UNITED STATES PATENT AND TRADEMARK OFFICE
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`MYLAN PHARMACEUTICALS INC
`Petitioner,
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`v.
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`BIOGEN MA, INC.
`Patent Owner.
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`Case IPR2018-01403
`Patent No. 8,399,514
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`REPLY DECLARATION OF JOEL W. HAY, PH.D. IN SUPPORT OF
`PETITIONER’S REPLY TO PATENT OWNER’S RESPONSE
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`MYLAN PHARMS. INC. EXHIBIT 1120 PAGE 1
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`TABLE OF CONTENTS
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`Page
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`INTRODUCTION ..............................................................................................3
`I.
`BACKGROUND AND QUALIFICATIONS ....................................................4
`II.
`III. BASES OF OPINIONS AND MATERIALS CONSIDERED ..........................9
`IV. LEGAL CONCEPTS ....................................................................................... 10
`V.
`SUMMARY OF OPINIONS ........................................................................... 12
`VI. BACKGROUND ............................................................................................. 13
`A.
`Tecfidera Development, Approval, and Orange Book Patents ............. 13
`B. MS Market ............................................................................................. 14
`VII. MR. JAROSZ FAILED TO ACCOUNT FOR ECONOMIC
`DISINCENTIVES THAT RENDER SECONDARY
`CONSIDERATIONS IRRELEVANT ............................................................ 16
`VIII. MR. JAROSZ FAILED TO ACCOUNT FOR UNCLAIMED DRIVERS
`OF TECFIDERA’S MARKETPLACE PERFORMANCE ............................ 20
`A.
`Features of the ’514 Patent Known in the Prior Art Contributed to
`Tecfidera’s Marketplace Performance .................................................. 20
`B. Marketing and Promotion Contributed to Tecfidera’s Marketplace
`Performance ........................................................................................... 23
`Biogen’s Leadership in the MS Market Contributed to Tecfidera’s
`Marketplace Performance ..................................................................... 25
`D. Discounts and Allowances Contributed to Tecfidera’s
`Marketplace Performance ..................................................................... 29
`IX. MR. JAROSZ RELIED EXCLUSIVELY ON LIMITED THIRD-
`PARTY SALES DATA ................................................................................... 32
`TECFIDERA PERFORMANCE COMPARED TO ANALYST
`PROJECTIONS FAILS TO SUPPORT NON-OBVIOUSNESS ................... 35
`XI. BIOGEN MARKETING MATERIALS TOUTED PRIOR ART
`FEATURES AND CANNOT SUPPORT NON-OBVIOUSNESS ................ 35
`XII. RESERVATION OF RIGHTS AND EXHIBITS ........................................... 36
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`X.
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`C.
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`I.
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`INTRODUCTION
`1. My name is Joel W. Hay, Ph.D. I have been retained by Petitioner
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`Mylan Pharmaceuticals Inc. (“Mylan”) to express my opinions responding to the
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`May 30, 2019 declaration of Mr. John C. Jarosz (Ex. 2202), which was filed in this
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`proceeding on behalf of Patent Owner Biogen MA, Inc. (“Biogen”). I was also
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`retained to express my opinions responding to Mr. Jarosz’s deposition testimony in
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`this proceeding, which he gave on August 1, 2019 (Ex. 1123). I understand that, in
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`this proceeding, Mylan asserts the claims of Biogen’s U.S. Patent No. 8,399,514
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`(“the ’514 Patent”) are unpatentable.
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`2.
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`A copy of my curriculum vitae is attached as Exhibit A. A listing of
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`the legal cases in which I have testified at trial or by deposition since 2015 is attached
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`as Exhibit B. A list of the materials I rely on is attached as Exhibit C.
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`3.
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`This Declaration discloses my opinions regarding “secondary
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`consideration” as they pertain to the ’514 Patent, in particular, the issue of
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`commercial success.
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`4.
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`I reserve the right to supplement this declaration as new or additional
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`information becomes available to me.
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`5.
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`I am being compensated for my testimony in this proceeding at my
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`standard rate of $1,250 per hour, plus any reasonable out-of-pocket expenses. No
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`payments to me are contingent upon the outcome of this proceeding or any other
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`MYLAN PHARMS. INC. EXHIBIT 1120 PAGE 3
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`hearing or litigation or upon the nature of my opinions.
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`II. BACKGROUND AND QUALIFICATIONS
`In 1974, I received my B.A. in Economics, summa cum laude, from
`6.
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`Amherst College. I then went on to receive my M.A. in Economics in 1975 and my
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`M.Ph. in Economics in 1976 from Yale University. In 1980, I received my Ph.D. in
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`Economics from Yale.
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`7.
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`I am a tenured Full Professor and Founding Chair of Pharmaceutical
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`Economics and Policy in the School of Pharmacy, with joint appointments in the
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`Department of Economics and at the Schaeffer Center for Health Policy and
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`Economics at the University of Southern California (USC). I also served for 15 years
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`as the USC Project Coordinator for the Rand Evidence-Based Medicine Practice
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`Centers of Southern California funded by the U.S. Agency for Healthcare Research
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`and Quality. I am a Health Economics Research Scholar at the UCLA Center for
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`Pediatric Vaccine Research. I am a founding member and founding Executive Board
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`member of the American Society for Health Economics (ASHEcon) and a founding
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`member and founding Executive Board member of the International Society of
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`Pharmacoeconomics and Outcomes Research (ISPOR).
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`8.
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`From 1978 to 1980, I was an Assistant Research Professor at USC.
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`Then from 1980 to 1984, I was an Assistant Professor in the Department of
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`Behavioral Sciences and Community Health, and the Department of Economics at
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`the University of Connecticut. I was also a Senior Policy Analyst with Project Hope
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`from 1983 to 1985. Then from 1985 to 1992, I was a Senior Research Fellow at the
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`Hoover Institution at Stanford University. In 1992, I was recruited to USC to found
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`the Department of Pharmaceutical Economics and Policy. I have been a tenured USC
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`faculty member since then.
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`9.
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`I have authored or coauthored over 600 scientific abstracts, reports, and
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`presentations, including 200+ peer-reviewed scientific articles and commentaries in
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`the fields of pharmaceutical markets, pharmaceutical economics, health economics,
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`outcomes research, disease management, statistics, econometrics, epidemiology,
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`and health care in journals including: American Journal of Cardiology; American
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`Journal of Health-Systems Pharmacy; American Journal of Managed Care;
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`American Journal of Public Health; Archives of Neurology; Cancer; CNS Drugs;
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`Haemophilia; Health Care Financing Review; Health Economics; Health Policy;
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`JAMA; JAMA Internal Medicine; Journal of AIDS; Journal of the American
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`Geriatrics Society; Journal of Business & Economic Statistics; Journal of Clinical
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`Gastroenterology; Journal of Health Economics; Journal of Health Politics, Policy
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`and Law; Journal of Human Resources; Journal of Managed Care and Specialty
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`Pharmacy; Journal of the Royal Statistical Association; Medical Care; New England
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`Journal of Medicine; Pediatrics; and Value in Health.
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`10.
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`In addition to the hundreds of pharmacoeconomic studies that I have
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`conducted, I have published numerous peer-reviewed scientific articles and abstracts
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`on the cost effectiveness and the economic value of drugs, screening programs, and
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`prevention programs. I recently co-authored a peer-reviewed scientific article on the
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`economic value of newer medications in the treatment of Multiple Sclerosis (MS)
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`and I have given formal presentations on this topic at recent scientific conferences.1
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`11.
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`In April 2015, I was one of three invited outside experts who presented
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`to the Directors and Staff of the Office of Medical Policy (Dr. Jonathan Jarow) and
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`the Center for Drug Evaluation and Research (Dr. Robert Temple) at the U.S. Food
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`and Drug Administration (FDA) on the regulation of economics claims for
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`pharmaceutical products. I also contributed on this topic as an invited speaker to the
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`Academy of Managed Care Pharmacy Partnership Forum, FDAMA 114: Improving
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`the Exchange of Pharmacoeconomic Data in March 2016.
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`12.
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`I have served as a consultant to the U.S. Centers for Medicare and
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`Medicaid Services, U.S. Agency for Healthcare Research and Quality, U.S. Centers
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`1 Xinke Zhang, Joel W. Hay & Xiaoli Niu, Cost Effectiveness of Fingolimod,
`Teriflunomide, Dimethyl Fumarate and Intramuscular Interferon-β1a in Relapsing-
`Remitting Multiple Sclerosis, 29 CNS DRUGS 71 (2015); Xinke Zhang, MS & Joel
`W. Hay, PhD, Cost-effectiveness of Fingolimod, Teriflunomide, Dimethyl
`Fumarate and Intramuscular Interferon Beta-1a in Relapsing-remitting Multiple
`Sclerosis, Poster, Monday Morning, PND20, ISPOR 19th Annual International
`Conference, May 2014, Montreal, Quebec, Canada; Xinke Zhang, MS & Joel W.
`Hay, PhD, Cost-effectiveness of Fingolimod, Teriflunomide, Dimethyl Fumarate
`and Intramuscular Interferon Beta-1a in Relapsing-remitting Multiple Sclerosis,
`American Society for Health Economics 5th Biennial Conference, June 2014, Los
`Angeles, CA.
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`for Disease Control and Prevention, U.S. Public Health Service, U.S. Food and Drug
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`Administration (FDA), U.S. Environmental Protection Agency, Revenue Canada,
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`Department of Justice Canada, Government of Hungary, Hong Kong Centre for
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`Economic Research, Hong Kong Medical Executives Association, World Bank,
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`California AIDS Commission, California Medi-Cal Drug Advisory Board, County
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`of San Diego Medically Indigent Adult Program, and County of Sacramento
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`Homeless Program.
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`13.
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`I have also written numerous health-related op-eds published in papers
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`such as Los Angeles Times, New York Times, Newsday, Sacramento Bee, San
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`Diego Union, San Francisco Chronicle, and Wall Street Journal. I have been
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`interviewed numerous times on television and radio regarding health-related and
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`drug-related policy issues, including media networks such as American Public
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`Media, Australian Broadcasting Corporation, BBC, PBS, CBS, ABC, NBC, NPR,
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`Fox News, C-SPAN, Al Jazeera, and Air America.
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`14.
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`I have served as a member of the Expert Advisory Panel on Drug
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`Utilization Review, United States Pharmacopeial Convention; an Executive
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`Committee member for the federally sponsored Southern California Evidence-Based
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`Medicine Practice Center; and a member of the JAMA Web Site HIV/AIDS
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`Editorial Review Panel. I also just completed a third consecutive two-year term as a
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`Study Section member for the Extramural Grants Review Program for the Agency
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`for Healthcare Research and Quality of the U.S. Department of Health and Human
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`Services.
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`15. From 2004 to 2010, I was a founding member of the Health Policy
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`Scientific Council of the International Society for Pharmacoeconomics and
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`Outcomes Research (ISPOR). From 2006 to 2010, I was founding Co-Chair of
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`ISPOR’s Drug Cost Task Force. In 2010, this Task Force published six peer-
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`reviewed guideline papers on pharmaceutical costing methodology in the journal
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`Value in Health, all of which I edited and co-authored.
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`16.
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`I served as the Founding Editor-in-Chief of Value in Health, the peer-
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`reviewed scientific journal of ISPOR, from its 1998 inception until 2003. In its first
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`scientific citation impact factor, Value in Health was ranked number one in two
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`categories for the year 2004 by the ISI Journal Citation Reports (JCR) with an impact
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`factor of 3.657. Value in Health led all other journals listed in both the Health Care
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`Sciences and Services category of the JCR Science Edition and in the Health Policy
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`& Services category of the JCR Social Sciences Edition. These categories include
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`all journals relating to health economics and pharmaceutical economics. Value in
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`Health is currently ranked third among all scientific peer-reviewed health
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`economics, pharmaceutical economics, health policy and health services research
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`journals.2 It is ranked third among all economics journals, which is remarkable,
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`2 https://www.valueinhealthjournal.com/ (last visited Sept. 21, 2019).
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`given that Value in Health only celebrated its 20th anniversary this year while the top
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`5 economics journals have all been around for many decades.3
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`17.
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`I have provided sworn testimony and expert opinions in numerous legal
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`cases and arbitration hearings on issues relating to pharmaceuticals, pharmaceutical
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`markets, and prescription medications. In particular, I have provided expert opinions
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`on the commercial success for pharmaceutical products in numerous legal cases (see,
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`e.g., Exhibit B). In various separate cases I have testified both for plaintiffs and for
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`defendants in these and other legal matters.
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`III. BASES OF OPINIONS AND MATERIALS CONSIDERED
`18. This report states my objective opinion, based on my professional
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`experience spanning over four decades, and my review of certain materials. The list
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`of materials I considered in forming the opinions set forth in this report is set forth
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`in Exhibit C. To the extent any materials cited in this report are not listed Exhibit
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`C, I have considered those materials too.
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`19.
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`I have reviewed the Expert Declaration of Dr. John R. Corboy in
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`Support of Inter Partes Review of U.S. Patent No. 8,399,514 (Ex. 1002), which has
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`provided me with an understanding of the multiple sclerosis (“MS”) treatment field
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`in the context of this proceeding, the claims of the ’514 Patent, and certain aspects
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`3 https://www.psc.isr.umich.edu/dis/infoserv/journal/search.html (last visited Sept.
`21, 2019).
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`of the prior art to the ’514 Patent, as discussed below.
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`IV. LEGAL CONCEPTS
`I understand that Mylan has the burden to show the ’514 Patent is
`20.
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`unpatentable, and Biogen has the burden to show the existence of secondary
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`considerations of non-obviousness.
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`21.
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`I understand that commercial success of a product is a “secondary
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`consideration” that the PTO may consider in their determination of the validity of a
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`patent. I understand that a showing of commercial success can provide potential
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`evidence that the invention disclosed in a patent was non-obvious at the time that the
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`application for the patent was filed.
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`22.
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`I have been advised that commercial success is a legal construct that
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`has been established through case law. I understand that the PTO considers a number
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`of factors in determining whether a product is a “commercial success,” including,
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`but not limited to: (1) sales; (2) profits; (3) total prescriptions; (4) market share in
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`prescriptions and dollar shares; (5) rate and growth in market share; (6) displacement
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`of existing products in the market; and (7) the standing or “rank” of the product in
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`the market. I also understand that sales figures alone are not evidence of commercial
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`success—rather, sales must be considered in light of the relevant market and the
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`product’s return on investment. I further understand that courts have found that one
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`cannot merely rely on total sales alone to establish “commercial success.” These
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`factors are consistent with my experience and understanding in evaluating the
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`success of pharmaceutical products, but are by no means exhaustive.
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`23.
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`I understand further that, in order for the commercial success of the
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`product incorporating the patented technology to be relevant for the purpose of
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`evaluating non-obviousness, there must be a demonstrable nexus between the
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`claimed invention and the product’s commercial success. I understand this to mean
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`that Biogen must show any alleged commercial success is driven by and attributable
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`to a patented feature as opposed to some other characteristic of the product or method
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`of selling. I further understand that where commercial success can be attributed to
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`characteristics of the invention that were already disclosed in the prior art, non-
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`obviousness is not supported by the supposed commercial success.
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`24.
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`I have been informed that another secondary consideration of non-
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`obviousness is the satisfaction of a long-felt but unmet need. I understand that, to
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`show long-felt but unmet need, Biogen must demonstrate there was a long-standing
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`problem in the art which the alleged invention solved.
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`25.
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`I understand that any support for non-obviousness based on secondary
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`considerations, including commercial success and long-felt but unmet need, is less
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`persuasive when disincentives existed in the market for others to successfully
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`exploit the patented idea. That is, when market entry by others was impeded by
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`some reason other than the supposed non-obviousness of the patented invention,
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`secondary considerations fail to support validity.
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`26.
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`It is my understanding that the earliest possible priority date for the ’514
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`Patent is February 8, 2007.
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`V.
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`SUMMARY OF OPINIONS
`27. Mr. Jarosz has not established the commercial success of Tecfidera, the
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`dimethyl fumarate product Biogen asserts embodies the claims of the ’514 Patent.
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`The performance of Tecfidera fails to provide secondary consideration of non-
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`obviousness because economic disincentives existed that would have discouraged
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`others from developing a product that practices the ’514 Patent.
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`28. Mr. Jarosz failed establish a demonstrable nexus between the
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`commercial performance of Tecfidera and the novel aspects of the claims of the ’514
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`Patent. Mr. Jarosz attributed to the ’514 Patent certain characteristics of Tecfidera
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`that are not claimed in the ’514 Patent, and attempted to establish a nexus between
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`those unclaimed characteristics and Tecfidera’s performance. Mr. Jarosz also failed
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`to acknowledge that those unclaimed characteristics of Tecfidera were disclosed in
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`the prior art, and therefore cannot establish a nexus to the claims of the ’514 Patent.
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`29. Mr. Jarosz also failed to consider other possible drivers of Tecfidera’s
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`marketplace performance, including Biogen’s extensive marketing and advertising
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`for Tecfidera, Biogen’s extensive experience in the MS therapeutic area, and
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`Biogen’s significant discounts and allowances for Tecfidera. These marketplace
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`drivers are all unrelated to the claims of the ’514 Patent and significantly affected
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`Tecfidera’s marketplace performance. Mr. Jarosz’s commercial success analysis is
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`therefore incomplete and unreliable.
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`VI. BACKGROUND
`A. Tecfidera Development, Approval, and Orange Book Patents
`In September 2003, Biogen entered into a license agreement with
`30.
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`Fumapharm AG (“Fumapharm”), through which Biogen licensed the product now
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`known as Tecfidera (called BG-12 during development). See Ex. 1077 at 13 (“BG-
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`12 is an oral fumarate that is a second-generation fumarate derivative with an
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`immunomodulatory mechanism of action, which we licensed from Fumapharm.”);
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`id. at 69 (“In September 2003, Biogen, Inc. entered into a license agreement with
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`Fumapharm AG, or Fumapharm, under which Biogen, Inc. obtained exclusive rights
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`to develop and market a second-generation fumarate derivative with an
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`immunomodulatory mechanism of action, which is currently in clinical trials in
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`Europe.”).
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`31.
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` In June 2006, Biogen acquired Fumapharm and Tecfidera, as well as
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`Fumapharm’s Fumaderm product for psoriasis. See Ex. 1079 at 103 (“In June 2006,
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`we completed the acquisition of 100% of the stock of Fumapharm, a privately held
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`pharmaceutical company based in Switzerland that develops therapeutics derived
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`from fumaric acid esters. As part of the acquisition, we acquired FUMADERM, a
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`commercial product available in Germany for the treatment of psoriasis, and BG-12,
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`a clinical-stage compound being studied for the treatment of MS and psoriasis that
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`was being jointly developed by Fumapharm and us.”); Ex. 1080 at 9 (“We acquired
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`TECFIDERA as part of our acquisition of Fumapharm AG in 2006.”).
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`32. Tecfidera was approved by FDA on March 27, 2013. See Ex. 2132.
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`33. Biogen has listed five patents in the FDA’s “Orange Book” entry for
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`Tecfidera: U.S. Patent Nos. 6,509,376 (“the ’376 Patent”), 7,320,999 (“the ’999
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`Patent”), 7,619,001 (“the ’001 patent”), 7,803,840 (“the ’840 Patent”), and the ’514
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`Patent. Ex. 1071. The ’376 Patent, ’999 Patent, ’011 Patent, and ’840 Patent were
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`originally assigned to Fumapharm and were transferred to Biogen in 2007 (’840
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`Patent) and 2008 (’376 Patent, ’999 Patent, and ’011 Patent). See Exs. 1108-1111.
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`34.
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`I understand the ’514 Patent at issue in this proceeding claims a method
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`of treating patients with MS through the oral administration of a pharmaceutical
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`composition consisting of therapeutically effective amount of dimethyl fumarate,
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`monomethyl fumarate, or a combination thereof, and one or more pharmaceutically
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`acceptable excipients, wherein the therapeutically effective amount is about 480 mg
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`per day. Ex. 1002 ¶¶ 24–33.
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`B. MS Market
` I understand that MS is a chronic neurodegenerative disease of the
`35.
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`central nervous system. Id. ¶ 35. I further understand that MS develops in phases,
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`including (1) a clinically isolated syndrome; (2) the relapsing-remitting multiple
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`sclerosis (“RRMS”) phase; (3) the secondary progressive multiple sclerosis
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`(“SPMS”) phase; and (4) the primary progressive multiple sclerosis (“PPMS”)
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`phase. Id. ¶ 39.
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`36.
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`I understand that MS is treated with “disease modifying therapeutics”
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`or “DMTs.” Id. ¶ 45. According to the National MS Society, currently seventeen
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`DMTs are used to treat MS. Ex. 1075. This includes five oral medications: “Aubagio
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`(teriflunomide), Gilenya (fingolimod), Tecfidera (dimethyl fumarate), Mavenclad
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`(cladribine), and Mayzent (siponimod).” Id. There are also eight injectable
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`medications: “Avonex (interferon beta-1a), Betaseron (interferon beta-1b),
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`Copaxone (glatiramer acetate), Extavia (interferon beta-1b), Glatiramer Acetate
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`Injection (glatiramer acetate -generic equivalent of Copaxone 20 mg and 40 mg
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`doses), Glatopa (glatiramer acetate - generic equivalent of Copaxone 20mg and
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`40mg doses), Plegridy (peginterferon beta-1a),” and “Rebif (interferon beta-1a)”. Id.
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`There are also four infused medications: “Lemtrada (alemtuzumab), Novantrone
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`(mitoxantrone), Ocrevus (ocrelizumab), and Tysabri (natalizumab).” Id.
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`37. Mr. Jarosz stated in his declaration that “Tecfidera competes in the MS
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`DMTs marketplace with other oral medications, self-injected medications, and
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`infused medications.” Ex. 2202 ¶ 48. I agree that Tecfidera competes with all
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`available MS treatments.
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`VII. MR. JAROSZ FAILED TO ACCOUNT FOR ECONOMIC
`DISINCENTIVES THAT RENDER SECONDARY
`CONSIDERATIONS IRRELEVANT
`38. As explained above, any support for the non-obviousness of a patent
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`based on secondary considerations, including commercial success and long-felt but
`
`unmet need, is not persuasive when disincentives unrelated to the non-obviousness
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`of the patented invention were present, which impeded others from entering the
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`market and exploiting the patented technology. In my opinion, there were
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`economic disincentives in the case of Tecfidera.
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`39. From an economic perspective, disincentives were presented by the
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`’376 Patent and the 10/197,007 (the “’007 Application”) (the application that I
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`understand issued as the ’999 Patent) that render the market performance of
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`Tecfidera irrelevant to the supposed non-obviousness of the asserted claims of the
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`’514 Patent. The ’376 Patent and ’077 Application would have discouraged others
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`from developing or commercializing a product that would practice the asserted
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`claims of the ’514 Patent before the ’514 Patent’s earliest possible priority date
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`(February 8, 2007) through at least April 1, 2019 (the expiration date of the ’376
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`Patent). Mr. Jarosz failed to address the disincentives raised by the ’376 Patent and
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`’007 Application, making his report incomplete in my opinion.
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`40. The ’376 Patent issued on January 21, 2003. I understand Mylan’s
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`experts Drs. Greenberg and Corboy have stated that the ’376 Patent is directed
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`towards a pharmaceutical preparation of dialkyl fumarates in the form of micro-
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`tablets or pellets for the therapy of numerous diseases, including MS. Ex. 1002 ¶¶
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`107–111. Biogen obtained the exclusive rights to the ’376 Patent in September 2003
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`through a license agreement with Fumapharm. Ex. 1076 at 102. In June 2006,
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`Biogen acquired Fumapharm, Fumapharm assigned the ’376 Patent to Biogen,
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`Biogen acquired Fumaderm, a dimethyl fumarate product for the treatment of
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`psoriasis marketed in Germany, and intellectual property rights related to the
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`treatment of psoriasis. See Ex.1078 at 105; Ex. 1089. Accordingly, prior to February
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`2007, others knew that Biogen possessed intellectual property rights related to
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`dimethyl fumarate for the treatment of MS (including the ’376 Patent) and was
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`developing dimethyl fumarate for the treatment of patients with relapsing forms of
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`MS.
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`41.
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`I understand Mylan’s experts Drs. Greenberg and Corboy have stated
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`that the ’376 Patent is directed towards a pharmaceutical preparation of dialkyl
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`fumarates in the form of micro-tablets or pellets for the therapy of numerous
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`diseases, including MS. Ex. 1002 ¶¶ 107–111. Those in the field therefore knew of
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`Biogen’s development efforts and would understand that Biogen preferred a
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`microtablet dimethyl fumarate formulation for MS. They would also know based on
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`public information that Biogen was progressing with these development efforts. See
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`Ex. 1016. Therefore, even though the ’376 Patent is directed to micropellet or
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`microtablet formulations of dialkyl fumarates, the ’376 Patent along with Biogen’s
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`known preference and advanced development of a microtablet formulation of
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`dimethyl fumarate to treat MS, would have disincentivized others from developing
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`not only the dimethyl fumarate formulations covered by the ’376 Patent, but also
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`any alternative formulations covered by the ’514 Patent. The ’376 Patent and
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`publicly known information would have discouraged others from developing a
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`product that practiced the ’514 Patent.
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`42. The ’077 Application was filed on July 17, 2002 and was published in
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`January 2003 as Pub. No. US 2003/0018072. I understand the file history for the
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`’007 Application became publicly at the time of publication. I have been informed
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`that, according to Dr. Greenberg, as early as November 22, 2004, the applicants of
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`the ’077 Application added claims that fully subsumed the claims of the ’514 Patent.
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`That is, the pending claims covered, among other things, the treatment of MS with
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`oral formulations of dimethyl fumarate, monomethyl fumarate, or a combination of
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`the two, at a dose of 480 mg per day. For example, I understand from Dr. Greenberg
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`that claim 124 added on November 22, 2004 covered methods of treating MS with
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`a broad range of dialky fumarates (including dimethyl fumarate, monomethyl
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`fumarate, and combinations of the two). Ex. 1112 at 3.
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`43. Because the file history of the ’077 Application was publicly available,
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`skilled artisans would have known about the scope of pending claim 124 prior to the
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`’514 Patent’s priority date. I have been informed that claim 124 remained pending
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`without rejection until March 2, 2007, when the applicants cancelled it in favor of
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`new claims that also overlap the claims of the ’514 Patent and are not limited to
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`micro-tablet/micro-pellet formulations (for example, pending claims 166 and 201).
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`See Ex. 1112 at 10 (see claim 166); id. at 18 (see amended claim 201). Those claims
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`eventually issued on January 22, 2008 as the ’999 Patent.
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`44. The claims pending from 2004 to 2008 that encompassed the subject
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`matter of the ’514 Patent would have discouraged others in the field from developing
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`a dimethyl fumarate product to treat MS due to a risk of infringing those claims (as
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`well as the already issued claims of the ’376 Patent).
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`45. Mr. Jarosz did not consider the disincentives raised by the ’376 Patent,
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`’077 Application, and Biogen’s known development of Tecfidera. His analysis of
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`secondary considerations is therefore incomplete in my opinion. Because of the
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`disincentives, Tecfidera has not competed in an objective market such that
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`competitors could market the treatment claimed in the ’514 Patent. Its marketplace
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`performance therefore fails to provide secondary considerations of the non-
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`obviousness of the ’514 Patent.
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`VIII. MR. JAROSZ FAILED TO ACCOUNT FOR UNCLAIMED DRIVERS
`OF TECFIDERA’S MARKETPLACE PERFORMANCE
`Features of the ’514 Patent Known in the Prior Art Contributed
`A.
`to Tecfidera’s Marketplace Performance
`46. As explained above, if features known in the prior art drove the
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`supposedly commercial success of Tecfidera, there is no nexus between the
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`marketplace performance and the secondary consideration of non-obviousness. The
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`sales of Tecfidera are not relevant to the validity because the patented features did
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`not cause the marketplace performance.
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`47. Mr. Jarosz asserts that claims of the ’514 Patent “generally enable” the
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`“efficacy, tolerability, safety, and convenience advantages that are key to
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`Tecfidera’s success in the U.S.” Ex. 2202 ¶ 86. He also claims that Tecfidera
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`embodies the claims of the ’514 Patent. Id.
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`48.
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` First, I understand that the ’514 Patent does not explicitly claim the
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`“tolerability, safety, and convenience” of a DMF treatment for MS, and only refers
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`to “efficacy” in the phrase “therapeutically effective amount.” See, e.g., Ex. 1002 ¶¶
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`24–33; Ex. 1001 at claim 1. This may explain Mr. Jarosz’s statement that the
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`“inventions of the ’514 Patent generally enable” these characteristics. Mr. Jarosz
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`never explains which of the features he mentioned are attributable to the ’514 Patent
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`as opposed to other patents that Biogen listed in the Orange Book for Tecfidera.
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`49. Based on the testimony of Mylan’s technical experts, I understand that
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`the efficacy of Tecfidera is due to the active ingredient dimethyl fumarate’s
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`effectiveness for treating MS. Ex. 1002 ¶ 11. I also understand the use of dimethyl
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`fumarate for treating MS was known in the prior art to the ’514 Patent. See id. ¶¶ 11–
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`14, 66–74. Mr. Jarosz cannot rely on Tecfidera’s marketplace performance to the
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`extent it was driven by dimethyl fumarate’s efficacy for MS because that feature was
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`known in the prior art and not a novel characteristic claimed in the ’514 Patent.
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`50. Moreover, Biogen’s technical experts have asserted a 480 mg/day dose
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`of dimethyl fumarate was just as effective as a 720 mg/day dose of dimethyl
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`fumarate. Ex. 2061 ¶¶ 125, 129–133; Ex. 2058 ¶¶ 165, 171–172. If they are right,
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`because the 720 mg/day dose of dimethyl fumarate was known in the prior art, the
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`efficacy of a dimethyl fumarate treatment for MS was known in the prior art to the
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`’514 Patent. See Ex. 1002 ¶¶ 11–12, 47–60, 66–74.
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`51. Based on the testimony of Mylan’s technical experts, I understand that
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`the safety of a dimethyl fumarate treatment for MS was known in the prior art to the
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`’514 Patent. See Ex. 1002 ¶¶ 66–67. Mr. Jarosz cannot rely on Tecfidera’s
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`marketplace performance to the extent it was driven by dimethyl fumarate’s safety
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`because that feature was known in the prior art and not a novel characteristic claimed
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`in the ’514 Patent.
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`52. Based on the testimony of Mylan’s technical experts, I understand that
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`d