UNITED STATES PATENT AND TRADEMARK OFFICE
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`MYLAN PHARMACEUTICALS, INC.
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`Petitioner
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`v.
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`YEDA RESEARCH AND DEVELOPMENT CO. LTD.
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`Patent Owner
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`Case No. IPR2015-00644
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`Patent No. 8,399,413
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`CORRECTED DECLARATION OF HENRY G. GRABOWSKI, PH.D., IN
`SUPPORT OF PATENT OWNER YEDA’S RESPONSE TO INSTITUTION
`OF INTER PARTES REVIEW
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`YEDA EXHIBIT NO. 2133
`MYLAN PHARM. v YEDA
`IPR2015-00644
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`V. 
`
`I. 
`II. 
`III. 
`IV. 
`
`Table of Contents
`Qualifications ...................................................................................................................... 1 
`Assignment ......................................................................................................................... 2 
`Summary of Opinions ......................................................................................................... 3 
`Background on Copaxone® and Other Drugs for the Treatment of Relapsing-Forms of
`Multiple Sclerosis ............................................................................................................... 5 
`Commercial Success of Copaxone® 40mg/mL ................................................................... 6 
`A.  Indicators of Commercial Success ...................................................................................... 6 
`B.  Copaxone® 40mg/mL’s High Level of U.S. Sales and Continued Sales Growth Are
`Evidence of Its Commercial Success .................................................................................. 7 
`C.  Copaxone® 40mg/mL’s High Level of U.S. Prescriptions and Continued Growth in
`Prescriptions are Evidence of Its Commercial Success ...................................................... 7 
`D.  Copaxone® 40mg/mL’s Performance Relative to Other Drugs for the Treatment of
`Relapsing-Forms of Multiple Sclerosis is Evidence of Its Commercial Success ............... 8 
`E.  Analyst Reports Discuss Copaxone® 40mg/mL’s Commercial Success ............................ 9 
`The Commercial Success of Copaxone® 40mg/mL is the Result of Its Patented Features
`VI. 
`........................................................................................................................................... 10 
`A.  The Patented Features of Copaxone® 40mg/mL Were Marketed by Teva and Valued by
`Physicians and Patients ..................................................................................................... 10 
`B.  The Continued Success of Copaxone® 40mg/mL in the Face of Generic Glatopa™ Entry
`Demonstrates that Physicians, Patients, and Payers Obtain Benefits from the Patented
`Features of the Drug.......................................................................................................... 14 
`C.  The Patents Covering the Active Ingredient of Copaxone® Did Not Block Other
`Companies from Researching Other Formulations of Glatiramer Acetate ....................... 16 
`D.  The Success of Copaxone® 40mg/mL is Not Attributable to the Marketing and
`Promotional Activities of Copaxone® 40mg/mL Apart from their Educational Function 18 
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`YEDA EXHIBIT NO. 2133
`MYLAN PHARM. v YEDA
`IPR2015-00644
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`I.
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`Qualifications
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`1.
`I, Henry G. Grabowski, Ph.D., have personal knowledge of the facts set forth in this
`Declaration and am competent to testify to the same.
`2.
` I am currently Professor Emeritus of Economics and the Director of the Program in
`Pharmaceuticals and Health Economics at Duke University. I received my Bachelor of Science
`degree in Engineering Physics from Lehigh University in 1962. In 1967, I obtained a doctorate
`in economics from Princeton University. My academic and research specialties are in the
`pharmaceutical industry—health economics, economics of innovation, and government
`regulation.
`3.
`I have studied the economics of the pharmaceutical industry over much of my career, and
`I have published numerous articles and books on this industry. I created a graduate course at
`Duke on economics and policy issues in the pharmaceutical industry. Under a series of grants
`from the National Science Foundation, I have examined the economics of pharmaceutical
`research and development (“R&D”) and the effect of various government policy actions on drug
`innovation. I have testified several times before Congressional committees in the United States
`on pharmaceutical industry issues. For example, since 1994, I have testified on issues involving
`effective patent life and generic competition in pharmaceuticals, biosimilars, the Clinton
`Administration’s health reform legislation, and the federal government’s policy toward
`children’s vaccines.
`4.
`I have been an advisor and consultant to the National Academy of Sciences, Institute of
`Medicine, Federal Trade Commission, General Accounting Office, and Office of Technology
`Assessment. I have also held visiting scholar appointments at the International Institute of
`Management in Berlin, Germany, the Health Care Financing Administration in Washington,
`D.C., the Office of Health Economics in London, and the Centre for Medicines Research in
`London. Until its acquisition by Gilead Sciences in 2003, I served on the Board of Directors of
`Triangle Pharmaceuticals, Inc., a development-stage company that specialized in antiviral drug
`therapies.
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`5.
`I have done extensive research on the economics of competition in the pharmaceutical
`industry, including the role of patents and the importance of R&D. I have also performed several
`studies on pharmaceutical R&D costs and profits. The Congressional Budget Office has used
`my work in this regard to analyze the effects of the Hatch-Waxman Act on R&D returns, and to
`analyze the proposed changes associated with the Clinton Health Reform Act of 1993.
`6.
`I attach as Exhibit 2104 a copy of my curriculum vitae, which includes a more detailed
`description of my education and professional experience, as well as a list of my publications
`from the last forty years.
`7.
`I have served as an expert witness in several prior cases. A list of all cases in which I
`have testified at trial or by deposition in the last four years is provided in Exhibit 2105.
`
`II.
`
`Assignment
`
`8.
`I have been asked by counsel for Teva to determine, as a matter of economics, whether
`Teva’s drug Copaxone® 40mg/mL, a drug for the treatment of relapsing-forms of multiple
`sclerosis, is a commercial success. I have also been asked to analyze the determinants of
`Copaxone® 40mg/mL’s commercial success, if any, and whether a nexus exists between the
`commercial success and the inventions claimed in U.S. Patent Nos. 8,232,250 (the “’250
`patent”), 8,399,413 (the “’413 patent”), and 8,969,302 (the “’302 patent”). In that context, I
`have been asked to discuss the marketing of prescription drug products, both generally and for
`Copaxone® 40mg/mL in particular.
`9.
`In connection with the opinions and conclusions contained within this report, I reviewed
`and considered the references cited throughout the report and the attached Exhibits. I have also
`reviewed the expert declaration of Dr. Fox and the deposition transcript of Dr. Green. Finally, I
`have relied on my training, my years of experience as an economist, my regular review and
`knowledge of the economics literature, and presentations at academic and industry conferences.
`A complete list of materials I relied upon for this report is provided in Exhibit 2106.
`10.
`I am being compensated for my time and services at my regular hourly rate of $800. I
`will also be reimbursed for my expenses. I have been assisted in this matter by staff of
`Cornerstone Research, who worked under my direction. I receive compensation from
`Cornerstone Research based on its collected staff billings for its support of me in this matter.
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`Neither my compensation in this matter nor my compensation from Cornerstone Research is in
`any way contingent or based on the content of my opinions or the outcome of this or any other
`matter.
`11. My opinions are based on currently available information. I reserve the right to
`supplement my analyses and opinions if new information becomes available that is pertinent to
`this case.
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`III.
`
`Summary of Opinions
`
`Based on my research and analysis summarized in this report, I conclude that Copaxone®
`12.
`40mg/mL is a commercial success. In addition, I conclude that Copaxone® 40mg/mL is a
`success due to the patented features of the product, in particular its dosage regimen of three
`injections per week, and corresponding benefits. I further conclude that the commercial success
`of Copaxone® 40mg/mL is not attributable to excessive marketing or promotion of the drug or
`the presence of patents covering the active ingredient of Copaxone® (i.e., glatiramer acetate).
`Copaxone® 40mg/mL’s commercial success is demonstrated by its levels of, and growth
`13.
`in, prescriptions, dollar sales, and extended unit sales. Since Copaxone® 40mg/mL launched in
`January 2014, the drug has generated over $
` billion in wholesale sales and sales of over
`
`million extended units. In addition, total prescriptions of Copaxone® 40mg/mL have exceeded
` and new prescriptions have achieved nearly
` since the launch of the drug.
`The commercial success of Copaxone® 40mg/mL is further demonstrated by its
`14.
`performance relative to other drugs prescribed for the treatment of relapsing-forms of multiple
`sclerosis. Copaxone® 40mg/mL’s share of wholesale sales and prescriptions among drugs
`prescribed for relapsing-forms of multiple sclerosis has steadily increased since it was first
`launched. Moreover, for the most recent quarter with available data, Copaxone® 40mg/mL had
`the highest number of total prescriptions, the second highest number of new prescriptions, and
`the second highest wholesale sales out of all drugs approved for the treatment of relapsing-forms
`of multiple sclerosis.
`Copaxone® 40mg/mL’s commercial success is attributable to its patented features, most
`15.
`notably its dosage regimen of three injections per week. Teva’s promotional materials
`consistently highlight the Copaxone® 40mg/mL dosing regimen, and surveys of physicians and
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`patients indicate that they value the dosing regimen of Copaxone® 40mg/mL. Analyst reports
`that discuss Copaxone® 40mg/mL’s successful launch also highlight that the product’s success is
`due to the improved dosing frequency.
`The large number of patients that switched from Copaxone® 20mg/mL to Copaxone®
`16.
`40mg/mL following the launch of Copaxone® 40mg/mL confirms the preference of patients and
`physicians for Copaxone® 40mg/mL over Copaxone® 20mg/mL. Furthermore, the introduction
`of Copaxone® 40mg/mL appears to have helped reverse a decline in Copaxone® 20mg/mL
`prescriptions that started in 2013 after the introduction of new oral competitors.
`The flow of new prescriptions for Copaxone® 40mg/mL after the entry of a generic
`17.
`product for Teva’s Copaxone® 20mg/mL product, Glatopa™, further demonstrates that
`Copaxone® 40mg/mL’s commercial success is due to its unique dosing regimen and
`corresponding benefits. The steady flow of new prescriptions for Copaxone® 40mg/mL after the
`launch of a less expensive generic with the same active ingredient indicates that Copaxone®
`40mg/mL’s success stems from its patented features and three injections per week dosing
`regimen.
`The patents covering the active ingredient of Copaxone® did not block other companies
`18.
`from researching new formulations or dosage regimens of Copaxone®. In fact, under the Hatch-
`Waxman Act companies can perform research on patented compounds, and if a company
`develops a method of use or a formulation patent on a compound patented by another company,
`the two companies can sign licensing agreements that allow one of them to market the product.
`Finally, Copaxone® 40mg/mL’s commercial success is not attributable to excessive
`19.
`marketing of the product by Teva. The content of Copaxone® 40mg/mL’s marketing materials
`addressing physicians and patients is primarily educational. Furthermore, marketing
`expenditures for Copaxone® 40mg/mL have been modest, and the marketing-to-sales ratio for
`Copaxone® 40mg/mL has been lower than that for other drugs recently approved for the
`treatment of relapsing-forms of multiple sclerosis.
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`IV.
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`Background on Copaxone® and Other Drugs for the Treatment of Relapsing-Forms
`of Multiple Sclerosis
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`20. Multiple sclerosis is a “disease of the central nervous system that disrupts the flow of
`information within the brain, and between the brain and the body.”1 For individuals with
`multiple sclerosis, the “immune system attacks myelin,” or the “substance that surrounds and
`insulates the nerve fibers,” leading to scar tissue.2 The presence of this scar tissue causes the
`distortion or interruption of nerve impulses, which can lead to several types of symptoms
`including fatigue, difficulty walking, numbness, tingling, spasticity, weakness, problems with
`vision, and other symptoms.3 The most common type of multiple sclerosis is relapsing-remitting
`multiple sclerosis, in which individuals experience “clearly defined attacks of worsening
`neurologic function,” or relapses, “followed by partial or complete recovery periods,” or
`remissions.4
`Copaxone® is an injectable prescription drug administered subcutaneously for the
`21.
`treatment of relapsing-forms of multiple sclerosis.5 The active ingredient in Copaxone® is
`glatiramer acetate.6 Teva currently produces two formulations of Copaxone®: Copaxone®
`20mg/mL, which is injected daily, and Copaxone® 40mg/mL, which is injected three times per
`week.7 The FDA approved the 20mg formulation in December 1996 while the FDA approved
`the 40mg/mL formulation in January 2014; see Exhibit 2107.
`22.
`Other drugs frequently prescribed for the treatment of relapsing-forms of multiple
`sclerosis include Aubagio®, Avonex®, Betaseron®, Extavia®, Gilenya®, Glatopa™, Lemtrada®,
`
`
`1 National Multiple Sclerosis Society, “What Is MS?” available at http://www.nationalmssociety.org/What-is-MS (last
`visited on 11/12/2015).
`2 National Multiple Sclerosis Society, “Definition of MS,” available at http://www.nationalmssociety.org/What-is-
`MS/Definition-of-MS (last visited on 11/12/2015).
`3 National Multiple Sclerosis Society, “Definition of MS,” available at http://www.nationalmssociety.org/What-is-
`MS/Definition-of-MS (last visited on 11/12/2015); National Multiple Sclerosis Society, “MS Symptoms,” available at
`http://www.nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms (last visited on 11/12/2015).
`4 National Multiple Sclerosis Society, “Types of MS,” available at http://www.nationalmssociety.org/What-is-
`MS/Types-of-MS (last visited on 11/12/2015).
`5 Copaxone® label, January 28, 2014. I understand that treatments such as Copaxone® 40mg/mL for relapsing-forms
`of multiple sclerosis are designed to “[r]educe the frequency and severity of clinical attacks,” or relapses, and to
`“[r]educe the accumulation of lesions (damaged or active disease areas) within the brain and spinal cord,” for
`individuals with multiple sclerosis. National Multiple Sclerosis Society, “The MS Disease-Modifying Medications,”
`January 2015, available at http://www.nationalmssociety.org/dmd (last visited on 11/12/2015).
`6 Copaxone® label.
`7 Copaxone® label.
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`Plegridy®, Rebif®, Tecfidera®, and Tysabri®.8 Exhibit 2107 provides the formulation and date of
`FDA approval for all the drugs approved by the FDA for relapsing-forms of multiple sclerosis.
`Prior to 2010, all of the FDA-approved treatments for this indication, including Copaxone®
`20mg/mL, were injectable or intravenous drugs. In 2010, the FDA approved the first oral
`prescription drug for relapsing-forms of multiple sclerosis, Gilenya®; the FDA subsequently
`approved additional oral therapies for the disease in 2012 (Aubagio®) and 2013 (Tecfidera®).
`The FDA has also approved other injectable and intravenous treatments for relapsing-forms of
`multiple sclerosis since 2010, including Plegridy®, Lemtrada®, and Glatopa™.
`23.
`Of particular note is the most recent drug approved for the treatment of relapsing-forms
`of multiple sclerosis, Glatopa™. Glatopa™ was approved in April 2015 as the first substitutable
`generic equivalent for Copaxone®
` 20mg/mL.9
`
`V.
`
`Commercial Success of Copaxone® 40mg/mL
`
`A.
`
`Indicators of Commercial Success
`
`24.
`There are several indicators that can be used to examine whether a patented product has
`achieved commercial success. The important indicators for the success of a patented drug
`product include levels of, and growth trends in, the sales and prescriptions of the product. Levels
`of, and growth trends in, shares of sales and prescriptions relative to competing products are also
`indicators of commercial success.
`25.
`A product does not have to satisfy all of these indicators to be considered commercially
`successful. Rather, each of these indicators can demonstrate, either alone or together, the
`commercial success of a product.
`
`
`8 Aubagio® label, October 17, 2014; Avonex® label, August 28, 2014; Betaseron® label, September 25, 2015;
`Extavia® label, August, 14, 2015; Gilenya® label, August 4, 2015; Glatopa™ label, April 16, 2015; Lemtrada® label,
`November 14, 2014; Plegridy® label, August 15, 2014; Rebif® label, March 10, 2015; Tecfidera® label, December 3,
`2014; Tysabri® label, May 12, 2015. In addition to the prescription drugs approved for relapsing-forms of multiple
`sclerosis, the intravenous drug Novantrone® is approved for “reducing neurologic disability and/or the frequency of
`clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-
`remitting multiple sclerosis (i.e., patients whose neurologic status is significantly abnormal between relapses).”
`Novantrone® label, March 23, 2012.
`9 The active ingredient in Glatopa™, glatiramer acetate, is the same active ingredient as in Copaxone® 20mg/mL.
`Unlike other generic drugs which are named according to the active ingredient, Glatopa™ is sold under a trademarked
`name. See Glatopa™ label.
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`B.
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`Copaxone® 40mg/mL’s High Level of U.S. Sales and Continued Sales Growth
`Are Evidence of Its Commercial Success
`
`Copaxone® 40mg/mL has generated a high level of U.S. sales since it was first introduced
`26.
`to the market in January 2014, demonstrating the product’s commercial success. Exhibit 2108
`illustrates Copaxone® 40mg/mL’s quarterly wholesale sales based on data from IMS Health
`(“IMS”).10 Quarterly wholesale sales of Copaxone® 40mg/mL exceeded $
` million in the
`second quarter of 2014, the first full quarter of sales for the drug. Wholesale sales of Copaxone®
`40mg/mL have increased in nearly every quarter since the launch of the product, and by the
`second quarter of 2015 (the last full quarter of sales available in the data), quarterly wholesale
`sales had grown to over $
` million, a growth rate of over
` percent since the second quarter
`of 2014.11 In the first year of sales, January 2014 to December 2014, wholesale U.S. sales of
`Copaxone® 40mg/mL exceeded $
` billion. Overall, the product has generated over $
` billion
`in wholesale sales through August 2015 despite having only been on the market for 20 months.
`Copaxone® 40mg/mL has also sold a high number of wholesale extended units (i.e., the
`27.
`number of injectable units) since launch of the product. Exhibit 2109 graphs wholesale extended
`units of Copaxone® 40mg/mL by quarter using IMS data. Total extended units of Copaxone®
`40mg/mL grew from over
` million units in the second quarter of 2014 (the first full quarter of
`sales) to over
` million units in the second quarter of 2015 (the last full quarter of sales). This
`represents a growth rate of approximately
` percent in extended units sold. Through August
` million extended units of Copaxone® 40mg/mL have been sold, providing further
`2015, over
`evidence of Copaxone® 40mg/mL’s commercial success.
`
`C.
`
`Copaxone® 40mg/mL’s High Level of U.S. Prescriptions and Continued
`Growth in Prescriptions are Evidence of Its Commercial Success
`
`The total number of prescriptions for Copaxone® 40mg/mL has also grown considerably
`28.
`since the product was launched in January 2014, further demonstrating that the product is a
`
`
`10 IMS Health is a leading provider of pharmaceutical data, widely used by the pharmaceutical industry, government,
`and academia. IMS Health, “Our Company,” available at http://www.imshealth.com/en/about-us/our-company (last
`visited on 11/16/2015).
`11 The only quarter-to-quarter decline in wholesale sales occurred in the third quarter of 2015; however, wholesale
`sales for this quarter are estimated based on wholesale sales in July 2015 and August 2015 since wholesale sales
`are unavailable for September 2015 in the IMS data.
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`commercial success. Exhibit 2110 shows quarterly total prescriptions for Copaxone® 40mg/mL
`based on IMS data. Quarterly total prescriptions grew from approximately
` prescriptions
`in the first full quarter of sales (the second quarter of 2014) to over
` prescriptions in the
`third quarter of 2015, a growth rate of
` percent over this time period. In the first year of
`sales, January 2014 to December 2014, total prescriptions of Copaxone® 40mg/mL exceeded
`. Through September 2015, Copaxone® 40mg/mL has achieved over
` total
`prescriptions.
`29.
`IMS data also indicate a consistently high level of new prescriptions (all prescriptions
`excluding refills) for Copaxone® 40mg/mL, as shown in Exhibit 2111. In the second quarter of
`2014, the first full quarter of Copaxone® 40mg/mL sales, the product had over
` new
`prescriptions. In each subsequent quarter, the number of new prescriptions of Copaxone®
`40mg/mL exceeded
`.12 In the first year of sales, January 2014 to December 2014, new
`prescriptions of Copaxone® 40mg/mL exceeded
`. Through September 2015, Copaxone®
`40mg/mL has achieved nearly
` new prescriptions. The continued high level of total
`prescriptions and new prescriptions for Copaxone® 40mg/mL provides further evidence that the
`drug is a commercial success.
`
`D.
`
`Copaxone® 40mg/mL’s Performance Relative to Other Drugs for the
`Treatment of Relapsing-Forms of Multiple Sclerosis is Evidence of Its
`Commercial Success
`
`As another indicator of commercial success, I have examined Copaxone® 40mg/mL’s
`30.
`performance relative to other drugs approved for relapsing-forms of multiple sclerosis.
`31.
`Exhibit 2112 displays the relative share of wholesale sales from the fourth quarter of
`2009 to the third quarter of 2015 for each drug approved for relapsing-forms of multiple
`sclerosis.13 The share of wholesale sales for a given quarter is calculated by dividing the
`wholesale sales for a particular drug in that quarter by the total wholesale sales for the entire set
`of drugs approved for relapsing-forms of multiple sclerosis sold in that quarter. The chart shows
`
`
`12 The number of new prescriptions of Copaxone® 40mg/mL falls from one quarter to the next in some instances. In
`particular, the number of new prescriptions declines between the second and third quarter in both 2014 and 2015.
`This seasonal pattern of decreased new prescriptions in the third and fourth quarter of each year is also present for
`competing drugs.
`13 The multiple sclerosis drugs included in this chart include those drugs listed in Exhibit 2107.
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`a consistent rise in Copaxone® 40mg/mL’s share of total wholesale sales, growing from
`percent in the first quarter of 2014 to
` percent in the third quarter of 2015. Moreover,
`Copaxone® 40mg/mL’s wholesale sales have exceeded the sales of all other drugs approved for
`relapsing-forms of multiple sclerosis other than Tecfidera® in recent quarters. Copaxone®
`40mg/mL’s significant level of, and growth in, share of wholesale sales indicates its commercial
`success.
`Similarly, Exhibit 2113 graphs Copaxone® 40mg/mL’s relative share of total
`32.
`prescriptions and Exhibit 2114 graphs Copaxone® 40mg/mL’s relative share of new prescriptions
`among drugs approved for relapsing-forms of multiple sclerosis.14 Copaxone® 40mg/mL’s share
`of total prescriptions rose from
` percent in the first quarter of 2014 to
` percent in the third
`quarter of 2015. In fact, for both the second and third quarters of 2015, Copaxone® 40mg/mL
`was the market leader with more total prescriptions than any other drug approved for the
`treatment of relapsing-forms of multiple sclerosis. Copaxone® 40mg/mL’s share of new
`prescriptions has similarly increased since launch, rising from
` percent of new prescriptions in
`the first quarter of 2014 to
` percent of new prescriptions in the third quarter of 2015. In
`addition, Copaxone® 40mg/mL has had the second highest number of new prescriptions (after
`Tecfidera®) in every quarter since the first quarter of 2015. Copaxone® 40mg/mL’s significant
`share of total and new prescriptions provides further indication of the product’s commercial
`success.
`
`E.
`
`Analyst Reports Discuss Copaxone® 40mg/mL’s Commercial Success
`
`In order to further assess the commercial success of Copaxone® 40mg/mL, I have
`33.
`reviewed seven analyst reports discussing the market performance of Copaxone® 40mg/mL
`between February and April 2014 (the three months after Copaxone® 40mg/mL was approved by
`the FDA).15 The sales of Copaxone® 40mg/mL exceeded the expectations formulated by the
`analysts before its launch. Among others, a Morgan Stanley report from March 3, 2014 that
`
`
`14 The drug Tysabri® is subject to a restricted distribution program so the majority of Tysabri® prescriptions are not
`reported to IMS. As a result, I exclude Tysabri® from Exhibit 2113 and Exhibit 2114.
`15 These reports were obtained by searching Thompson One for "Copaxone" or "Teva" as the primary keywords, and
`for "Multiple Sclerosis" or "MS" as secondary keywords. From the search results, I selected the reports whose
`subtitles referenced either the performance of Copaxone® and its competitors, or general trends in multiple sclerosis
`drugs.
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`analyzed Copaxone® 40mg/mL’s new and total prescriptions featured the characterizations
`“Copax 3TW uptake strong” and “Teva’s 3TW launch upside surprise” in its subtitle and
`headline.16 Similarly, a Credit Suisse report from April 30, 2014 described the launch of
`Copaxone® 40mg/mL as “the best MS drug launch ever.”17 In particular, the number of total
`Copaxone® 40mg/mL prescriptions and its market share during the first eleven weeks after
`launch were considerably higher than the expectations expressed in an earlier Credit Suisse
`report from December 12, 2013.18 Furthermore, according to the Credit Suisse report from April
`30, 2014, the shift of patients from Copaxone® 20mg/mL to Copaxone® 40mg/mL “shows the
`obvious benefits of improved dosing frequency,” and among patients choosing Copaxone®
`40mg/mL there were “returning quitters” and switches from orals/interferons.19 As a result, the
`fact that Copaxone® 40mg/mL’s sales performance exceeded analysts’ expectations indicates its
`commercial success.
`
`VI.
`
`The Commercial Success of Copaxone® 40mg/mL is the Result of Its Patented
`Features
`
`A.
`
`The Patented Features of Copaxone® 40mg/mL Were Marketed by Teva and
`Valued by Physicians and Patients
`
`34.
`I understand that a patent can be found invalid if the invention described in the patent
`would have been considered “obvious” by a person of ordinary skill in the art based upon what
`was already known at the time of the invention. I also understand that the commercial success of
`a patented product is one type of evidence showing that the patented invention is not “obvious,”
`provided there is a “nexus” between the invention and its commercial success.
`In my opinion, the commercial success of Copaxone® 40mg/mL is attributable to the
`35.
`features claimed in the patents at issue in this matter. It is my understanding that the three
`patents at issue cover a “method of alleviating a symptom of relapsing-remitting multiple
`sclerosis” by administering glatiramer acetate according to a certain dosage regimen.20 In
`
`16 “Spec Pharmaceuticals,” Morgan Stanley, March 3, 2014. “3TW” stands for “three-times-a-week,” Exhibit 2141.
`17 “Global Biotechnology and Pharmaceuticals – AAN 2014,” Credit Suisse, April 30, 2014, Exhibit 2143.
`18 “Multiple Sclerosis: It’s a Revolution! (vs. Evolution),” Credit Suisse, December 12, 2013, Exhibit 2144; referenced
`in “Global Biotechnology and Pharmaceuticals – AAN 2014,” Credit Suisse, April 30, 2014, Exhibit 2143.
`19 “Global Biotechnology and Pharmaceuticals – AAN 2014,” Credit Suisse, April 30, 2014, Exhibit 2143.
`20 U.S. Patent No. 8,232,250; U.S. Patent No. 8,399,413; U.S. Patent No. 8,969,302.
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`Page 10
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`YEDA EXHIBIT NO. 2133
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`

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`particular, I understand that the patents claim a dosage regimen of three injections per week with
`at least one day between injections.21 This dosage regimen represents an advantage over
`Copaxone® 20mg/mL, which required daily injections. For example, I understand that the
`GLACIER Extension Study, which randomly assigned study participants to receive either the
`Copaxone® 40mg/mL product or the Copaxone® 20mg/mL product, demonstrated that the
`Copaxone® 40mg/mL product was perceived to be more convenient.22
`36.
`I have also reviewed the expert declaration of Dr. Fox in this matter and I understand that
`the introduction of Copaxone® 40mg/mL satisfied a “long-felt but unmet need” for a treatment of
`multiple sclerosis that offers “the same safety and efficacy as GA 20 mg daily” and is “more
`convenient and tolerable” relative to the daily Copaxone® 20mg/mL product.23 In particular,
`based on this declaration, I understand that the GALA study showed that the Copaxone®
`40mg/mL three times per week glatiramer acetate product is “a safe and effective alternate
`regimen for the treatment of MS,” and that it increases tolerability relative to the daily
`Copaxone® 20mg/mL product, due to the lower observed incidence of injection site reactions and
`of immediate post-injection reactions (“IPIRs”).24 Furthermore, based on Dr. Fox’s declaration, I
`understand that the GLACIER study established that the Copaxone® 40mg/mL three times per
`week glatiramer acetate product had a lower rate of injection-related adverse events (“IRAEs”)
`and therefore had a higher tolerability relative to the daily Copaxone® 20mg/mL product. I also
`understand that the GLACIER study established that the Copaxone® 40mg/mL three times per
`week glatiramer acetate product had a higher average perceived convenience score relative to the
`daily Copaxone® 20mg/mL product.25 Finally, I have reviewed the deposition of Dr. Green who
`testified that patients who talk to him about Copaxone® 40mg/mL most often do so because they
`prefer fewer injections.26
`Teva’s promotional materials for Copaxone® 40mg/mL have consistently highlighted the
`37.
`product’s dosage regimen and have focused on the flexibility of the three times per week dosing.
`
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`21 U.S. Patent No. 8,232,250; U.S. Patent No. 8,399,413; U.S. Patent No. 8,969,302.
`22 Wynn D., et al., “Patient Experience with Glatiramer Acetate 40 mg/1 mL Three-Times Weekly Treatment for
`Relapsing-Remitting Multiple Sclerosis: Results from the GLACIER Extension Study,” The American Academy of
`Neurology 2015 Annual Meeting, Washington, D.C., April 18–25, 2015.
`23 Declaration of Edward J. Fox, M.D., P