,
`
`JSN2-17)\
`EXHIBIT NO._
`'L-l \.o..- \1 V/\C..
`
`Volume 146
`
`December 1991
`
`Number 6
`
`The Journal of
`
`\
`
`®
`
`Annual Meeting, American Urological Association, Inc., Washington, D. C., May 10-14, 1992
`
`JANSSEN EXHIBIT 2011
`Mylan v. Janssen IPR2016-01332
`
`

`

`The Journal of
`
`UROLOGY®
`
`Editor
`John T. Grayhack
`1120 North Charles Street
`Baltimore, Maryland 21201
`
`Associate Editor
`Terry D. Allen
`Dallas, Texas
`
`Section Editor
`Stuart S. Howards
`Charlottesville, Virginia
`
`Associate Editor
`Jay Y. Gillenwater
`Charlottesville, Virginia
`
`Section Editor
`Patrick C. Walsh
`Baltimore, Maryland
`
`EDITORIAL BOARD
`
`Mid-Atlantic
`A. Barry Belman
`Washington, D. C.
`
`New England
`Bernard Lytton
`New Haven, Connecticut
`
`New York
`Michael J. Droller
`New York, New York
`
`North Central
`Joseph W. Segura
`Rochester, Minnesota
`
`Northeastern
`Abraham T. K. Cockett
`Rochester, New York
`
`South Central
`Robert E. Donohue
`Denver, Colorado
`
`Southeastern
`Floyd A. Fried
`Chapel Hill, North Carolina
`
`Western
`Duncan E. Govan
`Stanford, California
`
`BOARD OF CONSULTANTS
`
`Marc Garnick
`Boston, Massachusetts
`
`Allyn W. Kimball
`Baltimore, Maryland
`
`Bruce McClennan
`St. Louis, Missouri
`
`William M. Murphy
`Memphis, Tennessee
`
`Ryoichi Oyasu
`Chicago, Illinois
`
`Howard Pollack
`Cheltenham, Pennsylvania
`
`William U. Shipley
`Boston, Massachusetts
`
`Lynwood H. Smith, Jr.
`Rochester, Minnesota
`
`Colin White
`New Haven, Connecticut
`
`FORMER EDITORS
`
`Hugh H. Young
`1917-1945
`
`J. A. Campbell Colston
`1945-1966
`
`Hugh J. Jewett
`1966-1977
`
`William W. Scott
`1977-1983
`
`Herbert Brendler
`1983-1985
`
`The Journal of Urology (ISSN 0022-5347) is the Official Journal of the American Urological Association, Inc., and is published monthly by
`Williams & Wilkins, 428 East Preston Street, Baltimore, MD 21202. Second class postage paid at Baltimore, MD, and at additional mailing
`offices. Subscription rates individual $169.00 ($234.00 foreign); institutions $189.00 ($254.00 foreign); in-training $83.00 ($148.00 foreign); single
`copy $23.00 ($28.00 foreign).
`Subscription prices subject to change. The GST number for Canadian subscribers is 123394371. To order call 1-800-638-6423 from anywhere in
`the U.S.; in Maryland call 1-800-638-4007. POSTMASTER: Send address changes to The Journal of Urology, 428 East Preston Street, Baltimore,
`MD 21202. Indexed by Current Contents and Index Medicus. Copyright© 1991 by American Urological Association, Inc.
`A4
`
`

`

`•
`
`LETTERS TO THE EDITOR
`
`1621
`3. Bruskewitz, R. C., Iversen, P. and Madsen, P. 0.: Value ofpostvoid
`residual urine determination in evaluation of prostatism. Urol(cid:173)
`ogy, 20: 602, 1982.
`
`mate interchange might possibly be misinterpreted and misused. I,
`therefore, asked Dr. H. Logan Holtgrewe, whose opinions I value highly
`as a urologist and as a leader in the interactions on the social scene,
`about his reaction to publication of the Letter. I received the following
`Letter in reply and believe that it warranted sharing with all of you.
`
`Note by Dr. H. Logan. Holtgrewe. The thrust of the paper by Katz et
`al was to extol the virtue of transurethral incision over transurethral
`resection of small prostate glands. They dealt lightly, if at all, with the
`indications for the operation. As Doctor Rohlf notes, the only specific
`reference was "patients were candidates for incision if they had a
`clinically benign prostate, peak urinary flow rate of less than 15 ml.
`per second and an estimate 15 gm. or less ofresectable prostatic tissue."
`Katz et al may well have insisted upon other criteria before operating
`but if they did so, their paper fails to state these additional criteria,
`leaving the reader with the assumption that a slow stream was the sole
`indication for the operation.
`Doctor Rohlf is right on! A flow rate of less than 15 cc per second is
`certainly not of itself an indication for a prostate operation. Doctor
`Rohlf also is correct that variation in practice styles of urologists
`accounts for the variation in the .incidence of prostatic surgery in age(cid:173)
`adjusted populations in different geographic areas of our country-the
`variation is as· great as 3-fold. He is equally correct that this variation
`in the incidence of prostate surgery has brought this operation to the
`attention of the Government and its health care agencies, including
`the Health Care Financing Administration. It also may account for the
`fact that benign prostatic hyperplasia was among the first 3 diseases
`for which the Federal Government decreed there would be guidelines
`of treatment. Fortunately, due to the fact that the American Urological
`Association was already well along in a scholarly construction of
`guidelines for the treatment of benign prostatic hyperplasia, the gov(cid:173)
`ernmental agency that the Congress created to oversee guideline de(cid:173)
`velopment literally hired the existing American Urological Associ~tion
`committee chaired by Dr. John McConnell to complete these guidelines,
`which were in the hands of the Federal Government by December 1,
`1990.
`
`Reply by Authors. Our patients were not selected for transurethral
`incision of the bladder neck and prostate based on a single parameter.
`We agree with Doctor Rohlf that a transurethral operation should not
`be performed solely for a slow urinary stream. We evaluated men 50
`years and older who presented with symptoms of prostatism. As noted
`in the Methods Section, our patient assessment included a symptoms
`questionnaire, physical examination, urine culture, uroflowmetry and
`cystoscopy. The symptoms evaluated included force of stream, hesi(cid:173)
`tancy, intermittency, daytime and nighttime urinary frequency and
`urgency/incontinence. The symptom scoring system is given in table 1
`in the article. Treatment recommendations were based on this evalua(cid:173)
`tion and not on a single factor. After evaluation those patients who
`decided to proceed with surgical intervention underwent examination
`while they were under anesthesia. The decision was then made to
`proceed with either transurethral prostatectomy or, for patients with a
`small prostate, incision.
`Except for a total outflow obstruction, the indications for a bladder
`outlet operation are not absolute. We excluded symptomatic patients
`with peak urinary flow rates of greater than 15 ml. per second because
`they are less likely to have bladder outlet obstruction and have signif(cid:173)
`icantly lower success rate after a prostatic operation than those with
`lower preoperative flow rates.' Doctor Rohlf discusses other criteria for
`bladder outlet obstruction, including residual urine without stating
`what volume he considers to be significant. However, residual urine
`may occur in the absence of bladder. outflow obstruction and markedly
`obstructed bladders may empty completely.i"
`We believe that our selection criteria were appropriate in identifying
`symptomatic patients with bladder outlet obstruction. With a mean
`followup of more than 2 years, the incisional procedure resulted in a
`statistically and clinically significant decrease in total symptom scores
`(table 3 in article) and an increase in peak flow urinary flow (table 2
`in article).
`
`1. Jensen, K. M.-E., Jergenson, J.B. and Mogensen, P.: Urodynamics
`in prostatism. I. Prognostic value of uroflowmetry. Scand. J.
`Urol. Nephrol., 22: 109, 1988.
`.
`2. Abrams, P. H. and Griffiths, D. J. The assessment of prostatic
`obstruction from urodynamic measurements and from residual
`urine. Brit. J. Urol., 51: 129, 1979.
`
`RE: PROSTATE SPECIFIC ANTIGEN FOR ASSESSING
`RESPONSE TO KETOCONAZOLE AND PREDNISONE IN
`PATIENTS WITH HORMONE REFRACTORY METASTATIC
`PROSTATE CANCER
`
`G. S. Gerber and G. W. Chodak
`
`J. Urol., 144: 1177-1179, 1990
`
`To the Editor. Since so much of the literature pertaining to prostate
`cancer is directed toward treating potentially curable or endocrine
`responsive tumors, it was gratifying to read an article directed toward
`endocrine unresponsive carcinoma of the prostate. This is an area that
`requires much more basic and clinical research. In 1973 the Veterans
`Administration Cooperative Urological Research Group suggested that
`when a patient with advanced prostate cancer became refractory to 1
`form of androgen deprivation and had relapse it was unlikely he would
`respond significantly to any other form of endocrine therapy.1 In 1976
`Prout et al suggested that prostate cancer consists of a heterogeneous
`population of cancer cells, some of which are androgen sensitive and
`others that are not." The further proliferation and spread of the latter
`group of cells eventually causes endocrine refractory prostate cancer.
`The authors reported on 15 patients with endocrine refractory met(cid:173)
`astatic carcinoma of the prostate who were treated with ketoconazole
`and prednisone. All patients had been treated previously with bilateral+(cid:173)
`orchiectomy alone or with luteinizing hormone-releasing hormone ag-
`onist alone. Of the 15 patients 10 had also received radiotherapy. None
`of these 15 patients showed a significant improvement i!l-te.rms of ;
`e exc t for a
`increased survival, or an objective or subjective res
`decrease in prostate specific antigen (PSA) a
`bone pain Since
`ketoconazole presumably acts by inhibiting gonad and adr cortical
`steroid synthesis, the authors have again substitute
`orm of endo-
`crine therapy for another. Therefore, one would not expect a significant
`improvement unless the new therapy had an effect beyond androgen
`deprivation, for example a direct cytotoxic effect. Eichenberger et al
`
`\~
`
`recently suggested a direct cytotoxic effect for ketoconazole.3 Perhaps r(cid:173)
`
`a reason why estramustine phosphate has not been too successful in
`the treatment of endocrine refractory prostate cancer patients is that
`the principal activity of this drug has been largely through its estradiol ~
`moiety.'
`---
`It is likely that the effects of ketoconazole and prednisone in decreas-
`ing PSA levels have little or nothing to do with clinical improvement.
`All of us who treat prostate cancer patients have noted an increasing
`PSA value when a patient has a relapse after radical prostatectomy or
`radiation therapy. After androgen ablation the PSA level often de(cid:173)
`creased or returned to normal even though the prostate cancer was
`progressing clinically. Kaplan et al suggested that this phenomenon
`might occur partly because "testosterone is required to drive the syn(cid:173)
`thesis of PSA by prostatic tissue."! Therefore, a decrease in the PSA
`level after endocrine intervention is not necessarily synchronous with
`clinical improvement.
`Reduction in bone pain is largely subjective and difficult to evaluate.
`The reduction in bone pain reported by the authors could have been
`related par I to bed rest, simultaneously administered analgesics and/
`or the prednisone.
`s a o us can
`prostatic carcmoma still responsive to androgen deprivation but what
`can we do for the patient with endocrine unresponsive carcinoma of
`the prostate? We definitely need more research in this area.
`
`Respectfully,
`Clyde E. Blackard
`Park Nicollet Medical Center
`Minneapolis, Minnesota 55416
`1. Hurst, K. S. and Byar, D. P.: An analysis of the effects of changes
`from the assigned treatment in a clinical trial of treatment for
`prostatic cancer. J. Chron. Dis., 26: 311, 1973.
`2. Prout, G. R., Jr., Kliman, B., Daly, J. J., MacLaughlin, R. A.,
`Griffin, P. P. and Young, H. H., II: Endocrine changes after
`diethylstilbestrol therapy; effects on prostatic neoplasm and
`pituitary-gonadal axis. Urology, 7: 148, 1976.
`3. Eichenberger, T., Trachtenberg, J., Toor, P. and Keating, A.:
`Ketoconazole: a possible direct cytotoxic effect on prostate car(cid:173)
`cinoma cells. J. Urol., 141: 190, 1989.
`4. McMillin, J. M., Seal. U. S. and Doe, R. P.: Effect of oral estra-
`
`

`

`1622
`
`LETTERS TO THE EDITOR
`
`mustine phosphate on pituitary, gonadal, and adrenal function
`in the green monkey (Cercopithecus aethiops sabaeus). Invest.
`Urol., 15: 151, 1977.
`.
`5. Kaplan, I., Prestidge, B. R., Cox, R. S. and Bagshaw, M. A.:
`Prostate specific antigen after irradiation for prostatic carci(cid:173)
`noma. J. Urol., 144: 1172, 1990.
`
`Reply by Authors. Doctor Blackard raises important questions about·
`the significance of our observations regarding the effect of ketoconazole
`in patients with hormone refractory prostate cancer. Secondary hor-
`. monal therapy in various forms has been used for many years with a
`small but real response rate of approximately 20%. As cited in our
`paper, other studies observed an objective response in approximately
`20% of the patients treated with ketoconazole using other objective
`tests. The focus of our report was to show that perhaps this subset can
`e identified more easily by following serum PSA levels, thereby
`bviating the need for the other studies and identifying nonresponders
`more rapidly. Doctor Blackard suggests that a decrease in PSA may
`have no clinical significance and he states that the PSA level often
`decreases or returns to normal when the patient has clinical progres(cid:173)
`ion. This latter comment is an uncommon event, however, since less
`
`than 10% of the patients demonstrate progressive disease without first
`having an increasing PSA level. Furthermore, we have not said that
`survival was unaffected but, rather, we have insufficient data o deter(cid:173)
`mine the imp
`rv1v . We ac now edge that t e improvement
`In bone pain is-snbjective and may be due to the simultaneous admin(cid:173)
`istration of prednisone. However, the clear reduction in analgesics by
`many of these patients would argue that the benefit is real, even if
`short-Jived. Furthermore, a recent report by Trachtenberg provides
`evidence that ketoconazole is effective in the absence of steroids.1
`Finally, although radiation had been previously administered to some
`of these patients, the timin of the k toconazole and the demonstration
`of an increase in PSA after radiation but be ore e
`a 10n argue
`for attributing this-response to the drug. ViTe certainly agree that more
`research is needed but the observations by others as well as our own
`findings suggest that more investigation with ketoconazole or its ana(cid:173)
`logue appears to be warranted, since the drug does appear to have some
`clinical benefit in these patients in addition to its effect on serum PSA.
`
`1. Trachtenberg, J.: Ketoconazole therapy in advanced prostatic can(cid:173)
`cer. J. Urol., 137: 959, 1987.
`
`\;
`/f--
`
`

`

`..
`
`In the United States Patent and Trademark Office
`
`Before the Patent Trial and Appeal Board
`
`MYLAN PHARMACEUTICALS IN CORPORA TED,
`
`Petitioner
`
`V.
`
`JANSSEN ONCOLOGY, INC.,
`
`Patent Owner
`
`U.S. Patent No. 8,822,438 to Auerbach et al.
`Issue Date: September 2, 2014
`Title: Methods and Compositions for Treating Cancer
`
`Inter Partes Review No. IPR2016-01332
`
`DECLARATION OF MARC B. GARNICK, M.D.
`
`MYLAN PHARMS. INC. EXHIBIT 1002 PAGE 1
`
`

`

`I, Marc B. Garnick, M.D., do hereby declare:
`
`I.
`
`INTRODUCTION
`
`1.
`
`I am making this declaration at the request of Mylan Pharmaceuticals
`
`Inc., in the matter of the Inter Partes Review (IPR) of U.S. Patent No. 8,822,438
`
`(the "'438 Patent"), as set forth in the above caption.
`
`A.
`
`Education and Professional Background
`
`2.
`
`I am a medical oncologist specializing in the care of patients with
`
`prostate cancer in the Division of Hematology and Oncology, Department of
`
`Medicine at the Beth Israel Deaconess Medical Center, Harvard Medical School, in
`
`Boston MA. My clinical and research interests have focused on urologic cancers,
`
`with a special interest in prostate cancer. I am actively involved in clinical
`
`research and in the past have devoted my professional activities to the development
`
`of drugs that are currently being used in the management of prostate cancer. I
`
`serve as the medical director for Cancer Services Brockton Hospital/Signature
`
`Health Care, Cambridge Health Alliance, which includes Cambridge Hospital and
`
`Whidden Memorial Hospital and the medical liaison for all of the cancer services
`
`that the BIDMC provide. I am the director of Cancer Programs for Network
`
`Development at the Beth Israel Deaconess Medical Center. I am Gorman Brothers
`
`Clinical Professor of Medicine at Harvard Medical School, an endowed
`
`professorial chair in medicine.
`
`MYLAN PHARMS. INC. EXHIBIT 1002 PAGE 2
`
`

`

`3.
`
`I received a Bachelor of Arts degree in Biology from Bowdoin
`
`College, Brunswick, Maine. I obtained my medical degree from the University of
`
`Pennsylvania School of Medicine (now the Perelman School of Medicine at the
`
`University of Pennsylvania) in 1972. I completed my internship and residency in
`
`internal medicine at the Hospital of the University of Pennsylvania in 1974. I then
`
`completed two fellowships: one at the National Institutes of Health in the National
`
`Institute of Arthritis, Metabolism and Digestive Diseases in 1976 and then a
`
`fellowship in Medical Oncology at the Dana Farber Cancer Institute, Boston MA
`
`in 1978. My curriculum vitae is attached as Exhibit A.
`
`4.
`
`From 1978 until 1996, I practiced medicine at the Dana Farber Cancer
`
`Institute and Brigham and Women's Hospital in Boston, MA. Since 1996, I have
`
`practiced at the Beth Israel Deaconess Medical Center. Between the years of 1987
`
`and 2006, I also held positions at the Genetics Institute and Praecis
`
`Pharmaceuticals where my responsibilities dealt with the development of new drug
`
`therapies for cancer, including prostate cancer and other medical illnesses.
`
`I
`
`served as the academic principal investigator for the development and approval of
`
`leuprolide acetate (Lupron®), one of the world's most widely-prescribed
`
`medicines for prostate cancer, and most recently served as the industry leader for
`
`abarelix, a pharmaceutical that is used for a subset of patients with prostate cancer,
`
`which was previously marketed in the United States and Europe.
`
`MYLAN PHARMS. INC. EXHIBIT 1002 PAGE 3
`
`

`

`5.
`
`I have been directly involved in the development of multiple drugs
`
`that have gained approval by both United States regulatory agencies and European
`
`regulatory agencies. I have participated as either an academic or industry leader
`
`and principal investigator/contributor for multiple drugs that have gained either
`
`FDA or European regulatory approvals.
`
`6.
`
`I have had issued to me over 20 patents, mainly dealing with drug
`
`development and treatments for prostate cancer.
`
`7.
`
`I enclose a representative sample of the types of activities I have been
`
`involved in relating to the diagnosis, treating, and evaluation of therapies for
`
`-----12rostate cancer, with an emphasis on Lupron® and other hormonal therapies:
`
`- B. Representative sample of accomplishments related to prostate
`
`disorders, prostate cancer, and Lupron®-treated related
`disorders"
`
`1.
`
`Prostate cancer and Lupron®-related accomplishments
`
`a.
`
`Lupron®-related and LHRH analogue-related
`
`•
`
`Academic Principal Investigator and one of three academic presenters to the
`
`FDA advisory committee related to the initial FDA approval of Lupron® for
`
`prostate cancer;
`
`1Lupron® is one of the world's most prescribed therapies for prostate cancer; I
`
`served as the principal investigator that led to its approval by FDA and other
`
`worldwide regulatory bodies in the mid- l 980s.
`
`MYLAN PHARMS. INC. EXHIBIT 1002 PAGE 4
`
`

`

`•
`
`Lead investigator on multiple Phase II studies and the pivotal Phase III study
`
`ofLupron® for prostate cancer, published in the New England Journal of
`
`Medicine;
`
`•
`
`Investigator on multiple follow-on studies following the approval of
`
`Lupron®, in order to assess its post-marketing safety and efficacy;
`
`•
`
`Lead developer of abarelix, the first approved LHRH/GnRH antagonist for
`
`prostate cancer in the U.S., Germany, and other EU Countries;
`
`•
`
`Co-organizer (with the late William Fair, M.D.) of the annual International
`
`Conferences on Neoadjuvant Hormonal Therapy for Prostate Cancer; and
`
`•
`
`Inventor listed on multiple patents related to the use of LHRH analogues for
`
`the management of prostate cancer and other Lupron®-related disorders
`
`outside of prostate cancer (adjunct to mammography for dense breast
`
`imaging, differential suppression of FSH (follicle-stimulating hormone)
`
`between Lupron® and LHRH antagonists).
`
`b.
`
`Prostate cancer-related
`
`•
`
`Founder of Hershey Foundation for Basic and Clinical Research in Prostate
`
`Cancer, housed at the Beth Israel Deaconess Medical Center, that
`
`established basic and clinical research programs, young investigator awards,
`
`educational colloquia and de nova establishment of a prostate cancer tissue
`
`bank, available for use by all Massachusetts researchers;
`
`MYLAN PHARMS. INC. EXHIBIT 1002 PAGE 5
`
`

`

`•
`
`Reviewer for SPORE (Specialized Program of Research Excellence) grant
`
`applications in the formative years of the SPORE program;
`
`•
`
`Panel Reviewer on NIH Consensus Development Conference for
`
`management of clinically localized prostate cancer; and
`
`•
`
`Special Government Employee (SOE) for United States Food and Drug
`
`Administration (FDA) and have served on approximately 15 advisory
`
`committees as an invited and voting member in multiple divisions of FDA.
`
`2.
`
`Publishing and educational accomplishments
`
`•
`
`Author, The Patient's Guide to Prostate Cancer, published by
`
`Viking/Penguin Imprints (a lay book on prostate cancer, based upon several
`
`articles initially published in Scientific American);
`
`•
`
`Editor in chief and founder of Perspectives on Prostate Diseases, a quarterly
`
`journal published by Harvard Medical School's Harvard Health
`
`Publications, and founder of a companion website (available to anyone with
`
`an internet connection) at www.harvardprostateknowledge.org. This has
`
`now been supplanted by The Harvard Medical School Annual Report on
`
`Prostate Diseases;
`
`•
`
`Founder and director (until 1992), HMS Continuing Medical Educational
`
`program entitled Urologic Cancer, the premier course in Urologic Cancer for
`
`physicians;
`
`MYLAN PHARMS. INC. EXHIBIT 1002 PAGE 6
`
`

`

`•
`
`Author, American College of Physicians policy statement on Screening for
`
`Prostate Cancer, published through its PIER (Physician Information
`
`Educational Resource), a point of care resource for physicians worldwide;
`
`•
`
`Author (along with three others) of a widely distributed prostate cancer and
`
`PSA decision tool for internists and primary care physicians, for Harvard
`
`Institutions Risk Management Foundation;
`
`•
`
`Lecturer at multiple national and international colloquia on prostate-related
`
`disorders and prostate cancer and LHRH analogues, including Lupron® and
`
`other hormonal therapies for prostate cancer;
`
`•
`
`Founder of Prostate Cancer Educational Breakfast Series, a series of
`
`colloquia for general education related to prostate cancer;
`
`•
`
`Participant in several regional programs to increase awareness of prostate
`
`cancer issues for the African-American Communities;
`
`•
`
`Lead author on two review articles on prostate cancer screening, published
`
`in Annals of Internal Medicine; and
`
`•
`
`First author on three separate Scientific American articles on issues relating
`
`to prostate cancer, including an evaluation of the effectiveness of various
`
`therapies.
`
`MYLAN PHARMS. INC. EXHIBIT 1002 PAGE 7
`
`

`

`8.
`
`In 20 I 0, I was appointed as a Special Government Employee (SGE) to
`
`the United States Food and Drug Administration (FDA) Oncology Drug Advisory
`
`Committee (ODAC) to review matters related to cancer in general and prostate
`
`cancer specifically.
`
`I was a member of the FDA ODAC review panel that
`
`deliberated on the use of the five-alpha-reductase inhibitors, finasteride and
`
`dutasteride, as a means of preventing the development of prostate cancer, and
`
`recently served on the FDA ODAC advisory panel that deliberated the issues in
`
`drug development associated with non-metastatic castrate resistant prostate cancer.
`
`In 2014, I was a voting member of the FDA advisory committee in the
`
`deliberations of testosterone replacement therapy conducted by FDA m a joint
`
`meeting of Drug Safety and Division of Urologic Drug products.
`
`9.
`
`I have participated as both an academic and industry investigator in
`
`the development of agents for the treatment of prostate cancer, and lecture
`
`nationally and internationally on issues related to prostate cancer diagnosis,
`
`management, treatment and assessment of outcomes.
`
`10.
`
`I am Board Certified in both Internal Medicine and Medical
`
`Oncology. My clinical practice at the Beth Israel Deaconess Medical Center
`
`focuses on the management and counseling of patients who have been diagnosed
`
`with all stages of prostate cancer, including those eligible for treatments such as
`
`abiraterone and prednisone, as well as individuals who are questioning their risk of
`
`MYLAN PHARMS. INC. EXHIBIT 1002 PAGE 8
`
`

`

`having prostate cancer.
`
`The discussion about the use of alternate or
`
`complementary forms of interventions is discussed frequently. In my position as
`
`Editor in Chief of the HMS Annual Report on Prostate Diseases, we cover, assess
`
`and write about information related to complementary and alternative methods of
`
`prostate cancer interventions.
`
`11.
`
`I am an affiliate member of the American Urological Association;
`
`Fellow of the American College of Physicians; member of the American Society of
`
`Clinical Oncology and have held leadership positions in that organization; as well
`
`as other organizations.
`
`I have been asked to provide plenary lectures at the
`
`National Meetings of the American Urological Association and the American
`
`College of Physicians on topics that include an understanding of prostate cancer. I
`
`have also completed 15- and 9-year terms, respectively, as Trustee of Bowdoin
`
`College (2011 ); and Trustee of Penn Medicine and the Perelman School of
`
`Medicine of the University of Pennsylvania, where I have served as interim
`
`chairperson of its subcommittee on Research, Education and Patient Care.
`
`12.
`
`I am, and have been, a reviewer for a number of medical journals,
`
`including New England Journal of Medicine; Annals of Internal Medicine; Journal
`
`of Clinical Oncology; Urology; British Journal of Urology International; and
`
`others. Over the past 30 years, I have peer reviewed numerous papers submitted
`
`for publication to scientific and medical journals which will often include studies
`
`MYLAN PHARMS. INC. EXHIBIT 1002 PAGE 9
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`

`

`that employ randomized, double-blind, placebo controlled studies. As part of this
`
`review process, I will evaluate the adequacy of the design, the conduct of the study
`
`and clinical research; and make an assessment as to the integrity of the data
`
`presented, and accuracy and rigor of the statistical methodologies employed. I also
`
`serve as the only physician-medical advisor to the World Book Encyclopedia.
`
`I
`
`have written and reviewed numerous US FDA regulatory submissions dealing with
`
`the evaluation of novel and investigational agents and have authored multiple
`
`Integrated Summary Basis of Risk Benefit documents, Integrated Summary of
`
`Safety and Efficacy, and Clinical Investigational Brochures, and contributed in
`
`meaningful ways to regulatory submissions from IND filings to NDA filings and
`
`post marketing approvals.
`
`13.
`
`As detailed in my CV, I have engaged in scholarly research and
`
`writing from several perspectives: that of an academic principal investigator on
`
`many drugs that were approved or that had their label extended; as a leader in
`
`industry teams that develop pharmaceuticals, leading to approval by both U.S. and
`
`foreign regulatory bodies; and as a governmental employee who has advised
`
`members of FDA on the adequacy, conduct and interpretation of studies related to
`
`prostate cancer, including endpoints of studies, modulation of safety issues related
`
`to treatments, and surrogate markers of prostate cancer outcomes.
`
`MYLAN PHARMS. INC. EXHIBIT 1002 PAGE 10
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`

`

`14.
`
`I have authored several hundred articles, book chapters, books,
`
`reviews, and monographs pertaining to prostate cancer.
`
`15.
`
`Based upon my education, training and experience, as summarized
`
`above, I believe I am qualified to provide opinion testimony as an expert in 1)
`
`medical oncology; 2) urologic cancer; 3) prostate cancer, including diagnosis,
`
`treatment, prevention, assessment of metrics to evaluate the disease, regulatory
`
`conduct of studies of prostate cancer, and evaluation of methods that claim efficacy
`
`and safety in prostate cancer; 4) all hormonal therapies for prostate cancer; and 5)
`
`assessment of adequate study design and conduct of studies that evaluate safety
`
`and efficacy carried out by academic, industry and government bodies.
`
`16.
`
`In the past four years, I have testified as an expert in either deposition
`
`or trial in approximately 10 separate medical malpractice proceedings. I am being
`
`compensated at an hourly rate of $750/hour and am available to appear live for
`
`testimony in support of my opinions. My compensation in no way depends on the
`
`outcome of this proceeding. The opinions to which I will testify are based on the
`
`education, experience, training and skill that I have accumulated in the course of
`
`my career as a practicing medical oncologist and researcher, as well as materials I
`
`have reviewed in connection with this case.
`
`MYLAN PHARMS. INC. EXHIBIT 1002 PAGE 11
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`

`

`II. MATERIALS CONSIDERED
`
`1 7.
`
`The list of materials I considered in forming the opinions set forth in
`
`this declaration includes the following:
`-
`
`Exhibit
`
`Description
`
`..
`
`-
`
`MYL 1001 U.S. Patent No. 8,822,438 to Auerbach and Belldegrun, "Methods
`and Compositions for Treating Cancer" ("the '438 patent")
`MYL 1003 O'Donnell, A. et al., "Hormonal impact of the l 7a-
`hydroxylase/Cl 7,20-lyase inhibitor abiraterone acetate (CB7630) in
`patients with prostate cancer," Br. J. Cancer 90:2317-2325 (2004)
`("O'Donnell")
`MYL 1004 Gerber, G.S. et al., "Prostate specific antigen for assessing response
`to ketoconazole and prednisone in patients with hormone refractory
`metastatic cancer," J. Urology 144(5):1177-9 (1990) ("Gerber")
`MYL 1005 U.S. Patent No. 5,604,213, Barrie S.E. et al., "17-Substituted
`Steroids Useful In Cancer Treatment" ("the '213 patent")
`MYL 1006 Tannock, I. et al., "Chemotherapy with mitoxantrone plus
`prednisone or prednisone alone for symptomatic hormone- resistant
`prostate cancer," J. Clin. Oncology 14(6):1756-1764 (1996)
`MYL 1009 Ryan, C.J. et al., "Abiraterone in metastatic prostate cancer without
`previous chemotherapy," New Engl. J. Med. 368:138-148 (2012).
`MYL 1010 January 11, 2013 Response ( excerpt from prosecution history of
`'438 patent)
`MYL 1012 June 4, 2013 Response (excerpt from prosecution history of '438
`patent)
`MYL 1018 Zytiga® Prescribing Information (2011)
`MYL 1019 Zytiga® Prescribing Information and Co-administration Brochure
`(2015)
`MYL 1020 Harris, K.A. et al., "Low dose ketoconazole with replacement doses
`of hydrocortisone in patients with progressive androgen
`independent prostate cancer," J. Urol. 168(2):542-5 (2002)
`MYL 1021 Oh, W., "Secondary hormonal therapies in the treatment of prostate
`cancer," Urology, 60(Supp. 3A):87-93 (2002)
`MYL 1022 Tannock, I. et al., "Docetaxel plus prednisone or mitoxantrone plus
`prednisone for advanced prostate cancer," N. Eng. J. Med.
`351: 1502-12 (2004)
`
`MYLAN PHARMS. INC. EXHIBIT 1002 PAGE 12
`
`

`

`Exhibit
`
`Description
`
`MYL 1028
`
`MYL 1023 Attard, G. et al., "Selective blockade of androgenic steroid
`synthesis by novel lyase inhibitors as a therapeutic strategy for
`treating metastatic prostate cancer," Br. J. Urol. 96(9):1241-1246
`(2005)
`MYL 1024 Hellerstedt et al., "The Current State of Hormonal Therapy for
`Prostate Cancer," CA Cancer J. Clin. 52: 154-179 (2002)
`MYL 1025 Kasper, D.L. et al. (Eds.), Harrison's Principles of Internal
`Medicine 549 (16th ed. 2005)
`MYL 1026 Auchus, R.J. "The genetics, pathophysiology, and management of
`human deficiencies of P450cl 7," Endocrinol. Metab. Clin. North
`Am. 30(1):101-119 (2001)
`MYL 1027 Costa-Santos, M. et al., "Two prevalent CYPl 7 mutations and
`genotype-phenotype correlations in 24 Brazilian patients with 1 7-
`hydroxylase deficiency," J. Clin. Endocrin. & Metabol. 89(1):49-60
`(2004)
`Jubelirer, S.J. et al., "High dose ketoconazole for the treatment of
`hormone refractory metastatic prostate carcinoma," J. Urol.
`142(1):89-901 (1989)
`MYL 1029 U.S. Patent 5,688,977, Sisti, N.J. et al., "Method f