throbber
1103
`
`UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF NEW JERSEY
`__________________________________
`HORIZON PHARMA, INC. and POZEN,
`INC.,
`
`Plaintiffs,
`-vs-
`DR. REDDY'S LABORATORIES, INC.,
`et al.,
`
`CIVIL ACTION NUMBER:
`3:11-CV-02317(MLC)
`TRIAL
`VOLUME 6
`
`Defendants.
`__________________________________
`Clarkson S. Fisher United States Courthouse
`402 East State Street
`Trenton, New Jersey 08608
`January 20, 2017
`B E F O R E:
`THE HONORABLE MARY L. COOPER
`UNITED STATES DISTRICT JUDGE
`
`A P P E A R A N C E S:
`MCCARTER & ENGLISH
`JOHN E. FLAHERTY, ESQUIRE
`BY:
`ATTORNEY FOR PLAINTIFF, HORIZON
`FINNEGAN HENDERSON
`BY:
`JAMES B. MONROE, ESQUIRE
`DANIELLE C. PFIFFERLING, ESQUIRE
`ATTORNEYS FOR PLAINTIFF, HORIZON
`
`(Continued)
`
`Certified as True and Correct as required by Title 28, U.S.C.,
`Section 753
`/S/ Carol Farrell, CCR, CRCR, CRR, FCRR, RMR, CCP
`/S/ Regina A. Berenato-Tell, CCR, CRR, RDR
`
`United States District Court
`Trenton, New Jersey
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`MYLAN PHARMS. INC. EXHIBIT 1075 PAGE 1
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`

`

`1104
`
`A P P E A R A N C E S: (Continued)
`COOLEY LLP
`BY:
`ELLEN SCORDINO, ESQUIRE
`SUSAN KRUMPLITSCH
`ATTORNEYS FOR PLAINTIFF, HORIZON
`BAKER BOTTS, LLP
`STEPHEN M. HASH, Ph.D.
`BY:
`JEFF GRITTON, ESQUIRE
`ATTORNEYS FOR PLAINTIFF, POZEN
`BUDD LARNER, P.C.
`BY:
`ALAN H. POLLACK, ESQUIRE
`STUART D. SENDER, ESQUIRE
`ALFRED HANK HECKEL, ESQUIRE
`DMITRY V. SHELHOFF, ESQUIRE
`ATTORNEYS FOR DEFENDANT, DR. REDDY'S
`RIVKIN RADLER, LLP
`BY:
`GREGORY D. MILLER, ESQUIRE
`ATTORNEY FOR DEFENDANT, MYLAN
`PERKINS COIE, LLP
`BY:
`SHANNON M. BLOODWORTH, ESQUIRE
`AUTUMN N. NERO, ESQUIRE
`BRYAN D. BEEL, Ph.D.
`ROBERT D. SWANSON, ESQUIRE
`MELODY GLAZER, ESQUIRE
`ATTORNEYS FOR DEFENDANT, MYLAN
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`MYLAN PHARMS. INC. EXHIBIT 1075 PAGE 2
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`

`

`I N D E X
`
`Examinations
`
`DAVID A. JOHNSON
`
`1105
`
`Page
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`VOIR DIRE EXAMINATION OF DAVID A. JOHNSON BY MR. MONROE:
`DIRECT EXAMINATION OF DAVID A. JOHNSON BY MR. MONROE:
`CROSS-EXAMINATION OF DAVID A. JOHNSON BY MS. NERO:
`CROSS EXAMINATION OF DAVID A. JOHNSON BY MR. HECKEL:
`REDIRECT EXAMINATION OF DAVID A. JOHNSON BY MR. MONROE:
`RECROSS EXAMINATION OF DAVID A. JOHNSON BY MS. NERO:
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`1106
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`(In open court on January 20, 2017, at 9:06 a.m.)
`THE COURT: Good morning, everyone.
`: Good morning, your Honor.
`THE COURT: Yes?
`MR. POLLACK: Your Honor, we have two brief
`housekeeping matters, if we could.
`THE COURT: Yes, Mr. Pollack.
`MR. POLLACK: Dr. Reddy's would like to move for a
`pro hac vice admission of my colleague, Hank Heckel, who was
`admitted in the State of New York as well as the Eastern
`District and the Southern District of New York.
`THE COURT: For purposes of today or --
`MR. POLLACK: Yes.
`THE COURT: Just for today?
`MR. POLLACK: For purposes of today.
`THE COURT: Just for today?
`MR. POLLACK: Well, for the balance of the case, but
`beginning today.
`THE COURT: The reason I ask, Mr. Pollack, is that
`it's not usually done as a standing motion. It's usually done
`as a filed motion --
`MR. POLLACK: Sure.
`THE COURT: -- before the Magistrate Judge with the
`accompanying payment of the fee --
`MR. POLLACK: Right.
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`

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`1107
`
`THE COURT: -- and affidavit. So --
`MR. POLLACK: We can certainly do all that.
`THE COURT: Okay, fine.
`Welcome, Mr. Heckel.
`MR. POLLACK: And one other matter. When we come to
`the end of the trial and we're putting in the designated
`deposition testimony, I understand that the plaintiffs will be
`using three Dr. Reddy's witnesses to talk about the
`particulars of our product. We would again at that point
`request that we seal the courtroom. And I might suggest that
`those witnesses be put in at the very end so we can just seal
`the courtroom once, and the people that don't wish to hear
`that perhaps may choose to leave.
`THE COURT: That's just fine. Thank you, counsel.
`MR. POLLACK: Thank you very much.
`THE COURT: Yes.
`MS. BLOODWORTH: One more housekeeping matter.
`Before we play Dr. Horn's deposition testimony which has been
`designated by plaintiffs, we do have an objection for that
`testimony. We're happy to take it up at that time or now,
`whichever your Honor --
`THE COURT: Oh, let's go ahead with the morning's
`agenda, and then we'll get to that.
`MS. BLOODWORTH: Thank you, your Honor.
`THE COURT: Mr. Monroe?
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`MYLAN PHARMS. INC. EXHIBIT 1075 PAGE 5
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`

`

`JOHNSON - VOIR DIRE - MONROE
`
`1108
`
`MR. MONROE: Good morning, your Honor. We'd like to
`call our last witness, live witness, Dr. Johnson, to the
`stand. We have already handed in our notebooks, your Honor.
`THE DEPUTY CLERK: Please raise your right hand.
`(DAVID A. JOHNSON, HAVING BEEN DULY SWORN/AFFIRMED, TESTIFIED
`AS FOLLOWS:)
`THE WITNESS: I do.
`THE DEPUTY CLERK: Please state and spell your full
`name for the record and have a seat.
`THE WITNESS: David A. Johnson, D-A-V-I-D, A.,
`Johnson, J-O-H-N-S-O-N.
`(VOIR DIRE EXAMINATION OF DAVID A. JOHNSON BY MR. MONROE:)
`Q. Good morning, Dr. Johnson.
`A. Good morning.
`Q. Could you also state your city and state of residence?
`A. Sure. Norfolk, N-O-R-F-O-L-K, Virginia.
`Q. And where do you currently work?
`A. I'm currently a gastroenterologist partner at Digestive &
`Liver Disease Specialists, a division of Gastrointestinal
`Liver Disease Specialists of Tidewater, and I'm professor of
`medicine and chief of gastroenterology at Eastern Virginia
`Medical School in Norfolk, Virginia.
`Q. And we have provided you with a notebook. If you could
`turn to that notebook and, in particular, turn to what is
`marked as PTX-224.
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`MYLAN PHARMS. INC. EXHIBIT 1075 PAGE 6
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`

`

`JOHNSON - VOIR DIRE - MONROE
`
`1109
`
`A. Yes.
`Q. Is that a copy of your C.V.?
`A. Yes.
`Q. And is it current?
`A. Relatively.
`Q. And in your practice as a gastroenterologist at
`Tidewater, can you provide us with a brief background as to
`what your responsibilities are?
`A. Well, I'm a clinical gastroenterologist who treats
`patients every day. I have a fundamental practice that sees
`specialty referral patients in the field of gastroenterology,
`so diseases that deal with that specific organ system or
`related consequences of chronicity in that organ system. And
`I also have responsibilities as an educator and teach at the
`Medical School on a regular basis.
`Q. And can you also describe your work at Eastern Virginia
`Medical School?
`A. Sure. I'm the professor of medicine and chief of
`gastroenterology and responsible for the developmental
`education of students in the area of study in medicine who
`have a need for learning and knowledge in the field of
`diseases that are within my purview specialty,
`gastroenterology.
`Q. And are you involved in any clinical research at Eastern
`Virginia Medical School?
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`

`

`JOHNSON - VOIR DIRE - MONROE
`
`1110
`
`A. Yes.
`Q. And could you provide a brief summary of that?
`A. Well, I have been there for a long time, so I have a lot
`of clinical research experience, both at that institution and
`others.
`
`My primary focus of research has been in the area of
`acid-related diseases such as reflux disease and in other
`areas such as colon screening, more recently involved in a lot
`of sleep research, and involved also in areas of human
`microbiome and gut bacterial changes as it relates to
`different disease states.
`Q. And, in addition to your teaching and research
`background, do you also hold any leadership positions or have
`you held any leadership positions in your field?
`A. I have.
`Q. And could you describe those for the Court, please.
`A. Well, I was honored to be the president of the American
`College of Gastroenterology in 2006 and 2007, held a number of
`positions in the ascension to that -- that ultimate position.
`I've most recently assumed a position on the Board of
`Trustees at the American College of Gastroenterology Research
`Institute.
`I have served as a technical advisor for Centers for
`Medicare and Medicaid Services, CMS, in the GI component areas
`of questioning.
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`

`

`JOHNSON - VOIR DIRE - MONROE
`
`1111
`
`I've also been the cofounder and treasurer of the
`national database for gastroenterologists for their endoscopic
`procedures; it's called the "GI Quality Improvement
`Consortium."
`And I've also been the GI board representative for the
`National Quality Forum in the past.
`Q. And have you written any publications in your practice
`area?
`A. Yes.
`Q. And can you give us an idea of generally how many?
`A. I've published over 600 chapters, abstracts, several
`textbooks, most recently in the area of microbiology, diseases
`that we talked about, human microbiome and translational
`opportunities for improvement; coedited a book on "Dyspepsia"
`by the American College of Physicians. It was published
`by the American College of Physicians. And also a book on
`"Horizons on Gastroesophageal Reflux Disease." It was
`published by the Cleveland Clinic a number of years ago.
`Q. And have you received any awards from your peers in your
`practice area?
`A. I have.
`Q. And can you briefly summarize those for the Court, too?
`A. It's humbling, but to be recognized by your peers is
`perhaps the greatest honor, just to even say thank you. But
`the ideas of recognition, on a local level, I've been
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`

`

`JOHNSON - VOIR DIRE - MONROE
`
`1112
`
`recognized as the Outstanding Physician in the Department of
`Internal Medicine at Eastern Virginia Medical School;
`subsequently received the Dean's Award for the Outstanding
`Faculty at Eastern Virginia Medical School. In regard to the
`American College of Gastroenterology, in addition to being
`president, I was awarded the Berk/Fise Award, which is the
`highest award given by the American College for lifetime
`commitment, service, and dedication and contributions to the
`American College. I was honored the following year to be
`awarded the title of Master of Gastroenterology. In the
`subsequent year was awarded the Berk -- the Curry Award by the
`Board of Governors. This is kind of the infrastructure of the
`American College of Gastroenterology, and the 50 Governors
`pick somebody to honor, again, for lifetime achievements and
`contributions in the field of gastroenterology.
`In 2013, I was awarded and invited as a Great Teacher
`to the National Institutes of Health. They invite two people
`annually from the -- not -- that are gainfully employed at the
`National Institute of Health.
`I've also been awarded the -- the great educator --
`Distinguished Educator Award most recently by the American
`Gastroenterologic Association, again, a different organization
`than where I've spent my primary focus with the American
`College.
`And on a state level, in Virginia I've been awarded,
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`

`

`JOHNSON - VOIR DIRE - MONROE
`
`1113
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`again, a presidential award by the American College, the State
`of Virginia, and also been given the title of Master.
`So a lot of stuff, but humbling in and of themselves.
`Q. And maybe if we could step back a little bit, now, also.
`If you could provide the Court with a brief summary of your
`educational background.
`A. Sure.
`I obtained a Bachelor's of Art Degree from University
`of Virginia in psychology in 1976.
`In 1980, I received my Medical Doctorate Degree at the
`Medical College of Virginia in Richmond, Virginia.
`Q. And did you have any internships or residencies?
`A. I did.
`Q. And can you describe those, please.
`A. I did my internship at the Naval Regional Medical Center
`in Portsmouth, Virginia, in 1980 to '81.
`From 1981 to '82, I served as a medical officer for the
`U.S.S. Sylvania, so I had a hiatus out of my residency pursuit
`for -- it was a commitment that -- because I was a U.S. Naval
`officer. And then I returned in 1982 to Naval Regional
`Medical Center in Portsmouth and finished my residency in
`1984.
`Q. And did you have a fellowship following that?
`A. I did.
`Q. And can you describe where that was?
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`

`

`JOHNSON - VOIR DIRE - MONROE
`
`1114
`
`A. In 1984, I moved to Bethesda and assumed a position of
`Gastrointestinal Fellow and completed that fellowship in 1986;
`and did board certification in '87; and was invited from '86
`to the time I left in 1989 to remain on as staff at Bethesda
`National Naval Medical Center.
`Q. And you've mentioned "board certification." Can you
`explain what that is?
`A. Well, it's a process that the board exam is given, as I'm
`sure you have in the legal field and other professionals have
`here as well, that a group of experts gets together and
`decides, based on their knowledge of the scientific literature
`and the understanding that would be to apply that literature
`to optimize patient care within that particular specialty,
`what would be the necessary foundation, knowledge, to really
`test the individuals to make sure that they're performing
`according to the highest standards, and establish that as a
`criterion to practice and use that application as a
`gastroenterologist that you would be certified with that
`degree.
`Q. And you mentioned a "group." Are you part of that group?
`Are you on that committee?
`A. I am. I'm -- I've been -- it's a group of seven experts,
`and we have been on that committee for the last six years.
`THE COURT: In other words, you set the standards for
`board certification in the specialty of gastroenterology?
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`

`

`JOHNSON - DIRECT - MONROE
`
`1115
`
`THE WITNESS: Yes, ma'am.
`BY MR. MONROE:
`Q. And if we could get back to your practice again.
`Before 2001, which is the time period we're looking at,
`did you treat patients for GI injury as a result of NSAID use
`prior to that period?
`A. Yes.
`Q. And have you continued to treat patients for that type of
`injury?
`A. Yes. It's a prevalent problem.
`MR. MONROE: Your Honor, we'd like to offer
`Dr. Johnson as an expert in gastroenterology.
`MS. NERO: No objections.
`THE COURT: Certainly.
`(DIRECT EXAMINATION OF DAVID A. JOHNSON BY MR. MONROE:)
`Q. Dr. Johnson, were you retained as an expert for the
`plaintiffs in this case?
`A. Yes.
`Q. If I could direct your attention to PTX-001 in your
`binder. What is that document?
`A. This is a patent numbered 6,926,907.
`Q. And is it okay if we refer to it this morning as "the
`'907 patent" moving forward?
`A. I would understand that reference.
`Q. Okay. And if you could turn to PTX-002. And can you
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`

`

`JOHNSON - DIRECT - MONROE
`
`1116
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`identify that document, please?
`A. This is a patent numbered U.S. 8,557,285.
`Q. And would you understand me this morning if I refer to
`that as "the '285 patent" moving forward?
`A. I would understand that reference.
`Q. Is Vimovo a commercial embodiment of those two patents?
`A. Yes.
`Q. And what were you asked to do with respect to these two
`patents?
`A. To review the patents and the -- the interpretations and
`challenges as put forward by Drs. Mayersohn and Kibbe and
`Dr. Metz.
`Q. And what were your conclusions?
`A. They were in error.
`Q. And we'll get to that in a moment, but first I'd like to
`step back and --
`We have been here and heard a lot about the background
`of GI issues, and so we've already been educated and the
`Court's aware of a lot of issues. So I'm going to try and
`streamline my questioning to issues that are directly relevant
`to the testimony that you're going to provide today and
`provide sort of a tutorial on certain issues in your own words
`regarding these issues.
`So, first, you mentioned earlier that you had treated
`patients suffering from GI injury as a result of NSAID use.
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`

`

`JOHNSON - DIRECT - MONROE
`
`1117
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`Can you explain what "NSAID use" is or what NSAIDs are?
`A. "NSAIDs" is an abbreviation or acronym for a class of
`drugs that are used to treat inflammation, particular
`arthritic conditions, so it stands for nonsteroidal
`anti-inflammatory drugs or "NSAIDs."
`Q. And does the use of NSAIDs result in GI injuries?
`A. It can.
`Q. And what type of GI injury can result by NSAID use?
`A. Well, it can result in a lot of different injuries, but
`the predominant injury is in what we call the upper GI tract,
`which is the area of the stomach and the upper intestine.
`Q. And will that be the -- primarily the issue we'll be
`discussing today?
`A. Yes, sir.
`Q. And back in 2001, generally how common was it to have
`upper GI injury as a result of NSAID use?
`A. Well, the data was remarkably consistent. It was
`estimated that approximately 25 percent of people that were
`consuming these on a regular basis would incur a gastric
`ulcer.
`Q. And did you prepare demonstratives for today's hearing?
`A. I did.
`Q. If we could put PDX-502 on the screen. Is this one of
`those demonstratives that you prepared?
`THE COURT: Let's move the mic just about an inch
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`

`

`JOHNSON - DIRECT - MONROE
`
`1118
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`away from the doctor as he leans into it.
`THE WITNESS: Okay.
`THE COURT: Go ahead, Mr. Monroe.
`BY MR. MONROE:
`Q. And to be clear, this is -- is this one of the
`demonstratives that you prepared for today's hearing?
`A. It is.
`Q. And this comes from PTX-572 in your notebook. Could you
`turn to PTX-572 first?
`A. I have it.
`Q. And can you identify what that document is?
`A. This is a review article by Dr. Wolfe and colleagues on
`gastrointestinal toxicity of nonsteroidal anti-inflammatory
`drugs.
`Q. And what is the date of that publication of that article?
`A. 1999, June 17.
`Q. And for clarity, we will be discussing two Wolfe articles
`today: One is published in 1999; one is published in 2000.
`Is it okay if I refer to this as "the Wolfe 1999 article"
`during our discussions?
`A. I would understand that reference.
`Q. Okay. So what are you trying to show in PDX-502 which is
`taken from PTX-572 at the first page?
`A. Well, this was just a -- described the scope of the use
`of these medications against the context of, in particular,
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`

`

`JOHNSON - DIRECT - MONROE
`
`1119
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`those patients at risk, but these were incredibly widely
`prescribed medications, with more than 70 million
`prescriptions acknowledged here, and even more so formidably,
`the over-the-counter use, which accounted for over 30 billion
`tablets sold annually in the United States at the time of this
`publication.
`Q. And approximately how many -- from a percentage level,
`what percentage of the patients would develop NSAID use?
`A. Well, of --
`Q. NSAID injury. Sorry.
`A. Injury to the upper GI tract, it was estimated that 25
`percent would have this development of an ulcer and, perhaps
`even more formidably, 2 to 4 percent would have a
`complication, and potentially a life-threatening complication,
`of bleeding or perforation.
`Q. And does that type of injury result in hospitalization?
`A. Absolutely.
`Q. And do you have an estimate as to how many patients might
`end up in a hospital as a result of GI injury?
`A. I do.
`Q. And could you provide that?
`A. Well, it was estimated that over a hundred thousand
`hospitalizations were a consequence of nonsteroidal or NSAID
`type of upper GI injury.
`Q. And if I could direct your attention to PDX-503 on the
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`MYLAN PHARMS. INC. EXHIBIT 1075 PAGE 17
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`JOHNSON - DIRECT - MONROE
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`1120
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`screen. And that's taken from PTX-572 that you were just
`looking at, the Wolfe 1999 article, at Page 2. This is
`another demonstrative that you prepared. Can you explain what
`you're trying to highlight to the Court with this slide?
`A. Well, this is a comparison of the consequences of causal
`death in relation to the prevalence in the United States at
`the time of this analysis. And what it particularly calls out
`here for emphasis is the bar that says -- the third bar that
`talks to NSAID toxicity, and this is toxicity resulting in
`death. And it's important to recognize that this was 16,500
`deaths, so on an annual basis of causality of use of NSAIDs
`resulting in death.
`And, to put it in perspective, when you take a disease
`which was catastrophic at the time, in particular with HIV and
`AIDS, it was essentially on par with this.
`But it's really important to point out here that this
`is the tip of the iceberg because this is prescription NSAID
`use. Remember I said that 30 billion tablets? Those aren't
`accounted for in these statistics. So if we gave you the
`best-case scenario of minimum death -- it's kind of a paradox
`of phrase here -- the worst-case scenario going way over this,
`potentially and conceptually, this is just to put in
`perspective how significant the problem was.
`Q. Okay. And we've talked about gastrointestinal issues, GI
`tract. Can you explain what the GI tract is?
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`MYLAN PHARMS. INC. EXHIBIT 1075 PAGE 18
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`JOHNSON - DIRECT - MONROE
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`1121
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`A. Well, the gastrointestinal tract essentially is the tract
`that begins at the mouth and ends at the rectum or the anus.
`And for the purposes of ingesting of food or vitamins or
`minerals, this is a processing plant that allows the
`individual to have agents come through the gastrointestinal
`tract and be processed for appropriate distribution to where
`it needs. Combined with this, there are other organs in the
`gastrointestinal tract or gastrointestinal system that are a
`little beyond the scope of today's discussion, to some degree,
`but not when we talk about the liver, and perhaps we can talk
`about that later, but the idea is that there are other organs
`that perhaps aren't shown in this demonstrative.
`But we're talking about the hollow organs here, so
`we're talking about the mouth and beginning the esophagus and
`getting to the stomach and then to the intestines and then to
`the colon and out the anus. But other organs in the
`gastrointestinal system would include things like the liver,
`the gallbladder, the bile ducts and the pancreas.
`Q. And you mentioned "demonstrative." Just for clarity for
`the record, are you referring to PDX-504 that is on the
`screen?
`A. Yes, sir.
`So this would show more in a pictorial display of the
`transits through what we would call the GI tract with the --
`we call this the hollow or viscous organ, which means that
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`MYLAN PHARMS. INC. EXHIBIT 1075 PAGE 19
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`

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`JOHNSON - DIRECT - MONROE
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`1122
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`it's a hollow system, the tubes, if you will, from ingestion
`to excretion, not necessarily involving the other we call
`solid organs like the pancreas and the liver and the bile
`ducts in the gallbladder system.
`Q. And if you could turn to PTX-331 in your notebook?
`A. I have it.
`Q. What is that document?
`A. Well, this is a document that is developed by the
`National Institutes of Health, the NIDDK, of digestive disease
`and kidney diseases. So it's an informatic description of
`what the digestive system sees as relates to gastrointestinal
`diseases, what the GI tract is, and what some of the
`complications, in particular, as it relates to issues like
`bleeding of the digestive disease tract.
`Q. And the pictorial that you're showing in PDX-504, does
`that come from that document?
`A. It does.
`Q. At what page of that document?
`A. It's 331.002.
`Q. Okay. Thank you.
`I'd like to now direct your attention to PDX-505.
`THE COURT: Where does the upper GI tract end, the
`way that you think of it?
`THE WITNESS: That's a good question. The short
`answer is, in the upper intestine.
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`MYLAN PHARMS. INC. EXHIBIT 1075 PAGE 20
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`

`

`JOHNSON - DIRECT - MONROE
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`1123
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`THE COURT: Which is the small intestine?
`THE WITNESS: The upper small intestine. So there's
`a point of -- of what we call the "fourth portion" of the
`upper GI tract, and it ends in the first couple feet of the
`small intestine.
`THE COURT: Okay.
`BY MR. MONROE:
`Q. And so now if we could move to PDX-505. This comes from
`PTX-572, the Wolfe 1999 article that we discussed previously.
`Can you explain what you were trying to show the Court here?
`A. Well, this is really to put in perspective, your Honor, I
`know you've seen a lot of slides, just to point out a little
`different on the idea by which NSAIDs can cause injury.
`So we know that NSAIDs can cause injury both from a
`local effect and a systemic effect. So the local effect means
`the pill can do damage just by sitting on top of the tissue
`itself. So it can cause an ulcer. If I put it on your skin,
`unless you had protection, something could damage it and
`create an ulcer. So we know that the pills can do that.
`We do know, too, that the pills, when they get absorbed
`and they're metabolized -- and this is why I said it would be
`helpful to remember the liver.
`So the liver is where these drugs are broken down and
`metabolized. And then they're excreted back, so they're sent
`back to the system, but now not as the pill but as ingredients
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`MYLAN PHARMS. INC. EXHIBIT 1075 PAGE 21
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`

`

`JOHNSON - DIRECT - MONROE
`
`1124
`
`in the blood or in the excretion into the bile duct; so the
`drainage tube from the liver is the bile duct. But if you
`look at where the liver is, it sits very close to the
`intestinal tract. So these bile ducts drain in -- within a
`first couple inches of the stomach. So that metabolite in the
`NSAID comes back into that first couple inches from the
`stomach and can go backwards into the stomach.
`And we know that those agents, those metabolites, are
`extremely toxic to the stomach lining as well. So they can,
`if they get into the lining of the stomach, they are very
`toxic and deadly to the what we call the "battery system" or
`the "mitochondria"; it's just a term, but if you think about
`the function of the energy system of the cell, these NSAIDs,
`having gone through absorption, been metabolized and now
`coming back not as a topical pill but as a topical component
`of the pill, can be very toxic on a local level. So that's
`one element of how these drugs cause injury.
`We know, too, that the injury occurs from what we call
`a "systemic effect." And the systemic effect is basically
`because they suppress prostaglandins, and prostaglandins are
`the agents that promote the integrity and the viability and
`the resiliency of the stomach to sustain a defense against
`injury.
`Q. And you were not in court for the first day when Dr. Metz
`testified; is that correct?
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`MYLAN PHARMS. INC. EXHIBIT 1075 PAGE 22
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`

`

`JOHNSON - DIRECT - MONROE
`
`1125
`
`A. Correct.
`Q. But did you review his transcript?
`A. I did.
`Q. And Dr. Metz testified that the topical or local effect
`is a minor effect and the systemic effect is the major effect.
`Do you agree with that?
`A. No.
`Q. And why? Why not?
`A. Well, there is no qualifying evidence of numbers or
`percentages, and the idea of studying that would be
`comparison. So they both have an effect. Whether one has
`slightly more effect I think is really an element of opinion,
`but to say that one has a "minor effect" would be that you've
`highly qualified that description and you've studied it and
`there's evidence to support -- and the definition of "minor"
`would be a question from my standpoint.
`Q. And you've mentioned the GI lining. If we could turn to
`PDX-506 on the screen, please. And also turn to PTX-292 in
`your notebook.
`And can you identify what PTX-292 is?
`A. So this is a review on the pathophysiology or the ways
`that the development of an injury can occur in the stomach.
`And, in particular, this talks to how the NSAID or the
`nonsteroidal anti-inflammatory drugs can induce the injury to
`the gastric mucosa.
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`MYLAN PHARMS. INC. EXHIBIT 1075 PAGE 23
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`

`

`JOHNSON - DIRECT - MONROE
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`1126
`
`Q. And you've prepared a demonstrative to tutorially
`illustrate what is on the first page of this document. Can
`you explain to the Court what you are trying to show here?
`And keep in mind, if you need it, we've also provided you with
`a little pointer if you need it.
`A. Thank you.
`THE WITNESS: And, your Honor, I'll be happy to use
`the pointer if you'd like. I generally try not to speak with
`pointers, but if there's something that you would like to see
`emphasized, I'd be happy to point that out for you.
`THE COURT: If I need it, I'll let you know. I
`should be able to follow what you're saying because you've got
`the words up on the screen.
`THE WITNESS: Yes, ma'am.
`So, the lining of the stomach and the defense against
`the injuries that could potentially occur in the stomach are
`complex and very much a sequential level of protection.
`So, on one hand, you think about you've got this
`introduction of things that are coming into the stomach. And,
`in particular, in the stomach there's a component of acid, and
`the pH of acid is very low.
`And I think, your Honor, you saw some variations on
`what pH means, but battery acid on your skin would be bad;
`battery acid in the stomach potentially may not be bad because
`that's normative for what -- the way we were functionally
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`MYLAN PHARMS. INC. EXHIBIT 1075 PAGE 24
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`

`

`JOHNSON - DIRECT - MONROE
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`1127
`
`created. But you've got a balance, then, of potential very
`ominous injury against the potential to sustain that on a
`daily basis and in a minute-to-minute basis to deal with
`changes that occur in the complexity of what's in the stomach.
`Well, when you look at this, it's very much analogous
`to if you were putting a roof over your living room. So you
`start with the top, and you have the top coating of the roof,
`and you've got the shingles on the roof, and I'd say that's
`more what is described here as the "pre-epithelial mechanism."
`So you've got secretions of things. And if you think
`about the -- jello with foam on it, that's kind of the mucus
`layer, so it's really a layer of agents and things that can
`buffer -- bicarbonate allows the acid pH to rise -- and
`different components of other products that the body makes.
`And that's called "surface-active phospholipids." So you've
`got this roof effect, number one, and that's the mucous layer.
`But then if the roof has some damage and you've got a
`hail storm or something that comes along, you've got to have a
`second level of defense, and that's what's described here in
`pictorial fashion of the epithelial mechanisms. And this,
`again, is very complicated, but it looks at ways that the body
`can maintain even a leak in the roof. So you're now at the
`structure of the roof and the ability to sustain the leak in
`the roof as you go along. So the epithelial layer relates to
`the cells are always on challenge to reproduce and replace
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