera, et cetera, et cetera. So, to try and

push that aside they say, well, it is a formulator. And all

he is going to be concerned about is making a more stable

formulation of palonosetron. Everything else about what you

pick as the active ingredient and so on, all that's out of his

bailiwick. So, it's an attempt to sweep that more meaningful

issue regarding the preamble language to the side.

Now, where that leaves them, though, I believe, is

between a rock and a hard place. All the testimony you heard

this morning and testimony you're going to hear about what one

of ordinary skill would have done to pick a dose with respect

to the dose limitation in our claims, either you're going to

hear irrelevant testimony of what the POSA's work colleague

would have done -- this clinician, not the POSA -- or you'll

hear testimony from a formulator who never picks doses.

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Colloquy

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Trenton, New Jersey

102

Either way, legally irrelevant.

So, I would submit it's a rather fundamental and

important disagreement between the parties with respect to the

POSA standard.

MR. LOMBARDI: And I don't know if you want to hear

more about the legal consequences of this, but I do think it's

very interesting to hear Mr. O'Malley articulate this. I

don't think it's been articulated before, but I look forward

to briefing this, because I think this shows why Mr. O'Malley

can't have it both ways.

He wants, for purposes of claim construction, to make

this an FDA-approved product. You have to have an

FDA-approved product as part of it, but he wants it, also, to

involve just a formulator because that's who he put on the

witness stand was a formulator, was -- you heard from -- we

just talked to him for two days -- Calderari, I'm sorry, was a

formulator. But, anyhow, I can talk about what I believe are

just rank inconsistencies in what --

THE COURT: He came along here as a fact witness.

MR. LOMBARDI: He did. But, your Honor, I would say

what happened at Helsinn is indicative of exactly what both

parties have said is going on with a person of skill in the

art.

He was a chemist, a formulator, who dealt with others.

He dealt with clinicians. He dealt with other scientists in

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Colloquy

United States District Court

Trenton, New Jersey

103

informing his opinions on what he was going to do.

Now, I think you say that by analogy. I think that is

similar to the situation in the real world with formulation

and clinical approvals. You have teams. They deal together.

They interact together.

So, somebody like Dr. Fruehauf could be talking to

somebody like Dr. Calderari -- I can't believe I'm having

trouble with that name already, Judge. I apologize.

THE COURT: It's going to get worse.

MR. LOMBARDI: I think it probably will be.

But you would have people like Dr. Fruehauf talking to

chemical formulators. That's the way it works. I'm not aware

of any case that says that you can't have that kind of POSA

definition. In fact, we've seen it in other cases, and, your

Honor, you probably referenced it in the DRL, the related

case. I think your definition of POSA that you adopted there

did make reference to the collaboration.

THE COURT: It was yours.

MR. LOMBARDI: Yes. Well, not mine. We weren't

there, but DRL's. But it is included in the definition.

But the bottom line here is that a POSA includes this

collaborative effort. And, so, the collaborative effort means

that a formulator would be -- talk to a clinician about what

the meaning of the trials meant. The clinician would be

talking to the formulator about stability issues --

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Colloquy

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Trenton, New Jersey

104

THE COURT: You're repeating, I know.

MR. LOMBARDI: Okay. So, I'm sorry. I'll stop. And

I will save for later what I think are very problematic

inconsistencies in plaintiffs' position, but that I think is

probably better dealt with on briefing.

THE COURT: I'm not going to rule on it right now

anyway.

MR. LOMBARDI: Okay. But that, I think, that's our

position.

THE COURT: I see.

MR. O'MALLEY: I just want to correct something Mr.

Lombardi said. He said, well, we put a formulator up; but

letting aside your accurate observation, he was a fact

witness, the difference is our definition is broader. It

includes anyone involved in the development of pharmaceutical

products, a multidisciplinary team. That's the only -- that's

the only POSA who can develop a new drug product.

You need a formulator. You need a clinician. Dr.

Fruehauf is a person of ordinary skill under our definition.

He is not under theirs. So, there's no contradiction. Our

definition is simply broader.

And, again, it gets back to the point of the preamble

and is it meaningful? And if it's meaningful, how in the

world is a formulator alone going to develop this new

treatment for emesis?

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Colloquy

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105

MR. LOMBARDI: And, your Honor --

THE COURT: No.

MR. LOMBARDI: No?

THE COURT: No.

MR. LOMBARDI: Okay.

THE COURT: Okay. From there.

MR. LOMBARDI: Okay. From there.

We are not trying to pigeonhole this into just a

formulator. As counsel knows, we are calling -- he referenced

specifically the obviousness inquiry. You'll hear from a

formulator, and you'll also hear from a clinician on our side

on obviousness.

And on the preamble, we are not ignoring the preamble

at all. We're trying to keep -- we understand exactly what

your Honor's ruling was, and we're conforming to that ruling

and we're making our proofs conform to that ruling.

What we're objecting to, as I think your Honor has

probably picked up, is the idea that that ruling indicates

that FDA approval is somehow incorporated into the claim terms

of the patent, which we say there's absolutely no support for.

And that's our position.

THE COURT: Okay. This has been a useful discussion.

I don't have any trouble hearing, so far, the expert testimony

that I've heard couched in terms of whoever is speaking within

the range of their expertise. Later we'll figure out who this

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Fruehauf - Cross

United States District Court

Trenton, New Jersey

106

hypothetical construct person of ordinary skill regarding

these patents is, and I don't think that we are losing the

benefit of going forward with testimony now with each of these

experts.

If they render an opinion as they do from the

standpoint of a POSA, you can incorporate your definition of

POSA and have it in front of them, and I will understand that

they are speaking from the definition of POSA that the party

bringing the witness is proposing. I think that's the best I

can do right now.

MR. O'MALLEY: Thank you.

THE COURT: Okay. So, you can put it on an index

card. Put it up here with your expert, and you can state for

the record at that time that you're incorporating by reference

your proposed definition.

Will that at least get us moving forward?

MR. LOMBARDI: No problem from our point of view.

MR. O'MALLEY: Yes, your Honor.

THE COURT: Okay. Good.

MR. LOMBARDI: Should we bring the witness back into

the room, your Honor?

THE COURT: Sure.

MR. LOMBARDI: Okay.

MR. O'MALLEY: I have a book of exhibits for the

witness.

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Fruehauf - Cross

United States District Court

Trenton, New Jersey

107

THE COURT: Okay. Fine.

MR. O'MALLEY: And the exhibits we use will be in the

books, but they'll also appear on the screen, whichever is

easier.

THE WITNESS: Okay. Thank you.

I can do that. Thank you so much.

CROSS-EXAMINATION BY MR. O'MALLEY:

Q. Dr. Fruehauf, you've been retained by Teva in this case

to offer opinions as to how a person of ordinary skill in the

art in clinical sciences would have interpreted various

information; is that correct?

A. Yes, sir.

Q. Now, Dr. Fruehauf, you finished your fellowship in

oncology in 1992; is that correct?

A. Yes, sir.

Q. And since 1992, you've been at UC, Irvine where you've

been involved in laboratory and clinical research; is that

correct?

A. Approximately.

Q. In the two decades since then, you've only been involved

in one clinical trial, I believe you told me, involving

antiemetics; is that correct?

A. Yes.

Q. And that clinical trial, I believe you testified, was so

long ago you do not remember the details; is that correct?

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A. True.

Q. But, in any event, that antiemetic trial did not result

in an FDA-approved drug; correct?

A. No, it did not.

Q. And in the two decades that you've been at UC, Irvine,

you've only worked on two or three trials that resulted in

FDA-approved methods of treatment, correct?

A. Yes.

Q. And those trials did not involve antiemetics, correct?

A. No.

THE COURT: Correct? Yes?

BY MR. O'MALLEY:

Q. No, it's not correct?

A. No, they did not involve antiemetics.

Q. Okay. Thank you.

In fact, the emphasis of your research efforts has not

been on research or clinical trials that will get a drug

approved, correct?

A. No, that's not correct.

Q. So, you say that the emphasis isn't so much to work on a

drug that will get approved --

THE COURT: You're talking emphasis? Emphasis.

BY MR. O'MALLEY:

Q. Emphasis.

So, it's your testimony today that the emphasis of your

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research hasn't been so much to work on a drug that will be

approved because that's what big companies do. That's not

your testimony today?

A. I don't think I gave that testimony today. I'm happy to

try and --

Q. Is that accurate? Yes or no?

A. No.

Q. Okay. Let me show you your deposition transcript.

A. Thank you.

MR. O'MALLEY: And, Roy, if you can give me Page 18,

Line 24 to 20, Line 6.

BY MR. O'MALLEY:

Q. Okay. So, the question was: "It could be participation

in Phase II trials that eventually lead to an approved method

of treatment by the FDA. So, with that understanding, are

there any others beyond the Votrient®" -- and you understand

the context was regarding clinical trials that lead to an

FDA-approved method of treatment; you understand the context

of that question?

A. Yes, sir.

Q. And then I'll read the full answer for the sake of the

record: "Well, I guess the GOG trial on Avastin®, that was

the Phase II study of Avastin®. I participated in the

translational endpoints for evaluating markers that would

predict response to Avastin® in ovarian cancer and then

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subsequently, it has been approved now for ovarian cancer.

I'm, you know, working on the biomarkers for cervical cancer.

It was just approved for cervical cancer, and I'm

participating in an R21 grant study on markers linked to

treatment response in cervical cancer.

"But the emphasis for investigators in the university

setting at a comprehensive cancer center where I am, the

emphasis is not to do the pharmaceutical company trials as

much as it is to develop your own trials and do your own

investigations because the NCI values that. And when you

receive the large grant from the NCI -- there's 30, 31

comprehensive cancer centers in the United States -- and, so,

to maintain our standing and our grant, the emphasis for our

faculty who do investigational clinical trials is to do

hypothesis-driven investigational trials rather than the large

pharmaceutical trials or to do cooperative group trials.

So, the emphasis isn't so much to work on a drug that

will get approved because that's what big companies do."

Did I read that correctly?

THE COURT: Read the last sentence. You misread it.

BY MR. O'MALLEY:

Q. Oh, I'm sorry.

"So, the emphasis isn't so much to work on a drug that

will get approved because that's what big drug companies do."

Did I read that correctly?

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A. You read that correctly.

THE COURT: Sir, Doctor, what does NCI stand for

there?

THE WITNESS: National Cancer Institute.

THE COURT: And that's where the grants come from?

These grants you're talking about here.

THE WITNESS: These grants come from the National

Cancer Institute, and so for promotion in the cancer center

program, we're asked to do, to come up with our own ideas for

clinical trials; but we still have to do all of the other

Phase III trials that we're involved in. So the emphasis

academically is what I was talking about.

THE COURT: Okay. Let me ask the questions.

THE WITNESS: Oh, I'm sorry.

THE COURT: I was just looking for what the

abbreviation was.

THE WITNESS: Yes, ma'am.

BY MR. O'MALLEY:

Q. So the emphasis of your research efforts has not been on

selection of an efficacious dose for a drug to obtain FDA

approval, correct?

A. No, that's not correct.

Q. Well, in fact, you've never been personally involved in

the selection of a specific dosage of a drug in a treatment

that was eventually approved by the FDA, correct?

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A. And you asked me that during my deposition, and I was

explaining that as clinicians, we are involved --

Q. Sir, can you answer that yes or no? It is a simple

yes-or-no question.

A. Okay. I wouldn't be the only one involved in choosing

the dose, that's correct.

Q. No, the question is: In fact, you've never been

personally involved in the selection of a specific dosage of a

drug in a treatment that was eventually approved by the FDA,

correct?

A. I'll say yes.

Q. Yes, you've never been personally involved?

I'm just trying to see what your "yes" is. Is that --

did I interpret that correctly?

A. Well, it depends on the definition of "personally

involved", but --

Q. Is that what you meant by your "yes"? That's simply the

question.

A. Yes, that's what I meant by my yes.

Q. Okay. Thank you.

Now, have you ever done a formal pharmacology research

fellowship?

A. My Ph.D. is in pharmacology. There's no fellowship

associated with that.

Q. You've never done a formal pharmacology research

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fellowship; correct?

THE COURT: Is there such a thing? Are you assuming

there is such a thing?

MR. O'MALLEY: I know there to be such a thing, your

Honor.

THE WITNESS: I did receive a fellowship grant during

my Ph.D. in pharmacology at Rush.

BY MR. O'MALLEY:

Q. Was that what you would consider a formal pharmacology

research fellowship?

A. Research fellowship, yes.

Q. Are you associated with the American Society of Clinical

Pharmacology and Therapeutics?

A. Not at this time.

Q. Are you associated with the American College of Clinical

Pharmacology?

A. No.

Q. Are you board certified in clinical pharmacology?

A. No.

Q. Now, I believe you testified that you're not a

pharmaceutical formulator, correct?

A. Correct.

Q. And you understand Teva's definition of a person of

ordinary skill, correct?

A. I'm not sure at this time.

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Q. Do you understand that it's a pharmaceutical formulator?

A. I believe that's true.

Q. And that's not you, correct?

A. Correct.

Q. However, because the '219 patent involves a method of

treating CINV with a specific dosage of palonosetron --

THE COURT: It's actually a compound, not a method

patent, counsel, right?

MR. O'MALLEY: Okay.

THE COURT: A composition patent?

BY MR. O'MALLEY:

Q. Okay. However, because the '219 patent has a preamble

involving treatment of CINV with a specific dosage of

palonosetron, then evaluating that limitation of the patent

claims would bring in the experience of a clinician, right?

A. Yes, sir.

Q. Now, you gave an opinion as to written description. Do

you understand what I mean by "written description"?

THE COURT: In your expert report, not here.

THE WITNESS: Yes.

BY MR. O'MALLEY:

Q. Well, do you understand that the testimony at the end of

your testimony today related to the issue of written

description?

A. I understand that.

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Q. Okay. In fact, you presented opinions that our patent

claims are invalid for lack of written description in your

expert report, correct?

A. Yes, sir.

Q. Now, you signed an expert report in this case on

August 15, 2014; is that correct?

A. I believe that's correct.

Q. And that expert report accurately reflects the opinions

you gave in court earlier today, correct?

A. I believe so.

Q. And do you recall you told me at your deposition that the

opinions set forth in your expert report were developed from

June through August of 2014? Do you recall that?

A. I believe so.

Q. Now, if you could take a look at DTX-1168 previously

marked at your deposition as Deposition Exhibit 4.

MR. O'MALLEY: We're not going to go -- we probably

don't need to go into the substance of this, your Honor, but

it's in the rack if you need it. It is just a couple

questions. Mostly regarding dates and overall content.

BY MR. O'MALLEY:

Q. Do you understand what this document is?

THE COURT: He can read the title. I don't think you

can ask him if he understands what it is.

BY MR. O'MALLEY:

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Q. Well, let me read the title into the record. It's "Teva

Pharmaceutical U.S.A., Inc. and Teva Pharmaceutical

Industries, Limited, Invalidity Contentions Pursuant to

L.Pat.R.3.6(c)."

Do you see that?

A. Yes.

MR. WONG: Objection. Counsel asked the witness the

same question at his deposition, and there's no foundation.

THE COURT: I'll listen.

BY MR. O'MALLEY:

Q. And do you see that this document is dated, and we can go

to -- should be .0128 dated March 17, 2014?

A. Uh-huh.

Q. So, this document was completed prior to the time you

developed your opinions in this case, correct?

A. I believe so. I'm not really sure about all the dates.

Q. Okay. Well, you told me that your opinions were from

June to August, correct? Developed from June to August?

A. It's an approximate -- it's an approximate estimation. I

don't know the exact dates.

Q. But that's what you told me at your sworn deposition.

A. Yes.

Q. And you see this is dated a couple months before that,

correct?

A. Evidently, yes.

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Q. Okay. So, if the dates you told me were accurate at your

deposition, then this document was completed prior to the time

you developed your opinions in this case, correct?

A. Evidently.

Q. And do you recall we looked at DTX-1168.0093 under

heading C?

A. During my deposition?

Q. During your deposition. We'll get there in a moment.

And if you recall, this summarized Teva's opinions

regarding lack of written description. Do you recall

generally us --

A. Yes.

Q. -- discussing that?

A. Yes.

Q. And at your deposition, you agreed that Teva's invalidity

contentions with respect to lack of written description were

roughly the same opinion that you provided in your summary

opinions in your August 15, 2014 report.

Do you recall that?

A. Yes.

Q. Now, you were not involved in reviewing or preparing any

drafts of Teva's invalidity contentions, correct?

A. Not that I know of.

Q. Okay. Now, I'd like to discuss your opinion that you

provided at the end of your testimony this morning regarding

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the conclusion that the '219 claims are invalid for lacking

adequate written description, okay?

A. Uh-huh.

THE COURT: Mr. O'Malley, I do not hear that in Dr.

Fruehauf's testimony here, and expert reports are not

evidentiary. They're not admitted as exhibits.

MR. O'MALLEY: Your Honor, about five, six questions

back, he admitted that that was the gravamen of those opinions

that he offered at the end of the day.

THE COURT: He said he was asked questions about

those, about that topic.

You can elicit an opinion from him if you want, but I'm

sorry, maybe I misheard.

MR. WONG: That's correct, your Honor. I never asked

the witness his overall opinion on the written description

defense.

MR. O'MALLEY: Okay. We will assume that opinion is

not in evidence.

THE COURT: Is that right, Mr. Wong? Not from Dr.

Fruehauf.

MR. WONG: To be clear, I asked him about facts

related to his review of the patent specification. I did not

elicit his overall opinion on the written description defense.

THE COURT: That's right. You didn't.

BY MR. O'MALLEY:

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Q. Okay. Now, let's take a look at the '219 patent, and

let's look at Claim 1 and look at lines -- let's look at the

preamble, and let's start with 4 in the preamble "for

intravenous administration to a human to reduce the likelihood

of cancer chemotherapy-induced nausea and vomiting."

Do you see that?

A. Yes, sir.

Q. Now, first of all, in the U.S. in order to treat a human

with a pharmaceutical formulation to reduce the likelihood of

CINV, that pharmaceutical single-use unit-dose formulation has

to be approved by the FDA, correct?

A. You know, there are natural products that are used for

reducing nausea in patients, like ginger; but if you're

talking about a drug that's for the purpose that's on a

package insert, then, yes, it requires FDA approval.

Q. Now --

THE COURT: And you couldn't get a formulation of

ginger and inject it.

THE WITNESS: People do things like that.

THE COURT: Okay. Never mind.

BY MR. O'MALLEY:

Q. Now, in your opening expert report -- well, let me strike

that.

Today when you were asked about the subject matter of

the '219 patent, you said it relates to a formulation and it

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relates to stability.

Do you recall that testimony?

A. Yes.

Q. And you didn't state that it relates in any manner to

the likely -- to the intravenous administration to a human to

reduce the likelihood of cancer chemotherapy-induced nausea

and vomiting.

Do you recall you didn't discuss that as part of the

subject matter of this patent? Do you recall?

A. No, I did. I said that I believe the patent is based on

a formulation for stability, but there is a component within

the claim, which was determined to be a limitation, where my

being a person in the skill of the clinical sciences impinges

on that component of the first section, which is when you

start to give things to humans -- now we're not talking about

a formulation. Now we're talking about a clinical use and a

claim about reducing nausea and vomiting in people, so --

that's related to chemotherapy.

Q. Now, I just want to make sure I understand. Is your

testimony now that the preamble is part of the subject matter

of the '219 patent?

A. I am not an attorney to make decisions about that.

Q. So, you have no --

A. I'm not a patent attorney.

Q. You have no opinion on that now.

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A. I was just -- no. I was asked to give an opinion as a

person of skill in the art of the clinical sciences, which is

different than a POSA, who's a formulator, to address that

element of the claim which was determined to be a limitation,

that it's used for treating people with chemotherapy-induced

nausea and vomiting. So, they have asked me to come and talk

about that part of the claim.

Q. Now, I'm talking about the question you were asked this

morning to the effect of what is the subject matter of the

'219 patent.

Do you recall that question?

A. Yes.

Q. And do you recall your answer was limited to the

formulation and to stability?

A. I believe --

Q. Do you recall that?

A. That's my opinion.

Q. That's your opinion.

So, this preamble then, therefore, logically is not

part of the subject matter of the patent.

MR. WONG: Objection.

THE COURT: Sustained. He can't be drawn into that

dispute. We've resolved it as a legal matter.

BY MR. O'MALLEY:

Q. Now, in your opening expert report, you state -- you

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stated that nothing in the '219 disclosure relates to reducing

CINV specifically.

Do you recall that?

A. This morning?

Q. In your expert report.

A. In my expert report?

Q. Yeah.

A. I was referring to the fact that there's no clinical data

to support the claim in the body of the patent.

Q. Beyond clinical data, you know or you realize that

there's a number of excerpts of the disclosure that discuss

treatment of CINV specifically without data; do you realize

that?

A. Yes.

Q. Okay. Now, in this afternoon you offered opinions that

discussed the fact that there was no data in the patent

specification.

Do you recall that?

A. I believe that Mr. Wong asked me if I had seen any of the

Phase III clinical trial data anywhere in the patent, and I

answered no.

Q. Okay. Now, you're aware that this hypothetical person of

ordinary skill in the art has all the relevant publicly

available prior art before him or her, correct?

A. I'm not sure what that means.

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Q. You're not -- you don't have any opinion on that one way

or the other?

A. Maybe if you ask the question a different way.

Q. Well --

THE COURT: It depends for what purpose, I would say.

BY MR. O'MALLEY:

Q. Are you aware that the hypothetical person of ordinary

skill in the art for the purpose of interpreting the patent

and the prior art has all the relevant --

THE COURT: And the prior art?

BY MR. O'MALLEY:

Q. -- and the prior art has all the relevantly publicly

available prior art before him or her?

A. This is a question of the public availability?

Q. That was part of the question, yes. Are you aware of

that?

MR. WONG: Objection, Your Honor, to the extent it

goes to a legal issue or a legal conclusion.

THE COURT: He can explore a little bit.

MR. O'MALLEY: Do you understand that?

THE COURT: Well, is your question directed to how

would a person of ordinary skill in the art, looking at a

patent in which they are a person of ordinary skill in the

art, read that patent? How would that person understand that

patent?

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MR. O'MALLEY: Yeah. It is really more general than

that with respect to almost any doctrine in patent law; but

the point is when Dr. Fruehauf and I discussed this at his

deposition, he did have a clear understanding of this

doctrine.

THE COURT: Are we talking about claim

interpretation, or are we talking about obviousness, or are we

talking about on-sale bar?

MR. O'MALLEY: I believe that with respect to all of

those doctrines as a matter of patent law, the POSA is

presumed to have the prior art in front of him and her and

uses that body of knowledge whether it's to interpret what a

claim limitation means, whether to judge whether a claim is

obviousness, et cetera.

THE COURT: Well, sir, at least -- and this is beside

the point of Dr. Fruehauf's knowledge, so give us a second.

THE WITNESS: Yes, ma'am.

THE COURT: At least we know that the POSA looks for

certain questions at a patent. He looks at the patent as of

the date it was applied for.

MR. O'MALLEY: Very true.

THE COURT: You know, and then for this on-sale bar

business, he needs to look at what has been called a critical

date, which is a year before.

And I'm not going to allow Dr. Fruehauf to be

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instructed on whether publicly available information for

purposes of the on-sale bar is all a POSA is assumed to know.

So, if you would like to continue to inquire, please feel free

to do so, but make your question clear to him.

MR. O'MALLEY: Sure.

BY MR. O'MALLEY:

Q. Now, let me build on the judge's observation.

With respect to the notion -- you've reviewed -- let me

back up -- Dr. Saab's and Dr. Peck's report.

A. Yes.

Q. And you have reviewed their opinions relating to whether

a person of ordinary skill reviewing the patent description

and disclosure as of the date the patent was filed would

believe the inventors to be in possession of the invention.

Do you recall that?

A. Yes.

Q. And, so, you're aware that the focus on that analysis is

on the date the patent application is filed, correct?

A. Yes.

Q. Okay. Now, with respect to this -- you've also seen

testimony relating to whether the patent-in-suit was on sale;

is that correct?

A. Yes.

THE COURT: Opinions, you mean.

MR. O'MALLEY: Opinions.

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BY MR. O'MALLEY:

Q. And you're aware that focus for that analysis is one year

prior to the patent application date, correct?

A. I believe I heard testimony to that effect on Tuesday.

Q. Okay. Now, in terms of our case, you're aware that some

significant information enters the public domain regarding the

status of Helsinn's development efforts in that one-year

period between the critical date and the filing dates of the

patents, correct?

A. I'm not sure what information you're speaking of that

reached the public domain.

Q. Sure. Let's turn to PTX-0297.

And, again, it's in your -- it's in your notebook. You

can look at as much as you like. And you've seen that

document before?

A. I don't recall.

Q. Why don't we turn to the conclusion section at the bottom

of the chart.

Do you recall us reviewing this publication at your

deposition?

A. I don't recall, but I'll accept your assertion.

Q. Okay. And you see the date of this publication if we go

back to the first page, June 23 to 26, 2002.

Do you see that?

A. Yes, yes.

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THE COURT: Is this a paper presented at that

meeting, conference?

MR. O'MALLEY: Well, perhaps I should ask the

question.

BY MR. O'MALLEY:

Q. You understand this to be an abstract?

A. It says "oral presentation."

Q. Okay. And what form of publication is this, to your

understanding?

A. I guess the -- there may be a journal of the

Multi-National Association of Supportive Care In Cancer.

Q. Okay.

A. Usually they will publish a proceedings for their

journal, which would include abstracts from the national

meeting. And while the oral presentation is not included in

the publication, the abstract is included in the publication.

Q. And you understand that an abstract like this would be

publicly available in this case prior to the filing date of

the '219 patent?

A. Yes, sir.

Q. Okay. And then if we look at the conclusions -- well,

first of all, if we blow up the box above the conclusions.

Now, you recall or perhaps you now note that this MASCC

abstract reports some Phase III clinical data for palonosetron

with respect to CINV?

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A. These data look to me to be from 99-04.

Q. Okay. And you understand that to be Phase III clinical

data for palonosetron with respect to treatment of CINV.

A. Yes.

Q. And you see that there is some treatment rate reported

there?

A. Yes.

Q. And for the .25, the acute response is 63 percent.

Do you see that?

A. The -- that would be the complete response in the acute

phase.

Q. Yes.

A. Of 63 percent control.

Q. Right. And there is data for complete response in the

delayed phase, 24 to 120 hours.

Do you see that?

A. Yes, sir.

Q. And for .25 milligrams, there's a response rate report of

54 percent?

A. Yes.

Q. And do you see that --

THE COURT: The comparator is different in that 04

Phase III study, isn't it?

THE WITNESS: It was dolasetron here, and it was

dolasetron was --

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THE COURT: At 100 milligrams.

THE WITNESS: At 100 milligrams.

THE COURT: Okay. Fine.

THE WITNESS: So it's a setron that was less potent

than ondansetron.

BY MR. O'MALLEY:

Q. Now, if we go to the conclusion, it states, "Palonosetron

has demonstrated significant activity in preventing both acute

and delayed emesis with a single I.V. dose. In patients

receiving moderately emetogenic chemotherapy, palonosetron was

safe and well tolerated."

Do you see that?

A. Yes, I do.

Q. And you agree that the data supports that conclusion,

correct?

A. Yes.

Q. Now, in your opening report, you stated -- and if you

don't recall this, we'll put it in front of you -- "Phase II

trials are designed to assess and establish an indication of

clinical efficacy of the drug compound for treating particular

disease conditions or symptoms," correct?

A. I'm not sure if those are the exact words, but --

Q. Well, why don't we pull up DTX-1179-0010, Paragraph 23.

And we've highlighted the words, and let me just read that

into the record, and I'll finish the sentence for

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completeness: "Phase II trials are designed to assess and

establish an indication of clinical efficacy of the drug

compound for treating particular disease conditions or

symptoms, and includes finding the minimum effective dose of

the drug."

Do you see that?

A. Yes, sir.

Q. And you were in the courtroom when Dr. Calderari

testified?

A. Yes.

Q. And you heard that he called it -- he referred to it as a

signal of efficacy.

Do you recall that?

A. Yes. That's a pharma -- pharmaceutical company jargon.

Q. Okay. And indication of clinical efficacy, does that

mean something different than Dr. Calderari's signal? I

believe in your direct testimony, you likened the two terms.

A. I agree.

Q. Okay. Now, you provided some opinions regarding 2330,

the Helsinn's -- well, Syntex's Phase II study, correct?

A. Yes.

Q. And Study 2330 reported data as you noted for a

3-microgram-per-kilogram dose, correct?

A. Yes.

Q. And that corresponds to roughly a .21-milligram total

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dose; is that correct?

A. Yes. I think that we were sort of rounding it to the

.25.

Q. Fine. I'm making no distinction.

The study also reported data on other doses, correct?

A. Yes, it did.

Q. There was the .3- to 1-microgram-per-kilogram dose,

correct?

A. Well, those were separate doses, but those doses were

combined into one category.

Q. Right.

A. So, there's that one category of the lower doses combined

together.

Q. And those lower doses combined together were considered

the control in the study.

Do you understand that?

A. I believe that was the intent.

Q. Okay. And then there was a number of other doses,

1 microgram per kilogram, correct?

A. Point -- it was .3 to 1 was the low dose.

Q. I'm sorry. I didn't mean this to be a memory test. Why

don't we get it up there. DTX-0227-0015.

And let's highlight the summary and conclusions and

down through the chart and footnote.

So, the other doses studied besides what was intended

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to be the control, as you put it, were the 3 microgram per

kilogram, correct?

A. Yes.

Q. The 10 microgram per kilogram?

A. Yes.

Q. The 30 microgram per kilogram, and the 90 microgram per

kilogram?

A. Yes, sir.

Q. Now, if you look at the summary and conclusions, it

concludes that "All four doses were approximately equally

effective as compared with the combined results from a cohort

of .3 and 1 microgram per kilogram."

Do you see that?

A. Yes.

Q. And that phrase "cohort" is -- refers to what you mean

they combine the data from doses in that range?

A. Yes, sir.

Q. Okay. And then it has the table.

Now, underneath the table, there is an indication of an

asterisk and with respect to statistically significant

differences p less than .05 versus lowest dose group.

Do you see that?

A. Yes, I do.

Q. And you provided a brief explanation of what this -- what

do we call the p-value in statistics, again?

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A. The probability that an event could occur by chance

alone.

Q. Right. And this -- this designation under the chart that

regarded statistically significant differences is only those

differences that had a P less than .05. That's rather

standard in the pharmaceutical industry. You know that?

A. Yes, it's an arbitrary choice.

Q. But it's standard, correct?

A. It -- it is a standard.

Q. Yes.

Now, with respect to the results for complete control

after 23 -- 24 hours, rather, you see there's a value of 24

for the cohort of .3 to 1?

Do you see that?

A. Yes.

Q. And do you see the value for 3 microgram per kilogram is

46?

A. Yes.

Q. But you recognize that there's no asterisk next to the

46?

A. Correct.

Q. And according to the authors of this study, that means

there was no statistically significant difference between that

value for complete control at 24 hours and the value for the

cohort, correct?

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A. That is correct from a statistical perspective.

Q. Okay. Now, in fact --

THE COURT: Is there an asterisk on some of those

hour figures down on the bottom row? But not otherwise.

THE WITNESS: Yes, that's right. 22.7 has the

asterisk for the time to failure, so that was statistically

significantly different for the .25 compared to the .3 to 1.

BY MR. O'MALLEY:

Q. Now, in reviewing these clinical trials, you're familiar

with the notion of a primary endpoint.

A. Yes, sir.

Q. And can you explain to the judge what primary endpoint

means?

A. The primary endpoint would be the endpoint around which

you design your trial.

Q. And in this case and in the case of these other clinical

trials you've testified about today, the primary endpoint is

percent complete control, correct?

A. Yes.

Q. Now, with respect to that primary endpoint, the only

value that showed statistically significant difference

compared to the lowest cohort was the value at 30 microgram

per kilogram, correct?

A. Yes.

Q. And that's roughly a 2.1-milligram dose roughly; do you

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agree with that?

A. Yes.

Q. Now, you're aware that in general the FDA will not allow

you to claim an indication if you do not show statistical

significance for an outcome for a primary endpoint in the

study. You're aware of that, correct?

A. Yes.

THE COURT: Could I just interpose one question,

please?

MR. O'MALLEY: Certainly.

THE COURT: Just looking at our column for the

3-microgram dosage, and it says 46 percent --

THE WITNESS: Yes, ma'am.

THE COURT: -- complete control in the first

24 hours. This is 46 percent of the people tested reported

complete control; is that what it's telling us?

THE WITNESS: 46 percent of the people who got the

drug --

THE COURT: Right.

THE WITNESS: -- had complete control compared to

24 percent of the patients who got only .3 to 1, and I had

testified earlier that you can imagine there's people that

would get nothing. There's zero.

THE COURT: Right.

THE WITNESS: But here we're comparing 3 to .3 to 1,

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where there's some benefit from the .3 to 1, and -- but they

combine that data just to have some comparator, but it may

come out later what was actually asked for.

THE COURT: No, the direction of my question was just

that that number, 46, is percentage of patients receiving the

particular drug at that dosage who exhibited or reported

complete control --

THE WITNESS: Yes, ma'am.

THE COURT: -- of their symptoms.

THE WITNESS: Yes, ma'am.

THE COURT: So, no nausea.

THE WITNESS: No nausea and no need for rescue

medication.

THE COURT: Okay. If they were, like, you know,

better, but not greater on the nausea scale, they didn't make

it into the 46 percent, right?

THE WITNESS: Correct. They could have had a

benefit, but it wouldn't have been to the degree that was

required for this analysis.

THE COURT: Okay.

BY MR. O'MALLEY:

Q. Now, you're aware, Dr. Fruehauf, that the FDA concluded

that study 2330 did not establish efficacy, correct?

A. My opinion on that question --

Q. I didn't ask your opinion on that question.

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A. But it has to do with the context of what their decision

was.

Q. Are you aware that the FDA concluded that; yes or no?

A. Eventually, they did conclude that it was.

Q. Eventually they --

A. That's why they allowed it to go to the Phase II -- Phase

III.

Q. Dr. Fruehauf, let me ask my question again. Are you

aware that the FDA concluded that the Study 2330 did not

establish efficacy?

A. There were various communications with the FDA about

whether the .25 dose was correct as being the minimally

effective dose.

Q. Now, let me pull up the transcript at Page 165:17 to

165:5.

"QUESTION: Now, are you aware" --

THE COURT: What transcript are you reading from?

MR. O'MALLEY: Dr. Fruehauf's transcript.

THE COURT: Deposition?

MR. O'MALLEY: Deposition transcript, thank you.

BY MR. O'MALLEY:

Q. And I passed up a copy of that.

"QUESTION: Are you aware that the FDA concluded in

reviewing this data that it could not be used as evidence of

efficacy because of a lack of dose response?

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"ANSWER: You know, I've heard that -- I've seen

that. And I think that, you know, I did work closely with the

FDA when I was at NCI as a fellow and CBER and those people.

I even imagined at one time that I might even work in the FDA.

And, you know, those are human beings, just like the patent

reviewer people are human beings, and they can make mistakes."

Did I read that correctly?

MR. WONG: Objection, Your Honor. That's not

impeachment.

THE COURT: He can ask whether this has been read

correctly, Mr. Wong.

BY MR. O'MALLEY:

Q. Did I read that correctly?

A. That's read correct.

MR. O'MALLEY: Let's pull up PTX-0261, Page 5, and

let's go down to --

THE COURT: Now, what is this?

MR. O'MALLEY: Let's go to the cover page of this.

BY MR. O'MALLEY:

Q. And do you recall that Dr. Calderari presented some

testimony regarding this document during his testimony?

A. Yes, sir.

Q. And do you recall that this was described by him as an

end of Phase II meeting minutes?

A. Yes, sir.

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Q. And that the meeting minutes were prepared by the FDA?

A. Yes, sir.

Q. And the date of this is March 10, 1999.

Do you see that?

A. Yes, sir.

Q. And Dr. Calderari testified that he attended that

meeting, correct?

A. Yes, sir.

Q. Now, if you go down to Page 0005 in Question 6, and you

understand that the format of this document is that the

pharmaceutical company poses certain questions at the meeting

in the minutes with the highlighted bullet points are meant to

summarize the FDA's response to those questions?

A. Yes, sir.

Q. Okay. And in Question 6 Helsinn asked, "Is 2330

sufficient to support the label claim 'including high-dose

Cisplatin' should a historical control analysis be conducted?"

Do you see that?

A. Yes, sir.

Q. And I'll skip down to the bullet: "Due to the lack of a

dose response in this study, these data are inadequate to

serve as pivotal efficacy support (although they may be useful

as supportive data)."

Do you see that?

A. Yes, sir.

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Q. Now, when we discussed this at your deposition, do you

believe -- do you recall telling me that you believed the FDA

was wrong?

A. Well --

Q. Yes or no; do you recall that?

A. Yes.

Q. Okay.

A. But that was in a different context.

Q. I see.

Now, are you aware that Helsinn was asked to reanalyze

Study 2330 by the FDA?

A. Yes.

Q. Now, in discussing why you thought the FDA was wrong in

specific to this conclusion, you testified that "I would think

if they were pharmacologists, they would have come to a

different conclusion or they didn't look at all the data

correctly."

Do you recall providing that testimony?

A. Yes.

Q. And, again, you've never been personally involved in the

selection of a specific dosage of a drug in a treatment that

was eventually approved by the FDA, correct?

A. Yes.

Q. Now, let's look at -- you cited to the August Consulting

letter, DTX-0293. Can we pull that up?

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Do you recall providing testimony about that document

in your --

A. Yes, sir.

Q. -- direct testimony?

A. Yes, sir.

Q. Do you need -- okay. You got some water.

Turning to Page 30 in the document, the last line of

the third paragraph reads -- if we can highlight that, Roy --

"Results achieved in Phase II CINV studies suggest that

palonosetron is safe and effective in preventing nausea and

vomiting following emetogenic chemotherapy, especially during

the 24 hours after administration."

Now, the word "suggest" as you interpret it from your

POSA in the clinical sciences standpoint, is that the same

thing, does that have the same meaning as "signal" or

"indication" as we discussed before, suggestion?

A. It has the meaning of probability from the standpoint of

that it's likely to reduce the risk, and likely to reduce the

risk is not a statistical assertion, so likely to reduce the

risk/suggest go together, likely and suggest.

Q. Now, looking further down to the last line of the page,

it states that "This study is designed to support the

hypotheses that palonosetron is not inferior to currently

available 5-HT3 receptor antagonists and is effective in

preventing nausea and vomiting following moderately emetogenic

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chemotherapy."

The study they're referring to, again, is Study 2330.

Do you understand that?

A. They've referred to it in the past tense already. It

said, "Given the high affinity and efficacy results in both

end walls in Phase II" --

Q. Yeah, and, by the way, why don't I interrupt you because

I misspoke. This is referring to study, as you testified,

99-03, correct?

A. Right. It's not for the Phase II study.

Q. Yeah. And, so, you agree that this is an accurate

description of the hypotheses that Study 99-03 was designed to

test?

A. Yes, 99-03 was designed to test a noninferiority

endpoint.

Q. And you understand in order to get a MEC indication from

the FDA, they needed an additional study, 99-04 in addition to

this noninferiority study, 99-03, correct?

A. Um, I don't know what the FDA told them as to what would

be required for approval.

Q. You're not aware that that was an agreed-upon requirement

between Helsinn and the FDA?

A. No. I know that they went and they had their meeting and

they discussed all three trials, three studies.

Q. But are you aware then in order to get an indication for

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MEC, they had to have a successful showing not only in 99-03,

the noninferiority study, but, also, in 99-04?

A. You know, as to what would happen after the results of

those trials are in and when they filed or for an NDA, it's

hard to say; but I think the pre-IND meeting that they had,

that the FDA is telling them, gee, if you do a good job on

these studies, you have a high likelihood of getting approval.

Q. So, you don't understand that prior to Phase III, there

was an agreement at that time between Helsinn and the FDA that

they would need to show a successful outcome, not only

in 99-03 for MEC, but, also, 99-04 for MEC; you don't

understand that?

A. No, I understand that, you know, they tried to get, you

know -- they tried use the Phase II study as the pivotal

study. That was the prior discussion we had.

They didn't allow them to use it as the pivotal study

for purposes of approval, so they said if you want approval,

you need to do pivotal studies, and they told them to do --

THE COURT: Before Phase III?

THE WITNESS: They tried to -- the prior discussion

was related to trying to use the Phase II study as the

labeling study.

THE COURT: Don't you always have to do Phase III

studies?

THE WITNESS: Not always. But because they did this

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prospective, randomized, double-blinded Phase II study, but

they were told no, you didn't get this right, you didn't get

that right, you need to go forward and do Phase III studies.

BY MR. O'MALLEY:

Q. My question is more specific, and if you can't answer it,

just please tell me and I'll move on.

Did you understand that prior to Phase III that Helsinn

understood, and the FDA had so told them, that in order to get

an indication for MEC, they had to have a successful outcome

out of both 99-03 and 99-04?

A. For moderately emetogenic chemotherapy --

Q. Yes.

A. For moderately emetogenic chemotherapy --

Q. Okay.

A. -- because that was the key, was the indication was

moderately emetogenic chemotherapy.

Q. Correct, and to get an indication for HEC, highly

emetogenic chemotherapy, they needed, one, to reanalyze the

2330 Study and get a successful outcome in 99-05.

Do you understand that?

A. Yes. They were going to allow them to use the Phase II

study as supportive data, so they really only needed one Phase

III trial for highly emetogenic chemotherapy and then based on

the Phase II study and the Phase III, they would approve it

for that indication.

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THE COURT: But they did have to reanalyze the Phase

II HEC data --

THE WITNESS: And that's what --

THE COURT: -- is that right?

THE WITNESS: Yes, because I was, you know saying

earlier, you can imagine if you had no treatment. So they

went back and they put in a sort of like if it was a placebo

category of historical controls, and then they reran their

statistical analysis, and now it was significant.

BY MR. O'MALLEY:

Q. But it wasn't before in the FDA's eyes, in any event?

A. No. It wasn't adequate for labeling at that time.

That's really the distinction. In other words, the context

was they didn't feel it was adequate for labeling at that

time.

Q. Now, let's turn to the Formulation Book DTX-0254.

And you've reviewed this book before?

A. I don't remember seeing the Formulations Book.

Q. I'm sorry?

A. I don't remember seeing the Formulation Book. I knew it

was discussed at the -- I know it was previously discussed. I

can't remember looking at it.

Q. Okay. Are you aware, and we can go through it if we need

to, that as a result of its analysis or analyses of the Phase

II study, 2330, that Roche/Syntex recommended a dose for Phase

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III clinical trials for CINV of 1 milligram?

A. This is May 1995?

Q. This publication is, yeah.

A. So, you're referring to this publication?

Q. My question is more general.

Are you aware that Roche/Syntex made that

recommendation based on its analyses of Study 2330?

A. At what time?

Q. At any time.

A. I don't remember seeing that --

Q. So you're not aware --

A. -- in the material I read.

Q. You're not aware of that?

A. I'm not aware of that.

Q. Why are you focusing on the time frame in this question?

A. I was trying to understand what the Formulation Book is.

I don't know this and how that would relate to clinical

trials' outcomes.

Q. Are you aware of when 2330 was finalized?

A. I thought it was June of 1995.

MR. O'MALLEY: Okay. And in that, why don't -- can

we pull out 2330. And find the signature page. Likely around

the last page, Roy.

BY MR. O'MALLEY:

Q. Now, while he's looking for that, with respect to the

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date that the final report is signed, that's a date that you

have in mind? Whether it's accurate or not, you're thinking

of the date the final report was signed?

A. Yeah, I mean, I'm thinking about it would be difficult to

reach a conclusion without knowing the 2330 data about what

dose should go forward, and you need to go through a whole lot

of different processes, so July 1995.

Q. Do you recognize this to be the final report for 2330?

A. Yes. And the report is July 1995.

Q. And let's go to the last page.

And you see it was signed even after that in September

of 1995?

A. Yes.

Q. Now, are you aware the Formulation Book discusses the

results of Study 2330?

A. No.

Q. No. But you are aware that results are available, that

seemed to be a theme of your testimony this morning, before

the final report on any given study is both prepared and

signed, correct?

A. Now this Phase II study would be much more difficult to

try and do an analysis on blinded data, if that's what you're

alluding to.

Q. No, I'm just saying before the final study report is

executed and signed, often results are available, preliminary

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may they be, correct?

A. I don't know when the, you know, data analysis were done.

I just -- what I'm saying is, to me, the company prepared this

report and finally signed it in September of 1995, and you're

showing me a book from May. So I don't know what the

connection is between who was writing these different things

and what they were referring to and thinking about when they

wrote them.

Q. But, in any event, you're not aware that Roche/Syntex

made a recommendation based on its review of Study 2330 that

Phase III trials employ 1 milligram total dose in CINV?

A. I'm not aware of that.

Q. Okay.

A. I'm not aware of that.

Q. Let's turn to DTX-1023.

Now, in your expert report, you discuss the fact that

you reviewed Dr. Candiotti's expert reports and exhibits. Do

you believe that?

A. Candiotti?

Q. Candiotti.

A. Yes.

Q. And do you recall this was one of Dr. Candiotti's

exhibits?

A. I don't remember, but I'll say yes, I mean.

Q. Okay. Now, this is a letter dated January 7, 1998 from

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Kathleen Lee.

Do you see that?

A. Yes.

Q. And you are aware Dr. Lee is listed as one of the

inventors on the face of the patents-in-suit?

A. Okay. Yes.

Q. And you were here when Dr. Calderari testified that she

was formerly, before this date of this document, affiliated

with Roche Palo Alto, which was formerly Syntex, correct?

A. Yes.

Q. And you heard that Dr. Lee oversaw Phase II palonosetron

clinical studies while at Syntex?

A. Yes.

Q. Now, if you turn to the first page of this document and

the first sentence of the third paragraph, it states, "The

RS-25259-197 program was halted by Roche following completion

of clinical Phase II studies."

Have you heard testimony about that?

A. Yes.

Q. Now, are you aware that prior to terminating the

palonosetron project, I know you said you weren't aware of the

specific dose, but are you aware that Roche did, in fact,

determine a dosage of palonosetron to carry forward to the

clinical studies?

A. I'm not aware of that.

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Q. Could you turn to the second page, the table?

And specifically let's turn to 003, and do you see a

product definition?

A. Yes.

Q. And Table 2 is entitled, "Developmental Assumptions"?

A. Yes.

Q. And do you see that with respect to the CINE dose that's

defined here, the total dose is 1 milligram?

A. Yes.

Q. Now, are you aware of any evidence in the documents

you've reviewed whereby Roche/Syntex recommended a dose other

than 1 milligram for Phase III CINV?

A. So, I'm understanding, this is Dr. Lee's letter from a

third party now. She doesn't work for Roche or Syntex or --

Q. My question has nothing to do with the letter at this

point.

A. I'm just trying to understand what we just looked at.

Q. My question to you is are you aware of any documents, yes

or no, whereby Roche/Syntex recommends a dose other than

1 milligram for Phase III clinical trials?

A. I said I wasn't really aware that they recommended the

1-milligram dose. I don't know about other doses.

Q. So, your answer is you're not aware?

A. The only thing I'm aware of of what Syntex was saying was

their participation in the meeting with Helsinn, where the

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Syntex people that were there cooperated with Helsinn, and

what the conclusions of that joint Syntex/Helsinn meeting

those conclusions were. And we saw from my testimony earlier,

it was .25 and .75.

That's the only knowledge I have about the interaction

between Syntex people and Helsinn people on dose selection.

Q. Well, to be accurate in that document, it was .25, .75,

and 2 milligrams.

A. Correct. I correct myself. There was also a 2-milligram

recommendation, but there was not a 1-milligram

recommendation.

Q. Let's look at Roche 7739 to 7742. Have you seen this

document before?

A. No, I have not.

Q. Now, I'm just going to -- and you understand that Roche

Bioscience was by this time a division of Syntex U.S.A.?

A. Gosh, I thought Syntex was a division of Roche.

Q. So, you're not aware who Roche Bioscience is?

A. I mean, Roche, I believed, acquired Syntex.

THE COURT: Maybe Roche Bioscience is actually a sub

under Syntex and Roche --

THE WITNESS: Okay. So, I see. So they just

transferred their -- so they have two layers and Syntex is in

between maybe.

THE COURT: I don't know.

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Counsel, what's the date of this?

MR. O'MALLEY: The date of this is 18 October 1995.

BY MR. O'MALLEY:

Q. Do you see that, sir?

A. Yes, I do.

Q. And are you aware by this time Roche had decided to

discontinue the palonosetron product?

A. I'll accept that.

Q. And are you aware that during this period of time, Roche

was looking to out-license palonosetron to a different

pharmaceutical company?

A. Okay.

Q. And do you see this as a communication to Bristol-Myers

Squibb?

Do you see that?

A. Yes.

Q. And on the second page of this document, there's an

outline of Draft 3 of Draft Phase III Protocol.

Do you see that?

A. Yes.

Q. And under study medications it states, "RS-25259: Based

on the Phase II study results, it is expected that a dose of

1 milligram I.V. RS-25259 will be effective."

Do you see that?

A. Yes, I do.

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Q. And you've not seen this before, I take it?

A. No.

Q. Now, you referred to a meeting that involves some Syntex

scientists. Was that your 1998 meeting minutes you had in

mind?

A. Yes, sir.

Q. Why don't we turn to that, PTX-0015.

Now, again, you don't have any basis for believing this

document was publicly available, correct?

A. I don't know that.

Q. You don't know --

A. I don't know that it was publicly available or not.

Q. Any reason to believe it is?

A. No.

Q. Do you see in the upper left-hand corner, it says

"confidential"?

A. Yes.

Q. Now, it appears that these are minutes from a series of

meetings that took place that day?

A. Yes.

Q. And I believe you were referring to -- well, let me ask

you: In your prior testimony, were you referring to

DTX-15-0008, the minutes of the clinical meeting?

A. DTX-0015.

Q. 0015-0008. In any event --

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A. Yes.

Q. -- is this the page you were referring to?

A. Correct. Yes, sir.

Q. Okay. And I believe you directed our attention this

morning to testimony regarding the CINV proposed doses?

A. Yes, sir.

Q. And at this point in time among Helsinn internally, the

recommendation was still to keep 2 milligrams as one of the

Phase III doses.

Do you see that?

A. Yes. Not the 1 milligram, but a different one than they

were, I guess, thinking about earlier. They've switched from

1 to 2 now, but they brought in the .25 and the .75 after

reanalysis of the data with other people from the outside.

Q. Sir, do you see that?

A. Yes, I see that.

Q. Okay. That's all I'm asking you is --

A. Yes, sir.

Q. -- yes-or-no questions. Your counsel's going to get a

chance to let you pontificate.

A. My apologies.

Q. Now, that 2.1 -- 2.0-milligram dose, that's equivalent to

30 microgram per kilogram, correct?

A. Yes, sir.

Q. And you recall when we looked at 2330, the 30 microgram

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per kilogram was the only dose that showed statistically

significant difference relative to that cohort, correct?

A. For the 24-hour --

Q. For the primary endpoint.

A. -- complete control. Yes.

Q. Yes.

Now, do you recall Dr. Calderari's testimony to the

effect that his clinical colleagues were lobbying to test a

higher dose than they eventually tested in Phase III clinical

trials?

A. I don't remember that, but I'll accept that.

Q. And that he had a concern, based on this balancing,

between efficacy and stability.

Do you recall that testimony?

A. I do remember that. That went to the -- okay. Yes.

Q. And, so, based on his concerns about that balance and how

many doses it was practical for Helsinn to take into Phase

III, they decided that they could not take the 2-milligram

dose into Phase III.

Do you recall that generally?

A. No, but I'll accept that.

Q. Okay. Now, if you turn to the next page of the clinical

meeting minutes, and specifically under CINE dosing, the

minutes from that meeting of the clinical team included a

conclusion that "In a review of the study data, the

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3-microgram-per-kilogram dose may not be the most effective."

Do you see that?

A. Yes, I do.

MR. O'MALLEY: I'm not really keeping track of time,

your Honor, so I assume you'll tell me if we get to where you

want to break.

THE COURT: You read my mind.

MR. O'MALLEY: Okay. Then I'm at a stopping point,

so we can break here.

THE COURT: Perfect. Thank you. We'll take a little

recess.

(Brief Recess.)

THE COURT: Continue.

BY MR. O'MALLEY:

Q. I would like to turn to DTX-0287-0413. And this is a

declaration you provided testimony about in the morning. Do

you recall that?

A. Yes, sir.

Q. And for shortness, I'm just going to refer to that

periodically as the Cantoreggi declaration. Is that okay?

A. Yes, sir.

Q. Now, this is a declaration on -- given by Sergio

Cantoreggi, Enrico Braglia, and Riccardo Braglia. Do you see

that on the first line?

A. Yes, I do.

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Q. I'm sorry?

A. Yes, I do.

Q. Okay. And then it states that, in Paragraph 3, "In

particular, we submit this declaration to establish that

Alberto Macciocchi" -- and I'm mispronouncing that and my

client will please forgive me -- "Enrico Braglia and Riccardo

Braglia, had conceived the idea to use palonosetron for the

treatment of acute and delayed-onset CINV, and had conducted

clinical trials in humans to test this idea, at least as early

as October 2, 2001." Do you see that?

A. Yes, I do.

Q. And although Sergio Cantoreggi is one of the declarants,

there is no assertion in here that he was part of the

conception of the idea to use palonosetron for treatment of

CINV, correct?

A. Correct.

Q. Now, going back to Paragraph 2, it says, "We submit this

declaration to establish that Alberto Macciocchi, Enrico

Braglia, and Riccardo Braglia had conceived the invention

defined by claim one of this application, and reduced it to

practice, before November 16, 2001, the date that

Dr. Piraccini published abstract Number 5169 in Blood, Volume

98, No. 11 Part 2." Do you see that?

A. Yes, sir.

Q. What does "reduced to practice" mean?

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A. I'm not an attorney. I would not want to take a stab at

that. If there was a clinical thing, to me, it means you're,

you know, doing something for patients, but this is a patent

question.

Q. It's a legal term.

A. It's a legal term.

Q. And you're an American, correct? You live in California.

A. Yes, sir.

Q. Indeed, you're an inventor on a number of United States

patents, correct?

A. Yes, sir.

Q. But you're not clear on what the term "reduced to

practice" means. As you put it, it's a legal term.

A. It's a legal term.

Q. Yeah. Now, you understand that the declarants of this

declaration are Italian speaking?

THE COURT: You can assume that.

THE WITNESS: I assume that.

BY MR. O'MALLEY:

Q. Okay. And are you aware that these patents relating to

palonosetron were either their first patents ever or among

their first United States patents ever? Are you aware of

that?

A. No.

Q. Have you seen any testimony from any of the declarants in

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this case?

THE COURT: Any of these folks, the four of them?

BY MR. O'MALLEY:

Q. The declarants, Sergio Cantoreggi, Enrico Braglia or

Riccardo Braglia, have you seen any testimony from them in

this litigation?

A. Was it Sergio Cantoreggi here on Tuesday? No. That

was -- that's a different person.

THE COURT: Calderari.

THE WITNESS: Calderari. I'm confusing the Italian

names. So no, I don't believe I've ever seen them give

testimony.

BY MR. O'MALLEY:

Q. Okay. So, you have no basis for knowing or speculating

how they interpreted this legal term, "reduced to practice,"

correct?

A. No, sir.

Q. Now, if you turn to Paragraph 9, it says, "Enrico Braglia

and Riccardo Braglia worked with Dr. Macciocchi as he

developed the clinical protocol for PALO-99-03," and it goes

on from there. As you read that sentence, the "he" clearly

refers to Dr. Macciocchi?

A. Yes.

Q. Now, nowhere in this declaration does it assert that the

Braglia brothers, and I'll call them that for short, were

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personally involved in any aspect of PALO-99-03, other than

working with the person who developed the clinical protocol,

correct?

A. Yes. I don't know how to interpret this paragraph in

terms of what intimate knowledge they would have had in the

process.

Q. But there is no assertion that they were personally

involved in these clinical studies, correct?

A. Just says they worked with him as he developed the

clinical protocol.

Q. Now, you've -- are you aware that the Braglia brothers in

the time period when palonosetron was being developed were

co-CEOs of the company? Do you recall Dr. Calderari's

testimony to that effect?

A. I remember there was a time I think their father ran the

company and they worked for him and -- but I don't know the

dates of --

Q. Okay.

A. -- how the family --

Q. Fair enough.

You've reviewed a number of documents relating to the

clinical studies -- meeting minutes, study reports, et cetera.

Do you recall the Braglia brothers, either one of them,

attending any of these meetings, either with the FDA, with

Syntex, et cetera, to discuss these clinical studies?

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A. I don't know.

Q. You don't recall that, do you?

A. No.

Q. Okay. Now, there's no assertion in this declaration that

Dr. Cantoreggi was personally involved in these clinical

studies, correct?

THE COURT: You could show him the portions of the

declaration where Dr. Cantoreggi has something attributed to

him.

BY MR. O'MALLEY:

Q. Yeah, let me see. Let's go back to Page 1.

Now, the paragraph with respect to Dr. Cantoreggi's

connection is, I believe, and the only place I see it is

Paragraph 10. It says, "Sergio Cantoreggi has since worked

extensively with Palo and is very familiar with the work

reported in Palo 99-03." Do you see that?

A. Yes, I do.

Q. And they don't assert the -- whomever drafted this does

not assert that Mr. Cantoreggi was personally involved at the

time with the work reported in PALO-99-03. Do you see that?

A. Well, Number 4, they're mentioning.

Q. I'm sorry?

A. Number 4.

Q. Number 4, let me see what you're -- let's pull up Number

4. And what are you -- why are you citing that to me?

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A. Well, Sergio Cantoreggi is employed by Helsinn, the

assignee.

Q. At the time this declaration is signed?

A. Yes. So he was working with the company. That's --

yes, that's what we know.

Q. Do you have any basis for knowing that Dr. Cantoreggi was

involved with the clinical trials while they were being

undertaken?

A. I don't really know what their management structure was

or how they organized their --

Q. You don't know one way or the other?

A. No, sir, not one way or the other.

Q. When you were listening to Dr. Calderari's testimony, do

you recall him testifying that Dr. Cantoreggi, in the time

period when palonosetron was being developed, worked in the

toxicology lab?

A. I don't remember that but I'll accept that as true.

Q. Okay. Do you understand that from Helsinn's standpoint

in the relevant time period Dr. Macciocchi was in charge of

the clinical trials?

A. It's -- it seems to be that way from this document.

Q. And, unfortunately, at the time of this declaration, he

had passed away. Do you understand that?

A. No.

Q. Okay. It states it but it's not important enough to go

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back.

A. Okay.

Q. Now, you had focused on Paragraph 18 of this declaration.

And, as I recall your testimony, you read this to mean that

the declarants had seen some indication of success of 99-03

before October 2, 2001. Is that fair? Is that an accurate

characterization of your testimony?

A. Yes, it is.

Q. Now, October 2, 2001, is the date the study was

completed; is that correct?

A. Yes, sir.

Q. That's --

THE COURT: Last patient out.

THE WITNESS: Yes, ma'am.

MR. O'MALLEY: Last patient out, correct?

THE WITNESS: Yes, sir.

BY MR. O'MALLEY:

Q. And it's sometime before the data is unblinded, correct?

A. Yes, sir.

Q. So, for this statement to have been accurate, according

to your interpretation, one or more of the declarants would

have had to have determined some signal of success prior to

the last patient out, correct?

A. Or at the time of the last patient out.

Q. Well, it actually says "before." Right?

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A. Yes.

Q. Okay. So before the last patient was out of the clinic,

the way you interpret this paragraph, one or more of the

declarants would have had to have done some analysis to see

some indication of success of the trial, correct?

A. I think that was really saying that they could have.

Q. They could have?

A. And that could have led to them reaching the conclusion

of a successful test.

Q. You say they could have because you don't know, correct?

A. No, I don't know.

Q. So you're speculating.

A. Yes.

Q. Now, you don't know who actually prepared this English

language document, I take it?

A. I would imagine an attorney.

Q. Okay. A U.S. Attorney?

A. I don't know.

Q. All right. Now, do you -- are you familiar with the

extent to which the three declarants speak English?

A. No.

Q. All right. Do you know whether a translation was

prepared for them?

A. I don't know.

Q. Now, in speculating as to how one might see an indication

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United States District Court

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165

of success from 99-03 prior to October 2, 2001, you went

through some analysis of comparing blinded data to historical

efficacy data. Do you recall that?

A. Yes, sir.

Q. Okay. I want to try and understand that in a moment but

before I get there, you have no basis to believe that any of

the declarants actually did that analysis, correct? Well, I'm

sorry, let me rephrase that.

You have not seen any documents or evidence otherwise

indicating that, in fact, the declarants had done that

analysis, correct?

A. This is the only document that I can look at that

suggests that they had successfully tested it, and to make

that statement, I was trying to come up with, well, how could

you have done that, if the data are blinded, and that's what I

did.

Q. So the answer to my question is yes?

A. This is the only -- this document is what I was going by.

Q. Okay. And you've not seen any --

A. Other document.

Q. -- Helsinn documents or other evidence indicating that

Helsinn or the declarants ever did the analysis you posited?

A. No, sir.

Q. No, sir, you haven't seen that?

A. No, sir, I haven't seen them.

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Fruehauf - Cross

United States District Court

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166

Q. Okay. I just wanted to understand the "no."

A. Yes, sir.

Q. Okay. Let's take a look at your Fruehauf Demonstrative

Slide 9.

Now, you have a 70 percent in the bar, the red bar for

historical efficacy of ondansetron; is that correct?

A. Yes, sir.

Q. And you have that drawn lower than the bar that shows

74.4 percent blinded data average for the other three,

correct?

A. Well, for ondansetron and the other two.

Q. Yeah.

Now, and you believe it's fair to represent that the 70

percent as being lower than the 74.4 percent?

A. Yes. By 4.4 percent.

Q. Okay. Now, you -- I believe you explained that you

obtained that 70 percent historical number from DTX-0288-0064.

Do you recall that?

A. Correct.

Q. Okay. But you didn't, as I recall, actually refer to --

bring up the exhibit to show us how you obtained that number.

Do you recall that?

A. Yes, sir.

Q. So I want to try and understand that number. If we could

pull up DTX-0288-0064. And let's go down to the lower

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167

paragraph, the number of patients.

THE COURT: So this is from the 99-03 Phase III study

report? Yes?

MR. O'MALLEY: Can you answer the Judge's question?

THE WITNESS: Yes. 99-03.

MR. O'MALLEY: 99-03. Okay.

BY MR. O'MALLEY:

Q. And I'll represent this was the only place I could find

that 70 percent, namely, and the sentence says, "The sample

size was based on the assumption of a responder rate of 70

percent in the palonosetron and ondansetron groups and a

difference of no more than 15 percent in the complete response

rate." Is this the basis for your 70 percent historical

evidence?

A. Well, the basis is actually from a prior part, but this

is where the number came out because they did the calculations

based on the meta-analysis. The meta-analysis is on the prior

page.

We looked at 7,000 patients, and I briefly did explain

that, but -- so the 70 percent is the number they use for the

clinical trial to design the power of the study. They

needed --

Q. Now --

A. This is a non-inferiority study.

Q. Now, the 70 percent isn't referred to as a historical

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168

efficacy from ondansetron. There is no designation of that

number as historical. Do you see that?

A. Well, you'd have to go back, as I said, to the prior

page, at the bottom, where they describe the methods they used

to get the 70 percent number.

Q. My question is far easier. At least in this section,

it's not described as a historical efficacy number, correct?

A. Because they've already explained how they got it.

Q. Uh-huh.

Now, did you find this number or was it pointed out to

you by contrast by counsel?

A. I take personal responsibility for finding this myself.

Q. So you looked through the entirety of the document to

glean a historical efficacy number for ondansetron?

A. Well, I wanted to understand the design of the study.

And it's a non-inferiority study, so they have to have an

assumption of what the comparator will do in the study, and

then they have to be non-inferior to that assumption. You

can't just do the study and say I'm going to put ten people on

each arm and get an answer. You have to have how many people

am I going to need in each arm and what will the response

rates be of the control group, which is ondansetron. And so

they're assuming that the control group, the ondansetron arm,

will have a response rate of 70 percent based on the

meta-analysis that's described on the prior page.

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Fruehauf - Cross

United States District Court

Trenton, New Jersey

169

THE COURT: When you say response rate of 70

percent --

THE WITNESS: Control, control. So they say

responder rate there, 70 percent in the sentence. But what

responder rate really means is they respond to the drug by

having complete control of their -- complete control of the

emesis. Complete response is how they refer to it, complete

response, so you didn't feel nauseated and you didn't need a

rescue medication.

BY MR. O'MALLEY:

Q. Now, let's turn to DTX-0288.0100. And let's look at

Table 7.1.1.2. And you understand this is from the same

document?

A. Well, that is from the same document, yes.

Q. And the heading says, comparison of complete response,

zero to 24 hours, between the ondansetron group and modelled

historical ondansetron group. Do you see that?

A. Yes.

Q. And with respect to the data for modelled historical

ondansetron, do you see there is a complete response rate

stated there of 79.3 percent?

A. Yes.

Q. Now --

THE COURT: And then the next column is the

ondansetron dosage and the number of people and the result in

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United States District Court

Trenton, New Jersey

170

this Phase III, 99-03 study.

THE WITNESS: Yes, ma'am.

THE COURT: Correct? 68.6.

THE WITNESS: 68.6.

BY MR. O'MALLEY:

Q. Now, if we can pull up PTX-075. PTX, the demonstrative.

Now, with this demonstrative, we inserted into your

form of demonstrative --

A. Um-hum.

Q. -- the number that was listed for the historical

ondansetron complete response rate, do you see that, of 79.3

percent?

A. Yes.

Q. And you see that was -- that was about 5 percent greater

than the actual response rate for the combined blinded data?

A. Yes.

Q. Do you see that?

A. Yes.

Q. Now, again, you have no basis for believing anyone at

Helsinn did this particular analysis that you've described?

A. No. I only -- what we saw that they had stipulated or

stated in their patent -- claim --

THE COURT: Declaration.

THE WITNESS: Thank you, declaration -- that they had

successfully tested the hypothesis.

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Fruehauf - Cross

United States District Court

Trenton, New Jersey

171

BY MR. O'MALLEY:

Q. Now, you began your opinions today that a POSA in the

field of clinical science would have known that palonosetron

at .25 mgs reduces CINV, correct?

A. Yes.

Q. Now, you did not describe to the Court all of the

documents that that POSA would have available to it to judge

the efficacy of palonosetron in humans, correct?

A. I'm not sure what all the documents would be.

Q. Well, let's turn to DTX-0276. And you recognize this

document, correct?

A. Yes, I do.

Q. And the parties have referred to this throughout the

litigation as Tang 1998; is that correct?

A. Yes, sir.

Q. Now, as of the critical date, you understand that Tang

1998 contains the only publicly available, fully peer-reviewed

human clinical data regarding the efficacy of palonosetron?

A. Yes.

Q. I'm sorry. Do you understand that?

A. I understand that this was the only prior art that was

published for I.V. palonosetron and that it was for an

indication of postoperative nausea and vomiting, after

hysterectomy.

Q. But my question was a little broader.

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Fruehauf - Cross

United States District Court

Trenton, New Jersey

172

As of the critical date, it's actually the only

peer-reviewed, publicly available publication containing human

efficacy data regarding palonosetron, period, correct?

A. Human efficacy data for postoperative nausea and

vomiting.

Q. Of any type.

A. But that's what was studied here.

Q. Of any type.

THE COURT: You mean any type of emesis?

MR. O'MALLEY: Correct. Can you answer that

question?

THE WITNESS: It could be. It probably is.

BY MR. O'MALLEY:

Q. Okay. Now, we discussed the fact at your deposition that

experts in this case have taken the position that any dose

that's effective for CINV for a drug of this class is

generally going to be higher than the dose required for PONV,

and you weren't able to really take issue with that. Do you

recall that?

A. No, I did -- I didn't agree with it.

Q. You didn't -- fair enough. You didn't have any basis to

agree or disagree, correct?

A. No, I did. I said that I didn't necessarily agree with

it and that there are different doses for different drugs, and

you know, for example, ondansetron is used at 16 milligrams

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United States District Court

Trenton, New Jersey

173

for postoperative nausea and vomiting, and 8 milligrams, half

the dose, for chemotherapy-induced nausea and vomiting.

But in my deposition, I said that, you know, there are

different doses and different drugs and I didn't -- I wouldn't

take that has as a hard-and-fast rule.

Q. Well, I just want to make sure I understand. You have no

basis to dispute the general proposition that the approved

dosages for treating CINV are generally higher than the

approved dosages for PONV for the 5-HT3s, correct?

THE COURT: Are you just --

THE WITNESS: Are you asking me that question now?

THE COURT: Pardon me, sir.

THE WITNESS: I'm sorry.

THE COURT: You just gave an example?

MR. O'MALLEY: I'm just asking -- I need to know

whether he -- I didn't understand his example.

BY MR. O'MALLEY:

Q. Do you have any basis to dispute that?

A. Yes.

Q. All right. Can we pull up the transcript, please, 138:23

and 139:7.

"QUESTION: But my question was simple. Just the

approved dosages. Are you aware that for this class of drugs,

generally, CINV has higher approved dosages than PONV?

"MR. WONG: Objection.

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Trenton, New Jersey

174

"THE WITNESS: That may be.

"QUESTION: You have no basis to dispute that?

"ANSWER: I have no basis to dispute it or confirm it."

Did I read that correctly?

A. Yes.

Q. Now, the authors of Tang concluded that with respect to

the PONV they studied, only the 30-microgram-per-kilogram dose

was effective in reducing postoperative nausea and vomiting.

Are you aware of that?

A. I wouldn't agree with that characterization.

Q. Are you aware that they concluded that, whether or not

you agree with it?

A. No, they concluded that it was the dose that

significantly decreased the incidence of vomiting.

Q. Now, let's go to the abstract. And on the right,

beginning towards the bottom, implications. "Implications:

RS-25259, a long-acting 5-HT3 antagonist, was effective in

reducing postoperative vomiting only at the largest dose

studied, 30 micrograms per kilogram. However, RS-25259 had no

antinausea activity, and the larger doses were associated with

an increased incidence of headaches in the postoperative

period." Do you see that, sir?

A. Yes.

Q. And there is no word "significantly." Do you see that?

A. In that sentence, there is not.

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Fruehauf - Cross

United States District Court

Trenton, New Jersey

175

Q. Now, let's go to the -- let's go to DTX-0276-0005. And

midway down the page, there is -- at the margin there is a

sentence beginning "Only the largest dose." "Only the largest

dose of RS-25259, 30-microgram-per-kilogram I.V. was effective

in decreasing vomiting and the need for rescue antiemetic

drugs during the first 24 hours after major gynecologic

surgical procedures." Correct?

A. Yes.

Q. And no use of the word "significantly," correct?

A. Correct.

Q. And right above that, the sentence says that "These

results," referring to the summary results, "suggest that

smaller doses of RS-25259 are ineffective in preventing PONV."

Do you see that?

A. Yes.

Q. Now, in turning to the conclusion, right above the

references, "In conclusion, RS-25259,

30-microgram-per-kilogram was effective in preventing PONV in

women undergoing major gynecologic surgery. However, it did

not decrease postoperative nausea or improve patient

satisfaction." Do you see that?

A. Yes.

THE COURT: Just a second, counsel.

PONV, postoperative nausea and vomiting, in one

breath they say it's effective in preventing that; then they

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Trenton, New Jersey

176

say yeah, but not the nausea part.

MR. O'MALLEY: Yeah.

THE COURT: Right, Doctor?

THE WITNESS: Yes, ma'am.

BY MR. O'MALLEY:

Q. Right. And recall, complete response is vomit -- I

shouldn't be testifying -- but vomiting or retching; isn't

that true, Doctor?

A. Yes, sir.

Q. Okay. And then that secondary indication, you've

testified that they often use a questionnaire, how do you

feel?

A. Yes. I think they would rather have worded it preventing

POV, rather than PONV, and then it wouldn't be confusing. I

think that's a misstatement.

Q. Yeah.

Now, nowhere in --

THE COURT: Just a second. In the Phase III trial,

99-03, when you get a complete response figure, as I

understood the testimony earlier today, Doctor, complete

response includes the questionnaire of the patient, are you

experiencing nausea, and they have to say no in order to

qualify as complete response.

THE WITNESS: Correct.

THE COURT: In that Phase III trial.

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United States District Court

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177

THE WITNESS: Yes.

THE COURT: Okay. Thank you.

MR. O'MALLEY: Okay. Thank you.

BY MR. O'MALLEY:

Q. Now, in -- nowhere else in Tang do they use the word

"effective" in connection with any other dosage, correct?

Other than 30 microgram per kilogram?

A. Okay. I'll say yes.

Q. Okay. Now, again, to catch us up, 30 microgram per

kilogram was the dosage that in Study 2330 was the only dose

showing a statistically significant complete response versus

the combined control group. Do you recall that?

A. Yes.

Q. And, again, that 30 microgram per kilogram corresponds to

2 milligrams, correct?

A. I believe that's correct.

Q. And then we saw subsequently in the meeting minutes of

1998 involving Helsinn and Syntex people that with respect to

the recommendation to go forward in Phase III, at that point

in time there was still a recommendation to still use that

2-milligram dose. Do you recall that?

A. Yes.

Q. Now --

THE COURT: But that would be for the CINV, not for

the PONV?

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Fruehauf - Cross

United States District Court

Trenton, New Jersey

178

MR. O'MALLEY: Yes.

THE WITNESS: Yes, ma'am.

MR. O'MALLEY: Yes. Correct, Your Honor.

BY MR. O'MALLEY:

Q. Now, let's turn to DTX-0264. And let's turn to the

0264.0009, the table of data.

Now, again, you provided testimony about that table,

correct?

A. Yes, sir.

Q. And the table is called preliminary data; is that right?

A. It just says, "Table, Summary of Complete Response."

Q. Within the document it's referred to as preliminary data;

do you recall that?

A. It may be, yes.

Q. And there were no statistics in connection with this

particular preliminary data; is that right?

A. Not in this table.

Q. And there is no safety data presented for these

preliminary results; is that correct?

A. Not in this table.

Q. And, again, this is just the preliminary results from

99-03; is that correct?

A. These are the results for what is stated here, which is

the complete response proportion in the intent-to-treat

cohort.

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Fruehauf - Cross

United States District Court

Trenton, New Jersey

179

Q. From Study 99-03, correct?

A. Yes.

Q. And, as you testified previously, in order to get a MEC

indication, there would also have to be satisfactory results

from 99-04, correct?

A. Well, I mean, I'm not testifying with respect to FDA

approval. I'm testifying with respect to the reduction in the

risk of nausea and vomiting.

Q. When my question involves indication, my question is --

implicitly involves FDA approval. Do you understand --

A. Oh, okay, yes.

Q. -- to get FDA approval for an indication of MEC, they

needed satisfactory results from 99-04?

A. Yes, sir.

Q. Okay. Now, you heard Dr. Calderari testify yesterday

that these results just made them hopeful. Did you hear him

testify to that?

A. Was that yesterday?

Q. Oh, gosh, I don't know, honestly, if it was yesterday or

the day before. But did you hear that testimony?

A. I remember him saying that he was an organic chemist and

he wasn't a clinician.

Q. But you heard him say it just made Helsinn hopeful?

A. That these results made them hopeful?

Q. Just made them hopeful, yeah. Do you recall that?

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United States District Court

Trenton, New Jersey

180

A. No.

THE COURT: Seeing these preliminary results made

them hopeful?

MR. O'MALLEY: Made them hopeful.

THE WITNESS: Okay, they were hopeful.

BY MR. O'MALLEY:

Q. But you believe it would demonstrate to a POSA in the

clinical science that, in fact, palonosetron would have been

known to -- at .25 mgs would have been known by that POSA to

reduce CINV, correct?

A. Well, I guess it's possible that since he speaks

Swiss-Italian and he's translating into English, we don't know

would what the word really means in his mind but it could be

that he thinks that he's won, that this is going to be

approved based on these results, and that going forward

everything is going to be great.

Q. So it's -- in your mind, when he said hopeful, he got the

English mixed up; he actually meant "we won" and that's what

you believe?

A. I don't know. I don't know what's in his mind and I

would say that it's difficult to interpret simply because of

the language difficulties.

Q. I see.

You previously testified about a press release from

2000. Do you recall that?

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United States District Court

Trenton, New Jersey

181

A. Yes, sir.

Q. And do you know that the quote that you cited to was

attributed to a Luigi Baroni, Senior Director of Scientific

Affairs; do you recall that?

A. Yes, sir.

Q. And do you know anything about his English language

capability?

A. No, I do not, sir.

Q. Could we pull up DTX-0040? And let's make that a little

bit larger, if we can. And let's scroll up to the date.

And do you see this is January 16, 2002?

A. Yes, sir.

Q. Do you see that date?

A. Um-hum.

Q. Do you see the title is "Helsinn and MGI Pharma announce

completion of pivotal Phase III trials of palonosetron"? Do

you see that?

A. Yes.

Q. And do you see that this is about a week or so later than

the date of the August Consulting letter that attached that

table of preliminary results? Do you see that?

A. Yes. Yes.

Q. Now, if you go down to the third paragraph, it states,

"We are pleased to have completed all patient treatment and to

have begun analysis of the data collected in the palonosetron

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3 clinical program," said Luigi Baroni, Senior Director of

Scientific Affairs Division at Helsinn. Do you see that?

A. Yes.

Q. And that's pretty accurate in light of the August

Consulting letter we saw, correct, as of this moment in time?

A. That they had done the analysis by the date that is on

this press release.

Q. Well, strictly speaking, it says, "We have begun the

analysis." Do you see that?

A. Yeah, I mean --

Q. Do you see that?

A. Yes.

Q. Okay.

A. They had seen the SAS output. They began the analysis of

the data collected.

Q. Begun.

A. Yes.

Q. That's what it says.

A. Yes.

Q. Not finished. Okay.

And then it goes on to say, "The Phase II clinical

trial results were promising." Do you see that?

A. Yes.

Q. "And we are hopeful that the Phase III palonosetron data

will demonstrate that it can make a difference for cancer

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patients suffering from CINV." Correct?

A. Yes.

Q. And this press release was publicly available, just like

the 2000 press release, correct?

A. Yes.

Q. I have no further questions.

THE COURT: I would just like to know what this word

"pivotal" --

THE WITNESS: Yes, ma'am.

THE COURT: -- that you've been exchanging back and

forth means to you, sir.

THE WITNESS: To me, the pharma company -- well, in

the drug development process, the pivotal trial is the trial

that is what the FDA is looking for to give the NDA license.

THE COURT: Okay.

REDIRECT EXAMINATION BY MR. WONG:

Q. Dr. Fruehauf, Mr. O'Malley began by asking you about your

educational training and background in pharmacology.

A. Yes, sir.

Q. Do you recall that?

A. Yes, sir.

Q. When did you get your pharmacology degree?

A. My Ph.D. was in 1996 in pharmacology.

Q. And when did you start that degree?

A. I started that degree in an M.D./Ph.D. program in 1980 --

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I started the laboratory part in 1984.

Q. So how many years in total did you spend studying

pharmacology?

A. A long time. So from 1984 to 1996.

THE COURT: You got your M.D. what year, sir?

THE WITNESS: 1985.

THE COURT: So you just kept going on this, working

on this Ph.D. --

THE WITNESS: (Nods head.)

THE COURT: -- for another decade really.

THE WITNESS: My advisor wanted additional

experiments, and so I carried out more experiments as a

fellow, and then I carried out experiments after I came to UC

Irvine, and eventually, he was satisfied.

THE COURT: And you prevailed.

THE WITNESS: And I prevailed.

BY MR. WONG:

Q. During the course of your career, how many clinical

trials have you been involved with?

MR. O'MALLEY: Asked and answered, Your Honor.

THE WITNESS: Yes.

MR. O'MALLEY: In the direct.

MR. WONG: I think the original question was how many

clinical trials were you currently involved with.

THE WITNESS: Yes.

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MR. WONG: This one is over the course of your

career.

THE WITNESS: Yes.

BY MR. WONG:

Q. How many clinical trials have you been involved with?

A. Hundreds.

Q. And your clinical practice at UC Irvine, how long have

you had that clinical practice?

A. 1993.

Q. So how long -- how many years?

THE COURT: What year?

THE WITNESS: 1993. So I've been taking care of

patients and seeing patients on trials for five years as a

fellow at the NCI, and then from 1993 to the present time is

22 years. So 27 years I've been working with patients on

clinical trials.

BY MR. WONG:

Q. Okay. And have you been principal investigator on any of

those trials?

A. Yes, I have.

Q. How many -- do you recall how many -- how many times

you've been a principal investigator on a clinical trial?

A. Well, so, at an institution, the person who's running the

study at the institution is the principal investigator, and

there are other principal investigators at other places. And

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so whoever is running that at an institution is the PI, and so

I've been PI on, you know, 50 or 60 trials.

MR. WONG: Let's go back to DTX-0 264. Let's go to

Page 9, the Appendix I, the preliminary analysis. Blow up the

data, please, on Page 9.

BY MR. WONG:

Q. Dr. Fruehauf, do you recall Mr. O'Malley asking you about

the data here?

A. Yes, sir, I do.

Q. Let's start with ondansetron, okay? Is ondansetron

effective for reducing CINV in patients?

A. Yes, it is.

Q. And in this data, how many people got ondansetron?

A. 185.

Q. And ondansetron is effective for this indication; is that

correct?

A. It's approved for --

Q. This indication?

A. It is approved for chemotherapy-induced nausea and

vomiting, and it is approved for postoperative nausea and

vomiting.

Q. Okay. So -- and in the zero- to 24-hour row, what

percentage of people getting ondansetron had that primary

output?

MR. O'MALLEY: I'll just object, it is beyond the

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direct. I asked no questions about this table about

ondansetron.

THE COURT: I'll permit it.

THE WITNESS: 69 percent. I'm rounding up.

BY MR. WONG:

Q. Now let's go back to palonosetron, 0.25 milligrams. What

was the response rate for this dosage form, .25 milligrams?

A. The complete response rate was 81 percent.

Q. And how did that compare to the ondansetron response --

response rate?

A. It's 13 percent better or -- 12 percent better.

Q. And how does that inform your opinions on -- on whether

or not the 0.25 milligrams was effective to reduce CINV?

A. I would say that it was not inferior, which is what the

study was designed to show; therefore, if it's not inferior,

it's at least equivalent; and here, these numbers show it may

be a little better.

Q. And for the numbers for palonosetron, 0.25 milligrams,

how many patients received that dose?

A. 189.

Q. And so 81 of those 189 patients --

THE COURT: 81 percent.

BY MR. WONG:

Q. 81 percent of those 189 patients had a complete response;

is that correct?

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A. Yeah, 153 out of the 189 had complete response.

Q. So, based on this data, did 153 people have a reduction

in the likelihood of CINV?

A. They certainly did.

Q. Okay. Let's go to DTX-0276, the Tang article. Let me

start with this. Is Tang a study on palonosetron for PONV?

A. No, it is not.

Q. I'm sorry. For CINV?

A. I mean, it is not a study for CINV. It is a study for

postoperative nausea and vomiting.

Q. And do you have any opinions as to the difference between

a study on PONV and a study on CINV?

A. Yes. And I think that I, during my deposition, I

explained why it's so different, because you have -- in a

postoperative setting, you have the anesthesia, which is the

major cause of the nausea and vomiting, and as the anesthesia

is leaving the brain, and then you have the pain medications

that the patient is given because of the surgery. And, of

course, we know that morphine and morphine-type drugs cause

nausea and vomiting.

So we have a bunch of things going on in those

patients, and it's complicated, and there are a lot of

variables in terms of the people that go in the study, what

their predisposition is to the anesthesia to cause nausea and

vomiting. There's a lot of variables.

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Q. And for a CINV study, are there as many variables as

there are in a PONV study?

A. It's a little easier. They're not getting pain

medication, so you don't have to treat the nausea from the

pain medicine. You're really focused on the nausea from the

chemotherapy.

THE COURT: And no anesthesia either, right?

THE WITNESS: And no anesthesia.

BY MR. WONG:

Q. So let's look at the actual data in the Tang study.

Let's go to 276, Page 4, Table 2.

MR. WONG: Can you blow up -- can you highlight the

data for the 3-microgram-per-kilogram dose?

BY MR. WONG:

Q. And this is the .25 milligram dose; is that correct?

A. Yes.

Q. What does this data report?

A. It shows of the 40 people, the percent that vomited

within zero to 24 hours was 30 percent, so that would --

THE COURT: The percent that -- that did vomit.

THE WITNESS: Yes.

THE COURT: So this is not a control --

THE WITNESS: So the flip side would be 70 percent

control and -- at 24 hours versus 30, 26 percent vomited, so

there's a 4 percent difference between the percent that

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vomited.

BY MR. WONG:

Q. So in the Tang study, the patients that actually got the

3 mg per kg dose, did they experience a reduction in PONV?

A. Well, if you look at the .1 which is similar to how they

did the 2330 analysis in terms of the .1 was the low dose,

we'll use that sort of as a control, so 44 percent vomited,

versus 30 percent, so 14 percent reduction with the 3, and 26

percent with the 30.

Q. Okay. And let's go to Page 3. Does the Tang reference

actually talk about the lower doses and the effectiveness of

lower doses? I can point your direction to the left column.

A. Okay. Now I can see it.

Q. About eight lines down, starting with the sentence

"Although." Can you read that?

A. Although the need for rescue antiemetics within the first

two hours was similar among all groups, 1, 3, 30, -- okay.

So, although the need for rescue antiemetics within the first

two hours was similar among all groups, 1, 3 and 30

significantly decreased the antiemetic requirement compared

with saline within the first 12 hours after surgery.

Q. And the 3-microgram-per-kilogram dose is a 0.25 milligram

dose, correct?

A. Correct.

Q. Can we zoom out again, go to the right side, look at

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right first paragraph. Can you read the sentence there?

A. Read which sentence?

Q. Sorry. The sentence starting RS-25259, 1.0 micrograms

per kilogram.

A. All right. RS-25259, 1 milligram [sic] per kilogram I.V.

was also effective in reducing the number of emetic episodes

and the need for antiemetic rescue medication within 12 hours

compared with saline.

Q. And is that a lower dose than the

3.0-micrograms-per-kilogram dose?

A. That is a lower dose.

Q. So does Tang, the data and descriptions in Tang --

THE COURT: Counsel, I'm not sure you put your

question right. I didn't understand it.

MR. WONG: The 1.0 microgram-per-kilogram dose is

lower than the dose we're discussing, 3.0, and that's what

this sentence is discussing.

Let me ask another question. Maybe that can --

THE COURT: I'm getting the 30 and the 3 in the

text -- I can't follow it.

BY MR. WONG:

Q. Okay. Let's go back to Table 2 on the following page.

So Tang, the conclusion in Tang only referenced the

30-microgram-per-kilogram dose, is that correct, the one on

the right?

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A. Yes.

Q. And I'm going to ask about questions on the lower

doses --

A. Yes.

Q. -- based on the data in Tang. And the lower doses

include the 3-microgram-per-kilogram dose, correct?

A. Yes.

Q. And that's the 0.25 milligram dose that we're talking

about?

A. Yes.

Q. Okay. So, based on the data in Tang, as well as the

descriptions in Tang, do those data and descriptions tell you

anything about the lower doses that were administered in Tang?

A. Yes. So we can see here, the 1 microgram per kilogram,

which is one-third of the 3 which is the .25, we come down

here, what they're saying is there was a significant decrease

for the need for rescue anti-nausea medicines from the zeroto 12-hour point. It was identical pretty much across here

for all three doses that the need for an extra pill was

reduced by 40 percent. 70 percent of the people that got

saline needed that extra pill, but only 43 percent of the

people that got the palonosetron at those doses needed an

extra rescue pill.

Q. So would a person of ordinary skill in the clinical

sciences reading Tang, would they understand that doses less

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than 30 micrograms per kilogram showed efficacy for this

study?

A. Yes, they would.

Q. Okay. Let's go to the Syntex, let's start at the Syntex

2330 study, and that is DTX-0227. And let's go back to the

results on Page 15.

So Mr. O'Malley asked you about the

30-microgram-per-kilogram dose, correct?

A. Yes.

Q. And he pointed out that only that dose had statistical

significance, correct?

A. Yes.

MR. O'MALLEY: Objection, mischaracterized the

question. But go ahead.

BY MR. WONG:

Q. He pointed out that that dose at percent complete control

was statistically --

THE COURT: Can't hear you.

BY MR. WONG:

Q. He pointed out that that dose, 30 micrograms per

kilogram, at the percent complete control, 24 hours, was

statistically significant, correct?

A. Yes.

Q. And that number is 50 percent, correct?

A. Yes.

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Q. The percentage for the three -- the .25 dose is 46

percent, correct?

A. Correct.

Q. Does a difference in 46 and 50 percent affect your

opinions as to whether or not the 3-microgram-per-kilogram

dose reduces the likelihood of CINV in humans?

A. No.

Q. And why is that?

A. Because it isn't a statistical thing here. It's that we

know that this is the plateau, and if you look across at these

numbers, there's other points that are significant, and this

is just one of them. But that was the primary endpoint, and I

think that what -- the questions about statistical

significance are really directed to FDA and using this as a

pivotal study, and I'm really opining on, did -- was it known

that the drug reduced nausea and vomiting at that dose, and it

was.

THE COURT: The 3 dose.

THE WITNESS: At the 3. This is a reduction,

compared to, you know, only 24 percent had control and, you

know, we've talked about, you know, what saline would do.

Nobody is going to be controlled.

So I think a person of ordinary skill would look at

that 46 and say that that is the lowest effective dose, and I

think my testimony substantiates over and over again that in

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various documents, they concluded that -- Helsinn concluded

that .25 was the minimal effective dose, and FDA agreed with

them and allowed them to go forward in Phase III with that

minimally effective dose.

BY MR. WONG:

Q. Okay. And so, just to be sure we're clear, the Syntex,

Syntex scientists who performed this study concluded that 3

micrograms per kilogram was among the effective doses based on

this data; is that correct?

A. Yes, sir.

Q. And you mentioned the FDA -- the meeting minutes with

Helsinn. During those meeting minutes, Helsinn also based

their decision to go with 3 micrograms per kilogram in the

Phase III studies on the Syntex data; is that correct?

A. Absolutely.

Q. And Helsinn also went to then -- went to FDA and made a

statement to say that this data clearly demonstrated that 3

micrograms per kilogram was the minimum effective dose; is

that correct?

MR. O'MALLEY: Objection, Your Honor. It's become

counsel's testimony. These are all leading questions.

THE COURT: I'll let him answer this one and then

we'll be done with leading questions.

THE WITNESS: Yes. The FDA, as I said just a minute

ago, said, yes, take the .25 forward and .75 forward into the

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three pivotal Phase III trials, and so they agreed that .25

was an effective dose to be studied in Phase III.

BY MR. WONG:

Q. And did Helsinn also issue a press release in September,

2000, stating that Phase II studies demonstrated efficacy in

emesis?

A. Yes, they did.

Q. Let's go to PTX-2061. Before we get there, let me just

take a step back.

Let's go to DTX-0015. These are the 1998 meeting

minutes that we reviewed earlier; is that right?

A. Yes, sir.

Q. Okay. Let's go to the portion that Mr. O'Malley

referenced to you, Page 9. I think it's right in the middle,

CINE dosing.

A. Yes.

Q. And he took you to the first bullet point. Can you read

that again?

A. "In a review of the study data, the

3-microgram-per-kilogram dose may not be the most effective."

Q. Okay. Does that say that 3 micrograms per kilogram is

not effective?

A. No. It just says it might not be the most effective.

Q. Is that consistent with the Syntex data that the

3-micrograms-per-kilogram dose was among four that they found

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to be effective?

A. Yes.

Q. Let's go to PTX-2016. And I think Mr. O'Malley directed

your attention to -- okay.

Let's go to DTX number of the same document, DTX-1017.

And I think Mr. O'Malley asked you questions on Clinical

Question Number 6 that's on Page 6 at the bottom.

THE COURT: This is the FDA and Helsinn meeting?

MR. WONG: Yes, the end of Phase II meeting.

BY MR. WONG:

Q. So Helsinn's questions are at the top; is that correct?

A. Yes.

Q. And is the FDA response below?

A. Yes.

Q. Okay. So can you read -- what is Helsinn asking in

Clinical Question Number 6?

A. They want to know if the 2330 can be a pivotal study and

use it to get approval. They want to know if it's sufficient

to support the labeled claim.

Q. And when it says labeled claim, including high-dose

cisplatin, is that for approval?

A. That's for approval.

Q. And what's the second question?

A. "Should a historical control analysis be conducted?"

Q. Okay. And --

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THE COURT: What does that mean?

THE WITNESS: That's where we went back and we looked

at, you know, how the 99-03, they came up with a historical

control number for emesis control for ondansetron.

BY MR. WONG:

Q. And the Clinical Question 6, is Helsinn asking whether

the 2330 study is sufficient to support whether palonosetron

reduces the likelihood of CINV?

A. No.

Q. And the FDA's response, can you read the first bullet

point, starting, "due to the lack"?

A. "Due to the lack of a dose response in this study, these

data are inadequate to serve as a pivotal efficacy support,

although they may be useful as supportive data."

Q. So what does it mean where FDA is saying for 2330 data is

not -- is inadequate to serve as pivotal efficacy support?

A. That they won't get approval just for that one study.

THE COURT: In other words, Phase II is not enough?

THE WITNESS: In this case, this Phase II study was

not enough.

THE COURT: Could I just ask, since we're there

again, I didn't understand this phrase, "due to the lack of a

dose response in this study." What does that mean to you,

Doctor?

THE WITNESS: So, I think it did have the dose

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response. I think it was just a misunderstanding on the part

of the reviewer because --

THE COURT: You mean Phase II had a dose response?

THE WITNESS: Yes, because we saw that the low doses

had a low effect. And then the next set of doses were all

equivalent. And you just have to --

THE COURT: So there was --

THE WITNESS: So there was an increased effect with a

higher dose which is a dose response.

THE COURT: All right. But, still, the FDA was not

satisfied with the Phase II.

THE WITNESS: I think that was really -- they weren't

going to be -- you know, we don't usually in America, in our

FDA, approve studies just on one Phase II study. We usually

ask for a little more. But I think that it's interesting that

they did allow them, for regulatory purposes, to use it in

support of their one Phase III study for highly emetogenic

chemotherapy. So it was ultimately --

THE COURT: Whoa, whoa. In support of their one

Phase III study for highly emetogenic -- they still had to do

a Phase III study for highly emetogenic, didn't they?

THE WITNESS: One. So they only had to do one for

highly emetogenic because they were able to use this one as a

second study in support of that indication.

THE COURT: Was the Phase II directed to the highly

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emetogenic?

THE WITNESS: Yes, ma'am. So this study was done on

the highly emetogenic, and it was used in combination with

99-05 for two studies to support the label, whereas 99-03 and

99-04 were two studies for the moderately emetogenic

chemotherapy.

BY MR. WONG:

Q. So, just to be clear, is Helsinn asking in this Question

6 whether or not the study, the Phase II study, 2330 alone was

sufficient to get approval for a labeled claim including

high-dose cisplatin?

A. Yes. So it says, "Is 2330 sufficient to support the

labeled claim including high-dose cisplatin?" That was their

question.

Q. They wanted to skip Phase III.

MR. O'MALLEY: Leading.

MR. WONG: I'll rephrase.

THE WITNESS: And I think that means they wanted to

get approval just on their --

THE COURT: Sustained. You don't have to answer.

THE WITNESS: Okay, sorry.

BY MR. WONG:

Q. Just one last point.

So, at the last bullet point we stopped at, to serve as

pivotal efficacy support, but what is stated in the

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parentheses?

A. That's what I was saying, that although they may be

useful as supportive data -- so the data were good and were

ultimately used. Those data were used for approval of the

drug for the highly emetogenic indication in combination with

the Phase III study.

Q. Okay. Let's go to --

MR. WONG: Can you put up PTX-297? An Exhibit

Mr. O'Malley showed.

BY MR. WONG:

Q. Do you remember this abstract that Mr. O'Malley showed

you?

A. Yes, I do.

Q. Okay. And let's just confirm the date. What is the

publication date of this abstract?

A. Probably June 23rd, 2002.

Q. Okay.

MR. WONG: Let's go to the second page, Page 2. And

you can blow up the top.

BY MR. WONG:

Q. Just to confirm, was this for PALO -- was this the study

results for PALO-99-04?

A. Yes.

Q. And does the abstract contain only the study data for

PALO-99-04?

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A. Yes.

Q. Does the abstract contain any other data from any of the

other two clinical trials?

A. No.

Q. So, just based on this data alone, for one Phase III

trial, would that satisfy your understanding of what Dr. Saab

is requiring?

A. No.

Q. Okay. Why is that?

A. Because he said you need two confirmatory Phase III

trials.

Q. And --

THE COURT: Well, they had the other one. This paper

doesn't say --

THE WITNESS: No.

THE COURT: -- doesn't pull out those results, right,

of 99-03?

THE WITNESS: Correct.

BY MR. WONG:

Q. To the best of your understanding, was any other Phase

III trial published in the art between 2002 and 2003?

A. No.

Q. Do you recall what the date of completion of the final

study report was for PALO-99-04?

A. August, 2002, I believe.

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Q. And if we go to the analysis, the section above. So this

data was an analysis that was performed prior to the final

study report being completed?

A. Yes.

Q. Okay. And --

THE COURT: Which data? Your question refers to --

MR. WONG: The data in this table that is published

on --

THE COURT: In that abstract?

MR. WONG: In this abstract.

THE COURT: In the meeting abstract?

MR. WONG: Yes.

BY MR. WONG:

Q. The abstract June, 2002. This data was published -- was

this data published before the final study report for

PALO-99-04 was written?

A. I believe it was.

Q. So this was preliminary with respect to the final study

report?

A. Yes.

Q. Okay. And, based on this data, what were Helsinn

scientists able to report in the conclusion?

MR. WONG: If you can blow up the conclusion.

THE WITNESS: They were able to conclude that

palonosetron was effective at reducing the risk of emesis.

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BY MR. WONG:

Q. And this was before the final study report was written?

A. Correct.

THE COURT: So this would be a chart of preliminary

data?

THE WITNESS: Well, as I said before --

THE COURT: No, no.

THE WITNESS: The data are final. When the data is

locked, that's it. And so this data was an analysis that was

done on the locked data for 99-04 and presented at a meeting,

but they hadn't written their final report yet. So there were

other things, statistics and other things that might be done

to analyze it.

MR. WONG: Thank you. No further questions.

RECROSS EXAMINATION BY MR. O'MALLEY:

Q. Pull up DTX-0264 again. Now, let's go to the table, I

think the third page or so. Was it 009? There we go.

Now, you were talking about the ondansetron data. Do

you recall that?

A. Yes.

Q. Now, this is data that was generated through 99-03,

correct?

A. Yes.

Q. This isn't a historical efficacy data for ondansetron,

correct?

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A. Correct.

Q. Now, you said that the data showed non-inferiority of

palonosetron, correct?

A. Yes.

Q. Now, then you showed -- then you stated that it maybe

even shows that palonosetron's a little better. Do you recall

that?

A. Yes.

Q. Now, you're aware that a non-inferiority study cannot be

used to show superiority, correct?

A. Correct.

Q. Now, let's talk about Tang. Tang, and correct me if I

heard you wrong, but I believe I heard that you don't believe

that cancer patients in CINV -- experiencing CINV would also

be on pain medications?

A. You know, most of my patients who are getting

chemotherapy are not taking high doses of I.V. pain

medications at the time they're getting their chemotherapy.

Q. At the moment they're getting their chemotherapy?

A. Correct.

Q. But they're getting pain medications, these cancer

patients, at other times, correct?

A. Some of them.

Q. Yeah.

THE COURT: Including emetic-type pain meds?

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BY MR. O'MALLEY:

Q. Opioids?

A. Yeah. So what happens is, when you're on a chronic

opioid, you have what's called tachyphylaxis which is you get

used to the side effects. So the nausea event from a morphine

goes down over time, and so the people that are chronically

treated for pain do not have the nausea from the pain

medicine. It's the acute phase of giving it. So if

postoperatively, they're given the morphine, they have that

acute reaction.

Q. Now, going back to the MASCC abstract, I think it was

PTX-0297. Now, counsel for Teva made the point that this is

preliminary data. Did you hear that?

A. He did say that.

Q. Now, as I believe you've discussed today, you don't

expect the data to change from the preliminary data to the

final data; in fact, I think you've stated so strongly as it

can't, correct?

A. Well, you have your data, and it is the data. Then you

have your analysis of the data. And you could do different

types of analysis.

Q. So --

A. So the preplanned analysis is the critical analysis

that's in the protocol that is required for the FDA.

Q. So with respect --

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A. And you can do it -- the first time you do it, I wouldn't

call it preliminary. I would call it the first analysis of

the locked database.

Q. So with respect to the preliminary data in here, it might

have changed from here to the final study report?

A. I think the point was that --

Q. Yes or no? Could it have changed?

A. No.

Q. No. Thank you.

THE COURT: You mentioned that there's something

about statistics, that they can do some more statistical

analysis --

THE WITNESS: Yes.

THE COURT: -- after they get the preliminary data?

THE WITNESS: Yes.

THE COURT: But it doesn't change the raw numbers?

THE WITNESS: No.

THE COURT: Anything else?

MR. WONG: No further questions.

THE COURT: Thank you.

THE WITNESS: Thank you very much.

THE COURT: Thank you for traveling, Doctor, and safe

travels home.

THE WITNESS: Thank you, ma'am.

(The witness left the stand.)

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MR. LOMBARDI: And Your Honor -- yes.

THE COURT: I'll see counsel at the side off the

record.

(A sidebar discussion was held off the record.)

(Proceedings adjourned at 3:58 p.m.)

- - - - -

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 208 of 236 PageID: 18791
'

'219 [21] - 14:20, 14:22,

14:25, 15:3, 15:8, 15:17,

16:7, 85:8, 89:9, 92:10,

93:22, 94:11, 114:5, 114:12,

118:1, 119:1, 119:25,

120:21, 121:10, 122:1,

127:19

'including [1] - 139:16

/

/S [2] - 1:24, 1:25

0

0.05 [1] - 47:10

0.25 [20] - 37:2, 37:10, 41:2,

41:5, 47:9, 61:3, 64:12,

64:19, 71:2, 82:16, 83:13,

84:24, 85:3, 85:6, 89:14,

187:6, 187:13, 187:18,

190:22, 192:8

0005 [1] - 139:9

0015-0008 [1] - 153:25

003 [1] - 150:2

009 [1] - 204:17

0128 [1] - 116:12

0264.0009 [1] - 178:6

03 [1] - 79:24

04 [1] - 128:22

0413 [1] - 67:25

05 [2] - 132:21, 133:5

08608 [1] - 1:12

1

1 [39] - 37:19, 38:2, 60:14,

60:16, 61:3, 63:17, 69:24,

70:13, 70:14, 71:22, 89:9,

92:10, 95:13, 119:2, 131:19,

131:20, 132:12, 133:13,

134:7, 135:21, 135:25,

136:1, 146:1, 148:11, 150:8,

150:12, 150:20, 152:23,

154:11, 154:13, 161:11,

190:5, 190:6, 190:17,

190:19, 191:5, 192:14

1,000 [1] - 10:20

1-90 [1] - 35:17

1-microgram-perkilogram [1] - 131:7

1-milligram [2] - 150:22,

151:10

1.0 [2] - 191:3, 191:15

10 [14] - 37:19, 37:23,

39:18, 47:14, 47:15, 49:11,

54:9, 69:8, 69:9, 82:8, 95:11,

132:4, 139:3, 161:14

100 [3] - 45:23, 129:1,

129:2

11 [7] - 15:1, 70:1, 70:19,

85:8, 88:21, 98:4, 157:23

11-3962 [1] - 1:6

11/129,839 [1] - 68:6

12 [8] - 49:24, 70:20, 71:7,

71:8, 95:11, 187:11, 190:21,

191:7

12-2867 [1] - 99:24

120 [1] - 128:15

12:30 [1] - 95:13

12-hour [1] - 192:18

13 [3] - 36:23, 36:25,

187:11

138:23 [1] - 173:20

139:7 [1] - 173:21

14 [4] - 3:7, 35:9, 58:6,

190:8

15 [5] - 37:14, 115:6,

117:18, 167:12, 193:6

153 [2] - 188:1, 188:2

15th [1] - 52:20

16 [4] - 69:25, 157:21,

172:25, 181:11

161 [2] - 36:22, 36:25

165:17 [1] - 137:14

165:5 [1] - 137:15

17 [3] - 71:17, 71:18,

116:12

1737321 [1] - 60:9

18 [5] - 71:17, 71:18,

109:10, 152:2, 163:3

185 [1] - 186:14

189 [4] - 187:20, 187:21,

187:24, 188:1

19 [4] - 39:18, 59:21, 62:4,

67:8

1980 [1] - 183:25

1984 [2] - 184:1, 184:4

1985 [2] - 5:24, 184:6

1992 [2] - 107:14, 107:16

1993 [4] - 5:15, 185:9,

185:12, 185:14

1995 [14] - 32:9, 32:10,

34:24, 35:1, 42:25, 43:2,

44:2, 146:2, 146:20, 147:7,

147:9, 147:12, 148:4, 152:2

1996 [2] - 183:23, 184:4

1998 [11] - 33:15, 44:9,

44:11, 45:13, 51:4, 148:25,

153:4, 171:14, 171:17,

177:18, 196:10

1999 [4] - 33:18, 51:5,

52:20, 139:3

1:00 [1] - 95:24

1st [1] - 59:17

2

2 [23] - 16:18, 46:20, 49:13,

66:25, 67:9, 69:18, 69:21,

70:1, 70:15, 150:5, 151:8,

154:8, 154:13, 157:10,

157:17, 157:23, 163:6,

163:9, 165:1, 177:15,

189:11, 191:22, 201:18

2-milligram [3] - 151:9,

155:18, 177:21

2.0-milligram [1] - 154:22

2.1 [1] - 154:22

2.1-milligram [1] - 134:25

20 [2] - 97:9, 109:11

2000 [10] - 56:17, 56:19,

57:3, 59:17, 67:4, 67:15,

70:14, 180:25, 183:4, 196:5

2001 [26] - 59:19, 62:5,

67:6, 67:17, 69:25, 70:8,

70:15, 71:10, 71:16, 71:22,

72:1, 72:4, 72:20, 72:23,

76:11, 76:15, 78:9, 79:24,

79:25, 80:8, 81:23, 157:10,

157:21, 163:6, 163:9, 165:1

2002 [24] - 21:12, 30:18,

31:4, 59:21, 62:8, 62:13,

63:11, 63:23, 64:4, 64:7,

64:18, 65:12, 66:2, 67:8,

67:19, 89:13, 93:21, 94:8,

126:23, 181:11, 201:16,

202:21, 202:25, 203:14

2003 [4] - 93:23, 94:4, 94:9,

202:21

2006 [2] - 7:14, 7:18

2010 [1] - 69:17

2014 [4] - 115:6, 115:13,

116:12, 117:18

2015 [2] - 1:13, 4:1

21 [2] - 52:11, 99:24

21-milligram [1] - 130:25

21.8 [1] - 39:19

22 [1] - 185:15

22.7 [3] - 39:18, 41:4, 134:5

23 [4] - 99:25, 126:23,

129:23, 133:12

2330 [32] - 33:9, 34:7, 36:4,

36:21, 37:17, 42:23, 130:19,

130:22, 136:23, 137:9,

139:15, 140:11, 142:2,

144:19, 145:25, 146:7,

146:19, 146:22, 147:5,

147:8, 147:15, 148:10,

154:25, 177:10, 190:6,

193:5, 197:17, 198:7,

198:15, 200:9, 200:12

2332 [1] - 50:9

23rd [2] - 69:17, 201:16

24 [25] - 15:5, 37:7, 38:9,

38:11, 38:20, 39:19, 60:17,

United States District Court

1

64:11, 64:25, 65:2, 109:11,

128:15, 133:12, 133:24,

135:15, 135:21, 141:12,

169:16, 175:6, 189:19,

189:24, 193:21, 194:20

24-hour [5] - 39:4, 60:19,

64:17, 155:3, 186:22

25 [49] - 37:6, 39:17, 44:4,

46:20, 47:6, 49:13, 49:21,

50:15, 52:15, 53:12, 54:22,

55:6, 55:18, 56:2, 60:4, 60:6,

60:8, 60:20, 64:13, 66:6,

66:8, 68:17, 71:14, 71:20,

79:7, 82:15, 89:21, 93:1,

93:2, 93:11, 93:15, 128:8,

128:18, 131:3, 134:7,

137:12, 151:4, 151:7,

154:13, 171:4, 180:9, 187:7,

189:15, 192:15, 194:1,

195:2, 195:25, 196:1

250 [1] - 12:14

26 [3] - 126:23, 189:24,

190:8

264 [1] - 186:3

27 [1] - 185:15

276 [1] - 189:11

27th [1] - 67:6

28 [1] - 1:23

2nd [16] - 59:19, 62:8,

67:19, 70:8, 71:10, 71:16,

72:1, 72:4, 72:11, 72:20,

72:22, 76:11, 76:15, 78:9,

79:25, 81:22

3

3 [53] - 31:12, 37:5, 37:6,

37:19, 37:23, 38:2, 39:23,

39:24, 41:21, 41:23, 42:4,

42:13, 42:21, 49:10, 50:10,

50:21, 51:2, 55:5, 56:4, 59:7,

65:25, 67:20, 69:18, 70:2,

70:3, 131:7, 131:20, 132:1,

132:12, 133:13, 133:16,

134:7, 135:21, 135:25,

136:1, 152:18, 157:3, 182:1,

190:4, 190:8, 190:10,

190:17, 190:19, 191:19,

192:15, 194:18, 194:19,

195:7, 195:13, 195:17,

196:21

3-microgram [1] - 135:12

3-microgram-perkilogram [8] - 41:3, 130:23,

156:1, 189:13, 190:22,

192:6, 194:5, 196:20

3-micrograms-perkilogram [3] - 37:5, 39:17,

196:25

3.0 [1] - 191:16

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3.0-micrograms-perkilogram [1] - 191:10

30 [28] - 37:19, 37:23, 38:5,

39:19, 49:11, 65:3, 93:23,

94:4, 94:9, 110:11, 132:6,

134:22, 141:7, 154:23,

154:25, 174:19, 177:7,

177:9, 177:14, 189:19,

189:24, 190:8, 190:9,

190:17, 190:19, 191:19,

193:1, 193:20

30-microgram-perkilogram [5] - 174:7, 175:4,

175:18, 191:24, 193:8

30th [3] - 30:18, 31:3, 89:13

31 [2] - 67:17, 110:11

32 [3] - 48:11, 48:14, 52:16

34 [2] - 52:21, 52:23

39 [1] - 41:4

3:58 [1] - 208:5

3rd [2] - 67:4, 80:8

4

4 [14] - 1:13, 3:7, 4:1, 65:9,

65:14, 68:18, 115:16, 119:3,

161:21, 161:23, 161:24,

161:25, 189:11, 189:25

4.4 [1] - 166:15

40 [2] - 189:18, 192:20

402 [1] - 1:12

416 [1] - 69:15

43 [2] - 5:9, 192:21

44 [1] - 190:7

46 [12] - 41:3, 54:9, 133:17,

133:20, 135:12, 135:15,

135:17, 136:5, 136:16,

194:1, 194:4, 194:24

5

5 [11] - 34:4, 46:18, 49:16,

76:23, 76:24, 86:25, 87:3,

87:8, 88:9, 138:15, 170:14

5-HT [3] - 11:21, 40:6, 49:8

5-HT3 [4] - 40:7, 97:11,

141:24, 174:17

5-HT3s [1] - 173:9

5.0 [2] - 88:6, 88:13

5.8.1 [1] - 61:16

50 [5] - 24:13, 40:11, 186:2,

193:24, 194:4

502 [1] - 99:23

505(b)(2 [1] - 99:23

5169 [2] - 70:1, 157:22

54 [1] - 128:19

56 [1] - 61:15

6

6 [10] - 67:15, 70:9, 109:11,

139:9, 139:15, 197:7,

197:16, 198:6, 200:9

60 [1] - 186:2

63 [2] - 128:8, 128:13

64 [1] - 78:18

68.6 [2] - 170:3, 170:4

69 [1] - 187:4

7

7 [5] - 60:1, 63:23, 65:12,

70:9, 148:25

7,000 [2] - 78:18, 167:19

7.1.1.2 [1] - 169:12

7.4 [6] - 86:15, 86:16,

86:23, 86:25, 87:6, 87:16

70 [16] - 78:23, 79:5, 166:5,

166:13, 166:17, 167:9,

167:10, 167:13, 167:20,

167:25, 168:5, 168:24,

169:1, 169:4, 189:23, 192:20

73 [1] - 77:4

74.4 [3] - 79:5, 166:9,

166:14

75 [10] - 46:20, 47:6, 49:13,

52:15, 60:4, 79:7, 151:4,

151:7, 154:13, 195:25

753 [1] - 1:23

7739 [1] - 151:12

7742 [1] - 151:12

79.3 [2] - 169:21, 170:11

7th [7] - 62:13, 63:11, 64:4,

64:7, 64:18, 66:2, 89:19

8

8 [3] - 46:8, 173:1

80 [1] - 13:20

81 [10] - 60:20, 64:14,

64:16, 64:23, 64:24, 77:4,

187:8, 187:21, 187:22,

187:24

9

9 [10] - 60:13, 63:17, 63:18,

64:10, 68:21, 159:18, 166:4,

186:4, 186:5, 196:14

90 [6] - 37:19, 37:23, 39:19,

41:10, 75:15, 132:6

98 [2] - 70:1, 157:23

99-03 [28] - 52:13, 52:22,

58:25, 59:13, 60:3, 80:8,

94:3, 142:9, 142:12, 142:14,

142:18, 143:1, 143:11,

144:10, 161:16, 163:5,

165:1, 167:2, 167:5, 167:6,

170:1, 176:19, 178:22,

179:1, 198:3, 200:4, 202:17,

204:21

99-04 [12] - 58:25, 66:21,

94:3, 128:1, 142:17, 143:2,

143:11, 144:10, 179:5,

179:13, 200:5, 204:10

99-05 [5] - 58:25, 66:21,

67:14, 144:19, 200:4

99-05 [1] - 94:3

9:30 [1] - 4:1

A

a.m [1] - 4:1

abbreviation [1] - 111:16

able [6] - 10:10, 26:7,

172:18, 199:23, 203:22,

203:24

abreast [1] - 58:3

absolutely [4] - 20:11,

27:17, 105:20, 195:15

abstract [16] - 70:1, 127:6,

127:16, 127:17, 127:24,

157:22, 174:15, 201:11,

201:15, 201:24, 202:2,

203:9, 203:10, 203:11,

203:14, 206:11

abstracts [1] - 127:14

academically [1] - 111:12

accept [5] - 126:21, 152:8,

155:11, 155:21, 162:17

accepted [2] - 13:10, 62:1

access [2] - 97:1, 99:10

accomplished [1] - 57:5

according [4] - 48:9, 61:18,

133:22, 163:20

accrual [3] - 25:13, 25:19,

26:11

accrued [2] - 25:11, 25:12

accurate [10] - 90:24,

104:13, 109:6, 117:1,

142:11, 147:2, 151:7, 163:6,

163:20, 182:4

accurately [1] - 115:8

achieved [1] - 141:9

acid [3] - 87:16, 88:11

acidic [1] - 86:12

acknowledge [1] - 101:3

acquired [2] - 33:12,

151:19

acting [1] - 174:17

ACTION [1] - 1:5

active [9] - 15:6, 24:19,

82:12, 82:14, 83:1, 84:9,

89:4, 90:17, 101:15

actively [2] - 98:12, 100:13

activity [3] - 84:15, 129:8,

174:20

actual [2] - 170:15, 189:10

United States District Court

2

acute [10] - 69:5, 70:6,

70:24, 71:21, 128:8, 128:10,

129:8, 157:8, 206:8, 206:10

ad [1] - 29:10

add [3] - 9:23, 40:17, 91:10

added [1] - 77:5

adding [2] - 25:13, 87:6

addition [4] - 12:11, 29:14,

77:17, 142:17

additional [2] - 142:17,

184:11

address [4] - 43:14, 87:14,

95:19, 121:3

addressing [1] - 52:14

adequate [3] - 118:2,

145:12, 145:14

adjourned [1] - 208:5

administered [11] - 23:23,

31:4, 35:22, 37:9, 37:11,

38:4, 60:3, 82:17, 83:24,

84:25, 192:13

administering [4] - 23:20,

30:19, 71:1, 71:5

administration [7] - 15:20,

50:23, 50:25, 119:4, 120:5,

141:12

admitted [3] - 14:15, 118:6,

118:8

adopted [1] - 103:16

adult [1] - 70:24

advance [1] - 66:15

advantage [1] - 78:7

adverse [2] - 19:1, 74:9

advise [1] - 7:2

advisor [1] - 184:11

Affairs [2] - 181:4, 182:2

affect [2] - 83:12, 194:4

affects [1] - 85:24

affiliated [1] - 149:8

affinity [1] - 142:5

afternoon [1] - 122:15

agent [1] - 20:6

agents [2] - 6:24, 11:16

ago [2] - 107:25, 195:25

agree [14] - 19:21, 43:10,

50:12, 55:9, 74:20, 129:14,

130:18, 135:1, 142:11,

172:20, 172:22, 172:23,

174:10, 174:12

agreed [4] - 117:15, 142:21,

195:2, 196:1

agreed-upon [1] - 142:21

agreement [1] - 143:9

ahead [5] - 16:24, 43:21,

61:22, 65:1, 193:14

ahold [1] - 82:1

air [2] - 91:21, 91:23

Alberto [4] - 69:22, 70:4,

157:5, 157:18

alia [1] - 99:4

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 210 of 236 PageID: 18793
ALLEN [1] - 2:8

allow [7] - 31:16, 37:8,

124:25, 135:3, 143:16,

144:21, 199:16

allowed [5] - 74:8, 80:16,

81:5, 137:6, 195:3

alluded [1] - 101:10

alluding [1] - 147:23

almost [3] - 60:23, 89:23,

124:2

alone [6] - 54:5, 93:14,

104:24, 133:2, 200:9, 202:5

ALTO [1] - 1:4

Alto [2] - 45:11, 149:9

amalgam [1] - 11:16

amending [1] - 51:19

amendments [1] - 22:1

America [1] - 199:13

American [5] - 13:13,

13:14, 113:12, 113:15, 158:7

amount [4] - 22:12, 22:17,

71:2, 85:6

amounts [1] - 18:10

analogy [1] - 103:2

analyses [2] - 145:24,

146:7

analysis [75] - 19:24, 27:22,

28:5, 28:11, 28:14, 28:16,

28:18, 28:22, 28:23, 29:1,

29:2, 29:4, 29:8, 29:10,

29:19, 32:5, 36:24, 43:15,

60:11, 61:16, 61:18, 61:24,

62:2, 62:3, 62:9, 62:12,

62:15, 63:20, 63:22, 65:5,

65:6, 65:18, 66:1, 76:14,

76:17, 78:10, 81:12, 81:18,

81:24, 89:18, 125:17, 126:2,

136:19, 139:17, 145:9,

145:24, 147:22, 148:2,

164:4, 165:2, 165:7, 165:11,

165:22, 167:17, 168:25,

170:20, 181:25, 182:6,

182:9, 182:14, 186:4, 190:6,

197:24, 203:1, 203:2, 204:9,

206:20, 206:21, 206:23,

207:2, 207:12

analyze [1] - 204:13

analyzed [5] - 27:25, 61:13,

78:18, 93:20, 94:15

analyzing [4] - 62:23,

62:24, 65:12, 73:7

ANDREW [1] - 2:8

anesthesia [5] - 188:15,

188:16, 188:24, 189:7, 189:8

ANGELA [1] - 2:4

animal [5] - 17:8, 17:14,

18:2, 18:3, 18:8

animal's [1] - 17:15

animals [10] - 8:25, 17:7,

17:8, 17:18, 17:21, 17:22,

18:13, 18:14, 19:6, 19:13

announce [1] - 181:15

ANSWER [2] - 138:1, 174:3

answer [19] - 31:17, 43:24,

62:17, 72:14, 72:16, 72:19,

90:4, 90:12, 109:21, 112:3,

121:13, 144:5, 150:23,

165:17, 167:4, 168:20,

172:10, 195:22, 200:20

answered [2] - 122:21,

184:20

antagonist [1] - 174:17

antagonists [2] - 97:11,

141:24

anti [1] - 192:17

anti-nausea [1] - 192:17

antidiarrheal [1] - 11:2

antiemetic [6] - 45:22,

78:19, 108:2, 175:5, 190:20,

191:7

antiemetics [6] - 11:8,

107:22, 108:9, 108:14,

190:16, 190:18

antinausea [2] - 11:1,

174:20

anyhow [1] - 102:17

anyway [1] - 104:7

apologies [1] - 154:21

apologize [4] - 15:24, 70:9,

97:3, 103:8

appear [1] - 107:3

Appendix [2] - 63:17, 186:4

Application [4] - 18:4, 20:5,

22:2, 68:6

application [11] - 28:1,

63:8, 68:5, 68:7, 68:10,

68:14, 69:24, 94:5, 125:18,

126:3, 157:20

applied [2] - 15:19, 124:20

applying [1] - 93:6

approach [1] - 13:4

approached [1] - 96:25

appropriate [4] - 85:14,

96:8, 98:7, 99:5

approval [18] - 20:5,

105:19, 111:21, 119:15,

142:20, 143:7, 143:17,

179:7, 179:10, 179:12,

197:18, 197:21, 197:22,

198:17, 200:10, 200:19,

201:4

approvals [1] - 103:4

approve [2] - 144:24,

199:14

approved [28] - 22:24,

25:10, 102:12, 102:13,

108:3, 108:7, 108:18,

108:21, 109:2, 109:14,

109:18, 110:1, 110:3,

110:18, 110:24, 111:25,

112:9, 119:11, 140:22,

173:7, 173:9, 173:23,

173:24, 180:15, 186:17,

186:19, 186:20

approximate [2] - 116:19

apropos [1] - 88:22

arbitrary [1] - 133:7

areas [2] - 97:2, 99:11

argue [1] - 43:19

argument [2] - 95:17, 96:2

arm [13] - 22:23, 23:1,

23:13, 23:16, 23:22, 24:2,

24:22, 54:7, 168:20, 168:21,

168:23

arms [6] - 22:22, 23:5, 23:6,

23:8, 77:9

array [1] - 5:12

arrive [1] - 85:14

art [30] - 15:8, 15:15, 43:16,

43:17, 44:1, 55:23, 57:9,

91:12, 91:13, 91:16, 96:14,

96:19, 96:25, 97:9, 100:20,

102:23, 107:10, 121:2,

122:23, 122:24, 123:8,

123:9, 123:10, 123:12,

123:13, 123:22, 123:24,

124:11, 171:21, 202:21

article [1] - 188:5

articles [1] - 13:23

articulate [1] - 102:7

articulated [1] - 102:8

artisan [2] - 31:18, 31:25

arts [2] - 89:17, 90:5

ASHKENAZI [1] - 2:3

aside [3] - 12:25, 101:12,

104:13

aspect [1] - 160:1

assert [3] - 159:24, 161:18,

161:19

asserted [3] - 14:22, 68:10,

99:3

assertion [5] - 126:21,

141:19, 157:13, 160:7, 161:4

assess [4] - 39:8, 44:13,

129:19, 130:1

assigned [2] - 23:5, 29:16

assignee [1] - 162:2

associated [4] - 112:24,

113:12, 113:15, 174:20

Association [2] - 13:14,

127:11

assume [4] - 118:17, 156:5,

158:17, 158:18

assumed [1] - 125:2

assuming [2] - 113:2,

168:23

assumption [3] - 167:10,

168:17, 168:18

assumptions [1] - 26:5

Assumptions [1] - 150:5

United States District Court

3

asterisk [4] - 132:20,

133:19, 134:3, 134:6

attach [3] - 51:22, 70:10,

70:12

attached [4] - 52:8, 63:15,

63:19, 181:20

attack [2] - 11:14, 11:17

attempt [1] - 101:16

attended [3] - 45:14, 45:16,

139:6

attending [1] - 160:24

attention [2] - 154:4, 197:4

attorney [4] - 120:22,

120:24, 158:1, 164:16

Attorney [1] - 164:17

Attorneys [3] - 2:5, 2:8,

2:13

attributed [2] - 161:8, 181:3

August [17] - 51:15, 59:17,

63:4, 67:19, 69:17, 70:14,

71:22, 93:21, 115:6, 115:13,

116:18, 117:18, 140:24,

181:20, 182:4, 202:25

Austin [1] - 51:15

authors [2] - 133:22, 174:6

availability [1] - 123:14

available [22] - 31:18,

31:24, 32:1, 32:10, 34:21,

34:23, 34:24, 64:3, 76:12,

122:24, 123:13, 125:1,

127:18, 141:24, 147:17,

147:25, 153:9, 153:12,

171:7, 171:17, 172:2, 183:3

Avastin® [3] - 109:22,

109:23, 109:25

average [6] - 77:17, 77:19,

77:24, 78:1, 79:3, 166:9

averaged [2] - 77:5, 77:16

averaging [1] - 78:6

avoid [6] - 22:16, 23:10,

23:13, 24:9, 50:18

avoided [1] - 29:24

aware [49] - 100:18, 103:12,

122:22, 123:7, 123:15,

125:17, 126:2, 126:5, 135:3,

135:6, 136:22, 137:3, 137:9,

137:16, 137:23, 140:10,

142:21, 142:25, 145:23,

146:6, 146:11, 146:13,

146:14, 146:19, 147:14,

147:17, 148:9, 148:12,

148:14, 149:4, 149:20,

149:21, 149:22, 149:25,

150:10, 150:18, 150:21,

150:23, 150:24, 151:18,

152:6, 152:9, 158:20,

158:22, 160:11, 173:23,

174:9, 174:11, 205:9

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 211 of 236 PageID: 18794
B

bachelor's [2] - 5:18

background [2] - 4:23,

183:18

bad [2] - 73:25, 86:17

bag [2] - 24:13, 24:18

bailiwick [1] - 101:16

balance [1] - 155:16

balanced [4] - 24:3, 86:12,

86:22

balancing [1] - 155:12

bar [10] - 31:21, 77:23,

78:5, 124:8, 124:22, 125:2,

166:5, 166:8

Barbara [1] - 5:17

BARKER [1] - 2:11

Baroni [2] - 181:3, 182:1

base [1] - 43:11

based [34] - 7:2, 9:12,

24:22, 29:1, 33:20, 41:4,

46:2, 46:22, 46:24, 57:18,

64:1, 82:16, 87:16, 89:17,

100:19, 120:10, 144:23,

146:7, 148:10, 152:21,

155:12, 155:16, 167:10,

167:17, 168:24, 180:15,

188:2, 192:5, 192:11, 195:8,

195:12, 202:5, 203:21

basic [5] - 5:12, 12:23,

86:12, 87:7, 88:10

basis [14] - 20:21, 32:23,

153:8, 159:14, 162:6, 165:6,

167:13, 167:15, 170:19,

172:21, 173:7, 173:18,

174:2, 174:3

batch [3] - 60:6, 60:8

batches [2] - 59:22, 59:23

become [3] - 10:15, 30:12,

195:20

bedside [3] - 7:24, 8:1,

13:15

began [5] - 33:19, 71:23,

171:2, 182:14, 183:17

beginning [3] - 39:22,

174:16, 175:3

begun [3] - 181:25, 182:8,

182:16

behalf [1] - 51:14

behave [1] - 85:7

beings [2] - 138:5, 138:6

believes [1] - 92:18

below [6] - 35:11, 36:1,

39:24, 46:17, 69:8, 197:13

bench [4] - 7:24, 8:1, 9:22,

13:15

bench-to-bedside [2] -

7:24, 8:1

benefit [7] - 39:8, 40:4,

74:2, 77:18, 106:3, 136:1,

136:18

Berenato [1] - 1:24

Berenato-Tell [1] - 1:24

beside [1] - 124:15

best [5] - 40:12, 40:13,

91:24, 106:9, 202:20

Bethesda [1] - 6:11

better [13] - 8:7, 20:1,

23:13, 29:10, 78:4, 79:1,

101:7, 104:5, 136:15,

187:11, 187:17, 205:6

between [19] - 38:19,

38:23, 59:1, 91:11, 100:11,

101:19, 102:3, 126:8,

133:23, 142:22, 143:9,

148:6, 151:6, 151:24,

155:13, 169:16, 188:11,

189:25, 202:21

beyond [4] - 83:16, 109:16,

122:10, 186:25

bias [5] - 23:10, 23:13,

24:9, 24:11, 36:8

big [5] - 13:6, 13:15, 109:2,

110:18, 110:24

bind [3] - 22:14, 40:3, 48:20

binding [2] - 40:2, 48:23

binds [1] - 48:24

biology [3] - 5:19, 17:24,

21:2

biomarkers [1] - 110:2

Bioscience [3] - 151:16,

151:18, 151:20

biotechnology [2] - 6:11,

6:20

bit [7] - 15:25, 46:9, 79:22,

88:8, 92:21, 123:19, 181:10

bladder[1] - 8:12

blind [4] - 25:1, 80:1, 91:7,

93:13

blind-sided [1] - 91:7

blinded [31] - 23:19, 23:21,

24:6, 24:8, 26:17, 36:6,

36:13, 72:23, 73:3, 73:5,

73:8, 76:12, 76:14, 77:2,

77:14, 78:10, 79:4, 79:5,

80:13, 80:20, 81:13, 81:24,

89:20, 92:18, 93:13, 144:1,

147:22, 165:2, 165:15,

166:9, 170:15

blinding [2] - 24:9, 24:20

block [1] - 48:21

blocked [1] - 40:3

Blood [2] - 70:1, 157:22

blood [12] - 17:15, 18:24,

22:13, 29:9, 83:4, 84:8, 86:8,

86:9, 86:13, 88:10

blow [11] - 46:9, 49:24,

55:1, 59:8, 63:18, 63:21,

127:22, 186:4, 189:12,

201:19, 203:23

blue [2] - 77:23, 78:5

Board [5] - 53:3, 73:22,

73:24, 74:13

board [3] - 25:10, 74:7,

113:18

Boards [1] - 75:3

body [12] - 12:5, 12:7,

83:25, 85:21, 86:15, 86:16,

86:23, 88:12, 88:24, 88:25,

122:9, 124:12

body's [2] - 85:22, 87:19

bolus [2] - 24:15, 38:5

Book [5] - 145:16, 145:18,

145:20, 146:16, 147:14

book [3] - 106:24, 145:17,

148:5

books [1] - 107:3

bottle [2] - 85:19, 86:3

bottom [11] - 52:22, 60:1,

61:15, 63:21, 65:14, 103:21,

126:17, 134:4, 168:4,

174:16, 197:7

boundary [1] - 74:25

box [3] - 26:25, 127:22

Braglia [21] - 68:20, 68:23,

68:24, 69:22, 69:23, 70:5,

156:23, 157:6, 157:7,

157:19, 159:4, 159:5,

159:18, 159:19, 159:25,

160:11, 160:23

brain [4] - 12:3, 12:8, 40:8,

188:17

break [2] - 156:6, 156:9

breath [1] - 175:25

BRENDAN [1] - 2:11

Brief [2] - 99:17, 156:12

brief [3] - 97:8, 97:25,

132:24

briefing [2] - 102:9, 104:5

briefly [2] - 5:16, 167:19

briefs [2] - 91:2, 97:6

bring [4] - 29:21, 106:20,

114:15, 166:21

bringing [3] - 88:7, 88:9,

106:9

Bristol [1] - 152:13

Bristol-Myers [1] - 152:13

broader [3] - 104:14,

104:21, 171:25

broadly [1] - 76:19

brothers [3] - 159:25,

160:11, 160:23

brought [1] - 154:13

BUDD [1] - 2:7

buffer [2] - 82:24, 87:11

buffered [2] - 87:18, 88:12

buffering [3] - 85:11, 88:6,

89:1

buffers [2] - 87:13, 87:14

build [1] - 125:7

United States District Court

4

building [1] - 55:19

built [1] - 12:5

bullet [5] - 139:12, 139:20,

196:17, 198:10, 200:24

bunch [1] - 188:21

business [3] - 58:9, 84:16,

124:23

busy [1] - 10:2

button [1] - 28:5

BY [137] - 2:3, 2:5, 2:7,

2:12, 4:15, 6:13, 9:7, 9:25,

10:17, 12:10, 12:24, 14:17,

16:3, 20:13, 21:11, 22:3,

24:5, 25:4, 26:1, 28:15,

30:14, 31:1, 32:4, 32:14,

33:6, 34:5, 34:22, 35:12,

36:2, 36:19, 37:15, 41:1,

42:20, 43:23, 45:9, 48:2,

49:4, 49:9, 50:1, 51:1, 52:6,

54:23, 55:22, 57:17, 58:12,

59:5, 61:11, 65:24, 66:17,

69:7, 72:21, 74:4, 76:10,

79:17, 80:24, 81:21, 82:3,

83:11, 83:20, 84:20, 88:20,

89:8, 92:8, 93:4, 94:10,

107:7, 108:12, 108:23,

109:12, 110:21, 111:18,

113:8, 114:11, 114:21,

115:21, 115:25, 116:10,

118:25, 119:21, 121:24,

123:6, 123:11, 125:6, 126:1,

127:5, 129:6, 134:8, 136:21,

137:21, 138:12, 138:19,

144:4, 145:10, 146:24,

152:3, 156:14, 158:19,

159:3, 159:13, 161:10,

163:17, 167:7, 169:10,

170:5, 171:1, 172:13,

173:17, 176:5, 177:4, 178:4,

180:6, 183:16, 184:17,

185:4, 185:17, 186:6, 187:5,

187:23, 189:9, 189:14,

190:2, 191:21, 193:15,

193:19, 195:5, 196:3,

197:10, 198:5, 200:7,

200:22, 201:10, 201:20,

202:19, 203:13, 204:1,

204:15, 206:1

C

calculation [1] - 78:20

calculations [1] - 167:16

Calderari [13] - 51:6, 51:11,

54:8, 56:10, 102:16, 103:7,

130:8, 138:20, 139:6, 149:7,

159:9, 159:10, 179:15

Calderari's [5] - 34:14,

130:16, 155:7, 160:13,

162:13

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 212 of 236 PageID: 18795
California [4] - 4:25, 5:2,

45:11, 158:7

Cancer [12] - 5:7, 5:11,

6:10, 6:14, 6:18, 10:23,

13:14, 13:25, 111:4, 111:8,

127:11

cancer [33] - 5:5, 5:8, 5:9,

5:10, 6:17, 8:11, 8:12, 10:5,

10:18, 11:7, 11:10, 14:1,

15:20, 15:21, 16:11, 19:16,

30:11, 34:11, 45:23, 93:16,

109:25, 110:1, 110:2, 110:3,

110:5, 110:7, 110:12, 111:8,

119:5, 120:6, 182:25,

205:14, 205:21

Candiotti [2] - 148:19,

148:20

Candiotti's [2] - 148:17,

148:22

cannabinoid [1] - 11:20

cannot [1] - 205:9

Cantoreggi [16] - 33:24,

68:20, 69:10, 79:19, 156:20,

156:23, 157:12, 159:4,

159:7, 161:5, 161:8, 161:14,

161:19, 162:1, 162:6, 162:14

Cantoreggi's [3] - 79:20,

89:19, 161:12

capability [1] - 181:7

car [1] - 84:18

card [1] - 106:13

care [7] - 10:5, 10:16,

10:22, 10:24, 10:25, 14:13,

185:12

Care [1] - 127:11

career [3] - 10:18, 184:18,

185:2

carefully [1] - 76:4

Carol [1] - 1:25

carried [3] - 66:7, 184:12,

184:13

carries [4] - 21:25, 84:15,

84:16

carry [4] - 8:8, 8:10, 62:22,

149:23

carrying [7] - 7:23, 8:13,

20:22, 21:20, 33:20, 35:20,

84:18

case [34] - 4:19, 14:19,

20:12, 30:16, 31:7, 60:20,

63:13, 68:11, 68:13, 71:12,

90:21, 91:5, 91:7, 97:1, 98:5,

98:11, 99:13, 99:19, 99:23,

99:24, 100:9, 103:13,

103:16, 107:8, 115:5,

116:15, 117:3, 126:5,

127:18, 134:16, 159:1,

172:15, 198:19

cases [1] - 103:14

catch [1] - 177:9

category [3] - 131:10,

131:12, 145:8

causes [1] - 11:13

CBER [1] - 138:3

CC [1] - 53:24

CCP [1] - 1:25

CCR [2] - 1:24, 1:25

cell [4] - 7:11, 8:4, 21:2,

48:25

cells [7] - 7:7, 9:1, 9:22,

86:7, 86:10, 86:13

cellular [1] - 5:19

center [7] - 5:5, 5:8, 5:9,

6:17, 30:11, 110:7, 111:8

Center [2] - 5:7, 51:16

centers [2] - 5:10, 110:12

CEOs [1] - 160:13

certain [7] - 17:14, 17:15,

34:1, 40:4, 78:21, 124:19,

139:11

certainly [4] - 20:12, 80:4,

135:10, 188:4

Certified [1] - 1:23

certified [1] - 113:18

cervical [3] - 110:2, 110:3,

110:5

cetera [6] - 101:11, 124:14,

160:22, 160:25

chairman [1] - 73:23

chance [7] - 54:5, 54:9,

54:13, 62:21, 133:1, 154:20

change [14] - 27:5, 27:10,

27:12, 29:5, 29:11, 40:25,

65:21, 66:16, 80:15, 89:2,

91:4, 91:6, 206:16, 207:16

changed [3] - 28:19, 207:5,

207:7

Chao [1] - 5:7

characterization [2] -

163:7, 174:10

characterize [2] - 21:12,

36:3

charge [1] - 162:19

CHARLES [1] - 2:5

chart [4] - 126:18, 131:24,

133:3, 204:4

charts [1] - 10:8

check [2] - 18:23, 18:24

checking [2] - 17:24, 18:19

chemical [1] - 103:12

chemist [2] - 102:24,

179:21

chemistry [3] - 97:14,

98:20, 98:21

chemotherapy [55] - 6:24,

11:9, 15:21, 15:22, 16:11,

17:11, 19:16, 34:11, 34:12,

35:18, 35:19, 38:6, 38:9,

39:13, 41:10, 45:22, 46:15,

48:13, 50:11, 55:7, 60:17,

60:24, 61:1, 64:22, 65:4,

66:9, 68:9, 70:23, 70:25,

71:15, 78:21, 89:22, 93:3,

93:16, 119:5, 120:6, 120:18,

121:5, 129:10, 141:11,

142:1, 144:11, 144:13,

144:16, 144:18, 144:23,

173:2, 186:19, 189:6,

199:18, 200:6, 205:17,

205:18, 205:19

chemotherapy-induced

[18] - 15:21, 15:22, 16:11,

46:15, 48:13, 50:11, 55:7,

64:22, 66:9, 68:9, 71:15,

89:22, 93:16, 119:5, 120:6,

121:5, 173:2, 186:19

chemotherapy-naive [1] -

34:11

chemotherapy-related [1] -

35:19

chemotherapy-induced [1]

- 52:18

Chicago [1] - 5:21

chief [1] - 58:5

chloride [2] - 83:6

choice [1] - 133:7

choosing [1] - 112:5

chosen [4] - 46:20, 46:21,

46:22, 52:15

Christmas [2] - 62:17

chronic [1] - 206:3

chronically [1] - 206:6

CINE [5] - 47:15, 47:18,

150:7, 155:23, 196:15

CINV [56] - 16:4, 30:20,

31:5, 31:14, 35:3, 35:22,

37:10, 38:9, 41:6, 46:14,

46:17, 46:20, 47:7, 47:19,

50:22, 61:4, 61:8, 64:20,

69:5, 70:7, 71:21, 85:4,

89:15, 92:13, 114:6, 114:13,

119:10, 122:2, 122:12,

127:25, 128:3, 141:9, 146:1,

148:11, 150:12, 154:5,

157:8, 157:15, 171:4,

172:16, 173:8, 173:24,

177:24, 180:10, 183:1,

186:11, 187:13, 188:3,

188:8, 188:9, 188:12, 189:1,

194:6, 198:8, 205:14

cisplatin [3] - 197:21,

200:11, 200:13

Cisplatin [1] - 17:11

Cisplatin' [1] - 139:17

cited [5] - 45:24, 45:25,

100:5, 140:24, 181:2

citing [1] - 161:25

CIVIL [1] - 1:5

Claim [2] - 89:9, 119:2

claim [29] - 16:6, 69:23,

United States District Court

5

70:19, 70:21, 70:23, 71:22,

89:10, 100:5, 100:7, 100:23,

101:5, 102:11, 105:19,

120:12, 120:17, 121:4,

121:7, 122:9, 124:6, 124:13,

135:4, 139:16, 157:20,

170:22, 197:19, 197:20,

200:10, 200:13

claims [8] - 14:22, 15:1,

88:21, 99:3, 101:22, 114:15,

115:2, 118:1

Clarkson [1] - 1:11

class [4] - 12:13, 13:6,

172:16, 173:23

clean [1] - 27:2

cleaned [3] - 27:2, 30:5,

80:20

cleaned-up [1] - 80:20

cleaning [2] - 26:23, 29:25

cleanup [1] - 80:2

clear [17] - 41:7, 44:4, 47:7,

50:15, 54:19, 66:5, 83:5,

89:16, 89:20, 90:5, 93:15,

118:21, 124:4, 125:4,

158:12, 195:6, 200:8

clearinghouses [1] - 58:1

clearly [4] - 32:25, 55:5,

159:21, 195:17

CLERK [1] - 4:12

client [1] - 157:6

clients [1] - 58:8

clinic [3] - 7:22, 10:13,

164:2

clinical [143] - 4:22, 5:3,

5:4, 5:13, 6:15, 6:17, 7:21,

7:22, 8:6, 8:8, 8:10, 8:14,

9:8, 10:1, 10:2, 10:7, 10:21,

12:21, 13:5, 14:9, 14:12,

16:8, 16:12, 16:13, 16:16,

16:19, 17:2, 20:23, 21:13,

21:17, 21:20, 22:19, 25:5,

26:15, 27:14, 27:16, 28:7,

31:3, 33:1, 33:17, 33:20,

34:8, 41:8, 43:1, 44:1, 47:11,

49:17, 55:23, 57:9, 57:14,

58:15, 58:19, 59:23, 62:2,

67:13, 67:14, 68:25, 70:7,

70:12, 73:18, 81:3, 81:23,

85:2, 89:10, 89:17, 90:5,

90:9, 90:10, 91:14, 91:17,

93:9, 93:18, 93:19, 93:25,

94:15, 94:19, 97:18, 97:20,

98:21, 99:5, 103:4, 107:10,

107:17, 107:21, 107:24,

108:17, 109:17, 110:14,

111:10, 113:18, 120:13,

120:16, 121:2, 122:8,

122:10, 122:20, 127:24,

128:2, 129:20, 130:2,

130:15, 134:9, 134:16,

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 213 of 236 PageID: 18796
141:14, 146:1, 146:17,

149:12, 149:17, 149:24,

150:20, 153:23, 155:8,

155:9, 155:22, 155:24,

157:9, 158:2, 159:20, 160:2,

160:8, 160:10, 160:22,

160:25, 161:5, 162:7,

162:20, 167:21, 171:3,

171:18, 180:8, 182:1,

182:21, 184:18, 184:24,

185:5, 185:7, 185:8, 185:16,

185:22, 192:24, 202:3

Clinical [7] - 13:13, 13:25,

113:12, 113:15, 197:6,

197:16, 198:6

clinician [12] - 7:3, 84:1,

84:5, 97:21, 101:7, 101:24,

103:23, 103:24, 104:18,

105:11, 114:15, 179:22

clinicians [6] - 21:9, 97:2,

97:3, 100:15, 102:25, 112:2

clock [1] - 27:25

close [1] - 28:6

closed [2] - 62:3, 62:4

closely [1] - 138:2

co [1] - 160:13

co-CEOs [1] - 160:13

codified [1] - 20:18

cohort [8] - 38:1, 132:11,

132:15, 133:13, 133:25,

134:22, 155:2, 178:25

coin [2] - 23:3, 23:7

cold [1] - 42:7

collaborate [2] - 96:23,

97:17

collaborates [1] - 99:2

collaboration [2] - 97:16,

103:17

collaborative [3] - 98:14,

103:22

colleague [2] - 100:19,

101:23

colleagues [1] - 155:8

collect [2] - 81:11

collected [3] - 77:9, 181:25,

182:15

college [1] - 5:17

College [1] - 113:15

Column [1] - 41:21

column [8] - 41:23, 42:4,

42:7, 53:19, 64:13, 135:11,

169:24, 190:12

combination [3] - 8:5,

200:3, 201:5

combine [4] - 40:10, 54:18,

132:16, 136:2

combined [7] - 38:1,

131:10, 131:12, 131:14,

132:11, 170:15, 177:12

combining [1] - 11:24

coming [3] - 12:14, 17:17,

101:10

commercialize [1] - 20:6

committee [5] - 73:6,

73:15, 73:19, 73:21, 74:7

common [1] - 62:1

communicate [2] - 51:12,

51:14

communication [1] -

152:13

communications [1] -

137:11

community [1] - 46:1

companies [7] - 7:9, 7:12,

26:22, 30:10, 109:2, 110:18,

110:24

Company [1] - 51:15

company [24] - 6:20, 6:22,

25:3, 28:8, 57:13, 58:10,

58:17, 61:25, 73:18, 74:12,

81:4, 81:10, 81:15, 81:17,

110:8, 130:14, 139:11,

148:3, 152:11, 160:13,

160:16, 162:4, 183:12

comparator[15] - 22:23,

23:2, 24:12, 77:13, 77:15,

77:16, 77:20, 77:25, 78:1,

78:4, 78:7, 78:8, 128:22,

136:2, 168:17

compare [5] - 19:24, 48:11,

77:6, 77:9, 187:9

compared [12] - 38:1,

39:18, 48:15, 65:5, 79:5,

132:11, 134:7, 134:22,

135:20, 190:20, 191:8,

194:20

comparing [2] - 135:25,

165:2

comparison [2] - 82:6,

169:15

Compazine [2] - 11:22

compete [2] - 48:19, 49:1

complete [46] - 5:12, 37:24,

38:11, 38:15, 38:19, 38:20,

38:24, 53:21, 53:23, 53:24,

60:16, 60:21, 64:14, 64:15,

64:16, 128:10, 128:14,

133:11, 133:24, 134:18,

135:14, 135:16, 135:20,

136:7, 155:5, 167:12, 169:6,

169:7, 169:15, 169:20,

170:11, 176:6, 176:19,

176:20, 176:23, 177:11,

178:24, 187:8, 187:24,

188:1, 193:16, 193:21

Complete [1] - 178:11

completed [10] - 59:18,

70:14, 72:5, 93:19, 94:15,

116:14, 117:2, 163:10,

181:24, 203:3

completed) [1] - 72:1

completely [2] - 48:19, 49:2

completeness [1] - 130:1

completion [3] - 149:16,

181:16, 202:23

complicated [2] - 28:13,

188:22

component [4] - 13:6, 16:8,

120:11, 120:14

components [1] - 82:21

composite [1] - 99:4

composition [1] - 114:10

compound [6] - 15:6,

27:19, 96:21, 114:7, 129:20,

130:3

compounds [1] - 7:10

Comprehensive [1] - 5:7

comprehensive [4] - 5:8,

5:9, 110:7, 110:12

comprising [1] - 71:1

compromised [1] - 81:19

compromising [1] - 80:14

computation [1] - 29:21

computer[1] - 28:5

conceived [6] - 69:23, 70:5,

71:9, 71:20, 157:7, 157:19

conceives [1] - 17:4

concentration [5] - 17:15,

22:13, 46:19, 47:8, 47:10

concentrations [1] - 46:14

concept [3] - 12:6, 74:25,

97:20

conception [1] - 157:14

concepts [2] - 12:21, 12:23

concern [1] - 155:12

concerned [1] - 101:13

concerning [1] - 95:18

concerns [1] - 155:16

conclude [3] - 41:5, 137:4,

203:24

concluded [14] - 32:9,

37:18, 92:7, 96:4, 136:22,

137:3, 137:9, 137:23, 174:6,

174:11, 174:13, 195:1, 195:7

concludes [1] - 132:10

conclusion [23] - 16:9,

37:13, 37:17, 48:9, 50:20,

73:1, 73:2, 79:6, 118:1,

123:18, 126:17, 129:7,

129:14, 140:14, 140:16,

147:5, 155:25, 164:8,

175:16, 175:17, 191:23,

203:22, 203:23

conclusions [8] - 43:3,

44:3, 127:21, 127:22,

131:23, 132:9, 151:2, 151:3

concomitantly [1] - 11:6

conditions [2] - 129:21,

130:3

conduct [1] - 81:24

United States District Court

6

conducted [7] - 28:17,

59:2, 70:7, 139:17, 157:8,

197:24

conducting [1] - 21:13

conference [1] - 127:2

confidential [7] - 31:22,

32:16, 32:18, 33:1, 63:24,

74:14, 153:16

confirm [4] - 19:23, 174:3,

201:14, 201:21

confirmatory [1] - 202:10

confirmed [2] - 19:4, 93:12

conform [1] - 105:16

conforming [1] - 105:15

confusing [2] - 159:10,

176:14

connection [4] - 148:6,

161:13, 177:6, 178:15

consent [3] - 25:11, 25:20,

25:23

consequences [1] - 102:6

consider[2] - 25:23, 113:9

considered [5] - 44:7, 51:3,

51:5, 56:6, 131:14

considering [1] - 89:11

consist [1] - 8:20

consistent [3] - 39:20,

39:23, 196:24

constantly [2] - 73:4, 73:7

construct [1] - 106:1

construction [3] - 100:5,

100:7, 102:11

consult [2] - 91:12, 91:15

consultants [2] - 45:15,

45:16

consulting [2] - 51:14, 81:2

Consulting [5] - 51:15,

63:4, 140:24, 181:20, 182:5

contain [2] - 201:24, 202:2

containing [1] - 172:2

contains [1] - 171:17

content [1] - 115:20

contention [1] - 71:19

contentions [2] - 117:16,

117:22

Contentions [1] - 116:3

context [5] - 109:17,

109:18, 137:1, 140:8, 145:13

continue [4] - 76:6, 95:20,

125:3, 156:13

continued [1] - 9:13

continuously [1] - 73:21

contract [1] - 81:7

contradiction [1] - 104:20

contrast [1] - 168:11

control [50] - 37:22, 37:24,

38:11, 38:20, 40:11, 40:17,

41:25, 48:7, 53:24, 54:9,

64:14, 64:15, 73:9, 77:6,

77:10, 77:14, 78:6, 78:22,

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 214 of 236 PageID: 18797
78:24, 79:9, 80:2, 128:13,

131:15, 132:1, 133:11,

133:24, 134:18, 135:14,

135:16, 135:20, 136:7,

139:17, 155:5, 168:22,

168:23, 169:3, 169:6,

177:12, 189:22, 189:24,

190:7, 193:16, 193:21,

194:20, 197:24, 198:4

controlled [1] - 194:22

controls [1] - 145:8

COOPER [1] - 1:14

cooperated [1] - 151:1

cooperative [1] - 110:16

coordinator[1] - 73:19

copy [1] - 137:22

core [1] - 13:2

corner [1] - 153:15

Correct [1] - 1:23

correct [159] - 26:24, 29:15,

36:14, 40:21, 47:20, 50:11,

50:22, 75:22, 79:12, 80:3,

104:11, 107:11, 107:14,

107:18, 107:22, 107:25,

108:3, 108:7, 108:9, 108:11,

108:13, 108:18, 108:19,

111:21, 111:22, 111:25,

112:6, 112:10, 113:1,

113:21, 113:22, 113:24,

114:3, 114:4, 115:3, 115:6,

115:7, 115:9, 116:15,

116:18, 116:24, 117:3,

117:22, 118:14, 119:11,

122:24, 125:18, 125:22,

126:3, 126:9, 129:15,

129:21, 130:20, 130:23,

131:1, 131:5, 131:8, 131:19,

132:2, 133:8, 133:21,

133:25, 134:1, 134:18,

134:23, 135:6, 136:17,

136:23, 137:12, 138:14,

139:7, 140:22, 142:9,

142:18, 144:17, 147:20,

148:1, 149:9, 151:9, 153:9,

154:3, 154:23, 155:2,

157:15, 157:16, 158:7,

158:10, 159:16, 160:3,

160:8, 161:6, 163:10,

163:15, 163:18, 163:23,

164:5, 164:10, 165:7,

165:11, 166:6, 166:10,

166:19, 168:7, 170:3, 171:4,

171:8, 171:11, 171:14,

172:3, 172:10, 172:22,

173:9, 175:7, 175:9, 175:10,

176:24, 177:6, 177:15,

177:16, 178:3, 178:8,

178:19, 178:22, 179:1,

179:5, 180:10, 182:5, 183:1,

183:4, 186:16, 187:25,

189:15, 190:23, 190:24,

191:24, 192:6, 193:8,

193:11, 193:22, 193:24,

194:2, 194:3, 195:9, 195:14,

195:19, 197:11, 202:18,

204:3, 204:22, 204:25,

205:1, 205:3, 205:10,

205:11, 205:12, 205:20,

205:22, 206:18

correctly [9] - 110:19,

110:25, 111:1, 112:14,

138:7, 138:11, 138:13,

140:17, 174:4

correlating [1] - 9:14

corresponds [2] - 130:25,

177:14

couched [1] - 105:24

could.. [1] - 97:7

counsel [13] - 31:16, 83:8,

89:25, 95:8, 105:9, 114:8,

116:7, 152:1, 168:11,

175:23, 191:13, 206:12,

208:2

counsel's [2] - 154:19,

195:21

couple [6] - 20:8, 21:16,

28:13, 49:22, 115:19, 116:23

course [8] - 13:1, 21:4,

40:17, 58:4, 65:15, 184:18,

185:1, 188:19

court [6] - 4:1, 22:4, 34:13,

51:6, 56:10, 115:9

Court [8] - 16:18, 51:10,

52:1, 56:8, 56:9, 73:12,

78:15, 171:6

COURT [321] - 1:1, 4:2, 6:1,

6:3, 6:5, 8:17, 8:19, 9:3, 9:6,

9:19, 10:6, 12:2, 12:16,

14:15, 15:25, 16:22, 18:16,

18:19, 20:8, 21:1, 21:8,

21:17, 21:22, 23:15, 23:19,

23:22, 23:25, 24:4, 25:1,

25:12, 25:15, 28:4, 29:3,

29:13, 29:19, 30:1, 30:24,

31:16, 31:20, 31:24, 32:2,

32:10, 32:21, 33:3, 34:20,

35:5, 36:12, 36:15, 38:8,

38:19, 39:3, 39:6, 39:9,

39:22, 40:5, 40:7, 40:12,

40:14, 40:19, 40:22, 41:12,

41:14, 41:21, 41:23, 42:4,

42:6, 42:14, 42:16, 42:18,

43:9, 43:18, 43:21, 44:23,

45:1, 45:6, 45:8, 47:18,

47:21, 47:23, 47:25, 48:14,

49:6, 50:23, 52:3, 53:16,

53:19, 53:23, 54:3, 54:11,

54:15, 55:19, 57:16, 57:19,

57:21, 57:23, 59:3, 61:7,

61:9, 65:22, 66:12, 69:2,

72:10, 72:13, 72:16, 73:15,

74:6, 74:17, 75:4, 75:8,

75:12, 75:16, 75:19, 75:21,

75:23, 76:1, 76:8, 79:10,

79:13, 79:23, 80:1, 80:4,

80:6, 80:10, 80:12, 80:16,

80:18, 80:20, 80:22, 81:1,

81:7, 81:14, 81:20, 82:1,

83:8, 83:16, 83:19, 84:11,

84:13, 85:10, 85:16, 85:18,

85:21, 85:24, 86:3, 86:8,

86:25, 87:3, 87:5, 87:9,

87:14, 87:18, 87:21, 87:23,

87:25, 88:3, 88:5, 88:8,

88:13, 88:15, 88:18, 88:22,

89:6, 89:24, 90:3, 91:1,

91:15, 91:21, 92:2, 92:4,

92:20, 93:1, 94:4, 94:25,

95:5, 95:8, 95:11, 95:15,

95:23, 96:2, 96:6, 96:10,

98:3, 98:16, 99:14, 99:16,

99:18, 102:19, 103:9,

103:18, 104:1, 104:6,

104:10, 105:2, 105:4, 105:6,

105:22, 106:12, 106:19,

106:22, 107:1, 108:11,

108:22, 110:20, 111:2,

111:5, 111:13, 111:15,

113:2, 114:7, 114:10,

114:19, 115:23, 116:9,

118:4, 118:10, 118:19,

118:24, 119:17, 119:20,

121:22, 123:5, 123:10,

123:19, 123:21, 124:6,

124:15, 124:18, 124:22,

125:24, 127:1, 128:22,

129:1, 129:3, 134:3, 135:8,

135:11, 135:14, 135:19,

135:24, 136:4, 136:9,

136:11, 136:14, 136:20,

137:17, 137:19, 138:10,

138:17, 143:19, 143:23,

145:1, 145:4, 151:20,

151:25, 156:7, 156:10,

156:13, 158:17, 159:2,

159:9, 161:7, 163:13, 167:2,

169:1, 169:24, 170:3,

170:23, 172:9, 173:10,

173:12, 173:14, 175:23,

176:3, 176:18, 176:25,

177:2, 177:24, 180:2, 183:7,

183:10, 183:15, 184:5,

184:7, 184:10, 184:15,

185:11, 187:3, 187:22,

189:7, 189:20, 189:22,

191:13, 191:19, 193:18,

194:18, 195:22, 197:8,

198:1, 198:18, 198:21,

199:3, 199:7, 199:10,

199:19, 199:25, 200:20,

202:13, 202:16, 203:6,

United States District Court

7

203:9, 203:11, 204:4, 204:7,

205:25, 207:10, 207:14,

207:16, 207:18, 207:20,

207:22, 208:2

Courthouse [1] - 1:11

courtroom [1] - 130:8

cover [2] - 18:12, 138:18

CR [1] - 53:21

credibility [1] - 29:17

criteria [2] - 93:7, 93:8

critical [11] - 17:18, 20:3,

31:15, 66:2, 89:13, 90:7,

124:23, 126:8, 171:16,

172:1, 206:23

critically [1] - 19:24

CRO [3] - 81:6, 81:7, 81:15

CROSS [2] - 3:5, 107:7

cross [1] - 91:23

CROSS-EXAMINATION [1]

- 107:7

CRR [2] - 1:24, 1:25

culture [1] - 9:23

curiosity [1] - 79:23

curious [1] - 101:2

current [2] - 5:1, 20:16

customer[1] - 81:16

cytometry [1] - 9:23

D

daily [1] - 10:15

Data [5] - 73:22, 73:24,

74:12, 74:13, 75:3

data [190] - 10:12, 16:12,

26:16, 26:18, 26:20, 26:23,

26:24, 27:2, 27:3, 27:4, 27:5,

27:6, 27:7, 27:10, 27:12,

27:22, 28:14, 28:17, 28:19,

29:5, 29:11, 29:12, 29:24,

30:5, 35:2, 41:2, 41:3, 41:4,

43:2, 43:17, 44:2, 46:6,

46:21, 46:22, 50:7, 53:1,

53:11, 53:12, 53:14, 53:16,

54:17, 54:25, 55:4, 61:3,

61:13, 61:16, 61:18, 62:3,

62:9, 62:15, 62:23, 62:24,

63:9, 63:21, 64:3, 64:10,

64:12, 64:13, 64:18, 65:5,

65:6, 65:13, 65:20, 72:23,

73:2, 73:4, 73:6, 73:8, 74:15,

76:12, 76:14, 76:25, 77:2,

77:9, 77:14, 78:10, 79:5,

80:1, 80:14, 81:6, 81:11,

81:12, 81:13, 81:18, 81:24,

82:1, 89:18, 89:20, 93:10,

93:18, 93:19, 93:25, 94:15,

94:19, 94:22, 122:8, 122:10,

122:12, 122:16, 122:20,

127:24, 128:1, 128:3,

128:14, 129:14, 130:22,

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 215 of 236 PageID: 18798
131:5, 132:16, 136:2,

137:24, 139:21, 140:16,

144:22, 145:2, 147:5,

147:22, 148:2, 154:14,

155:25, 163:18, 165:2,

165:3, 165:15, 166:9,

169:19, 170:15, 171:18,

172:3, 172:4, 178:6, 178:10,

178:12, 178:16, 178:18,

181:25, 182:15, 182:24,

186:5, 186:8, 186:13, 188:2,

189:10, 189:13, 189:17,

191:12, 192:5, 192:11,

192:12, 195:9, 195:14,

195:17, 196:19, 196:24,

198:13, 198:14, 198:15,

201:3, 201:4, 201:24, 202:2,

202:5, 203:2, 203:6, 203:7,

203:14, 203:15, 203:21,

204:5, 204:8, 204:9, 204:10,

204:18, 204:21, 204:24,

205:2, 206:13, 206:16,

206:17, 206:19, 206:20,

207:4, 207:14

data) [1] - 139:23

database [6] - 28:9, 28:10,

62:4, 62:6, 77:1, 207:3

date [60] - 25:6, 26:3,

26:15, 27:15, 30:18, 31:15,

42:23, 42:24, 42:25, 52:19,

56:16, 63:10, 63:11, 66:1,

66:3, 67:3, 67:5, 67:16,

67:18, 67:19, 68:14, 69:15,

69:25, 71:23, 72:1, 72:5,

72:13, 72:14, 72:19, 72:23,

76:12, 78:10, 89:13, 90:7,

124:20, 124:24, 125:13,

125:18, 126:3, 126:8,

126:22, 127:18, 139:3,

147:1, 147:3, 149:8, 152:1,

152:2, 157:21, 163:9,

171:16, 172:1, 181:10,

181:13, 181:20, 182:6,

201:14, 201:15, 202:23

dated [4] - 116:11, 116:12,

116:23, 148:25

dates [7] - 62:15, 115:20,

116:16, 116:20, 117:1,

126:8, 160:17

David [1] - 45:17

Davis [1] - 45:17

days [5] - 10:3, 18:23,

28:13, 70:25, 102:16

deal [1] - 103:4

dealt [5] - 90:22, 102:24,

102:25, 104:5

decade [1] - 184:10

decades [2] - 107:20, 108:5

December [3] - 62:5, 67:6,

67:17

decided [2] - 152:6, 155:18

decision [9] - 69:2, 69:3,

69:4, 74:1, 100:5, 100:7,

100:18, 137:1, 195:13

decisions [2] - 74:9, 120:22

declarants [18] - 68:15,

68:19, 68:22, 69:13, 69:16,

70:10, 71:7, 157:12, 158:15,

158:25, 159:4, 163:5,

163:21, 164:4, 164:20,

165:7, 165:10, 165:22

declaration [26] - 33:24,

68:4, 68:19, 69:13, 69:16,

69:21, 70:4, 70:11, 70:22,

71:18, 79:19, 89:19, 156:16,

156:20, 156:22, 157:4,

157:18, 158:16, 159:24,

161:4, 161:8, 162:3, 162:22,

163:3, 170:23, 170:24

decrease [2] - 175:20,

192:16

decreased [2] - 174:14,

190:20

decreases [1] - 36:8

decreasing [1] - 175:5

Defendant [2] - 2:8, 2:13

defendants [4] - 4:6, 4:8,

4:11, 14:11

Defendants [1] - 1:10

defendants' [2] - 99:1,

99:25

defense [2] - 118:16,

118:23

defer [1] - 43:18

define [1] - 90:13

defined [6] - 19:20, 19:21,

39:10, 69:23, 150:8, 157:20

definitely [1] - 75:5

definition [32] - 31:20,

38:11, 90:21, 91:6, 95:18,

96:13, 96:18, 96:22, 97:23,

98:2, 98:5, 98:7, 98:8, 98:12,

98:25, 99:1, 99:5, 99:12,

99:25, 100:15, 103:14,

103:16, 103:20, 104:14,

104:19, 104:21, 106:6,

106:8, 106:15, 112:15,

113:23, 150:3

definitions [2] - 99:8,

100:11

degree [11] - 5:18, 5:24,

29:17, 40:17, 47:13, 98:20,

136:18, 183:22, 183:24,

183:25

delay [1] - 54:22

delayed [8] - 39:16, 69:5,

70:6, 70:24, 71:21, 128:15,

129:9, 157:8

delayed-onset [4] - 69:5,

70:6, 71:21, 157:8

demonstrate [3] - 55:5,

180:7, 182:25

demonstrated [4] - 56:25,

129:8, 195:17, 196:5

Demonstrative [1] - 166:3

demonstrative [5] - 16:15,

16:23, 170:6, 170:7, 170:8

denial [1] - 101:3

DePALMA [1] - 2:12

Deposition [1] - 115:16

deposition [18] - 109:8,

112:1, 115:11, 115:16,

116:8, 116:21, 117:2, 117:7,

117:8, 117:15, 124:4,

126:20, 137:19, 137:20,

140:1, 172:14, 173:3, 188:13

DEPUTY [1] - 4:12

describe [7] - 5:16, 59:22,

59:23, 68:21, 90:23, 168:4,

171:6

described [9] - 46:25,

71:17, 71:21, 74:25, 80:12,

138:23, 168:7, 168:25,

170:20

description [11] - 114:17,

114:18, 114:24, 115:2,

117:10, 117:16, 118:2,

118:15, 118:23, 125:12,

142:12

DESCRIPTION [1] - 3:10

descriptions [3] - 191:12,

192:12

design [10] - 21:17, 26:4,

36:11, 37:8, 47:11, 69:1,

86:15, 134:15, 167:21,

168:15

designated [1] - 5:11

designation [2] - 133:3,

168:1

designed [6] - 129:19,

130:1, 141:22, 142:12,

142:14, 187:15

designing [2] - 98:18,

98:23

designs [2] - 19:14, 47:16

despite [1] - 50:8

details [1] - 107:25

determination [2] - 35:21,

37:9

determine [3] - 27:8, 35:16,

149:23

determined [5] - 19:3,

61:20, 120:12, 121:4, 163:22

determining [1] - 19:11

develop [4] - 90:23, 104:17,

104:24, 110:9

developed [11] - 11:14,

68:24, 115:12, 116:15,

116:18, 117:3, 159:20,

160:2, 160:9, 160:12, 162:15

United States District Court

8

developing [3] - 17:13,

98:18, 98:23

development [16] - 4:22,

5:13, 7:6, 12:21, 14:9, 16:8,

33:18, 44:13, 57:7, 58:3,

98:13, 100:13, 104:15,

126:7, 183:13

Developmental [1] - 150:5

developmental [3] - 5:4,

7:9, 8:15

dibasic [2] - 83:6, 87:12

dice [1] - 23:8

difference [12] - 38:19,

38:22, 100:10, 104:14,

133:23, 134:21, 155:2,

167:12, 182:25, 188:11,

189:25, 194:4

differences [5] - 26:6, 59:1,

132:21, 133:4, 133:5

different [40] - 6:24, 8:10,

11:15, 11:17, 11:24, 20:9,

21:20, 22:22, 40:10, 43:16,

48:19, 48:24, 53:20, 88:24,

90:16, 93:8, 96:24, 97:23,

98:9, 98:10, 99:8, 121:3,

123:3, 128:22, 130:16,

134:7, 140:8, 140:16, 147:7,

148:6, 152:10, 154:11,

159:8, 172:24, 173:4,

188:14, 206:20

differently [1] - 58:16

difficult [3] - 147:4, 147:21,

180:21

difficulties [1] - 180:22

diluted [1] - 83:4

dim [1] - 91:1

DIRE [2] - 3:5, 4:15

direct [5] - 91:24, 130:17,

141:4, 184:22, 187:1

DIRECT [2] - 3:5, 14:17

directed [7] - 95:17, 99:3,

123:21, 154:4, 194:14,

197:3, 199:25

direction [2] - 136:4,

190:12

directly [1] - 51:12

director[2] - 5:3, 8:15

Director[2] - 181:3, 182:1

disagree [3] - 92:12, 93:7,

172:22

disagreement [3] - 91:11,

91:19, 102:3

disciplines [3] - 98:14,

100:15, 100:18

disclose [1] - 46:11

disclosed [1] - 52:12

discloses [1] - 46:12

disclosure [4] - 57:3,

122:1, 122:11, 125:13

discontinue [1] - 152:7

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 216 of 236 PageID: 18799
discuss [7] - 17:3, 90:20,

117:24, 120:8, 122:11,

148:16, 160:25

discussed [13] - 43:3, 44:3,

47:12, 62:16, 122:16, 124:3,

140:1, 141:16, 142:24,

145:21, 172:14, 206:15

discusses [1] - 147:14

discussing [5] - 4:9,

117:13, 140:13, 191:16,

191:17

Discussion [1] - 95:14

discussion [8] - 46:23,

91:24, 95:2, 96:6, 105:22,

143:15, 143:20, 208:4

disease [2] - 129:21, 130:3

diseases [1] - 8:11

disodium [1] - 87:12

dispute [11] - 90:14, 91:18,

96:15, 99:6, 100:1, 100:6,

121:23, 173:7, 173:18,

174:2, 174:3

distinction [4] - 32:22,

33:3, 131:4, 145:13

distribute [1] - 24:1

DISTRICT [3] - 1:1, 1:2,

1:14

Division [1] - 182:2

division [3] - 12:15, 151:16,

151:17

DJ [1] - 97:7

doc [2] - 10:11, 10:14

Docket [1] - 99:24

doctor[7] - 23:12, 23:20,

25:3, 31:16, 32:3, 40:5

Doctor [13] - 8:17, 29:18,

32:11, 47:21, 53:16, 81:3,

87:9, 111:2, 176:3, 176:8,

176:20, 198:24, 207:22

doctor's [1] - 90:4

doctors [1] - 97:19

doctrine [2] - 124:2, 124:5

doctrines [1] - 124:10

document [57] - 34:3, 34:6,

34:14, 34:23, 34:24, 35:1,

35:6, 35:14, 43:8, 44:7,

44:10, 44:20, 51:3, 51:7,

51:9, 51:10, 52:4, 52:21,

56:5, 56:8, 56:11, 59:11,

63:1, 63:3, 63:4, 63:12, 64:6,

65:10, 67:10, 67:12, 68:1,

115:22, 116:11, 116:14,

117:2, 126:15, 138:21,

139:10, 141:1, 141:7, 149:8,

149:14, 151:7, 151:13,

152:17, 153:9, 162:21,

164:15, 165:12, 165:18,

165:20, 168:13, 169:13,

169:14, 171:11, 178:12,

197:5

documents [24] - 31:7,

31:10, 31:13, 31:17, 31:22,

31:23, 32:7, 32:16, 32:19,

33:1, 33:7, 33:8, 52:1, 67:21,

82:16, 150:10, 150:18,

160:21, 165:9, 165:21,

171:7, 171:9, 195:1

dolasetron [2] - 128:24,

128:25

dollars [1] - 27:18

domain [2] - 126:6, 126:11

done [29] - 20:12, 20:24,

21:3, 21:25, 24:11, 26:14,

27:23, 27:24, 44:15, 60:25,

61:21, 71:25, 72:4, 81:19,

89:23, 96:9, 101:21, 101:24,

112:21, 112:25, 148:2,

164:4, 165:10, 165:15,

182:6, 195:23, 200:2,

204:10, 204:12

dopamine [1] - 11:23

Dosage [1] - 41:23

dosage [16] - 20:9, 39:22,

39:23, 90:6, 111:24, 112:8,

114:6, 114:13, 135:12,

136:6, 140:21, 149:23,

169:25, 177:6, 177:10, 187:7

dosages [4] - 173:8, 173:9,

173:23, 173:24

dose [157] - 17:14, 17:18,

18:8, 18:12, 18:14, 19:4,

19:5, 19:12, 19:20, 19:21,

22:7, 22:9, 22:10, 23:24,

34:8, 35:17, 36:9, 36:10,

37:3, 37:5, 37:7, 37:19, 40:4,

41:6, 42:2, 44:5, 46:18,

46:19, 46:20, 47:1, 47:8,

48:6, 48:12, 49:21, 49:22,

50:4, 50:7, 50:11, 50:16,

50:18, 50:22, 52:17, 52:25,

53:9, 53:11, 53:12, 54:22,

55:3, 55:6, 55:7, 55:15,

55:18, 56:2, 60:6, 60:9,

64:12, 64:13, 65:3, 66:6,

66:8, 68:17, 71:2, 83:13,

84:24, 89:21, 92:24, 93:1,

93:2, 93:11, 93:15, 97:20,

101:21, 101:22, 111:20,

112:6, 119:10, 129:9, 130:4,

130:23, 131:1, 131:7,

131:20, 132:21, 134:25,

137:12, 137:13, 137:25,

139:16, 139:21, 145:25,

147:6, 148:11, 149:22,

150:7, 150:8, 150:11,

150:19, 150:22, 151:6,

152:22, 154:22, 155:1,

155:9, 155:19, 156:1,

172:15, 172:17, 173:2,

174:7, 174:13, 174:18,

175:3, 175:4, 177:10,

177:21, 187:19, 189:13,

189:15, 190:4, 190:6,

190:22, 190:23, 191:9,

191:10, 191:11, 191:15,

191:16, 191:24, 192:6,

192:8, 193:8, 193:10,

193:16, 193:20, 194:1,

194:6, 194:16, 194:18,

194:24, 195:2, 195:4,

195:18, 196:2, 196:20,

196:25, 197:20, 198:12,

198:23, 198:25, 199:3,

199:9, 200:11

dose-ranging [1] - 36:9

doses [60] - 17:11, 17:21,

18:1, 18:11, 19:3, 34:9,

37:18, 37:25, 38:5, 41:25,

42:3, 46:12, 46:13, 46:20,

46:21, 46:22, 47:2, 47:4,

48:8, 48:10, 49:10, 49:12,

49:15, 49:23, 50:18, 50:19,

52:14, 52:16, 60:2, 77:15,

101:25, 131:5, 131:9,

131:12, 131:14, 131:18,

131:25, 132:10, 132:16,

150:22, 154:5, 154:9,

155:17, 172:24, 173:4,

174:20, 175:13, 190:11,

190:12, 192:3, 192:5,

192:13, 192:19, 192:22,

192:25, 195:8, 199:4, 199:5,

205:17

dosing [2] - 155:23, 196:15

double [6] - 23:21, 25:1,

36:6, 60:22, 93:13, 144:1

double-blind [1] - 25:1

double-blinded [4] - 23:21,

36:6, 93:13, 144:1

down [25] - 15:25, 35:10,

47:6, 62:18, 63:22, 70:19,

75:5, 77:18, 83:8, 84:18,

88:6, 91:8, 94:25, 131:24,

134:4, 138:16, 139:9,

139:20, 141:21, 166:25,

175:2, 181:23, 190:14,

192:15, 206:6

down-regulated [1] - 49:2

Dr [104] - 2:8, 4:8, 4:16,

4:18, 4:23, 14:11, 14:18,

15:2, 20:14, 24:7, 30:15,

31:13, 34:6, 34:13, 35:13,

36:3, 36:20, 42:22, 45:17,

45:18, 45:20, 45:21, 50:5,

50:6, 50:12, 50:20, 51:2,

51:6, 51:11, 54:8, 56:5,

56:10, 59:7, 59:9, 60:2,

61:16, 62:25, 65:9, 66:25,

67:9, 67:21, 67:25, 68:24,

69:1, 69:9, 69:19, 69:25,

United States District Court

9

70:21, 72:2, 83:21, 89:11,

92:11, 92:17, 92:22, 93:5,

93:25, 94:24, 97:3, 97:21,

99:25, 100:23, 103:6, 103:7,

103:11, 104:18, 107:8,

107:13, 118:4, 118:19,

124:3, 124:16, 124:25,

125:9, 130:8, 130:16,

136:22, 137:8, 137:18,

138:20, 139:6, 148:17,

148:22, 149:4, 149:7,

149:11, 150:13, 155:7,

157:22, 159:19, 159:22,

160:13, 161:5, 161:8,

161:12, 162:6, 162:13,

162:14, 162:19, 179:15,

183:17, 186:7, 202:6

DR [2] - 1:7, 1:8

Draft [2] - 152:18

drafted [1] - 161:18

drafts [1] - 117:22

dramatic [1] - 91:19

dramatically [1] - 98:9

draw [1] - 18:24

drawn [2] - 121:22, 166:8

driven [1] - 110:15

DRL [1] - 103:15

DRL's [1] - 103:20

Drug [4] - 18:4, 20:5, 22:2,

51:16

drug [98] - 7:3, 7:5, 8:24,

9:17, 12:20, 12:21, 13:10,

16:9, 17:4, 17:5, 17:12,

17:14, 17:21, 18:9, 18:10,

19:8, 19:15, 19:18, 19:25,

21:6, 22:12, 22:14, 22:17,

22:24, 22:25, 23:2, 23:11,

23:23, 23:24, 24:13, 24:14,

26:13, 26:19, 27:8, 27:20,

28:8, 33:25, 37:21, 39:8,

39:11, 40:2, 40:4, 40:15,

40:16, 44:4, 44:15, 46:13,

46:18, 48:18, 48:22, 49:3,

53:6, 54:19, 57:6, 63:8,

74:15, 74:23, 75:1, 76:18,

77:19, 77:20, 77:25, 78:1,

79:1, 83:24, 84:2, 84:3, 84:6,

90:6, 90:9, 90:15, 98:18,

104:17, 108:3, 108:17,

108:21, 109:1, 110:17,

110:23, 110:24, 111:20,

111:24, 112:9, 119:14,

129:20, 130:2, 130:5,

135:18, 136:6, 140:21,

169:5, 172:16, 183:13,

194:16, 201:5

drugs [24] - 5:23, 7:1, 8:4,

9:23, 11:14, 11:24, 12:22,

13:8, 20:14, 24:12, 24:21,

40:10, 40:18, 40:19, 53:9,

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 217 of 236 PageID: 18800
58:3, 77:17, 78:3, 78:6,

172:24, 173:4, 173:23,

175:6, 188:19

DSC [1] - 46:8

DSMB [1] - 74:19

DTX [2] - 47:15, 197:5

DTX-0 [1] - 186:3

DTX-0015 [3] - 44:16,

153:24, 196:10

DTX-0040 [1] - 181:9

DTX-0227 [3] - 34:3, 34:6,

193:5

DTX-0227-0015 [1] - 131:22

DTX-0254 [1] - 145:16

DTX-0264 [3] - 62:25,

178:5, 204:16

DTX-0268 [1] - 14:25

DTX-0276 [2] - 171:10,

188:5

DTX-0276-0005 [1] - 175:1

DTX-0287 [1] - 67:25

DTX-0287-0413 [1] - 156:15

DTX-0288 [2] - 59:7, 61:15

DTX-0288-0064 [2] -

166:17, 166:25

DTX-0288.0100 [1] - 169:11

DTX-0289 [1] - 66:24

DTX-0290 [1] - 67:9

DTX-0293 [3] - 51:9, 51:10,

140:25

DTX-1017 [1] - 197:5

DTX-1023 [1] - 148:15

DTX-1168 [1] - 115:15

DTX-1168.0093 [1] - 117:5

DTX-1179-0010 [1] - 129:23

DTX-1227 [1] - 56:8

DTX-15-0008 [1] - 153:23

Due [1] - 139:20

due [3] - 198:11, 198:12,

198:22

during [15] - 60:17, 64:16,

64:25, 71:5, 112:1, 113:6,

117:7, 117:8, 138:21,

141:11, 152:9, 175:6,

184:18, 188:13, 195:12

E

e-mails [1] - 57:25

early [5] - 20:19, 70:8,

71:22, 75:9, 157:9

earthshaking [1] - 90:3

easier [3] - 107:4, 168:6,

189:3

East [1] - 1:12

eat [1] - 12:6

educational [2] - 5:16,

183:18

effect [22] - 22:11, 22:18,

26:13, 33:20, 37:20, 37:21,

39:8, 41:20, 82:25, 83:2,

84:6, 84:15, 88:24, 88:25,

89:2, 100:6, 121:9, 126:4,

155:8, 160:14, 199:5, 199:8

effective [70] - 7:4, 16:9,

17:17, 18:2, 19:6, 19:8,

19:13, 19:20, 19:21, 20:2,

20:4, 22:7, 22:9, 27:9, 34:1,

35:3, 37:25, 38:1, 41:19,

42:1, 42:2, 47:1, 48:7, 49:21,

50:18, 53:6, 55:7, 55:15,

55:18, 66:6, 66:8, 68:15,

71:2, 71:14, 75:2, 77:20,

77:24, 85:4, 90:6, 93:15,

130:4, 132:11, 137:13,

141:10, 141:24, 152:23,

156:1, 172:16, 174:8,

174:17, 175:4, 175:18,

175:25, 177:6, 186:11,

186:15, 187:13, 191:6,

194:24, 195:2, 195:4, 195:8,

195:18, 196:2, 196:20,

196:22, 196:23, 197:1,

203:25

effectively [2] - 17:16, 41:7

effectiveness [1] - 190:11

effects [8] - 6:24, 22:15,

22:16, 40:18, 50:19, 57:1,

83:24, 206:5

efficacious [1] - 111:20

efficacy [41] - 4:9, 17:19,

20:15, 28:17, 34:8, 36:9,

36:24, 56:25, 60:10, 60:14,

64:19, 78:24, 83:13, 84:24,

90:16, 90:17, 129:20, 130:2,

130:12, 130:15, 136:23,

137:10, 137:25, 139:22,

142:5, 155:13, 165:3, 166:6,

168:1, 168:7, 168:14, 171:8,

171:18, 172:3, 172:4, 193:1,

196:5, 198:13, 198:16,

200:25, 204:24

effort [3] - 30:4, 103:22

efforts [3] - 108:16, 111:19,

126:7

eight [3] - 9:9, 62:18,

190:14

either [7] - 90:12, 101:22,

102:1, 158:21, 160:23,

160:24, 189:7

element [1] - 121:4

elicit [2] - 118:12, 118:23

elicited [1] - 91:9

Emend [1] - 11:20

emesis [18] - 39:16, 47:24,

48:13, 57:1, 57:11, 68:9,

70:24, 71:4, 99:4, 101:4,

101:7, 104:25, 129:9, 169:7,

172:9, 196:6, 198:4, 203:25

emesis-inducing [1] - 71:4

emesis-inducing [1] -

70:25

emetic [3] - 39:10, 191:6,

205:25

emetic-type [1] - 205:25

emetogenic [24] - 19:17,

34:12, 35:18, 41:10, 52:17,

60:24, 60:25, 78:22, 129:10,

141:11, 141:25, 144:11,

144:13, 144:16, 144:18,

144:23, 199:17, 199:20,

199:21, 199:23, 200:1,

200:3, 200:5, 201:5

emphasis [13] - 108:16,

108:20, 108:22, 108:24,

108:25, 110:6, 110:8,

110:13, 110:17, 110:23,

111:11, 111:19

employ [1] - 148:11

employed [2] - 4:24, 162:1

end [9] - 26:9, 28:22, 84:16,

114:22, 117:25, 118:9,

138:24, 142:6, 197:9

endothelial [1] - 86:10

endpoint [12] - 38:15,

60:18, 134:10, 134:12,

134:14, 134:17, 134:20,

135:5, 142:15, 155:4, 194:12

endpoints [2] - 38:10,

109:24

English [5] - 164:14,

164:20, 180:12, 180:18,

181:6

enjoy [1] - 13:4

enlarge [1] - 45:14

Enrico [9] - 68:20, 68:23,

69:22, 70:4, 156:23, 157:6,

157:18, 159:4, 159:18

enters [1] - 126:6

entire [4] - 10:18, 59:8,

63:18, 98:5

entirety [1] - 168:13

entitled [2] - 50:3, 150:5

episode [1] - 39:10

episodes [1] - 191:6

equal [1] - 49:11

equally [4] - 37:25, 42:1,

77:24, 132:10

equation [1] - 78:19

equivalent [12] - 20:1, 37:4,

37:6, 37:24, 48:1, 48:9,

48:10, 54:18, 77:25, 154:22,

187:16, 199:6

especially [1] - 141:11

ESQUIRE [11] - 2:3, 2:3,

2:4, 2:5, 2:7, 2:8, 2:10, 2:10,

2:11, 2:11, 2:12

essentially [2] - 97:24,

100:21

establish [8] - 69:22, 70:4,

United States District Court

10

129:19, 130:2, 136:23,

137:10, 157:4, 157:18

established [2] - 47:18,

52:2

estimation [1] - 116:19

et [6] - 101:11, 124:14,

160:22, 160:25

ethical [3] - 48:6, 75:11,

75:13

ethics [6] - 73:6, 73:15,

73:19, 73:20, 74:7

evaluating [4] - 90:16,

98:23, 109:24, 114:14

Evaluation [1] - 51:17

evaluation [1] - 97:4

event [10] - 19:1, 54:10,

71:1, 71:4, 108:2, 133:1,

145:11, 148:9, 153:25, 206:5

eventually [8] - 109:14,

111:25, 112:9, 137:4, 137:5,

140:22, 155:9, 184:14

EVID [1] - 3:10

evidence [7] - 89:11,

118:18, 137:24, 150:10,

165:9, 165:21, 167:14

evidentiary [1] - 118:6

evidently [2] - 116:25,

117:4

evolution [1] - 12:6

EWING [1] - 2:4

exact [2] - 116:20, 129:22

exactly [2] - 102:21, 105:14

EXAMINATION [5] - 4:15,

14:17, 107:7, 183:16, 204:15

example [7] - 58:10, 81:1,

81:2, 97:18, 172:25, 173:14,

173:16

exceeding [1] - 79:13

excerpts [1] - 122:11

exchanging [1] - 183:10

excipients [6] - 82:22, 83:5,

83:6, 84:23, 86:11, 90:15

exclude [1] - 96:8

excluded [2] - 36:23, 37:1

excuse [4] - 64:15, 87:9,

97:2, 99:14

executed [1] - 147:25

Exhibit [5] - 70:13, 70:16,

71:8, 115:16, 201:8

exhibit [1] - 166:21

exhibited [1] - 136:6

EXHIBITS [1] - 3:10

exhibits [5] - 106:24, 107:2,

118:6, 148:17, 148:23

existing [1] - 20:1

expect [4] - 53:7, 61:1,

85:7, 206:16

expected [4] - 37:20, 64:5,

77:13, 152:22

experience [25] - 8:13,

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 218 of 236 PageID: 18801
8:21, 8:22, 9:13, 10:22, 11:4,

11:8, 27:14, 41:8, 57:18,

64:1, 64:5, 64:8, 72:2, 72:6,

72:16, 74:11, 76:16, 79:6,

80:21, 98:16, 98:17, 98:22,

114:15, 190:4

experiencing [2] - 176:22,

205:14

experiments [5] - 8:3,

10:12, 184:12, 184:13

expert [21] - 4:18, 14:2,

14:12, 45:4, 92:17, 95:21,

99:25, 105:23, 106:13,

114:19, 115:3, 115:5, 115:8,

115:12, 118:5, 119:22,

121:25, 122:5, 122:6,

148:16, 148:17

expertise [11] - 14:8, 15:19,

16:7, 16:13, 83:15, 98:10,

98:15, 99:5, 99:11, 105:25

expertises [1] - 96:24

experts [6] - 43:9, 91:25,

92:12, 92:16, 106:4, 172:15

explain [7] - 11:8, 16:15,

73:11, 76:20, 78:15, 134:12,

167:19

explained [4] - 78:17,

166:16, 168:8, 188:14

explaining [3] - 33:17,

40:9, 112:2

explanation [4] - 54:15,

54:16, 90:25, 132:24

explore [1] - 123:19

extended [1] - 17:22

extensively [2] - 69:10,

161:15

extent [2] - 123:17, 164:20

extra [4] - 95:24, 192:19,

192:21, 192:23

extravasation [2] - 86:19,

86:20

extrude [1] - 12:7

eyes [1] - 145:11

F

F-R-U-E-H-A-U-F [1] - 4:14

face [1] - 149:5

fact [19] - 6:16, 30:9, 43:10,

102:19, 103:14, 104:13,

108:16, 111:23, 112:7,

115:1, 122:8, 122:16, 134:2,

148:16, 149:22, 165:10,

172:14, 180:8, 206:17

facts [2] - 101:10, 118:21

faculty [1] - 110:14

failure [6] - 39:10, 39:17,

53:25, 54:13, 54:22, 134:6

fair [4] - 160:20, 163:6,

166:13, 172:21

fall [1] - 12:13

familiar [4] - 69:11, 134:9,

161:15, 164:19

Family [1] - 5:7

family [1] - 160:19

far [5] - 30:10, 44:15, 100:7,

105:23, 168:6

Farrell [1] - 1:25

fashion [2] - 85:7, 100:10

fast [1] - 173:5

father [1] - 160:15

FDA [70] - 17:19, 18:3, 18:6,

19:7, 19:21, 21:21, 27:4,

28:20, 30:8, 30:9, 33:17,

51:5, 51:12, 51:14, 51:17,

52:25, 53:1, 55:3, 55:9,

55:24, 63:5, 81:13, 93:7,

102:12, 102:13, 105:19,

108:3, 108:7, 109:15,

109:18, 111:20, 111:25,

112:9, 119:11, 119:15,

135:3, 136:22, 137:3, 137:9,

137:11, 137:23, 138:3,

138:4, 139:1, 140:2, 140:11,

140:13, 140:22, 142:17,

142:19, 142:22, 143:6,

143:9, 144:8, 160:24, 179:6,

179:10, 179:12, 183:14,

194:14, 195:2, 195:11,

195:16, 195:24, 197:8,

197:13, 198:15, 199:10,

199:14, 206:24

FDA's [3] - 139:13, 145:11,

198:10

FDA-approved [5] - 102:12,

102:13, 108:3, 108:7, 109:18

features [1] - 71:9

February [1] - 63:11

fell [1] - 39:24

fellow [3] - 138:3, 184:13,

185:14

fellows [2] - 13:2, 13:3

fellowship [8] - 6:8, 107:13,

112:22, 112:23, 113:1,

113:6, 113:10, 113:11

felt [4] - 7:11, 38:25, 39:1,

39:4

females [1] - 36:22

ferret [1] - 17:12

ferrets [2] - 17:10, 17:11

field [7] - 13:12, 13:18,

97:10, 97:12, 97:14, 98:22,

171:3

figure [3] - 9:15, 105:25,

176:19

figures [3] - 80:18, 80:20,

134:4

file [2] - 18:3, 94:4

filed [8] - 51:19, 93:22,

93:24, 94:9, 99:19, 125:13,

125:18, 143:4

filing [2] - 126:8, 127:18

filled [1] - 39:1

filling [1] - 42:8

final [22] - 34:7, 59:13,

60:10, 65:6, 65:15, 65:17,

87:16, 96:2, 147:1, 147:3,

147:8, 147:19, 147:24,

202:23, 203:2, 203:15,

203:18, 204:2, 204:8,

204:11, 206:17, 207:5

finalized [1] - 146:19

finally [2] - 13:10, 148:4

fine [11] - 9:6, 17:25, 25:15,

35:7, 35:8, 52:3, 59:4, 96:6,

107:1, 129:3, 131:4

finish [2] - 67:5, 129:25

finished [3] - 95:1, 107:13,

182:20

firm [2] - 51:14, 81:2

first [53] - 4:8, 4:23, 8:22,

8:23, 8:24, 9:1, 25:6, 25:21,

25:24, 27:22, 28:25, 29:3,

33:10, 34:2, 37:16, 38:3,

38:14, 39:10, 47:14, 47:15,

53:19, 55:1, 59:6, 59:16,

60:17, 62:21, 64:11, 64:13,

64:25, 65:2, 67:15, 73:23,

95:21, 119:8, 120:14,

126:23, 127:22, 135:14,

149:14, 149:15, 156:24,

158:21, 158:22, 175:6,

190:16, 190:18, 190:21,

191:1, 196:17, 198:10,

207:1, 207:2

first-in-man [2] - 8:23, 8:24

Fisher [1] - 1:11

five [5] - 70:25, 71:5, 92:3,

118:7, 185:13

five-day [1] - 71:5

fixed [2] - 27:5, 49:12

flip [3] - 23:3, 23:7, 189:23

flow [1] - 9:23

focus [7] - 6:21, 7:19,

14:13, 38:7, 41:2, 125:17,

126:2

focused [3] - 92:5, 163:3,

189:5

focusing [1] - 146:15

folks [3] - 18:16, 33:13,

159:2

follow [7] - 10:8, 20:18,

21:15, 28:24, 58:1, 72:22,

191:20

following [7] - 46:13, 90:2,

95:10, 141:11, 141:25,

149:16, 191:22

food [1] - 95:12

footnote [1] - 131:24

FOR [1] - 1:2

United States District Court

11

forgive [1] - 157:6

form [5] - 30:23, 71:3,

127:8, 170:8, 187:7

formal [3] - 112:21, 112:25,

113:9

format [1] - 139:10

formed [1] - 33:8

formerly [2] - 149:8, 149:9

forming [8] - 14:19, 32:19,

44:7, 56:6, 63:12, 66:18,

67:22, 71:12

formula [2] - 85:16, 88:23

formulated [1] - 88:23

formulating [1] - 90:15

Formulation [4] - 145:16,

145:20, 146:16, 147:14

formulation [27] - 15:5,

47:8, 82:10, 82:11, 82:20,

83:15, 83:24, 84:7, 84:21,

84:24, 85:3, 85:5, 85:14,

86:4, 87:2, 88:15, 90:18,

96:21, 101:14, 103:3, 119:9,

119:10, 119:17, 119:25,

120:11, 120:16, 121:14

formulations [9] - 82:4,

82:6, 82:13, 82:17, 82:21,

97:11, 97:15, 98:19, 98:24

Formulations [1] - 145:18

formulator[26] - 15:9,

15:10, 85:12, 90:9, 91:13,

97:1, 97:12, 99:2, 100:16,

100:23, 101:12, 101:25,

102:14, 102:15, 102:17,

102:24, 103:23, 103:25,

104:12, 104:18, 104:24,

105:9, 105:11, 113:21,

114:1, 121:3

formulators [1] - 103:12

forth [3] - 17:25, 115:12,

183:11

forward [16] - 22:2, 46:6,

47:2, 58:11, 66:7, 102:8,

106:3, 106:16, 144:3, 147:6,

149:23, 177:19, 180:15,

195:3, 195:25

foundation [6] - 33:2,

34:17, 43:4, 57:15, 83:18,

116:8

foundational [1] - 51:25

four [8] - 6:10, 23:6, 37:18,

37:25, 41:25, 132:10, 159:2,

196:25

frame [1] - 146:15

framing [2] - 100:25, 101:5

free [1] - 125:3

frequently [1] - 11:22

Freuhauf [1] - 4:8

front [4] - 69:18, 106:7,

124:11, 129:18

FRUEHAUF [2] - 3:6, 4:10

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 219 of 236 PageID: 18802
Fruehauf [68] - 4:14, 4:16,

4:18, 4:23, 14:11, 14:18,

15:2, 16:18, 20:14, 24:7,

30:15, 31:12, 31:13, 34:6,

34:13, 35:13, 36:3, 36:20,

42:13, 42:21, 42:22, 51:2,

56:4, 56:5, 59:7, 59:9, 60:2,

61:16, 62:25, 65:9, 65:14,

65:25, 66:25, 67:9, 67:20,

67:21, 67:25, 69:9, 69:19,

70:21, 72:2, 76:23, 82:8,

83:21, 85:8, 88:21, 89:11,

92:11, 94:24, 97:3, 97:21,

100:23, 103:6, 103:11,

104:19, 107:8, 107:13,

118:20, 124:3, 124:25,

136:22, 137:8, 166:3,

183:17, 186:7

Fruehauf's [3] - 118:5,

124:16, 137:18

full [4] - 4:12, 7:18, 37:20,

109:21

full-time [1] - 7:18

fully [3] - 93:20, 94:15,

171:17

function [1] - 17:24

fund [1] - 69:6

fundamental [1] - 102:2

fundamentals [1] - 12:20

futility [6] - 74:21, 74:22,

74:25, 75:8, 75:12, 75:23

future [1] - 12:23

G

Gandara [9] - 45:17, 45:18,

45:20, 45:21, 50:3, 50:5,

50:6, 50:8, 50:20

Gandara's [1] - 50:12

gee [3] - 29:9, 54:20, 143:6

general [10] - 4:21, 16:19,

46:10, 59:1, 96:16, 96:18,

124:1, 135:3, 146:5, 173:7

generally [6] - 14:7, 117:11,

155:20, 172:17, 173:8,

173:24

generated [1] - 204:21

generation [2] - 49:3, 49:8

generator [1] - 23:4

GEORGE [1] - 2:10

German [4] - 73:18, 81:10,

81:15, 81:17

ginger [2] - 119:13, 119:18

given [15] - 8:25, 18:11,

23:13, 23:23, 23:24, 24:13,

24:14, 35:17, 61:4, 78:20,

147:19, 156:22, 188:18,

206:9

Given [1] - 142:5

glad [1] - 92:4

glean [1] - 168:14

glossary [1] - 25:5

goal [3] - 19:10, 26:11,

55:15

GOG [1] - 109:22

gosh [3] - 93:10, 151:17,

179:19

graduate [2] - 10:11, 61:24

grant [4] - 110:4, 110:11,

110:13, 113:6

grants [3] - 111:5, 111:6,

111:7

gravamen [1] - 118:8

great [1] - 180:16

greater [3] - 39:18, 136:15,

170:14

GREENBERG [1] - 2:12

grew [1] - 11:4

gross [2] - 80:18, 80:20

group [11] - 18:9, 19:9,

19:23, 64:14, 110:16,

132:21, 168:22, 168:23,

169:16, 169:17, 177:12

groups [3] - 167:11,

190:17, 190:19

grow [1] - 9:22

growing [1] - 7:1

guess [6] - 87:1, 89:2,

109:22, 127:10, 154:12,

180:11

gut [2] - 12:4, 12:7

guy [2] - 90:9, 90:11

gynecologic [2] - 175:6,

175:19

H

half [2] - 53:4, 173:1

halted [1] - 149:16

hand [3] - 9:5, 30:8, 153:15

handles [1] - 28:9

happy [1] - 109:4

hard [4] - 62:22, 101:19,

143:5, 173:5

hard-and-fast [1] - 173:5

HASTINGS [1] - 2:2

hate [1] - 51:24

head [1] - 184:9

headaches [1] - 174:21

heading [2] - 117:6, 169:15

HEALTHCARE [1] - 1:4

Healthcare [1] - 63:25

healthy [4] - 9:3, 9:5, 18:9,

21:5

hear [17] - 8:19, 22:4, 22:7,

34:13, 100:3, 101:20,

101:23, 101:25, 102:5,

102:7, 105:10, 105:11,

118:4, 179:16, 179:20,

193:18, 206:13

heard [15] - 51:11, 82:23,

97:12, 101:19, 102:15,

105:24, 126:4, 130:11,

138:1, 149:11, 149:18,

179:15, 179:23, 205:13

hearing [1] - 105:23

heavy [1] - 10:6

HEC [2] - 144:17, 145:2

height [1] - 77:23

held [3] - 45:10, 95:14,

208:4

help [5] - 10:14, 12:23,

27:18, 38:13, 75:10

helpful [2] - 43:14, 67:22

HELSINN [1] - 1:4

Helsinn [67] - 33:11, 33:12,

44:9, 44:12, 44:17, 44:21,

45:3, 46:5, 47:16, 48:4,

49:14, 49:20, 51:5, 51:11,

51:16, 53:14, 54:25, 55:11,

56:7, 56:13, 57:10, 58:14,

58:16, 59:2, 63:5, 63:25,

64:6, 67:22, 68:1, 70:14,

73:15, 73:18, 80:7, 81:15,

81:17, 93:24, 102:21,

139:15, 140:10, 142:22,

143:9, 144:7, 150:25, 151:1,

151:6, 154:7, 155:17, 162:1,

165:21, 165:22, 170:20,

177:18, 179:23, 181:15,

182:2, 195:1, 195:12,

195:16, 196:4, 197:8,

197:15, 198:6, 200:8, 203:21

Helsinn's [7] - 47:4, 56:23,

64:4, 126:7, 130:20, 162:18,

197:11

herein [1] - 32:15

high [8] - 17:11, 29:9,

139:16, 142:5, 143:7,

197:20, 200:11, 205:17

high-dose [3] - 139:16,

197:20, 200:11

higher [13] - 17:21, 40:24,

49:23, 50:18, 61:1, 78:5,

78:6, 155:9, 172:17, 173:8,

173:24, 199:9

highlight [3] - 131:23,

141:8, 189:12

highlighted [2] - 129:24,

139:12

highly [16] - 19:17, 34:12,

35:18, 41:10, 60:25, 78:21,

144:17, 144:23, 199:17,

199:20, 199:21, 199:23,

199:25, 200:3, 201:5

high-dose [1] - 200:13

hire [1] - 51:13

hired [3] - 51:15, 73:18,

81:9

historical [22] - 77:7, 77:10,

United States District Court

12

77:13, 78:1, 78:23, 79:8,

139:17, 145:8, 165:2, 166:6,

166:17, 167:13, 167:25,

168:2, 168:7, 168:14,

169:17, 169:19, 170:10,

197:24, 198:3, 204:24

history [1] - 5:16

hitting [1] - 90:24

hoc [1] - 29:10

home [1] - 207:23

honestly [1] - 179:19

Honor [42] - 4:5, 14:11,

24:6, 34:17, 42:12, 42:19,

43:4, 43:7, 43:13, 47:20,

59:4, 80:23, 83:10, 83:14,

88:19, 89:7, 90:19, 92:6,

96:9, 96:11, 96:12, 97:3,

97:11, 98:5, 99:13, 102:20,

103:15, 105:1, 105:17,

106:18, 106:21, 113:5,

115:18, 118:7, 118:14,

123:17, 138:8, 156:5, 178:3,

184:20, 195:20, 208:1

Honor's [1] - 105:15

HONORABLE [1] - 1:14

hopeful [9] - 179:16,

179:23, 179:24, 179:25,

180:3, 180:4, 180:5, 180:17,

182:24

hospital [2] - 10:5, 81:3

hour [1] - 134:4

hours [26] - 38:9, 38:11,

38:20, 39:10, 39:18, 41:4,

54:1, 60:17, 64:11, 64:25,

65:2, 128:15, 133:12,

133:24, 135:15, 141:12,

169:16, 175:6, 189:19,

189:24, 190:17, 190:19,

190:21, 191:7, 193:21

HPA003 [1] - 60:9

HPLC [1] - 9:24

hum [2] - 170:9, 181:14

human [20] - 7:10, 8:25,

15:20, 17:9, 18:25, 31:4,

37:11, 61:5, 70:25, 71:1,

71:25, 72:3, 119:4, 119:8,

120:5, 138:5, 138:6, 171:18,

172:2, 172:4

humans [11] - 10:1, 19:4,

19:13, 30:19, 35:23, 70:7,

71:10, 120:15, 157:9, 171:8,

194:6

hundred [1] - 54:13

hundreds [1] - 185:6

hurry [1] - 92:4

hurting [3] - 74:16, 75:1,

75:5

hydrochloric [1] - 88:11

hydrochloride [3] - 71:4,

87:7, 87:16

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 220 of 236 PageID: 18803
hydroxide [2] - 87:7, 87:15

hypotheses [2] - 141:23,

142:12

hypothesis [2] - 110:15,

170:25

hypothesis-driven [1] -

110:15

hypothetical [6] - 31:18,

31:24, 43:11, 106:1, 122:22,

123:7

hypotheticals [1] - 43:10

hysterectomy [1] - 171:24

I

I.V [10] - 24:14, 50:9, 52:14,

88:23, 129:9, 152:23,

171:22, 175:4, 191:5, 205:17

ID [1] - 3:10

idea [11] - 70:5, 70:8, 71:20,

96:18, 96:19, 96:23, 99:7,

105:18, 157:7, 157:9, 157:14

ideas [2] - 7:21, 111:9

identical [8] - 53:18, 65:16,

65:17, 65:18, 82:14, 85:7,

97:24, 192:18

identified [1] - 20:19

identify [1] - 46:25

ignoring [1] - 105:13

II [92] - 8:16, 19:10, 19:11,

19:20, 20:9, 21:15, 25:8,

28:2, 32:8, 33:9, 33:21, 34:3,

35:14, 35:15, 36:3, 36:5,

36:11, 36:12, 36:21, 37:8,

41:20, 46:23, 46:24, 46:25,

47:1, 47:16, 48:4, 48:8, 48:9,

49:20, 53:11, 53:13, 54:25,

55:5, 55:14, 55:17, 55:19,

56:2, 56:23, 56:24, 57:6,

60:18, 60:25, 61:2, 66:6,

82:5, 82:10, 82:18, 82:20,

82:21, 84:7, 85:3, 87:5,

87:10, 87:23, 89:1, 89:17,

93:10, 94:19, 109:14,

109:23, 129:18, 130:1,

130:20, 137:6, 138:24,

141:9, 142:6, 142:10,

143:14, 143:21, 144:1,

144:21, 144:24, 145:2,

145:25, 147:21, 149:11,

149:17, 152:22, 182:21,

196:5, 197:9, 198:18,

198:19, 199:3, 199:11,

199:14, 199:25, 200:9

III [85] - 8:16, 19:22, 19:24,

20:2, 20:4, 20:10, 21:25,

25:8, 28:2, 28:3, 28:21,

33:19, 33:22, 33:23, 42:22,

47:3, 47:5, 47:11, 49:23,

51:21, 52:7, 55:12, 58:19,

59:2, 66:7, 66:11, 66:18,

75:10, 81:3, 82:5, 82:11,

82:18, 84:21, 84:23, 85:5,

87:3, 87:25, 88:23, 92:23,

93:12, 93:25, 94:3, 111:11,

122:20, 127:24, 128:2,

128:23, 137:7, 143:8,

143:19, 143:23, 144:3,

144:7, 144:23, 144:24,

146:1, 148:11, 150:12,

150:20, 152:18, 154:9,

155:9, 155:18, 155:19,

167:2, 170:1, 176:18,

176:25, 177:19, 181:16,

182:24, 195:3, 195:14,

196:1, 196:2, 199:17,

199:20, 199:21, 200:15,

201:6, 202:5, 202:10, 202:21

illness [1] - 19:5

imagine [3] - 135:22, 145:6,

164:16

imagined [1] - 138:4

immediately [2] - 86:7,

88:12

impact [3] - 7:1, 84:24, 89:4

impeachment [1] - 138:9

impinges [1] - 120:13

implement [2] - 69:6, 81:11

implications [2] - 174:16

implicitly [1] - 179:10

important [7] - 27:15,

44:10, 86:3, 86:5, 89:5,

102:3, 162:25

importantly [1] - 71:24

impossible [1] - 30:3

improper [1] - 90:12

improve [3] - 17:6, 40:16,

175:20

impulse [1] - 11:18

in-license [1] - 33:14

in-licensed [1] - 33:15

inactive [5] - 82:22, 82:24,

83:5, 83:6, 84:23

inadequate [3] - 139:21,

198:13, 198:16

INC [2] - 1:8, 1:8

Inc [1] - 116:2

incidence [2] - 174:14,

174:21

include [10] - 7:5, 9:10,

35:21, 77:14, 77:15, 94:14,

94:18, 94:21, 127:14, 192:6

included [6] - 65:6, 87:11,

103:20, 127:15, 127:16,

155:24

includes [6] - 73:15, 99:5,

103:21, 104:15, 130:4,

176:21

including [9] - 91:13,

91:14, 91:17, 100:15, 101:6,

197:20, 200:10, 200:13,

205:25

inconsistencies [2] -

102:18, 104:4

incorporate [1] - 106:6

incorporated [3] - 96:18,

96:22, 105:19

incorporating [1] - 106:14

increased [2] - 174:21,

199:8

increasing [1] - 18:10

IND [5] - 21:22, 21:24, 25:7,

51:18, 143:5

indeed [1] - 158:9

independent [1] - 73:17

index [1] - 106:12

indicate [6] - 49:21, 56:1,

62:3, 62:6, 64:2, 64:23

indicated [1] - 100:12

indicates [3] - 64:3, 71:13,

105:18

indicating [2] - 165:10,

165:21

indication [25] - 76:17,

129:19, 130:2, 130:15,

132:19, 135:4, 141:16,

142:16, 142:25, 144:9,

144:15, 144:17, 144:25,

163:5, 164:5, 164:25,

171:23, 176:10, 179:4,

179:9, 179:12, 186:15,

186:18, 199:24, 201:5

indicative [1] - 102:21

individual [2] - 99:9

INDs [2] - 21:19, 51:18

induced [18] - 15:21, 15:22,

16:11, 46:15, 48:13, 50:11,

55:7, 64:22, 66:9, 68:9,

71:15, 89:22, 93:16, 119:5,

120:6, 121:5, 173:2, 186:19

inducing [1] - 71:4

Industries [1] - 116:3

INDUSTRIES [1] - 1:9

industry [1] - 133:6

ineffective [1] - 175:13

inferior [4] - 141:23,

168:18, 187:14, 187:15

inferiority [4] - 167:24,

168:16, 205:2, 205:9

inflexion [1] - 50:16

inform [4] - 66:4, 79:18,

97:4, 187:12

information [10] - 17:19,

18:6, 19:7, 49:18, 49:19,

97:4, 107:11, 125:1, 126:6,

126:10

informing [1] - 103:1

infrequently [1] - 58:1

ingredient [9] - 15:6, 24:19,

82:12, 82:14, 83:1, 84:9,

United States District Court

13

89:4, 90:17, 101:15

inhibitor[2] - 11:21, 49:8

inhibitors [1] - 11:21

initial [5] - 28:16, 28:18,

62:9, 62:12, 65:5

initiated [2] - 59:16, 70:14

inject [2] - 86:16, 119:18

injected [5] - 83:1, 84:8,

85:21, 86:18, 88:25

injection [6] - 24:19, 38:5,

49:14, 83:9, 83:12, 86:5

inpatient [1] - 10:4

input [1] - 28:10

inquire [1] - 125:3

inquiry [2] - 93:6, 105:10

insert [1] - 119:15

inserted [1] - 170:7

inserts [1] - 13:9

inside [3] - 45:3, 86:8, 86:9

instance [7] - 11:19, 17:10,

22:23, 28:21, 53:10, 77:7,

97:2

Institute [7] - 5:11, 6:11,

6:14, 6:18, 10:24, 111:4,

111:8

institution [4] - 53:7,

185:23, 185:24, 186:1

instructed [1] - 125:1

intend [1] - 25:24

intended [9] - 17:5, 19:9,

22:11, 22:15, 22:18, 39:8,

82:25, 84:6, 131:25

intent [2] - 131:17, 178:24

intent-to-treat [1] - 178:24

intentions [1] - 33:17

inter [1] - 99:4

interact [2] - 86:7, 103:5

interaction [1] - 151:5

interesting [2] - 102:7,

199:15

interface [1] - 18:5

interfere [1] - 84:3

interfering [1] - 84:6

internal [2] - 44:23, 99:24

internally [1] - 154:7

interpose [1] - 135:8

interpret [10] - 49:18,

55:24, 56:1, 100:24, 112:14,

124:12, 141:13, 160:4,

164:3, 180:21

interpretation [3] - 44:14,

124:7, 163:21

interpreted [4] - 49:20,

100:20, 107:10, 159:15

interpreting [1] - 123:8

interrupt [2] - 51:24, 142:7

intervention [1] - 11:6

intimate [1] - 160:5

intravenous [8] - 34:9,

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 221 of 236 PageID: 18804
38:5, 50:23, 50:24, 88:13,

97:10, 119:4, 120:5

invalid [2] - 115:2, 118:1

invalidity [3] - 100:19,

117:15, 117:22

Invalidity [1] - 116:3

invention [4] - 69:23,

101:4, 125:14, 157:19

inventor [1] - 158:9

inventors [3] - 72:17,

125:14, 149:5

investigation [1] - 53:3

Investigation [1] - 53:3

investigational [2] -

110:14, 110:15

Investigational [2] - 18:4,

22:1

investigations [1] - 110:10

investigator[4] - 53:2,

185:18, 185:22, 185:24

investigators [4] - 27:15,

73:1, 110:6, 185:25

investment [1] - 27:17

invited [1] - 45:4

involve [3] - 102:14, 108:9,

108:14

involved [28] - 8:16, 9:8,

13:11, 29:6, 36:20, 85:16,

98:12, 100:13, 104:15,

107:17, 107:20, 111:11,

111:23, 112:2, 112:5, 112:8,

112:12, 112:16, 117:21,

140:20, 160:1, 160:8, 161:5,

161:19, 162:7, 184:19,

184:24, 185:5

involves [6] - 98:13,

100:14, 114:5, 153:3, 179:9,

179:10

involving [5] - 97:14, 98:9,

107:21, 114:13, 177:18

IRB [1] - 53:3

irrelevant [2] - 101:23,

102:1

irritate [3] - 86:12, 86:16,

86:24

Irvine [15] - 4:25, 5:2, 5:6,

5:14, 6:8, 7:16, 7:19, 9:10,

12:11, 13:11, 73:24, 107:16,

108:5, 184:14, 185:7

ISAAC [1] - 2:3

issue [8] - 57:13, 90:22,

98:8, 101:17, 114:23,

123:18, 172:18, 196:4

issued [2] - 58:13, 58:17

issues [4] - 21:16, 95:17,

97:19, 103:25

Italian [3] - 158:16, 159:10,

180:12

itself [3] - 21:24, 78:8, 84:9

J

January [17] - 30:18, 31:3,

62:8, 62:13, 63:23, 64:4,

64:6, 64:18, 65:12, 66:2,

89:13, 89:19, 93:23, 94:4,

94:9, 148:25, 181:11

jargon [1] - 130:14

JERSEY [1] - 1:2

Jersey [1] - 1:12

job [1] - 143:6

John [2] - 4:8, 4:14

JOHN [2] - 3:6, 4:10

JOHNSON [1] - 2:11

joint [1] - 151:2

JOSEPH [1] - 2:3

journal [2] - 127:10, 127:14

journals [2] - 13:22, 14:1

Jovial [1] - 4:6

JOVIAL [1] - 2:10

judge [4] - 76:20, 124:13,

134:12, 171:7

Judge [1] - 103:8

JUDGE [1] - 1:14

judge's [1] - 125:7

Judge's [1] - 167:4

JULIA [1] - 2:11

July [10] - 42:25, 44:9,

44:11, 45:13, 51:3, 59:21,

67:8, 67:15, 147:7, 147:9

jumping [1] - 70:10

June [9] - 1:13, 4:1, 115:13,

116:18, 126:23, 146:20,

201:16, 203:14

justification [1] - 52:25

K

Kathleen [1] - 149:1

keep [6] - 33:3, 48:22, 52:4,

85:12, 105:14, 154:8

keeping [1] - 156:4

kept [2] - 58:3, 184:7

key [4] - 16:10, 31:13, 33:8,

144:15

kg [1] - 190:4

Kibbe [1] - 100:1

kidney [1] - 8:11

kidneys [1] - 17:24

kilogram [32] - 35:17, 37:6,

38:2, 49:11, 50:10, 50:22,

55:5, 131:19, 132:2, 132:4,

132:6, 132:7, 132:12,

133:16, 134:23, 154:23,

155:1, 174:19, 177:7,

177:10, 177:14, 191:4,

191:5, 191:15, 192:14,

193:1, 193:21, 195:8,

195:13, 195:18, 196:21

kind [8] - 8:20, 10:6, 32:6,

42:1, 54:18, 78:21, 96:16,

103:13

knowing [3] - 147:5,

159:14, 162:6

knowledge [5] - 94:2,

124:12, 124:16, 151:5, 160:5

known [9] - 30:18, 30:22,

34:19, 89:13, 92:12, 171:3,

180:9, 194:15

knows [3] - 24:19, 24:23,

105:9

L

L.Pat.R.3.6(c) [1] - 116:4

lab [3] - 10:8, 10:11, 162:16

label [2] - 139:16, 200:4

labeled [4] - 197:19,

197:20, 200:10, 200:13

labeling [3] - 143:22,

145:12, 145:14

labels [1] - 53:19

Laboratories [1] - 2:8

laboratories [1] - 9:19

LABORATORIES [2] - 1:7,

1:8

laboratory [7] - 6:23, 7:22,

8:3, 9:13, 9:22, 107:17,

184:1

lack [8] - 115:2, 117:10,

117:16, 137:25, 139:20,

198:11, 198:12, 198:22

lacking [1] - 118:1

language [6] - 97:16, 99:20,

101:17, 164:15, 180:22,

181:6

large [2] - 110:11, 110:15

larger [5] - 19:22, 19:23,

58:17, 174:20, 181:10

largest [3] - 174:18, 175:3

LARNER [1] - 2:7

last [29] - 26:2, 26:11,

26:12, 26:15, 26:17, 26:21,

39:9, 59:19, 67:16, 67:17,

69:15, 72:23, 76:12, 78:9,

79:23, 80:14, 110:20, 141:7,

141:21, 146:23, 147:10,

163:13, 163:15, 163:23,

163:24, 164:2, 200:23,

200:24

last-patient-out [1] - 67:16

late [1] - 13:24

law [2] - 124:2, 124:10

lawyers [2] - 8:20, 95:2

lay [2] - 34:16, 83:18

layers [1] - 151:23

lead [3] - 37:21, 109:14,

109:17

leading [3] - 195:21,

195:23, 200:16

United States District Court

14

leak [1] - 86:20

leaked [1] - 86:18

learn [1] - 33:13

learned [1] - 29:13

least [11] - 22:12, 70:8,

71:22, 92:4, 95:19, 106:16,

124:15, 124:18, 157:9,

168:6, 187:16

leave [1] - 90:18

leaves [1] - 101:18

leaving [1] - 188:17

lecture [1] - 13:3

led [1] - 164:8

Lee [3] - 149:1, 149:4,

149:11

Lee's [1] - 150:13

left [6] - 42:21, 82:9, 95:7,

153:15, 190:12, 207:25

left-hand [1] - 153:15

legal [10] - 31:20, 102:6,

121:23, 123:18, 158:5,

158:6, 158:13, 158:14,

159:15

legally [1] - 102:1

less [7] - 7:3, 77:19, 77:20,

129:4, 132:21, 133:5, 192:25

letter [19] - 33:16, 51:5,

51:16, 51:22, 52:8, 63:5,

63:10, 63:11, 63:15, 63:19,

74:12, 74:19, 76:5, 140:25,

148:25, 150:13, 150:15,

181:20, 182:5

letting [1] - 104:13

level [3] - 10:15, 21:3, 97:8

levels [2] - 18:25, 20:9

license [3] - 33:14, 152:10,

183:14

licensed [4] - 33:12, 33:15,

51:18, 57:6

licensed-in [1] - 51:18

licensure [2] - 63:8, 63:9

life [1] - 11:5

light [1] - 182:4

likelihood [29] - 15:20,

16:11, 30:19, 31:5, 31:14,

35:19, 35:22, 37:10, 41:6,

44:5, 57:11, 61:4, 61:7,

64:20, 64:21, 66:9, 89:15,

89:21, 92:13, 92:25, 93:3,

93:16, 119:4, 119:9, 120:6,

143:7, 188:3, 194:6, 198:8

likely [13] - 7:3, 7:4, 22:13,

29:19, 50:10, 50:19, 50:22,

120:5, 141:18, 141:19,

141:20, 146:22

likened [1] - 130:17

limitation [6] - 101:5,

101:22, 114:14, 120:12,

121:4, 124:13

limited [2] - 99:1, 121:13

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 222 of 236 PageID: 18805
Limited [1] - 116:3

limiting [1] - 99:21

Line [2] - 109:11

line [5] - 89:24, 103:21,

141:7, 141:21, 156:24

lines [4] - 7:12, 8:4, 119:2,

190:14

linked [1] - 110:4

list [1] - 46:18

listed [5] - 46:19, 82:9,

84:23, 149:4, 170:10

listen [1] - 116:9

listening [1] - 162:13

LITE [1] - 2:12

literature [3] - 57:19, 57:21,

57:23

litigation [2] - 159:6,

171:14

live [1] - 158:7

liver [1] - 17:25

LIZZA [1] - 2:5

LLC [2] - 1:4, 2:12

lobbying [1] - 155:8

local [1] - 13:16

lock [2] - 27:3, 27:4

locked [11] - 27:6, 27:12,

62:4, 65:21, 65:22, 65:23,

77:1, 80:4, 204:9, 204:10,

207:3

logically [1] - 121:19

Lombardi [2] - 100:12,

104:12

LOMBARDI [21] - 2:10,

43:13, 90:19, 96:11, 98:4,

98:17, 99:15, 102:5, 102:20,

103:10, 103:19, 104:2,

104:8, 105:1, 105:3, 105:5,

105:7, 106:17, 106:20,

106:23, 208:1

long-acting [1] - 174:17

look [38] - 26:16, 29:22,

45:14, 52:10, 54:17, 54:20,

59:6, 60:1, 60:14, 64:10,

64:12, 66:24, 70:19, 77:2,

78:12, 87:2, 102:8, 115:15,

119:1, 119:2, 124:23,

126:14, 127:21, 128:1,

132:9, 140:16, 140:24,

151:12, 165:12, 166:3,

169:11, 189:10, 190:5,

190:25, 194:10, 194:23

looked [12] - 6:25, 33:9,

33:11, 60:18, 60:23, 60:24,

117:5, 150:17, 154:25,

167:19, 168:13, 198:2

looking [17] - 17:23, 29:12,

35:14, 38:8, 54:7, 62:18,

73:25, 99:18, 101:7, 111:15,

123:22, 135:11, 141:21,

145:22, 146:25, 152:10,

183:14

looks [5] - 76:6, 87:5, 93:9,

124:18, 124:19

losing [1] - 106:2

low [9] - 35:10, 37:19, 48:5,

77:17, 78:21, 131:20, 190:6,

199:4, 199:5

lower [18] - 18:8, 38:16,

38:24, 39:20, 52:16, 131:12,

131:14, 166:8, 166:14,

166:25, 190:11, 190:12,

191:9, 191:11, 191:16,

192:2, 192:5, 192:13

lowest [3] - 132:21, 134:22,

194:24

LTD [2] - 1:7, 1:9

Luigi [2] - 181:3, 182:1

lunch [1] - 95:24

Luncheon [1] - 96:5

lung [1] - 45:23

M

M.D [3] - 6:3, 184:5

M.D./Ph.D [2] - 5:20, 183:25

ma'am [43] - 6:4, 16:2,

18:18, 23:18, 25:17, 38:10,

42:5, 47:22, 48:17, 49:7,

50:24, 55:21, 57:20, 57:22,

57:24, 66:14, 69:4, 75:18,

75:20, 76:9, 79:15, 80:5,

81:9, 82:2, 85:15, 85:17,

85:20, 86:2, 87:22, 87:24,

95:4, 111:17, 124:17,

135:13, 136:8, 136:10,

163:14, 170:2, 176:4, 178:2,

183:9, 200:2, 207:24

Macciocchi [9] - 68:24,

69:1, 69:22, 70:4, 157:5,

157:18, 159:19, 159:22,

162:19

mails [1] - 57:25

maintain [2] - 82:24, 110:13

maintains [1] - 15:5

major [3] - 175:6, 175:19,

188:16

majority [1] - 11:10

majors [1] - 12:18

males [1] - 36:22

man [2] - 8:23, 8:24

manage [1] - 11:5

management [1] - 162:9

managing [1] - 10:14

manner [1] - 120:4

MANO [1] - 2:11

manuscript [1] - 13:24

March [2] - 116:12, 139:3

margin [1] - 175:2

Marinol [1] - 11:19

marked [1] - 115:16

markers [3] - 9:16, 109:24,

110:4

MARY [1] - 1:14

MASCC [2] - 127:23,

206:11

match [1] - 87:19

matches [1] - 19:5

material [1] - 146:12

matter [10] - 15:3, 15:4,

23:6, 119:24, 120:9, 120:20,

121:9, 121:20, 121:23,

124:10

maximal [1] - 41:20

MAYRA [1] - 2:12

mean [37] - 7:25, 9:12,

22:19, 24:7, 25:6, 26:3,

27:17, 28:6, 28:12, 30:2,

30:3, 41:8, 53:2, 53:6, 72:2,

72:6, 72:17, 74:1, 93:14,

114:18, 125:24, 130:16,

131:21, 132:15, 147:4,

148:24, 151:19, 157:25,

163:4, 172:9, 179:6, 182:10,

188:9, 198:1, 198:15,

198:23, 199:3

meaning [3] - 103:24,

141:15, 141:17

meaningful [5] - 100:10,

101:5, 101:16, 104:23

means [16] - 38:11, 39:15,

63:6, 77:17, 86:23, 103:22,

122:25, 124:13, 133:22,

134:13, 158:2, 158:13,

169:5, 180:13, 183:11,

200:18

meant [5] - 103:24, 112:17,

112:19, 139:12, 180:18

measured [1] - 26:13

MEC [7] - 142:16, 143:1,

143:11, 144:9, 179:3, 179:12

mechanism [1] - 48:18

mechanisms [1] - 11:13

median [2] - 38:18, 39:9

mediate [1] - 83:2

mediating [2] - 84:9, 84:11

medical [12] - 5:20, 5:24,

6:6, 6:10, 7:16, 12:16, 13:1,

15:13, 18:20, 45:21, 97:19,

99:2

medication [5] - 38:23,

136:13, 169:9, 189:4, 191:7

medications [9] - 11:1,

11:2, 11:11, 152:21, 188:17,

205:15, 205:18, 205:21

medicine [10] - 5:3, 18:23,

38:13, 38:14, 38:17, 39:13,

39:14, 98:21, 189:5, 206:8

medicines [1] - 192:17

meds [1] - 205:25

meet [1] - 98:19

United States District Court

15

meeting [40] - 33:11, 33:13,

33:15, 44:9, 44:10, 44:18,

45:5, 45:16, 46:2, 46:4,

46:11, 46:23, 50:2, 50:6,

51:4, 63:6, 127:2, 127:15,

138:24, 139:1, 139:7,

139:11, 142:23, 143:5,

150:25, 151:2, 153:3, 153:4,

153:23, 155:23, 155:24,

160:22, 177:17, 195:11,

195:12, 196:10, 197:8,

197:9, 203:11, 204:10

Meeting [1] - 50:3

Meetings [1] - 44:21

meetings [8] - 13:15, 45:10,

45:12, 45:15, 46:3, 47:12,

153:19, 160:24

meets [1] - 84:17

melanoma [4] - 8:11, 13:3,

13:4, 21:20

member [1] - 13:13

membrane [1] - 12:22

memory [1] - 131:21

mentioned [3] - 24:6,

195:11, 207:10

mentioning [1] - 161:21

message [1] - 13:23

met [1] - 26:11

meta [3] - 167:17, 168:25

meta-analysis [3] - 167:17,

168:25

method [9] - 70:23, 71:9,

71:10, 71:25, 72:3, 109:14,

109:18, 114:5, 114:7

methodology [1] - 35:25

methods [2] - 108:7, 168:4

mg [1] - 190:4

MGI [1] - 181:15

mgs [2] - 171:4, 180:9

microgram [18] - 50:10,

50:21, 55:5, 131:19, 132:1,

132:4, 132:6, 132:12,

133:16, 134:22, 154:23,

154:25, 177:7, 177:9,

177:14, 191:15, 192:14

microgram-per-kilogram

[1] - 191:15

micrograms [13] - 35:17,

37:5, 37:6, 38:2, 49:11,

174:19, 191:3, 193:1,

193:20, 195:8, 195:13,

195:18, 196:21

microscope [1] - 17:23

middle [2] - 29:23, 196:14

midway [1] - 175:2

might [16] - 6:24, 20:3,

23:1, 26:6, 38:17, 38:25,

39:1, 43:14, 45:24, 90:16,

95:19, 138:4, 164:25,

196:23, 204:12, 207:4

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 223 of 236 PageID: 18806
milligram [34] - 37:2, 41:2,

44:5, 48:15, 48:16, 49:21,

50:16, 52:16, 53:12, 55:6,

55:18, 56:2, 60:6, 60:9,

64:12, 64:13, 66:8, 68:17,

71:20, 83:13, 84:24, 85:6,

89:21, 146:1, 148:11, 150:8,

150:12, 150:20, 152:23,

154:11, 189:15, 190:22,

191:5, 192:8

milligrams [28] - 37:10,

41:5, 47:9, 47:10, 48:11,

48:15, 49:13, 60:5, 61:3,

64:19, 71:3, 71:14, 82:15,

82:17, 85:3, 89:14, 128:18,

129:1, 129:2, 151:8, 154:8,

172:25, 173:1, 177:15,

187:6, 187:7, 187:13, 187:18

milliliter[2] - 46:18, 47:10

milliliters [2] - 24:13, 49:16

millions [1] - 27:18

mind [8] - 85:12, 119:20,

147:2, 153:5, 156:7, 180:13,

180:17, 180:20

mine [1] - 103:19

minimal [5] - 42:2, 49:21,

55:6, 66:6, 195:2

minimally [6] - 46:25,

50:17, 55:15, 55:18, 137:12,

195:4

minimum [5] - 22:7, 22:9,

22:17, 130:4, 195:18

minute [4] - 74:6, 81:14,

87:9, 195:24

minutes [24] - 33:11, 38:5,

44:9, 44:11, 44:18, 46:2,

46:11, 50:2, 51:4, 65:3, 92:3,

138:24, 139:1, 139:12,

153:4, 153:18, 153:23,

155:23, 155:24, 160:22,

177:17, 195:11, 195:12,

196:11

mischaracterized [1] -

193:13

misheard [1] - 118:13

mispronouncing [1] -

157:5

misread [1] - 110:20

misspoke [1] - 142:8

misstatement [1] - 176:15

mistake [2] - 29:23, 54:14

mistakes [3] - 26:24, 30:3,

138:6

misunderstanding [1] -

199:1

mitigate [1] - 17:9

mixed [1] - 180:18

model [2] - 18:2, 18:14

modelled [2] - 169:16,

169:19

models [1] - 17:8

moderate [1] - 78:21

moderately [8] - 52:17,

60:24, 129:10, 141:25,

144:11, 144:13, 144:16,

200:5

modern [1] - 61:25

molecules [1] - 48:22

moment [6] - 16:22, 90:1,

117:8, 165:5, 182:5, 205:19

monitor[1] - 74:15

Monitoring [5] - 73:22,

73:24, 74:13, 75:3

monobasic [2] - 83:7,

87:12

month [2] - 10:4, 13:2

months [2] - 15:5, 116:23

morning [14] - 4:2, 4:5,

4:16, 4:17, 13:24, 62:17,

100:22, 101:20, 117:25,

121:9, 122:4, 147:18, 154:5,

156:16

morphine [4] - 188:19,

206:5, 206:9

morphine-type [1] - 188:19

most [11] - 7:12, 10:16,

50:10, 50:22, 62:1, 90:4,

92:3, 156:1, 196:20, 196:23,

205:16

mostly [2] - 12:18, 115:20

Mostly [1] - 71:24

move [4] - 44:6, 59:3, 91:5,

144:6

moved [1] - 33:21

moving [2] - 58:11, 106:16

MR [272] - 4:5, 4:15, 6:13,

9:7, 9:25, 10:17, 12:10,

12:24, 14:11, 14:14, 14:16,

14:17, 16:3, 20:7, 20:13,

21:11, 22:3, 24:5, 25:4, 26:1,

28:15, 29:18, 30:14, 30:21,

30:25, 31:1, 31:19, 31:21,

32:1, 32:3, 32:4, 32:13,

32:14, 32:24, 33:5, 33:6,

34:2, 34:5, 34:16, 34:22,

35:4, 35:8, 35:12, 35:25,

36:2, 36:17, 36:19, 37:13,

37:15, 41:1, 42:12, 42:15,

42:19, 42:20, 43:4, 43:7,

43:13, 43:20, 43:22, 43:23,

45:9, 47:20, 48:2, 49:4, 49:9,

49:24, 50:1, 51:1, 51:24,

52:5, 52:6, 54:23, 55:22,

57:15, 57:17, 58:12, 59:4,

59:5, 61:8, 61:10, 61:11,

65:24, 66:17, 69:7, 72:21,

74:4, 76:7, 76:10, 79:16,

79:17, 80:23, 80:24, 81:21,

82:3, 83:9, 83:11, 83:14,

83:17, 83:20, 84:20, 88:19,

88:20, 89:7, 89:8, 90:19,

91:10, 91:17, 91:19, 92:1,

92:3, 92:6, 92:8, 93:4, 94:10,

95:22, 96:9, 96:11, 98:4,

98:17, 99:15, 100:4, 102:5,

102:20, 103:10, 103:19,

104:2, 104:8, 104:11, 105:1,

105:3, 105:5, 105:7, 106:11,

106:17, 106:18, 106:20,

106:23, 106:24, 107:2,

107:7, 108:12, 108:23,

109:10, 109:12, 110:21,

111:18, 113:4, 113:8, 114:9,

114:11, 114:21, 115:17,

115:21, 115:25, 116:7,

116:10, 118:7, 118:14,

118:17, 118:21, 118:25,

119:21, 121:21, 121:24,

123:6, 123:11, 123:17,

123:20, 124:1, 124:9,

124:21, 125:5, 125:6,

125:25, 126:1, 127:3, 127:5,

129:6, 134:8, 135:10,

136:21, 137:18, 137:20,

137:21, 138:8, 138:12,

138:15, 138:18, 138:19,

144:4, 145:10, 146:21,

146:24, 152:2, 152:3, 156:4,

156:8, 156:14, 158:19,

159:3, 159:13, 161:10,

163:15, 163:17, 167:4,

167:6, 167:7, 169:10, 170:5,

171:1, 172:10, 172:13,

173:15, 173:17, 173:25,

176:2, 176:5, 177:3, 177:4,

178:1, 178:3, 178:4, 180:4,

180:6, 183:16, 184:17,

184:20, 184:22, 184:23,

185:1, 185:4, 185:17, 186:3,

186:6, 186:25, 187:5,

187:23, 189:9, 189:12,

189:14, 190:2, 191:15,

191:21, 193:13, 193:15,

193:19, 195:5, 195:20,

196:3, 197:9, 197:10, 198:5,

200:7, 200:16, 200:17,

200:22, 201:8, 201:10,

201:18, 201:20, 202:19,

203:7, 203:10, 203:12,

203:13, 203:23, 204:1,

204:14, 204:15, 206:1,

207:19, 208:1

Multi [1] - 127:11

Multi-National [1] - 127:11

multicenter[2] - 36:6, 36:7

multidisciplinary [2] -

85:13, 104:16

multiple [1] - 93:25

mutation [1] - 9:17

Myers [1] - 152:13

United States District Court

16

N

naive [1] - 34:11

name [4] - 4:5, 4:13, 81:10,

103:8

namely [1] - 167:9

names [1] - 159:11

NaOH [1] - 83:12

National [8] - 5:11, 6:10,

6:14, 6:18, 10:23, 111:4,

111:7, 127:11

national [1] - 127:14

natural [2] - 41:17, 119:12

nature [1] - 25:18

nature's [2] - 41:12, 41:13

nausea [75] - 11:11, 11:15,

11:25, 15:21, 15:22, 16:10,

16:12, 17:16, 18:17, 19:17,

19:18, 22:12, 34:10, 35:19,

36:10, 37:22, 40:8, 44:5,

46:15, 46:16, 48:13, 48:23,

50:11, 52:18, 54:19, 55:7,

56:3, 57:8, 64:22, 64:24,

65:2, 66:9, 68:16, 71:15,

73:9, 79:7, 83:3, 84:10,

89:22, 92:25, 93:3, 93:11,

93:16, 119:5, 119:13, 120:6,

120:17, 121:6, 136:11,

136:12, 136:15, 141:10,

141:25, 171:23, 172:4,

173:1, 173:2, 174:8, 175:20,

175:24, 176:1, 176:22,

179:8, 186:19, 186:20,

188:10, 188:16, 188:20,

188:24, 189:4, 189:5,

192:17, 194:16, 206:5, 206:7

nausea-provoking [1] -

19:17

nauseated [4] - 38:13,

38:25, 39:1, 169:8

NCI [6] - 8:2, 110:10,

110:11, 111:2, 138:3, 185:14

NDA [4] - 28:1, 63:6, 143:4,

183:14

near [1] - 86:25

necessarily [1] - 172:23

necessary [1] - 96:7

need [34] - 11:11, 13:8,

20:17, 38:13, 53:8, 55:13,

75:5, 78:25, 92:18, 92:22,

95:16, 95:19, 96:3, 104:18,

115:18, 115:19, 136:12,

141:6, 143:10, 143:18,

144:3, 145:23, 147:6,

168:21, 169:8, 173:15,

175:5, 190:16, 190:18,

191:7, 192:17, 192:19,

202:10

needed [12] - 18:1, 38:17,

38:23, 44:13, 78:24, 142:17,

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 224 of 236 PageID: 18807
144:18, 144:22, 167:22,

179:13, 192:21, 192:22

needs [1] - 124:23

neutral [1] - 86:14

never [11] - 28:19, 74:23,

75:1, 101:25, 111:23, 112:7,

112:12, 112:25, 118:14,

119:20, 140:20

NEW [1] - 1:2

new [15] - 8:4, 13:3, 19:25,

22:25, 23:2, 51:20, 58:4,

63:8, 77:19, 77:25, 78:3,

78:6, 79:1, 104:17, 104:24

New [4] - 1:12, 18:4, 20:5,

22:2

next [21] - 4:3, 13:2, 36:17,

44:7, 46:19, 51:3, 51:20,

53:14, 54:24, 54:25, 56:5,

58:4, 77:8, 77:22, 78:4,

78:14, 89:24, 133:19,

155:22, 169:24, 199:5

NI [1] - 2:4

nights [1] - 30:5

NK-1 [2] - 11:20

NK-1s [1] - 101:10

nobody [3] - 24:19, 24:23,

194:22

non [5] - 167:24, 168:16,

168:18, 205:2, 205:9

non-inferior [1] - 168:18

non-inferiority [4] - 167:24,

168:16, 205:2, 205:9

noninferiority [3] - 142:14,

142:18, 143:2

normal [2] - 18:25, 19:5

note [3] - 52:3, 97:9, 127:23

notebook [1] - 126:13

noted [2] - 32:24, 130:22

nothing [3] - 122:1, 135:23,

150:15

nothing's [1] - 75:10

notice [1] - 29:8

noticed [1] - 29:8

notion [2] - 125:8, 134:10

November [4] - 33:18,

52:20, 69:25, 157:21

nowhere [4] - 86:25,

159:24, 176:17, 177:5

number [39] - 23:4, 24:21,

26:6, 26:9, 26:25, 36:18,

38:24, 54:1, 54:20, 60:8,

60:22, 60:23, 61:1, 68:5,

98:13, 100:14, 122:11,

131:18, 136:5, 158:9,

160:21, 166:17, 166:21,

166:24, 167:1, 167:16,

167:20, 168:2, 168:5, 168:7,

168:10, 168:14, 169:25,

170:10, 191:6, 193:24,

197:5, 198:4

NUMBER [1] - 1:5

Number [11] - 68:6, 70:1,

99:24, 157:22, 161:21,

161:23, 161:24, 197:7,

197:16

numbers [11] - 38:16,

39:19, 39:20, 54:6, 54:22,

60:7, 79:3, 187:16, 187:18,

194:11, 207:16

numerical [1] - 29:20

nurse [1] - 10:13

O

O'MALLEY [104] - 2:3,

14:14, 30:21, 32:24, 34:16,

35:4, 43:4, 51:24, 57:15,

83:14, 91:19, 96:9, 100:4,

104:11, 106:11, 106:18,

106:24, 107:2, 107:7,

108:12, 108:23, 109:10,

109:12, 110:21, 111:18,

113:4, 113:8, 114:9, 114:11,

114:21, 115:17, 115:21,

115:25, 116:10, 118:7,

118:17, 118:25, 119:21,

121:24, 123:6, 123:11,

123:20, 124:1, 124:9,

124:21, 125:5, 125:6,

125:25, 126:1, 127:3, 127:5,

129:6, 134:8, 135:10,

136:21, 137:18, 137:20,

137:21, 138:12, 138:15,

138:18, 138:19, 144:4,

145:10, 146:21, 146:24,

152:2, 152:3, 156:4, 156:8,

156:14, 158:19, 159:3,

159:13, 161:10, 163:15,

163:17, 167:4, 167:6, 167:7,

169:10, 170:5, 171:1,

172:10, 172:13, 173:15,

173:17, 176:2, 176:5, 177:3,

177:4, 178:1, 178:3, 178:4,

180:4, 180:6, 184:20,

184:22, 186:25, 193:13,

195:20, 200:16, 204:15,

206:1

O'Malley [14] - 3:7, 32:23,

100:3, 102:7, 102:9, 118:4,

183:17, 186:7, 193:7,

196:13, 197:3, 197:6, 201:9,

201:11

object [2] - 34:16, 186:25

objecting [1] - 105:17

objection [16] - 14:14,

30:21, 30:23, 35:4, 43:4,

52:4, 57:15, 83:14, 116:7,

121:21, 123:17, 138:8,

173:25, 193:13, 195:20

objections [1] - 35:10

objective [3] - 35:14, 35:15,

35:20

objectives [1] - 35:11

observation [2] - 104:13,

125:7

observed [1] - 32:22

obtain [1] - 111:20

obtained [2] - 166:17,

166:21

obviously [3] - 24:16,

97:21, 98:4

obviousness [8] - 98:1,

99:6, 101:1, 101:5, 105:10,

105:12, 124:7, 124:14

occur [1] - 133:1

occurred [7] - 54:5, 54:9,

54:10, 54:13, 66:2, 90:2,

95:10

October [22] - 59:19, 70:8,

70:15, 71:10, 71:16, 72:1,

72:4, 72:11, 72:20, 72:22,

76:11, 76:15, 78:9, 79:24,

79:25, 80:8, 81:22, 152:2,

157:10, 163:6, 163:9, 165:1

OF [1] - 1:2

offer [1] - 107:9

offered [2] - 118:9, 122:15

offering [2] - 14:8, 16:7

Office [3] - 67:22, 68:1,

93:8

officer [1] - 58:6

often [2] - 147:25, 176:11

old [1] - 62:18

on-sale [4] - 31:21, 124:8,

124:22, 125:2

once [12] - 19:2, 25:10,

25:20, 25:21, 25:23, 26:21,

27:2, 27:4, 27:6, 28:14, 83:1,

85:21

oncologist [3] - 7:17,

15:13, 45:21

oncology [7] - 6:10, 8:11,

10:21, 13:19, 14:13, 46:1,

107:14

Oncology [1] - 13:14

Oncotech [9] - 6:20, 6:21,

6:22, 7:5, 7:13, 7:15, 7:17,

9:13, 58:6

ondansetron [33] - 48:11,

48:12, 48:14, 52:16, 77:7,

77:13, 78:22, 78:24, 79:2,

129:5, 166:6, 166:11,

167:11, 168:1, 168:14,

168:22, 168:23, 169:16,

169:17, 169:20, 169:25,

170:11, 172:25, 186:10,

186:13, 186:15, 186:23,

187:2, 187:9, 198:4, 204:18,

204:24

ondansetron-only [2] -

United States District Court

17

79:11, 79:13

one [65] - 5:10, 6:11, 14:6,

20:3, 22:23, 23:1, 23:2, 23:5,

23:16, 24:13, 24:17, 40:15,

54:9, 54:12, 54:13, 68:10,

75:2, 78:3, 91:2, 91:9, 93:7,

98:6, 98:11, 99:18, 99:19,

101:20, 107:21, 112:5,

123:1, 126:2, 126:7, 131:10,

131:12, 135:8, 138:4,

144:18, 144:22, 148:22,

149:4, 154:8, 154:11,

157:12, 157:20, 160:23,

162:11, 162:12, 163:21,

164:3, 164:25, 175:24,

185:1, 191:24, 192:15,

194:12, 195:22, 198:17,

199:14, 199:17, 199:19,

199:22, 199:23, 200:23,

202:5, 202:13

one-third [1] - 192:15

one-year [1] - 126:7

ones [1] - 61:25

onset [4] - 69:5, 70:6,

71:21, 157:8

open [3] - 4:1, 53:5, 62:20

opening [5] - 22:4, 101:10,

119:22, 121:25, 129:17

opined [1] - 89:10

opining [1] - 194:15

opinion [26] - 15:2, 15:7,

33:8, 34:18, 66:4, 89:12,

92:12, 93:5, 99:18, 99:19,

99:22, 106:5, 114:17,

117:17, 117:24, 118:12,

118:15, 118:17, 118:23,

120:25, 121:1, 121:17,

121:18, 123:1, 136:24,

136:25

opinions [36] - 4:19, 4:21,

14:18, 14:19, 30:16, 31:8,

32:15, 32:19, 44:8, 56:6,

63:12, 66:19, 67:23, 68:13,

71:12, 79:18, 103:1, 107:9,

115:1, 115:8, 115:12,

116:15, 116:17, 117:3,

117:9, 117:18, 118:8,

122:15, 125:11, 125:24,

125:25, 130:19, 171:2,

187:12, 188:11, 194:5

opioid [1] - 206:4

opioids [1] - 206:2

opponent [1] - 101:2

optimal [1] - 22:10

oral [5] - 50:9, 50:25, 95:17,

127:7, 127:15

order [6] - 119:8, 142:16,

142:25, 144:8, 176:22, 179:3

ordinary [24] - 15:7, 15:15,

31:2, 58:15, 81:23, 85:2,

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 225 of 236 PageID: 18808
96:13, 96:19, 96:25, 97:8,

97:17, 100:12, 101:21,

104:19, 106:1, 107:9,

113:24, 122:23, 123:7,

123:22, 123:23, 125:12,

192:24, 194:23

organic [1] - 179:21

organismal [1] - 5:19

organization [1] - 81:8

organizations [2] - 13:12,

13:17

organized [1] - 162:10

organs [1] - 17:23

orient [2] - 44:17, 56:9

original [1] - 184:23

others' [1] - 99:11

otherwise [2] - 134:4, 165:9

ourselves [1] - 44:17

out-license [1] - 152:10

outcome [6] - 77:21, 78:2,

135:5, 143:10, 144:9, 144:19

outcomes [4] - 17:6, 77:10,

77:12, 146:18

outline [1] - 152:18

output [6] - 63:21, 63:24,

65:11, 89:18, 182:14, 186:24

outside [5] - 13:11, 45:4,

45:15, 45:16, 154:14

ovarian [2] - 109:25, 110:1

overall [8] - 66:4, 77:5,

81:18, 86:11, 90:14, 115:20,

118:15, 118:23

overarching [1] - 34:18

oversaw [1] - 149:11

overview [3] - 16:21, 16:25,

46:13

own [3] - 110:9, 111:9

P

p-value [3] - 54:3, 54:4,

132:25

p.m [1] - 208:5

package [6] - 13:9, 61:24,

62:1, 62:19, 63:7, 119:15

page [26] - 42:7, 53:15,

54:24, 54:25, 63:18, 63:22,

69:15, 98:3, 126:23, 138:18,

141:21, 146:22, 146:23,

147:10, 149:14, 150:1,

152:17, 154:2, 155:22,

167:18, 168:4, 168:25,

175:2, 191:22, 201:18,

204:17

Page [41] - 15:1, 34:4, 35:9,

37:14, 46:8, 47:14, 47:15,

49:24, 52:11, 52:21, 52:23,

59:7, 60:1, 60:13, 61:15,

63:17, 63:18, 64:10, 66:25,

67:9, 67:25, 70:13, 78:17,

92:10, 97:9, 98:4, 109:10,

137:14, 138:15, 139:9,

141:7, 161:11, 186:4, 186:5,

189:11, 190:10, 193:6,

196:14, 197:7, 201:18

Pages [2] - 99:24

paid [2] - 18:22, 45:6

pain [10] - 11:1, 188:17,

189:3, 189:5, 205:15,

205:17, 205:21, 205:25,

206:7

palliative [1] - 10:24

PALO [2] - 1:4, 201:21

Palo [4] - 45:11, 149:9,

161:15, 161:16

PALO-99-03 [12] - 59:24,

68:25, 69:6, 69:11, 69:12,

70:12, 70:14, 78:11, 89:18,

159:20, 160:1, 161:20

PALO-99-04 [5] - 67:1,

201:22, 201:25, 202:24,

203:16

PALO-99-05 [1] - 67:13

PALO-99-03 [2] - 51:21,

59:6

palonosetron [89] - 4:9,

4:22, 11:21, 15:6, 30:19,

31:4, 31:14, 32:6, 33:10,

34:10, 35:3, 35:16, 35:22,

37:3, 37:9, 38:4, 40:1, 40:14,

41:5, 44:22, 48:16, 48:24,

49:6, 49:7, 52:14, 55:6,

56:25, 57:8, 57:10, 60:2,

60:5, 60:20, 61:4, 64:20,

65:3, 68:15, 69:4, 70:6, 71:3,

71:5, 71:20, 77:16, 79:7,

82:15, 82:17, 83:1, 83:2,

83:13, 84:18, 84:25, 87:18,

89:14, 92:13, 101:14, 114:6,

114:14, 127:24, 128:3,

129:10, 141:10, 141:23,

149:11, 149:21, 149:23,

152:7, 152:10, 157:7,

157:14, 158:21, 160:12,

162:15, 167:11, 171:3,

171:8, 171:18, 171:22,

172:3, 180:8, 181:16,

181:25, 182:24, 187:6,

187:18, 188:6, 192:22,

198:7, 203:25, 205:3

Palonosetron [3] - 44:21,

68:8, 129:7

palonosetron's [1] - 205:6

PALO-03 [1] - 94:15

PALO-04 [1] - 94:16

PALO-05 [1] - 94:16

PALO-99-03 [4] - 62:10,

65:7, 70:16, 71:23

PALO-99-04 [1] - 51:21

PALO-99-05 [1] - 51:21

paper [4] - 45:24, 45:25,

127:1, 202:13

papers [3] - 13:18, 45:23

paradigm [1] - 16:19

Paragraph [20] - 68:18,

68:21, 69:8, 69:21, 70:2,

70:3, 70:9, 70:19, 70:20,

71:7, 71:8, 71:17, 71:18,

129:23, 157:3, 157:17,

159:18, 161:14, 163:3

paragraph [11] - 55:1,

56:21, 56:22, 141:8, 149:15,

160:4, 161:12, 164:3, 167:1,

181:23, 191:1

paragraphs [5] - 47:14,

47:15, 68:21, 69:20, 71:11

Paragraphs [1] - 69:18

paraphrase [1] - 15:24

pardon [1] - 64:25

Pardon [1] - 173:12

parentheses [1] - 201:1

Part [2] - 70:1, 157:23

part [19] - 7:17, 10:21, 16:6,

17:20, 55:2, 89:10, 96:20,

99:10, 102:13, 120:8,

120:20, 121:7, 121:20,

123:15, 157:13, 167:15,

176:1, 184:1, 199:1

part-time [1] - 7:17

partially [1] - 41:19

participate [1] - 6:15

participated [3] - 27:21,

68:25, 109:23

participating [2] - 36:8,

110:4

participation [2] - 109:13,

150:25

particular[9] - 5:5, 42:3,

70:3, 129:20, 130:3, 136:6,

157:4, 170:20, 178:16

parties [10] - 90:22, 91:11,

91:18, 91:20, 96:15, 96:24,

99:7, 102:3, 102:22, 171:13

parties' [3] - 96:18, 96:22,

99:6

party [2] - 106:8, 150:14

passed [2] - 137:22, 162:23

past [1] - 142:4

patent [64] - 14:3, 14:20,

14:23, 14:25, 15:3, 15:4,

15:8, 15:18, 16:7, 68:5, 68:6,

68:7, 68:14, 85:9, 89:9,

90:14, 92:10, 93:22, 93:24,

94:5, 94:11, 94:12, 94:14,

94:18, 94:21, 98:6, 98:7,

100:19, 105:20, 114:5,

114:8, 114:10, 114:12,

114:14, 115:1, 118:22,

119:1, 119:25, 120:9,

120:10, 120:21, 120:24,

United States District Court

18

121:10, 121:20, 122:9,

122:16, 122:20, 123:8,

123:23, 123:24, 123:25,

124:2, 124:10, 124:19,

125:12, 125:13, 125:18,

125:21, 126:3, 127:19,

138:5, 158:3, 170:22

Patent [3] - 67:22, 68:1,

93:8

patent-in-suit [1] - 125:21

patenting [1] - 43:15

patents [10] - 68:10, 97:10,

98:9, 106:2, 126:9, 149:5,

158:10, 158:20, 158:21,

158:22

patents-in-suit [2] - 97:10,

149:5

pathways [2] - 11:15, 11:17

patient [47] - 6:16, 6:22,

7:4, 9:18, 10:8, 10:16, 11:1,

11:3, 11:5, 23:3, 23:4, 23:13,

24:10, 24:20, 24:22, 25:2,

25:6, 25:10, 26:3, 26:11,

26:12, 26:15, 26:17, 26:19,

59:16, 59:19, 67:15, 67:16,

67:17, 72:23, 76:12, 78:9,

78:20, 79:23, 84:4, 84:8,

84:25, 163:13, 163:15,

163:23, 163:24, 164:2,

175:20, 176:21, 181:24,

188:18

patient's [4] - 6:25, 9:16,

26:21, 80:14

patients [50] - 8:6, 10:3,

10:5, 10:19, 10:22, 11:10,

19:9, 19:16, 21:5, 26:7, 26:9,

34:11, 35:18, 36:20, 36:22,

36:23, 36:25, 37:2, 37:7,

38:17, 41:6, 53:7, 58:4,

60:16, 64:24, 71:25, 72:4,

73:8, 75:10, 78:18, 119:13,

129:9, 135:21, 136:5, 158:3,

167:1, 167:19, 183:1,

185:13, 185:15, 186:11,

187:19, 187:21, 187:24,

188:22, 190:3, 205:14,

205:16, 205:22

PAUL [1] - 2:2

Peck's [1] - 125:9

peek [1] - 80:7

peer [5] - 13:20, 13:21,

13:23, 171:17, 172:2

peer-reviewed [3] - 13:20,

171:17, 172:2

peer-reviewer [1] - 13:21

pemetrexed [1] - 14:10

pending [3] - 70:20, 70:21,

90:12

people [68] - 9:15, 10:14,

11:14, 17:1, 17:20, 18:11,

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 226 of 236 PageID: 18809
18:15, 18:22, 19:15, 19:23,

21:4, 24:1, 24:10, 24:23,

25:13, 26:23, 27:18, 29:9,

30:4, 30:6, 33:10, 36:7,

38:24, 44:23, 44:25, 45:3,

45:4, 45:25, 54:1, 54:6,

58:11, 62:16, 64:5, 68:18,

74:1, 74:16, 75:1, 75:5,

75:14, 75:21, 78:25, 97:2,

103:11, 119:19, 120:17,

121:5, 135:15, 135:17,

135:22, 138:3, 138:6, 151:1,

151:6, 154:14, 168:19,

168:20, 169:25, 177:18,

186:13, 186:23, 188:2,

188:23, 189:18, 192:20,

192:22, 206:6

people's [1] - 17:6

per [35] - 35:17, 37:5, 37:6,

38:2, 47:10, 49:11, 50:10,

50:21, 54:7, 55:5, 131:19,

132:1, 132:4, 132:6, 132:12,

133:16, 134:23, 154:23,

155:1, 174:19, 177:7, 177:9,

177:14, 190:4, 191:4, 191:5,

191:15, 192:14, 193:1,

193:20, 195:8, 195:13,

195:18, 196:21

percent [70] - 37:24, 40:11,

41:3, 41:4, 41:10, 53:21,

54:9, 60:20, 64:14, 64:16,

64:23, 64:24, 75:15, 78:23,

79:5, 128:8, 128:13, 128:19,

134:18, 135:12, 135:15,

135:17, 135:21, 136:16,

166:5, 166:9, 166:14,

166:15, 166:17, 167:9,

167:11, 167:12, 167:13,

167:20, 167:25, 168:5,

168:24, 169:2, 169:4,

169:21, 170:12, 170:14,

187:4, 187:8, 187:11,

187:22, 187:24, 189:18,

189:19, 189:20, 189:23,

189:24, 189:25, 190:7,

190:8, 190:9, 192:20,

192:21, 193:16, 193:21,

193:24, 194:2, 194:4, 194:20

percentage [5] - 38:23,

73:8, 136:5, 186:23, 194:1

percentages [1] - 41:24

perfect [1] - 156:10

performed [8] - 61:17,

61:18, 62:12, 62:15, 76:14,

82:5, 195:7, 203:2

performing [1] - 7:8

perhaps [2] - 127:3, 127:23

period [12] - 17:22, 39:5,

60:19, 64:17, 71:6, 126:8,

152:9, 160:12, 162:15,

162:19, 172:3, 174:22

periodically [1] - 156:20

permission [1] - 21:22

permit [4] - 43:9, 43:11,

57:16, 187:3

person [53] - 9:2, 15:7,

15:15, 21:4, 21:6, 24:16,

25:21, 25:25, 31:2, 31:3,

32:5, 43:1, 43:8, 43:17, 44:1,

49:17, 55:23, 57:9, 58:15,

81:23, 83:2, 85:2, 85:4,

89:16, 90:5, 93:9, 96:13,

96:19, 96:20, 96:23, 96:25,

98:12, 100:12, 100:13,

100:17, 102:22, 104:19,

106:1, 107:9, 113:23,

120:13, 121:2, 122:22,

123:7, 123:22, 123:23,

123:24, 125:12, 159:8,

160:2, 185:23, 192:24,

194:23

personal [1] - 168:12

personally [9] - 111:23,

112:8, 112:12, 112:15,

140:20, 160:1, 160:7, 161:5,

161:19

persons [3] - 97:17, 98:15,

100:17

perspective [4] - 9:4, 46:5,

100:24, 134:1

pH [17] - 85:11, 85:14,

85:19, 85:22, 86:3, 86:11,

86:14, 86:22, 86:23, 87:8,

87:14, 87:16, 87:19, 88:7,

88:12

Ph.D [10] - 5:21, 6:1, 9:21,

83:22, 97:13, 97:18, 112:23,

113:7, 183:23, 184:8

Ph.D.s [2] - 20:25, 21:1

Pharma [1] - 181:15

pharma [4] - 74:12, 81:4,

130:14, 183:12

PHARMACEUTICAL [1] -

1:9

Pharmaceutical [2] - 116:2

pharmaceutical [30] - 7:9,

12:18, 15:6, 26:22, 30:10,

58:17, 82:14, 90:17, 96:21,

97:13, 97:14, 98:13, 98:18,

98:20, 98:22, 98:24, 100:14,

100:16, 104:15, 110:8,

110:16, 113:21, 114:1,

119:9, 119:10, 130:14,

133:6, 139:11, 152:11

PHARMACEUTICALS [1] -

1:8

pharmacist [1] - 13:7

pharmacokinetic [1] - 34:9

pharmacologist [5] - 15:13,

83:21, 83:23, 84:4

pharmacologists [3] -

20:25, 97:18, 140:15

pharmacology [20] - 5:4,

5:21, 5:22, 5:23, 6:2, 14:12,

21:2, 83:22, 84:12, 98:21,

112:21, 112:23, 112:25,

113:7, 113:9, 113:18,

183:18, 183:22, 183:23,

184:3

Pharmacology [2] - 113:13,

113:16

pharmacy [1] - 98:21

Phase [188] - 8:16, 8:17,

8:18, 8:20, 8:23, 18:7, 18:15,

18:21, 19:9, 19:11, 19:20,

19:22, 19:24, 20:2, 20:4,

20:9, 20:10, 21:10, 21:15,

21:23, 21:25, 25:8, 28:1,

28:2, 28:3, 28:21, 32:8, 33:9,

33:19, 33:21, 33:23, 34:3,

35:14, 35:15, 36:3, 36:5,

36:11, 36:12, 36:21, 37:8,

41:20, 42:22, 46:23, 46:24,

46:25, 47:1, 47:3, 47:4,

47:11, 47:16, 48:4, 48:8,

48:9, 49:20, 49:23, 51:20,

52:7, 53:11, 53:13, 54:25,

55:4, 55:12, 55:14, 55:17,

55:19, 56:2, 56:23, 56:24,

57:6, 58:19, 59:2, 60:18,

60:25, 61:2, 66:6, 66:7,

66:11, 66:18, 75:10, 81:3,

82:5, 82:10, 82:11, 82:18,

82:20, 82:21, 84:7, 84:21,

84:23, 85:3, 85:5, 87:3, 87:5,

87:10, 87:23, 87:25, 88:23,

89:1, 89:17, 92:23, 93:10,

93:12, 93:25, 94:2, 94:18,

94:19, 109:14, 109:23,

111:11, 122:20, 127:24,

128:2, 128:23, 129:18,

130:1, 130:20, 137:6,

138:24, 141:9, 142:6,

142:10, 143:8, 143:14,

143:19, 143:21, 143:23,

144:1, 144:3, 144:7, 144:21,

144:22, 144:24, 145:1,

145:24, 145:25, 147:21,

148:11, 149:11, 149:17,

150:12, 150:20, 152:18,

152:22, 154:9, 155:9,

155:17, 155:19, 167:2,

170:1, 176:18, 176:25,

177:19, 181:16, 182:21,

182:24, 195:3, 195:14,

196:1, 196:2, 196:5, 197:9,

198:18, 198:19, 199:3,

199:11, 199:14, 199:17,

199:20, 199:21, 199:25,

200:9, 200:15, 201:6, 202:5,

United States District Court

19

202:10, 202:20

phase [4] - 17:4, 128:11,

128:15, 206:8

phases [2] - 8:13, 12:21

phosphate [4] - 83:7,

87:12, 87:13

phrase [2] - 132:15, 198:22

physician [2] - 21:7, 23:11

physicians [1] - 27:20

physiology [1] - 21:2

PI [2] - 186:1, 186:2

pick [3] - 29:22, 101:15,

101:21

picked [4] - 53:9, 73:19,

99:25, 105:18

picking [1] - 23:9

picks [1] - 101:25

pieces [2] - 11:25, 19:6

pigeonhole [1] - 105:8

pill [3] - 192:19, 192:21,

192:23

Piraccini [2] - 69:25,

157:22

pivotal [13] - 139:22,

143:14, 143:16, 143:18,

181:16, 183:8, 183:13,

194:15, 196:1, 197:17,

198:13, 198:16, 200:25

place [7] - 24:21, 45:12,

48:25, 101:19, 153:19,

161:13, 167:8

placebo [2] - 24:18, 145:7

places [2] - 22:14, 185:25

plaintiffs [1] - 97:23

Plaintiffs [2] - 1:5, 2:5

plaintiffs' [5] - 92:11,

92:15, 92:17, 97:25, 104:4

plan [7] - 18:7, 61:12, 62:3,

62:6, 66:14, 66:15, 66:16

planned [1] - 49:16

plateau [1] - 194:10

played [1] - 90:21

playing [1] - 97:22

pleased [2] - 57:4, 181:24

plenty [1] - 16:1

point [24] - 26:20, 43:14,

50:16, 75:16, 90:13, 90:24,

94:25, 104:22, 106:17,

124:3, 124:16, 131:20,

150:16, 154:7, 156:8,

177:19, 190:12, 192:18,

196:17, 198:11, 200:23,

200:24, 206:12, 207:6

pointed [4] - 168:10,

193:10, 193:16, 193:20

pointer [1] - 42:6

pointing [1] - 46:12

points [2] - 139:12, 194:11

poison [4] - 12:6, 12:7,

41:15, 41:17

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 227 of 236 PageID: 18810
pontificate [1] - 154:20

PONV [14] - 46:14, 172:17,

173:9, 173:24, 174:7,

175:13, 175:18, 175:24,

176:14, 177:25, 188:6,

188:12, 189:2, 190:4

population [2] - 24:1, 77:6

portion [6] - 46:10, 46:11,

61:15, 65:10, 65:11, 196:13

portions [1] - 161:7

POSA [59] - 15:14, 15:15,

15:17, 32:25, 34:18, 34:19,

34:21, 34:23, 43:5, 43:15,

90:8, 90:10, 90:14, 90:15,

90:16, 90:22, 91:3, 91:6,

91:11, 91:12, 91:15, 91:20,

95:18, 97:12, 97:16, 98:2,

98:5, 98:6, 98:7, 98:8, 98:11,

98:20, 99:4, 99:12, 99:22,

99:25, 100:6, 100:20,

100:24, 101:6, 101:24,

102:4, 103:13, 103:16,

103:21, 104:17, 106:6,

106:7, 106:8, 121:3, 124:10,

124:18, 125:2, 141:14,

171:2, 171:7, 180:7, 180:9

POSA's [1] - 101:23

POSAs [2] - 32:25, 98:10

poses [1] - 139:11

posited [1] - 165:22

position [6] - 5:1, 100:6,

104:4, 104:9, 105:21, 172:15

possession [1] - 125:14

possible [4] - 22:16, 64:9,

77:12, 180:11

possibly [1] - 81:1

post [2] - 10:11, 10:14

postoperative [12] - 46:16,

171:23, 172:4, 173:1, 174:8,

174:18, 174:21, 175:20,

175:24, 186:20, 188:10,

188:15

postoperatively [1] - 206:9

potency [1] - 48:18

potent [2] - 40:1, 129:4

potential [1] - 90:17

potentially [1] - 89:20

POV [1] - 176:14

power [1] - 167:21

practical [1] - 155:17

practice [12] - 10:1, 10:2,

10:21, 21:12, 40:10, 69:24,

157:21, 157:25, 158:13,

159:15, 185:7, 185:8

practicing [1] - 97:19

pre [3] - 63:6, 65:20, 143:5

pre-IND [1] - 143:5

pre-NDA [1] - 63:6

pre-stipulated [1] - 65:20

preamble [10] - 99:20,

101:17, 104:22, 105:13,

114:12, 119:3, 120:20,

121:19

precise [1] - 99:9

preclinical [12] - 7:10, 9:10,

10:7, 14:9, 16:13, 16:19,

17:1, 17:4, 20:23, 20:24,

21:3, 94:21

precluded [1] - 81:13

predict [4] - 9:17, 18:12,

78:20, 109:25

predisposition [1] - 188:24

preindustry [1] - 12:20

preliminarily [1] - 95:20

preliminary [19] - 62:15,

65:18, 66:1, 147:25, 178:10,

178:12, 178:16, 178:19,

178:21, 180:2, 181:21,

186:4, 203:18, 204:4,

206:13, 206:16, 207:2,

207:4, 207:14

premed [1] - 12:19

premedication [1] - 41:9

preordained [2] - 28:19,

29:1

prepare [1] - 78:11

prepared [9] - 16:15, 31:10,

73:11, 76:21, 139:1, 147:19,

148:3, 164:14, 164:23

preparing [1] - 117:21

prepharmacy [1] - 12:19

preplanned [3] - 29:16,

61:19, 206:23

present [1] - 185:14

presentation [2] - 127:7,

127:15

presentations [1] - 13:16

presented [5] - 115:1,

127:1, 138:20, 178:18,

204:10

press [18] - 33:19, 56:7,

56:13, 56:16, 56:18, 56:22,

56:24, 57:2, 57:13, 58:1,

58:6, 58:13, 58:16, 180:24,

182:7, 183:3, 183:4, 196:4

pressure [2] - 18:24, 29:9

presumed [1] - 124:11

pretty [7] - 28:6, 39:20,

39:23, 54:18, 76:4, 182:4,

192:18

prevailed [2] - 184:15,

184:16

prevent [2] - 19:18, 48:12

preventing [8] - 55:7,

129:8, 141:10, 141:25,

175:13, 175:18, 175:25,

176:13

prevention [3] - 34:10,

52:17, 56:25

preview [1] - 90:19

previously [5] - 60:4,

115:15, 145:21, 179:3,

180:24

primary [15] - 7:8, 29:7,

35:13, 35:15, 35:20, 134:10,

134:12, 134:14, 134:17,

134:20, 135:5, 155:4,

186:23, 194:12

principal [4] - 185:18,

185:22, 185:24, 185:25

principle [2] - 7:24, 75:13

printed [1] - 63:23

private [3] - 31:22, 32:16,

32:18

probability [4] - 54:4, 54:8,

133:1, 141:17

problem [4] - 86:21, 95:19,

101:9, 106:17

problematic [1] - 104:3

problems [1] - 85:25

procedures [1] - 175:7

proceed [4] - 32:21, 74:20,

77:11, 96:7

proceeded [1] - 5:19

Proceedings [1] - 208:5

proceedings [1] - 127:13

process [14] - 11:14, 11:25,

12:4, 17:2, 20:16, 20:18,

29:2, 30:12, 44:13, 46:7,

85:14, 86:6, 160:6, 183:13

processes [2] - 16:20,

147:7

product [9] - 7:5, 88:23,

98:18, 100:14, 102:12,

102:13, 104:17, 150:3, 152:7

products [3] - 98:13,

104:16, 119:12

professional [1] - 13:12

professionals [1] - 99:3

professor [1] - 5:3

program [8] - 5:20, 28:11,

33:18, 61:23, 111:9, 149:16,

182:1, 183:25

programs [1] - 28:12

progress [1] - 58:9

project [1] - 149:21

promising [1] - 182:22

promotion [1] - 111:8

pronouncement [1] - 90:4

proofs [3] - 100:21, 100:22,

105:16

property [1] - 63:25

proponent [2] - 74:8, 75:24

proportion [1] - 178:24

proposal [2] - 51:20, 55:2

proposed [7] - 46:14, 52:7,

52:19, 52:22, 55:12, 106:15,

154:5

proposing [3] - 47:2, 48:7,

106:9

United States District Court

20

proposition [1] - 173:7

prospective [7] - 66:10,

66:12, 66:14, 92:18, 92:23,

93:13, 144:1

protected [2] - 10:9, 10:10

Protocol [1] - 152:18

protocol [19] - 25:9, 52:13,

52:19, 52:22, 53:1, 53:8,

55:2, 55:12, 61:19, 68:25,

73:5, 73:20, 74:24, 78:17,

159:20, 160:2, 160:10,

206:24

protocols [8] - 51:21,

51:22, 52:7, 52:10, 53:2,

53:4, 74:18

prove [4] - 18:25, 19:8,

20:21, 74:23

proves [1] - 71:8

provide [4] - 4:18, 53:1,

60:10, 61:12

provided [6] - 117:17,

117:25, 130:19, 132:24,

156:16, 178:7

providing [3] - 51:17,

140:18, 141:1

provoking [1] - 19:17

psychology [1] - 5:18

PTX [1] - 170:6

PTX-0015 [1] - 153:7

PTX-0261 [1] - 138:15

PTX-0297 [2] - 126:12,

206:12

PTX-075 [1] - 170:6

PTX-2016 [1] - 197:3

PTX-2061 [1] - 196:8

PTX-297 [1] - 201:8

public [13] - 31:20, 31:22,

32:16, 32:18, 43:17, 56:18,

56:22, 56:24, 57:19, 123:14,

126:6, 126:11

publication [9] - 126:19,

126:22, 127:8, 127:16,

146:3, 146:4, 172:2, 201:15

publications [1] - 13:20

publicly [11] - 32:10, 34:24,

122:23, 123:12, 125:1,

127:18, 153:9, 153:12,

171:17, 172:2, 183:3

publish [1] - 127:13

published [10] - 13:18,

45:21, 45:23, 69:25, 157:22,

171:22, 202:21, 203:7,

203:14, 203:15

pull [12] - 129:23, 137:14,

138:15, 140:25, 146:22,

161:24, 166:25, 170:6,

173:20, 181:9, 202:16,

204:16

pulling [1] - 77:18

purpose [9] - 17:5, 19:9,

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 228 of 236 PageID: 18811
22:11, 46:3, 46:4, 89:3,

119:14, 123:5, 123:8

purposes [9] - 29:15,

85:25, 89:5, 90:14, 99:13,

102:11, 125:2, 143:17,

199:16

Pursuant [1] - 116:3

push [2] - 28:4, 101:12

pushing [1] - 79:10

put [22] - 9:1, 20:9, 23:12,

24:21, 25:19, 26:10, 28:1,

33:19, 46:18, 58:6, 88:22,

102:14, 104:12, 106:12,

106:13, 129:18, 132:1,

145:7, 158:13, 168:19,

191:13, 201:8

putting [4] - 41:17, 63:7,

75:16, 75:21

Q

qualify [2] - 5:13, 176:23

quality [2] - 11:5, 80:2

quarter [2] - 48:15

QUESTION [4] - 137:16,

137:23, 173:22, 174:2

questioning [1] - 89:25

questionnaire [4] - 39:2,

39:7, 176:11, 176:21

questions [21] - 33:4,

42:15, 94:24, 111:13,

115:20, 118:7, 118:10,

124:19, 139:11, 139:13,

154:19, 183:6, 187:1, 192:2,

194:13, 195:21, 195:23,

197:6, 197:11, 204:14,

207:19

quick [2] - 24:14, 85:10

quickly [1] - 66:24

quite [2] - 28:5, 32:24

quote [2] - 50:8, 181:2

R

R21 [1] - 110:4

rack [1] - 115:19

radiotherapy [1] - 71:1

radiotherapy-induced [1] -

70:24

raise [1] - 92:20

ran [1] - 160:15

random [2] - 23:4, 54:10

randomized [9] - 22:20,

22:21, 25:21, 36:6, 66:10,

92:18, 92:23, 93:13, 144:1

randomizing [1] - 23:25

randomly [2] - 23:5, 23:9

range [4] - 19:2, 35:17,

105:25, 132:16

ranging [2] - 34:8, 36:9

rank [1] - 102:18

rate [25] - 40:17, 60:17,

60:21, 77:6, 77:7, 77:10,

77:14, 77:18, 78:6, 78:22,

78:24, 128:5, 128:18,

167:10, 167:13, 168:24,

169:1, 169:4, 169:5, 169:20,

170:11, 170:15, 187:7,

187:8, 187:10

rates [1] - 168:22

rather [6] - 102:2, 110:15,

133:5, 133:12, 176:13,

176:14

ratio [2] - 79:11, 79:14

rationale [1] - 55:3

raw [1] - 207:16

reach [3] - 79:6, 87:7, 147:5

reached [3] - 26:10, 74:22,

126:11

reaches [2] - 17:15, 88:10

reaching [1] - 164:8

react [1] - 86:11

reaction [2] - 41:17, 206:10

read [30] - 43:24, 57:2,

57:19, 57:23, 69:19, 100:9,

109:21, 110:19, 110:20,

110:25, 111:1, 115:23,

116:1, 123:24, 129:24,

138:7, 138:10, 138:13,

138:14, 146:12, 156:7,

159:21, 163:4, 174:4,

190:15, 191:1, 191:2,

196:17, 197:15, 198:10

reading [2] - 137:17,

192:25

reads [1] - 141:8

ready [2] - 4:3, 43:15

ready-for-patenting [1] -

43:15

real [1] - 103:3

realization [1] - 20:17

realize [2] - 122:10, 122:12

really [37] - 8:1, 10:13,

10:24, 11:2, 11:24, 16:10,

20:20, 24:20, 24:23, 25:23,

29:5, 38:22, 40:24, 44:12,

44:14, 54:7, 63:6, 74:2,

86:22, 96:14, 116:16, 124:1,

144:22, 145:13, 150:21,

156:4, 162:9, 164:6, 169:5,

172:18, 180:13, 184:10,

189:5, 194:14, 194:15,

199:12

reanalysis [1] - 154:14

reanalyze [3] - 140:10,

144:18, 145:1

reason [1] - 153:13

reasons [1] - 36:24

receive [2] - 110:11, 113:6

received [3] - 37:7, 43:5,

187:19

receiving [5] - 34:11, 65:3,

73:21, 129:10, 136:5

recent [1] - 90:4

receptor [13] - 11:20, 11:21,

11:23, 12:22, 40:2, 40:7,

40:8, 48:20, 48:21, 48:25,

49:2, 97:11, 141:24

receptors [7] - 11:20, 12:2,

40:3, 40:11, 40:20, 40:24,

50:17

recess [8] - 42:16, 95:2,

95:12, 95:15, 95:16, 96:5,

99:17, 156:11

Recess [1] - 156:12

recognize [7] - 34:6, 59:11,

62:25, 67:10, 133:19, 147:8,

171:10

recommendation [8] -

50:12, 146:7, 148:10,

151:10, 151:11, 154:8,

177:19, 177:20

recommended [4] - 50:8,

145:25, 150:11, 150:21

recommending [1] - 50:21

recommends [1] - 150:19

record [19] - 4:13, 42:6,

42:7, 43:21, 49:10, 58:13,

59:3, 66:24, 81:22, 90:1,

95:9, 95:13, 95:14, 106:14,

109:22, 116:1, 129:25,

208:3, 208:4

RECROSS [2] - 3:5, 204:15

red [2] - 77:23, 166:5

REDDY'S [2] - 1:7, 1:8

Reddy's [1] - 2:8

REDIRECT [2] - 3:5, 183:16

reduce [19] - 15:20, 16:11,

35:3, 35:19, 56:3, 57:8,

64:20, 64:21, 71:15, 89:15,

92:13, 119:4, 119:9, 120:6,

141:18, 141:19, 180:10,

187:13

reduced [17] - 31:14, 41:5,

41:7, 44:5, 47:6, 54:19,

57:11, 69:24, 89:21, 92:24,

93:2, 157:20, 157:25,

158:12, 159:15, 192:20,

194:16

reduces [10] - 30:19, 31:4,

35:22, 37:10, 61:4, 61:9,

93:11, 171:4, 194:6, 198:8

reducing [13] - 16:9, 66:8,

68:16, 79:7, 93:15, 119:13,

120:17, 122:1, 174:8,

174:18, 186:11, 191:6,

203:25

reduction [6] - 84:10,

179:7, 188:2, 190:4, 190:8,

194:19

United States District Court

21

refer [4] - 54:3, 156:19,

166:20, 169:7

reference [3] - 103:17,

106:14, 190:10

referenced [4] - 103:15,

105:9, 191:23, 196:14

references [1] - 175:17

referred [6] - 130:11, 142:4,

153:3, 167:25, 171:13,

178:12

referring [13] - 41:21, 42:4,

56:13, 68:2, 122:8, 142:2,

142:8, 146:4, 148:7, 153:21,

153:22, 154:2, 175:12

refers [3] - 132:15, 159:22,

203:6

refined [1] - 30:12

reflects [1] - 115:8

regarded [1] - 133:4

regarding [15] - 50:5,

91:20, 97:19, 101:17, 106:1,

109:17, 115:20, 117:10,

117:25, 126:6, 130:19,

138:21, 154:5, 171:18, 172:3

regimented [3] - 30:1, 30:2,

30:12

Regina [1] - 1:24

regular [1] - 9:22

regulated [1] - 29:25

regulatory [5] - 29:15, 46:7,

63:7, 98:19, 199:16

reins [1] - 44:12

reiterating [1] - 53:10

relate [4] - 4:21, 4:22,

97:10, 146:17

related [9] - 15:4, 35:19,

98:22, 99:23, 103:15,

114:23, 118:22, 120:18,

143:21

relates [4] - 119:25, 120:1,

120:4, 122:1

relating [6] - 72:13, 72:14,

125:11, 125:21, 158:20,

160:21

relative [1] - 155:2

release [16] - 33:19, 56:7,

56:13, 56:16, 56:18, 56:23,

56:24, 57:2, 57:13, 58:13,

58:16, 180:24, 182:7, 183:3,

183:4, 196:4

releases [2] - 58:2, 58:7

relevant [8] - 13:21, 15:14,

15:17, 68:13, 98:15, 122:23,

123:9, 162:19

relevantly [1] - 123:12

reliable [1] - 28:18

relied [2] - 33:7, 44:18

rely [4] - 32:18, 63:12,

89:20, 99:11

remember [13] - 81:10,

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 229 of 236 PageID: 18812
107:25, 145:18, 145:20,

145:22, 146:10, 148:24,

155:11, 155:15, 160:15,

162:17, 179:21, 201:11

remind [1] - 51:9

render [1] - 106:5

repeat [2] - 48:3, 52:5

repeating [1] - 104:1

rephrase [3] - 30:24, 165:8,

200:17

report [55] - 34:7, 42:23,

42:24, 42:25, 59:6, 59:13,

59:20, 59:21, 59:22, 59:23,

60:10, 60:15, 61:12, 65:7,

65:15, 65:18, 66:25, 67:7,

67:18, 67:19, 70:12, 70:16,

83:16, 83:17, 114:19, 115:3,

115:5, 115:8, 115:12,

117:18, 119:22, 121:25,

122:5, 122:6, 125:9, 128:18,

129:17, 147:1, 147:3, 147:8,

147:9, 147:19, 147:24,

148:4, 148:16, 167:3,

189:17, 202:24, 203:3,

203:15, 203:19, 203:22,

204:2, 204:11, 207:5

reported [9] - 69:11, 75:23,

128:5, 130:22, 131:5,

135:15, 136:6, 161:16,

161:20

reports [10] - 33:24, 58:20,

59:2, 60:16, 66:18, 93:18,

118:5, 127:24, 148:17,

160:22

represent [3] - 4:6, 166:13,

167:8

representative [1] - 7:11

representatives [1] - 73:16

representing [1] - 63:5

reproducing [1] - 17:9

request [1] - 63:6

requested [1] - 34:17

requesting [1] - 51:25

require [1] - 73:23

required [6] - 1:23, 26:7,

136:19, 142:20, 172:17,

206:24

requirement [3] - 43:16,

142:21, 190:20

requirements [1] - 98:19

requires [2] - 98:14, 119:15

requiring [2] - 94:1, 202:7

reran [1] - 145:8

rescue [11] - 38:17, 38:23,

39:10, 136:12, 169:9, 175:5,

190:16, 190:18, 191:7,

192:17, 192:23

research [20] - 5:13, 7:20,

10:7, 11:13, 12:11, 21:23,

28:7, 30:10, 30:11, 73:18,

81:7, 107:17, 108:16,

108:17, 109:1, 111:19,

112:21, 112:25, 113:10,

113:11

Research [4] - 13:14,

13:25, 51:17

residency [2] - 6:7, 6:9

residents [1] - 13:2

residual [1] - 7:7

resolve [1] - 99:6

resolved [1] - 121:23

respect [29] - 15:8, 16:6,

31:2, 50:4, 97:19, 97:24,

101:21, 102:3, 117:16,

124:2, 124:9, 125:8, 125:20,

127:25, 128:3, 132:20,

133:11, 134:20, 146:25,

150:7, 161:12, 169:19,

174:6, 177:18, 179:6, 179:7,

203:18, 206:25, 207:4

respected [1] - 46:1

respond [1] - 169:5

responder [3] - 167:10,

169:4, 169:5

response [48] - 38:15,

38:20, 38:24, 53:22, 53:23,

60:16, 60:21, 64:15, 64:16,

109:25, 110:5, 128:8,

128:10, 128:14, 128:18,

137:25, 139:13, 139:21,

167:12, 168:21, 168:24,

169:1, 169:7, 169:8, 169:15,

169:20, 170:11, 170:15,

176:6, 176:19, 176:21,

176:23, 177:11, 178:24,

187:7, 187:8, 187:9, 187:10,

187:24, 188:1, 197:13,

198:10, 198:12, 198:23,

199:1, 199:3, 199:9

RESPONSE [1] - 96:1

Response [1] - 178:11

responsibility [1] - 168:12

result [19] - 11:10, 28:2,

29:1, 29:7, 30:6, 47:2, 50:9,

53:7, 54:5, 55:14, 65:20,

71:14, 72:7, 72:18, 91:4,

91:7, 108:2, 145:24, 169:25

resulted [1] - 108:6

results [45] - 7:2, 13:16,

26:18, 27:25, 32:8, 33:21,

35:9, 38:1, 46:24, 49:20,

57:5, 60:11, 60:14, 62:21,

65:16, 65:17, 72:10, 73:2,

75:9, 78:15, 80:8, 132:11,

133:11, 142:5, 143:3,

147:15, 147:17, 147:25,

152:22, 175:12, 178:19,

178:21, 178:23, 179:4,

179:13, 179:16, 179:24,

180:2, 180:15, 181:21,

182:22, 193:6, 201:22,

202:16

Results [1] - 141:9

retained [1] - 107:8

retching [1] - 176:7

revealing [1] - 74:21

review [20] - 10:12, 13:23,

13:24, 25:9, 25:10, 32:7,

32:15, 33:16, 46:2, 50:6,

53:2, 53:4, 62:9, 64:4, 75:3,

82:16, 118:22, 148:10,

155:25, 196:19

Review [1] - 53:3

reviewed [27] - 13:20,

14:19, 14:22, 31:7, 32:8,

33:23, 53:11, 58:19, 66:11,

66:18, 67:21, 70:17, 73:4,

74:19, 76:5, 89:12, 94:11,

125:8, 125:11, 145:17,

148:17, 150:11, 160:21,

171:17, 172:2, 196:11

reviewer [3] - 13:21, 138:6,

199:2

reviewing [8] - 13:24, 35:2,

73:6, 117:21, 125:12,

126:19, 134:9, 137:24

Riccardo [9] - 68:20, 68:23,

69:23, 70:5, 156:23, 157:6,

157:19, 159:5, 159:19

risk [14] - 16:10, 41:7, 56:3,

57:8, 68:16, 71:15, 79:7,

84:10, 93:2, 93:11, 141:18,

141:19, 179:8, 203:25

risk/suggest [1] - 141:20

RMR [2] - 1:24, 1:25

road [4] - 84:17, 84:18,

84:19, 91:8

Roche [14] - 33:12, 149:9,

149:16, 149:22, 150:14,

151:12, 151:15, 151:17,

151:18, 151:19, 151:20,

151:21, 152:6, 152:9

ROCHE [1] - 1:4

Roche/Syntex [5] - 145:25,

146:6, 148:9, 150:11, 150:19

rock [1] - 101:19

role [3] - 43:14, 68:22,

97:21

room [3] - 30:3, 91:25,

106:21

roughly [4] - 117:17,

130:25, 134:25

rounding [2] - 131:2, 187:4

routine [3] - 21:14, 30:13,

76:3

row [4] - 39:9, 64:11, 134:4,

186:22

Roy [3] - 109:10, 141:8,

146:23

RPR [2] - 1:24, 1:25

United States District Court

22

RS-25259 [10] - 34:10,

152:21, 152:23, 174:17,

174:19, 175:4, 175:13,

175:17, 191:3, 191:5

RS-25259-197 [1] - 149:16

RSA [1] - 1:25

rubber [1] - 84:17

rule [2] - 104:6, 173:5

ruled [2] - 101:2, 101:4

ruling [4] - 105:15, 105:16,

105:18

run [4] - 28:12, 28:20,

62:20, 65:12

running [3] - 62:2, 185:23,

186:1

Rush [2] - 5:20, 113:7

S

S.A [2] - 1:4, 63:25

Saab [5] - 92:17, 92:22,

93:5, 93:25, 202:6

Saab's [1] - 125:9

sacrificing [1] - 17:22

safe [8] - 17:8, 18:8, 18:15,

19:12, 83:4, 129:11, 141:10,

207:22

safety [11] - 9:2, 17:19,

17:20, 18:19, 19:24, 20:15,

20:19, 34:8, 74:20, 97:20,

178:18

Safety [5] - 73:22, 73:24,

74:13, 75:3

sake [1] - 109:21

sale [5] - 31:21, 124:8,

124:22, 125:2, 125:21

saline [6] - 87:10, 87:19,

190:21, 191:8, 192:21,

194:21

sample [1] - 167:9

Santa [1] - 5:17

SAS [8] - 61:23, 61:25,

63:21, 63:22, 63:23, 65:11,

65:12, 182:14

satisfaction [1] - 175:21

satisfactory [2] - 179:4,

179:13

satisfied [2] - 184:14,

199:11

satisfy [1] - 202:6

saturated [1] - 50:17

saturation [1] - 40:23

SAUL [1] - 2:4

save [1] - 104:3

saw [10] - 6:16, 35:1, 53:17,

53:25, 64:18, 151:3, 170:21,

177:17, 182:5, 199:4

scale [1] - 136:15

scene [1] - 101:11

school [2] - 5:20, 61:24

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 230 of 236 PageID: 18813
science [4] - 33:14, 98:22,

171:3, 180:8

science-related [1] - 98:22

sciences [21] - 12:18,

14:12, 31:3, 43:1, 44:2,

49:17, 55:23, 57:10, 58:15,

81:24, 85:2, 91:14, 91:17,

93:9, 97:13, 97:18, 107:10,

120:13, 121:2, 141:14,

192:25

scientific [1] - 58:5

Scientific [2] - 181:3, 182:2

scientists [5] - 20:25,

102:25, 153:4, 195:7, 203:22

scientists' [1] - 6:9

screen [1] - 107:3

scroll [1] - 181:10

second [19] - 6:1, 16:22,

25:18, 38:15, 40:16, 49:3,

49:8, 53:16, 72:10, 77:21,

77:22, 124:16, 150:1,

152:17, 175:23, 176:18,

197:23, 199:24, 201:18

second-generation [2] -

49:3, 49:8

secondary [1] - 176:10

secret [2] - 74:8, 74:14

Section [1] - 1:23

section [14] - 35:25, 36:17,

36:18, 37:13, 49:25, 50:2,

50:4, 60:1, 60:13, 97:25,

120:14, 126:17, 168:6, 203:1

see [105] - 4:6, 8:6, 10:3,

14:25, 19:17, 39:19, 40:24,

43:2, 43:8, 44:2, 45:14,

47:21, 49:17, 55:24, 62:21,

63:22, 64:8, 67:25, 69:8,

74:14, 74:18, 75:9, 77:22,

78:5, 80:16, 81:5, 83:19,

89:25, 92:2, 95:8, 95:23,

97:6, 99:8, 104:10, 112:13,

116:5, 116:11, 116:23,

119:6, 126:22, 126:24,

128:5, 128:9, 128:16,

128:21, 129:12, 130:6,

132:13, 132:22, 133:12,

133:14, 133:16, 139:4,

139:18, 139:24, 140:9,

147:11, 149:2, 150:2, 150:7,

151:22, 152:4, 152:13,

152:15, 152:19, 152:24,

153:15, 154:10, 154:15,

154:16, 156:2, 156:23,

157:10, 157:23, 161:11,

161:13, 161:16, 161:20,

161:24, 164:4, 164:25,

168:2, 169:17, 169:20,

170:11, 170:14, 170:17,

174:22, 174:24, 175:14,

175:21, 180:23, 181:11,

181:13, 181:15, 181:17,

181:19, 181:21, 182:2,

182:9, 182:11, 182:22,

190:13, 192:14, 208:2

seeing [6] - 76:3, 145:18,

145:20, 146:10, 180:2,

185:13

select [1] - 20:8

selected [2] - 6:25, 49:14

selection [10] - 50:4, 50:7,

52:25, 53:12, 55:4, 111:20,

111:24, 112:8, 140:21, 151:6

send [1] - 58:2

SENDER [1] - 2:7

sends [3] - 12:8, 40:8,

74:19

Senior [2] - 181:3, 182:1

sense [3] - 23:8, 48:11,

78:25

senses [1] - 12:7

sent [2] - 6:23, 33:16

sentence [17] - 37:16, 38:3,

72:17, 110:20, 129:25,

149:15, 159:21, 167:9,

169:4, 174:25, 175:3,

175:11, 190:14, 191:1,

191:2, 191:3, 191:17

separate [1] - 131:9

September [6] - 56:17,

56:19, 57:2, 147:11, 148:4,

196:4

Sergio [8] - 68:20, 69:10,

156:22, 157:12, 159:4,

159:7, 161:14, 162:1

Serial [1] - 68:6

series [1] - 153:18

serotonin [5] - 12:5, 48:19,

48:20, 48:22, 49:1

serve [4] - 139:22, 198:13,

198:16, 200:24

served [1] - 14:2

service [1] - 10:4

services [1] - 5:12

session [1] - 42:18

set [4] - 28:10, 42:3,

115:12, 199:5

setron [1] - 129:4

setting [5] - 7:10, 78:23,

79:4, 110:7, 188:15

seven [1] - 9:9

shift [1] - 80:25

ship [1] - 24:22

short [1] - 159:25

shorthand [1] - 58:25

shortness [1] - 156:19

show [17] - 17:7, 17:14,

26:7, 26:8, 27:20, 61:3,

78:11, 96:17, 97:25, 109:8,

135:4, 143:10, 161:7,

166:21, 187:15, 187:16,

205:10

showed [9] - 31:13, 56:2,

134:21, 155:1, 193:1, 201:9,

201:11, 205:2, 205:5

showing [4] - 53:8, 143:1,

148:5, 177:11

shown [7] - 47:7, 52:22,

52:24, 65:9, 65:14, 75:1,

78:16

shows [6] - 60:19, 64:14,

102:9, 166:8, 189:18, 205:6

shut [1] - 75:5

sic [1] - 191:5

sick [5] - 11:18, 33:10,

39:16, 54:2, 74:2

side [16] - 22:15, 22:16,

26:2, 40:18, 50:19, 57:1,

82:9, 89:25, 91:2, 95:8,

101:17, 105:11, 189:23,

190:25, 206:5, 208:2

sidebar [3] - 90:2, 95:10,

208:4

Sidebar [2] - 92:7, 96:4

sided [2] - 23:8, 91:7

sides [2] - 91:9, 96:11

sign [4] - 25:11, 25:23,

69:13, 69:16

signal [6] - 12:8, 54:8,

130:12, 130:16, 141:15,

163:22

signaling [1] - 12:5

signalling [1] - 48:23

signals [2] - 20:19, 40:8

signature [1] - 146:22

signed [9] - 25:20, 115:5,

147:1, 147:3, 147:11,

147:20, 147:25, 148:4, 162:3

significance [3] - 135:5,

193:11, 194:14

significant [15] - 54:21,

57:1, 71:11, 126:6, 129:8,

132:20, 133:4, 133:23,

134:21, 145:9, 155:2,

177:11, 192:16, 193:22,

194:11

significantly [5] - 134:7,

174:14, 174:24, 175:9,

190:20

similar [8] - 19:12, 41:25,

97:14, 99:1, 103:3, 190:5,

190:17, 190:19

similarly [1] - 100:10

simple [3] - 23:7, 112:3,

173:22

simply [3] - 104:21, 112:17,

180:21

simultaneously [1] - 11:17

single [6] - 34:9, 38:4,

52:14, 71:2, 119:10, 129:9

single-intravenous [1] -

United States District Court

23

34:9

single-use [1] - 119:10

sit [1] - 62:19

situation [2] - 9:4, 103:3

six [1] - 118:7

sixties [1] - 20:17

size [1] - 167:10

skill [35] - 15:8, 15:15, 43:1,

43:17, 44:1, 49:17, 55:23,

57:9, 58:15, 81:23, 85:2,

89:16, 91:15, 93:9, 96:13,

96:19, 96:25, 97:9, 97:17,

100:12, 101:21, 102:22,

104:19, 106:1, 107:9,

113:24, 120:13, 121:2,

122:23, 123:8, 123:22,

123:23, 125:12, 192:24,

194:23

skilled [5] - 31:18, 31:24,

90:5, 91:12, 91:13

skills [1] - 31:2

skip [2] - 139:20, 200:15

slapped [1] - 30:8

Slide [1] - 166:4

slide [8] - 33:2, 65:11, 77:8,

77:22, 78:5, 78:11, 78:14,

82:9

slides [2] - 73:11, 76:21

slightly [1] - 97:23

slow [2] - 15:25, 83:8

small [2] - 54:6, 54:22

smaller [2] - 54:6, 175:13

Society [2] - 13:13, 113:12

sodium [8] - 83:5, 83:6,

83:7, 87:7, 87:12, 87:15

software [1] - 61:23

solution [3] - 24:14, 83:12,

86:15

someone [3] - 41:9, 72:3,

84:2

sometime [2] - 93:21,

163:18

sometimes [3] - 74:22,

76:1, 91:6

somewhat [1] - 88:10

soon [2] - 27:24, 64:8

sorry [18] - 51:24, 84:14,

98:17, 102:16, 104:2,

110:22, 111:14, 118:13,

131:21, 145:19, 157:1,

161:22, 165:8, 171:20,

173:13, 188:8, 191:3, 200:21

sort [16] - 9:14, 11:15,

11:16, 13:8, 13:15, 20:17,

22:1, 22:10, 23:11, 26:21,

29:21, 39:21, 78:25, 131:2,

145:7, 190:7

speaking [6] - 14:7, 105:24,

106:8, 126:10, 158:16, 182:8

speaks [1] - 180:11

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 231 of 236 PageID: 18814
specialize [1] - 6:5

specialty [1] - 10:24

specific [8] - 111:24, 112:8,

114:6, 114:13, 140:14,

140:21, 144:5, 149:22

specifically [5] - 105:10,

122:2, 122:12, 150:2, 155:23

specification [6] - 94:11,

94:14, 94:18, 94:21, 118:22,

122:17

specifics [1] - 96:17

speculating [3] - 159:14,

164:12, 164:25

speculation [1] - 35:4

spell [1] - 4:12

spend [1] - 184:2

sponsors [1] - 27:15

spreadsheet [1] - 26:18

Squibb [1] - 152:14

stab [1] - 158:1

stability [6] - 15:5, 103:25,

120:1, 120:11, 121:14,

155:13

stabilizers [1] - 88:1

stable [1] - 101:13

stand [5] - 95:3, 95:7,

102:15, 111:2, 207:25

standard [7] - 22:24, 48:12,

93:5, 102:4, 133:6, 133:8,

133:9

standing [2] - 58:9, 110:13

standpoint [4] - 106:6,

141:14, 141:17, 162:18

start [10] - 21:9, 67:3, 68:4,

96:12, 119:3, 120:15,

183:24, 186:10, 188:6, 193:4

started [6] - 59:15, 67:14,

90:8, 101:8, 183:25, 184:1

starting [7] - 13:3, 18:7,

39:15, 63:17, 190:14, 191:3,

198:11

starts [2] - 12:5, 64:11

state [13] - 4:12, 17:9, 38:3,

38:4, 50:5, 56:23, 69:9,

70:13, 71:7, 71:8, 106:13,

120:4, 121:25

State [1] - 1:12

statement [12] - 55:9,

55:12, 55:13, 55:16, 55:24,

55:25, 56:1, 79:20, 96:16,

163:20, 165:14, 195:17

statements [3] - 22:5,

58:16, 79:18

states [18] - 46:13, 50:7,

56:24, 62:4, 63:24, 68:14,

68:23, 69:10, 69:21, 70:3,

70:23, 129:7, 141:22,

149:15, 152:21, 157:3,

162:25, 181:23

STATES [2] - 1:1, 1:14

States [8] - 1:11, 5:10,

51:13, 73:22, 74:12, 110:12,

158:9, 158:22

stating [1] - 196:5

statistical [18] - 20:21,

26:4, 28:11, 28:16, 54:15,

54:16, 61:24, 62:1, 62:2,

62:6, 134:1, 135:4, 141:19,

145:9, 193:10, 194:9,

194:13, 207:11

statistically [10] - 54:21,

132:20, 133:4, 133:23,

134:6, 134:21, 155:1,

177:11, 193:17, 193:22

statistics [5] - 28:9, 132:25,

178:15, 204:12, 207:11

status [1] - 126:7

stay [1] - 85:18

stays [1] - 98:8

steady [1] - 76:8

stem [1] - 12:8

stems [1] - 16:12

step [5] - 29:25, 51:20,

94:25, 95:5, 196:9

stick [2] - 15:23, 82:20

still [12] - 11:9, 17:24, 58:9,

72:23, 73:3, 101:3, 111:10,

154:8, 177:20, 199:10,

199:20

stimulate [1] - 11:15

stipulated [2] - 65:20,

170:21

stop [3] - 74:1, 74:3, 104:2

stopped [1] - 200:24

stopping [1] - 156:8

STRAWN [1] - 2:9

Street [1] - 1:12

strength [1] - 93:14

stress [1] - 30:6

strictly [1] - 182:8

strike [1] - 119:22

strong [2] - 36:5, 36:11

strongly [1] - 206:17

structure [1] - 162:9

STUART [1] - 2:7

student [1] - 18:20

students [8] - 9:21, 10:11,

12:14, 12:16, 12:25, 13:1,

13:5, 17:3

studied [6] - 47:4, 131:25,

172:7, 174:7, 174:19, 196:2

studies [27] - 18:21, 20:2,

20:23, 20:24, 33:19, 47:17,

48:4, 93:14, 94:3, 141:9,

142:24, 143:7, 143:18,

143:24, 144:3, 149:12,

149:17, 149:24, 160:8,

160:22, 160:25, 161:6,

195:14, 196:5, 199:14,

200:4, 200:5

Study [16] - 36:4, 36:21,

37:17, 42:22, 42:23, 130:22,

137:9, 140:11, 142:2,

142:12, 144:19, 146:7,

147:15, 148:10, 177:10,

179:1

study [171] - 5:23, 6:23, 7:9,

9:16, 19:14, 20:4, 22:22,

22:23, 23:1, 24:13, 25:11,

25:14, 26:8, 26:10, 27:19,

28:2, 29:1, 32:8, 33:10,

33:21, 34:4, 34:9, 35:10,

35:14, 35:15, 35:21, 36:5,

36:9, 37:8, 38:12, 42:23,

42:24, 42:25, 43:2, 47:16,

48:10, 49:23, 53:5, 53:13,

55:5, 56:2, 59:2, 59:6, 59:13,

59:15, 59:16, 59:18, 59:20,

59:22, 59:23, 60:3, 60:10,

60:24, 60:25, 61:12, 61:19,

61:21, 65:6, 66:6, 66:25,

67:3, 67:5, 67:7, 69:4, 70:12,

70:15, 72:1, 72:5, 72:7,

72:11, 72:18, 73:2, 74:1,

74:9, 74:20, 75:6, 75:24,

76:5, 79:24, 81:11, 81:19,

82:18, 83:23, 89:17, 93:10,

93:12, 109:23, 110:4,

128:23, 130:20, 131:5,

131:15, 133:22, 135:6,

136:23, 139:21, 141:22,

142:2, 142:8, 142:10,

142:17, 142:18, 143:2,

143:14, 143:15, 143:16,

143:21, 143:22, 144:1,

144:22, 144:24, 145:25,

147:19, 147:21, 147:24,

152:21, 152:22, 155:25,

160:22, 163:9, 167:2,

167:21, 167:24, 168:15,

168:16, 168:17, 168:19,

170:1, 185:24, 187:15,

188:6, 188:9, 188:12,

188:23, 189:1, 189:2,

189:10, 190:3, 193:2, 193:5,

194:15, 195:7, 196:19,

197:17, 198:7, 198:12,

198:17, 198:19, 198:23,

199:14, 199:17, 199:20,

199:21, 199:24, 200:2,

200:9, 201:6, 201:21,

201:24, 202:24, 203:3,

203:15, 203:18, 204:2,

205:9, 207:5

studying [1] - 184:2

stuff [2] - 9:24, 84:17

sub [1] - 151:20

subconsciously [1] - 23:12

subject [7] - 15:2, 15:4,

119:24, 120:9, 120:20,

United States District Court

24

121:9, 121:20

subjects [2] - 36:18, 80:25

submission [1] - 63:7

submit [5] - 69:21, 70:3,

102:2, 157:4, 157:17

submitted [1] - 68:4

subsequently [2] - 110:1,

177:17

subsets [1] - 12:19

subsidiary [1] - 51:13

substance [3] - 23:16,

23:17, 115:18

substantiates [1] - 194:25

substantive [1] - 99:19

success [5] - 19:19, 163:5,

163:22, 164:5, 165:1

successful [9] - 55:17,

57:6, 72:8, 72:19, 143:1,

143:10, 144:9, 144:19, 164:9

successfully [4] - 71:24,

72:3, 165:13, 170:25

suffering [2] - 18:16, 183:1

sufficient [5] - 139:16,

197:18, 198:7, 200:10,

200:12

suggest [4] - 141:9, 141:13,

141:20, 175:12

suggested [1] - 95:18

suggestion [1] - 141:16

suggests [1] - 165:13

suit [3] - 97:10, 125:21,

149:5

summarize [1] - 139:13

summarized [1] - 117:9

summary [7] - 31:10, 37:13,

60:13, 117:17, 131:23,

132:9, 175:12

Summary [1] - 178:11

summer [2] - 94:7, 94:8

superior[1] - 30:10

superiority [1] - 205:10

supervise [1] - 21:18

supervisor [1] - 10:15

supplied [1] - 100:1

support [21] - 11:1, 11:2,

31:8, 53:11, 63:9, 82:23,

105:20, 122:9, 139:16,

139:22, 141:22, 197:19,

198:7, 198:13, 198:16,

199:17, 199:19, 199:24,

200:4, 200:12, 200:25

supported [1] - 100:18

supporting [1] - 71:19

supportive [7] - 10:22,

10:25, 14:13, 139:23,

144:22, 198:14, 201:3

Supportive [1] - 127:11

supports [2] - 79:20,

129:14

supposed [2] - 17:13,

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 232 of 236 PageID: 18815
85:18

suppress [5] - 11:11,

17:13, 36:10, 41:16, 83:3

suppresses [1] - 17:16

suppressing [3] - 11:17,

22:12, 38:8

suppressor[1] - 11:23

surface [1] - 48:25

surgery [3] - 175:19,

188:18, 190:21

surgical [1] - 175:7

surprised [2] - 55:11, 62:14

surprising [1] - 65:17

sustained [3] - 35:5,

121:22, 200:20

sweep [1] - 101:16

Swiss [1] - 180:12

Swiss-Italian [1] - 180:12

switched [1] - 154:12

sworn [2] - 4:11, 116:21

symptoms [3] - 129:21,

130:4, 136:9

synonymous [1] - 47:19

synopsis [1] - 35:10

Syntex [33] - 32:8, 33:9,

33:12, 33:13, 34:3, 42:22,

43:2, 44:2, 44:25, 46:6,

51:19, 89:17, 149:9, 149:12,

150:14, 150:24, 151:1,

151:6, 151:16, 151:17,

151:19, 151:21, 151:23,

153:3, 160:25, 177:18,

193:4, 195:6, 195:7, 195:14,

196:24

Syntex's [2] - 37:16, 130:20

Syntex/Helsinn [1] - 151:2

T

Table [9] - 60:14, 60:16,

61:3, 150:5, 169:12, 178:11,

189:11, 191:22

table [16] - 46:17, 47:7,

53:17, 65:11, 132:18,

132:19, 150:1, 178:6, 178:7,

178:10, 178:17, 178:20,

181:21, 187:1, 203:7, 204:16

tables [1] - 63:23

tachyphylaxis [1] - 206:4

Tang [20] - 171:14, 171:16,

174:6, 177:5, 188:5, 188:6,

189:10, 190:3, 190:10,

191:12, 191:23, 192:5,

192:11, 192:12, 192:13,

192:25, 205:12

TARANTINO [1] - 2:12

target [4] - 22:15, 26:9,

26:10, 40:19

teach [6] - 12:12, 12:13,

12:20, 12:25, 13:1, 13:5

teaching [2] - 12:15, 13:4

Team [1] - 44:21

team [6] - 47:12, 96:20,

99:7, 99:10, 104:16, 155:24

teams [1] - 103:4

teamwork [1] - 98:14

technical [1] - 57:23

teed [1] - 100:9

ten [1] - 168:19

tend [1] - 19:14

tender [1] - 14:11

tense [1] - 142:4

term [17] - 7:24, 15:15,

22:7, 23:23, 25:6, 25:19,

26:2, 26:22, 48:18, 84:12,

86:20, 158:5, 158:6, 158:12,

158:13, 158:14, 159:15

terminating [1] - 149:20

terms [11] - 25:5, 57:6,

78:22, 88:24, 105:19,

105:24, 126:5, 130:17,

160:5, 188:23, 190:6

test [13] - 7:1, 9:14, 9:19,

17:7, 17:17, 48:7, 70:7,

131:21, 142:13, 142:14,

155:8, 157:9, 164:9

tested [10] - 20:15, 23:16,

23:17, 71:10, 71:24, 72:3,

135:15, 155:9, 165:13,

170:25

testified [14] - 51:6, 56:10,

107:24, 113:20, 130:9,

134:17, 135:22, 139:6,

140:14, 142:8, 149:7,

176:11, 179:3, 180:24

testify [2] - 179:15, 179:17

testifying [4] - 162:14,

176:7, 179:6, 179:7

testimony [53] - 34:14,

43:5, 82:23, 89:3, 90:8, 91:8,

91:9, 95:1, 95:20, 96:7,

101:19, 101:20, 101:23,

101:25, 105:23, 106:3,

108:25, 109:3, 109:4,

114:22, 114:23, 117:25,

118:5, 120:2, 120:20,

125:21, 126:4, 130:17,

138:21, 140:18, 141:1,

141:4, 147:18, 149:18,

151:3, 153:22, 154:5, 155:7,

155:14, 156:16, 158:25,

159:5, 159:12, 160:14,

162:13, 163:4, 163:7,

176:20, 178:7, 179:20,

194:25, 195:21

testing [2] - 7:8, 98:23

TEVA [2] - 1:8, 1:9

Teva [6] - 2:13, 4:6, 107:8,

116:1, 116:2, 206:12

Teva's [4] - 113:23, 117:9,

117:15, 117:22

Texas [1] - 51:15

text [3] - 13:23, 15:23,

191:20

THE [536] - 1:2, 1:14, 4:2,

4:12, 4:14, 6:1, 6:2, 6:3, 6:4,

6:5, 6:7, 8:17, 8:18, 8:19,

8:22, 9:3, 9:4, 9:6, 9:19,

9:21, 10:6, 10:9, 12:2, 12:4,

12:16, 12:17, 14:15, 15:25,

16:2, 16:22, 16:25, 18:16,

18:18, 18:19, 18:20, 20:8,

20:11, 21:1, 21:2, 21:8, 21:9,

21:17, 21:19, 21:22, 21:24,

23:15, 23:18, 23:19, 23:21,

23:22, 23:24, 23:25, 24:3,

24:4, 25:1, 25:2, 25:12,

25:13, 25:15, 25:17, 28:4,

28:6, 29:3, 29:5, 29:13,

29:15, 29:19, 29:24, 30:1,

30:2, 30:24, 31:16, 31:20,

31:24, 32:2, 32:10, 32:12,

32:21, 33:3, 34:20, 35:5,

36:12, 36:14, 36:15, 36:16,

38:8, 38:10, 38:19, 38:22,

39:3, 39:4, 39:6, 39:7, 39:9,

39:12, 39:22, 39:25, 40:5,

40:6, 40:7, 40:9, 40:12,

40:13, 40:14, 40:15, 40:19,

40:21, 40:22, 40:23, 41:12,

41:13, 41:14, 41:15, 41:21,

41:22, 41:23, 41:24, 42:4,

42:5, 42:6, 42:10, 42:14,

42:16, 42:18, 43:9, 43:18,

43:21, 44:23, 44:24, 45:1,

45:2, 45:6, 45:7, 45:8, 47:18,

47:21, 47:22, 47:23, 47:24,

47:25, 48:1, 48:14, 48:17,

49:6, 49:7, 50:23, 50:24,

52:3, 53:16, 53:18, 53:19,

53:21, 53:23, 53:24, 54:3,

54:4, 54:11, 54:12, 54:15,

54:16, 55:19, 55:21, 57:16,

57:19, 57:20, 57:21, 57:22,

57:23, 57:24, 59:3, 61:7,

61:9, 65:22, 65:23, 66:12,

66:14, 69:2, 69:3, 72:10,

72:12, 72:13, 72:15, 72:16,

72:20, 73:15, 73:17, 74:6,

74:11, 74:17, 74:18, 75:4,

75:7, 75:8, 75:11, 75:12,

75:13, 75:16, 75:18, 75:19,

75:20, 75:21, 75:22, 75:23,

75:25, 76:1, 76:2, 76:8, 76:9,

79:10, 79:12, 79:13, 79:15,

79:23, 79:25, 80:1, 80:3,

80:4, 80:5, 80:6, 80:9, 80:10,

80:11, 80:12, 80:13, 80:16,

80:17, 80:18, 80:19, 80:20,

80:21, 80:22, 81:1, 81:6,

81:7, 81:9, 81:14, 81:17,

United States District Court

25

81:20, 82:1, 82:2, 83:8,

83:16, 83:19, 84:11, 84:12,

84:13, 84:14, 85:10, 85:15,

85:16, 85:17, 85:18, 85:20,

85:21, 85:23, 85:24, 86:2,

86:3, 86:5, 86:8, 86:9, 86:25,

87:1, 87:3, 87:4, 87:5, 87:6,

87:9, 87:11, 87:14, 87:15,

87:18, 87:20, 87:21, 87:22,

87:23, 87:24, 87:25, 88:2,

88:3, 88:4, 88:5, 88:7, 88:8,

88:9, 88:13, 88:14, 88:15,

88:16, 88:18, 88:22, 89:3,

89:6, 89:24, 90:3, 91:1,

91:15, 91:21, 92:2, 92:4,

92:20, 92:22, 93:1, 93:2,

94:4, 94:7, 94:25, 95:4, 95:5,

95:8, 95:11, 95:15, 95:23,

96:2, 96:6, 96:10, 98:3,

98:16, 99:14, 99:16, 99:18,

102:19, 103:9, 103:18,

104:1, 104:6, 104:10, 105:2,

105:4, 105:6, 105:22,

106:12, 106:19, 106:22,

107:1, 107:5, 108:11,

108:22, 110:20, 111:2,

111:4, 111:5, 111:7, 111:13,

111:14, 111:15, 111:17,

113:2, 113:6, 114:7, 114:10,

114:19, 114:20, 115:23,

116:9, 118:4, 118:10,

118:19, 118:24, 119:17,

119:19, 119:20, 121:22,

123:5, 123:10, 123:19,

123:21, 124:6, 124:15,

124:17, 124:18, 124:22,

125:24, 127:1, 128:22,

128:24, 129:1, 129:2, 129:3,

129:4, 134:3, 134:5, 135:8,

135:11, 135:13, 135:14,

135:17, 135:19, 135:20,

135:24, 135:25, 136:4,

136:8, 136:9, 136:10,

136:11, 136:12, 136:14,

136:17, 136:20, 137:17,

137:19, 138:10, 138:17,

143:19, 143:20, 143:23,

143:25, 145:1, 145:3, 145:4,

145:5, 151:20, 151:22,

151:25, 156:7, 156:10,

156:13, 158:17, 158:18,

159:2, 159:9, 159:10, 161:7,

163:13, 163:14, 163:16,

167:2, 167:5, 169:1, 169:3,

169:24, 170:2, 170:3, 170:4,

170:23, 170:24, 172:9,

172:12, 173:10, 173:11,

173:12, 173:13, 173:14,

174:1, 175:23, 176:3, 176:4,

176:18, 176:24, 176:25,

177:1, 177:2, 177:24, 178:2,

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 233 of 236 PageID: 18816
180:2, 180:5, 183:7, 183:9,

183:10, 183:12, 183:15,

184:5, 184:6, 184:7, 184:9,

184:10, 184:11, 184:15,

184:16, 184:21, 184:25,

185:3, 185:11, 185:12,

187:3, 187:4, 187:22, 189:7,

189:8, 189:20, 189:21,

189:22, 189:23, 191:13,

191:19, 193:18, 194:18,

194:19, 195:22, 195:24,

197:8, 198:1, 198:2, 198:18,

198:19, 198:21, 198:25,

199:3, 199:4, 199:7, 199:8,

199:10, 199:12, 199:19,

199:22, 199:25, 200:2,

200:18, 200:20, 200:21,

202:13, 202:15, 202:16,

202:18, 203:6, 203:9,

203:11, 203:24, 204:4,

204:6, 204:7, 204:8, 205:25,

207:10, 207:13, 207:14,

207:15, 207:16, 207:17,

207:18, 207:20, 207:21,

207:22, 207:24, 208:2

theirs [1] - 104:20

theme [1] - 147:18

theoretically [1] - 40:20

therapeutic [2] - 88:25,

89:2

Therapeutics [1] - 113:13

therapeutics [2] - 5:4, 8:15

therapies [1] - 20:1

therapy [1] - 78:19

therefore [2] - 121:19,

187:15

they've [7] - 27:17, 47:1,

52:15, 62:22, 142:4, 154:12,

168:8

thinking [4] - 147:2, 147:4,

148:7, 154:12

thinks [2] - 50:21, 180:14

third [11] - 40:16, 56:21,

56:22, 78:2, 78:3, 141:8,

149:15, 150:14, 181:23,

192:15, 204:17

thousand [1] - 45:25

three [27] - 10:3, 18:23,

20:3, 20:9, 23:6, 23:7, 23:8,

47:4, 48:15, 51:20, 58:23,

59:2, 69:16, 77:9, 77:12,

93:18, 93:19, 94:2, 94:8,

108:6, 142:24, 164:20,

166:9, 192:19, 194:1, 196:1

three-quarter [1] - 48:15

three-sided [1] - 23:8

throughout [1] - 171:13

throw [7] - 11:18, 12:8,

23:8, 38:12, 38:25, 41:11,

41:15

throwing [1] - 75:15

ticking [1] - 27:25

timeline [6] - 42:13, 42:21,

51:2, 56:4, 65:25, 67:20

tissue [2] - 9:23, 86:19

Title [1] - 1:23

title [7] - 44:20, 50:2, 68:7,

68:8, 115:23, 116:1, 181:15

today [18] - 4:3, 10:25,

11:9, 11:16, 32:15, 35:15,

61:25, 89:12, 108:25, 109:3,

109:4, 114:23, 115:9,

119:24, 134:17, 171:2,

176:20, 206:15

together[8] - 24:21, 28:1,

79:3, 103:4, 103:5, 131:13,

131:14, 141:20

tolerated [1] - 129:11

tonicity [1] - 82:24

took [3] - 54:1, 153:19,

196:17

top [6] - 49:25, 65:10,

65:11, 68:4, 197:11, 201:19

topic [1] - 118:11

total [5] - 36:20, 130:25,

148:11, 150:8, 184:2

touched [1] - 27:7

towards [1] - 174:16

toxic [1] - 19:3

toxicity [1] - 18:2

toxicology [1] - 162:16

track [2] - 6:9, 156:4

train [1] - 9:21

trained [3] - 8:1, 10:23,

10:25

training [5] - 6:6, 6:9,

15:12, 15:17, 183:18

transcript [6] - 109:8,

137:14, 137:17, 137:18,

137:20, 173:20

transferred [1] - 151:23

translate [1] - 7:21

translating [1] - 180:12

translation [1] - 164:22

translational [1] - 109:24

traveling [1] - 207:22

travels [1] - 207:23

treat [5] - 11:6, 25:24,

119:8, 178:24, 189:4

treated [5] - 10:19, 25:21,

35:18, 78:18, 206:7

treating [7] - 70:23, 99:4,

114:6, 121:5, 129:20, 130:3,

173:8

treatment [26] - 23:5, 64:14,

68:8, 69:5, 70:6, 71:2, 71:21,

73:10, 101:4, 101:7, 104:25,

108:7, 109:15, 109:18,

110:5, 111:24, 112:9,

114:13, 122:12, 128:3,

128:5, 140:21, 145:6, 157:8,

157:14, 181:24

treatment-effective [1] -

71:2

treatments [1] - 8:5

tree [1] - 62:19

tremendous [2] - 30:4, 30:6

tremendously [1] - 10:14

trend [1] - 54:7

Trenton [1] - 1:12

trial [72] - 6:17, 8:6, 9:11,

14:3, 14:6, 14:7, 16:12,

16:20, 17:2, 19:22, 22:20,

24:7, 25:20, 26:5, 26:15,

26:17, 27:16, 28:21, 32:9,

33:9, 33:20, 34:8, 36:11,

41:20, 46:24, 47:1, 49:20,

50:9, 50:10, 50:15, 54:6,

55:12, 55:17, 57:7, 58:19,

59:23, 60:18, 61:2, 62:21,

66:8, 66:10, 67:13, 67:14,

81:3, 82:10, 82:11, 91:2,

92:23, 93:25, 94:15, 94:19,

97:8, 97:25, 107:21, 107:24,

108:2, 109:22, 122:20,

134:15, 144:23, 164:5,

167:21, 176:18, 176:25,

182:22, 183:13, 185:22,

202:6, 202:21

TRIAL [1] - 1:7

trials [81] - 5:13, 6:15, 7:21,

7:22, 8:8, 8:10, 8:14, 8:16,

9:8, 9:9, 10:7, 13:5, 16:16,

19:11, 20:10, 21:13, 21:17,

21:20, 22:19, 22:21, 25:6,

27:14, 33:23, 33:24, 34:3,

36:7, 36:12, 45:22, 46:14,

46:16, 47:5, 47:11, 56:23,

56:24, 57:14, 62:2, 70:7,

82:5, 92:19, 92:23, 93:19,

94:9, 103:24, 108:6, 108:9,

108:17, 109:14, 109:17,

110:8, 110:9, 110:14,

110:15, 110:16, 111:10,

111:11, 129:19, 130:1,

134:9, 134:17, 142:24,

143:4, 146:1, 148:11,

150:20, 155:10, 157:9,

162:7, 162:20, 181:16,

184:19, 184:24, 185:5,

185:13, 185:16, 185:19,

186:2, 196:1, 202:3, 202:11

trials' [1] - 146:18

tried [3] - 143:13, 143:14,

143:20

trouble [2] - 103:8, 105:23

troubleshoot [1] - 29:4

true [6] - 80:21, 108:1,

114:2, 124:21, 162:17, 176:8

True [1] - 1:23

United States District Court

26

truly [1] - 100:8

try [7] - 42:10, 48:21,

101:11, 109:5, 147:22,

165:5, 166:24

trying [16] - 9:15, 11:5,

15:22, 17:9, 24:9, 46:25,

86:14, 86:15, 86:22, 105:8,

105:14, 112:13, 143:21,

146:16, 150:17, 165:14

tube [3] - 7:1, 9:14, 9:19

Tuesday [5] - 22:4, 34:13,

82:23, 126:4, 159:7

tumor [4] - 6:22, 6:25, 7:7,

9:16

tumors [2] - 7:1, 7:10

turn [17] - 49:12, 75:2,

126:12, 126:17, 145:16,

148:15, 149:14, 150:1,

150:2, 153:7, 155:22,

156:15, 159:18, 169:11,

171:10, 178:5

turned [1] - 75:14

turning [2] - 141:7, 175:16

two [37] - 6:8, 13:15, 19:6,

20:3, 20:8, 21:19, 23:1, 23:5,

24:12, 47:6, 47:14, 47:15,

52:16, 75:4, 77:15, 77:17,

92:18, 92:23, 92:24, 93:8,

93:14, 98:9, 100:11, 102:16,

107:20, 108:5, 108:6,

130:17, 151:23, 166:11,

190:17, 190:19, 200:4,

200:5, 202:3, 202:10

two-arm [1] - 23:1

type [8] - 6:25, 16:7, 78:10,

172:6, 172:8, 172:9, 188:19,

205:25

types [4] - 8:8, 16:16,

20:22, 206:21

typical [1] - 7:11

typically [1] - 27:23

U

U.S [2] - 119:8, 164:17

U.S.A [2] - 116:2, 151:16

U.S.C [1] - 1:23

UC [15] - 5:6, 5:14, 5:17,

6:7, 7:16, 7:19, 9:10, 12:11,

13:11, 45:17, 73:24, 107:16,

108:5, 184:13, 185:7

ultimately [2] - 199:18,

201:4

um-hum [2] - 170:9, 181:14

unblind [1] - 27:7

unblinded [20] - 19:14,

26:20, 27:10, 27:22, 28:14,

62:7, 62:8, 62:9, 62:23,

62:24, 63:20, 65:13, 65:20,

65:23, 74:15, 76:25, 80:6,

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 234 of 236 PageID: 18817
81:19, 89:18, 163:18

unblinding [3] - 27:15,

27:24, 62:14

under [18] - 41:2, 41:23,

42:4, 46:13, 47:15, 60:13,

61:16, 62:18, 64:14, 97:8,

98:1, 104:19, 104:20, 117:5,

133:3, 151:21, 152:21,

155:23

undergoing [1] - 175:19

undergrad [1] - 13:6

undergrads [1] - 12:25

undergraduate [3] - 12:13,

12:14, 17:3

undergraduates [1] - 12:17

underneath [1] - 132:19

underpinning [1] - 57:7

understood [6] - 42:10,

85:3, 96:12, 100:1, 144:8,

176:20

undertaken [1] - 162:8

unexpected [1] - 19:1

unfortunately [2] - 11:9,

162:22

unit [1] - 119:10

unit-dose [1] - 119:10

UNITED [1] - 1:1

United [8] - 1:11, 5:10,

51:13, 73:22, 74:11, 110:12,

158:9, 158:22

uNITED [1] - 1:14

university [2] - 7:18, 110:6

University [3] - 4:25, 5:1,

5:21

unless [1] - 42:15

unusual [2] - 50:9, 57:13

up [68] - 8:4, 11:4, 11:18,

12:8, 12:14, 13:9, 17:17,

18:11, 19:2, 21:15, 28:10,

29:22, 38:12, 38:25, 39:23,

41:11, 41:16, 42:22, 46:9,

49:24, 50:19, 52:4, 55:1,

59:8, 63:18, 63:21, 72:22,

75:15, 77:5, 78:19, 79:11,

80:20, 86:10, 98:8, 99:25,

100:9, 104:12, 105:18,

106:13, 111:9, 125:9,

127:22, 129:23, 131:22,

137:14, 137:22, 138:15,

140:25, 161:24, 165:14,

166:21, 166:25, 170:6,

173:20, 177:9, 180:18,

181:9, 181:10, 186:4, 187:4,

189:12, 198:3, 201:8,

201:19, 203:23, 204:16

updates [2] - 73:21, 74:19

upper [2] - 12:15, 153:15

urological [1] - 8:11

USA [1] - 1:8

useful [4] - 105:22, 139:22,

198:14, 201:3

useless [1] - 91:9

uses [1] - 124:12

utilize [1] - 7:12

V

vague [2] - 30:21, 30:23

value [9] - 54:3, 54:4,

132:25, 133:12, 133:16,

133:24, 134:21, 134:22

values [1] - 110:10

variables [3] - 188:23,

188:25, 189:1

variety [1] - 36:7

various [7] - 8:10, 14:1,

16:16, 36:24, 107:10,

137:11, 195:1

vast [1] - 11:10

vein [7] - 86:6, 86:7, 86:8,

86:9, 86:10, 86:17

veins [1] - 41:18

versus [5] - 52:16, 132:21,

177:11, 189:24, 190:8

vial [2] - 84:2, 88:23

view [3] - 58:16, 91:1,

106:17

voice [1] - 92:20

VOIR [2] - 3:5, 4:15

volume [3] - 46:19, 49:14,

49:16

Volume [2] - 70:1, 157:22

volunteers [4] - 9:3, 9:5,

18:9, 21:5

vomit [3] - 17:12, 176:6,

189:20

vomited [4] - 189:18,

189:24, 190:1, 190:7

vomiting [57] - 11:12,

11:15, 15:21, 15:22, 16:10,

17:13, 34:11, 37:22, 44:5,

46:15, 46:16, 47:24, 50:11,

52:18, 54:20, 55:8, 56:3,

57:8, 64:22, 64:25, 65:2,

66:9, 68:16, 71:15, 73:9,

79:8, 83:3, 84:10, 89:22,

92:25, 93:3, 93:11, 93:16,

119:5, 120:7, 120:17, 121:6,

141:11, 141:25, 171:23,

172:5, 173:1, 173:2, 174:8,

174:14, 174:18, 175:5,

175:24, 176:7, 179:8,

186:20, 186:21, 188:10,

188:16, 188:20, 188:25,

194:16

Votrient® [1] - 109:16

vs [1] - 1:6

W

wait [2] - 74:6, 91:21

waiting [1] - 58:4

walk [2] - 16:18, 82:8

walls [1] - 142:6

wants [6] - 12:7, 23:11,

27:21, 58:10, 102:11, 102:13

watch [1] - 95:5

water [6] - 82:24, 83:9,

83:12, 87:13, 87:19, 141:6

ways [1] - 102:10

wear [1] - 39:14

week [3] - 10:3, 62:14,

181:19

weekends [1] - 30:5

weighted [1] - 49:10

whereas [2] - 60:24, 200:4

whereby [2] - 150:11,

150:19

whichever [1] - 107:3

whoa [2] - 199:19

whole [2] - 11:3, 147:6

widely [2] - 45:22, 62:1

WINSTON [1] - 2:9

witness [14] - 4:4, 4:8, 4:10,

14:2, 91:22, 102:15, 102:19,

104:14, 106:9, 106:20,

106:25, 116:7, 118:15,

207:25

WITNESS [214] - 3:5, 4:14,

6:2, 6:4, 6:7, 8:18, 8:22, 9:4,

9:21, 10:9, 12:4, 12:17, 16:2,

16:25, 18:18, 18:20, 20:11,

21:2, 21:9, 21:19, 21:24,

23:18, 23:21, 23:24, 24:3,

25:2, 25:13, 25:17, 28:6,

29:5, 29:15, 29:24, 30:2,

32:12, 36:14, 36:16, 38:10,

38:22, 39:4, 39:7, 39:12,

39:25, 40:6, 40:9, 40:13,

40:15, 40:21, 40:23, 41:13,

41:15, 41:22, 41:24, 42:5,

42:10, 44:24, 45:2, 45:7,

47:22, 47:24, 48:1, 48:17,

49:7, 50:24, 53:18, 53:21,

53:24, 54:4, 54:12, 54:16,

55:21, 57:20, 57:22, 57:24,

65:23, 66:14, 69:3, 72:12,

72:15, 72:20, 73:17, 74:11,

74:18, 75:7, 75:11, 75:13,

75:18, 75:20, 75:22, 75:25,

76:2, 76:9, 79:12, 79:15,

79:25, 80:3, 80:5, 80:9,

80:11, 80:13, 80:17, 80:19,

80:21, 81:6, 81:9, 81:17,

82:2, 84:12, 84:14, 85:15,

85:17, 85:20, 85:23, 86:2,

86:5, 86:9, 87:1, 87:4, 87:6,

87:11, 87:15, 87:20, 87:22,

United States District Court

27

87:24, 88:2, 88:4, 88:7, 88:9,

88:14, 88:16, 89:3, 92:22,

93:2, 94:7, 95:4, 107:5,

111:4, 111:7, 111:14,

111:17, 113:6, 114:20,

119:19, 124:17, 128:24,

129:2, 129:4, 134:5, 135:13,

135:17, 135:20, 135:25,

136:8, 136:10, 136:12,

136:17, 143:20, 143:25,

145:3, 145:5, 151:22,

158:18, 159:10, 163:14,

163:16, 167:5, 169:3, 170:2,

170:4, 170:24, 172:12,

173:11, 173:13, 174:1,

176:4, 176:24, 177:1, 178:2,

180:5, 183:9, 183:12, 184:6,

184:9, 184:11, 184:16,

184:21, 184:25, 185:3,

185:12, 187:4, 189:8,

189:21, 189:23, 194:19,

195:24, 198:2, 198:19,

198:25, 199:4, 199:8,

199:12, 199:22, 200:2,

200:18, 200:21, 202:15,

202:18, 203:24, 204:6,

204:8, 207:13, 207:15,

207:17, 207:21, 207:24

Witness [1] - 95:7

witnesses [1] - 96:8

women [1] - 175:19

won [2] - 180:14, 180:18

wonder[1] - 42:16

wondering [2] - 90:11,

90:13

WONG [150] - 2:10, 4:5,

4:15, 6:13, 9:7, 9:25, 10:17,

12:10, 12:24, 14:11, 14:16,

14:17, 16:3, 20:7, 20:13,

21:11, 22:3, 24:5, 25:4, 26:1,

28:15, 29:18, 30:14, 30:25,

31:1, 31:19, 31:21, 32:1,

32:3, 32:4, 32:13, 32:14,

33:5, 33:6, 34:2, 34:5, 34:22,

35:8, 35:12, 35:25, 36:2,

36:17, 36:19, 37:13, 37:15,

41:1, 42:12, 42:15, 42:19,

42:20, 43:7, 43:20, 43:22,

43:23, 45:9, 47:20, 48:2,

49:4, 49:9, 49:24, 50:1, 51:1,

52:5, 52:6, 54:23, 55:22,

57:17, 58:12, 59:4, 59:5,

61:8, 61:10, 61:11, 65:24,

66:17, 69:7, 72:21, 74:4,

76:7, 76:10, 79:16, 79:17,

80:23, 80:24, 81:21, 82:3,

83:9, 83:11, 83:17, 83:20,

84:20, 88:19, 88:20, 89:7,

89:8, 91:10, 91:17, 92:1,

92:3, 92:6, 92:8, 93:4, 94:10,

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 235 of 236 PageID: 18818
95:22, 116:7, 118:14,

118:21, 121:21, 123:17,

138:8, 173:25, 183:16,

184:17, 184:23, 185:1,

185:4, 185:17, 186:3, 186:6,

187:5, 187:23, 189:9,

189:12, 189:14, 190:2,

191:15, 191:21, 193:15,

193:19, 195:5, 196:3, 197:9,

197:10, 198:5, 200:7,

200:17, 200:22, 201:8,

201:10, 201:18, 201:20,

202:19, 203:7, 203:10,

203:12, 203:13, 203:23,

204:1, 204:14, 207:19

Wong [8] - 3:7, 4:6, 33:4,

34:20, 43:21, 118:19,

122:19, 138:11

word [10] - 25:16, 66:13,

81:14, 84:11, 141:13,

174:24, 175:9, 177:5,

180:13, 183:7

worded [1] - 176:13

words [7] - 19:19, 39:22,

76:8, 129:22, 129:24,

145:13, 198:18

wore [1] - 39:15

works [8] - 8:6, 27:20,

74:14, 74:23, 90:25, 96:20,

100:17, 103:12

world [2] - 103:3, 104:24

worry [1] - 42:8

worse [1] - 103:9

wrapping [1] - 42:22

write [1] - 8:5

writing [2] - 7:22, 148:6

written [15] - 59:20, 59:21,

67:7, 114:17, 114:18,

114:23, 115:2, 117:10,

117:16, 118:2, 118:15,

118:23, 203:16, 204:2,

204:11

wrote [1] - 148:8

Y

year [8] - 6:11, 7:18, 10:4,

124:24, 126:2, 126:7, 184:5,

185:11

years [10] - 6:8, 6:10, 28:25,

58:6, 62:18, 184:2, 185:10,

185:13, 185:15

yes-or-no [2] - 112:4,

154:19

yesterday [3] - 179:15,

179:18, 179:19

younger [1] - 18:22

yourself [1] - 13:21

United States District Court

28

Z

zero [10] - 37:21, 41:8,

60:19, 64:11, 64:17, 135:23,

169:16, 186:22, 189:19,

192:17

zoom [1] - 190:25

Case 3:11-cv-03962-MLC-DEA Document 324 Filed 06/05/15 Page 236 of 236 PageID: 18819