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`
`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 Owner.
`______________________
`
`Case No. IPR2021-00816
`U.S. Patent No. 9,220,631
`______________________
`
`PETITIONER’S OPPOSITION TO
`PATENT OWNER’S CONTINGENT MOTION TO AMEND
`
`
`
`
`
`
`
`
`
`

`

`I. 
`
`II. 
`
`B. 
`
`B. 
`
`C. 
`
`B. 
`
`
`
`
`
`2. 
`
`TABLE OF CONTENTS
`
`THE SUBSTITUTE CLAIMS INTRODUCE NEW MATTER AND LACK
`WRITTEN DESCRIPTION SUPPORT .......................................................... 1 
`A. 
`The Original Disclosure Does Not Convey Possession of a Syringe
`Having 1-25 µg or 3-25 µg of Silicone Oil, a Break Loose Force of
`Less Than 11N, and a Shelf Life of at Least 12 Months ...................... 2 
`The Original Disclosure Does Not Convey Possession of a 1 mL
`Syringe Having 1-25 µg or 3-25 µg of Silicone Oil and a Break Loose
`Force of Less Than 11N ........................................................................ 8 
`THE SUBSTITUTE CLAIMS ARE UNPATENTABLE UNDER 35 U.S.C.
`§ 102(F).......................................................................................................... 10 
`A. 
`The Numerical Ranges of Silicone Oil to Yield the Claimed Forces
`Are a Significant Aspect of the Claimed Invention ............................ 11 
`Vetter Employees Made Significant Contributions to the Conception
`of the Numerical Ranges of Silicone Oil ............................................ 12 
`1. 
`The Novartis Inventors Did Not Possess a Concept before
`Working with Vetter ................................................................. 12 
` and
` Made Significant
`Contributions to the Conception of the Silicone Oil Ranges .... 15 
`Post-Conception Documents Confirm That Vetter Employees Made
`Significant Contributions to the Conception of the Silicone Oil
`Ranges ................................................................................................. 18 
`III.  THE SUBSTITUTE CLAIMS ARE NOT ENABLED ................................ 20 
`A. 
`The Specification Does Not Enable the Open-Ended “Shelf Life”
`Limitation ............................................................................................ 20 
`The Specification Does Not Enable a Syringe Having about 1 µg or
`about 3 µg of Silicone Oil ................................................................... 22 
`IV.  THE SUBSTITUTE CLAIMS ARE INDEFINITE ...................................... 25 
`V. 
`THE SUBSTITUTE CLAIMS ARE UNPATENTABLE UNDER 35 U.S.C.
`§ 103 .............................................................................................................. 28 
`A.  Disclosure of New Limitations and Motivation to Combine .............. 30 
`B. 
`Reasonable Expectation of Success .................................................... 33 
`
`
`
`i
`
`

`

`
`
`
`
`C. 
`Claim Chart ......................................................................................... 35 
`VI.  CONCLUSION .............................................................................................. 45 
`
`
`
`
`
`
`
`
`ii
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`

`

`
`
`
`
`PETITIONER’S EXHIBIT LIST
`
`Ex. 1001 U.S. Patent No. 9,220,631 (“the ’631 Patent”)
`
`Ex. 1002
`
`Prosecution File History of U.S. Patent No. 9,220,631
`
`Ex. 1003 Declaration of Horst Koller under 37 C.F.R. § 1.68.
`
`Ex. 1004
`
`Curriculum Vitae of Horst Koller
`
`Ex. 1005
`
`Ex. 1006
`
`Ex. 1007
`
`Ex. 1008
`
`Ex. 1009
`
`Ex. 1010
`
`Ex. 1011
`
`ITC Investigation No. 337-TA-1207, Staff’s Pre-Hearing Brief
`(public version)
`
`ITC Investigation No. 337-TA-1207, Complainant’s Unopposed
`Motion to Terminate
`
`PCT Patent Publication No. WO 2011/006877 to Sigg et al.
`(“Sigg”)
`
`PCT Patent Publication No. WO 2009/030976 to Boulange et al.
`(“Boulange”)
`
`Internet Archive WayBack Machine, March 7, 2011 Record of
`Drugs.com, Macugen Prescribing Information, available at
`https://web.archive.org/web/20110307065238/http://www.drugs.c
`om: 80/pro/macugen.html (“2008 Macugen Label”)
`ITC Investigation No. 337-TA-1207, Initial Determination
`Terminating the Investigation
`
`Bhavnesh D. Shah & Bhupendra G. Prajapati, Pre-Filled
`Syringes: A New Concept, PHARMA BIO WORLD 51 (2009)
`(“Shah”)
`
`Ex. 1012 Arno Fries, Drug Delivery of Sensitive Biopharmaceuticals With
`Prefilled Syringes, 9(5) DRUG DELIVERY TECH. 22 (2009)
`(“Fries”)
`
`Ex. 1013
`
`Thomas Schoenknecht, Prefilled Syringes: Why New
`Developments Are Important In Injectable Delivery Today, in
`PREFILLED SYRINGES INNOVATIONS THAT MEET THE GROWING
`DEMAND (OnDrugDelivery 2005) (“Schoenknecht”)
`
`iii
`
`

`

`
`
`
`
`Ex. 1014 U.S. Patent Publication No. 2012/0091026 to Chacornac et al.
`(“Chacornac”)
`
`Ex. 1015
`
`Ex. 1016
`
`Sandeep Nema & John D. Ludwig, Pharmaceutical Dosage
`Forms: Parenteral Medications, Volume 1: Formulation and
`Packaging (3rd ed. 2010) (“Nema Vol. 1”)
`
`Sandeep Nema & John D. Ludwig, Pharmaceutical Dosage
`Forms: Parenteral Medications, Volume 2: Facility Design,
`Sterilization and Processing (3rd ed. 2010) (“Nema Vol. 2”)
`
`Ex. 1017
`
`PCT Patent Publication No. WO 2007/035621 to Scypinski et al.
`(“Scypinski”)
`
`Ex. 1018 U.S. Patent Publication No. 2003/0003014 to Metzner et al.
`(“Metzner”)
`
`Ex. 1019 U.S. Pharmacopeia, USP 789, Particulate Matter in Ophthalmic
`Solutions, USP 34 NF 29 (2011)
`
`Ex. 1020 U.S. Patent Publication No. 2011/276005 to Hioki et al. (“Hioki”)
`
`Ex. 1021
`
`PCT Patent Publication No. WO 2007/149334 to Furfine et al.
`(“Furfine”)
`
`Ex. 1022 Michael W. Stewart et al., Fresh From the Pipeline Aflibercept,
`11 NAT. REV. DRUG DISCOV. 269 (2012) (“Stewart”)
`
`Ex. 1023 U.S. Patent No. 7,060,269 to Baca et al. (“Baca”)
`
`Ex. 1024 Gerald McDonnel and Denver Russell, Antiseptics and
`Disinfectants: Activities, Action, and Resistance, Clinical
`Microbiology Review, (Jan. 1999) (“McDonnel”).
`
`Ex. 1025
`
`Lu Liu et al., Silicone Oil Microdroplets and Protein Aggregates
`in Repackaged Bevacizumab and Ranibizumab: Effects of Long-
`term Storage and Product Mishandling, 52(2) INVESTIGATIVE
`OPHTHALMOLOGY & VISUAL SCIENCE 1023 (2011) (“Liu”)
`
`Ex. 1026 U.S. Patent No. 7,404,278 to Wittland et al. (“Wittland”)
`
`iv
`
`

`

`
`
`
`
`Ex. 1027 U.S. Food and Drug Administration, Lucentis® Highlights of the
`Prescribing Information, (June 2010) (“Lucentis Label”)
`
`Ex. 1028
`
`Ex. 1029
`
`Ex. 1030
`
`International Organization for Standardization, ISO 11040-4
`Prefilled Syringes – Part 4: Glass Barrels for Injectables (2nd ed.
`2007) (“ISO 11040-4”)
`
`PCT Patent Publication No. WO 2008/077155 to Lam et al.
`(“Lam”)
`
`James A. Dixon, et al. "VEGF Trap-Eye for the treatment of
`neovascular age-related macular degeneration." Expert opinion on
`investigational drugs 18.10 (2009): 1573-1580. (“Dixon”)
`
`Ex. 1031 Declaration of Dr. Szilard Kiss under 37 C.F.R. § 1.68.
`
`Ex. 1032
`
`Curriculum Vitae of Dr. Szilard Kiss
`
`Ex. 1033 Declaration of James L. Mullins, Ph.D.
`
`Ex. 1034 Dow Corning® 365 35% Dimethicone NF Emulsion – Frequently
`Asked Questions (2002) (“DC365 FAQ”)
`
`Ex. 1035
`
`European Patent Application No. 12174860 to Novartis AG
`
`Ex. 1036 U.S. Food and Drug Administration, Guidance for Industry:
`Sterile Drug Products Produced by Aseptic Processing—Current
`Good Manufacturing Practice (September 2004)
`
`Ex. 1037 Affidavit of Internet Archive Office Manager
`
`Ex. 1038
`
`Ex. 1039
`
`Internet Archive WayBack Machine, March 8, 2011 Record of
`Drugs.com, Welcome to Drugs.com, available at
`https://web.archive.org/web/20110308203650/http://www.drugs.c
`om:
`80/
`
`Internet Archive WayBack Machine, February 25, 2011 Record
`of Drugs.com, FDA Professional Drug Information, available at
`https://web.archive.org/web/20110225193929/http://www.drugs.c
`om:
`80/pro/
`
`v
`
`

`

`
`
`
`
`Ex. 1042
`
`Ex. 1043
`
`Ex. 1040 U.S. Food and Drug Administration, Eylea® Highlights of the
`Prescribing Information, (November 2011) (“Eylea label”)
`Ex. 1041 U.S. Food and Drug Administration, Guidance for Industry:
`Container Closure Systems for Packaging Human and Biologics –
`Chemistry, Manufacturing, and Controls Documentation (May
`1999), available at
`https://www.fda.gov/downloads/drugs/guidances/ucm070551.pdf
`International Standard ISO-7864, Sterile hypodermic needles for
`single use, ISO 7864:1993(E) (“ISO-7864”)
`International Standard ISO-9626, Stainless steel needle tubing for
`the manufacture of medical devices – Amendment 1, ISO
`9626:1991/Amd.1:2001(E) (“ISO-9626”)
`Ex. 1044 Advait Badkar, et al. Development of Biotechnology Products in
`Pre-filled Syringes: Technical Considerations and Approaches,
`American Association of Pharmaceutical Sciences, June 2011,
`12(2): 564-572 (“Badkar”)
`Ex. 1045 William Leventon, “Medical Device Sterilization: What
`Manufacturers Need to Know” (MDDI online, Sept. 1, 2002),
`available at https://www.mddionline.com/medical-device-
`sterilization-what-manufacturers-need-know (“Leventon”)
`Pamela Carter, et al. The lowdown on low temperature
`sterilization for packaged devices, Healthcare Purchasing News,
`July 2008, 42-45. (“Carter”)
`Ex. 1047 U.S. Patent Publication No. 2005/0182370 to Hato (“Hato”)
`
`Ex. 1046
`
`Ex. 1049
`
`Ex. 1048 U.S. Department of Labor, Occupational Safety & Health
`Administration, Ethylene Oxide (EtO): Understanding OSHA’s
`Exposure monitoring Requirements, 2007 OSHA3325-01N
`(2007), available at
`https://www.osha.gov/Publications/ethylene_oxide.html (“OSHA
`Guidelines”)
`Bryon Lambert, et al. Radiation and Ethylene Oxide Terminal
`Sterilization Experiences with Drug Eluting Stent Products,
`American Association of Pharmaceutical Sciences, December
`2011, 12(4):1116-1126 (“Lambert”)
`IPR2020-1317, Paper No. 10, Patent Owner’s Preliminary
`Response
`IPR2020-1317, Paper No. 14, Patent Owner’s Sur-Reply
`
`
`Ex. 1050
`
`Ex. 1051
`
`vi
`
`

`

`
`
`
`
`Ex. 1052
`
`Ex. 1053
`
`Ex. 1055
`
`Ex. 1057
`
`Ex. 1058
`
`John R. Gillis & Gregg Mosley, Validation of Pharmaceutical
`Processes, Chapter 16 – Validation of Ethylene Oxide
`Sterilization Processes (2011), pp.241-262 (“Gillis”)
`FDA Pesticide Analytical Manual Vol. 1, Chapter 6 - HPLC,
`available at
`https://www.fda.gov/downloads/Food/FoodScienceResearch/
`ucm113651.pdf
`Ex. 1054 Kim, Leo & D’Amore, Patricia, ASIP Centennial Commentary –
`A Brief History of Anti-VEGF for the Treatment of Ocular
`Angiogenesis, The American Journal of Pathology, August 2012
`182(2):376-379, available at (note: published online July 2,
`2012 https://ajp.amjpathol.org/article/S0002-9440(12)00442-
`7/fulltext )
`J.S. Penn, et al. Vascular Endothelial Growth Factor in Eye
`Disease, Prog. Retin Eye Res., July 2008, 27(4):331-371.
`(“Penn2008”)
`Ex. 1056 U.S. Food and Drug Administration, Trivaris ® Highlights of the
`Prescribing Information, (May 2008) (“Trivaris label”)
`Internet Archive WayBack Machine, May 17, 2011 Record of
`U.S. Pharmacopeia, Understanding USP–NF, available at
`https://web.archive.org/web/20110517215303/http://www.usp.org
`/
`USPNF/understandingUSPNF.html
`Christine I. Falkner-Radler, et al. Needle Size in Intravitreal
`Injections-Preliminary Results of a Randomized Clinical Trial,
`AVRO Annual Meeting Abstract, March 2012, 54(884), available
`at https://iovs.arvojournals.org/article.aspx?articleid=2350271
`(“ARVO abstract”)
`Carsten H. Meyer, et al. Steps for a Safe Intravitreal Injection
`Technique – A look at how European and American approaches
`compare, Retinal Physician (July 1, 2009), available at
`https://www.retinalphysician.com/issues/2009/july-aug/steps-for-
`a-safe-intravitreal-injection-technique (“Meyer”)
`Curriculum Vitae of James L. Mullins, Ph.D.
`
`Ex. 1059
`
`Ex. 1060
`
`Ex. 1061 DUPONT™ TYVEK® COMPLIANCE TO ISO 11607-1:2006
`(2011)
`Center for Drug Evaluation and Research, Application Number:
`21-756, Approved Labeling, Macugen® (pegaptanib sodium
`injection) (December 17, 2004) (“2004 Macugen Label”)
`
`Ex. 1062
`
`vii
`
`

`

`
`
`
`
`Ex. 1063
`
`Ex. 1064
`
`Evangelos S. Gragoudas, et al. Pegaptanib for Neovascular Age-
`Related Macular Degeneration, New England Journal of
`Medicine 2004; 351:2805-16, with Supplementary Appendix.
`IPR2020-1317, Paper No. 15, Institution Decision
`
`Ex. 1067
`
`Ex. 1065 Anita M. Leys, et al. Neovascular Growth Following
`Photodynamic Therapy for Choroidal Hemangioma and
`Neovascular Regression after Intravitreous Injection of
`Triamcinolone, Retina 2006; 26(6):693-7, available at
`https://pubmed.ncbi.nlm.nih.gov/16829815/ (“Leys”)
`Ex. 1066 Australian Government, Department of Health and Ageing,
`Australian Public Assessment Report for Aflibercept, (July 2012)
`Sophie J. Bakri and Noha S. Ekdawi, Intravitreal Silicone Oil
`Droplets after Intravitreal Drug Injections, Retina 2008; 20:996-
`1001, available at https://pubmed.ncbi.nlm.nih.gov/18698303/
`(“Bakri”)
`Jared S. Bee, et al. Effects of Surfaces and Leachables on the
`Stability of Biopharmaceuticals, Journal of Pharmaceutical
`Science (Oct. 2011), available at
`https://pubmed.ncbi.nlm.nih.gov/21523787/ (“Bee”)
`Ex. 1069 Michael Colucciello, Prefilled Syringe Delivery of Intravitreal
`Anti-VEGF Medications: Advantages for Patients and Physicians,
`Retinal Physician (Mar. 1, 2019), available at
`https://www.retinalphysician.com/issues/2019/march-
`2019/prefilled-syringe-delivery-of-intravitreal-anti-ve
`(“Colucciello”)
`Ex. 1070 Declaration of Juergen Sigg (“Sigg Declaration”)
`
`Ex. 1068
`
`Ex. 1072
`
`Ex. 1071 Department of Health & Human Services, Macugen Approval
`Letter (Dec. 18, 2004)
`Lonny Wolgemuth, Challenges with Prefilled Syringes: The
`Parylene Solution, ONdrugDelivery (Oct. 2012), available at
`https://ondrugdelivery.com/wp-
`content/uploads/2018/11/Oct2012.pdf
`Therese M. Sassalos, Prefilled Syringes for Intravitreal Drug
`Delivery, Clinical Ophthalmology 2019:13 701-706, available at
`https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485318/
`
`Ex. 1073
`
`viii
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`

`

`
`
`
`
`Ex. 1074
`
`Ex. 1075
`
`SCS Coating Systems, SCS Parylene Properties (2007), available
`at
`https://www.physics.rutgers.edu/~podzorov/parylene%20properti
`es.pdf (“SCS”)
`Lonny Wolgemuth, Assessing the Effects of Sterilization Methods
`on Parylene Coating, Medical Device & Diagnostic Industry,
`(Aug. 2002)
`Ex. 1076 David E. Overcashier, et al. Technical Considerations in the
`Development of Pre-filled Syringes for Protein Products, Am.
`Pharm. Rev. 2006;9(7): 77-83 (“Overcashier”)
`SDNY 20-5502 Docket
`
`Ex. 1077
`
`Ex. 1078
`
`Federal Court Statistics
`
`Ex. 1079 Novartis Letter to NDNY Court
`
`Ex. 1080 Mehmet S. Kocabora, et al. Intravitreal Silicone Oil Droplets
`Following Pegaptanib Injection, Acta Ophthalmologica 2010,
`available at
`https://onlinelibrary.wiley.com/doi/full/10.1111/j.1755-
`3768.2008.01336.x (“Kocabora”)
`Ex. 1081 Macugen Label (2008)
`
`Ex. 1082 U.S. Pharmacopeia, USP 789, Particulate Matter in Ophthalmic
`Solutions, USP 32 NF 27 (2009)
`
`Ex. 1083 Novartis NDNY Complaint
`
`Ex. 1084 Novartis Letter to SDNY Court
`
`Ex. 1086
`
`Ex. 1085
`
`ITC Investigation No. 337-TA-1207, Statement on the Public
`Interest by Proposed Respondent Regeneron Pharmaceuticals,
`Inc.
`ITC Investigation No. 337-TA-1207, Statement on the Public
`Interest by Szilard Kiss
`Ex. 1087 Nitin Rathore, et al. Variability in Syringe Components and its
`Impact on Functionality of Delivery Systems, PDA Journal of
`Pharmaceutical Science and Technology 2011, 65 468-480
`(“Rathore”)
`
`ix
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`

`
`
`
`
`
`
`Ex. 1088
`Ex. 1088
`
`PCT Patent Publication No. WO 2007/084765 to Deschatelets et
`PCT Patent Publication No. WO 2007/084765 to Deschatelets et
`al.
`al.
`
`
`
`Ex. 1089
`Ex. 1089
`
`PCT Patent Publication No. WO 97/44068 to Tack et al.
`PCT Patent Publication No. WO 97/44068 to Tacket al.
`
`Text Minute Entry re Rule 16 Conference held on August 18,
`Ex. 1090
`Ex. 1090|Text Minute Entry re Rule 16 Conference held on August 18,
`2021, Novartis Pharma AG et al v. Regeneron Pharma., Inc., No.
`2021, Novartis Pharma AG et al v. Regeneron Pharma., Inc., No.
`1:20-cv-00690 (N.D.N.Y. Aug. 18, 2021)
`1:20-cv-00690
`(N.D.N.Y. Aug. 18, 2021
`Ex. 1091 Declaration of Juergen Sigg (Not Filed)
`Ex. 1091|Declaration of Juergen Sigg (Wot Filed)
`
`
`Ex. 1092
`Supplemental Declaration of Horst Koller under 37 C.F.R. § 1.68
`Ex. 1092|Supplemental Declaration of Horst Koller under 37 C.F.R. § 1.68
`(Not Filed)
`(Not Filed)
`Supplemental Declaration of Szilard Kiss under 37 C.F.R. § 1.68
`Ex. 1093
`Ex. 1093|Supplemental Declaration of Szilard Kiss under 37 C.F.R. § 1.68
`(Not Filed)
`NotFilea
`Ex. 1094 ONDrugDelivery, Prefilled Syringe, available at
`Ex. 1094|ONDrugDelivery, Prefilled Syringe, available at
`https://ondrugdelivery.com/magazines/prefilled-syringes-the-rise-
`https://ondrugdelivery.com/magazines/prefilled-syringes-the-rise-
`ofthe-
`ofthe-
`delivery-device-portfolio/ (Not Filed)
`delivery-device-portfolio/ (Not Filea
`Ex. 1095 Declaration of Petra Scamborova, PhD, JD In Support of Motion
`Ex. 1095|Declaration of Petra Scamborova, PhD, JD In Support of Motion
`for Pro Hac Vice Admission Under 37 C.F.R. § 42.10
`for Pro Hac Vice Admission Under 37 C.F.R. § 42.10
`Biography of Petra Scamborova, PhD, JD
`Ex. 1096
`
`Ex. 1096__|Biography of Petra Scamborova, PhD, JD
`
`January 6, 2022, Telephonic Conference Transcript
`Ex. 1097
`Ex. 1097|January 6, 2022, Telephonic Conference Transcript
`
`Ex. 1098 Declaration of Robert T. Vlasis in Support of Motion for Pro Hac
`Ex. 1098|Declaration of Robert T. Vlasis in Support of Motion for Pro Hac
`Vice Admission Under 37 C.F.R. § 42.10
`Vice Admission Under 37 C.F.R. § 42.10
`Ex. 1099
`Biography of Robert T. Vlasis
`Ex. 1099‘|Biography of Robert T. Vlasis
`
`Ex. 1100 Declaration of James Agalloco – Filed Under Seal
`Ex. 1100|Declaration of James Agalloco — Filed Under Seal
`
`Ex. 1101 Declaration of Dr. Gregory Sawyer – Filed Under Seal
`Ex. 1101|Declaration of Dr. Gregory Sawyer — Filed UnderSeal
`
`
`Ex. 1102 Declaration of Dr. Kenneth Graham – Filed Under Seal
`Ex. 1102|Declaration of Dr. Kenneth Graham — Filed Under Seal
`
`Ex. 1103
`Second Declaration of James L. Mullins, Ph.D.
`Ex. 1103|Second Declaration of James L. Mullins, Ph.D.
`
`Ex. 1104
`Intentionally Left Blank
`Ex. 1104|Intentionally Left Blank
`
`Reply Declaration of Horst Koller – Filed Under Seal
`Ex. 1105
`Ex. 1105|Reply Declaration of Horst Koller — Filed Under Seal
`
`Reply Declaration of Dr. Szilard Kiss – Filed Under Seal
`Ex. 1106
`Ex. 1106|Reply Declaration of Dr. Szilard Kiss — Filed Under Seal
`
`x
`
`

`

`Ex. 1107 Declaration of Lisa Cameron – Filed Under Seal
`
`Ex. 1108 Declaration of Joel M. Cohen
`
`
`
`
`
`Ex. 1110
`
`Ex. 1115
`
`Ex. 1109 Deposition of Kim Cameron, Ph.D., IPR2021-00816 (3/17/2022)
`– Filed Under Seal
`Persson, et. al., Elastic contact mechanics: Percolation of the
`contact area and fluid squeeze-out, Eur. Phys. J. E. (2012)
`
`Ex. 1111 Nishimoto, et al., Determination of Conditions for the Production
`Scale Sterilization of Prefilled Syringes, 57 PDA J Pharm Sci. &
`Tech, 378-386 (2003)
`Ex. 1112 NOVITC(CH)00137958 – Novartis Confidential Internal
`Memorandum – Filed Under Seal
`Ex. 1113 NOVITC(CH)00143346 – Novartis Confidential Internal
`Memorandum – Filed Under Seal
`Ex. 1114 NOVITC(CH)00258369 – Novartis Confidential Internal
`Presentation – Filed Under Seal
`“Highlights of Prescribing Information,” Lucentis, FDA, June
`2006, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/1251
`56lbl.pdf
`Ex. 1116 NOVITC(CH)00195649 – Vetter Confidential Memorandum –
`Filed Under Seal
`Ex. 1117 NOVITC(CH)00145642 – Novartis Confidential Meeting
`Minutes – Filed Under Seal
`Ex. 1118 NOVITC(CH)00144912 – Novartis Confidential Meeting
`Minutes – Filed Under Seal
`Ex. 1119 NOVITC(CH)00205699 – Vetter Confidential Presentation –
`Filed Under Seal
`Ex. 1120 NOVITC(CH)00184035 – Vetter Confidential Memorandum –
`Filed Under Seal
`Ex. 1121 NOVITC(CH)00198709 – Vetter Confidential Presentation –
`Filed Under Seal
`Ex. 1122 NOVITC(CH)00867567 – Vetter Confidential Memorandum –
`Filed Under Seal
`Ex. 1123 NOVITC(CH)00150140 – Vetter Confidential Emails – Filed
`Under Seal
`Ex. 1124 NOVITC(CH)00337493 – Vetter Confidential Presentation –
`Filed Under Seal
`
`xi
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`

`

`
`
`
`
`
`
`Ex. 1125 NOVITC(CH)00352054 – Vetter Confidential Emails – Filed
`Ex.1125|NOVITC(CH)00352054 — Vetter Confidential Emails — Filed
`Under Seal
`Under Seal
`Ex. 1126 VETTER_00001432 – Vetter Confidential Presentation – Filed
`Ex. 1126|VETTER_00001432 — Vetter Confidential Presentation — Filed
`Under Seal
`Under Seal
`Ex. 1127 NOVITC(CH)00170626 – Vetter Confidential Memorandum –
`Ex. 1127|NOVITC(CH)00170626 — Vetter Confidential Memorandum —
`Filed Under Seal
`Filed UnderSeal
`Ex. 1128 NOVITC(CH)00170434 – Vetter Confidential Letter – Filed
`Ex.1128|NOVITC(CH)00170434 — Vetter Confidential Letter — Filed
`Under Seal
`Under Seal
`REGITC01116474 – DE 20 2012 011 016.0
`Ex. 1129
`Ex.1129|REGITCO1116474 — DE 20 2012 011 016.0
`
`
`
`
`
`
`Ex. 1130 NOVITC(CH)00170689 – Novartis Confidential Agreement –
`Ex. 1130|NOVITC(CH)00170689 — Novartis Confidential Agreement —
`Filed Under Seal
`Filed Under Seal
`Ex. 1131 NOVITC(CH)00217299 – Novartis Confidential Presentation –
`Ex. 1131|NOVITC(CH)00217299 — Novartis Confidential Presentation —
`Filed Under Seal
`Filed Under Seal
`Ex. 1132 NOVITC(CH)00311660 – Novartis Confidential Report – Filed
`Ex. 1132|NOVITC(CH)00311660 — Novartis Confidential Report — Filed
`Under Seal
`Under Seal
`Ex. 1133 NOVITC(CH)00133717 – Novartis Confidential Report – Filed
`Ex. 1133.|NOVITC(CH)00133717 — Novartis Confidential Report — Filed
`Under Seal
`
`Under Seal
`Ex. 1134 NOVITC(CH)03375527 – Novartis Confidential Presentation –
`Ex. 1134|NOVITC(CH)03375527 — Novartis Confidential Presentation —
`Filed Under Seal
`Filed Under Seal
`Ex. 1135 NOVITC(CH)03530811 – Novartis Confidential Presentation –
`Ex. 1135|NOVITC(CH)03530811 — Novartis Confidential Presentation —
`Filed Under Seal
`Filed Under Seal
`Ex. 1136 NOVITC(CH)03540210 – Novartis Confidential Presentation –
`Ex. 1136|NOVITC(CH)03540210 — Novartis Confidential Presentation —
`Filed Under Seal
`Filed Under Seal
`Ex. 1137
`REGITC00114439 – Regeneron Confidential Report – Filed
`Ex.1137|REGITC00114439 — Regeneron Confidential Report — Filed
`Under Seal
`
`Under Seal
`REGITC00042686 – Vetter Confidential Report – Filed Under
`Ex. 1138
`Ex. 1138|REGITC00042686 — Vetter Confidential Report — Filed Under
`Seal
`Seal
`
`Ex. 1139
`REGITC00264748 – Regeneron Confidential Report – Filed
`Ex. 1139|REGITC00264748 — Regeneron Confidential Report — Filed
`Under Seal
`UnderSeal
`Ex. 1140
`REGITC00149282 – Regeneron Confidential Report – Filed
`Ex. 1140|REGITC00149282 — Regeneron Confidential Report — Filed
`Under Seal
`UnderSeal
`Ex. 1141
`STERIS_00000489 – Steris Report – Filed Under Seal
`Ex. 1141|STERIS00000489 — Steris Report — Filed Under Seal
`
`
`REGITC00122265 – Regeneron Confidential Report – Filed
`Ex. 1142
`Ex. 1142|REGITC00122265 — Regeneron Confidential Report — Filed
`Under Seal
`UnderSeal
`REGITC00116953 – Vetter Confidential Report – Filed Under
`Ex. 1143
`Ex. 1143.|REGITC00116953 — Vetter Confidential Report — Filed Under
`Seal
`Seal
`
`
`xii
`Xi
`
`

`

`
`
`
`
`Ex. 1144
`REGITC01008782 – Vetter Confidential Report – Filed Under
`Ex. 1144|REGITC01008782 — Vetter Confidential Report — Filed Under
`Seal
`Seal
`Ex. 1145
`REGITC00381349 – Regeneron Confidential Report – Filed
`Ex. 1145|REGITC00381349 — Regeneron Confidential Report — Filed
`Under Seal
`UnderSeal
`Ex. 1146
`REGITC00255816 – Bayer Correspondence with EMEA – Filed
`Ex. 1146|REGITC00255816 — Bayer Correspondence with EMEA — Filed
`Under Seal
`UnderSeal
`Ex. 1147
`REGITC00883958 – Regeneron Confidential Memorandum –
`Ex. 1147|REGITC00883958 — Regeneron Confidential Memorandum —
`Filed Under Seal
`
`Filed UnderSeal
`Ex. 1148
`REGITC00264472 – Regeneron Confidential Memorandum –
`Ex. 1148|REGITC00264472 — Regeneron Confidential Memorandum —
`Filed Under Seal
`Filed UnderSeal
`Ex. 1149
`REGITC01066319 – Regeneron Confidential Memorandum –
`Ex. 1149|REGITC01066319 — Regeneron Confidential Memorandum —
`Filed Under Seal
`Filed UnderSeal
`REGITC00149657 – EMA Assessment Report – Filed Under
`Ex. 1150
`Ex. 1150|REGITC00149657 — EMA Assessment Report — Filed Under
`Seal
`Seal
`Ex. 1151
`REGITC00381924 – Regeneron Confidential Memorandum –
`Ex. 1151|REGITC00381924 — Regeneron Confidential Memorandum —
`Filed Under Seal
`
`Filed UnderSeal
`Ex. 1152
`REGITC00041726 – Regeneron Confidential Presentation – Filed
`Ex. 1152|REGITC00041726 — Regeneron Confidential Presentation — Filed
`Under Seal
`UnderSeal
`Ex. 1153
`REG_SDNY_02214433 – EMA Correspondence – Filed Under
`Ex. 1153.|REG_SDNY_02214433 —- EMA Correspondence — Filed Under
`Seal
`Seal
`Ex. 1154
`REGITC00160863 – Regeneron Confidential Memorandum –
`Ex. 1154|REGITC00160863 — Regeneron Confidential Memorandum —
`Filed Under Seal
`Filed UnderSeal
`Ex. 1155
`REGITC00110725 – Regeneron Confidential Emails – Filed
`Ex. 1155|REGITC00110725 — Regeneron Confidential Emails — Filed
`Under Seal
`UnderSeal
`Ex. 1156
`REGITC00117031 – Regeneron Confidential FDA
`Ex. 1156|REGITC00117031 — Regeneron Confidential FDA
`Correspondence – Filed Under Seal
`Correspondence — Filed UnderSeal
`Ex. 1157 REGITC01116755 – Confidential Sales Data – Filed Under Seal
`REGITC01116755 — Confidential Sales Data — Filed Under Seal
`Ex. 1157
`
`Sigg ITC Deposition Transcript (12/17/2020) – Filed Under Seal
`Ex. 1158
`Ex. 1158|Sigg ITC Deposition Transcript (12/17/2020) — Filed Under Seal
`
`
`
`
`
`
`
`Roettelle ITC Deposition Transcript (12/14/2020) – Filed Under
`Ex. 1159
`Ex. 1159|Roettelle ITC Deposition Transcript (12/14/2020) — Filed Under
`Seal
`Seal
`Ex. 1160
`Picci ITC Deposition Transcript (12/16/2020) – Filed Under Seal
`Ex. 1160|Picci ITC Deposition Transcript (12/16/2020) — Filed Under Seal
`
`Sauer ITC Deposition Transcript (12/18/2020) – Filed Under Seal
`Ex. 1161
`Ex. 1161|Sauer ITC Deposition Transcript (12/18/2020) — Filed Under Seal
`
`
`Ex. 1162
`BD-ITC-000069 – Becton Dickinson Presentation – Filed Under
`Ex. 1162|BD-ITC-000069 — Becton Dickinson Presentation — Filed Under
`Seal
`Seal
`Ex. 1163
`REGITC00138524 – Requirements on pre-fillable glass syringes
`Ex. 1163|REGITC00138524 — Requirements on pre-fillable glass syringes
`
`xiii
`xiii
`
`

`

`
`
`
`
`Ex. 1165
`
`Ex. 1166
`
`Ex. 1164 Optical in Situ Micro Tribometer for Analysis of Real Contact
`Area for Contact Mechanics, Adhesion, and
`Sliding Experiments, B. A. Krick, J. R. Vail, B. N. J. Persson, and
`W. G. Sawyer, Tribology Letters 45 (2012) 185-
`194
`Plasmonic Diagnostics for Tribology: In Situ Observations using
`Surface Plasmon Resonance in Combination
`with Surface-Enhanced Raman Spectroscopy, B. A. Krick, D. H.
`Hahn, and W. G. Sawyer, Tribology Letters, 49
`(2013) 95-102.
`Accessing Inaccessible Interfaces: In Situ Approaches to
`Materials Tribology, W. G. Sawyer & K. J. Wahl, Guest
`Editors MRS Bulletin 33 (2008) 1145-1189
`Ex. 1167 VETTER_10013300_EN (Certified Translation) – Vetter
`Confidential Emails – Filed Under Seal
`Ex. 1168 VETTER_10001435_EN (Certified Translation) – Vetter
`Confidential Emails – Filed Under Seal
`Lorenz, et al., Static or breakloose friction for lubricated
`contacts: the role of surface roughness and dewetting, J. Phys.
`Condens. Matter 25 (2013)
`Curriculum Vitae of Lisa Cameron
`
`Ex. 1169
`
`Ex. 1170
`
`Ex. 1171 Declaration of Lisa Cameron – List of Materials Considered
`
`Ex. 1173
`
`Ex. 1174
`
`Ex. 1172 Deposition of James E. Malackowski, IPR2021-00816
`(3/29/2022) – Filed Under Seal
`Jesse David and Marion Stewart, Commercial Success: Economic
`Principles Applied to Patent Litigation
`T. McNelis, “New Designs: Licenses May Be Evidence of the
`Nonobviousness of an Invention,” Fenwick & West LLP, 1998,
`available at
`https://assets.fenwick.com/legacy/FenwickDocuments/New_Desi
`gns.pdf
`Turbert, “Anti-VEGF Treatments,” American Academy of
`Ophthalmology, March 2, 2019, available at
`https://www.aao.org/eye-health/drugs/anti-vegf-treatments
`“Highlights of Prescribing Information,” Lucentis, FDA, revised
`March 2018, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/1251
`56s117lbl.pdf
`
`Ex. 1175
`
`Ex. 1176
`
`xiv
`
`

`

`
`
`
`
`“Highlights of Prescribing Information,” Eylea, FDA, revised
`Ex. 1177
`Ex. 1177|“Highlights of Prescribing Information,” Eylea, FDA, revised
`March 2021, available at
`March 2021, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/1253
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/1253
`87s069lbl.pdf
`87s069Ibl.pdf
`“Novartis Ophthalmics and Genentech announce development
`Ex. 1178
`Ex. 1178|“Novartis Ophthalmics and Genentech announce development
`and commercialization agreement for age-related macular
`and commercialization agreement for age-related macular
`degeneration treatment, Lucentis(TM),” Novartis Pharma AG
`degeneration treatment, Lucentis(TM),” Novartis Pharma AG
`press release, June 25, 2003, available at
`press release, June 25, 2003, available at
`https://www.globenewswire.com/news-
`https://www.globenewswire.com/news-
`release/2003/06/25/1839492/0/en/Novartis-Ophthalmics-and-
`release/2003/06/25/1839492/0/en/Novartis-Ophthalmics-and-
`Genentech-announce-development-and-commercialization-
`Genentech-announce-development-and-commercialization-
`agreement-for-age-related-macular-degeneration-treatment-
`agreement-for-age-related-macular-degeneration-treatment-
`Lucentis-TM.html
`Lucentis-TM.html
`Ex. 1179
`“Bayer HealthCare AG And Regeneron Pharmaceuticals, Inc. To
`Ex. 1179|“Bayer HealthCare AG And Regeneron Pharmaceuticals, Inc. To
`Collaborate On VEGF Trap For The Treatment Of Eye Diseases;
`Collaborate On VEGF Trap For The Treatment Of Eye Diseases;
`Regeneron Retains U.S. Commercialization Rights, Receives $75
`Regeneron Retains U.S. Commercialization Rights, Receives $75
`Million Upfront, And Eligible For Up To $245 Million Of
`Million Upfront, And Eligible For Up To $245 Million Of
`Milestone Payments,” Bayer HealthCare press release, October
`Milestone Payments,” Bayer HealthCare press release, October
`19, 2006, available at
`19, 2006, available at
`https://www.biospace.com/article/releases/bayer-healthcare-ag-
`https://www.biospace.com/article/releases/bayer-healthcare-ag-
`and-regeneron-pharmaceuticals-inc-to-collaborate-on-vegf-trap-
`and-regeneron-pharmaceuticals-inc-to-collaborate-on-vegf-trap-
`for-the-treatment-of-eye-diseases-b-regeneron-b-retains-u-s-c/
`for-the-treatment-of-eye-diseases-b-regeneron-b-retains-u-s-c/
`Eylea prefilled syringe now available,” Healio, December 12,
`Ex. 1180
`Ex. 1180|Eylea prefilled syringe now available,” Healio, December12,
`2019, available at
`2019, available at
`https://www.healio.com/news/ophthalmology/20191212/eylea-
`https://www.healio.com/news/ophthalmology/20191212/eylea-
`prefilled-syringe-now-available
`prefilled-syringe-now-available
`Ex. 1181
`“Beovu (brolucizumab injection) now publicly reimbursed in
`Ex. 1181|“Beovu (brolucizumab injection) now publicly retrmbursed in
`Ontario and New Brunswick for the treatment of neovascular
`Ontario and New Brunswick for the treatment of neovascular
`(wet) age-related macular degeneration,” Yahoo Finanace,
`(wet) age-related macular degeneration,” Yahoo Finanace,
`December 16, 2021, available at
`December 16, 2021, available at
`https://finance.yahoo.com/news/beovu-brolucizumab-injection-
`https://finance.yahoo.com/news/beovu-brolucizumab-injection-
`now-publicly-120000109.html?guccounter=1
`now-publicly-120000109.html?guccounter=1
`Ex. 1182 Mali Okada et al., “Nonadherence or Nonpersistence to
`Ex. 1182|Mali Okadaetal., “Nonadherence or Nonpersistence to
`Intravitreal Injection Therapy for Neovascular Age-Related
`Intravitreal Injection Therapy for Neovascular Age-Related
`Macular Degeneration: A Mixed Methods Systematic Review,”
`Macular Degeneration: A Mixed Methods Systematic Review,”
`Ophthalmology 128(2):234-247, August 5, 2020, available at
`Ophthalmology 128(2):234-247, August 5, 2020, available at
`https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403101/
`https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403101/
`
`
`
`
`
`
`
`xv
`
`XV
`
`

`

`
`
`
`
`Ex. 1183 Mali Okada, Tien Yin Wong, Paul Mitchell, et al., “Defining
`Ex. 1183|Mali Okada, Tien Yin Wong,Paul Mitchell, et al., “Defining
`Nonadherence and Nonpersistence to Anti–Vascular Endothelial
`Nonadherence and Nonpersistence to Anti—Vascular Endothelial
`Growth Factor Therapies in Neovascular Age-Related Macular
`Growth Factor Therapies in Neovascular Age-Related Macular
`Degeneration,” JAMA Ophthalmology 139(7): 769-776, June 3,
`Degeneration,” JAMA Ophthalmology 139(7): 769-776, June 3,
`2021, available at
`2021, available at
`https://jamanetwork.com/journals/jamaophthalmology/fullarticle/
`https://jamanetwork.com/journals/jamaophthalmology/fullarticle/
`2780