DECLARATION OF PROFESSOR IAN JUDSON
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`I, Professor Ian Judson, of the Royal Marsden, Fulham Road, London SW3 6JJ, make the following
`declaration.
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`1.
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`2.
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`3.
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`I am a Consultant Medical Oncologist at the Royal Marsden. I was appointed Senior Lecturer
`at the Royal Marsden and The Institute of Cancer Research (ICR) in 1989, and became
`Professor of Cancer Pharmacology in 2001.1 have been involved in the early development of
`a number of anti-cancer drugs including carboplatin, temozolomide, raltitrexed, imatinib and
`abiraterone acetate.
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`I have been asked by Carpmaeis & Ransford LLP to prepare a short declaration concerning •
`certain issues relevant to EP 2 061 561. Other than compensation for discussions leading to
`this declaration, I have personally received no funding from Janssen Oncology Inc. but I have
`received what is termed Rewards to Inventors payments from the ICR for my involvement in
`the development of abiraterone. My CV is annexed to this declaration.
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`I was the principal investigator for a series of phase one trials carried out in 1998-1999 in
`which the 17a-hydroxylase/C17,20-lyase inhibitor abiraterone acetate (CB7630) was tested in
`humans for the first time. I was assisted by Professor David Dearnaley, a Clinical Oncologist
`at the Royal Marsden with a special interest in prostate cancer, and a number of investigators
`from other hospitals. The ICR / Royal Marsden was initially partnered with Boehringer
`Ingelheim for this project, and Boehringer Ingelheim assisted by synthesising a batch of
`clinical grade abiraterone acetate for the phase one trials.
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`4. The trials involved three studies conducted to determine the dose of abiraterone acetate that
`would result in suppression of testosterone and to obtain safety, pharmacokinetic and
`endocrine data. The scope of the studies, including the numbers of patients and duration of
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`1
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`JANSSEN EXHIBIT 2005
`Amerigen v. Janssen IPR2016-00286
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`treatment was restricted by tlie limited supply of clinical grade abiraterone acetate. The
`results of these phase one trials were eventually reported in O'Donnell et al., BJC, 90, 2317-
`2325 (2004).
`I have been asked to refer to this publication as "C1".
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`5. The studies showed that specific inhibition of the CYP17 enzyme by abiraterone acetate
`could reduce testosterone levels in both castrate and non-castrate males to below castrate
`levels. This was proof-of-principle of the action of the drug on testosterone levels.
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`6. Abiraterone acetate proved to be well tolerated. Mild side effects included headache, flushing
`and low mood. Cortisol levels were in general maintained. Although the response to an
`injection of synthetic ACTH (described as the "Synacthen test" in C1) was reduced, this was
`not thought at the time to be a major concern, since Cortisol levels were maintained and there
`was still some response to ACTH. Our conclusion, as summarised in at page 2323 of C1, was
`that there were three possibilities: (i) that concomitant therapy with glucocorticoid would be
`required on a continuous basis, (ii) that glucocorticoid would be needed only at times of
`physiological stress, when patients became symptomatic, or (ill) that there would be no
`requirement for glucocorticoid at all. Regarding (ii), the option discussed at the time, if there
`had been concerns (which there were not), was to give patients a steroid warning card, and a
`supply of hydrocortisone tablets to take in an emergency, such as infection, trauma etc. At the
`time, hydrocortisone was the standard steroid administered as a glucocorticoid replacement
`with ketoconazole and aminoglutethimide, which were inhibitors of steroid synthesis that were
`known to reduce Cortisol levels.
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`7. Subsequent to the completion of the study and submission of the final report at the end of
`1999, Boehringer Ingelheim decided not to continue their involvement in the project. Attempts
`to find an alternative commercial partner for clinical development proved extremely difficult. In
`the years following 2000, a number of major multinational pharmaceutical companies were
`approached. On one trip to the United States ! visited several such companies in Princeton
`and Philadelphia. In these meetings, we presented the results of the phase one trials reported
`in C 1. Following these meetings, none of these companies proved willing to support taking
`abiraterone acetate into further clinical trials.
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`8. During a similar period, we submitted the C1 manuscript to various medical journals, including
`Clinical Cancer Research, but were met with scepticism and the study was not published (as
`C I) until 2004, in the British Journal of Cancer. No further data were generated or analysis
`performed after the rejections and before the eventual publication in C I.
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`9.
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`In April 2004, Cougar Biotechnology Inc. signed a licence agreement giving it rights to
`develop and commercialise abiraterone acetate. I took part in initial discussions with Cougar
`at the end of 2003 / early 2004 but played no significant role in the subsequent clinical
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`development of the drug. The first clinical trials sponsored by Cougar Biotechnology Inc.
`started in December 2005 and were led by my colleague Professor Johann de Bono at the
`Royal Marsden.
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`10. I confirm the above to be true.
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`Signed
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`Date
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`Annex 1:
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`CV