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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`MYLAN PHARMACEUTICALS INC. and MYLAN LABORATORIES
`LIMITED,
`Petitioner,
`
`v.
`
`UCB PHARMA GMBH,
`Patent Owner.
`
`Case No. IPR2016-00510
`
`Patent No. 6,858,650
`
`
`
`
`PATENT OWNER’S AMENDED LIST OF EXHIBITS PURSUANT TO 37
`C.F.R. § 42.63(e)
`
`Americas 92223096
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`

`

`IPR2016-00510
`Patent 6,858,650
`
`
`Description
`
`Exhibit
`No.
`2001 Memorandum Opinion, Pfizer Inc. et al. v. Sandoz, Inc. et al, 13-cv-
`01110 (D. Del.).
`2002 Declaration of William R. Roush.
`2003
`C.V. of William R. Roush.
`Lisbeth Nilvebrant et al., Tolterodine – A New Bladder Selective
`2004
`Muscarinic Receptor Antagonist: Preclinical Pharmacological and
`Clinical Data, 60 Life Sciences 1129 (1997) (“Nilvebrant 1997 II”).
`British Journal of Clinical Pharmacology (2011), 72(2), 235-246 – “A
`comprehensive non-clinical evaluation of the CNS penetration potential
`of antimuscarinic agents for the treatment of overactive bladder”; E.
`Callegari, B. Malhotra, P. Bungay, R. Webster, K. Fenner, S.
`Kempshall, J. LaPerle, M. Michel, G. Kay (“Callegari 2011”).
`Trial Transcript, July 13-16, 2015, Pfizer Inc. et al. v. Sandoz, Inc. et al,
`13-cv-01110 (D. Del.).
`The file history of United States Patent No. 7,384,980.
`2007
`2008 Urodynamics: Principles, Practice and Application (1994), 43-70 –
`“Pharmacologic treatment of voiding dysfunction”; A.J. Wein, P.A.
`Longurst, R.M. Levin. ("Wein 1994").
`2009 Detrol® LA Label 2004.
`2010
`File History for U.S.P.N. 6,713,464.
`2011
`File History for U.S.P.N. 7,230,030.
`2012
`File History for U.S.P.N. 6,858,650.
`Jeffrey P. Krise et al., Novel Prodrug Approach for Tertiary Amines:
`2013
`Synthesis and Preliminary Evaluation of N-Phosphonooxymethyl
`Prodrugs, 42 J. Med. Chem. 3094 (1999) (“Krise”).
`2014 A.A. Sinkula et al., Rationale for Design of Biologically Reversible
`Drug Derivatives: Prodrugs, 64 J. Pharm. Sci. 181 (1975) (“Sinkula”).
`2015 Hans Bundgaard, Novel Chemical Approaches in Prodrug Design, 16
`Drugs of the Future 443 (1991) (“Bundgaard (1991)”).
`2016 Michael W. Jann et al., Clinical Pharmacokinetics of the Depot
`Antipsychotics, 10 Clinical Pharmacokinetics 315 (1985) (“Jann”).
`R. Beresford et al., Haloperidol Decanoate a Preliminary Review of Its
`Pharmacodynamic and Pharmacokinetic Properties and Therapeutic
`Use in Psychosis, 22 Drugs 31 (1987) (“Beresford”).
`2018 United States Patent No. 7,384,980.
`
`2005
`
`2006
`
`2017
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`Americas 92223096
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`IPR2016-00510
`Patent 6,858,650
`
`2019 United States Patent No. 6,858,650.
`2020
`Transcript of the Deposition of Steven Patterson, Ph.D., dated October
`4, 2016, Case IPR2016-00510, Case IPR2016-00512, Case IPR2016-
`00514, Case IPR2016-00516, Case IPR2016-00517 (“Patterson Tr.”).
`2021 Declaration of Hans Maag, Sc.D.
`2022 Declaration of William R. Roush, Ph.D.
`2023 Declaration of Scott A. MacDiramid, M.D., FRCPSC.
`2024 Declaration of Leonard J. Chyall, Ph.D.
`2025 Declaration of Claus O Meese, Ph.D.
`2026
`Transcript of the Deposition of Culley C. Carson III, M.D., dated
`August 25, 2016, C.A. No. 15-cv-0079 (D. Del.).
`2026A Excerpts of Transcript of the Deposition of Culley C. Carson III, M.D.,
`dated August 25, 2016, C.A. No. 15-cv-0079 (D. Del.).1
`Transcript of the Deposition of David R. Janero, Ph.D., dated August
`16, 2016, C.A. No. 15-cv-0079 (D. Del.).
`2027A Excerpts of Transcript of the Deposition of David R. Janero, Ph.D.,
`dated August 16, 2016, C.A. No. 15-cv-0079 (D. Del.).2
`Jiunn H. Lin & Anthony Y.H. Lu, Role of Pharmacokinetics and
`Metabolism in Drug Discovery and Development, 49 Pharmacological
`Reviews 407 (1997) (“Lin & Lu”).
`2029 N. Brynne et al., Fluoxetine Inhibits the Metabolism of Tolterodine –
`Pharmacokinetic Implications and Proposed Clinical Relevance 48 BR.
`J. CLIN. PHARMACOL. 553-63 (“Brynne 1999”).
`C.V. of Hans Maag, Ph.D.
`2030
`2031 Alan J. Wein, Pharmacologic Options for the Overactive Bladder, 51
`Urology (SUPP. 2A) 43 (1998) (“Wein 1998”).
`Lisbeth Nilvebrant et al., Tolterodine – A New Bladder-Selective
`Antimuscarinic Agent, 327 Eur. J. Pharmacol. 196 (1997) (“Nilvebrant
`1997 III”).
`J. Andrew Fantl et al., Urinary Incontinence in Adults: Acute and
`Chronic Management, in Clinical Practice Guideline 1996 Update (U.S.
`Dep’t of Health & Human Servs., AHCPR Publication No. 96-0682,
`1996) (“AHCPR”).
`
`1 Served but not filed, as supplemental evidence, pursuant to 37 C.F.R. §
`42.64(b)(2).
`2 Served but not filed, as supplemental evidence, pursuant to 37 C.F.R. §
`42.64(b)(2).
`
`
`2032
`
`2027
`
`2028
`
`2033
`
`Americas 92223096
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`IPR2016-00510
`Patent 6,858,650
`
`
`2040
`
`2041
`
`2034 H. Madersbacher et al., Trospium Chloride Versus Oxybutynin: A
`Randomized, Double-Blind, Multicentre Trial in the Treatment of
`Detrusor Hyper-Reflexia, 75 Br. J. Urol. 452 (1995).
`2035 G. Schladitz-Keil et al., Determination of the Bioavailability of the
`Quaternary Ammonium Compound Trospium Chloride in Man from
`Urinary Excretion Data, 36 Arzneimittel Forschung/Drug Res. 984
`(1986).
`2036 Ditropan XL® Prescribing Information, Revised 07/2013.
`R.J. Baigre et al., Oxybutynin: Is It Safe?, 62 Brit. J. Urol. 319 (1988).
`2037
`2038 H. Madersbacher et al., A Urodynamically Controlled Multicenter
`Study in Patients with Urge Incontinence: Tolerability and Efficacy of
`Propiverine Hydrochloride
`in Comparison
`to Oxybutynin,
`in
`International Continence Society, 27th Annual Meeting, Yokohama,
`Abst. 187 (Sept. 1993) (“Madersbacher”).
`2039 Hiroyuki Miyachi et al., Novel Imidazole Derivatives with Subtype-
`Selective Antimuscarinic Activity (1), 8 Bioorg. Med. Chem. Lett. 2163
`(1998) (“Miyachi”).
`Lisbeth Nilvebrant, Clinical Experiences with Tolterodine, 68 Life. Sci.
`2549 (2001) (“Nilvebrant 2001”).
`Carolyn M. Smith & Rob M. Wallis, Characterization of [3H]-
`Darifenacin as a Novel Radioligand for the Study of Muscarinic M3
`Receptors, 17 J. Recept. Signal Tr. R. 177 (1997).
`2042 Karl-Erik Andersson, The Overactive Bladder: Pharmacologic Basis of
`Drug Treatment, 50 Urology (SUPP. 6A) 44 (1997) (“Andersson
`1997”).
`Taniguchi et al., Agents for the Treatment of Overactive Detrusor. IX.
`Synthesis and Pharmacological Properties of Metabolites of N-tert-
`Butyl-4,4-diphenyl-2-cyclopentenylamine (FK584) in Human Urine, 44
`CHEM. PHARM. BULL. 1188, (1996).
`2044 Yasuo Sasaki et al., Effect of NS-21, an Anticholinergic Drug with
`Calcium Antagonistic Activity, on Lower Urinary Tract Function in a
`Rat Model of Urinary Frequency, 4 Int. J. Urol. 401 (1997) (“Sasaki
`(1997)”).
`2045 Hiroaki Kikukawa, Pharmacologic Actions of Temiverine (p-INN) and
`its Active Metabolite, RCC-36, on Isolated Human Urinary Bladder
`Muscle, 5 Int. J. Urol. 268 (1998).
`2046 N. Mealy & J. Castañer, YM-905, 24 Drugs Future 871 (1999) (“Mealy
`& Castañer”).
`
`2043
`
`
`
`Americas 92223096
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`
`
`2047
`
`2050
`
`2051
`
`2052
`
`2056
`
`2057
`
`L.P. Balant et al., Prodrugs for the Improvement of Drug Absorption
`via Different Routes of Administration, 15 European J. Drug
`Metabolism & Pharmacokinetics 143 (1990) (“Balant”).
`2048 Kevin Beaumont et al., Design of Ester Prodrugs to Enhance Oral
`Absorption of Poorly Permeable Compounds: Challenges to the
`Discovery Scientist, 4 Curr. Drug. Metab. 461 (2003) (“Beaumont”).
`2049 Valentino J. Stella et al., Prodrugs and Site-Specific Drug Delivery, 23
`J. Medicinal Chemistry 1275 (1980) (“Stella”).
`from Marketed and
`Peter Ettmayer et al., Lessons Learned
`Investigational Prodrugs, 47 J. Med. Chem. 2393 (2004) (“Ettmayer”).
`Bruce D. Roth et al., Relationship Between Tissue Selectivity and
`Lipophilicity for Inhibitors of HMG-CoA Reductase, 34 J. Med. Chem.
`463 (1991) (“Roth”).
`J. Magyar et al., Effects of Norfluoxetine on the Action Potential and
`Transmembrane Ion Currents in Canine Ventricular Cardiomyocytes,
`370 Naunyn Schmiedebergs Arch. Pharmacol. 203 (2004) (“Magyar”).
`2053 United States Patent No. 5,382,600 (the “‘600 patent”).
`2054
`Prescribing Information for Accupril® retrieved on March 10, 2015.
`2055 Milind M. Narurkar et al., Synthesis, Physicochemical Properties, and
`Cytotoxicity of a Series of 5'-Ester Prodrugs of 5-Iodo-2'-
`Deoxyuridine, 5 Pharm. Res. 734, 734 (1988) (“Narurkar”).
`Thomas Hartung, Food for Thought Look Back in Anger – What
`Clinical Studies Tell Us About Preclinical Work, 30 Altex 275 (2013)
`(“Hartung”).
`Chart of FDA Approvals of New Drug Applications for New Molecular
`Entities and New Active Ingredients from January 1994 – December
`1998.
`2058 Daniel S. Sitar, Clinical Pharmacokinetics of Bambuterol, 31 Clin.
`Pharmacokinet. 246 (1996) (“Sitar”).
`J. Greg Slatter et al., Bioactivation of the Anticancer Agent CPT- 11 to
`SN-38 by Human Hepatic Microsomal Carboxylesterases and the in
`vitro Assessment of Potential Drug Interactions, 25 Drug Metabolism
`& Disposition 1157 (1997) (“Slatter”).
`C.V. of Scott A. MacDiramid, M.D., FRCPSC.
`Paul Abrams et al., The Standardisation of Terminology of Lower
`Urinary Tract Function, Neurourol. Uro. 21:167–78 (2002).
`2062 Abrams P, Cardozo L, Khoury S, Wein A (eds), Incontinence, 5th
`International Consultation on Incontinence (5th Ed. 2013).
`
`2059
`
`2060
`2061
`
`
`
`Americas 92223096
`
`4
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`IPR2016-00510
`Patent 6,858,650
`
`
`2063
`
`2065
`
`2066
`
`2067
`
`Paul Abrams et al., Overactive Bladder Significantly Affects Quality of
`Life, American Journal of Managed Care 6:11, S580-S590 (2000)
`(“Abrams 2000”).
`2064 Walter F. Stewart et al., The prevalence and impact of overactive
`bladder in the U.S.: results from the NOBLE program, Neurourol
`Urodyn. (2001).
`Christopher Chapple & Lisbeth Nilvebrant, Tolterodine: Selectivity for
`the Urinary Bladder Over
`the Eye (as Measured by Visual
`Accommodation) in Healthy Volunteers, Drugs R&D 2002, 3(2): 75-81.
`Christopher Chapple, et al., The Effects of Antimuscarinic Treatments
`in Overactive Bladder: An Update of a Systematic Review and Meta-
`Analysis, European Urology 54 (2008).
`FDA, Drugs@FDA:Ditropan, https://www.accessdata.fda.gov/scripts/
`cder/drugsatfda/ index.cfm (last visited Oct. 14, 2016).
`2068 Karl-Erik Andersson, Current Concepts in the Treatment of Disorders
`of Micturition, Drugs 35:477-494, 481 (1988) (“Andersson 1988”).
`2069 M.M.S. Stahl, Urodynamic and Other Effects of Tolterodine: a Novel
`Antimuscarinic Drug for the Treatment of Detrusor Overactivity,
`Neurourol. Uro. 14: 647-655 (1995).
`2070 Detrol® LA Prescribing Information, Revised 08/2012.
`Bimal Malhotra et al. Thorough QT Study with Recommended and
`2071
`Supratherapeutic Doses of Tolterodine, Clinical Pharmacology &
`Therapeutics 81:377-385 (2007).
`at
`available
`Package,
`2072 NDA
`20-771 Detrol Approval
`http://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20771_Detrol.c
`fm.
`2073 Martin C. Michel, Fesoterodine: A Novel Muscarinic Receptor
`Antagonist for the Treatment of Overactive Bladder Syndrome, Expert
`Opin. Pharmacother. 2008; 9: 1787-96.
`Bimal Malhotra, et al., The Design and Development of Fesoterodine as
`a Prodrug of 5-Hydroxymethyl Tolterodine (5-HMT), the Active
`Metabolite of Tolterodine, Current Medicinal Chemistry, 16:33, 4481-
`89 (2009).
`2075 Victor Nitti, et al., Fesoterodine is an Effective Antimuscarinic for
`Patients with Overactive Bladder (OAB): Results of a Phase 2 Trial.
`Paper presented at Int’l Continence Society, Montreal, Canada, August
`31-September 2, 2005, available at http://www.ics.org/Abstracts/
`Publish/43/000306.pdf.
`
`2074
`
`
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`Americas 92223096
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`IPR2016-00510
`Patent 6,858,650
`
`
`2076
`
`2077
`
`2080
`
`2082
`
`2083
`
`Christopher Chapple, Fesoterodine, a New Effective and Well-
`Tolerated Antimuscarinic for the Treatment of Urgency-Frequency
`Syndrome: Results of a Phase 2 Controlled Study, Neurourol. Urodyn.,
`23 (5-6) (2004) (“Chapple (2004)”).
`Chapple C, Van Kerrebroeck P, Tubaro A, et al. Clinical efficacy,
`safety, and tolerability of once-daily fesoterodine in subjects with
`overactive bladder. Eur Urol. 2007;52(4):1204-1212.
`2078 Nitti VW, Dmochowski R, Sand PK, et al. Efficacy, safety and
`tolerability of fesoterodine for overactive bladder syndrome. J Urol.
`2007; 178(6):2488-2494.
`2079 Dmochowski RR, Peters KM, Morrow JD, et al. Randomized, double-
`blind, placebo-controlled study of flexible-dose fesoterodine in subjects
`with overactive bladder. Urology. 2010; 75(1):62-68.
`Sender Herschorn et al., Efficacy and Tolerability of Fesoterodine in
`Men With Overactive Bladder: A Pooled Analysis of 2 Phase III
`Studies, J. Urology. 75 (5) 2010, 1149-1155.
`2081 Vik Khullar, et al., Fesoterodine Dose Response in Subjects with
`Overactive Bladder Syndrome, Female Urology (2008).
`Steve Chaplin and Adrian Wagg, Fesoterodine (Toviaz): New Option
`for Overactive Bladder, Prescriber 5
`(2008), available at
`www.prescriber.co.uk (Table 2).
`Bimal Malhotra, et al., Thorough QT Study of the Effect of
`Fesoterodine on Cardiac Repolarization, Int’l J. Pharmacology &
`Therapeutics, 48:309-18 (2010).
`2084 Gary Kay et al., Evaluation of Cognitive Function in Healthy Older
`Subjects Treated with Fesoterodine, Postgraduate Medicine, Volume
`124, Issue 3, 7-15. May 2012.
`Chapple, C. et al., Superiority of fesoterodine 8 mg vs 4 mg in reducing
`urgency urinary incontinence episodes in patients with overactive
`bladder: results of the randomised, double-blind, placebo-controlled
`EIGHT trial, Brit. J. Urology Int’l. (2014) 114:418-426.
`2086 Wyndaele, J.J. et al., Flexible dosing with fesoterodine 4 and 8 mg: a
`systematic review of data from clinical trials, Int’l J. Clin. Prac. (2014)
`68:7, 830-840.
`Sender Herschorn, et al., Comparison of Fesoterodine and Tolterodine
`Extended Release for the Treatment of Overactive Bladder: A Head-to-
`Head Placebo-Controlled Trial, BJU Int’l, 105:58-66 (2009).
`
`2085
`
`2087
`
`
`
`Americas 92223096
`
`6
`
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`

`

`IPR2016-00510
`Patent 6,858,650
`
`
`2088
`
`Steven A. Kaplan, et al., Superior Efficacy of Fesoterodine over
`Tolterodine Extended Release with Rapid Onset: a Prospective, Head-
`to-Head Placebo-Controlled Trial, Brit. J. Uro. 107, 1432-40 (2010).
`Christopher Chapple, et al., Comparison of Fesoterodine and
`Tolterodine in Patients with Overactive Bladder, BJU Int’l, 102:1128-
`32 (2008).
`Steven A. Kaplan, et al., Efficacy and Safety of Fesoterodine 8 mg in
`Subjects with Overactive Bladder after a Suboptimal Response to
`Tolterodine ER, Int’l J. Clin. Practice 68:9, 1065-1073 (2014).
`2091 MacDiarmid, S. Overactive Bladder: Improving the Efficacy of
`Anticholinergics by Dose Escalation, Current Urology Reports. 2003.
`4:446-451.
`C.V. of Leonard J. Chyall, Ph.D.
`“History of SPM 007” dated November 17, 2000.
`“Chemical Development Plan, Incontinence Project,” dated February
`20, 1998.
`“Timetable of the development of Fesoterodine.”
`“Minutes: Team Meeting, NCE Incontinence” [sic],” dated August 10,
`1998.
`“Chemical Development Plan, Incontinence Project,” dated February
`24, 1999.
`“Laborjournal: A. Cawello,” dated August 19, 1999.
`“NCE-Incontinence Meeting,” dated May 28, 1999.
`“Some information about SPM 8224” & “Some information about SPM
`8272.”
`Email from Dr. Christoph Arth to Dr. Claus Meese, dated August 31,
`1999.
`2102 Declaration of Kevin Adam Regarding Exhibit Nos. 2093-2101.3
`
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`2089
`
`2090
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`2092
`2093
`2094
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`2095
`2096
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`2097
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`2098
`2099
`2100
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`2101
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`
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`
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`3 Served but not filed, as supplemental evidence, pursuant to 37 C.F.R. §
`42.64(b)(2).
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`IPR2016-00510
`Patent 6,858,650
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`Respectfully submitted,
`
`Date: November 14, 2016
`
`
`
`
`
`
`WHITE & CASE LLP
`/Jeffrey J. Oelke/ (Electronically signed)
`Jeffrey J. Oelke, Reg. No. 37,409
`joelke@whitecase.com
`James S. Trainor, Jr., Reg. No. 52,297
`jtrainor@whitecase.com
`Robert E. Counihan, Reg. No. 61,382
`rcounihan@whitecase.com
`White & Case LLP
`1155 Avenue of the Americas
`New York, NY 10036
`(212) 819-8200
`
`Attorneys for UCB Pharma GmbH
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`
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`Americas 92223096
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`IPR2016-00510
`Patent 6,858,650
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`CERTIFICATE OF SERVICE
`
`The undersigned hereby certifies that a copy of the foregoing Patent
`
`Owner’s Amended List of Exhibits Pursuant to 37 C.F.R. § 42.63(e) was served
`
`on November 14, 2016, by filing this document through the Patent Review
`
`Processing System as well as delivering a copy via electronic mail upon the
`
`following attorneys of record for the Petitioner:
`
`Mitchell G. Stockwell, Reg. No. 39,389
`mstockwell@kilpatricktownsend.com
`D. Clay Holloway, Reg. No. 58,011
`cholloway@kilpatricktownsend.com
`Alyson L. Wooten, Reg. No. 58,045
`awooten@kilpatricktownsend.com
`Kilpatrick Townsend & Stockton LLP
`1100 Peachtree Street, NE Suite 2800
`Atlanta, Georgia 30309
`(404) 815-6500
`
`
`
`
`
`Date: November 14, 2016
`
`
`
`
`
`
`Americas 92223096
`
`
`/Jeffrey J. Oelke/ (Electronically signed)
`Jeffrey J. Oelke
`Reg. No. 37,409
`Phone: (212) 819-8200
`
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