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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`MYLAN PHARMACEUTICALS INC. Petitioners,
`V.
`JANSSEN ONCOLOGY, INC.
`Patent Owner.
`
`Case IPR2016-01332
`Patent 8,822,438 B2
`
`D E C L A R A T I ON OF IAN JUDSON, MD
`IN SUPPORT OF JANSSEN O N C O L O G Y, INC.'S
`PATENT OWNER RESPONSE
`
`JANSSEN EXHIBIT 2028
`Mylan v. Janssen IPR2016-01332
`
`
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`I, Ian Judson, M.D. hereby declare as follows:
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`1.
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`I am over the age of eighteen (18) and am otherwise competent to
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`make this Declaration. I have personal knowledge of the facts set forth in this
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`Declaration and am competent to testify to the same. I am a Consultant Medical
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`Oncologist at the Royal Marsden. I was appointed Senior Lecturer at the Royal
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`Marsden and The Institute of Cancer Research (ICR) in 1989, and became
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`Professor of Cancer Pharmacology in 2001. I have been involved in the early
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`development of a number of anti-cancer drugs including carboplatin,
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`temozolomide, raltitrexed, imatinib and abiraterone acetate.
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`2.
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`I have been asked by counsel for Patent Owner Janssen Oncology
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`Inc. ("Janssen") to provide a short declaration as background for the panel of
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`Administrative Patent Judges of the Patent Trial and Appeal Board of the United
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`States Patent and Trademark Office ("Panel") as it considers issues relating to the
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`patentability of U.S. Patent No. 8,822,438 (the '438 Patent) (Ex. 1001) in an inter
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`partes review requested by Mylan Pharmaceuticals, Inc. (hereinafter "Mylan") in
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`Case No. IPR2016-01332. Other than compensation for discussions leading to
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`this declaration, I have personally received no funding from Janssen Oncology
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`Inc. but I have received what is termed Rewards to Discoverers payments from
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`the ICR for my involvement in the development of abiraterone.
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`3.
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`I was the principal investigator for a series of phase one trials carried
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`out in 1998-1999 in which the 17a-hydroxylase/C17,20-lyase inhibitor
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`abiraterone acetate (CB7630) was tested in humans for the first time. I was
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`assisted by Professor David Deamaley, a Clinical Oncologist at the Royal
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`Marsden with a special interest in prostate cancer, and a number of investigators
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`from other hospitals. The ICR / Royal Marsden were initially partnered with
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`Boehringer Ingelheim for this project, and Boehringer Ingelheim assisted by
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`synthesising a batch of clinical grade abiraterone acetate for the phase one trials.
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`4.
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`The trials involved three studies conducted to determine the dose of
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`abiraterone acetate that would result in suppression of testosterone and to obtain
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`safety, pharmacokinetic and endocrine data. The scope of the studies, including
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`the numbers of patients and duration of treatment was restricted by the limited
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`supply of clinical grade abiraterone acetate. The results of these phase one trials
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`were eventually reported in O'Donnellet al, BJC, 90, 2317-2325 (2004). I have
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`been asked to refer to this publication as "O'Donnell" (Ex. 1003).
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`5.
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`The studies showed that specific inhibition of the CYPl 7 enzyme by
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`abiraterone acetate could reduce testosterone levels in both castrate and non-
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`castrate males to below castrate levels. This was proof-of-principle of the action
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`of the drug on testosterone levels.
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`3
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`
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`6. Abiraterone acetate proved to be well tolerated. Mild side effects
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`included headache, flushing and low mood. Cortisol levels were in general
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`maintained. Although the response to an injection of synthetic ACTH (described
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`as the "Synacthen test" in O'Donnell (Ex. 1003)) was reduced, this was not
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`thought at the time to be a major concern, since Cortisol levels were maintained
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`and there was still some response to ACTH. Our conclusion, as summarised in
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`page 2323 of O'Donnell (Ex. 1003), was that there were three possibilities: (i)
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`that concomitant therapy with glucocorticoid would be required on a continuous
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`basis, (ii) that glucocorticoid would be needed only at times of physiological
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`stress, when patients became symptomatic, or (iii) that there would be no
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`requirement for glucocorticoid at all. Regarding (ii), the option discussed at the
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`time, if there had been concerns (which there were not), was to give patients a
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`steroid warning card, and a supply of hydrocortisone tablets to take in an
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`emergency, such as infection, trauma etc. At the time, hydrocortisone was the
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`standard steroid administered as a glucocorticoid replacement with ketoconazole
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`and aminoglutethimide, which were inhibitors of steroid synthesis that were
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`known to reduce Cortisol levels.
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`7.
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`Subsequent to the completion of the study and submission of the
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`final report at the end of 1999, Boehringer Ingelheim decided not to continue
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`their involvement in the project. Attempts to find an alternative commercial
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`4
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`
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`partner for clinical development proved extremely difficult. In the years
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`following 2000, a number of major multinational pharmaceutical companies were
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`approached. On one trip to the United States 1 visited several such companies in
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`Princeton and Philadelphia. In these meetings, we presented the results of the
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`phase one trials reported in O'Donnell. Following these meetings, none of these
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`companies proved willing to support taking abiraterone acetate into further
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`clinical trials.
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`8.
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`During a similar period, we submitted the O'Donnell manuscript to
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`various medical journals, including Clinical Cancer Research, but were met with
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`scepticism and the study was not published (as O'Donnell) until 2004, in the
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`British Journal of Cancer. No further data were generated or analysis performed
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`after the rejections and before the eventual publication in O'Donnell.
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`9.
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`In response to our submission of the O'Donnell manuscript to
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`Clinical Cancer Research, I received a Clinical Cancer Research Peer Review
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`Letter dated May 12, 2003, a true and correct copy of which was filed as Exhibit
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`2030 in IPR2016-01332 on March 8, 2017.
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`10.
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`In April 2004, Cougar Biotechnology Inc. signed a licence
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`agreement giving it rights to develop and commercialise abiraterone acetate. I
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`took part in initial discussions with Cougar at the end of 2003 / early 2004 but
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`played no significant role in the subsequent clinical development of the drug.
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`5
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`The first cHnical trials sponsored by Cougar Biotechnology Inc. started in
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`December 2005 and were led by my colleague Professor Johann de Bono at the
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`Royal Marsden.
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`11.
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`I declare under penalty of perjury under the laws of the United States
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`of America that the foregoing is true and correct.
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`Executed on
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`ACTIVE 220289804V.2
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`By:
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`^ ^ t / T T L.
`Ian Judson, M.D.
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`