UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`MYLAN PHARMACEUTICALS INC., CELLTRION, INC., and
`APOTEX, INC.,
`Petitioners
`
`v.
`
`REGENERON PHARMACEUTICALS, INC.,
`Patent Owner
`
`____________
`
`Case IPR2021-008811
`Patent No. 9,254,338 B2
`____________
`
`EXPERT DECLARATION OF RICHARD MANNING, PH.D.
`
`CONFIDENTIAL MATERIAL - SUBJECT TO PROCTECTIVE ORDER
`
`1 IPR2022-00258 and IPR2022-00298 have been joined with this proceeding.
`
`Exhibit 2052
`Page 001 of 289
`
`Regeneron Pharmaceuticals, Inc. Exhibit 2001 Page 1
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`

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`CONFIDENTIAL MATERIAL– SUBJECT TO PROTECTIVE ORDER
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`
`
` Summary of Contents
`
`1.
`Introduction ............................................................................................. 1
`2. Regeneron Pharmaceuticals, Inc. ............................................................ 8
`3. U.S. Patent No. 9,254,338 ..................................................................... 10
`4. Relevant Economic Principles .............................................................. 14
`5. Medical Conditions at Issue .................................................................. 17
`6. Overview of Treatment Options for Relevant Angiogenic Eye
`Disorders ............................................................................................... 24
`7. Medicare Part B Reimbursement Policy ............................................... 43
`8. Commercial Success ............................................................................. 52
`9. Dosing Regimen is an Important Driver of Demand for Eylea ............ 97
`10. Eylea’s Commercial Success Cannot be Explained by Factors Not
`Related to the Claimed Methods of Treatment ................................... 122
`
`
`
`
`
`
`
`
`Expert Declaration of Richard Manning, Ph.D.
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`Page i
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`Exhibit 2052
`Page 002 of 289
`
`Regeneron Pharmaceuticals, Inc. Exhibit 2001 Page 2
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`CONFIDENTIAL MATERIAL– SUBJECT TO PROTECTIVE ORDER
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`Table of Contents
`
`
`1.
`
`Introduction ............................................................................................. 1
`1.1. Qualifications .................................................................................... 1
`1.2. Scope of work ................................................................................... 3
`1.3. Framework for commercial success ................................................. 4
`2. Regeneron Pharmaceuticals, Inc. ............................................................ 8
`3. U.S. Patent No. 9,254,338 ..................................................................... 10
`4. Relevant Economic Principles .............................................................. 14
`5. Medical Conditions at Issue .................................................................. 17
`6. Overview of Treatment Options for Relevant Angiogenic Eye
`Disorders ............................................................................................... 24
`6.1. Laser-based treatment options available prior to anti-VEGF
`therapies .......................................................................................... 24
`6.2. Anti-VEGF treatment options ........................................................ 26
`6.2.1. Macugen ................................................................................. 27
`6.2.2. Avastin .................................................................................... 28
`6.2.3. Lucentis .................................................................................. 29
`6.2.4. Eylea ....................................................................................... 31
`6.2.5. Beovu ...................................................................................... 34
`6.2.6. FDA approvals for anti-VEGF treatments ............................. 38
`6.2.7. FDA-approved dosing schedules for anti-VEGF
`treatment options .................................................................... 39
`7. Medicare Part B Reimbursement Policy ............................................... 43
`8. Commercial Success ............................................................................. 52
`8.1. U.S. Eylea sales and revenue .......................................................... 52
`8.1.1. Gross sales .............................................................................. 53
`8.1.2. Net sales ................................................................................. 54
`8.2. U.S. Eylea profits............................................................................ 56
`8.3. Eylea’s share of anti-VEGF sales ................................................... 60
`8.3.1. Data sources ........................................................................... 61
`Medicare Part B services and procedures ........................ 61
`
`Expert Declaration of Richard Manning, Ph.D.
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`Page ii
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`Exhibit 2052
`Page 003 of 289
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`Regeneron Pharmaceuticals, Inc. Exhibit 2001 Page 3
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`CONFIDENTIAL MATERIAL– SUBJECT TO PROTECTIVE ORDER
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`Vestrum Health ................................................................ 64
`Regeneron ATU surveys .................................................. 66
`8.3.2. Eylea’s historic patient share as an indicator of
`commercial success ................................................................ 69
`8.3.3. Eylea’s displacement of other anti-VEGF treatments as
`an indicator of commercial success ........................................ 80
`8.3.4. Eylea status as physicians’ most used treatment .................... 86
`8.4. Price has not hindered Eylea’s commercial success ...................... 89
`9. Dosing Regimen is an Important Driver of Demand for Eylea ............ 97
`9.1. Eylea’s patented dosing regimen addressed an unmet need for
`longer dosing intervals ................................................................... 99
`9.2. Eylea’s patented dosing regimen is a key differentiating factor .. 103
`9.2.1. Regeneron has promoted the patented dosing schedule
`and credits it as a key factor causing commercial
`success .................................................................................. 104
`9.2.2. Regeneron ATU surveys show that dosing interval has
`been an important driver of Eylea prescribing ..................... 109
`9.2.3. Members of the ASRS identified Eylea as allowing the
`longest treatment interval ..................................................... 114
`9.2.4. Regeneron public statements demonstrate the
`importance of the patented dosing schedule to Eylea’s
`commercial success .............................................................. 117
`9.3. Eylea is more effective at treating patients with worse visual
`acuity, which imparts a downward bias to its observed treatment
`interval .......................................................................................... 118
`10. Eylea’s Commercial Success Cannot be Explained by Factors Not
`Related to the Claimed Methods of Treatment ................................... 122
`10.1. Regeneron’s marketing efforts have been limited and have
`included promotion of the patented dosing regimen .................... 122
`10.2. Regeneron has had limited discounting and rebate programs ...... 126
`10.3. Regeneron’s sampling program is unlikely to have driven
`Eylea’s commercial success ......................................................... 129
`
`
`
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`
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`Expert Declaration of Richard Manning, Ph.D.
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`Page iii
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`Exhibit 2052
`Page 004 of 289
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`Regeneron Pharmaceuticals, Inc. Exhibit 2001 Page 4
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Table of Attachments
`
`
`Expert Materials
`Section A
`Attachment A-1 Curriculum Vitae of Richard Manning, Ph.D.
`
`Dosing Directions
`Section B
`Attachment B-1 Dosing Directions on FDA Labels
`
`Sales Shares
`Section C
`Attachment C-1 Sales Share Summary - All Indications
`Attachment C-2 Sales Share Summary - Wet AMD
`Attachment C-3 Sales Share Summary - DME
`Attachment C-4 Sales Share Summary - DR without DME
`Attachment C-5 Sales Share Summary - RVO
`Attachment C-6 Eylea's Sales Share Across Different Data Sources - All
`Indications
`Attachment C-7 Eylea's Sales Share Across Different Data Sources - Wet AMD
`Attachment C-8 Eylea's Sales Share Across Different Data Sources - DME
`Attachment C-9 Eylea's Sales Share Across Different Data Sources - DR
`without DME
`Attachment C-10 Eylea's Sales Share Across Different Data Sources - RVO
`Attachment C-11 Percentage Point Change in Total Sales Share Since Eylea
`Launch – ATU Data
`Attachment C-12 Percentage Point Change in Total Sales Share Since Eylea
`Launch – Medicare Part B Data
`
`
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`Expert Declaration of Richard Manning, Ph.D.
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`Page iv
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`Exhibit 2052
`Page 005 of 289
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`Regeneron Pharmaceuticals, Inc. Exhibit 2001 Page 5
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`Financials
`Section D
`Attachment D-1 Eylea Profit and Loss Data (Actuals, 2011–2021)
`Attachment D-2 Eylea Volume and Revenue Performance (2011–2021)
`Attachment D-3 Eylea Promotional and Marketing Expenses As Share of Net
`Sales (2011–2021)
`Attachment D-4 Eylea Samples As Share of Total Unit Sales (2011–2020)
`Attachment D-5 Summary of Payment Allowance Limits for Medicare Part B
`Drugs (2012–2021)
`Attachment D-6 Payment Limit per Injection for Anti-VEGF Treatment Options
`(2012–2021)
`Attachment D-7 U.S. Eylea Net Sales (2011–2021)
`Attachment D-8 Payment Limit per Injection for Different Treatments (2012–
`2021)
`
`
`Other Analyses
`Section E
`Attachment E-1 Most Prescribed Treatment Options (2012–2019)
`Attachment E-2 Volume of Medicare Patients by Brand – Medicare Part B
`
`Data
`Section X
`Attachment X-1 Vestrum Sales Share Data by Indication
`Attachment X-2 ATU Sales Share Data by Indication
`Attachment X-3 Medicare Part B Sales Shares Data (2012–2019)
`Attachment X-4 Payment Allowance Limits for Medicare Part B Drugs (2012–
`2021)
`
`
`
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`Expert Declaration of Richard Manning, Ph.D.
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`Page v
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`Exhibit 2052
`Page 006 of 289
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`Regeneron Pharmaceuticals, Inc. Exhibit 2001 Page 6
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`CONFIDENTIAL MATERIAL– SUBJECT TO PROTECTIVE ORDER
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`I, Richard Manning, Ph.D., do hereby declare:
`
`1. Introduction
`
`1.1. Qualifications
`
`(1)
`
`I am a Managing Director at Intensity, LLC. I provide data-driven insights to
`
`help clients address complex economic questions. Among other things, I have
`
`experience conducting economic analyses in matters involving breach of
`
`contract, fraud, pricing, economic valuation, intellectual property, antitrust,
`
`patent infringement, business strategy, and public policy.
`
`(2)
`
`I earned my B.A. in Economics from Brigham Young University. I received
`
`my Ph.D. in Economics from the University of Chicago. After obtaining my
`
`Ph.D., I was an economics professor at Brigham Young University and a
`
`visiting professor in the Graduate School of Business at the University of
`
`Chicago. As an academic, my teaching and research focused on price theory,
`
`the economic analysis of law, industrial organization, and the economics of
`
`government regulation.
`
`(3) My career includes 14 years as an executive at multinational pharmaceutical
`
`companies. I was Executive Director at Merck & Co., Inc. and Senior Director
`
`at Pfizer, Inc. I led economic analysis and strategy development to shape
`
`practices related to emerging business concerns. Examples of my work
`
`include:
`
`Expert Declaration of Richard Manning, Ph.D.
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`Page 1
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`Exhibit 2052
`Page 007 of 289
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`Regeneron Pharmaceuticals, Inc. Exhibit 2001 Page 7
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` Leading and undertaking economic analysis and strategy relative to
`
`challenges affecting pricing, reimbursement, and intellectual property
`
`protection in global markets.
`
` Collaborating with outside academic economists to analyze critical issues
`
`including healthcare benefit design, healthcare system reform proposals,
`
`marketing and advertising,
`
`intellectual property protection, FDA
`
`regulatory reform, including biosimilars approval processes and safety,
`
`and new product R&D.
`
`(4)
`
`Previously, I also was a Director in the Advisory Strategy Group at
`
`PricewaterhouseCoopers where my responsibilities included working on
`
`strategic partnerships, merger and acquisitions activity, economic valuation
`
`of early-stage companies, and other economic analyses for biopharmaceutical,
`
`medical device, financial, and healthcare clients.
`
`(5)
`
`Prior to joining Intensity, I was a Partner at Bates White, an economics
`
`consulting firm offering analysis and expert testimony services to law firms,
`
`Fortune 500 companies, and government agencies.
`
`(6) My areas of expertise include:
`
` Economic Valuation and Damages
`
` Breach of Contract, Fraud, and other Commercial Litigation
`
` Intellectual Property
`
`Expert Declaration of Richard Manning, Ph.D.
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`Page 2
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`Exhibit 2052
`Page 008 of 289
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`Regeneron Pharmaceuticals, Inc. Exhibit 2001 Page 8
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` Securities Litigation
`
` Tax, Antitrust and Competition
`
` Public Policy
`
`(7)
`
`I have testified before U.S. District Court, the Delaware Court of Chancery,
`
`and the International Chamber of Commerce; served as consulting expert; and
`
`prepared reports on various matters in the biopharmaceutical and healthcare
`
`industries.
`
`1.2. Scope of work
`
`(8)
`
`Intensity has been retained by Arnold & Porter Kaye Scholer LLP on behalf
`
`of Regeneron Pharmaceuticals, Inc. (Regeneron). Intensity
`
`is being
`
`compensated at my standard hourly rate for my work in this matter. Intensity
`
`is being compensated for time spent by others on my team at rates lower than
`
`my hourly rate. The compensation of Intensity does not depend on the
`
`substance of my testimony or the outcome of this matter.
`
`(9)
`
`I was asked to evaluate and, if called upon, to testify concerning commercial
`
`success as an objective indicia of non-obviousness in Inter Partes review No.
`
`IPR2021-00881 regarding U.S. Patent No. 9,254,338 (the ’338 Patent).
`
`(10) In forming the opinions expressed in this declaration, I relied upon my
`
`education, experience, and knowledge of the subjects discussed. Additionally,
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`Expert Declaration of Richard Manning, Ph.D.
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`Page 3
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`Exhibit 2052
`Page 009 of 289
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`Regeneron Pharmaceuticals, Inc. Exhibit 2001 Page 9
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`I relied on the declarations of Dr. David M. Brown and Dr. Diana Do. I also
`
`have considered documents and other materials, which are cited herein.
`
`(11) In connection with my work in this matter, I have been informed by interviews
`
`with the following individuals:
`
`a. Regeneron Director, Customer Insights, interviewed on November 30th,
`
`2021.
`
`b. Regeneron Associate Director, Field Force Effectiveness and
`
`Ophthalmology, and Regeneron Associate Director, Sample Operations
`
`and Accountability, interviewed on December 15th, 2021.
`
`c. Regeneron Executive Director, Commercial Finance & Business Planning
`
`and Regeneron Senior Director, FP&A, interviewed on December 16th,
`
`2021.
`
`d. Regeneron Senior Director, Market Access Strategy, interviewed on
`
`February 9th, 2022.
`
`1.3. Framework for commercial success
`
`(12) I understand that evidence of commercial success is one of the objective
`
`indicia that a patent owner may rely upon to support an argument of non-
`
`Expert Declaration of Richard Manning, Ph.D.
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`Page 4
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`Exhibit 2052
`Page 010 of 289
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`Regeneron Pharmaceuticals, Inc. Exhibit 2001 Page 10
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`obviousness of a claimed invention.2 I understand that the Federal Circuit has
`
`stated that “[c]ommercial success is relevant because the law presumes an idea
`
`would successfully have been brought to market sooner, in response to market
`
`forces, had the idea been obvious to persons skilled in the art.”3 I understand
`
`that, for commercial success to constitute evidence of non-obviousness of a
`
`patent, there must be a nexus between the claimed technology and evidence
`
`of commercial success, and that the evidence must demonstrate that the
`
`commercial success is due at least in part to the claimed features of the
`
`invention and not to factors unrelated to the claimed invention.4 I further
`
`
` Demaco Corp. v. F. Von-Langsdorff Licensing Ltd., 851 F.2d 1387, at PDF 3
`
` 2
`
`(Fed. Cir. 1988).
`
`3 Merck v. Teva, 395 F.3d 1364, 1376 (Fed. Cir. 2005).
`
`4 United States Patent and Trademark Office, Manual of Patent Examining
`
`Procedure, Eighth Edition, Revision: 7/2010, 716.03 I., at 700-298. (“An
`
`applicant who is asserting commercial success to support its contention of
`
`nonobviousness bears the burden of proof of establishing a nexus between the
`
`claimed invention and evidence of commercial success.”) (“The term “nexus”
`
`designates a factually and legally sufficient connection between the evidence
`
`
`Expert Declaration of Richard Manning, Ph.D.
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`Page 5
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`Exhibit 2052
`Page 011 of 289
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`Regeneron Pharmaceuticals, Inc. Exhibit 2001 Page 11
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`understand that Federal Circuit case law holds that “if the commercial success
`
`is due to an unclaimed feature or device, the commercial success is
`
`irrelevant.”5
`
`(13) It is my understanding that the courts commonly accept indicators including
`
`significant sales levels, significant sales growth, substitution towards the
`
`
`
`
`of commercial success and the claimed invention so that the evidence is of
`
`probative value in the determination of nonobviousness.”) (“In considering
`
`evidence of commercial success, care should be taken to determine that the
`
`commercial success alleged is directly derived from the invention claimed, in
`
`a marketplace where the consumer is free to choose on the basis of objective
`
`principles, and that such success is not the result of heavy promotion or
`
`advertising, shift in advertising, consumption by purchasers normally tied to
`
`applicant or assignee, or other business events extraneous to the merits of the
`
`claimed invention, etc.”)
`
`
`
`Demaco Corp. v. F. Von-Langsdorff Licensing Ltd., 851 F.2d 1387, at PDF 3
`
`(Fed. Cir. 1988).
`
`5 Ormco Corporation, et al. v. Align Technology, Inc., 463 F.3d 1299, 1312 (Fed.
`
`Cir. 2006).
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`Expert Declaration of Richard Manning, Ph.D.
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`Page 6
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`Exhibit 2052
`Page 012 of 289
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`Regeneron Pharmaceuticals, Inc. Exhibit 2001 Page 12
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`novel product or method and away from alternative products or methods, price
`
`premiums, or the absence of substantial discounting, and other economic
`
`indicators as evidence of commercial success of a novel product.6 In the
`
`context of pharmaceutical products (and by extension biologic products),
`
`sales can be measured in terms of revenues, prescriptions, or daily doses, and
`
`sales growth can be measured in terms of sales or share of sales within a
`
`product category.7
`
`
`Ex. 2201 (Guha, Rahul, Jian Li, and Andrea L. Scott (2009), “The Economics
`
`
`
` 6
`
`of Commercial Success in Pharmaceutical Patent Litigation,” Landslide 1(5)).
`
`7
`
`Ex. 2201 (Guha (2009)).
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`Expert Declaration of Richard Manning, Ph.D.
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`Page 7
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`Exhibit 2052
`Page 013 of 289
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`Regeneron Pharmaceuticals, Inc. Exhibit 2001 Page 13
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`2. Regeneron Pharmaceuticals, Inc.
`
`(14) Regeneron Pharmaceuticals, Inc. (Regeneron) is a biotechnology company
`
`that discovers and develops biotherapeutics for people with serious illnesses.8
`
`Regeneron was incorporated in the state of New York in 1988 and has its
`
`corporate headquarters is in Tarrytown, New York.9 Regeneron was publicly
`
`listed on NASDAQ in 1991.10
`
`(15) The company’s approved therapeutic products and its therapeutic candidates
`
`in development target eye diseases, allergic and inflammatory diseases,
`
`cancer, cardiovascular and metabolic diseases, pain, infectious diseases, and
`
`other rare diseases.11 Regeneron’s portfolio includes “over 30 investigational
`
`medicines.”12
`
`
`Ex. 2246 (Regeneron Website, About, https://www.regeneron.com/about
`
`
`
` 8
`
`(accessed 11/3/2021)).
`
`9
`
`Ex. 2254 (Regeneron, Form 10-K, 2020, at 37).
`
`10 Ex. 2254 (Regeneron, Form 10-K, 2020, at 37).
`
`11 Ex. 2254 (Regeneron, Form 10-K, 2020, at 3).
`
`12 Ex.
`
`2253
`
`(Regeneron
`
`Website,
`
`Research
`
`Areas,
`
`https://www.regeneron.com/science/research-areas (accessed 11/3/2021)).
`
`Expert Declaration of Richard Manning, Ph.D.
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`Page 8
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`Exhibit 2052
`Page 014 of 289
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`Regeneron Pharmaceuticals, Inc. Exhibit 2001 Page 14
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`(16) In 2011, the FDA approved Regeneron’s EYLEA (aflibercept) injection for
`
`the treatment of wet age-related macular degeneration (wet AMD).13 EYLEA
`
`is a prescription medicine approved for the treatment of patients with a variety
`
`of angiogenic eye diseases and is the subject of this proceeding.14
`
`
`13 Ex.
`
`
`
`2251
`
`(Regeneron
`
`Website,
`
`History,
`
`https://www.regeneron.com/about/history (accessed 12/15/2021)).
`
`
`
`Ex. 2185 (Drugs@FDA, Eylea Label, 11/2011, at 1, available at:
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125387lbl.pdf).
`
`14 Ex. 2254 (Regeneron, Form 10-K, 2020, at 3).
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`Expert Declaration of Richard Manning, Ph.D.
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`Page 9
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`Exhibit 2052
`Page 015 of 289
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`Regeneron Pharmaceuticals, Inc. Exhibit 2001 Page 15
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`3. U.S. Patent No. 9,254,338
`
`(17) U.S. Patent No. 9,254,338, entitled “Use of a VEGF Antagonist to Treat
`
`Angiogenic Eye Disorders,” was issued on February 9, 2016.15 The ’338
`
`Patent lists George D. Yancopoulos as its inventor and Regeneron
`
`Pharmaceuticals, Inc. as its assignee.16 The ’338 Patent claims a priority date
`
`of January 13, 2011, and the application resulting in the ’338 Patent was filed
`
`on July 12, 2013.17
`
`(18) The abstract of the ’338 Patent reads as follows:18
`
`The present invention provides methods for treating angiogenic
`eye disorders by sequentially administering multiple doses of a
`VEGF antagonist to a patient. The methods of the present
`invention include the administration of multiple doses of a VEGF
`antagonist to a patient at a frequency of once every 8 or more
`weeks. The methods of the present invention are useful for the
`treatment of angiogenic eye disorders such as age-related
`
`
`
`15 Ex. 1001 (Use of a VEGF Antagonist to Treat Angiogenic Eye Disorders, U.S.
`
`Patent No. 9,254,338 (filed 7/12/2013, issued 2/9/2016)).
`
`16 Ex. 1001 (U.S. Patent No. 9,254,338).
`
`17 Ex. 1001 (U.S. Patent No. 9,254,338).
`
`18 Ex. 1001 (U.S. Patent No. 9,254,338).
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`Expert Declaration of Richard Manning, Ph.D.
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`Page 10
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`Exhibit 2052
`Page 016 of 289
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`Regeneron Pharmaceuticals, Inc. Exhibit 2001 Page 16
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`macular degeneration, diabetic retinopathy, diabetic macular
`edema, central retinal vein occlusion, branch retinal vein
`occlusion, and corneal neovascularization.
`
`(19) The ’338 Patent has 26 claims.19 Of these 26 claims, 22 are currently under
`
`review in this proceeding: claims 1, 3-11, 13, 14, 16-24, and 26.20 Generally,
`
`I understand that the ’338 Patent teaches the use of a VEGF antagonist made
`
`from specific amino acid sequences or a specific nucleic acid sequence to treat
`
`angiogenic eye disorders according to a dosing regimen that includes three
`
`phases: a single initial dose; one or more secondary doses administered 2 to 4
`
`weeks after the preceding dose; and one or more tertiary doses administered
`
`at least 8 weeks after the preceding dose.21
`
`
`
`19 Ex. 1001 (U.S. Patent No. 9,254,338).
`
`20 Decision Granting Institution of Inter Partes Review, 11/10/2021, at 2.
`
`21 Ex. 1001 (U.S. Patent No. 9,254,338).
`
`
`
`Ex. 2050 (Expert Declaration of David M. Brown, M.D. (“Brown
`
`Declaration”), 2/10/2022. at ¶94). (“The dosing regimen of Claim 1 requires
`
`treatment of an angiogenic eye disorder by administration of an initial dose of
`
`the claimed VEGF antagonist followed by one or more “secondary” doses
`
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`Expert Declaration of Richard Manning, Ph.D.
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`Page 11
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`Exhibit 2052
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`(20) I understand that Eylea is administered according to the claimed dosing
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`regimen.22 For example, the FDA approved label for Eylea for wet AMD
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`recommends a monthly injection for the first three to five months, depending
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`on the indication, followed by an on-going 8-week or longer maintenance
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`dosing schedule.23 I will refer to these initial monthly doses (i.e., the single
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`administered two to four weeks after the preceding dose, and then one or more
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`“tertiary” doses that are administered at least eight weeks following the
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`preceding dose.
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`Ex. 2051 (Declaration of Diana V. Do, M.D. (“Do Declaration”), 2/10/2022, at
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`¶35). (“The dosing regimen of Claim 1 requires treatment of an angiogenic eye
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`disorder by administration of an initial dose of the claimed VEGF antagonist
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`followed by one or more “secondary” doses administered two to four weeks
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`after the preceding dose, and then one or more “tertiary” doses that are
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`administered at least eight weeks following the preceding dose.”)
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`22 Ex. 2051 (Do Declaration, 2/10/2022, at ¶¶ 135–139).
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`23 Ex. 2189 (Drugs@FDA, Eylea Label, 3/2021, at 3, available at:
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`https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125387s069lbl.p
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`df). (“The recommended dose for EYLEA is 2 mg (0.05 mL) administered by
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`initial dose and the one or more secondary doses administered 2 to 4 weeks
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`after the preceding dose) as the “loading doses” or loading period, and tertiary
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`doses as the “maintenance doses” or maintenance phase.
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`intravitreal injection every 4 weeks (approximately every 28 days, monthly) for
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`the first 3 months, followed by 2 mg (0.05 mL) via intravitreal injection once
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`every 8 weeks (2 months).”)
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`Expert Declaration of Richard Manning, Ph.D.
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`4. Relevant Economic Principles
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`(21) The economic theory of demand dictates that consumers choose to buy goods
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`and services to achieve satisfaction, or to meet various wants and needs.24
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`Demand theory also dictates that consumers only buy things when the good
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`purchased provides them greater value than the cost they incur to acquire the
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`good.25 The cost incurred includes more than the money paid.26
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`(22) As a consumer evaluates a purchase, he or she considers other things that are
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`“bundled” with the purchase, and, importantly, a consumer considers the
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`
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`24 Ex. 2219 (Mankiw, Nicholas Gregory (2009), Principles of Microeconomics,
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`5th ed., Mason, OH: South-Western Cengage Learning, at 6). (“You will also
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`encounter individuals who decide how much time to spend working and what
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`goods and services to buy with the resulting income to achieve the highest
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`possible level of satisfaction.”)
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`25 Ex. 2219 (Mankiw (2009), at 5). (“Because people face trade-offs, making
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`decisions requires comparing the costs and benefits of alternative courses of
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`actions.”)
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`26 Ex. 2219 (Mankiw (2009), at 5). (“In many cases, however, the cost of an action
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`is not as obvious as it might appear.”)
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`alternative consumption opportunities that are given up in exchange for the
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`purchased good.27 Within the consumption bundle, the consumer may find
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`things both good and bad that contribute to the “price” paid in exchange for
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`the thing he or she wants to buy. When a consumption bundle includes bad
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`things, demand for the bundle is diminished.28
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`(23) In this matter, the medical treatments provide significant benefits and value to
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`patients by preventing vision loss and restoring some lost vision caused by the
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`relevant medical conditions. However, as discussed subsequently in my
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`declaration, the most commonly used treatments for these conditions
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`(including Eylea) involve ongoing treatments, which impose certain “bads”
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`on patients. See Section 9. In particular, these treatments are administered by
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`injection into patients’ eyes, compounding the negative impact of ongoing
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`
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`27 Ex. 2219 (Mankiw (2009), at 5–6). (“The opportunity cost of an item is what
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`you give up to get that item. When making any decision, decision makers
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`should be aware of the opportunity costs that accompany each possible
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`action.”)
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`28 Ex. 2245 (Pindyck, Robert and Daniel Rubinfeld (2013), Microeconomics,
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`Upper Saddle River, NJ: Prentice Hall, at 76-77). (“However, some things are
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`bads: Less of them is preferred to more.”)
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`treatment.29 Hence, economic theory indicates, all else the same, that a
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`treatment that requires fewer or less frequent doses and/or evaluations will be
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`in greater demand by consumers than is a treatment that requires more
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`evaluations, and/or more frequent dosing.
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`29 Ex. 2221
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`(Mayo Clinic Website, Wet Macular Degeneration,
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`https://www.mayoclinic.org/diseases-conditions/wet-macular-
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`degeneration/diagnosis-treatment/drc-20351113 (accessed 11/11/2021)).
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`5. Medical Conditions at Issue
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`(24) The ’338 Patent teaches “methods for treating angiogenic eye disorders.”30 I
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`understand that angiogenic eye disorders result from the growth of abnormal
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`blood vessels in the eyes31 when a naturally-produced protein, vascular
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`endothelial growth factor (VEGF), is produced in excess amounts. The
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`creation of these abnormal blood vessels in eyes can damage the eye and
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`impair vision.32
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`(25) The ’338 Patent specifically identifies the patented methods as being useful
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`for the treatment of specific angiogenic eye disorders, including age-related
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`macular degeneration, diabetic retinopathy, diabetic macular edema, central
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