`
`
`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 No. IPR2021-008811
`U.S. Patent No. 9,254,338 B2
`
`
`
`
`
`EXPERT DECLARATION OF IVAN T. HOFMANN
`IN SUPPORT OF PETITIONER REPLY
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`
`
`
`
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`
` 1
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`
`
` I understand that IPR2022-00258 and IPR2022-00298 have been joined with this
`
`proceeding.
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`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 1
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`
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`I.
`
`II.
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` TABLE OF CONTENTS
`
`INTRODUCTION ........................................................................................... 1
`
`QUALIFICATIONS AND EXPERIENCE ..................................................... 3
`
`III. DOCUMENTS REVIEWED .......................................................................... 8
`
`IV. SUMMARY OF OPINIONS ......................................................................... 12
`
`V.
`
`CASE BACKGROUND ................................................................................ 14
`
`VI. THE DEFINITIONS OF COMMERCIAL SUCCESS AND NEXUS
`RELATIVE TO OBJECTIVE INDICIA OF NONOBVIOUSNESS ........... 18
`
`VII. ECONOMIC DISINCENTIVES TO DEVELOP THE CHALLENGED
`CLAIMS OF THE ’338 PATENT ................................................................ 19
`
`Earlier Regeneron Patents are “Blocking Patents” Which Presented
`A.
`Economic Disincentives for Others to Develop the Challenged Claims of the
`’338 Patent ..................................................................................................... 19
`B.
`The Acorda Factors ............................................................................. 30
`VIII. LACK OF NEXUS BETWEEN THE MARKETPLACE PERFORMANCE
`OF EYLEA® AND THE CHALLENGED CLAIMS OF THE ’338 PATENT
` ....................................................................................................................... 39
`
`The Manning Declaration Fails to Appropriately Address What I
`A.
`Understand Was Known in the Prior Art ...................................................... 41
`B.
`The Manning Declaration Fails to Appropriately Address the Efficacy
`and Safety of Eylea®, Which Are Key Drivers of the Marketplace
`Performance of Eylea® and I Understand Are Not Attributable to the
`Challenged Claims of the ’338 Patent ........................................................... 46
`
`
`
`ii
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`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 2
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`The Manning Declaration Fails to Appropriately Address the Number
`C.
`of Uses of Eylea® that Allegedly Practice the Challenged Claims of the ’338
`Patent ............................................................................................................. 52
`D.
`The Manning Declaration Fails to Appropriately Address the Impact
`of Payments to the Chronic Disease Fund on the Marketplace Performance
`of Eylea® ........................................................................................................ 60
`E.
`The Manning Declaration’s Discussion of Marketing Efforts is
`Incomplete and Misleading ........................................................................... 65
`F.
`The Manning Declaration Fails to Apportion the Marketplace
`Performance of Eylea® .................................................................................. 69
`
`iii
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`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 3
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`I, Ivan T. Hofmann, hereby declare as follows
`
`I.
`
`INTRODUCTION
`
`1.
`
`I am over the age of eighteen and am competent to make this
`
`declaration.
`
`2.
`
`I have been retained as an independent expert on behalf of Petitioner
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`Mylan Pharmaceuticals Inc. (“Mylan”) to provide economic analysis in the above-
`
`captioned inter partes review (“IPR”).
`
`3.
`
`I understand that this IPR involves U.S. Patent No. 9,254,338 B2 (the
`
`“’338 Patent” or the “Patent-at-Issue”).2 The Patent-at-Issue is entitled “Use of a
`
`VEGF Antagonist to Treat Angiogenic Eye Disorders,” issued on February 9, 2016,
`
`I understand claims priority to a provisional application filed on January 13, 2011,
`
`and expires on or about May 22, 2032.3 I understand that George D. Yancopoulos
`
`is the named inventor on the ’338 Patent and that, according to United States Patent
`
`and Trademark Office (“USPTO”) records, the ’338 Patent is assigned to Regeneron
`
`
`
` EX 1001 (’338 Patent).
`
` 2
`
`3 EX 1001 (’338 Patent); and EX 1166 (https://purplebooksearch.fda.gov/patent-
`
`list, accessed May 13, 2022).
`
`
`
`1
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`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 4
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`Pharmaceuticals, Inc. (“Regeneron”).4 I understand that the ’338 Patent claims a
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`method for treating an angiogenic eye disorder in a patient by sequentially
`
`administering a single initial dose of a vascular endothelial growth factor (“VEGF”)
`
`antagonist, followed by one or more secondary doses of the VEGF antagonist two
`
`to four weeks after the immediately preceding dose, followed by one or more tertiary
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`doses of the VEGF antagonist at least eight weeks after the immediately preceding
`
`dose.5 I further understand that the VEGF antagonist claimed in the ’338 Patent is
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`aflibercept.6
`
`4.
`
`I have been asked to review and respond to the Expert Declaration of
`
`Richard Manning, Ph.D., dated February 11, 2022 (the “Manning Declaration”)7 as
`
`
`
` EX 1001 (’338 Patent).
`
` 4
`
`5 EX 1002 (Expert Declaration of Dr. Thomas A. Albini in Support of Petition for
`
`Inter Partes Review of U.S. Patent No. 9,254,338 B2, dated May 4, 2021 (the
`
`“Albini Declaration”), pars. 36-37).
`
`6 EX 1002 (Albini Declaration, par. 44). I understand that VEGF Trap-Eye is
`
`aflibercept. (Id.).
`
`7 EX 2052 (Manning Declaration).
`
`
`
`2
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`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 5
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`it relates to purported commercial success and nexus with respect to Regeneron’s
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`product Eylea® (aflibercept) and the challenged claims of the Patent-at-Issue.8, 9
`
`5. My company, Gleason IP (“Gleason”), is being compensated for the
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`work performed on this engagement based on the time incurred by me at a rate of
`
`$535 per hour. Our compensation is not affected by the outcome of this matter.
`
`II. QUALIFICATIONS AND EXPERIENCE
`
`6.
`
`I am a Vice President and Managing Director at Gleason. Gleason is
`
`an economic, accounting, and financial consulting firm. I am the leader of the
`
`Intellectual Property Practice. Before joining Gleason, I worked for the global firm
`
`of Deloitte.
`
`
`
` 8
`
` Paper 21 (Decision Granting Institution of Inter Partes Review, p. 2). I
`
`understand that the challenged claims are claims 1, 3-11, 13, 14, 16-24, and 26 of
`
`the ’338 Patent.
`
`9 Throughout this declaration, I address various areas where I disagree with the
`
`Manning Declaration. However, my silence on any particular issue raised in the
`
`Manning Declaration should not be interpreted as agreement with any particular
`
`opinions or conclusions in the Manning Declaration.
`
`
`
`3
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`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 6
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`7.
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`I graduated magna cum laude from the University of Notre Dame with
`
`a Bachelor of Business Administration degree and a double major in Economics and
`
`Accounting. I am a Certified Public Accountant (“CPA”). I am also Certified in
`
`Financial Forensics (“CFF”). I am a member of the Licensing Executives Society
`
`(“LES”) and have received my Certified Licensing Professional (“CLP”)
`
`designation, which is granted by the LES to professionals with demonstrated
`
`knowledge and experience in the areas of intellectual property and licensing. I am
`
`also a member of the American Economic Association. I have attended and
`
`instructed numerous continuing education seminars since the completion of my
`
`formal education and have been a speaker on numerous occasions on a variety of
`
`financial, economic, accounting, and valuation topics. I have presented to various
`
`bar associations and organizations on the issues of intellectual property, objective
`
`indicia of nonobviousness, financial damages, valuation, financial statement
`
`analysis, and other topics.
`
`8.
`
`I have extensive knowledge and experience in the areas of economic
`
`and market analysis. My intellectual property experience includes valuation of
`
`intellectual property, analysis of objective indicia of nonobviousness, market
`
`analysis involving product performance, the determination of damages associated
`
`with patent infringement and other intellectual property (including lost profits,
`
`disgorgement, and reasonable royalties, as applicable), consideration of irreparable
`
`
`
`4
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`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 7
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`harm, analysis of Panduit Factors, and analysis of Georgia-Pacific Factors. I have
`
`analyzed damages claims in trademark infringement, false advertising, and other
`
`cases involving the Lanham Act. I have experience in a broad range of industries
`
`including pharmaceutical and life sciences, manufacturing, retail, technology,
`
`healthcare, communications, construction, extractive, and other industries.
`
`9. My work experience includes litigation support and consulting
`
`engagements with a variety of pharmaceutical and biologics companies. In my work
`
`in the pharmaceutical and life sciences industry, I have performed financial and
`
`economic analysis for hundreds of prescription pharmaceutical and biologic
`
`products, including virtually every major therapeutic class of drugs. I have been
`
`asked to study and analyze objective indicia of nonobviousness (including
`
`commercial success and nexus), consider claims of irreparable harm, the balance of
`
`equities, and public interest factors (and related issues associated with bonds
`
`therewith), determine and quantify damages, and assist with licensing and settlement
`
`discussions.
`
`10. My work experience also includes assisting clients with product
`
`pipeline consulting. Specifically, I analyze markets and assess the impact that a
`
`launch of a product may have on a relevant market. In providing product pipeline
`
`consulting, I use my extensive experience in financial modeling for pharmaceutical
`
`and life science products that have not yet launched. More precisely, I develop
`
`
`
`5
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`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 8
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`
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`assumptions for financial models in order to project market formation, market
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`penetration, market share, and pricing on a regular basis. Global pharmaceutical and
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`life sciences companies often retain me and my firm to perform these analyses and
`
`make decisions based on the accuracy and reliability of the financial modeling that
`
`I perform.
`
`11.
`
`In the course of my work in providing consulting and expert services, I
`
`regularly analyze and review data for the pharmaceutical and life sciences industry,
`
`including data from IQVIA, Inc. (“IQVIA”), Symphony Health Solutions
`
`(“Symphony”), Truven Health Analytics (“Truven”), IntrinsiQ Specialty Solutions,
`
`Inc. (“IntrinsiQ”), and other service providers. I am knowledgeable regarding the
`
`role of pharmaceutical databases such as First Databank, Medispan, Gold Standard,
`
`and other information sources in the fulfillment of prescriptions. I am also
`
`knowledgeable regarding the process of prescription writing, fulfillment, and
`
`product substitution in the pharmaceutical and life sciences industry. I have
`
`analyzed data and information and testified as an expert witness numerous times in
`
`matters involving the pharmaceutical and life sciences industry and the role of brand
`
`versus generic competition. I have been qualified as an expert witness in
`
`pharmaceutical economics on numerous occasions by various federal courts and
`
`institutions.
`
`
`
`6
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`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 9
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`12.
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`I have been engaged by the USPTO and Office of the Solicitor as an
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`expert to analyze and testify on economic issues involving intellectual property in
`
`proceedings for the Honorable David Kappos, while Under Secretary of Commerce
`
`for Intellectual Property and Director of the USPTO; the Honorable Michelle Lee,
`
`while Under Secretary of Commerce for Intellectual Property and Director of the
`
`USPTO; the Honorable Joseph Matal, while performing the functions and duties of
`
`Under Secretary of Commerce for Intellectual Property and Director of the USPTO;
`
`and the Honorable Andrei Iancu, while Under Secretary of Commerce for
`
`Intellectual Property and Director of the USPTO.
`
`13.
`
`I also have extensive experience in analyzing, calculating, and
`
`determining damages and other financial and economic issues in various dispute
`
`settings. I have been designated as a testifying expert in federal and state courts,
`
`Chancery Court, the United States International Trade Commission, the Patent Trial
`
`and Appeal Board (“PTAB”), and on matters before various domestic and
`
`international arbitration panels. I have analyzed damages involving intellectual
`
`property disputes, breach of contract claims, shareholder disputes, insurance
`
`recovery, class actions, and others. I also have experience assessing claims of
`
`irreparable harm, the balance of equities, and public interest factors in connection
`
`with temporary restraining order hearings, preliminary injunction hearings, and
`
`
`
`7
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`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 10
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`
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`other injunctive relief and determining whether financial damages are calculable,
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`including issues associated with related bonds.
`
`14. My curriculum vitae and list of testimony in the past four years is
`
`included as EX 1136.
`
`III. DOCUMENTS REVIEWED
`
`15. The bases for my opinions herein are: (i) the materials and independent
`
`research identified throughout this declaration; (ii) the Exhibits set forth in this
`
`declaration; (iii) the exhibits attached to the Manning Declaration; (iv) the ’338
`
`Patent; and (v) my knowledge, education, and experience. The additional materials
`
`and exhibits that I have cited are among the types of information reasonably relied
`
`upon by experts in my field for the purposes of forming opinions or inferences on
`
`the matters that are the subject of my work in this case. Throughout this declaration,
`
`I cite portions of these documents. These citations are intended only as examples,
`
`however, and I reserve the right to rely on all portions of the documents cited herein.
`
`16. This declaration is based on information currently available to me. I
`
`reserve the right to expand or otherwise modify my opinions and conclusions, or to
`
`supplement my opinions and conclusions, in response to any additional information
`
`that becomes available.
`
`
`
`8
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`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
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`
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`1003
`
`1006
`
`1007
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`
`
`17.
`
`In formulating my opinions, I have reviewed the documents cited
`
`herein, including the following documents:10
`
`1002
`
`Exhibit/
`Document
`Paper No.
`Petition for Inter Partes Review of U.S. Patent No. 9,254,338
`Paper 1
`Paper 21 Decision Granting Institution of Inter Partes Review
`1001
`U.S. Patent No. 9,254,338
`Expert Declaration of Dr. Thomas A. Albini in Support of Petition
`for Inter Partes Review of U.S. Patent No. 9,254,338 B2, dated
`May 4, 2021
`Declaration of Mary Gerritsen, Ph.D. In Support of Petition for
`Inter Partes Review of U.S. Patent No. 9,254,338 B2, dated April
`26, 2021
`Dixon, et al. “VEGF Trap-Eye for the treatment of neovascular age-
`related macular degeneration,” Expert Opinion on Investigational
`Drugs, v. 18, no. 10 (Oct. 2009).
`Adis R&D Profile – “Aflibercept AVE 0005, AVE005, AVE0005,
`VEGF Trap – Regeneron, VEGF Trap (R1R2), VEGF Trap-Eye,”
`Drugs R D 2008.
`U.S. Patent No. 7,531,173
`1008
`U.S. Patent No. 7,374,758
`1010
`U.S. Patent Nos. 7,303,746 B2; 7,303,747 B2; 7,306,799 B2; and
`1016
`7,521,049 B2
`U.S. Patent No. 7,374,757
`1022
`U.S. Patent No. 7,070,959
`1023
`’758 Patent Term Extension
`1024
`Bayer Press Release, May 8, 2008
`1032
`Regeneron Press Release, August 2, 2007
`1054
`Regeneron Press Release, September 28, 2008
`1056
`Regeneron Press Release, September 14, 2009
`1068
`’959 Patent Term Extension
`1102
`Deposition of David M. Brown, M.D., dated April 26, 2022
`1110
`
`
`10 These exhibits are true and correct copies of documents I accessed.
`
`
`
`9
`
`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
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`
`
`Exhibit/
`Paper No.
`1114
`
`1115
`1136
`1139
`
`1146
`1147
`1149
`1151
`
`1152
`
`1153
`
`1154
`
`1156
`
`1157
`1158
`1159
`1160
`1161
`1162
`1163
`1164
`1165
`1166
`1167
`
`Document
`Expert Declaration of Dr. Thomas A. Albini In Support of
`Petitioner Reply, dated May 27, 2022
`Expert Declaration of Dr. Mary E. Gerritsen, Ph.D. In Support of
`Petitioner’s Reply, dated May 26, 2022
`Ivan T. Hofmann CV and Testimony
`ASRS Clinical Update—ASRS Fights Novitas Decision to Interpret
`Eylea Usage More Frequently than q8 as “Off Label”
`https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=o
`verview.process&ApplNo=125387, accessed May 18, 2022
`Regeneron Form 10-K for the year ended December 31, 2005
`Regeneron Form 10-K for the year ended December 31, 2011
`Deposition of Richard Manning, Ph.D., dated May 4, 2022
`(CONFIDENTIAL)
`Eylea® Label, revised June 2021, available at
`https://www.regeneron.com/downloads/eylea_fpi.pdf, accessed
`May 18, 2022
`https://www.regeneron.com/downloads/us-patent-products.pdf,
`accessed May 18, 2022
`Complaint, filed June 24, 2020. United States of America vs.
`Regeneron Pharmaceuticals, Inc., in the United States District
`Court for the District of Massachusetts (20-cv-11217)
`Eylea® Label, revised May 2016, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125387
`s051lbl.pdf, accessed May 18, 2022
`U.S. Patent No. 7,608,261
`U.S. Patent No. 7,972,598
`U.S. Patent No. 8,029,791
`U.S. Patent No. 8,092,803
`U.S. Patent No. 8,343,737
`U.S. Patent No. 8,647,842
`U.S. Patent No. 10,464,992
`U.S. Patent No. 11,066,458
`U.S. Patent No. 11,084,865
`https://purplebooksearch.fda.gov/patent-list, accessed May 13, 2022
`United Healthcare Ophthalmologic Policy: VEGF Inhibitors,
`effective January 1, 2022
`
`
`
`10
`
`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 13
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`
`
`Exhibit/
`Paper No.
`1168
`
`1169
`
`1170
`1171
`
`1172
`
`1173
`
`1174
`
`1175
`
`2051
`2052
`2103
`2138
`
`2140
`
`2176
`2185
`2186
`
`2196
`
`2197
`
`Document
`BCBS Florida VEGF Inhibitors for Ocular Neovascularization,
`revised April 1, 2022
`Eylea® FDA Summary Review
`https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/125387
`Orig1s000SumR.pdf, accessed May 20, 2022
`https://www.mygooddays.org/, accessed May 18, 2022
`https://eylea.us/, accessed May 18, 2022
`https://www.biospace.com/article/releases/bayer-healthcare-ag-and-
`regeneron-pharmaceuticals-inc-to-collaborate-on-vegf-trap-for-the-
`treatment-of-eye-diseases-b-regeneron-b-retains-u-s-c/, accessed
`May 18, 2022
`Complaint, filed April 4, 2022. Horizon Healthcare Services, Inc.
`D/B/A Horizon Blue Cross Blue Shield of New Jersey v. Regeneron
`Pharmaceuticals, Inc., in the United States District Court for the
`District of Massachusetts (22-cv-10493)
`https://oig.hhs.gov/documents/physicians-
`resources/980/121994.pdf, accessed May 20, 2022
`https://www.morganlewis.com/pubs/2021/04/taking-advantage-of-
`the-new-purple-book-patent-requirements-for-biologics, accessed
`May 25, 2022
`Declaration of Diana V. Do, M.D., dated February 10, 2022
`Expert Declaration of Richard Manning, Ph.D., dated February 11,
`2022 (CONFIDENTIAL)
`Retinal Physician article, October 1, 2007
`Regeneron Physician ATU: Wave 2, February 2013
`(CONFIDENTIAL)
`Regeneron Physician ATU: Wave 5, November 2013
`(CONFIDENTIAL)
`Regeneron Q4 2020 Performance Update, January 29, 2021
`(CONFIDENTIAL)
`Eylea® Label, revised November 2011
`Eylea® Label, revised September 2012
`Gagnon, Marc-Andre and Joel Lexchin (2008), “The Cost of
`Pushing Pills: A New Estimate of Pharmaceutical Promotion
`Expenditures in the United States,” PLoS Medicine 5(1): 29-33
`Eylea® Physician ATU Benchmark Wave, September 2011
`(CONFIDENTIAL)
`
`
`
`11
`
`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 14
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`
`
`Exhibit/
`Paper No.
`2243
`2244
`2250
`2278
`
`
`
`
`
`
`Document
`ASRS 2016 PAT Survey (CONFIDENTIAL)
`ASRS 2015 PAT Survey (CONFIDENTIAL)
`ASRS 2014 PAT Survey (CONFIDENTIAL)
`Regeneron Performance Update, September 2021
`(CONFIDENTIAL)
`
`IV. SUMMARY OF OPINIONS
`
`18. The marketplace performance of Eylea® does not provide objective
`
`evidence of nonobviousness of the challenged claims of the ’338 Patent for at least
`
`the following reasons:
`
`a. The performance of Eylea® in the commercial marketplace fails to provide
`
`objective indicia of nonobviousness of the challenged claims of the ’338
`
`Patent as a result of economic disincentives provided by the Blocking
`
`Patents and/or Eylea®’s regulatory exclusivity. The Blocking Patents
`
`presented economic disincentives for others to develop what became the
`
`challenged claims of the ’338 Patent and/or to otherwise independently
`
`commercialize an aflibercept product. The Manning Declaration fails to
`
`address or analyze the economic impact of the Blocking Patents and
`
`regulatory exclusivity (as acknowledged by Dr. Manning at his
`
`deposition).
`
`
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`12
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`Mylan Exhibit 1137
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`
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`b. The Manning Declaration fails to appropriately address features that I
`
`understand were known in the prior art to the ’338 Patent and also fails to
`
`appropriately address the efficacy and safety of Eylea®, which are key
`
`drivers of the marketplace performance of Eylea® and I understand are not
`
`attributable to the challenged claims of the ’338 Patent (and rather are
`
`attributable to the previously-patented aflibercept molecule).
`
`c. The Manning Declaration fails to analyze or determine the number of uses
`
`of Eylea® that allegedly practice the challenged claims of the ’338 Patent.
`
`Based upon my analysis, a significant percentage of Eylea® uses do not
`
`practice the challenged claims of the ’338 Patent. Furthermore, the
`
`Manning Declaration fails to appropriately address that treat and extend
`
`dosing regimens were being used by healthcare providers with other drugs
`
`prior to the launch of Eylea®.
`
`d. The Manning Declaration is internally inconsistent in its criteria for
`
`assigning uses of Eylea® to the ’338 Patent method when considering on-
`
`label and off-label uses, including for various diseases such as macular
`
`edema following retinal vein occlusion (“RVO”).
`
`e. The Manning Declaration further fails to address any impact of
`
`Regeneron’s payments to the Chronic Disease Fund (which are subject to
`
`13
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`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 16
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`
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`ongoing litigation regarding an allegedly illegal kickback scheme) on the
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`marketplace performance of Eylea®.
`
`f. The discussion of marketing efforts in the Manning Declaration is
`
`incomplete and misleading.
`
`g. The Manning Declaration fails to apportion the marketplace performance
`
`of Eylea® among the many patents that allegedly cover Eylea®.
`
`19. Based upon the above, and as set forth in detail below, the Manning
`
`Declaration is incomplete and unreliable, and the marketplace performance of
`
`Eylea® fails to provide objective indicia of nonobviousness of the challenged claims
`
`of the ’338 Patent.
`
`V. CASE BACKGROUND
`
`20.
`
`I understand that Regeneron is the owner of Biologic License
`
`Application (“BLA”) No. 125387 for Eylea® (aflibercept).11 The United States Food
`
`and Drug Administration (“FDA”) approved BLA No. 125387 on November 18,
`
`
`
`11 EX 1146
`
`(https://www.accessdata.fda.gov/scripts/cder/daf/indEX.cfm?event=overview.proc
`
`ess&ApplNo=125387, accessed May 18, 2022).
`
`
`
`14
`
`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 17
`
`
`
`
`2011 and Regeneron launched the product as Eylea® shortly thereafter.12 Eylea®
`
`(aflibercept) Injection, for intravitreal use, is a VEGF inhibitor indicated for the
`
`treatment of patients with: 1) neovascular (wet) age-related macular degeneration
`
`(“AMD”), 2) RVO, 3) diabetic macular edema (“DME”), and 4) diabetic retinopathy
`
`(“DR”).13
`
`21.
`
` I understand that various patents assigned to Regeneron include claims
`
`directed to certain VEGF antagonists, which include claims directed to the VEGF
`
`Trap-Eye/aflibercept molecule,
`
`the coding sequences, and methods
`
`for
`
`manufacturing VEGF Trap-Eye/aflibercept, as well as certain methods of treating
`
`angiogenic eye disorders using VEGF antagonists, in particular VEGF Trap-
`
`
`
`12 EX 1146
`
`(https://www.accessdata.fda.gov/scripts/cder/daf/indEX.cfm?event=overview.proc
`
`ess&ApplNo=125387, accessed May 18, 2022); and EX 1149 (Regeneron Form
`
`10-K for the year ended December 31, 2011, pp. 48 and 75).
`
`13 EX 1152 (Eylea® Label, revised June 2021, available at
`
`https://www.regeneron.com/downloads/eylea_fpi.pdf, accessed May 18, 2022).
`
`
`
`15
`
`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 18
`
`
`
`
`Eye/aflibercept.14 Although the ’338 Patent does not appear on the FDA label for
`
`Eylea®, Regeneron lists or has listed numerous other patents on the FDA label for
`
`Eylea® as detailed in the chart below.15
`
`U.S. Patent
`No.
`7,070,959
`(EX 1023)
`7,303,746
`(EX 1016,
`pp. 1-57)
`
`Issue Date
`
`Expiration
`Date16
`
`Jul. 4, 2006
`
`Jun. 16, 2023
`
`Dec. 4, 2007
`
`Jul. 22, 2021
`
`Title
`Modified chimeric polypeptides
`with improved pharmacokinetic
`properties
`Methods of treating eye disorders
`with modified chimeric
`polypeptides
`
`
`
`14 EX 1115 (Expert Declaration of Dr. Mary E. Gerritsen, Ph.D. In Support of
`
`Petitioner’s Reply, dated May 26, 2022 (the “Gerritsen Reply Declaration”), pars.
`
`87-88); and EX 1114 (Expert Declaration of Dr. Thomas A. Albini in Support of
`
`Petitioner Reply, dated May 27, 2022 (the “Albini Reply Declaration”), pars. 95-
`
`97).
`
`15 EX 2185 (Eylea® Label, revised November 2011); EX 1153
`
`(https://www.regeneron.com/downloads/us-patent-products.pdf, accessed May 18,
`
`2022); EX 1156 (Eylea® Label, revised May 2016, available at
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125387s051lbl.pdf,
`
`accessed May 18, 2022).
`
`16 I obtained the expiration dates for the patents listed in this table from Counsel.
`
`
`
`16
`
`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 19
`
`
`
`
`
`
`
`Issue Date
`
`Expiration
`Date16
`
`Dec. 4, 2007
`
`Jan. 17, 2021
`
`Dec. 11, 2007 Jan. 17, 2021
`
`U.S. Patent
`No.
`7,303,747
`(EX 1016,
`pp. 58-90)
`7,306,799
`(EX 1016,
`pp. 91-122)
`7,374,757
`(EX 1022) May 20, 2008 May 23, 2020
`
`Title
`Use of VEGF inhibitors for
`treatment of eye disorders
`
`Use of VEGF inhibitors for
`treatment of eye disorders
`
`Modified chimeric polypeptides
`with improved pharmacokinetic
`properties
`Modified chimeric polypeptides
`7,374,758
`with improved pharmacokinetic
`(EX 1010) May 20, 2008 Jul. 6, 2020
`properties and methods of using
`thereof
`7,531,173
`(EX 1008) May 12, 2009 May 23, 2020 Ophthalmic composition of a
`VEGF antagonist
`VEGF antagonist formulations
`7,608,261
`suitable for intravitreal
`(EX 1157) Oct. 27, 2009 May 23, 2020
`administration
`7,972,598
`Jul. 5, 2011 May 23, 2020 VEGF-binding fusion proteins
`(EX 1158)
`and therapeutic uses thereof
`Modified chimeric polypeptides
`8,029,791
`with improved pharmacokinetic
`(EX 1159)
`properties
`8,092,803
`Jan. 10, 2012 Jun. 21, 2027 VEGF antagonist formulations
`(EX 1160)
`for intravitreal administration
`Cell culture compositions capable
`8,343,737
`of producing a VEGF-binding
`(EX 1161)
`fusion polypeptide
`8,647,842
`Feb. 11, 2014 May 23, 2020 Methods for producing a fusion
`(EX 1162)
`protein capable of binding VEGF
`VEGF antagonist formulations
`10,464,992
`(EX 1163) Nov. 5, 2019
`suitable for intravitreal
`administration
`VEGF antagonist formulations
`suitable for intravitreal
`administration
`
`Oct. 4, 2011 May 23, 2020
`
`Jan. 1, 2013 May 23, 2020
`
`Jun. 14, 2027
`
`11,066,458
`(EX 1164)
`
`July 20, 2021 Jun. 14, 2027
`
`17
`
`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 20
`
`
`
`
`
`
`
`U.S. Patent
`No.
`11,084,865
`(EX 1165) Aug. 10, 2021 Jun. 14, 2027
`
`Expiration
`Date16
`
`Issue Date
`
`Title
`VEGF antagonist formulations
`suitable for intravitreal
`administration
`
`VI. THE DEFINITIONS OF COMMERCIAL SUCCESS AND NEXUS
`RELATIVE TO OBJECTIVE INDICIA OF NONOBVIOUSNESS
`
`22.
`
`It is my understanding that “commercial success” is a legal construct
`
`that has been established through case law. Analysis of commercial success is
`
`premised on the concept that if a product is economically successful, that economic
`
`success may provide objective evidence of nonobviousness.
`
`23.
`
`I further understand that the commercial success of the product must be
`
`attributable to the allegedly novel features of the claimed invention. I understand
`
`this to mean that, to support a finding of nonobviousness, commercial success must
`
`be driven by and attributable to the purported merits of the patented invention
`
`(viewing the claim as a whole). In other words, there must be a causal correlation,
`
`or “nexus,” between the unique merit of the claimed invention and the success of the
`
`product. I also understand that if purported commercial success is due to features of
`
`the product or method that were already known in the prior art, that will undermine
`
`the case for nexus. In essence, I understand that if the feature that drives the
`
`purported success was known in the prior art, such success is not pertinent to
`
`nonobviousness.
`
`
`
`18
`
`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 21
`
`
`
`
`
`24.
`
`I also understand that courts have found that commercial success may
`
`not provide objective indicia of nonobviousness for claims of patents where the
`
`underlying product is protected by a different patent (sometimes called a “blocking
`
`patent”) that creates economic disincentives to conceive of the alleged invention
`
`and/or precludes competition in the market.
`
`25.
`
` I further understand that courts have found that commercial success
`
`may not provide objective indicia of nonobviousness for claims of patents where the
`
`underlying product is protected by a regulatory exclusivity period by the FDA.
`
`26.
`
`I apply this understanding to my economic analysis of the issues in this
`
`matter regarding the ’338 Patent.
`
`VII. ECONOMIC DISINCENTIVES TO DEVELOP THE CHALLENGED
`CLAIMS OF THE ’338 PATENT
`
`A.
`
`Earlier Regeneron Patents are “Blocking Patents” Which Presented
`Economic Disincentives for Others to Develop the Challenged
`Claims of the ’338 Patent
`
`27.
`
`I understand that commercial success in an obviousness inquiry is based
`
`
`
`on the concept that a successful commercial product embodying the claimed features
`
`of an invention would have been brought to market sooner in response to market
`
`forces, had the idea been obvious to persons skilled in the art. However, the
`
`economic premise underlying this theory assumes that others would have been
`
`equally economically incentivized, and thus willing to invest the resources, to bring
`
`
`
`19
`
`Mylan Exhibit 1137
`Mylan v. Regeneron, IPR2021-00881
`Page 22
`
`
`
`
`the claimed invention to market sooner. This premise collapses in situations where
`
`disincentives exist in the market for others to commercially exploit the claimed
`
`invention. For example, even if the claimed features of an invention were obvious
`
`to persons skilled in the art, they may not be economically motivated to pursue such
`
`claimed inventions. As such, I understand that potential objective indicia, such as
`
`commercial success (if any), fail to support or indicate nonobviousness where
`
`market entry by others was impeded by a different reason (including when the use
`
`of the underlying product falls within the scope of another patent, or when a
`
`regulatory exclusivity period would block a competing product from entering the
`
`market). One such economic disincentive is the existence of a “blocking patent”—
`
`a patent that already exists and whose claimed technology must be used in order to
`
`practice the newly clai
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