`
`UNITED STATES PATENT AND TRADEMARK OFFICE
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`
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`
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`———————————
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`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`
`
`———————————
`
`REGENERON PHARMACEUTICALS, INC.
`
`Petitioner,
`
`v.
`
`NOVARTIS PHARMA AG,
`
`NOVARTIS TECHNOLOGY LLC,
`
`NOVARTIS PHARMACEUTICALS CORPORATION,
`
`Patent Owners.
`
`
`
`———————————
`
`
`
`Patent Number: 9,220,631
`
`
`
`———————————
`
`
`DECLARATION OF LISA J. CAMERON, Ph.D.
`
`
`
`
`
`
`
`
`Regeneron Exhibit 1107.001
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`CONTENTS
`
`
`
`Introduction.................................................................................................. 4
`A. Qualifications ............................................................................................... 4
`B. Assignment ................................................................................................... 5
`
`
`
`Summary of Findings .................................................................................. 8
`
`Background ................................................................................................ 18
`
`A. Angiogenic Eye Diseases and Anti-VEGF Treatments ......................... 18
`1. Lucentis ....................................................................................................................24
`
`2. Eylea .........................................................................................................................25
`
`3. Other Treatments ......................................................................................................30
`B. The ʼ631 Patent .......................................................................................... 36
`
`
`
`Applicable Patent Legal Standards ......................................................... 37
`A. Secondary Considerations of Non-Obviousness..................................... 38
`B. Nexus of Secondary Considerations ........................................................ 38
`
`
`
`Mr. Malackowski Fails to Demonstrate the Commercial Success (If
`Any) Achieved by the PFS Form of Lucentis ......................................... 40
`
` Mr. Malackowski Fails to Demonstrate the Existence of a Nexus
`Between the ’631 Patent and the Alleged Commercial Success of the
`Lucentis PFS .............................................................................................. 42
`
` Mr. Malackowski’s Analysis Does Not Demonstrate the Existence of a
`Nexus Between the PFS Form of Lucentis and Any Commercial
`Success ........................................................................................................ 45
`1.
`Internal Novartis Models ..........................................................................................48
`
`2. U.S. Lucentis Sales ...................................................................................................53
`
`3. Ex-U.S. Lucentis Sales .............................................................................................59
`
` Mr. Malackowski’s Licensing Analysis Does Not Support a Finding of
`Non-Obviousness with Respect to the Patented Claims ........................ 60
`
`A.
`
`
`
`
`
` 61
`
`
`
`
`
`
`Regeneron Exhibit 1107.002
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`B. Bayer’s Sub-License with Vetter Does Not Provide Evidence of
`Commercial Success or Commercial Acquiescence with Respect to the
`’631 Patent ................................................................................................. 72
`
`
`
`Conclusion .................................................................................................. 77
`
`
`
`
`
`
`Regeneron Exhibit 1107.003
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`
`
`
`
`INTRODUCTION
`
`A. QUALIFICATIONS
`
`1.
`
`My name is Dr. Lisa Cameron. I am a Principal in the Boston office of
`
`The Brattle Group, an economic consulting firm that provides consulting services
`
`to firms and governments. My professional career has spanned more than 25 years.
`
`I have broad experience in intellectual property, false advertising, competition, and
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`transfer pricing matters and have analyzed commercial success, licensing issues,
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`damages, liability, and requests for injunctive relief. My industry expertise
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`includes pharmaceuticals, biologics, medical devices, motor vehicles, consumer
`
`products, software, e-commerce, cryptocurrencies, telecommunications, and
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`energy.
`
`2.
`
`I regularly present on matters involving intellectual property issues
`
`and have published in leading academic and professional journals, including the
`
`American Economic Review. I have also previously testified on damages and
`
`commercial success in pharmaceutical industry patent disputes in U.S. Federal
`
`Court and on competition and investment incentives before the U.S. Federal
`
`Energy Regulatory Commission and U.S. state public utility commissions.
`
`3.
`
`Prior to becoming an economic consultant, I was a professor of
`
`economics in Carnegie Mellon University’s Graduate School of Business, where I
`
`
`
`
`
`
`Regeneron Exhibit 1107.004
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`taught courses in microeconomic theory, regulation, and antitrust policy. I received
`
`my Ph.D. in Economics from Stanford University and my B.Sc. in Business and
`
`Applied Economics from Cornell University. Exhibit 1170 provides my CV, which
`
`lists my publications, testifying experience, and selected presentations.
`
`B. ASSIGNMENT
`
`4.
`
`I have been retained by counsel for Regeneron Pharmaceuticals, Inc.
`
`(“Regeneron”; also “Petitioner”) in the above-captioned inter partes review of U.S.
`
`Patent No. 9,220,631 (“the ’631 Patent”) allegedly owned by Novartis Pharma AG,
`
`Novartis Technology LLC, and Novartis Pharmaceuticals Corporation
`
`(collectively, “Novartis”; also “Patent Owner”). I understand that the ’631 Patent
`
`relates to “a terminally sterilized, pre-filled glass syringe for intravitreal injection
`
`that includes a VEGF-antagonist solution.”1 In the present matter, Regeneron
`
`alleges that the claims of the ’631 Patent are obvious and, as such, has requested
`
`
`
`
`Paper No. 1, Petition for Inter Partes Review of U.S. Patent No. 9,220,631,
`
`
`
` 1
`
`Regeneron Pharmaceuticals, Inc. v. Novartis Pharma AG, Novartis Technology
`
`LLC, and Novartis Pharmaceuticals Corporation, April 16, 2021 (“Paper No. 1”),
`
`p. 1.
`
`
`
`Regeneron Exhibit 1107.005
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`
`
`
`that the Patent Trial and Appeal Board cancel all claims of the ’631 Patent as
`
`unpatentable.2
`
`5.
`
`I understand that Novartis can rebut a showing of obviousness using
`
`objective indicia related to certain so-called secondary considerations of non-
`
`obviousness. Among other factors, these secondary considerations include
`
`commercial success, licensing, praise, long-felt need, and failure of others. In the
`
`present matter, Mr. James Malackowski submitted a declaration on behalf of
`
`Novartis “regarding certain secondary considerations of non-obviousness
`
`concerning the ʼ631 Patent, specifically commercial success and licensing.”3 First,
`
`Mr. Malackowski opines that the pre-filled syringe (“PFS”) presentation of
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`Novartis’ anti-vascular endothelial growth factor (“anti-VEGF”) drug product—
`
`Lucentis—incorporates the claimed inventions of the ʼ631 Patent and is
`
`commercially successful.4 Second, Mr. Malackowski opines that the claimed
`
`inventions of the ʼ631 Patent have been licensed by third parties.5 Based on these
`
`Paper No. 1, p. 1.
`
`Ex. 2205 - Declaration of James E. Malackowski, In Support of Patent
`
`
`
` 2
`
`3
`
`Owner Response, January 18, 2022 (“Malackowski Declaration”), ¶ 2.
`
`4
`
`5
`
`Ex. 2205 - Malackowski Declaration, ¶ 11.
`
`Ex. 2205 - Malackowski Declaration, ¶ 12.
`
`
`
`Regeneron Exhibit 1107.006
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`opinions, Mr. Malackowski ultimately concludes that “these secondary
`
`considerations of non-obviousness tend to indicate that the ʼ631 Patent is not
`
`obvious.”6
`
`6.
`
`I have been asked by counsel for Regeneron to review the
`
`Malackowski Declaration, as well as his deposition in this matter,7 and respond to
`
`his claims regarding secondary considerations of non-obviousness. In particular, I
`
`have been asked to evaluate Mr. Malackowski’s opinions that: (i) Lucentis in its
`
`PFS form has achieved commercial success; (ii) there is a nexus between any
`
`commercial success of the PFS form of Lucentis and the ’631 Patent; and (iii)
`
`licenses to the ʼ631 Patent indicate non-obviousness.
`
`7.
`
`In order to accurately evaluate Mr. Malackowski’s opinions, I have
`
`relied upon: (i) documents produced in this matter by Regeneron and Novartis,
`
`such as license agreements, financial information, and company presentations; (ii)
`
`publicly available information; (iii) the ’631 Patent; and (iv) legal pleadings related
`
`to this matter. I have also relied upon my experience with patent infringement
`
`matters and industry knowledge of biologics and pharmaceuticals.
`
`Ex. 2205 - Malackowski Declaration, ¶ 13.
`
`Ex. 1172 - Deposition of James E. Malackowski, March 29, 2022
`
`
`
` 6
`
`7
`
`(“Malackowski Deposition”).
`
`
`
`
`
`
`Regeneron Exhibit 1107.007
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`8.
`
`Exhibit 1171 lists the documents that I considered in preparing this
`
`declaration. I reserve the right to supplement and/or amend my testimony and this
`
`declaration based on information produced by the parties in this matter, and/or in
`
`light of additional documents or testimony brought forth through ongoing
`
`discovery in this proceeding or otherwise, which may be brought to my attention
`
`after the date of my signature below.
`
`9.
`
`The Brattle Group is being compensated at a rate of $655 per hour for
`
`my time working on this matter and the rates for others working at my direction
`
`range from $325 to $550 per hour. Neither my compensation nor that of The
`
`Brattle Group is contingent on my findings or the outcome of this proceeding.
`
`
`
`SUMMARY OF FINDINGS
`
`10.
`
`While Mr. Malackowski has asserted that the secondary
`
`considerations of commercial success and licensing demonstrate the non-
`
`obviousness of the ’631 Patent, I disagree with his assertions. Below, I briefly
`
`describe the evidence supporting my conclusion.
`
`11.
`
`First, despite noting that commercial success for U.S. patent law
`
`should be shown in a marketplace context, Mr. Malackowski fails to provide a
`
`systematic analysis of Lucentis PFS revenues and sales relative to other anti-VEGF
`
`
`
`
`
`
`Regeneron Exhibit 1107.008
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`products.8 He also fails to assess whether the PFS form of Lucentis has generated
`
`substantial incremental profits over and above those associated with the vial form
`
`of Lucentis.9 As a result, it is my opinion that Mr. Malackowski has failed to
`
`
`
`Case law indicates that, in assessing commercial success for purposes of
`
`
`
` 8
`
`U.S. patent law, courts have traditionally considered characteristics such as
`
`increasing revenues and unit sales, as well as gains in share relative to other
`
`available products. See, e.g., Ex. 1197 - John Jarosz and Robert L. Vigil,
`
`“Assessing Commercial Success at the U.S. Patent Trial and Appeal Board,”
`
`International In-house Counsel Journal, Vol. 8, No. 32, Summer 2015, pp. 4-5;
`
`Ex. 1242 - R. DeForest McDuff, Ryan C. Andrews, and Matt D. Brundage,
`
`“Thinking Economically about Commercial Success,” Landslide, Vol. 9, Iss. 4,
`
`March-April 2017, pp. 1-5.
`
`9
`
`Some experts would reduce the analysis of commercial success to one
`
`criterion—the existence of substantial incremental profits deriving from the
`
`patented invention. See, e.g., Ex. 1173 - Jesse David and Marion B. Stewart,
`
`“Commercial Success: Economic Principles Applied to Patent Litigation,” in
`
`Economic Damages in Intellectual Property, ed. Daniel Slottje (Hoboken, NJ: John
`
`Wiley & Sons, Inc., 2006), p. 160 (“From an economic perspective, commercial
`
`success could in principle be defined by a single criterion: Does the patented
`
`
`
`
`
`
`Regeneron Exhibit 1107.009
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`appropriately specify—let alone perform—the analysis required to demonstrate
`
`commercial success of the PFS form of Lucentis.
`
`12.
`
`Second, Mr. Malackowski wrongly focuses on the nexus between
`
`Lucentis’ alleged commercial success and its PFS form. In order to support his
`
`claim of non-obviousness, he should have analyzed the nexus between the alleged
`
`commercial success of the Lucentis PFS and the claimed inventions of the ’631
`
`Patent.
`
` Mr. Malackowski notes that it is his understanding that: (i) “the
`
`Lucentis PFS is co-extensive with certain claims of the ’631 Patent”10 and (ii)
`
`“nexus is presumed to exist if the commercially successful product is coextensive
`
`with the invention disclosed and claimed in the patent.”11 However, Mr. Horst
`
`
`invention earn a positive net return (risk-adjusted) on invested capital after
`
`accounting for all relevant costs associated with developing and commercializing
`
`the patent, as well as any alternatives available to the patent holder?”).
`
`10
`
`11
`
`Ex. 2205 - Malackowski Declaration, ¶ 50.
`
`Ex. 2205 - Malackowski Declaration, ¶ 35.
`
`
`
`
`
`
`Regeneron Exhibit 1107.010
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`Koller explains that the Lucentis PFS is not coextensive with the claimed
`
`inventions of the ’631 Patent.12
`
` Moreover, Dr. Szilárd Kiss demonstrates that there is no nexus
`
`between the claimed inventions of the ’631 Patent and any alleged commercial
`
`success associated with the Lucentis PFS.13 Consistent with this, in an ITC matter
`
`involving the ’631 Patent, the ITC’s Investigative Staff, an independent
`
`government body, determined that there was no nexus between commercial
`
`success and the ’631 Patent.14
`
`
`12
`
`Ex. 1105 - Reply Declaration of Horst Koller, April 12, 2022 (“Koller Reply
`
`Declaration”), ¶¶ 98-100.
`
`13 Dr. Kiss explains that “the claimed features of the ’631 Patent do not
`
`contribute to commercial success in so far as they do not drive an
`
`ophthalmologist’s decision to choose a particular product for treatment.” See Ex.
`
`1106 - Reply Declaration of Dr. Szilárd Kiss, April 12, 2022 (“Kiss Reply
`
`Declaration”), ¶ 29.
`
`14
`
`Ex. 1005 - Commission Investigative Staff’s Pre-Hearing Brief (Public
`
`Version), In the Matter of Certain Pre-filled Syringes for Intravitreal Injections
`
`
`
`
`
`
`Regeneron Exhibit 1107.011
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
` Mr. Malackowski makes no attempt to establish a nexus between the
`
`claimed inventions of the ’631 Patent and any purported measure of commercial
`
`success.15 As a result, his analysis provides no information on non-obviousness
`
`that is independent of Mr. Leinsing’s claim that the Lucentis PFS is coextensive
`
`with the claimed inventions of the ’631 Patent.16
`
`
`and Components Thereof, Investigation No, 337-TA-1207 (“Staff’s Pre-Hearing
`
`Brief”), at 1005.104.
`
`15 While Mr. Malackowski could have conducted such an analysis, he did not.
`
`See, e.g., Ex. 1243 – Kevin L. Varghese, “No Need to Neglect Nexus: Prosecution
`
`Lessons from FOX Factory v. SRAM,” Intellectual Property & Technology Law
`
`Journal, Vol. 32, No. 6, June 2020, p. 16 (“On the ultimate question of nexus, even
`
`without the presumption [of nexus], the patent owner can evaluate the evidence of
`
`commercial success and determine which product feature (or combination of
`
`product features) the evidence may be attributed to.”).
`
`16
`
`Ex. 2205 - Malackowski Declaration, ¶ 50, citing to Ex. 2201 -
`
`Supplemental Declaration of Karl R. Leinsing, PE, In Support of Novartis’s Patent
`
`Owner Response, January 18, 2022 (“Leinsing Supplemental Declaration”), pp.
`
`107-147.
`
`
`
`
`
`
`Regeneron Exhibit 1107.012
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`13.
`
`Third, beyond focusing on both the wrong test of commercial success
`
`and the wrong nexus question, Mr. Malackowski fails to establish the existence of
`
`incremental sales associated with the PFS form of Lucentis (over and above those
`
`associated with the vial form of Lucentis). In order to identify incremental Lucentis
`
`sales (if any) arising from the PFS form, Mr. Malackowski should have rigorously
`
`controlled for factors that would be expected to drive Lucentis sales including (but
`
`not limited to) changes in price for the Lucentis PFS and other anti-VEGF
`
`products, changes in promotional activities for the Lucentis PFS and other anti-
`
`VEGF products, changes in product characteristics for the Lucentis PFS and other
`
`anti-VEGF products (such as FDA approval of new indications), and general
`
`
`
`
`
`
`Regeneron Exhibit 1107.013
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`marketplace trends.17, 18 Mr. Malackowski provides no such analysis nor does he
`
`identify such an analysis among the documents that he cites.19, 20 As a result, he has
`
`
`17
`
`See, e.g., Ex. 1198 - “Research Design: Model Specification,” Reference
`
`Manual on Scientific Evidence, 3rd edition, (Washington, DC: National Academics
`
`Press, 2011), pp. 313-314; Ex. 1199 - Jeffrey M. Wooldridge, Econometric
`
`Analysis of Cross Section and Panel Data, (Cambridge, MA: MIT Press, 2010), p.
`
`3; Ex. 1197 - John Jarosz and Robert L. Vigil, “Assessing Commercial Success at
`
`the U.S. Patent Trial and Appeal Board,” International In-house Counsel Journal,
`
`Vol. 8, No. 32, Summer 2015, p. 6 (“The commercial success of any product
`
`usually depends on contributions from a whole host of sources. Some of those
`
`sources are features and capabilities of the product itself. Others are non-product
`
`features, such as product pricing, promotional activities, and manufacturer brand
`
`name and reputation. Establishing causal nexus entails an assessment of the
`
`relative significance of the features/advantages enabled by the patent to the success
`
`of the patented product, separate from all of the other contributors of value.
`
`Though often quite difficult, the inquiry is critical.”).
`
`18 Numerous academic studies have analyzed how the demand for a drug is
`
`influenced by the drug’s own price (as well as that of competitors), promotional
`
`activities for the drug (as well as those of competitors), and characteristics of the
`
`
`
`
`
`
`Regeneron Exhibit 1107.014
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`failed to establish the existence of Lucentis sales enabled by the PFS form,
`
`separate from other contributors to sales in the pharmaceutical industry.21
`
`
`drug (as well as those of competitors). See, e.g., Ex. 1244 - Ernst R. Berndt et al.,
`
`“Information, Marketing, and Pricing in the U.S. Antiulcer Drug Market,” The
`
`American Economic Review 85(2), 1995, pp. 102-103.
`
`19
`
`See, e.g., Ex. 1172 - Malackowski Deposition, pp. 18:17-19:21. Mr.
`
`Malackowski affirms that a Novartis trend line he cites is based on historical sales
`
`of Lucentis vials and therefore does not account for factors such as new
`
`indications, price changes, and insurance coverage changes. As previously noted,
`
`however, these factors would be expected to have an important impact on Lucentis
`
`sales.
`
`20
`
`See also Ex. 1172 - Malackowski Deposition, pp. 22:11-23:1. Mr.
`
`Malackowski affirms that—although he claims that U.S. Lucentis sales increased
`
`by 1 percent in 2017 due to the PFS and new indications—he does not know how
`
`much of this asserted growth was attributable to one factor versus the other.
`
`21 Of course, even if Mr. Malackowski could rigorously establish that the PFS
`
`form of Lucentis generated substantial incremental revenues over and above those
`
`associated with the vial form of Lucentis (which he did not), it would also be
`
`incumbent upon him to establish that the PFS form of Lucentis generated
`
`
`
`
`
`
`Regeneron Exhibit 1107.015
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`14.
`
`Fourth, Mr. Malackowski wrongly opines that two agreements that
`
`refer to the ’631
`
`
`
`and an April 2014 sub-license between Vetter and Bayer—support
`
`a finding of non-obviousness.22 As an initial matter, Mr. Malackowski fails to
`
`demonstrate that the desire to obtain a license to the ’631 Patent drove either:
`
`
`
`decision to enter into its agreement with Vetter. Moreover, neither of the
`
`agreements cited by Mr. Malackowski specify any payment for the ’631 Patent.23
`
` or (ii) Bayer’s
`
`
`substantial incremental profits over and above those associated with the vial form
`
`of Lucentis (as discussed above).
`
`22
`
`I understand that licensing has been proffered as evidence of non-
`
`obviousness “under the theory that a license is generally a statement against the
`
`licensee’s interest . . . [and] a licensee does not generally act in a manner contrary
`
`to his economic self interest unless convinced of the validity of the patent.” See Ex.
`
`1174 - T. McNelis, “New Designs: Licenses May Be Evidence of the
`
`Nonobviousness of an Invention,” Fenwick & West LLP, 1998, p. 1,
`
`https://assets.fenwick.com/legacy/FenwickDocuments/New_Designs.pdf.
`
`23
`
`
`
`
`
`
`
`
`
`
`Regeneron Exhibit 1107.016
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`As a result, I believe that Mr. Malackowski’s review of these licenses fails to
`
`support his claims of non-obviousness.
`
`15.
`
`The remainder of this declaration proceeds as follows. Section III
`
`presents background on anti-VEGF treatments for angiogenic eye diseases
`
`(including Lucentis, Eylea, and others), as well as the ’631 Patent. Section IV
`
`summarizes applicable patent legal standards. Section V explains that Mr.
`
`Malackowski has failed to rigorously analyze commercial success with respect to
`
`the Lucentis PFS. Section VI explains why Mr. Malackowski’s presumption of
`
`nexus does not support his claims of non-obviousness for the ’631 Patent. Section
`
`VII explains why Mr. Malackowski fails in his attempt to establish incremental
`
`revenues due to the Lucentis PFS (over and above incremental revenues associated
`
`with the vial form). Section VIII explains why Mr. Malackowski’s licensing
`
`analysis also does not support a finding of non-obviousness with respect to the
`
`patented claims. Section IX concludes.
`
`
`
`
`
`
`
`
`
`
`
`
`Regeneron Exhibit 1107.017
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
` BACKGROUND
`
`A. ANGIOGENIC EYE DISEASES AND ANTI-VEGF
`TREATMENTS
`
`16.
`
`Angiogenic eye diseases are caused by the growth of abnormal blood
`
`vessels in the eye, which can damage the eye and lead to impaired vision or
`
`blindness.24 These diseases include wet age-related macular degeneration
`
`(“wAMD”), diabetic macular edema (“DME”), diabetic retinopathy (“DR”),
`
`macular edema following retinal vein occlusion (“RVO”), and myopic choroidal
`
`neovascularization (“mCNV”).25
`
`
`24
`
`Ex. 1175 - David Turbert, “Anti-VEGF Treatments,” American Academy of
`
`Ophthalmology, March 2, 2019, https://www.aao.org/eye-health/drugs/anti-vegf-
`
`treatments.
`
`25
`
`Ex. 1175 - David Turbert, “Anti-VEGF Treatments,” American Academy of
`
`Ophthalmology, March 2, 2019, https://www.aao.org/eye-health/drugs/anti-vegf-
`
`treatments; Ex. 1176 - “Highlights of Prescribing Information,” Lucentis, FDA,
`
`revised March 2018,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125156s117lbl.pdf;
`
`Ex. 1177 - “Highlights of Prescribing Information,” Eylea, FDA, revised March
`
`
`
`
`
`
`Regeneron Exhibit 1107.018
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`17.
`
`These angiogenic eye diseases are often treated with anti-VEGF
`
`prescription medicines.26 Anti-VEGF medicines can slow the growth of abnormal
`
`blood vessels in the eye and, in turn, slow down vision loss and potentially
`
`improve vision.27 Table 1 provides information about the two leading FDA-
`
`approved, anti-VEGF treatments: (i) Lucentis and (ii) Eylea. Below, I provide a
`
`brief summary of certain information about Lucentis and Eylea, as well as other
`
`anti-VEGF treatments for angiogenic eye diseases, for the purpose of responding
`
`to Mr. Malackowski’s opinions.
`
`
`2021,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125387s069lbl.pdf.
`
`26
`
`Ex. 1175 - David Turbert, “Anti-VEGF Treatments,” American Academy of
`
`Ophthalmology, March 2, 2019, https://www.aao.org/eye-health/drugs/anti-vegf-
`
`treatments.
`
`27
`
`Ex. 1175 - David Turbert, “Anti-VEGF Treatments,” American Academy of
`
`Ophthalmology, March 2, 2019, https://www.aao.org/eye-health/drugs/anti-vegf-
`
`treatments.
`
`
`
`
`
`
`Regeneron Exhibit 1107.019
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`TABLE 1: INFORMATION ABOUT LUCENTIS AND EYLEA
`
`
`
`Sources and Notes:
`
`Lucentis Sources: Ex. 1115 - “Highlights of Prescribing Information,” Lucentis,
`
`FDA, June 2006,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/125156lbl.pdf; Ex.
`
`1200 - “Highlights of Prescribing Information,” Lucentis, FDA, revised October
`
`2016,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125156s110lbl.pdf;
`
`
`
`
`
`
`Product
`
`Producer
`
`Indication
`
`Dosage
`Strength
`
`Recommended
`Frequency of
`Administration
`
`Dosage Form
`
`Approval
`
`Lucentis
`(ranibizumab)
`
`Genentech
`and Novartis
`
`wAMD
`
`0.5mg
`
`Monthly*
`
`RVO
`
`0.5mg
`
`Monthly
`
`mCNV
`
`0.5mg
`
`Monthly
`
`DME
`
`0.3mg
`
`Monthly
`
`DR
`
`0.3mg
`
`Monthly
`
`Eylea
`(aflibercept)
`
`Regeneron
`and Bayer
`
`wAMD
`
`2mg
`
`Monthly (First 3)***
`Every 2 Months After
`
`RVO
`
`2mg
`
`Monthly
`
`DME
`
`2mg
`
`Monthly (First 5)
`Every 2 Months After
`
`DR
`
`2mg
`
`Monthly (First 5)
`Every 2 Months After
`
`(i)
`(ii)
`
`(i)
`(ii)
`
`(i)
`(ii)
`
`(i)
`(ii)
`
`(i)
`
`(ii)
`
`(i)
`
`(ii)
`
`(i)
`(ii)
`
`(i)
`
`(ii)
`
`(i)
`
`(ii)
`
`10mg/mL Vial
`10mg/mL PFS
`
`10mg/mL Vial
`10mg/mL PFS
`
`10mg/mL Vial
`10mg/mL PFS
`
`6mg/mL Vial
`6mg/mL PFS
`
`6mg/mL Vial
`
`6mg/mL PFS
`
`Jun. 2006
`Oct. 2016
`
`Jun. 2010
`Oct. 2016
`
`Jan. 2017
`Jan. 2017
`
`Aug. 2012
`Mar. 2018
`
`Feb. 2015 &
`Apr. 2017**
`Mar. 2018
`
`40mg/mL Vial
`
`Nov. 2011
`
`40mg/mL PFS
`
`Aug. 2019
`
`40mg/mL Vial
`40mg/mL PFS
`
`Sept. 2012
`Aug. 2019
`
`40mg/mL Vial
`
`Oct. 2014
`
`40mg/mL PFS
`
`Aug. 2019
`
`40mg/mL Vial
`
`40mg/mL PFS
`
`Mar. 2015 &
`May 2019****
`Aug. 2019
`
`
`
`Regeneron Exhibit 1107.020
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`Ex. 1027 - “Highlights of Prescribing Information,” Lucentis, FDA, revised June
`
`2010,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/125156s053lbl.pdf;
`
`Ex. 1201 - “Highlights of Prescribing Information,” Lucentis, FDA, revised
`
`January 2017,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125156s111lbl.pdf;
`
`Ex. 1202 - “Highlights of Prescribing Information,” Lucentis, FDA, revised
`
`August 2012,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125156s0069s0076lbl.
`
`pdf; Ex. 1176 - “Highlights of Prescribing Information,” Lucentis, FDA, revised
`
`March 2018,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125156s117lbl.pdf;
`
`Ex. 1234 - “Highlights of Prescribing Information,” Lucentis, FDA, revised
`
`February 2015,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125156s106lbl.pdf.
`
`Eylea Sources: Ex. 1040- “Highlights of Prescribing Information,” Eylea, FDA,
`
`November 2011,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125387lbl.pdf; Ex.
`
`1235 - “Highlights of Prescribing Information,” Eylea, FDA, revised August 2019,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125387s060lbl.pdf;
`
`
`
`
`
`
`Regeneron Exhibit 1107.021
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`Ex. 1236 - “Highlights of Prescribing Information,” Eylea, FDA, revised
`
`September 2012,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125387s004lbl.pdf;
`
`Ex. 1237 - “Highlights of Prescribing Information,” Eylea, FDA, revised October
`
`2014,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125387s043lbl.pdf;
`
`Ex. 1238 - “Highlights of Prescribing Information,” Eylea, FDA, revised March
`
`2015,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125387s048lbl.pdf.
`
` * Note that Lucentis is also approved for other dosage frequencies for the
`
`treatment of wAMD. These additional dosage frequencies include: (i) three
`
`monthly doses followed by less frequent dosing and (ii) four monthly doses
`
`followed by one dose every three months. The Lucentis FDA label notes that these
`
`additional dosage frequencies are not as effective as the recommended dosage
`
`frequency. Ex. 1239 - “Highlights of Prescribing Information,” Lucentis, FDA,
`
`revised February 2013,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125156s081lbl.pdf.
`
`** Lucentis was approved for DR in patients with DME in February 2015 and
`
`approved for all patients in April 2017. Ex. 1234 - “Highlights of Prescribing
`
`Information,” Lucentis, FDA, revised February 2015,
`
`
`
`
`
`
`Regeneron Exhibit 1107.022
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125156s106lbl.pdf; Ex. 1240 -
`
`“Highlights of Prescribing Information,” Lucentis, FDA, revised April 2017,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125156s114lbl.pdf.
`
`*** Note that Eylea is also approved for other dosage frequencies for the treatment
`
`of wAMD. These additional dosage frequencies include: (i) monthly for all doses
`
`and (ii) every three months following one year of effective treatment. The Eylea
`
`FDA label notes that the monthly dosage frequency is no more effective than the
`
`recommended dosage frequency and that the three month dosage frequency is not
`
`as effective as the recommended dosage frequency. Ex. 1241 - “Highlights of
`
`Prescribing Information,” Eylea, FDA, revised May 2019,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125387s061lbl.pdf.
`
`**** Eylea was approved for DR in patients with DME in March 2015 and
`
`approved for all patients in May 2019. Ex. 1238 - “Highlights of Prescribing
`
`Information,” Eylea, FDA, revised March 2015,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125387s048lbl.pdf;
`
`Ex. 1241 - “Highlights of Prescribing Information,” Eylea, FDA, revised May
`
`2019,
`
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125387s061lbl.pdf.
`
`
`
`
`
`
`Regeneron Exhibit 1107.023
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`1.
`
`Lucentis
`
`18.
`
`Lucentis (ranibizumab) is an anti-VEGF treatment produced and
`
`marketed by Genentech (in North America) and Novartis (outside of North
`
`America).28 As shown in Table 1, Lucentis is indicated for the treatment of patients
`
`with wAMD, RVO, DME, DR, and mCNV.29 Table 1 also shows that Lucentis is
`
`approved in two dosage strengths, 0.5mg and 0.3mg.30 The 0.5mg dosage is used to
`
`
`28 Genentech and Novartis entered into a License and Collaboration Agreement
`
`in June 2003 that provided Novartis with an exclusive license to develop and
`
`market Lucentis outside of North America. See Ex. 2205 - Malackowski
`
`Declaration, ¶ 19; Ex. 2123 - NOVITC(CH)00007283, at 2123.008; Ex. 1178 -
`
`“Novartis Ophthalmics and Genentech announce development and
`
`commercialization agreement for age-related macular degeneration treatment,
`
`Lucentis(TM),” Novartis Pharma AG press release, June 25, 2003,
`
`https://www.globenewswire.com/news-release/2003/06/25/1839492/0/en/Novartis-
`
`Ophthalmics-and-Genentech-announce-development-and-commercialization-
`
`agreement-for-age-related-macular-degeneration-treatment-Lucentis-TM.html.
`
`29
`
`30
`
`See Table 1.
`
`See Table 1.
`
`
`
`
`
`
`Regeneron Exhibit 1107.024
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`treat patients with wAMD, RVO, and mCNV, while the 0.3mg dosage is used to
`
`treat patients with DME and DR.31
`
`19.
`
`While Lucentis was initially packaged only in a glass vial, Genentech
`
`received FDA approval for a 0.5mg PFS in October 2016 and a 0.3mg PFS in
`
`March 2018.32 Moreover, I understand that the 0.5mg PFS launched in January
`
`2017 and the 0.3mg PFS launched in April 2018.33
`
`2.
`
`Eylea
`
`20.
`
`Eylea (aflibercept) is an anti-VEGF treatment produced by Regeneron
`
`and Bayer.34 As shown in Table 1, it is indicated for the treatment of patients with
`
`
`31
`
`32
`
`33
`
`See Table 1.
`
`See Table 1.
`
`Ex. 2099 - GENEITC_1207-0000030.
`
`34 While Regeneron has exclusive commercialization rights for Eylea in the
`
`U.S., Regeneron and Bayer entered into a collaboration agreement in October 2006
`
`to jointly develop and commercialize Eylea outside of the U.S. See Ex. 1179 -
`
`“Bayer HealthCare AG And Regeneron Pharmaceuticals, Inc. To Collaborate On
`
`VEGF Trap For The Treatment Of Eye Diseases; Regeneron Retains U.S.
`
`Commercialization Rights, Receives $75 Million Upfront, And Eligible For Up To
`
`
`
`
`
`
`Regeneron Exhibit 1107.025
`Regeneron v. Novartis
`IPR2021-00816
`
`

`

`
`
`wAMD, RVO, DME, and DR.35 Unlike Lucentis, Eylea is available in only one
`
`dosage strength—2mg—which is approved for the treatment of all four
`
`indications.36 While Eylea was initially packaged only in a glass