`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`__________
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`__________
`
`
`REGENERON PHARMACEUTICALS, INC.,
`Petitioner
`
`v.
`
`NOVARTIS PHARMA AG,
`NOVARTIS TECHNOLOGY LLC,
`NOVARTIS PHARMACEUTICALS CORPORATION,
`Patent Owners
`
`__________
`
`
`Case IPR2021-00816
`Patent 9,220,631
`
`__________
`
`
`PATENT OWNER’S UPDATED EXHIBIT LIST
`
`
`
`0
`
`
`

`

`Pursuant to 37 C.F.R. § 42.63(e), Patent Owners Novartis Pharma AG,
`
`Novartis Technology LLC, and Novartis Pharmaceuticals Corporation
`
`(collectively. “Novartis”) hereby submit a current listing of Patent Owners’
`
`Exhibits.
`
`Exhibit
`
`Description
`
`Ex. 2001 Declaration of Karl R. Leinsing, PE
`
`Ex. 2002 Declaration of Marie Picci [Filed Under Seal]
`
`Ex. 2003 October 29, 2020 Telephonic Hearing Transcript, Regeneron
`Pharmaceuticals, Inc. v. Novartis Pharma AG et al., IPR2020-01317
`
`Ex. 2004 Redline comparison of Koller Declarations submitted in IPR2020-
`01317 and IPR2021-00816
`Ex. 2005 Court Notice setting Rule 16 Scheduling Conference (DI45), Novartis
`Pharma AG, et al. v. Regeneron Pharmaceuticals, Inc., 1:20-cv-
`00690-TJM-CFH (N.D.N.Y. June 22, 2021)
`
`Ex. 2006 Regeneron Pharmaceuticals, Inc.’s Partial Answer to Complaint
`(DI55), Novartis Pharma AG, et al. v. Regeneron Pharmaceuticals,
`Inc., 1:20-cv-00690-TJM-CFH (N.D.N.Y. July 11, 2021)
`
`Ex. 2007 Regeneron Pharmaceuticals, Inc.’s Complaint (DI01), Regeneron
`Pharmaceuticals, Inc. v. Novartis Pharma AG et al., 1:20-cv-005502
`(S.D.N.Y. July 17, 2020)
`
`Ex. 2008
`
`9220631 File History (Examiner's Search)
`
`Ex. 2009 WO 2007/084765 (Deschatelets)
`
`Ex. 2010 WO 1997/44068 (Tack)
`
`Ex. 2011
`
`English Translation of WO 1997/44068 (Tack)
`
`Ex. 2012
`
`IDS with Deschatelets (9220631 File History)
`
`1
`
`

`

`Exhibit
`
`Description
`
`Ex. 2013
`
`IDS with Tack (9220631 File History)
`
`Ex. 2014
`
`European Patent Application No. EP 12189649 (EP '649)
`
`Ex. 2015
`
`Screen capture of Genentech Press Release, “FDA Approves
`Genentech’s Lucentis (Ranibizumab Injection) Prefilled Syringe”
`(Oct. 14, 2016)
`Ex. 2016 Roche Finance Report 2018
`
`Ex. 2017
`
`Ex. 2018
`
`Eric Souied, Ranibizumab prefilled syringes: benefits of reduced
`syringe preparation times and less complex preparation procedures,
`EUR. J. OPHTHALMOL. 25(6): 529-34 (2015) (“Souied”)
`
`Thérèse M Sassalos and Yannis M Paulus, Prefilled syringes for
`intravitreal drug delivery, CLINICAL OPHTHALMOLOGY 13:701-
`06 (2019) (“Sassalos”)
`
`Ex. 2019 Gholam A. Peyman, Eleonora M. Lad and Darius M. Moshfeghi,
`Intravitreal Injection Of Therapeutic Agents, RETINA 29:875–912
`(2009) (“Peyman”)
`
`Ex. 2020
`
`Lloyd Aiello, et al., Evolving guidelines for intravitreous injections,
`RETINA (2004) (“Aiello”)
`
`Ex. 2021 Bruno Reuter and Claudia Petersen, Syringe Siliconisation Trends ,
`Methods, Analysis Procedures.” (2012) (“Reuter”)
`
`Ex. 2022
`
`Edwin Chan, et al., Syringe Siliconization Process Investigation and
`Optimization, PDA JOURNAL OF PHARMACEUTICAL SCIENCE
`AND TECHNOLOGY, 136-158 (2012) (“Chan”)
`
`Ex. 2023 Anita Leys, et al., Neovascular growth following photodynamic
`therapy for choroidal hemangioma and neovascular regression after
`intravitreous injection of triamcinolone, RETINA (2006) ul-Aug;
`
`Ex. 2024
`
`Joseph Remington and Paul Beringer, Remington: The Science and
`Practice of Pharmacy, Philadelphia: Lippincott Williams & Wilkins,
`776-801 (21st Ed. 2006) (“Remington”)
`
`2
`
`

`

`Exhibit
`
`Description
`
`Ex. 2025
`
`Ex. 2026
`
`Pearse Keane and Srinivas Sadda, Development of Anti-VEGF
`Therapies for Intraocular Use: A Guide for Clinicians, J
`OPTHAMOL. (2012) (“Keane”)
`
`FDA Alerts Health Care Professionals of Injection Risk from
`Repackaged Avastin Intravitreal Injections, U.S. Food and Drug
`Administration (Sep. 1, 2011),
`https://web.archive.org/web/20110901180651/https://www.fda.gov/Dr
`ugs/DrugSafety/ucm270296.htm (last accessed Nov. 10, 2020) (“FDA
`Alert”)
`
`Ex. 2027
`
`FDA Guidance for Industry – Q1A (R2) Stability Testing of New
`Drug Substances and Products (2003)
`
`Ex. 2028 Hultman, et al., The Physical Chemistry of Decontamination with
`Gaseous Hydrogen Peroxide, Pharmaceutical Engineering,
`January/February 2007, 27(1):1-6 (“Hultman”)
`
`Ex. 2029 Nitin Rathore, et al., Characterization of Protein Rheology and
`Delivery Forces for Combination Products, JOURNAL OF
`PHARMACEUTICAL SCIENCES, 101(12):4472-80 (Dec. 2012)
`(“Rathore 2012”)
`
`Ex. 2030
`
`Tracy Chang, et al., Cell and Protein Compatibility of Parylene-C
`Surfaces, Langmuir (2007) (“Chang”)
`
`Ex. 2031 Marta Kaminska, et al., Interaction of parylene C with biological
`objects, Acta Bioeng Biomech. (2009) (“Kaminska”)
`
`Ex. 2032 United States Patent Publication 2014/0012227A1
`
`Ex. 2033
`
`Joseph Remington and Paul Beringer, Remington: The Science and
`Practice of Pharmacy, Philadelphia: Lippincott Williams & Wilkins,
`1025-1036 (21st Ed. 2006) (“Remington”)
`
`Ex. 2034
`
`Sandeep Nema, et al., Antibody Structure, Instability, and
`Formulation, Wiley InterScience. (2006) (“Nema”)
`
`3
`
`

`

`Exhibit
`
`Description
`
`Ex. 2035 Gregory Sacha, et al., Practical fundamentals of glass, rubber, and
`plastic sterile packaging systems, PHARM DEV TECHNOL. (2010)
`(“Sacha”)
`
`Ex. 2036 MiniVision, Eylea Pre-Filled Syringe PBS Listed, Indication
`Expanded (Dec. 1, 2020)
`
`Ex. 2037
`
`Intentionally Omitted
`
`Ex. 2038
`
`Intentionally Omitted
`
`Ex. 2039
`
`Intentionally Omitted
`
`Ex. 2040
`
`Intentionally Omitted
`
`Ex. 2041
`
`Ingrid Markovic, Regulatory Perspective on Safety Qualification of
`Extractables and Leachables, (2011)
`
`Ex. 2042
`
`International Standard, Biological Evolution of medical devices – Part
`1: Evaluation and Testing Within a Risk Management Process, (2009)
`
`Ex. 2043
`
`Intentionally Omitted
`
`Ex. 2044 U.S. Lucentis® PFS Administration Flashcard (dated April 2018)
`
`Ex. 2045
`
`IPR2020-01317, Petition for Inter Partes Review
`
`Ex. 2046
`
`IPR2020-01318, Petition for Inter Partes Review
`
`Ex. 2047
`
`Ex. 2048
`
`IPR2020-01318 Novartis Pharma AG, Novartis Technology LLC, and
`Novartis Pharmaceuticals Corporation’s Patent Owner Preliminary
`Response
`
`International Conference on Harmonisation of Technical
`Requirements for Registration of Pharmaceuticals for Human Use,
`STABILITY TESTING OF NEW DRUG SUBSTANCES AND
`PRODUCTS Q1A(R2) GUIDELINE (Feb. 6, 2003)
`
`4
`
`

`

`Exhibit
`
`Description
`
`Ex. 2049 Glen Petrie, The Need for Specificity in Accelerated Aging, Medical
`Device & Diagnostic Industry (2006) (“Petrie”)
`
`Ex. 2050
`
`2020-01318 IPR, Paper No. 16, Petitioner’s Unopposed Motion to
`Terminate the Proceeding
`
`Ex. 2051
`
`2020-01317 IPR, Paper No. 13, Petitioner’s Reply Regarding 35
`U.S.C. §§ 314(a), 325(d)
`
`Ex. 2052 Regeneron Pharmaceuticals, Inc.’s First Amended Complaint (DI87),
`Regeneron Pharmaceuticals, Inc. v. Novartis Pharma AG et al., 1:20-
`cv-05502 (S.D.N.Y. January 25, 2021)
`
`Ex. 2053
`
`Ex. 2054
`
`Ex. 2055
`
`2020-01317 IPR, Paper No. 19, Petitioner’s Unopposed Motion to
`Withdraw its Request for Rehearing of the Board’s Decision Denying
`Inter Partes Review
`
`FDA Compliance Program Guidance Manual, Chapter 56 – Drug
`Quality Assurance, STERILE DRUG PROCESS INSPECTIONS
`(Sept. 11, 2015)
`
`FDA Guidance for Industry, for the Submission Documentation for
`Sterilization Process Validation in Applications for Human and
`Veterinary Drug Products (1994)
`
`Ex. 2056
`
`European Medicines Agency, Macugen: European Public Assessment
`Report – Scientific Discussion (May 31, 2007)
`
`Ex. 2057 Docket Text- Minute Entry for proceedings held before Magistrate
`Judge Hummel: Status Conference held on 6/11/2021, Novartis
`Pharma AG, et al. v. Regeneron Pharmaceuticals, Inc., 1:20-cv-
`00690-TJM-CFH (N.D.N.Y. June 11, 2021)
`
`Ex. 2058
`
`Letter from Jessica Falk to Novartis in Response to May 10 Letter
`Redacted, dated May 14, 2021
`
`Ex. 2059
`
`2020-01317 IPR, Ex. 3004, April 16, 2021 Email from Brian
`Ferguson to Board re Withdrawal of POP Consideration
`
`5
`
`

`

`Exhibit
`
`Description
`
`Ex. 2060 Uniform Pretrial Scheduling Order (DI67), Enthone Inc. v. Moses
`Lake Industries, Inc., 1:13-CV-1054 (N.D.N.Y. August 14, 2014)
`
`Ex. 2061 Uniform Pretrial Scheduling Order (DI22), Enthone Inc. v. BASF
`Corporation, 1:15-CV-233 (N.D.N.Y. June 4 2015)
`
`Ex. 2062 Declaration of Jeffrey Salling In Support of Novartis’s Patent Owner
`Preliminary Response
`
`Ex. 2063
`
`Lucentis Project Review_2011 10 05a.pptx [FILED UNDER SEAL]
`
`Ex. 2064 RFB002, RP01030A, Risk assessment: Changes in starting material
`and manufacturing process between registration stability and process
`validation campaigns [FILED UNDER SEAL]
`
`Ex. 2065 Metadata Report for Ex. 2063
`
`Ex. 2066
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Oct. 11, 2011)
`[FILED UNDER SEAL]
`
`Ex. 2067
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Oct. 27, 2011)
`[FILED UNDER SEAL]
`
`Ex. 2068
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Nov. 11, 2011 and
`Nov. 21, 2011) [FILED UNDER SEAL]
`
`Ex. 2069
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Dec. 5, 2011)
`[FILED UNDER SEAL]
`
`Ex. 2070
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Dec. 20, 2011)
`[FILED UNDER SEAL]
`
`Ex. 2071
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Jan. 9, 2012)
`[FILED UNDER SEAL]
`
`Ex. 2072
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Jan. 23, 2012)
`[FILED UNDER SEAL]
`
`6
`
`

`

`Exhibit
`
`Description
`
`Ex. 2073
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Feb. 20, 2012 and
`Mar. 6, 2012) [FILED UNDER SEAL]
`
`Ex. 2074
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Mar. 19, 2012)
`[FILED UNDER SEAL]
`
`Ex. 2075
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Apr. 2, 2012)
`[FILED UNDER SEAL]
`
`Ex. 2076
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Apr. 16, 2012)
`[FILED UNDER SEAL]
`
`Ex. 2077
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (May 3, 2012 and
`May 14, 2012) [FILED UNDER SEAL]
`
`Ex. 2078
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (May 31, 2012 and
`June 11, 2012) [FILED UNDER SEAL]
`
`Ex. 2079
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (June 25, 2012)
`[FILED UNDER SEAL]
`
`Ex. 2080
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (July 9, 2012)
`[FILED UNDER SEAL]
`
`Ex. 2081
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (July 23, 2012)
`[FILED UNDER SEAL]
`
`Ex. 2082
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Aug. 6, 2012)
`[FILED UNDER SEAL]
`
`Ex. 2083
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Aug. 20, 2012)
`[FILED UNDER SEAL]
`
`Ex. 2084
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Sept. 3, 2012)
`[FILED UNDER SEAL]
`
`Ex. 2085
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Oct. 1, 2012)
`[FILED UNDER SEAL]
`
`7
`
`

`

`Exhibit
`
`Description
`
`Ex. 2086
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Oct.15, 2012)
`[FILED UNDER SEAL]
`
`Ex. 2087
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Nov. 12, 2012)
`[FILED UNDER SEAL]
`
`Ex. 2088
`
`Lucentis® PFS TRD SubTeam Meeting Minutes (Dec. 10, 2012)
`[FILED UNDER SEAL]
`
`Ex. 2089
`
`Letter from Jessica Falk to Novartis in Response to June 9 Letter,
`dated June 11, 2021
`
`Ex. 2090
`
`Initial Determination Granting Complainants’ Motion for Summary
`Determination as to Direct Infringement and the Economic and
`Technical Prongs of the Domestic Industry Requirement, Certain Pre-
`Filled Syringes for Intravitreal Injection and Components Thereof,
`Inv. No. 337-TA-1207 (April 7, 2021)
`
`Ex. 2091 Modified Default Protective Order
`
`Ex. 2092 Redline of Modified Default Protective Order
`
`Ex. 2093
`
`Transcript of Proceedings Novartis Pharma AG, et al. v. Regeneron
`Pharmaceuticals, Inc., 1:20-cv-00690-TJM-CFH (N.D.N.Y. Aug. 18,
`2021)
`
`Ex. 2094 Uniform Pre-Trial Scheduling Order (DI 82), Novartis Pharma AG, et
`al. v. Regeneron Pharmaceuticals, Inc., 1:20-cv-00690-TJM-CFH
`(N.D.N.Y. Aug. 24, 2021)
`
`E-mail from Christopher Pepe to the PTAB, Re: IPR2021-00816 –
`Request for Authorization (Aug. 6, 2021)
`
`Ex. 2095
`
`Ex. 2096
`
`Stipulation and Order Modifying Case Schedule (DI 133), Regeneron
`Pharmaceuticals, Inc. v. Novartis Pharma AG et al., 1:20-
`cv-05502-AJN (S.D.N.Y. June 23, 2021)
`
`
`8
`
`

`

`Exhibit
`
`Description
`
`Ex. 2097 Declaration of Martina Athanas In Support of Novartis’s Second
`Motion to Seal
`Ex. 2098 Declaration of Nicholas K. Mitrokostas in support of Patent Owner’s
`Motion for Pro Hac Vice Admission
`Ex. 2099 GENEITC_1207-0000030 [Filed Under Seal]
`
`Ex. 2100 GENEITC_1207-0001660 [Filed Under Seal]
`
`Ex. 2101 GENEITC_1207-0001864 [Filed Under Seal]
`
`Ex. 2102 GENEITC_1207-0002423 [Filed Under Seal]
`
`Ex. 2103 GENEITC_1207-0002825 [Filed Under Seal]
`
`Ex. 2104 GENEITC_1207-0003003 [Filed Under Seal]
`
`Ex. 2105 GENEITC_1207-0003160 [Filed Under Seal]
`
`Ex. 2106 GENEITC_1207-0003163 [Filed Under Seal]
`
`Ex. 2107 GENEITC_1207-0003412 [Filed Under Seal]
`
`Ex. 2108 GENEITC_1207-0003418 [Filed Under Seal]
`
`Ex. 2109 GENEITC_1207-0003503 [Filed Under Seal]
`
`Ex. 2110 GENEITC_1207-0003545 [Filed Under Seal]
`
`Ex. 2111 GENEITC_1207-0003551 [Filed Under Seal]
`
`Ex. 2112 GENEITC_1207-0003675 [Filed Under Seal]
`
`Ex. 2113 GENEITC_1207-0003683 [Filed Under Seal]
`
`Ex. 2114 GENEITC_1207-0003704 [Filed Under Seal]
`Ex. 2115 GENEITC_1207-0002409 [Filed Under Seal]
`
`9
`
`

`

`Exhibit
`
`Description
`
`Ex. 2116
`
`Ex. 2117
`
`“FDA Approves Genentech’s Lucentis (Ranibizumab Injection)
`Prefilled Syringe,” Genentech Press Release (Oct. 14, 2016),
`https://www.gene.com/media/press-releases/14640/2016-10-14/fda-
`approves-genentechs-lucentis-ranibiz (“Genentech Press Release (Oct.
`14, 2016)”)
`“FDA Approves Lucentis (ranibizumab injection) 0.3 mg Prefilled
`Syringe for Diabetic Macular Edema and Diabetic Retinopathy,”
`Genentech Press Release (Mar. 21, 2018),
`https://www.gene.com/media/press-releases/14708/2018-03-21/fda-
`approves-genentechs-lucentis-ranibiz (“Genentech Press Release
`(Mar. 21, 2016)”)
`Ex. 2118 NOVITC(CH)00002720
`Ex. 2119 NOVITC(CH)00003455 [Filed Under Seal]
`Ex. 2120 NOVITC(CH)00004818 [Filed Under Seal]
`Ex. 2121 NOVITC(CH)00005765 [Filed Under Seal]
`Ex. 2122 NOVITC(CH)00006074
`Ex. 2123 NOVITC(CH)00007283 [Filed Under Seal]
`Ex. 2124 NOVITC(CH)00008409 [Filed Under Seal]
`Ex. 2125
`“Highlights of Prescribing Information – Lucentis,” Genentech,
`https://www.gene.com/download/pdf/lucentis_prescribing.pdf
`(revised Mar. 2018)
`Ex. 2126 NOVITC(CH)00054063 [Filed Under Seal]
`Ex. 2127
`Intentionally Omitted
`Ex. 2128 NOVITC(CH)00167663 [Filed Under Seal]
`Ex. 2129 NOVITC(CH)00168961 [Filed Under Seal]
`Ex. 2130 NOVITC(CH)00169036 [Filed Under Seal]
`
`10
`
`

`

`Exhibit
`
`Description
`
`Ex. 2131 NOVITC(CH)00170304 [Filed Under Seal]
`Ex. 2132
`
`NOVITC(CH)00170859 [Filed Under Seal]
`
`Ex. 2133
`
`Ex. 2134
`
`NOVITC(CH)00170896 [Filed Under Seal]
`
`NOVITC(CH)00170915 [Filed Under Seal]
`Ex. 2135
`Intentionally Omitted
`Ex. 2136 NOVITC(CH)00217349 [Filed Under Seal]
`Ex. 2137 NOVITC(CH)00217646 [Filed Under Seal]
`Ex. 2138 NOVITC(CH)00217650 [Filed Under Seal]
`Ex. 2139 NOVITC(CH)00810847 [Filed Under Seal]
`Ex. 2140 NOVITC(CH)00874056 [Filed Under Seal]
`Ex. 2141 NOVITC(CH)00880433 [Filed Under Seal]
`Ex. 2142 NOVITC(CH)01494800 [Filed Under Seal]
`Ex. 2143 NOVITC(CH)01495912 [Filed Under Seal]
`Ex. 2144 NOVITC(CH)01498292 [Filed Under Seal]
`Ex. 2145 NOVITC(CH)01863737 [Filed Under Seal]
`Ex. 2146
`NOVITC(CH)01863785 [Filed Under Seal]
`Ex. 2147 NOVITC(CH)01906307 [Filed Under Seal]
`Ex. 2148 NOVITC(CH)02022271 [Filed Under Seal]
`Ex. 2149
`Intentionally omitted
`Ex. 2150 NOVITC(CH)02929814 [Filed Under Seal]
`
`11
`
`

`

`Exhibit
`
`Description
`
`Ex. 2151
`Intentionally omitted
`Ex. 2152 NOVITC(US)00000788
`Ex. 2153 NOVITC(US)00000792
`Ex. 2154 NOVITC(US)00000795
`Ex. 2155
`
`NOVITC(US)00006213 [Filed Under Seal]
`Ex. 2160 Center for Drug Evaluation and Research, Application No.
`125156Orig1s110, Lucentis sBLA Approval (Oct. 13, 2016)
`
`Ex. 2156
`
`Ex. 2157
`
`Ex. 2158
`
`Ex. 2159
`
`Ex. 2161
`
`Ex. 2162
`
`Ex. 2163
`
`Ex. 2164
`
`Ex. 2165
`
`Ex. 2166
`
`Ex. 2167
`
`Ex. 2168
`
`Ex. 2169
`
`Ex. 2170
`
`NOVITC(US)00006151 [Filed Under Seal]
`
`NOVITC(US)00006173 [Filed Under Seal]
`
`NOVITC(US)00006182 [Filed Under Seal]
`
`NOVITC(US)00006196 [Filed Under Seal]
`
`Roche Finance Report for 2016
`
`Roche Finance Report for 2014
`
`Roche Finance Report for 2019
`
`Roche Finance Report for 2013
`Intentionally omitted
`
`NOVITC(US)00389194 [Filed Under Seal]
`
`NOVITC(US)00394737 [Filed Under Seal]
`
`NOVITC(US)00395564 [Filed Under Seal]
`
`NOVITC(US)00395565 [Filed Under Seal]
`
`NOVITC(US)00507243 [Filed Under Seal]
`
`12
`
`

`

`Exhibit
`
`Description
`
`NOVITC(US)00697489 [Filed Under Seal]
`
`Ex. 2171
`
`Ex. 2172
`
`Ex. 2173
`
`Ex. 2177
`
`Ex. 2178
`
`Ex. 2179
`
`Ex. 2180
`
`NOVITC(US)00718202 [Filed Under Seal]
`Intentionally omitted
`Ex. 2174 World Health Organization, Guidelines on Packaging for
`Pharmaceutical Products, WHO Technical Report Series, No. 902
`(2002)
`Ex. 2175 Michael J. Akers, Sterile Drug Products: Formulation, Packaging,
`Manufacturing, and Quality (2010) (“Akers 2010”)
`Ex. 2176 Katia Boven et al., The increased incidence of pure red cell aplasia
`with an Eprex formulation in uncoated rubber stopper syringes,
`Kidney Int’l (2005), 67:2346-2353 (“Boven 2005”)
`Stelios T. Tzannis et al., Irreversible inactivation of interleukin 2 in a
`pump-based delivery environment, PNAS (May 1996), 93:5460-5465
`(“Tzannis 1996”)
`Ingrid Markovic, Risk Management Strategies for Safety
`Qualification of Extractable and Leachable Substances in Therapeutic
`Biologic Protein Products, Extractables & Leachables (June 2009),
`96-101 (“Markovic 2009”)
`Ingrid Markovic, Regulatory Perspective on Safety Qualification of
`Extractables and Leachables, U.S. Food & Drug Admin. (Feb. 22-23,
`2011) (“Markovic 2011”)
`Frederick Silver, Biocompatibility of Materials in Medical Devices,
`Wiley Encyclopedia of Chemical Biology (2008), 1-7 (“Silver 2008”)
`International Organization for Standardization, ISO 10993-1
`Biological Evaluation of Medical Devices – Part 1: Evaluation and
`Testing Within a Risk Management Process (4th ed. 2009) (“ISO
`10993-1-2009")
`Ex. 2182 Michael N. Helmus, Donald F. Gibbons & David Cebon,
`Biocompatibility: Meeting a Key Functional Requirement of Next-
`Generation Medical Devices, Toxicologic Pathology (2008), 36:70-80
`(“Helmus 2008”)
`Ex. 2183 U.S. Food & Drug Admin., Use of International Standard ISO 10993-
`1, "Biological evaluation of medical devices - Part 1: Evaluation and
`testing within a risk management process": Guidance for Industry and
`
`Ex. 2181
`
`13
`
`

`

`Exhibit
`
`Description
`
`Ex. 2186
`
`Food and Drug Administration Staff (Sept. 4, 2020) (“FDA Use of
`ISO-10993”)
`Ex. 2184 Nitin Rathore & Rahul S. Rajan, Current Perspectives on Stability of
`Protein Drug Products during Formulation,
`Fill and Finish Operations, Biotechnol. Prog. (2008), 24:504-514
`(“Rathore 2008”)
`Ex. 2185 Howard C. Ansel, Nicholas G. Popovich & Loyd V. Allen, Jr.,
`Pharmaceutical Dosage Forms and Drug Delivery Systems (6th ed.
`1995) (“Ansel 1995”)
`Leon Lachman, Herbert A. Lieberman & Joseph L. Kanig, The
`Theory and Practice of Industrial Pharmacy (3d ed. 1986) (“Lachman
`1986”)
`Ex. 2187 Association for the Advancement of Medical Instrumentation,
`Sterilization of heath care products—Requirements and guidance for
`selecting a sterility assurance level (SAL) for products labeled
`“sterile,” American National Standards Institute (2011), ST67:2011
`(“ANSI/AAMI ST67-2011”)
`International Organization for Standardization, ISO 14161
`Sterilization of health care products – Biological indicators –
`Guidance for the selection, use and interpretation of results (1st ed.
`2000) (“ISO 14161")
`Ex. 2189 Deposition Transcript of Horst Koller (Dec. 16, 2021)
`
`Ex. 2188
`
`Ex. 2190 Winston D. Bash & Wilbur A. Gould, Food Processing and
`Technology 1984: A Summary of Research, Research Circular (1984)
`(“Bash and Gould 1984”)
`21 CFR § 201.57 (2004)
`
`Ex. 2191
`
`Ex. 2192
`
`21 CFR § 201.57 (2008)
`
`Ex. 2193
`
`21 CFR § 201.57 (2021)
`
`Ex. 2194 Deposition Transcript of David Overcashier (Dec. 9, 2020) [Filed
`Under Seal]
`Ex. 2195 Graciela Gutierrez, Researchers uncover mechanism blocking retina
`regeneration, Baylor College of Medicine (May 7, 2019),
`https://www.eurekalert.org/pub_releases/2019-05/bcom-
`rum050619.php (“Poche 2019”)
`
`14
`
`

`

`Exhibit
`
`Description
`
`Ex. 2196
`
`Ex. 2197
`
`International Organization for Standardization, ISO 10993-7
`Biological evaluation of medical devices – Part 7: Ethylene oxide
`sterilization residuals (2nd ed. 2008) (“ISO 10993-7")
`“Highlights of Prescribing Information – Eylea,” Regeneron,
`https://www.regeneron.com/sites/default/files/EYLEA_FPI.pdf
`(“Eylea PFS Label Aug. 2019”)
`Ex. 2198 Declaration of Rayna Venook, Ph.D. (Nov. 20, 2020)
`
`Ex. 2199
`
`Ex. 2200
`
`Ex. 2201
`
`International Organization for Standardization, ISO 11137-2
`Sterilization of Health Care Products – Radiation – Part 2:
`Establishing the Sterilization Dose (1st ed.) (“ISO 11137")
`Thomas V. Woedtke & Axel Kramer, The limits of sterility assurance,
`GMS Hygiene & Infection Control (2008), 3:3:1.
`Supplemental Declaration of Karl R. Leinsing, PE [Filed Under Seal]
`
`Ex. 2202 Declaration of John Dillberger, DVM, Ph.D.
`
`Ex. 2203 Declaration of Michael J. Miller, Ph.D. [Filed Under Seal]
`
`Ex. 2204 Declaration of Andrew F. Calman, M.D., Ph.D. [Filed Under Seal]
`
`Ex. 2205 Declaration of James E. Malackowski, Ph.D. [Filed Under Seal]
`
`Ex. 2206 Declaration of Juergen Sigg, Ph.D. [Filed Under Seal]
`
`Ex. 2207 Declaration of Jeffrey Salling
`
`Ex. 2208 Declaration of Kimberly Cameron, Ph.D. In Support of Novartis’s
`Motion to Amend [Filed Under Seal]
`Ex. 2209 Declaration of Jeremy Wolfe, M.D. In Support of Novartis’s Motion
`to Amend
`Ex. 2210 Curriculum Vitae of Dr. Kimberly Cameron
`
`Ex. 2211 Curriculum Vitae of Dr. Jeremy Wolfe
`
`Ex. 2212
`
`Eylea Label 2021
`
`Ex. 2213
`
`Lucentis Label 2017
`
`15
`
`

`

`Exhibit
`
`Description
`
`Ex. 2215
`
`Ex. 2214 Rahul Chaturvedi et al., Real World Trends in Intravitreal Injection
`Practices Among American Retina Specialists, Ophthalmology Retina
`(Aug. 2019), 3(8):656-662
`Phillip P. Storey et al., The Impact of Prefilled Syringes on
`Endophthalmitis Following Intravitreal Injection of Ranibizumab,
`Am. J. Ophthalmology (Mar. 2019), 199:200-208
`Intentionally Omitted
`
`Ex. 2216
`
`Ex. 2217
`
`Intentionally Omitted
`
`Ex. 2218
`
`Ex. 2219
`
`Francesco Cilurzo et al., Injectability Evaluation: An Open Issue,
`AAPS PharmSciTech (June 2011), 12(2):604-9
`Intentionally Omitted
`
`Ex. 2220
`
`Intentionally Omitted
`
`Ex. 2221
`
`Intentionally Omitted
`
`Ex. 2222
`
`Summary of EU Product Characteristics, Lucentis PFS (E.U.)
`
`Ex. 2223
`
`Intentionally Omitted
`
`Ex. 2224 DSR5092D [Filed Under Seal]
`
`Ex. 2225
`
`Intentionally Omitted
`
`Ex. 2226
`
`Intentionally Omitted
`
`Ex. 2227 Application No. 13/750,352
`
`Ex. 2228 U.S. Food & Drug Admin., Q1A (R2) Stability Testing of New Drug
`Substances and Products: Guidance for Industry (Nov. 2003)
`Ex. 2229 Nitin Rathore et al., Variability in Syringe Components and its Impact
`on Functionality of Delivery Systems, PDA J. Pharm. Sci. Tech.
`(2011), 65(5):468-480
`European Medicines Agency, ICH Topic Q 5 C, “Quality of
`Biotechnological Products,” CPMP/ICH/138/95 (July 1996)
`Intentionally Omitted
`
`Ex. 2230
`
`Ex. 2231
`
`16
`
`

`

`Exhibit
`
`Description
`
`Ex. 2232 K. Bailey Freund et al., Silicone Oil Droplets Following Intravitreal
`Injection, Retina (July 2006), 26(6):701-703
`Intentionally Omitted
`
`Ex. 2233
`
`Ex. 2234
`
`Intentionally Omitted
`
`Ex. 2235
`
`Intentionally Omitted
`
`Ex. 2236
`
`Intentionally Omitted
`
`Ex. 2237
`
`Intentionally Omitted
`
`Ex. 2238
`
`Intentionally Omitted
`
`Ex. 2239
`
`Intentionally Omitted
`
`Ex. 2240
`
`Intentionally Omitted
`
`Ex. 2241
`
`Intentionally Omitted
`
`Ex. 2242
`
`Intentionally Omitted
`
`Ex. 2243
`
`Intentionally Omitted
`
`Ex. 2244
`
`Intentionally Omitted
`
`Ex. 2245
`
`Intentionally Omitted
`
`Ex. 2246
`
`Intentionally Omitted
`
`Ex. 2247
`
`Intentionally Omitted
`
`Ex. 2248
`
`Intentionally Omitted
`
`Ex. 2249
`
`Intentionally Omitted
`
`Ex. 2250
`
`Intentionally Omitted
`
`Ex. 2251
`
`Intentionally Omitted
`
`17
`
`

`

`Exhibit
`
`Description
`
`Ex. 2252
`
`Intentionally Omitted
`
`Ex. 2253
`
`Latoya S. Jones, Allyn Kaufmann, C. Russell Middaugh, Silicone Oil
`Induced Aggregation of Proteins, J. Pharm. Sci. (Apr. 2005)
`94(4):918-927 (Note) (“Jones 2005”)
`Ex. 2254 NOVITC(CH)00885630
`
`Ex. 2255 Hongxiang Teng, Overview of the Development of the Fluoropolymer
`Industry, Appl. Sci. (2012), 2:496-512 (“Teng 2012”)
`Ex. 2256 Curriculum Vitae of Andrew F. Calman, M.D., Ph.D.
`
`Ex. 2257 Deposition Transcript of Szilard Kiss (Jan. 7, 2022)
`
`Ex. 2258
`
`Ex. 2259
`
`Ex. 2260
`
`Ex. 2261
`
`Ex. 2262
`
`Ex. 2263
`
`“Macular Degeneration Treatments,” American Macular
`Degeneration, https://www.macular.org/treatments.
`“Highlights of Prescribing Information – Avastin,” Genentech,
`https://www.gene.com/download/pdf/avastin_prescribing.pdf.
`“Comparison of Anti VEGF Treatments for Wet AMD,” American
`Academy of Ophthalmology (Feb. 3, 2020), https://www.aao.org/eye-
`health/diseases/avastin-eylea-lucentis-difference
`“Age-Related Macular Degeneration: Facts & Figures,” BrightFocus
`Foundation, https://www.brightfocus.org/macular/article/age-related-
`macular-facts-figures.
`“FDA Approves Avastin,” Drugs.com (Feb. 2004),
`https://www.drugs.com/newdrugs/avastin-approved-metastatic-
`colorectal-cancer-21.html.
`Intentionally omitted
`
`Ex. 2264
`
`“Investor Update,” Roche (Mar. 22, 2018),
`https://www.roche.com/investors/updates/inv-update-2018-03-22.htm.
`Ex. 2265 Genentech, Inc. 10-K for the year ended December 31, 2003, p. 6,
`https://www.sec.gov/Archives/edgar/data/318771/0000318771040000
`02/dna-10k_2003.htm
`“FDA Approves Lucentis (ranibizumab) for the Treatment of Wet
`Age-Related Macular Degeneration,” Drugs.com (June 30, 2006),
`https://www.drugs.com/newdrugs/fda-approves-lucentis-ranibizumab-
`wet-age-related-macular-degeneration-327.html
`
`Ex. 2266
`
`18
`
`

`

`Exhibit
`
`Description
`
`Ex. 2267
`
`Intentionally omitted
`
`Ex. 2268
`
`Intentionally omitted
`
`Ex. 2269
`
`Ex. 2270
`
`“FDA Approves Eylea,” Drugs.com (Nov. 18, 2011),
`https://www.drugs.com/newdrugs/fda-approves-eylea-wet-age-
`related-macular-degeneration-2955.html.
`“FDA Approves Eylea® (aflibercept) Injection Prefilled Syringe,”
`Regeneron (Aug. 13, 2019), https://investor.regeneron.com/news-
`releases/news-release-details/fda-approves-eylear-aflibercept-
`injection-prefilled-syringe.
`“Prefilled Syringe Delivery of Intravitreal Anti-VEGF Medications,”
`RetinalPhysician.com (Mar. 1, 2019),
`https://www.retinalphysician.com/issues/2019/march-2019/prefilled-
`syringe-delivery-of-intravitreal-anti-ve
`Excerpts from Deposition Transcript of Christopher Simms (Dec. 4,
`2020)
`Ex. 2273 Roche Finance Report for 2011
`
`Ex. 2271
`
`Ex. 2272
`
`Ex. 2274 Roche Finance Report for 2012
`
`Ex. 2275 Roche Finance Report for 2015
`
`Ex. 2276 Roche Finance Report for 2017
`
`Ex. 2277
`
`“Treatments for Wet AMD (Advanced Neovascular AMD),” National
`Eye Institute, https://www.nei.nih.gov/learn-about-eye-health/eye-
`conditions-and-diseases/age-related-macular-degeneration/treatments-
`wet-amd-advanced-neovascular-amd
`Eylea Pre-filled Syringe PBS Listed, Indications Expanded –
`minivision (Oct. 16, 2020)
`Ex. 2279 Macugen – European Medicines Agency – EPAR website
`
`Ex. 2278
`
`Ex. 2280
`
`Jean-Eric Michaud et al., Ranibizumab pre-filled syringe approved in
`the European Union: innovation to improve dose accuracy, reduce
`potential infection risk, and offer more efficient treatment
`administration, Inv. Ophthalmology & Visual Sci. (Apr. 2014), 55
`
`19
`
`

`

`Exhibit
`
`Description
`
`Ex. 2282
`
`Ex. 2281 Magdalena G. Krzystolik et al., Prevention of Experimental Choroidal
`Neovascularization With Intravitreal Anti-Vascular Endothelial
`Growth Factor Antibody Fragment, Arch. Ophthalmol. (Mar. 2002),
`120(3):338-46
`FDA Approval for Macugen®,
`https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-
`756_Macugen_approv.pdf.
`Ex. 2283 Drugs@FDA: FDA Approved Drugs Page for Macugen,
`https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=ove
`rview.process&ApplNo=021756 (last accessed on 1/17/2022)
`Ex. 2284 Ryan M. Rich et. al., Short-Term Safety and Efficacy of Intravitreal
`Bevacizumab (Avastin) for Neovascular Age-related Macular
`Degeneration, Retina (2006), 26(5):495-511
`Ex. 2285 Avastin® FDA label,
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125085s3
`37lbl.pdf last accessed on 01/17/2022
`FDA Approval Letter for Eylea®, from FDA approval package,
`https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/125387s00
`00TOC.cfm last accessed on 01/17/2022
`Jay L. Federman & Hermann D. Schubert, Complications Associated
`with the Use of Silicone Oil in 150 Eyes after Retina-vitreous Surgery,
`Ophthalmol. (July 1988), 95(7):870-6
`Ex. 2288 Q.H. Nguyen et al., Incidence and Management of Glaucoma after
`Intravitreal Silicone Oil Injection for Complicated Retinal
`Detachments, Ophthalmol. (Oct. 1992), 99(10):1520-6
`Ingrid U. Scott et al., Intravitreal Triamcinolone Acetonide for
`Idiopathic Cystoid Macular Edema, Am. J. Ophthalmol. (Nov. 2003),
`136(4):737-9
`Intentionally omitted
`
`Ex. 2286
`
`Ex. 2287
`
`Ex. 2289
`
`Ex. 2290
`
`Ex. 2291 Amy S. Rosenberg, Effects of Protein Aggregates: An Immunologic
`Perspective, AAPS J. (Aug. 2006), 8(3):E501-E507
`Steve Charles, Toxic Posterior Segment Syndrome Due to Reuse of
`Cannulated Tools, Retina Today (July/Aug. 2009), accessible at
`https://retinatoday.com/articles/2009-july-aug/0709_05-php
`
`Ex. 2292
`
`20
`
`

`

`Exhibit
`
`Description
`
`Ex. 2293 Kimberly E. Stepien et al., Increased Incidence of Sterile
`Endophthalmitis After Intravitreal Triamcinolone Acetonide in Spring
`2006, Retina (Feb. 2009), 29(2):207-213
`Ex. 2294 Beovu® FDA approval letter, from FDA approval package,
`https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761125_O
`rig1_toc.cfm
`Ex. 2295 Robert A. Mittra & William F. Mieler, Drug Toxicity of the Posterior
`Segment, Ryan’s Retina 1839-56 (Schachat, A.P., et al eds., 2006)
`Ex. 2296 Ricardo M. Santaella & Frederick W. Fraunfelder, Ocular Adverse
`Effects Associated with Systemic Medications: Recognition and
`Management, Drugs (2007), 67(1):75-93
`Ex. 2297 Omar Abbasi & Asheesh Tewari, Common Medications that May Be
`Toxic to the Retina, Rev. Ophthalmol. (June 11, 2009), accessed at
`https://www.reviewofophthalmology.com/article/common-
`medications-that-may-be-toxic-to-the-retina on 01/17/2022
`Ex. 2298 Howard Schatz & H. Richard McDonald, Acute Ischemic Retinopathy
`due to Gentamicin Injection, JAMA (1986), 256(13):1725-6
`Ex. 2299 Carolee M. Cutler Peck et al., Toxic anterior segment syndrome:
`common causes, J. Cataract Refract. Surg. (2010), 36(7):1073
`S.J. Yoon et al., Anatomic and Visual Outcomes of Noninfectious
`Endophthalmitis after Intravitreal Triamcinolone, Am. J. Ophthalmol.
`(2009), 147(6):1031-1036
`Ex. 2301 Y. Lang et al., Retinal Toxicity of Intravitreal Kenalog in Albino
`Rabbits, Retina (2007), 27:778-788
`Ex. 2302 Hao Chen et al., Different Intravitreal Properties of Three
`Triamcinolone Formulations and Their Possible Impact on Retina
`Practice, Invest. Oph. Vis. Sci. (2013), 54:2178-2185
`Ex. 2303 Valentina Sarao et al., Intravitreal Steroids for the Treatment of
`Retinal Diseases, Scientific World J. (2014),
`http://dx.doi.org/10.1155/2014/989501
`Florian Baudin et al., Association of Acute Endophthalmitis with
`Intravitreal Injections of Corticosteroids or Anti-Vascular Growth
`Factor Agents in a Nationwide Study in France, JAMA Oph. (2018),
`136(12):1352-1358
`Ex. 2305 M.E. Wilson et al., How to Give Intravitreal Injections, Eyenet 45
`(2013).
`
`Ex. 2300
`
`Ex. 2304
`
`21
`
`

`

`Exhibit
`
`Description
`
`Ex. 2306
`
`Ex. 2308
`
`Ex. 2310
`
`Ex. 2307
`
`S. Kamjoo, Intravitreal Injections, EyeWiki, accessed at
`https://eyewiki.aao.org/Intravitreal_Injections on 01/17/2022
`Jost B. Jonas et al., Intravitreal Injection Of Triamcinolone for Diffuse
`Diabetic Macular Edema, Arch. Ophthalmol. (2003), 121(1):57-61
`Pradeep Y. Ramulu, Use of Retinal Procedures in Medicare
`Beneficiaries from 1997 to 2007, Arch. Ophthalmol. (2010),
`128(10):1335-40
`Ex. 2309 Riva L. Asbell, An Analysis of CMS Retina Utilization Statistics,
`Retina Today 22 (2016), accessible at
`https://retinatoday.com/pdfs/0516RT_Coding.pdf
`EVS Study Group, Results of the Endophthalmitis Vitrectomy Study,
`Arch. Ophthalmol. (1995), 113(12):1479-96
`Ex. 2311 Denis Dossarps et al., Endophthalmitis After Intravitreal Injections:
`Incidence, Presentation, Management, and Visual Outcome, Am. J.
`Ophthalmol. (2015), 160(1):17-25
`Ex. 2312 Kathryn S. Klein et al., Endophthalmitis After Anti-VEGF Injections,
`Ophthalmol. (2009), 116(6):1225.e1
`Ex. 2313 Amy E. Green-Simms, Noha S. Ekdawi & Sophie J. Bakri, Survey of
`Intravitreal Injection Techniques Among Retinal Specialists in the
`U