Filed: December 21, 2015
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`————————————————
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`————————————————
`
`MYLAN PHARMACEUTICALS INC.
`
`Petitioner,
`
`v.
`
`YEDA RESEARCH & DEVELOPMENT CO. LTD.
`
`Patent Owner.
`
`————————————————
`
`Case IPR2015-00644
`
`Patent No. 8,399,413
`
`————————————————
`
`UPDATED LIST OF PATENT OWNER’S EXHIBITS
`
` 
`
`          
`
` 
`
` 
`
` 
`
` 
`
` 
`
` 
`
` 
`
` 
`
`

`
`Pursuant to 37 C.F.R. § 42.63(e), Patent Owner submits the following
`
`current exhibit list.
`
` 
`
`  
`
`  Exhibit No.
`2001
`2002
`
`2003
`
`2004
`
`2005
`2006
`
`2007
`
`2008
`2009
`
`2010
`
`
`2011
`
`
`2012
`
`
`2013
`
`
`Description
`Teva Provides Update on Forte Trial (July 7, 2008)
`Franscisco J. Quintana et al., Systems Biology
`Approaches for the Study of Multiple Sclerosis, 12 J. Cellular &
`Molecular Med. 1087 (2008)
`David Virley, Developing Therapeutics for the
`Treatment of Multiple Sclerosis, 2 J. Am. Soc. Experimental
`Neurotherapeutics 638 (Oct. 2005)
`Manuel A. Friese et al., The Value of Animal Models for Drug
`Development in Multiple Sclerosis, 129 Brain 1940 (2006)
`Copaxone Prescribing Information (Jan. 2014)
`Dvora Teitelbaum et al., Suppression of Experimental
`Allergic Encephalomyelitis by a Synthetic Polypeptide, 1
`Eur. J. Immunology 242 (1971)
`Jill Conner, Glatiramer Acetate and Therapeutic Peptide
`Vaccines for Multiple Mclerosis,1 J. Autoimmun. & Cell Responses
`3 (2014)
`Copaxone, Physicians Desk Reference 3231 (62 ed. 2008)
`Wiebke Schrempf and Tjalf Ziemssen, Glatiramer
`Acetate: Mechanisms of Action In Multiple Sclerosis, 6
`Autoimmun. Rev. 469 (2007)
`V. Wee Yong, Differential Mechanisms of Action of
`Interferon-β and Glatiramer Acetate in MS, 59
`Neurology 802 (2002)
`Suhayl Dhib-Jalbut, Mechanisms of Action of
`Interferons and Glatiramer Acetate in Multiple Sclerosis,
`58 Neurology S3 (Supp. 4 2002)
`O. Neuhaus et al., Pharmacokinetics and Pharmacodynamics of the
`Interferon-Betas, Glatiramer Acetate, and Mitoxantrone in Multiple
`Sclerosis, 259 (1-2) J. Neurol. Sci. 27 (2007)
`Oded Abramsky et al., Effect of A Synthetic Polypeptide (COP 1)
`on Patients with Multiple Sclerosis and with Acute Disseminated
`Encephalomyelitis, 31 J. Neurol. Sci. 433 (1977)
`
` 
`
`2
`
`

`
` 
`
` 
`
`2014
`
`2015
`
`2016
`
`2017
`
`2018
`
`
`2019
`
`
`2020
`2021
`
`2022
`
`2023
`
`2024
`
`2025
`
`2026
`
`
`2027
`
`Murry B. Bornstein et al., Treatment of Multiple Sclerosis with a
`Synthetic Polypeptide: Preliminary Results, 105 Tran. Am. Neurol.
`Assoc. 348 (1980)
`Murry B. Bornstein et al., Multiple Sclerosis: Trial of a
`Synthetic Polypeptide, 11 Annals Neurology 317 (1982)
`Murry B. Bornstein et al., A Pilot Trial of COP 1 in
`Exacerbating-Remitting Multiple Sclerosis, 13 New Engl. J. Med.
`408 (1987)
`Sage Journals, Table of Contents,
`http://msj.sagepub.com/content/14/1_suppl.toc (Sept. 2008)
`Massimo Filippi et al., Effects of Oral Glatiramer
`Acetate on Clinical and MRI Monitored Disease Activity in Patients
`with Relapsing Multiple Sclerosis: A Multicentre, Double-Blind,
`Randomised, Placebo-Controlled Study,
`http://neurology.thelancet.com (Jan. 20, 2006)
`Yuval Ramot et al., Comparative Long-Term Preclinical Safety
`Evaluation of Two Glatiramoid Compounds (Glatiramer Acetate,
`Copaxone1, and TV-5010, Protiramer) in Rats and Monkeys, 40
`Toxicol. Pathways 40 (2012)
`U.S. Patent Application No. 2007/0161566 A1
`T. Ziemssen et al., Risk-benefit Assessment of Glatiramer Acetate in
`Multiple Sclerosis, 24(13) Drug Safety 979 (2001)
`Teva News Release, Phase III Data Published in Annals of
`Neurology Show That a Higher Concentration Dose of Glatiramer
`Acetate Given Three Times a Week Reduced Annualized Relapse
`Rates in the Treatment of Relapsing-Remitting Multiple Sclerosis
`(July 1, 2013)
`Omar Khan et al., Three Times Weekly Glatiramer Acetate in
`Relapsing–Remitting Multiple Sclerosis, 73 Annals Neurology 705
`(2013)
`Teva Press Release, Teva Reports First Quarter 2015 Results (April
`30, 2015)
`Kate McKeage, Glatiramer Acetate 40 mg/mL in Relapsing-
`Remitting Multiple Sclerosis: A Review, CNS Drugs (April 24,
`2015)
`K.P. Johnson et al., Copolymer 1 reduces relapse rate and improves
`disability in relapsing-remitting multiple sclerosis: Results of Phase
`III Multicenter, Double-Blind, Placebo-Controlled Trial, 45
`Neurology 1268 (1995)
`Intentionally left Blank
`
`3
`
`

`
` 
`
` 
`
`2028
`
`2029
`
`
`2030
`
`
`2031
`
`2032
`
`2033
`
`
`2034
`
`
`2035
`
`2036
`
`2037
`2038
`
`
`Giancarlo Comi, Forte: Results from a phase II, 1-year,
`Randomized, Double-blind, Parallel-Group, Dose-Comparison
`Study with Glatiramer Acetate in Relapsing-Remitting Multiple
`Sclerosis, Presented at World Congress on Treatment and Research
`in Multiple Sclerosis: 2008 Joint Meeting of the American,
`European, and Latin America Committees on Treatment and
`Research in Multiple Sclerosis, San Raffaele, Italy (ACTRIMS,
`ECTRIMS, LACTRIMS) (2008)
`Jerry S. Wolinsky et al., GLACIER: An Open-Label, Randomized,
`Multicenter Study to Assess the Safety and Tolerability of
`Glatiramer Acetate 40 mg Three-times Weekly Versus 20 mg Daily
`in Patients with Relapsing-Remitting Multiple Sclerosis, 4 Multiple
`Sclerosis & Related Disorders 370 (2015).
`Cinthia Farina et al., Treatment of Multiple Sclerosis with Copaxone
`(COP): Elispot Assay Detects COP-Induced Interleukin-4 and
`Interferon-Gamma Response in Blood Cells, 124 Brain 705 (2001).
`Marketing Materials, PRA, Multiple Sclerosis: Transform Your
`Clinical Trial with PRA (2012) (on file with author) (Peroutka Dep.
`Ex. 4).
`Opinion, Endo Pharmaceuticals, Inc. v. Mylan Pharmaceuticals,
`Inc., No. 11-cv-00717, Document 226 (D. Del. Jan. 28, 2014)
`(Peroutka Dep. Ex. 6).
`Donna Oksenberg et al., A Single Amino-Acid Difference Confers
`Major Pharmacological Variation Between Human and Rodent 5-
`HT1B Receptors, 360 Nature 161 (1992) (Peroutka Dep. Ex. 9).
`M. Shalit et al., Abstract, Copolymer-1 (Copaxone®) Induces a
`Non-Immunologic Activation of Connective Tissue Type Mast Cells,
`97 J. Allergy & Clinical Immunology 345 (1996) (Peroutka Dep.
`Ex. 12).
`Order, Endo Pharmaceuticals, Inc. v. Mylan Pharmaceuticals, Inc.,
`No. 11-cv-00717, Document 310 (D. Del. Apr. 8, 2014) (Peroutka
`Dep. Ex.15).
`Masha Fridkis-Hareli et al., Binding Motifs of Copolymer 1 to
`Multiple Sclerosis- and Rheumatoid Arthritis-Associated HLA-DR
`Molecules, 162 J. Immunology 4697 (1999).
`Notice of Abandonment, APN 11/651,212, USPTO (Mar. 9, 2010).
`Bernd Meibohm & Hartmut Derendorf, Basic Concepts of
`Pharmacokinetic/Pharmacodynamic (PK/PD) Modelling, 35 Int’l J.
`Clinical Pharmacology & Therapeutics 401 (1997).
`
`4
`
`

`
` 
`
` 
`
`2039
`
`
`2040
`
`
`2041
`
`2042
`
`
`2043
`
`
`2044
`
`
`2045
`
`
`2046
`
`2047
`
`2048
`(corrected)
`
`2049
`(corrected)
`
`2050
`(corrected)
`
`2051
`(corrected)
`
`Paul Henri Lambert & Philippe E. Laurent, Intradermal Vaccine
`Delivery: Will New Delivery Systems Transform Vaccine
`Administration?, 26 Vaccine 3197 (2008).
`Gregory M. Glenn et al., Transcutaneous Immunization and
`Immunostimulant Strategies: Capitalizing on the
`Immunocompetence of the Skin, 2 Expert Rev. Vaccines 253 (2003).
`C.D. Partidos et al., Immunity Under the Skin: Potential Application
`for Topical Delivery of Vaccines, 21 Vaccine 776 (2003).
`Chandrabali Ghose et al., Transcutaneous Immunization with
`Clostridium difficile Toxoid A Induces Systemic and Mucosal
`Immune Responses and Toxin A-Neutralizing Antibodies in Mice, 75
`Infection & Immunity 2826 (2007).
`Gregory M. Glenn et al., Cutting Edge: Transcutaneous
`Immunization with Cholera Toxin Protects Mice Against Lethal
`Mucosal Toxin Challenge, 161 J. Immunology 3211 (1998).
`Rina Aharoni et al., Specific Th2 Cells Accumulate in the Central
`Nervous System of Mice Protected Against Experimental
`Autoimmune Encephalomyelitis by Copolymer 1, 97 Proc. Nat’l
`Acad. Sci. U.S.A. 11,472 (2000).
`Ruth Arnon & Rina Aharoni, Mechanism of Action of Glatiramer
`Acetate in Multiple Sclerosis and Its Potential for the Development
`of New Applications, 101 Proc. Nat’l Acad. Sci. U.S.A. 14,593
`(2004).
`Haim Varkony et al., The Glatiramoid Class of Immunomodulator
`Drugs, 10 Expert Opinion Pharmacotherapy 657 (2009).
`G. Comi & L. Moiola, Glatiramer Acetate, 17 Neurologia 244
`(2002).
`S. Chabot et al., Cytokine Production in T Lymphocyte-Microglia
`Interaction Is Attenuated by Glatiramer Acetate: A Mechanism for
`Therapeutic Efficacy in Multiple Sclerosis, 8 Multiple Sclerosis 299
`(2002).
`Tjalf Ziemssen, Neuroprotection and Glatiramer Acetate: The
`Possible Role in the Treatment of Multiple Sclerosis, in Frontiers in
`Clinical Neuroscience 111 (2004).
`Hana Schmeisser et al., Radioiodination of Human Interferon-α2
`Interferes with Binding of C-Terminal Specific Antibodies, 238 J.
`Immunological Methods 81 (2000).
`Y. M. Efimova et al., Changes in the Secondary Structure of
`Proteins Labeled with 125I: CD Spectroscopy and Enzymatic Activity
`Studies, 264 J. Radioanalytical & Nuclear Chemistry 91 (2005).
`
`5
`
`

`
` 
`
` 
`
`2052
`(corrected)
`2053
`(corrected)
`2054
`(corrected)
`
`2055
`(corrected)
`
`2056
`(corrected)
`
`2057
`(corrected)
`
`2058
`(corrected)
`
`2059
`(corrected)
`
`2060
`(corrected)
`2061
`(corrected)
`
`2062
`(corrected)
`
`2063
`(corrected)
`
`2064
`(corrected)
`
`2065
`(corrected)
`
`P. L. Toutain & A. Bousquet-Mélou, Plasma Terminal Half-Life, 27
`J. Veterinary Pharmacology & Therapeutics 427 (2004).
`Graeme B. Ryan & Guido Majno, Acute Inflammation: A Review,
`86 Am. J. Pathology 183 (1977).
`M. Shalit et al., Abstract, Copolymer-1 (Copaxone®) Induces in
`Non-Immunologic Activation of Connective Tissue Type Mast Cells,
`97 J. Allergy & Clinical Immunology 345 (1996)
`Peter Imming et al., Drugs, Their Targets and the Nature and
`Number of Drug Targets, 5 Nature Revs. Drug Discovery 821
`(2006) (Erratum in: 6 Nature Revs. Drug Discovery 126 (2007)).
`Candace B. Pert & Solomon H. Snyder, Properties of Opiate-
`Receptor Binding in Rat Brain,70 Proc. Nat’l Acad. Sci. U.S.A.
`2243 (1973).
`Brent G. Petty et al., The Effect of Systemically Administered
`Recombinant Human Nerve Growth Factor in Healthy Human
`Subjects, 36 Annals Neurology 244 (1994)
`Stephen J. Peroutka, Antimigraine Drug Interactions with Serotonin
`Receptor Subtypes in Human Brain, 23 Annals Neurology 500
`(1988).
`ALK Hestvik et al., Multiple Sclerosis: Glatiramer Acetate Induces
`Anti-Inflammatory T Cells in the Cerebrospinal Fluid, 14 Multiple
`Sclerosis 749 (2008).
`Rina Aharoni, The Mechanism of Action of Glatiramer Acetate in
`Multiple Sclerosis and Beyond, 12 Autoimmunity Revs. 543 (2013).
`Danielle Burger et al., Glatiramer Acetate Increases IL-1 Receptor
`Antagonist but Decreases T Cell-Induced IL-1β in Human
`Monocytes and Multiple Sclerosis, 106 Proc. Nat’l Acad. Sci.
`U.S.A. 4355 (2009).
`Amélia Mendes & Maria José Sá, Classical Immunomodulatory
`Therapy in Multiple Sclerosis: How It Acts, How It Works, 69
`Arquivos Neuropsiquiatria 536 (2011).
`Rina Aharoni et al., Copolymer 1 Induces T Cells of the T Helper
`Type 2 That Crossreact with Myelin Basic Protein and Suppress
`Experimental Autoimmune Encephalomyelitis, 94 Proc. Nat’l Acad.
`Sci. U.S.A. 10821 (1997).
`Rina Aharoni et al., Bystander Suppression of Experimental
`Autoimmune Encephalomyelitis by T Cell Lines and Clones of the
`Th2 Type Induced by Copolymer 1, 91 J. Neuroimmunology 135
`(1998).
`Oliver Neuhaus et al., Mechanisms of Action of Glatiramer Acetate
`in Multiple Sclerosis, 56 Neurology 702 (2001).
`6
`
`

`
` 
`
` 
`
`2066
`(corrected)
`
`2067
`(corrected)
`
`2068
`(corrected)
`
`2069
`(corrected)
`
`2070
`(corrected)
`2071
`(corrected)
`
`2072
`(corrected)
`
`2073
`
`
`2074
`
`2075
`
`
`2076
`
`
`2077
`
`2078
`
`
`2079
`
`
`Tjalf Ziemssen et al., Glatiramer Acetate-Specific T-Helper 1- and
`2-Type Cell Lines Produce BDNF: Implications for Multiple
`Sclerosis Therapy, 125 Brain 2381 (2002).
`Ariel Miller et al., Treatment of Multiple Sclerosis with Copolymer-
`1 (Copaxone®): Implicating Mechanisms of Th1 to Th2/Th3
`Immune-Deviation, 92 J. Neuroimmunology 113 (1998).
`Oliver Neuhaus et al., Multiple Sclerosis: Comparison of
`Copolymer-1-Reactive T Cell Lines from Treated and Untreated
`Subjects Reveals Cytokine Shift from T Helper 1 to T Helper 2 Cells,
`97 Proc. Nat’l Acad. Sci. U.S.A. 7452 (2000).
`Petra W. Duda et al., Glatiramer Acetate (Copaxone®) Induces
`Degenerate, Th2-Polarized Immune Responses in Patients with
`Multiple Sclerosis, 105 J. Clinical Investigation 967 (2000).
`Shohei Hori et al., Control of Regulatory T Cell Development by the
`Transcription Factor Foxp3, 299 Science 1057 (2003).
`Mary E. Brunkow et al., Disruption of a New Forkhead/Winged-
`Helix Protein, Scurfin, Results in the Fatal Lymphoproliferative
`Disorder of the Scurfy Mouse, 27 Nature Genetics 68 (2001).
`Vissia Viglietta et al., Loss of Functional Suppression by CD4+
`CD25+ Regulatory T Cells in Patients with Multiple Sclerosis, 199
`J. Experimental Med. 971 (2004).
`Jian Hong et al., Induction of CD4+CD25+ Regulatory T Cells by
`Copolymer-I Through Activation of Transcription Factor Foxp3,
`102 Proc. Nat’l Acad. Sci. U.S.A. 6449 (2005).
`H. Wekerle et al., Cellular Immune Reactivity within the CNS, 9
`Trends Neurosci. 271 (1986).
`William F. Hickey, Migration of Hematogenous Cells Through the
`Blood-Brain Barrier and the Initiation of CNS Inflammation, 1
`Brain Pathology 97 (1991).
`Martin S. Weber et al., Multiple Sclerosis: Glatiramer Acetate
`Inhibits Monocyte Reactivity in Vitro and in Vivo, 127 Brain 1370
`(2004).
`Til Menge et al., Disease-Modifying Agents for Multiple Sclerosis:
`Recent Advances and Future Prospects, 68 Drugs 2445 (2008).
`J. C. Sodoyez et al., 125I-Insulin: Kinetics of Interaction with Its
`Receptors and Rate of Degradation in Vivo, 239 Am. J. Physiology
`E3 (1980).
`Victor J. Wroblewski VJ, Mechanism of Deiodination of 125I-Human
`Growth Hormone in Vivo: Relevance to the Study of Protein
`Disposition, 42 Biochemical Pharmacology 889 (1991).
`
`7
`
`

`
` 
`
` 
`
`2080
`
`
`2081
`
`
`2082
`
`
`2083
`
`
`2084
`
`
`2085
`
`
`2086
`
`2087
`
`
`2088
`
`
`2089
`
`
`2090
`
`
`2091
`
`
`Alastair Monro, The Paradoxical Lack of Interspecies Correlation
`Between Plasma Concentrations and Chemical Carcinogenicity, 18
`Reg. Toxicology & Pharmacology 115 (1993).
`Robert T. O’Neill, Secondary Endpoints Cannot Be Validly
`Analyzed If the Primary Endpoint Does Not Demonstrate Clear
`Statistical Significance, 18 Controlled Clinical Trials 550 (1997).
`Karsten Beer et al., The Prevalence of Injection-Site Reactions with
`Disease-Modifying Therapies and Their Effect on Adherence in
`Patients with Multiple Sclerosis: An Observational Study, 11 BMC
`Neurology 144 (2011).
`Tjalf Ziemssen & Wiebke Schrempf, Glatiramer Acetate:
`Mechanisms of Action in Multiple Sclerosis, 79 Int’l Rev.
`Neurobiology 537 (2007).
`Tjalf Ziemssen, Modulating Processes Within the Central Nervous
`System Is Central to Therapeutic Control of Multiple Sclerosis, 252
`J. Neurology V/38 (2005) (Suppl. 5).
`Tjalf Ziemssen et al., Presence of Glatiramer Acetate-Specific TH2
`Cells in the Cerebrospinal Fluid of Patients with Multiple Sclerosis
`12 Months After the Start of Therapy with Glatiramer Acetate, 1 J.
`Neurodegeneration & Regeneration 1 (2008).
`H.P. Rang et al., Pharmacology (5th ed. 2005).
`
`Donald W. Paty, The Interferon-β1b Clinical Trial and Its
`Implications for Other Trials, 36 Annals Neurology S113 (1994)
`(Supp.).
`Leonora K. Fisniku et al., Gray Matter Atrophy Is Related to Long-
`Term Disability in Multiple Sclerosis, 64 Annals Neurology 247
`(2008).
`Omar Khan et al., Three Times Weekly Glatiramer Acetate in
`Relapsing–Remitting Multiple Sclerosis, 73 Annals Neurology
`705 (2013).
`Phillip D. Rumrill Jr., Multiple Sclerosis: Medical and Psychosocial
`Aspects, Etiology, Incidence, and Prevalence, 31 J. Vocational
`Rehabilitation 75 (2009).
`H.T. Katz et al., Successful Desensitization to Glatiramer Acetate
`(Copaxone) in Two Patients with Multiple Sclerosis, 92 Abstract
`Book 167 (2004) (Presented at the American College of Allergy,
`Asthma & Immunology 2003 Annual Meeting, New Orleans, LA
`(Nov. 7-12, 2015)).
`
`8
`
`

`
` 
`
` 
`
`2092
`
`
`2093
`
`
`2094
`
`2095
`(corrected)
`2096
`
`2097
`
`2098
`(corrected)
`2099
`
`2100
`2101
`
`2102
`
`2103
`2104
`2105
`2106
`2107
`2108
`
`2109
`
`Maria Zellner et al., Quantitative Validation of Different Protein
`Precipitation Methods in Proteome Analysis of Blood Platelets, 26
`Electrophoresis 2481 (2005).
`Mariana Castells, Rapid Desensitization for Hypersensitivity
`Reactions to Medications, 29 Immunology & Allergy Clinics N.
`Am. 585 (2009).
`Robert Zivadinov et al., MRI Indicators of Brain Tissue Loss: 3-
`Year Results of the Glatiramer Acetate Low-Frequency
`Administration (GALA) Open-Label Extension Study in Relapsing-
`Remitting Multiple Sclerosis, Presented at The American Academy
`of Neurology 2015 Annual Meeting, Washington, DC (Apr. 18-25,
`2015)
`E. Rubinchik et al., Responsiveness of Human Skin Mast Cells to
`Repeated Activation: An in Vitro Study, 53 Allergy 14 (1998).
`Daniel Wynn et.al., Patient Experience with Glatiramer Acetate
`40mg/1 ml Three-Times Weekly Treatment for Relapsing-Remitting
`Multiple Sclerosis: Results from the GLACIER Extension Study,
`Presented at The 8th Congress of the Pan-Asian Committee for
`Treatment and Research in Multiple Sclerosis, Seoul, Republic of
`Korea (Nov. 19-21, 2015).
`Press Release, Biogen Idec, Inc., Avonex® (Interferon beta-1a) IM
`Injection (Oct. 2008) (on file with author).
`Prescribing Information, EMD Serono, Rebif Prescribing
`Information (Sept. 2009) .
`Prescribing Information, (Interferon beta-1b) Kit for subcutaneous
`use Highlights of Prescribing Information (Aug. 2009) (on file with
`author).
`Curriculum Vitae of Edward J. Fox. MD., PhD., FAAN
`Per Soelberg Sorensen et al., Clinical Importance of Neutralizing
`Antibodies Against Interferon Beta in Patients with Relapsing-
`Remitting Multiple Sclerosis, 362 Lancet 1184 (2003).
`Jan J. M. de Vijlder, Primary Congenital Hypothyroidism: Defects
`in Iodine Pathways, 149 Eur. J. Endocrinology 247 (2003).
`Peptide and Protein Drug Delivery (Vincent H. L. Lee ed., 1991).
`Curriculum Vitae of Dr. Henry George Grabowski
`List of Testimony of Henry G. Grabowski
`Documents Relied Upon (Grabowski)
`Table: Approval Timeline, Multiple Sclerosis Drugs
`Figure: Copaxone® 40mg/mL Wholesale Dollar Sales (Q1 2014-
`Q3 2015)
`Figure: Copaxone® 40mg/mL Extended Units (Q1 2014- Q3 2015)
`9
`
`

`
` 
`
` 
`
`2110
`
`2111
`
`2112
`
`2113
`
`2114
`
`2115
`2116
`
`2117
`
`2118
`
`2119
`2120
`2121
`
`2122
`2123
`
`
`2124
`
`2125
`
`2126
`
`
`2127
`
`2128
`
`Figure: Copaxone® 40mg/mL Total Prescriptions (Q1 2014- Q3
`2015)
`Figure: Copaxone® 40mg/mL New Prescriptions (Q1 2014- Q3
`2015)
`Figure: Multiple Sclerosis Drugs Share of Wholesale Dollar Sales
`(Q4 2009- Q3 2015)
`Figure: Multiple Sclerosis Drugs Share of Total Prescriptions (Q4
`2009- Q3 2015)
`Figure: Multiple Sclerosis Drugs Share of New Prescriptions (Q4
`2009- Q3 2015)
`Figure: Rationale for Requesting Copaxone
`Figure: Perception of 3-times-a-week Copaxone 40mg compared to
`Daily Copaxone 20mg
`Figure: Rationale for Discussing 20mg and 40mg for First Line
`Patients
`Figure: Perceptions of Copaxone® 40mg compared to Daily
`Generic GA
`Figure: Perceptions of Copaxone® 40mg vs. 20mg
`Figure: Copaxone® Total Prescriptions (Q4 2009- Q3 2015)
`Figure: Copaxone® 20 mg/mL, Copaxone® 40 mg/mL, and
`Glatopa™ Net Prescriptions Flow (10/26/12-10/9/15)
`Table: Total Promotional Spending to Sales Ratio
`G. Comi et al., Effect of Glatiramer Acetate on Conversion to
`Clinically Definite Multiple Sclerosis in Patients with Clinically
`Isolated Syndrome (PreCISe study): A Randomised, Double-Blind,
`Placebo-Controlled Trial, 374 Lancet 1503 (2009).
`R.M. Valenzuela et al., Clinical Response to Glatiramer Acetate
`Correlates with Modulation of IFN-γ and IL-4 Expression in
`Multiple Sclerosis, 13 Multiple Sclerosis 754 (2007).
`Y. Blanco et al., Effect of Glatiramer Acetate (Copaxone®) on the
`Immunophenotypic and Cytokine Profile and BDNF Production in
`Multiple Sclerosis: A Longitudinal Study, 406 Neurosci. Letters 270
`(2006).
`M. Chen et al., Sustained Immunological Effects of Glatiramer
`Acetate in Patients with Multiple Sclerosis Treated for over 6 Years,
`201 J. Neurological Sci. 71 (2002).
`Zhao Rong Chen et al., MU Receptor Binding of Some Commonly
`Used Opioids and Their Metabolites, 48 Life Sci. 2165 (1991).
`Alison Palkhivala, Doubling the Dose of Glatiramer Acetate Does
`Not Increase Efficacy, Medscape Medical News (Sept. 22, 2008).
`
`10
`
`

`
` 
`
` 
`
`2129
`(corrected)
`2130
`2131
`(corrected)
`2132
`2133
`(corrected-
`confidential)
`2134
`(corrected)
`2135
`2136
`
`2137
`
`2138
`
`Declaration of Edward J. Fox, MD., PhD
`
`Curriculum Vitae of Robert William Gristwood PhD
`Curriculum Vitae of Tjalf Ziemssen
`
`Ziemssen’s MS clinical trials
`Declaration of Henry G. Grabowski, Ph.D.
`
`Declaration of Robert William Gristwood, Ph.D.
`
`Declaration of Tjalf Ziemssen, M.D., Ph.D
`Declaration of John T. Bennett in support of Patent Owner’s
`Motion for Pro Hac Vice Admission of John T. Bennett Under 37
`C.F.R. § 42.10(c)
`Declaration of Daryl L. Wiesen in support of Patent Owner’s
`Motion for Pro Hac Vice Admission of Daryl L. Wiesen Under 37
`C.F.R. § 42.10(c)
`Declaration of Nicholas K. Mitrokostas in support of Patent
`Owner’s Motion for Pro Hac Vice Admission of Nicholas K.
`Mitrokostas Under 37 C.F.R. § 42.10(c)
`
`11
`
`

`
`CERTIFICATION OF SERVICE
`
`The undersigned hereby certifies that the foregoing UPDATED LIST OF
`
`PATENT OWNER’S EXHIBITS was served electronically via e-mail on
`
`December 21, 2015 on the following:
`
`Jeffrey W. Guise
`
`jguise@wsgr.com
`
`Brandon M. White
`
`BMWhite@perkinscoie.com
`
`Shannon Bloodworth
`
`Sbloodworth@perkinscoie.com
`
`David Anstaett
`
`DAnstaett@perkinscoie.com
`
`Richard Torczon
`
`rtorczon@wsgr.com
`
`/Elizabeth Holland/
`Counsel for Patent Owner
`
`Dated:
`
`December 21, 2015
`
`12
`
` 
`
`  
`
`   
`
`   
`
`