`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`
`
`MYLAN PHARMACEUTICALS INC.
`and PFIZER INC.,
`Petitioners,
`
`v.
`
`SANOFI-AVENTIS DEUTSCHLAND GMBH,
`Patent Owner
`
`Case IPR2018-016761
`U.S. Patent No. 8,603,044
`
`
`
`
`
`PATENT OWNER’S SUR-REPLY
`
`
`
`
`
`
`
`
`
`
`1 Pfizer Inc., who filed a petition in IPR2019-00978, has been joined as petitioner in
`
`this proceeding.
`
`
`
`
`
`
`I.
`
`TABLE OF CONTENTS
`
`Page
`
`GROUND 1 DOES NOT RENDER THE CHALLENGED CLAIMS
`OBVIOUS ........................................................................................................ 1
`
`A.
`
`B.
`
`C.
`
`Steenfeldt-Jensen Does Not Suggest a Threaded Driver Tube ............. 1
`
`Even If Steenfeldt-Jensen Did Suggest a Threaded Driver Tube
`With Respect to Its First Embodiment, It Would Not Apply to
`the Fifth Embodiment ............................................................................ 1
`
`Even If Steenfeldt-Jensen Suggested a Threaded Driver Tube
`With Respect to Its First Embodiment, A POSA Would Not Be
`Motivated to Make Petitioners’ Modification to the Fifth
`Embodiment .......................................................................................... 3
`
`1.
`
`2.
`
`3.
`
`A High Injection Force Would Dissuade a POSA From
`Petitioners’ Modification ............................................................ 4
`
`Petitioners Argue that Their Modification is Obvious
`Solely On the Basis of Reasonable Expectation of Success
` ..................................................................................................... 4
`
`Sanofi Presented Non-Obviousness Arguments Beyond
`the Friction Collar Model ............................................................ 5
`
`D. Dr. Slocum’s Models Are Not Flawed .................................................. 5
`
`1.
`
`2.
`
`3.
`
`There is no Bias ........................................................................... 6
`
`The Analytical Model Tests Total Change in Friction ............... 7
`
`The Models Are Not Designed to Fail ........................................ 8
`
`E.
`
`Steenfeldt-Jensen Does Not Teach or Suggest an Internally
`Threaded Driver Tube in the Form of an Integrated Nut Member
`at Column 3, Lines 41-47 ...................................................................... 9
`
`1.
`
`Steenfeldt-Jensen Does Not Teach a Nut Member
`Integrally With a Driver Tube ................................................... 10
`i
`
`
`
`2.
`
`Steenfeldt-Jensen Does Not Suggest an Nut Member
`Integrally Formed With a Driver Tube ..................................... 11
`
`F.
`
`The Board Should Reject Petitioners’ New Argument that
`Steenfeldt-Jensen Suggests a Threaded Driver Tube Because of
`Disclosures in Giambattista ................................................................. 12
`
`II.
`
`GROUND 2 DOES NOT RENDER THE CHALLENGED CLAIMS
`OBVIOUS ...................................................................................................... 13
`
`A. A POSA Would Not Be Motivated To Combine Møller’s First
`and Second Embodiments ................................................................... 14
`
`B. Møller’s First and Second Embodiments Are Not Structurally or
`Functionally Equivalent ...................................................................... 16
`
`C. Møller And Steenfeldt-Jensen Do Not Render Obvious A Dose
`Dial Sleeve With Grooves On Its Outer Surface ................................ 17
`
`D. Møller and Steenfeldt-Jensen Do Not Render Obvious A Clicker
`With A Flexible Arm And Splines ...................................................... 18
`
`III. CONCLUSION .............................................................................................. 20
`
`
`
`
`ii
`
`
`
`
`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`Cases
`In re Gordon, 733 F.2d 900 ....................................................................................... 5
`Integra Lifesciences I, Ltd. v. Merck KGaA,
`496 F.3d 1334 (Fed. Cir. 2007) .............................................................................. 6
`Intelligent Bio-Systems, Inc. v. Illumina Cambridge Ltd.,
`821 F.3d 1359 (Fed. Cir. 2016) ................................................................. 5, 14, 19
`KSR Intern. Co. v. Teleflex, Inc.,
`550 U.S. 398 (2007) ............................................................................................. 19
`Personal Web Techs., LLC v. Apple, Inc.,
`848 F.3d 987 (Fed. Cir. 2017) .............................................................................. 14
`
`Plas-Pak Indus. v. Sulzer Mixpac AG
`600 F. App’x 755 (Fed. Cir. 2015) ........................................................................ 5
`Statutes and Regulations
`35 U.S.C. § 24 ............................................................................................................ 7
`35 U.S.C. §316(e) .................................................................................................... 17
`37 CFR § 42.24(a)(1)(i) ........................................................................................... 23
`37 CFR § 42.6(a)(2)(ii) ............................................................................................ 23
`37 CFR § 42.8 .......................................................................................................... 23
`
`
`
`
`iii
`
`
`
`
`
`
`
`Exhibit #
`
`2001
`
`2002
`
`2003
`
`2004
`
`2005
`
`2006
`
`2007
`
`2008
`
`2009
`
`2010
`
`EXHIBIT LIST
`
`Description
`Press Release, “Mylan Enhances Partnership with Biocon through
`Strategic Collaboration for Insulin Products”, Feb. 13, 2013 (PR
`Newswire), available at http://newsroom.mylan.com/press-
`releases?item=122834
`Press Release, “Mylan Commences Phase III Clinical Trials for
`its Generic Version of Advair Diskus® and Insulin Analog to
`Lantus®”, Sept. 16, 2014 (PR Newswire), available at
`http://newsroom.mylan.com/press-releases?item=123251
`Press Release, “Mylan and Biocon Present Clinical Data on
`Insulin Glargine at the American Diabetes Association’s 77th
`Scientific Sessions”, June 10, 2017 (PR Newswire), available at
`http://newsroom.mylan.com/2017-06-10-Mylan-and-Biocon-
`Present-Clinical-Data-on-Insulin-Glargine-at-the-American-
`Diabetes-Associations-77th-Scientific-Sessions
`Complaint for Patent Infringement, Sanofi-Aventis U.S. LLC,
`Sanofi-Aventis Deutschland GmbH v. Eli Lilly and Company,
`C.A. No. 1-14-cv-00113-RGA (D. Del), Dkt. No. 1
`Complaint for Patent Infringement, Sanofi-Aventis U.S. LLC,
`Sanofi-Aventis Deutschland GmbH, and Sanofi Winthrop
`Industrie v. Merck Sharp & Dohme Corp., C.A. No. 1-16-cv-
`00812-RGA (D. Del), Dkt. No. 1
`Stipulation and Proposed Order, Sanofi-Aventis U.S. LLC v.
`Mylan, N.V., Civil Action No. 17-9105-SRC-SLW (D.N.J. Feb 5,
`2018), Dkt. No. 45
`Complaint for Patent Infringement, Sanofi-Aventis U.S. LLC et al.
`v. Mylan N.V. et al., Case No. 2:17-cv-09105-SRC-CLW (D.N.J.
`Oct. 24, 2017), Dkt. No. 1
`Excerpts from Defendants’ Invalidity Contentions, dated Jan. 25,
`2018, Sanofi-Aventis U.S. LLC et al. v. Mylan N.V. et al., Case
`No. 2:17-cv-09105-SRC-CLW (D.N.J.)
`Excerpts from Mylan GMBH’s Amended Invalidity Contentions,
`dated April 25, 2018, Sanofi-Aventis U.S. LLC et al. v. Mylan
`N.V. et al., Case No. 2:17-cv-09105-SRC-CLW (D.N.J.)
`Excerpts from Mylan GMBH’s Exhibit C to Amended Invalidity
`
`iv
`
`
`
`
`
`Exhibit #
`
`2011
`
`2012
`
`2013
`
`2014
`2015
`
`2016
`
`2017
`2018
`
`2019
`
`2020
`
`2021
`
`2022
`
`2023
`
`Description
`Contentions, dated April 25, 2018, Sanofi-Aventis U.S. LLC et al.
`v. Mylan N.V. et al., Case No. 2:17-cv-09105-SRC-CLW (D.N.J.)
`Aug. 13, 2018 Service of Sanofi’s Responses to Mylan’s
`Amended Contentions, Sanofi-Aventis U.S. LLC et al. v. Mylan
`N.V. et al., Case No. 2:17-cv-09105-SRC-CLW (D.N.J.)
`MP4 file of Sanofi’s Patented Pen animation
`Excerpt from Defendants’ opening claim construction brief, dated
`October 12, 2018, Sanofi-Aventis U.S. LLC et al. v. Mylan N.V. et
`al., Case No. 2:17-cv-09105-SRC-CLW (D.N.J.)
`Memorandum Opinion, Sanofi-Aventis U.S. LLC v. Merck Sharp
`& Corp., Case No. 16-cv-812-RGA (D. Del.), Dkt. No. 192
`International Patent WO 99/3855
`Excerpt from Joint claim construction statement, Ex. A, dated
`October 8, 2018, Sanofi-Aventis U.S. LLC et al. v. Mylan N.V. et
`al., Case No. 2:17-cv-09105-SRC-CLW (D.N.J.)
`Animation depicting Møller’s first embodiment
`Animation depicting Møller’s second embodiment
`Defendants Opposition to Plaintiffs Motion to Stay dated Nov.
`22, 2017, Sanofi-Aventis U.S. LLC et al. v. Mylan N.V. et al.,
`Case No. 1:17-cv-00181-IMK (N.D. W. Va.), Dkt. No. 44
`Joint Proposed Discovery Plan dated Dec. 14, 2017, Sanofi-
`Aventis U.S. LLC et al. v. Mylan N.V. et al., Case No. 2:17-cv-
`09105-SRCCLW (D.N.J.)
`Letter from A. Calmann to Judge Waldor dated Apr. 24, 2018,
`Sanofi-Aventis U.S. LLC et al. v. Mylan N.V. et al., Case No.
`2:17-cv-09105-SRC-CLW (D.N.J.), Dkt. No. 90
`Motion to Expedite Defendants Motion Requesting an Expedited
`Scheduling Conference dated Nov. 22, 2017 , Sanofi-Aventis
`U.S. LLC et al. v. Mylan N.V. et al., Case No. 1:17-cv-00181-
`IMK (N.D. W. Va.), Dkt. No. 46
`Initial Planning Meeting Report and Discovery Proposals dated
`Dec. 22, 2017, Sanofi-Aventis U.S. LLC et al. v. Mylan N.V. et
`al., Case No. 1:17-cv-00181-IMK (N.D. W. Va.), Dkt. No. 61
`
`v
`
`
`
`
`
`Exhibit #
`
`2024
`
`2025
`
`2026
`
`2027
`2028-2099
`2100
`
`2101
`
`2102
`2103
`
`2104
`
`2105
`2106
`
`2107
`2108
`2109
`2110
`2111
`2112
`2113
`
`2114
`
`Description
`Transcript of Motion / Scheduling Conference dated Jan. 3,
`2018,Sanofi-Aventis U.S. LLC et al. v. Mylan N.V. et al., Case
`No. 1:17-cv-00181-IMK (N.D. W. Va.), Dkt. No. 64
`Redline of Amended Patent Owner Preliminary Response (filed
`February 20, 2019)
`Report of the Local Patent Rules Committee, Explanatory Notes
`for 2016 Amendments
`Transcript, Conference Call for Case IPR2018-01675, -01676, -
`01678, -01680 (P.T.A.B. Feb. 5, 2019)
`Reserved
`Leinsing Deposition Exhibit 2100: Thomas van der Burg,
`Injection Force of SoloSTAR® Compared with Other Disposable
`Insulin Pen Devices at Constant Volume Flow Rates, J. of
`Diabetes Sci. and Tech., Vol. 5, Issue 1, 150-155 (Jan. 2001)
`Leinsing Deposition Exhibit 2101: Estelle Davis, et. al., An
`evaluation of prefilled insulin pens: a focuse on the Next
`Generation FlexPen®, Med. Devices: Evidence & Research, 41-
`50 (2010:3)
`Leinsing Deposition Exhibit 2102: Hand drawings
`Leinsing Deposition Exhibit 2103: Annotations of Figures 6-15 of
`Burroughs
`Leinsing Deposition Exhibit 2104: Annotations of Figures 5-8 of
`the 486 Patent
`Leinsing Deposition Exhibit 2105: Hand drawings
`Leinsing Deposition exhibit 2106: Annotations of Figures 11 and
`12 of Giambattista
`Declaration of Alexander Slocum, Ph.D.
`Curriculum Vitae of Alexander Slocum, Ph.D.
`Expert Report of Henry R. Grabowski, Ph.D.
`Curriculum Vitae of Henry R. Grabowski, Ph.D.
`Declaration of Dr. Robin S. Goland
`Curriculum Vitae of Dr. Robin S. Goland
`Bradley M. Wright et al., A Review Of Insulin Pen Devices And
`Use In The Elderly Diabetic Population, 3 Clinical Medicine
`Insights: Endocrinology & Diabetes 54-63 (2010)
`Teresa L. Pearson, A-Practical-Review-of-Insulin-Pen-Devices,
`EMJ Diabet., 58-64 (2014:2)
`vi
`
`
`
`
`
`Exhibit #
`2115
`
`2116
`
`2117
`2118
`
`2119
`
`2120
`2121
`2122
`
`2123
`
`2124
`
`2125
`
`2126
`
`2127
`2128
`
`Description
`Arthritis & Diabetes, What do diabetes and arthritis have in
`common? Plenty., https://www.arthritis.org/living-with-
`arthritis/comorbidities/diabetes-and-arthritis/
`Andreas Bode, Development of the SoloSTAR insulin pen device
`design verification and validation, 6 Expert Opinion on Drug
`Delivery 103-112 (2008)
`Sanofi’s Patented Pen animation
`John Carter, Usability, Paticipant Acceptance, and Safety of a
`Prefilled Insulin Injection Device in a 3-Month Observational
`Survey in Everyday Clinical Practice in Australia, J. Diabetes Sci
`& Tech., Vol. 3, Issue 6, 1425-1438 (Nov. 2009)
`Sherwyn Schwartz, Correct Use of a New Reusable Insulin
`Injection Pen by Patients with Diabetes: A Design Validation
`Study, 4 J. Diabetes Sci. and Tech. 1229-1235 (2010)
`Reserved
`DBA Design Effectiveness Awards 2009
`SoloSTAR Disposable Pen Injector (The Grand Prix Oct. 22,
`2009)
`Arnd Friedrichs et al., Dose Accuracy and Injection Force of
`Different Insulin Glargine Pens, 7 J. Diabetes Sci. and Tech.
`1346-1353 (2013)
`Stacey A. Seggelke et al., Effect of Glargine Insulin Delivery
`Method (Pen Device Versus Vial/Syringe) on Glycemic Control
`and Patient Preferences in Patients with Type 1 and Type 2
`Diabetes, 20 ENDOCRINE PRACTICE, 536, 536, 538–539
`(2014)
`Julia Pfutzner et al., Evaluation of Dexterity in Insulin-Treated
`Patients with Type 1 and Type 2 Diabetes Mellitus, 5 J. Diabetes
`Sci. and Tech. 158-165 (2011)
`Jerome S. Fischer et al., United States Patient Preference and
`Usability for the New Disposable Insulin Device Solostar® versus
`Other Disposable Pens, 2 JOURNAL OF DIABETES SCIENCE
`AND TECHNOLOGY 1157-1160 (2008)
`U.S. Provisional Patent Application 60/073820
`Samita Garg et al., Insulin glargine and glulisine SoloSTAR pens
`for the treatment of diabetes, 5 Expert Rev. Med. Devices 113-
`123 (2008)
`
`vii
`
`
`
`
`
`Exhibit #
`2129
`
`2130
`
`2131
`
`2132
`
`2133
`2134
`
`2135
`
`2136
`2137
`2138
`
`2139
`
`2140
`
`2141
`
`2142
`
`Description
`Nicolae Hancu et al., A Pan-European and Canadian Prospective
`Survey to Evaluate Patient Satisfaction with the SoloSTAR Insulin
`Injection Device in Type 1 and Type 2 Diabetes, 5 J. Diabetes Sci.
`and Tech. 1224-1234 (2011)
`Norbert Hermanns, Bernhard Kulzer & Thomas Haak, Dosing
`Accuracy with a Novel Pen Device (SoloSTAR) as Performed by
`Patients with Diabetes in a Clinical Setting, 10 Diabetes Tech. &
`Threapeutics 322-327 (2008)
`ISO 11608-1, Pen-injectors for medical use (1st Ed. Dec. 15,
`2000)
`Meike Krzywon et al., Study on the Dosing Accuracy of
`Commonly Used Disposable Insulin Pens, 14 Diabetes Tech. &
`Therapeutics 804-809 (2012)
`Lantus SoloSTAR Pen Guide
`Arlan L. Rosenbloom, Limitation of Finger Joint Mobility in
`Diabetes Mellitus, 3 J. Diabetic Complications 77-87 (1989)
`Douglas Merritt et al., Dose Accuracy and Injection Force of
`Disposable Pens Delivering Pramlintide for the Treatment of
`Diabetes, 4 J. Diabetes Sci. and Tech. 1438-1446 (2010)
`
`Novo Nordisk Form 6-K (Feb. 9, 2009)
`Novo Nordisk History
`W. Schady et al, Observations on Severe Ulnar Neuropathy in
`Diabetes, 12 J Diabetes and Its Complications 128-132 (1998)
`
`Alfred Penfornis & Kristian Horvat, Dose Accuracy Compariosn
`Between SoloSTAR and FlexPen at Three Different Dose Levels,
`10 Diabetes Tech. & Therapeutics 359-362 (2008)
`
`Riccardo Perfetti, Reusable and Disposable Insulin Pens for the
`Treatment of Diabetes: Understanding the Global Differences in
`User Preference and an Evaluation of Inpatient Insulin Pen Use,
`12 Diabetes Tech. & Therapeutics 79-85 (2010)
`John Shelmet et al., Preference and resource utilization in elderly
`patients: InnoLet versus vial/syringe, 63 Diabetes Res. and
`Clinical Prac. 27-35 (2004)
`Prix Galien USA Announces 2009 Final Candidates (Prix Galien
`USA, August 7, 2009)
`
`viii
`
`
`
`
`
`Exhibit #
`2143
`
`2144
`
`2145
`
`2146
`
`2147
`2148
`2149
`2150
`2151
`
`2152
`
`2153
`2154
`2155
`2156
`2157
`2158
`
`2159
`
`2160
`
`2161
`
`2162
`
`Description
`Thomas Haak et al., Comparison of Usability and Patient
`Preference for the New Disposable Insulin Device SoloStar
`Versus FlexPen, Lilly Disposable Pen, and a Prototype Pen: An
`Open-Label Study, 29 CLINICAL THERAPEUTICS, 650-660
`(2007)
`Alastair Clarke & Geralyn Spollett, Dose accuracy and injection
`force dynamics of a novel disposable insulin pen, 4 EXPERT
`OPINION ON DRUG DELIVERY 165-174 (2007)
`US Lantus SoloSTAR Launch Book, 2007, PTX-0705, Document
`bates stamped SANOFI_00232909-45
`Lantus COMPASS Study Report (Nov. 29, 2007), PTX-0739,
`Document bates stamped SANOFI3_90330807-1025
`Steenfeldt-Jensen 5th Embodiment Animation
`Steenfeldt-Jensen 1st Embodiment Animation
`Steenfeldt-Jensen 2nd Embodiment Animation
`Steenfeldt-Jensen 5th Embodiment Thread and Slot Animation
`Steenfeldt-Jensen 5th Embodiment vs. Proposed Modification
`Animation
`Steenfeldt-Jensen 5th Embodiment vs. Proposed Modification
`Collar Friction Animation
`International Patent Application WO999038554A1
`Reserved
`Reserved
`Reserved
`Declaration of Chris Langley
`Geralyn Spollett, Insulin Devices, Addressing Barriers to Insulin
`Therapy With the Ideal Pen, 957-967 (The Diabetes
`EDUCATOR)
`Serpil Savas et al., The effects of the diabetes related soft tissue
`hand lesions and the reduced hand strength on functional
`disability of hand in type 2 diabetic patients, 77 Diabetes Res. and
`Clinical Prac. 77-83 (2007)
`Jean-Louis Selam, Evolution of Diabetes Insulin Delivery
`Devices, 4 J. Diabetes Sci. and Tech. 505-513 (2010)
`SoloSTAR Principles of Operation, PTX-0553, Document bates
`stamped SANOFI_00406383-94
`Sanofi Patent Drive Sleeve and Piston Rod Animation
`ix
`
`
`
`
`
`Exhibit #
`2163
`
`2164
`
`2165
`
`2166
`
`2167
`2168
`2169
`2170
`2171
`2172
`
`2173
`
`2174
`
`2175
`
`2176
`
`2177
`
`2178
`
`Description
`Deposition of Karl R. Leinsing, dated June 3, 2019 for IPR2018-
`01675, -01676, -01678, -01680
`Deposition of Karl R. Leinsing, dated June 4, 2019 for IPR2018-
`01675, -01676, -01678, -01680
`Opinion and Order regarding Claim Construction, Sanofi-Aventis
`U.S. LLC v. Mylan, N.V., Civil Action No. 17-9105-SRC-SLW
`(D.N.J. May 9, 2019), Dkt. No. 319
`
`Memorandum and Order regarding Claim Construction, Sanofi-
`Aventis U.S. LLC v. Merck, No. 16-812-RGA (D. Del. Jan. 12,
`2018), Dkt. No. 192
`Giambattista Animation (1)
`Giambattista Animation (2)
`U.S. Patent No. 4,648,872
`U.S. Patent No. 4,747,824
`U.S. Patent No. 6,248,093
`Karl R. Leinsing Declaration in Hologic, Inc. v. Minerva
`Surgical, Inc., No. 15-1031 (D. Del. Jan. 26, 2018), Dkt. No. 309
`Bruce A. Perkins, David Olaleye & Vera Bril, Carpal Tunnel
`Syndrome in Patients With Diabetic Polyneuropathy, 25 Diabetes
`Care 565-569 (2002)
`Jefferson Becker et al., An evaluation of gender, obesity, age and
`diabetes mellitus as risk factors for carpal tunnel syndrome, 113
`Clinical Neurophysiology 1429-1434 (2002)
`A. Pfutzner et al., Prefilled insulin device with reduced injection
`force: patient perception and accuracy, 24 Current Med. Res. and
`Opinion 2545-2549 (2008)
`Ercan Cetinus et al., Hand grip strength in patients with type 2
`diabetes mellitus, Diabetes Res. and Clinical Prac. 1-9 (2005)
`Ragnhild I. Cederlund et al., Hand disorders, hand function, and
`activities of daily living in elderly men with type 2 diabetes, 23 J.
`Diabetes and Its Complications 32-99 (2009)
`Shubha Gundmi et al., Hand dysfunction in type 2 diabetes
`mellitus: Systematic review with meta-analysis, 61 Annals of
`Physical and Rehabilitation Med. 99-104 (2018)
`
`x
`
`
`
`
`
`Exhibit #
`2179
`
`2180
`
`2181
`
`2182
`
`2183
`
`2184
`
`2185
`
`2186
`2187
`2188
`2189
`2190
`2191
`
`2192
`
`2193
`
`2194
`
`2195
`
`Description
`Joule J. Li et al., Muscle grip strength predicts incident type 2
`diabetes: Population-based cohort study, 65 Metabolism Clinical
`and Experimental 883-892 (2016)
`Considering Insulin Pens for Routine Hospital Use - Consider
`This... (ISMP article),
`https://www.ismp.org/resources/considering-insulin-pens-routine-
`hospital-use-consider
`Trigger Finger Overview (Mayo Clinic),
`https://www.mayoclinic.org/diseases-conditions/trigger-
`finger/symptoms-causes/syc-20365100
`Bone and joint problems associated with diabetes (Mayo Clinic),
`https://www.mayoclinic.org/diseases-conditions/diabetes/in-
`depth/diabetes/art-20049314
`Peripheral Neuropathy (Mayo Clinic),
`https://www.mayoclinic.org/diseases-conditions/peripheral-
`neuropathy/symptoms-causes/syc-20352061
`Charles E. Buban, A pen that seeks to improve diabetes care,
`INQUIRER.NET (2008), Document Bates stamped
`SANOFI_00006282-84
`"Sanofi-aventis’ SoloSTAR(R) Insulin Pen for Lantus and Apidra
`Receives the Prestigious GOOD DESIGN Award", (PR Newswire
`Feb. 14), Document Bates stamped SANOFI_00006299-301
`
`Select Injectable Insulin Drugs Approved by the FDA in the U.S.
`U.S. Dollar Sales of Lantus SoloSTAR
`U.S. New Prescriptions of Lantus SoloSTAR
`U.S. Total Prescriptions of Lantus SoloSTAR
`U.S. Share of Sales by Drugs in the Lantus Franchise
`Formulary Placement of Long-Acting Insulin Pen Products:
`Commercial Plans
`Formulary Placement of Long-Acting Insulin Pen Products:
`Medicare Plans
`Formulary Placement of Long-Acting Insulin Pen Products:
`Medicaid Plans
`Formulary Placement of Long-Acting Insulin Pen Products in
`Healthcare Exchanges
`U.S. Share of Long-Acting Pens Among All Pens
`
`xi
`
`
`
`
`
`Exhibit #
`2196
`2197
`2198
`2199
`2200
`
`2201
`
`2202
`
`2203
`
`2204
`
`2205
`
`2206
`2207
`2208
`
`2209
`
`2210
`
`2211
`
`2212
`
`2213
`
`2214
`
`2215
`2216
`
`Description
`U.S. Dollar Sales of Long-Acting Pens
`U.S. New Prescriptions of Long-Acting Pens
`U.S. Total Prescriptions of Long-Acting Pens
`U.S. Share of Long-Acting Pen Products
`Yuzu Sato et al., Clinical Aspects of physical exercise for
`diabetes/metabolic syndrome, 77S Diabetes Research and Clinical
`Practice S87 (2007)
`2007 Good Design Award from The Chicago Athenaeum:
`Museum of Architecture and Design
`Reserved
`
`U.S. Total Marketing Expenditure of Long Acting Insulin
`Franchises
`U.S. Total Marketing Expenditures of Long-Acting Insulin Pens
`
`U.S. Marketing-to-Sales Ratios of Select Injectable Insulin Drugs
`
`Møller First Embodiment Animation
`Møller Second Embodiment Animation
`Press Release, Lantus / Apdira SoloSTAR help to improve patient
`satisfaction (June 27, 2011), Document bates stamped
`SANOFI_00179886-88
`Henry Grabowski, John Vernon & Joseph A. DiMasi, Returns on
`Research and Development for 1990s New Drug Introductions,
`20 Pharmacoeconomics 15 (2002)
`Julie M. Donohue, Marisa Cevasco & Meredith B. Rosenthal, A
`Decade of Direct-to-Consumer Advertising of Prescription
`Drugs, 357 N. Engl. J. Med. 673 (2007)
`Collar Friction Model Demonstrator Animation
`
`Excerpts from Ernest Rabinowicz, Friction And Wear of
`Materials, 2nd Edition, 68-70 (John Wiley & Sons, Inc. 1995)
`Reserved
`
`Excerpts from Alexander H. Slocum, Precision Machine Design,
`706-709 (Prentice-Hall, Inc. 1992)
`Collar Friction Model Demonstration 1
`Collar Friction Model Demonstration 2
`xii
`
`
`
`
`
`
`
`
`Exhibit #
`2217
`2218
`2219
`2220
`2221
`2222
`2223
`2224
`2225
`
`2226-2315
`2316
`
`2317
`2318
`2319
`
`Description
`Collar Friction Model Demonstration 3
`SoloSTAR Dial Inject Video
`Declaration of Robert Vlasis
`Biography of Robert Vlasis
`Declaration of Anna E. Dwyer
`Biography of Anna E. Dwyer
`SoloSTAR wins the 2008 Good Design award (February 8, 2008)
`Expert Opinion on Drug Delivery
`Excerpt from the Trial Transcript for Sanofi v. Merck, 16cv812
`(RGA) (District of Delaware) (May 29, 2018)
`Reserved
`Deposition of Karl Robert Leinsing, MSME, P.E. (October 10,
`2019)
`Deposition of William C. Biggs, MD (October 15, 2019)
`Deposition of DeForest McDuff, Ph. D. (October 9, 2019)
`Declaration of Robert Veasey (July 15, 2019)
`
`xiii
`
`
`
`
`
`For the reasons discussed in the Patent Owner Response (“Response”) and
`
`below, the Board should affirm the patentability of claims 11, 14, 15, 18, and 19
`
`over Petitioners’ challenge.
`
`I.
`
`GROUND 1 DOES NOT RENDER THE CHALLENGED CLAIMS
`OBVIOUS
`A.
`Steenfeldt-Jensen Does Not Suggest a Threaded Driver Tube
`As a threshold matter, Steenfeldt-Jensen nowhere discloses a threaded driver
`
`tube. See Response, 29-31. Accordingly, the parties’ arguments about whether
`
`Steenfeldt-Jensen at 7:41-47 can be applied to the fifth embodiment are beside the
`
`point. In Reply, Petitioners argue that Sanofi unduly focuses on whether 7:41-47
`
`disclosed a threaded driver tube and does not consider three other passages that
`
`purportedly support a threaded driver tube. Reply, 4 (citing EX1014, 2:40-53, 3:10-
`
`20, 3:41-47). Sanofi, however, discussed these passages in its Response, 29-31 and
`
`Petitioners do not rebut Sanofi’s arguments (Reply, 4).
`
`B.
`
`Even If Steenfeldt-Jensen Did Suggest a Threaded Driver Tube
`With Respect to Its First Embodiment, It Would Not Apply to the
`Fifth Embodiment
`Even if Steenfeldt-Jensen discloses a threaded driver tube, a POSA would not
`
`have applied it to the fifth embodiment (the basis of Petitioners’ challenge). Notably,
`
`Petitioners concede that the passage at 7:41-47 (the passage that purports to disclose
`
`a threaded driver tube) is not a blanket statement covering every embodiment in
`
`Steenfeldt-Jensen. Reply, 4. Petitioners now argue that despite no express recitation
`
`1
`
`
`
`
`
`that the passage applies to the fifth embodiment, a POSA would have recognized
`
`that it applies to the fifth embodiment due to the “analogous structures and functions
`
`for driving the piston rod” in the fifth embodiment. Reply, 5-7. Petitioners explain
`
`away the lack of an express statement linking the passage to the fifth embodiment
`
`by arguing that, “Steenfeldt-Jensen frequently avoids redundant disclosures, relying
`
`on POSAs to recognize earlier discussions apply to analogous aspects of later
`
`embodiments.” Reply, 5.
`
`Mr. Leinsing, however, acknowledges that there are differences between the
`
`embodiments (EX1095, ¶68). Conveniently, he simply states that “while certain
`
`surrounding components may differ between the first and fifth embodiments, [a
`
`POSA] would have understood the driver tubes. . . and nut members . . . were
`
`analogous, both structurally and functionally, for driving the piston.” EX 1106, ¶69.
`
`In contrast, the Response, 22-25 explains that the embodiments are not
`
`analogous and a POSA would not apply a teaching specific to the first embodiment
`
`to the fifth embodiment. The first embodiment, for example, includes a rotatable,
`
`threaded ampoule holder 2, while the fifth embodiment includes a fixed end wall 4
`
`with a threaded bore forming a nut member. These differences mandate completely
`
`different methods for dialing and dose dispensing. Id.
`
`Petitioners further argue that Sanofi’s arguments against combining the
`
`disclosure at 7:41-47 with the fifth embodiment are undercut by Dr. Slocum’s
`
`2
`
`
`
`
`
`testimony. Petitioners argue that Dr. Slocum testified that applying the disclosure
`
`to the first embodiment would impair the first embodiment’s function. Reply, 9-10.
`
`Petitioners contend that Sanofi must be wrong about the first embodiment (i.e., why
`
`would Steenfeldt-Jensen make that disclosure if it would impair the first
`
`embodiment) and therefore wrong about the fifth embodiment. Dr. Slocum opined
`
`about Petitioners’ modification, a threaded driver tube. Dr. Slocum does not agree
`
`with Petitioners regarding what is disclosed at 7:41-47. See Section I.A.
`
`C. Even If Steenfeldt-Jensen Suggested a Threaded Driver Tube With
`Respect to Its First Embodiment, A POSA Would Not Be
`Motivated to Make Petitioners’ Modification to the Fifth
`Embodiment
`
`Even assuming that Steenfeldt-Jensen disclosed a threaded driver tube in the
`
`
`
`
`context of its first embodiment (it does not), Petitioners’ proposed modification to
`
`the fifth embodiment has substantial drawbacks that would counsel a POSA against
`
`the modification.
`
`
`
`Sanofi presented evidence by way of analytical and physical models from Dr.
`
`Slocum demonstrating that a POSA would not modify the fifth embodiment to
`
`include a threaded driver tube because it would result in an inferior pen having a
`
`51% higher injection force. Response, 36-45. In Reply, Petitioners presented no
`
`models or calculations rebutting Sanofi’s evidence. Instead, Petitioners argued that
`
`a higher injection force would not dissuade a POSA from the modification. Reply,
`
`11.
`
`3
`
`
`
`
`
`
`
`1. A High Injection Force Would Dissuade a POSA From
`Petitioners’ Modification
`Dr. Slocum concluded that Petitioners’ proposed modification to the fifth
`
`embodiment would have detrimentally affected the fifth embodiment—for example,
`
`a significantly higher injection force. Response, 36-45. Petitioner, however, argues
`
`that the Board should disregard Dr. Slocum’s findings because they assume “that a
`
`POSA was limited to designing insulin injector pens.” Reply, 10. Petitioners,
`
`however, identify no other application or circumstance where a higher injection
`
`force would be acceptable or even other considerations that would outweigh a higher
`
`injection force. Moreover, Steenfeldt-Jensen is directed to “syringes [that] are
`
`mainly made for users who have to inject themselves frequently, e.g., diabetics.”
`
`EX1014, 1:16-18. A POSA, when considering whether to combine the teachings of
`
`one embodiment in Steenfeldt-Jensen with another embodiment in Steenfeldt-
`
`Jensen, would consider the context of Steenfeldt-Jensen – injection pens, e.g.,
`
`diabetic injection pens.
`
`2. Petitioners Argue that Their Modification is Obvious Solely
`On the Basis of Reasonable Expectation of Success
`Petitioners argue that, despite Sanofi’s premise that higher injection force is
`
`
`
`undesirable, “Sanofi never alleges that the petition’s modification is unworkable or
`
`that a POSA would not have reasonably expected success.” Reply, 11. Obviousness
`
`requires “a motivation to combine accompanied by a reasonable expectation of
`
`4
`
`
`
`
`
`achieving what is claimed in the patent-in-suit.” Intelligent Bio-Systems, Inc. v.
`
`Illumina Cambridge Ltd., 821 F.3d 1359, 1367 (Fed. Cir. 2016) (emphasis added).
`
`That injection force would increase—a fact that does not appear to be disputed (only
`
`the amount of increase is disputed)—demonstrates that a POSA would not be
`
`motivated to make Petitioners’ modification, even if a POSA could do so. Plas-Pak
`
`Indus. v. Sulzer Mixpac AG, 600 F. App’x 755, 758-60 (Fed. Cir. 2015); In re
`
`Gordon, 733 F.2d 900.
`
`3. Sanofi Presented Non-Obviousness Arguments Beyond the
`Friction Collar Model
`Sanofi’s Response provided additional evidence that there would have been
`
`
`
`additional problems with Petitioners’ modification aside from an increase in
`
`injection force. These problems included that the flexible arms of the driver tube 85
`
`get stuck or get pressed into the ring-shaped wall, ultimately causing the flexible
`
`arms to break and ruin the device. Response, 45-47. In Reply, Petitioners dismiss
`
`this evidence, arguing that fixing these problems would be “straightforward”
`
`because “Mr. Leinsing explains that this would be the type of routine task that a
`
`POSA would have no difficulty addressing.” Reply, 16 citing EX1095, ¶ 76.
`
`Beyond saying so, Mr. Leinsing presents no evidence that doing so would be routine.
`
`D. Dr. Slocum’s Models Are Not Flawed
`
`5
`
`
`
`
`
`
`
`Petitioners further argue that Dr. Slocum’s models are flawed. Neither
`
`Petitioners nor its expert, however, inspected Sanofi’s model and Mr. Leinsing
`
`presented no model of his own.
`
`1. There is no Bias
`Petitioners argue that the models are unreliable due to bias because “they were
`
`
`
`primarily designed” by Mr. Veasey, an inventor of the 044 Patent. Reply, 11-12.
`
`First, Dr. Slocum independently verified the models, conducted his own
`
`experiments, and gathered his own data. EX2107, ¶¶ 242-255, Appendix B, E.
`
`Second, Petitioners fail to show how Mr. Veasey is biased simply because he is an
`
`inventor. Mr. Veasey is not an employee of Sanofi nor does he have a financial stake
`
`in this IPR. Third, even assuming, arguendo, that Mr. Veasey is an interested party,
`
`it is well-established that a party’s interest alone cannot affect the credibility of
`
`scientific evidence when Petitioners have presented no opposing evidence (e.g., no
`
`models). Integra Lifesciences I, Ltd. v. Merck KGaA, 496 F.3d 1334, 1346 (Fed.
`
`Cir. 2007) (rejecting a party’s challenge to witness credibility when the party
`
`presented no opposing evidence as to certain experiments).
`
`
`
`Furthermore, while Petitioners argue that Mr. Veasey selected 11 of 15
`
`variables for the analytical model, the only one they complain about is the coefficient
`
`of friction, arguing that the selected 0.1 should have been lower since “lubricious
`
`plastics can have a coefficient of 0.08 or lower.” Reply, 12-13. Dr. Slocum,
`
`6
`
`
`
`
`
`however, explained that 0.1 was selected to correspond to the parameters of the
`
`FlexPen, the commercial embodiment of Steenfeldt-Jensen’s fifth embodiment.
`
`Response, 37.
`
`
`
`Petitioners also complain that the physical model was “designed by Mr.
`
`Veasey (or others at Mr. Veasey’s company, DCA Design International Ltd.).”
`
`Reply, 13. But aside from a conclusory argument that the collar was too big