UNITED STATES PATENT AND TRADEMARK OFFICE
`
`________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`________________
`
`COALITION FOR AFFORDABLE DRUGS VI LLC
`Petitioner,
`
`v.
`
`CELGENE CORPORATION
`Patent Owner
`
`________________
`
`Case IPR2015-01102
`Patent 6,315,720
`________________
`
`
`
`DECLARATION OF
`DR. LOURDES M. FRAU, M.D., FAAP, FISPE
`
`
`Case IPR2015-01102
`
`CELGENE EXHIBIT 2059
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`Page 1 of 58
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`________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`________________
`
`COALITION FOR AFFORDABLE DRUGS VI LLC
`Petitioner,
`
`v.
`
`CELGENE CORPORATION
`Patent Owner
`
`________________
`
`Case IPR2015-01102
`Patent 6,315,720
`________________
`
`
`
`DECLARATION OF
`DR. LOURDES M. FRAU, M.D., FAAP, FISPE
`
`
`Case IPR2015-01102
`
`CELGENE EXHIBIT 2059
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`Page 1 of 58
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`I, Dr. Lourdes M. Frau, M.D., FAAP, FISPE do hereby declare as follows:
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`I.
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`INTRODUCTION
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`1.
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`I am over eighteen and otherwise competent to make this declaration.
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`I have been retained in this case by Patent Owner Celgene Corporation (“Celgene”
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`or “Patent Owner”).
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`2.
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`In this report, I have been asked to respond to the opinions in the
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`Declaration of Jeffrey Fudin (“Fudin Declaration”) regarding the alleged invalidity
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`of U.S. Patent No. 6,315,720 (the “’720 patent”) that was submitted on behalf of
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`Petitioner Coalition for Affordable Drugs VI LLC (“CFAD” or “Petitioner”), as
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`well as to provide my own understanding of the state of the relevant art at the time
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`of the invention claimed in the ’720 patent.
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`3.
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`I am being compensated for my time at my usual rate of $520 per hour.
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`My compensation does not depend in any way on the substance of my testimony or
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`on the outcome of this or any other case.
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`4.
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`I expressly reserve the right to supplement the opinions expressed
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`herein, as well as the bases for the opinions, in response to additional expert
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`declarations submitted by CFAD, or any additional discovery or other information
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`provided in this matter.
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`An identification of materials I have relied on is set forth in Appendix
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`5.
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`B hereto.
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`II. BACKGROUND, EXPERIENCE AND QUALIFICATIONS
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`6.
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`I am a physician and pharmacoepidemiologist. Since 2004, I have
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`been a consultant on matters pertaining to pharmaceutical safety and epidemiology.
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`7.
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`I am a Fellow of the International Society of Pharmacoepidemiology
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`and the American Academy of Pediatrics. I was a member of the Pharmaceutical
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`Research Manufacturers Association, Clinical Safety Surveillance Committee from
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`1994-1999. A complete list of my professional affiliations is provided in my
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`curriculum vitae, a copy of which is attached hereto as Appendix A.
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`8.
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`I received a Bachelor’s degree in chemistry from the University of
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`Connecticut in 1972, and an M.D. and M.M.S. from Robert Wood Johnson
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`Medical School at Rutgers University in 1976. I received postgraduate training at
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`Boston City Hospital, Tufts-New England Medical Center. A full description of
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`my formal education is provided in my curriculum vitae.
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`9.
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`I practiced general family medicine and pediatrics with the National
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`Health Service Corps in upstate New York and in Boston, MA, before training in
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`epidemiology at the Centers for Disease Control in Atlanta, Georgia as an
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`Epidemic Intelligence Service officer in the Division of Sexually Transmitted
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`Diseases, Epidemiology Research Branch. At the CDC, I was in charge of the
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`national surveillance of congenital syphilis and Chlamydia trachomatis, from
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`1983-1985.
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`10.
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`I am currently a Distinguished Lecturer at New York Medical
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`College, School of Health Sciences and Practice. I was an Instructor at Mercer
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`County Community College for continuing education courses on “Regulatory and
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`Legal Issues in Clinical Development” and “Introduction to Pharmacovigilance”
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`from 2005-2009.
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`11. After serving as a Senior Public Health Physician in the Division of
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`Maternal and Child Health, New Jersey Department of Health and Human
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`Services, I have worked in the pharmaceutical industry since 1988. Prior to my
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`current position, I served as the head of several pharmaceutical departments of
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`drug safety, pharmacovigilance, and epidemiology, for all drugs and devices, both
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`marketed and in clinical development. That includes domestic responsibilities at
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`Hoechst-Roussel Pharmaceuticals and Knoll Pharmaceuticals. It also includes
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`worldwide responsibilities at Bristol-Myers Squibb, Johnson & Johnson
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`Pharmaceutical Research Institute, Aventis Pharmaceuticals, and Cephalon. A full
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`description of my work history is provided in my curriculum vitae.
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`12.
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`In my professional career I have developed numerous risk
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`management plans (including RiskMAPs and REMS). I have overseen three risk
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`management programs within the U.S. and Europe, assuming responsibility for
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`their success. I served as a member of PhRMA’s Clinical Safety Surveillance
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`Committee in the 1990s. I have served as Chair of a corporate Risk Management
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`Strategy Team, which was a multi-disciplinary group supervising and coordinating
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`five Risk Minimization Plans for opioids and CNS products in the U.S. and
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`Europe. I developed and established a U.S. corporate drug safety department to
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`handle investigational and marketed products, and medical information services for
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`patient and health professional queries. A complete list of my past professional
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`responsibilities is provided in my curriculum vitae.
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`13.
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`I am an expert in the field of pharmaceutical risk management—in
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`particular safety surveillance, pharmacovigilance, and pharmacoepidemiology—
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`including the development and administration of restricted-distribution programs.
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`III. SUMMARY OF OPINIONS
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`14. Based on my knowledge, experience, and training and my review of
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`the ’720 patent, the alleged prior art relied on by Fudin, the IPR Petition, the Fudin
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`Declaration, the Fudin deposition, and other materials cited herein, it is my opinion
`
`that Petitioner has failed to establish that the claims of the ’720 patent would have
`
`been obvious over the cited references and/or general knowledge in the field, at the
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`time of the ’720 patent’s invention, which I understand to be October 23, 2000.
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`15. Specifically, it is my opinion that as of October 2000, a person of
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`ordinary skill in the art (“POSA”) would have had no motivation to combine the
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`cited references in order to come up with the inventions claimed by the ’720 patent,
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`nor would a person of ordinary skill in the art have recognized any need or
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`problem to be solved at the time of the ’720 patent’s invention.
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`16.
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`It is my further opinion that the cited references, separately or in
`
`combination, do not disclose each and every element of the claims of the ’720
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`patent.
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`17.
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`It is further my opinion that Petitioner’s expert, Jeffrey Fudin, has
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`improperly defined a person of ordinary skill in the art. As described further below,
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`it is my opinion that a person of ordinary skill would be experienced in
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`pharmaceutical risk management, and not a general practice pharmacist.
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`IV. BACKGROUND
`
`A. The history of thalidomide,
`S.T.E.P.S.®, and Enhanced S.T.E.P.S.®
`
`18.
`
`In my opinion, an analysis of the ’720 patent requires understanding
`
`the context of its disclosed inventions. Any understanding of the context of the
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`inventions must begin with the history and origination of thalidomide in the 1950s,
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`its subsequent removal from the market in 1962, its return to the U.S. market as a
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`beneficial drug in July 1998 in the form of Celgene’s Thalomid® brand thalidomide
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`capsules, and Celgene’s restricted distribution of Thalomid® (pursuant to the
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`System for Thalidomide Education and Prescribing Safety, or S.T.E.P.S.®) from
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`July 1998 until at least the filing of the ’720 patent in October 2000 and the launch
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`of Enhanced S.T.E.P.S.® in September 2001.
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`19. By July 1998, thalidomide was a well-known teratogen. (See e.g., Ex.
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`2066 at 2.) Thalidomide had been marketed in Europe by a different company (not
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`Celgene) in the late 1950s and early 1960s as a sedative and a treatment for
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`pregnant women with morning sickness. (Ex. 1001 at 1:39-45; Ex. 2002 at 1.) In
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`those years, thalidomide caused severe malformations in children of mothers who
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`took the drug during pregnancy, resulting in more than 10,000 birth defects. (Ex.
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`2002 at 1.) Fortuitously, FDA refused to approve thalidomide in the early 1960s,
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`preventing a similar result in the United States. (See, e.g., Ex. 2067.)
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`20. Thalidomide remained unlawful in the United States until Celgene
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`introduced Thalomid® in 1998. (Ex. 1031 at 0002-3.) At that time, FDA agreed to
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`end its 40-year ban on thalidomide, and to permit the marketing of Thalomid® in
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`the United States, only on the explicit condition that thalidomide would be
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`distributed under Celgene’s S.T.E.P.S.® program. (Id.) Indeed, the FDA’s
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`approval letter states that the “S.T.E.P.S. restricted distribution program is an
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`integral part of the approved NDA for this product and is an essential component
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`of the terms of this NDA’s approval by FDA for marketing this product in the
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`United States.” (Id. at 0003.)
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`21. The ’720 patent was filed in October 2000. (Ex. 1001 at Cover.)
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`From July 1998 until October 2000, S.T.E.P.S.® had proven 100% successful in
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`preventing birth defects of the type associated with thalidomide. (Ex. 2068 ¶ 7.)
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`In fact, not a single fetal exposure to thalidomide had been reported to occur under
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`the ’50l patent’s methods as of the ’720 patent’s October 2000 filing date. 2
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` — 2
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`In my opinion, as described below, nothing in the prior art taught or
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`2.
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`even suggested that there was any problem with S.T.E.P.S.® that needed to be
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`addressed, for thalidomide or for any other drug. In fact, S.T.E.P.S.® had
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`effectively prevented the second thalidomide tragedy that many had predicted and
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`thought inevitable before the launch of Thalomid® in July 1998. It was only years
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`later, in 2006, that Celgene (and others) explained in a publication that the original
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`implementation of S.T.E.P.S.® had “retrospectively identified patient behaviours
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`providing a risk of fetal exposure to thalidomide.” (Ex. 2006 at 328.) Before then,
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`from October 1999 to September 2001, the inventors focused on implementing
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`changes, based on confidential information—- that were
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`“designed to identify patients exhibiting behaviours providing risk for fetal
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`exposure and to remedy those behaviours prior to dispensing thalidomide.” (Ex.
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`2006 at 328.) These changes, called Enhanced S.T.E.P.S.®, were implemented for
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`the first time with the September 2001 Thalomid® package insert and “procedural
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`changes” that began in July 2001. (Ex. 2008; Ex. 2006 at 328.)
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`24.
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`The 720 patent is an improvement upon the ‘S01 patent, which I
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`discuss in detail in my declaration submitted in IPR20l5—0l092. Briefly, the ’SOI
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`patent is directed generally to a method of delivering a teratogenic drug to a patient
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`while preventing fetal exposure to the drug and the associated birth defects to the
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`fetus. (See, e.g., Ex. 1003 at Abstract.) The claims themselves require that all
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`participants in the teratogenic drug’s delivery (physicians, patients, and
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`pharmacists) are registered in a centralized computer readable storage medium that
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`contains, among other things, all information pertaining to all registered
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`physicians, patients, and pharmacists. (Id. at Claims.) S.T.E.P.S.® is an
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`embodiment of the ’501 patent. (Ex. 2061 at 377:19-378:1.)
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`25. The ’720 patent is also directed generally to a method of delivering a
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`drug to a patient while avoiding the side effects of the drug.
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`26. However, improvements were made “to minimize and simplify
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`demands on the pharmacy, thereby improving compliance with the system of
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`distribution, and reducing the risk that the drug will be dispensed to a
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`contraindicated individual.” (Ex. 1001 at 2:8-12.) As stated in the ’720 patent’s
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`specification, “it has surprisingly been found that by having the prescriber, rather
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`than the pharmacy, verify the patient’s informed consent,” increased efficiency, led
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`to “better compliance, and hence decreased risk that the adverse side effect will
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`occur.” (Ex. 1001 at 10:35-40.)
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`27. The inventors carried out these improvements through the claimed
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`prescription approval code. In the ’720 patent, the pharmacist “need only retrieve
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`the approval code” to comply with the methods described, which also increased
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`compliance. (Ex. 1001 at 13:55-64; see also Ex. 1002 at 0085 (“[W]hen the
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`patient presents a prescription to the pharmacy, all the registered pharmacy need do
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`is consult the computer readable storage medium, and the pharmacy is permitted to
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`dispense the drug upon successfully retrieving a prescription approval code
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`therefrom.”).)
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`28. Claim 1 of the ’720 patent is representative of the invention:
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`1. In a method for delivering a drug to a patient in need of the drug,
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`while avoiding the occurrence of an adverse side effect known or suspected
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`of being caused by said drug, wherein said method is of the type in which
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`prescriptions for said drug are filled only after a computer readable storage
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`medium has been consulted to assure that the prescriber is registered in said
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`medium and qualified to prescribe said drug, that the pharmacy is registered
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`in said medium and qualified to fill the prescription for said drug, and the
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`patient is registered in said medium and approved to receive said drug, the
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`improvement comprising:
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`
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`a. defining a plurality of patient risk groups based upon a
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`predefined set of parameters for said drug;
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`b. defining a set of information to be obtained from said
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`patient, which information is probative of the risk that said
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`adverse effect is likely to occur if said drug is taken by said
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`patient;
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`c. in response to said information set, assigning said patient to
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`at least one of said risk groups and entering said risk group
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`assignment in said medium;
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`d. based upon said information and said risk group assignment,
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`determining whether the risk that said adverse effect is likely to
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`occur is acceptable; and
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`e. upon a determination that said risk is acceptable, generating
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`a prescription approval code to be retrieved by said pharmacy
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`before said prescription is filled.
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`29. Thus, claim 1 is a method requiring that all participants in a drug’s
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`delivery (physicians, patients and pharmacists) are registered in a computer
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`readable storage medium; that patients’ information is obtained and they are
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`assigned to groups pursuant to their risks of exhibiting an adverse side effect; that
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`the potential risk group is assessed for whether the risk is acceptable; and, if it is
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`determined to be acceptable, an approval code is generated, which the pharmacy
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`retrieves prior to filling any prescription for the drug.
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`30. Claims 2-27 depend from claim 1 of the ’720 patent, and further
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`define the methods used to deliver a drug to a patient in need while avoiding the
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`occurrence of an adverse side effect. For example, claims 5 and 6 require that the
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`risk group assignment and informed consent is verified by the prescriber at the
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`time of patient registration; claim 10 requires that certain diagnostic testing
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`comprise genetic testing; and claim 17 requires that information from a survey is
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`collected via integrated voice response (“IVR”) before a patient is approved to
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`receive a drug.
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`V. LEGAL UNDERSTANDINGS
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`31. The following paragraphs in this section express my understanding of
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`certain legal principles related to patent validity that I considered in forming the
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`opinions I provide in this report. The legal standards were provided to me by
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`counsel.
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`A.
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`32.
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`Person of Ordinary Skill in the Art
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`I understand that a person having ordinary skill in the art (“POSA”) is
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`a hypothetical person having the understanding of those of ordinary skill in the
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`field pertinent to the subject matter of the patent.
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`B. Obviousness
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`33.
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`I understand that a patent claim is invalid on grounds of obviousness
`
`if the differences between the subject matter sought to be patented and the prior art
`
`are such that the subject matter as a whole would have been obvious to a POSA at
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`the time the invention was made.
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`34.
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`I further understand that obviousness is a question of law based on
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`underlying factual findings such as (1) the scope and content of the prior art, (2)
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`the level of ordinary skill in the art, (3) the differences between the claimed
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`invention and the prior art, and (4) evidence of secondary considerations, such as
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`unexpected results, long-felt need, failure of others, copying, and commercial
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`success.
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`35.
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`I understand that whether prior art invalidates a patent claim as
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`obvious is determined from the perspective of a POSA. Through the lens of a
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`POSA, a determination must be made not only of what the prior art teaches, but
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`also whether the prior art teaches away from the claimed invention and whether
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`there is a motivation to combine teachings from separate references. A
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`determination of obviousness cannot be based merely on the hindsight combination
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`of components selectively culled from the prior art to fit the parameters of the
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`patented invention. In other words, I understand that it is improper to use
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`hindsight to determine what the references disclosed to a POSA or to determine
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`whether a motivation to combine those disclosures existed in the prior art.
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`36.
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`I understand that a proper obviousness analysis involves what a POSA
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`would have done, not how the inventors arrived at their inventions.
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`37.
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`I understand that obviousness requires more than a mere showing that
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`the prior art includes separate references covering each separate claim limitation.
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`Rather, obviousness requires the additional showing that a POSA at the time of the
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`invention would have selected and combined those prior-art elements in the normal
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`course of research and development to yield the claimed invention. A party
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`seeking to invalidate a patent based on obviousness must demonstrate by a
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`preponderance of the evidence that a POSA would have been motivated to
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`combine the teachings of the prior-art references to achieve the claimed invention
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`and would have had a reasonable expectation of success in doing so.
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`VI. PERSON OF ORDINARY SKILL IN THE ART
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`38.
`
`I have been asked to opine on the qualifications of a POSA as of
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`October 2000. To help me ascertain the qualifications of a POSA, I reviewed the
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`’720 patent and its file history, as well as the materials cited in Appendix B.
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`39.
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`It is my opinion that a POSA, as of October 2000, would be a person
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`who held at least a bachelor’s degree and at least 2 years of experience in risk
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`management relating to pharmaceutical drug products, or a B.S. or M.S. in
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`pharmaceutical drug product risk management or a related field. Alternatively, a
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`POSA might have similar education, training, and industry experience that would
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`confer an equivalent level of skill in the development and/or implementation of
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`risk management relating to pharmaceutical drug products. At the time, “risk
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`management” would have included fields such as safety surveillance,
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`pharmacovigilance, or pharmacoepidemiology. A POSA would likely have been
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`an employee of a pharmaceutical company that manufactured potentially
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`dangerous drugs, or would worked in government or academia in a position that
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`required them to focus on pharmaceutical risk management.
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`40.
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`I base this opinion upon a review of the entire record. For example,
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`the specification states in the “Field of invention”:
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`
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`The present invention relates to improved methods for
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`delivering a drug to a patient. More particularly, the
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`present invention relates to novel methods for delivering
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`a teratogenic or other potentially hazardous drug to a
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`patient in need of the drug, while avoiding the occurrence
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`of known or suspected side effects of the drug. The
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`novel methods permit the distribution to patients of drugs,
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`particularly teratogenic drugs, in ways wherein such
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`distribution can or must be carefully monitored and
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`controlled.
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`(Ex. 1001 at 1:8-17.) The claims themselves are directed to a method which
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`incorporates a comprehensive computer registry of qualified patients, physicians,
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`and pharmacists; extensive qualitative risk assessment of patients; assignment of
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`patients based on risk profiles; and approval of those patients based on the
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`acceptability of the evaluated risk. (See, e.g., id. at claim 1.) A POSA would need
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`to have experience in the field of pharmaceutical risk management and/or in
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`developing or implementing programs to control access to and distribution of
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`hazardous drugs. It is my opinion that such experience is necessary because a
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`participant in only one aspect of a hazardous drug’s distribution would not have the
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`knowledge to effectively design and/or implement such an all-inclusive system.
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`41.
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`I therefore disagree with Fudin’s definition of a POSA. At the outset,
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`it is my opinion that Fudin improperly identifies the field of the invention. Fudin
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`concludes, without explanation, that the relevant field of invention is
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`“pharmaceutical prescriptions.” (Ex. 1027 ¶ 16.) Fudin’s definition vastly
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`oversimplifies the ’720 patent.
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`42. As stated above, the ’720 patent’s disclosure—including the claims
`
`themselves—is directed to “delivering a drug to a patient in need of the drug, while
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`avoiding the occurrence of an adverse side effect.” (See claim 1.) This is clearly
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`much more focused than “pharmaceutical prescriptions” in general. Fudin’s
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`definition thus completely ignores the scope of the disclosure and the elements of
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`the claims. Fudin provides no support for his overly generalized view of the field.
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`43. Based on this incorrect starting point, Fudin then surmises that a
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`POSA “would typically have either a Pharm.D. or a B.S. in pharmacy with
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`approximately 5-10 years of experience and a license to practice as a registered
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`pharmacist in any one or more of the United States.” (Ex. 1027 ¶ 16.) Fudin
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`further explained in his deposition that a POSA would include any registered
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`pharmacist that has practiced at least 4 years. (Ex. 2061 at 168:5-169:18.)
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`44. Fudin does not provide any support in the record or otherwise for his
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`conclusion that any general practice pharmacist would be a POSA. In my opinion,
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`the conclusion defies reason and is undermined by Fudin’s own testimony. For
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`example, Fudin claims that his POSA would not require (a) any degree focusing on
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`restricted distribution (Ex. 2061 at 171:15-21); or (b) any specific experience with
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`restricted distribution of pharmaceuticals (id. at 172:10-20) or designing and/or
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`implementing restricted distribution programs (id. at 174:13-18).
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`45. For Fudin’s definition of a POSA to be correct, a pharmacist who
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`merely had experience directly dealing with patients and dispensing general drugs
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`(id. at 184:3-16) should be able—without undue experimentation—to design the
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`entire method of the ’720 patent. But Fudin admits that his proposed POSA could
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`not design or implement the claimed inventions. (Id. at 193:12-194:10, 201:1-10;
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`246:17-247:2, 328:19-329:9.) And he excludes from his definition of a POSA
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`those who could design and implement the claimed methods, namely those with
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`pharmaceutical risk management education or experience. (Id. at 184:3-16.) He
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`also excludes all licensed healthcare professionals other than his POSA, a licensed
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`pharmacist. (Id. at 190:23-25.)
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`46. Under Fudin’s definition of a POSA, the inventors themselves would
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`not qualify as a POSA because they were not pharmacists. In contrast, under the
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`definition I propose above, pharmaceutical risk management specialists and
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`physicians or others with the required training and/or experience would be POSAs,
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`as well as the inventors that developed the claimed methods.
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`Page 18 of 58
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`47.
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`In my experience, the development of a restricted distribution system
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`is extremely complex and costly. The improvements claimed in the ’720 patent
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`involve intricate assessments of stratified risk which are conducted before the
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`medication is prescribed. As described below, an average pharmacist at the time of
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`the invention would have lacked the ability and the motivation to design an all-
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`inclusive system of drug delivery for a hazardous drug that is focused on pre-
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`prescription patient assessment.
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`VII. CLAIM CONSTRUCTION
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`48.
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`I have been informed by counsel that for the purposes of these
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`proceedings, terms are to be given their broadest reasonable construction as would
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`be understood by a POSA in view of the description of the invention in the
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`specification and the prosecution history of the ’720 patent. I further understand
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`from counsel that statements made by the patent applicant during prosecution of
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`the patent may define or limit the scope of the claims.
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`49. Fudin provides constructions for three terms found in the ’720
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`patent’s claims: “consulted,” “teratogenic effect,” and “adverse side effect.” (Ex.
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`1027 at ¶¶ 39-41.) These terms do not affect my opinions.
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`50. During the prosecution history of the ’720 patent, the Examiner
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`rejected claim 1 over U.S. Patent No. 6,202,932 to Boyer (Ex. 1005), stating that
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`Boyer “teaches a method of an automated pharmacy system … that improves
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`Page 19 of 58
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`prescription processing,” and that it would have been obvious to use Boyer’s
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`automation, “which includes a step for generating a prescription number or code
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`associated with said prescription by a computer workstation.” (Ex. 1002 at 0092.)
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`Yet, Fudin opines that the claimed prescription approval code is just a number and
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`could even be a credit card. Ex. 2061 at 432:21-24. In my opinion, this is
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`unreasonable.
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`51. The patent applicants successfully distinguished the claimed invention
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`from the prior art based on the term “approval code” by stating that in the claimed
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`system:
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`Upon a determination that the risk is acceptable, and only
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`upon such a determination, a prescription approval code
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`is generated, which must be retrieved by the pharmacy
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`before the prescription may be filled.
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` Thus, the
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`prescription approval code is not merely a number that is
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`associated with the prescription, but instead represents
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`the fact that a determination has been made that the risk
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`of the side effect occurring is acceptable, and that
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`approval-an affirmative decision- has been made for the
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`prescription to be filled. Boyer does not disclose or
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`suggest such an approval code.
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`* * *
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`Unlike the prescription approval code of the present
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`invention, the prescription number described in Boyer is
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`Page 20 of 58
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`simply a prescription identifier, and is in no way
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`connected to, or reflective of, a determination that the
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`risk of the side effect occurring has been found to be
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`acceptable. There is simply no correlation in Boyer
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`between the generation of the prescription number and
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`any risk assessment, and no indication that a prescription
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`approval code, as described and claimed in the instant
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`application, must be generated and retrieved by the
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`pharmacist before the prescription may be filled.
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`(See Ex. 1002 at 0107 (emphases in original).)
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`52. Thus, based on a review of the record, it is my opinion that the
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`“prescription approval code” claimed in the ’720 patent necessarily requires an
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`assessment of risk before it is generated and specifically means a “code
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`representing that an affirmative risk assessment has been made based upon risk-
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`group assignment and the information collected from the patient, and that is
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`generated only upon a determination that the risk of a side effect occurring is
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`acceptable.” I have used this construction for the purpose of my analysis in this
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`declaration.
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`VIII. THE ’720 PATENT’S CLAIMS WOULD NOT HAVE BEEN
`OBVIOUS
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`53. As explained below in regard to Fudin’s particular allegations, it is my
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`opinion that a POSA would not have found the claims of the ’720 patent to be
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`obvious.
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`Page 21 of 58
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`54. The alleged prior art cited by Fudin fail to provide sufficient guidance
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`or direction that would have led a POSA toward the claimed methods, and in some
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`instances, teach away from the claimed methods. In my opinion, Fudin was only
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`able to arrive at the claimed inventions by using the asserted claims as a roadmap
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`to piece the references together. I understand that such a hindsight analysis is
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`improper. In my opinion, a POSA would not have been motivated to combine the
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`selected references to arrive at claimed inventions, and he or she would have no
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`reasonable expectation of success based on their disclosures.
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`55. The Fudin Declaration cites to three primary prior art references as the
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`basis for its argument: Powell (Ex. 1006), Dishman (Ex. 1007), and Cunningham
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`(Ex. 1008). In my opinion, as discussed below, Fudin used hindsight to select
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`disclosures from the references out of context, ignored key elements that are
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`missing from the references or that teach away from the inventions, and improperly
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`attempted to fill in gaps in the references through unsubstantiated testimony as to
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`the “state of the relevant art” at the time of the inventions. I will discuss in more
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`detail below my opinions regarding non-obviousness and the disclosures of the
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`references that Fudin relies on.
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`Powell and the UK “Named Patient” Program
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`56. The Powell reference discloses recommendations for dispensing of
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`thalidomide in a limited, clinical setting in the United Kingdom. At the time of the
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`Page 22 of 58
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`publication, 1994, and at the time of the ’720 patent’s invention, thalidomide could
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`only be prescribed in the UK by hospital-based physicians to “named patients” in
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`accordance with legislation (similar to the United States’ Investigational New Drug
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`(“IND”) process), and only after other therapeutic options had been exhausted.
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`(Ex. 1006 at 901.) The Powell reference is therefore specially directed to
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`providing guidelines to hospital-based physicians on safe practices for “named
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`patients,” and does not suggest that its recommendations would be feasible for
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`distribution of the drug under a traditional prescription model and for wider use.
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`(See, e.g., id. (“Only severe disabling conditions that cause an unacceptable
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`interference with normal life should be treated with thalidomide, and only after
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`other treatments have been tried and failed.”).)
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`57. As stated previously, the S.T.E.P.S.® program was developed for use
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`in connection with a teratogenic product in a commercial setting—i.e., in the
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`context of obtaining approval of thalidomide outside the context of an IND—
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`therefore it is my opinion that a publication limited to small-scale, clinical use
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`would hold little significance to the development of an approved drug. In contrast,
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`Celgene’s claimed methods are directed to the safe delivery of potentially
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`dangerous drugs via general purpose pharmacy distribution for broader indications,
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`including first-line therapy. In my opinion, programs such as those described in
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`Powell would have little need to set up a comprehensive registry, go through
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`Page 23 of 58
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`categorized risk assessment, or require approval codes—as claimed in the ’720
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`patent—before delivering a drug because prescriptions were managed entirely
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`within the clinical setting and were only approved for a “small number of patients
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`who have exhausted other therapeutic options.” (Ex. 1006 at 0901001.)
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`58.
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`Indeed, because of its narrow focus, the Powell reference differs in a
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`number of significant ways from the ’720 patent. For example, Fudin agrees that
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`Powell does not disclose or suggest (a) maintaining a registry of patients,
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`physicians and prescribers (Ex. 2061 at 261:12-17); (b) keeping records in a
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`computer readable storage medium or retrieving information from such a source
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`(id. at 261:18-25); (c) pharmacist involvement in the distribution process (id. at
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`267:19-22, 268:5-13); (d) stratifying levels of risk am
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