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`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
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`SAMSUNG BIOEPIS CO., LTD.
`Petitioner,
`v.
`REGENERON PHARMACEUTICALS, INC.
`
`Patent Owner.
`
`Patent No. 11,253,572
`_______________
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`Inter Partes Review No. IPR2023-00884
`____________________________________________________________
`DECLARATION OF GEORGE YANCOPOULOS, M.D., PH.D.
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`CONFIDENTIAL MATERIAL – SUBJECT TO PROTECTIVE ORDER
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`Samsung et al. v. Regeneron IPR2023-00884
`Regeneron Pharmaceuticals, Inc. Exhibit 2063 Page 1
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`I.
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`I, George Yancopoulos, M.D., Ph.D., declare as follows:
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`BACKGROUND
`I have personal knowledge of the facts contained in this Declaration,
`1.
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`and if called upon to do so, I could and would testify competently thereto.
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`2.
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`I am the sole inventor on U.S. Patent No. 11,253,572 (“the ’572
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`patent”). Ex.1001.
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`3.
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`I was raised in New York City and attended its public schools,
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`eventually being accepted to The Bronx High School of Science, where I graduated
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`as valedictorian. I received my Bachelor of Arts degree in Biochemistry from
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`Columbia College, where I also graduated as valedictorian. I received my M.D.
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`from Columbia University’s College of Physicians and Surgeons, and I received
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`my Ph.D. in Biochemistry and Molecular Biophysics from Columbia University’s
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`Graduate School of Arts and Sciences. In 1989, I became the Co-Founder and
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`founding scientist of Regeneron Pharmaceuticals, where I currently serve as
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`President, Chief Scientific Officer, and Board Co-Chair of Regeneron.
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`4.
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`Over the course of my career, I have received numerous honors and
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`awards, including the Prix Galien USA Best Biotechnology Product in 2022, the
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`Prix Galien Roy Vagelos Pro Bono Humanum Award in 2021, Fortune’s World’s
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`25 Greatest Leaders: Heroes of the Pandemic in 2020, Forbes America’s 100 Most
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`Innovative Leaders in 2019, the Legends in Leadership Award, Yale School of
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`IPR2023-00884
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`Management, CEO Institute in 2017, and the Ernst & Young Life Sciences
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`Entrepreneurs of the Year National Award in 2016. During the 1990’s, I was
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`among the ten most highly cited scientists in the world.
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`5.
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`In addition to the ’572 patent, I am also named as an inventor of more
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`than 100 patents. I am the principal inventor of the aflibercept composition of
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`matter and several other important medicines, such as the world’s leading medicine
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`for allergic diseases (DUPIXENT®) and the first antibody cocktail treatment for
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`COVID (REGN-COV®) for which Regeneron received the U.S. Patent and
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`Trademark Office Patents for Humanity Award in 2020.
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`6.
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`I have personal knowledge of Exhibits 2005-2007, 2009-2011, 2015,
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`2017-2020, 2024, 2035, 2039-2045, and 2069-2075 cited in this declaration, which
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`are true and correct copies or excerpts of documents I received, sent, or reviewed.
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`They also are business records created during the ordinary course of Regeneron’s
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`business operations and documenting various activities and product development,
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`as is and was our practice at Regeneron.
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`II. DEVELOPMENT TIMELINE OF EYLEA®
`Aflibercept is a fusion protein, which I designed and led the clinical
`7.
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`development of, that inhibits vascular endothelial growth factor. Aflibercept is the
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`active ingredient in Regeneron’s EYLEA® product, which is FDA-approved for
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`the treatment of various angiogenic eye disorders. During clinical trials,
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`Regeneron used the name "VEGF Trap-Eye" for the drug later known as EYLEA®
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`(aflibercept). I also use that terminology in this Declaration, and any reference to
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`VEGF Trap-Eye below should be understood to refer to aflibercept.
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`8.
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`Prior to FDA approval of EYLEA®, Regeneron conducted clinical
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`trials to test the safety and efficacy of VEGF Trap-Eye for, among other
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`indications, neovascular age-related macular degeneration (“wet AMD” or
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`“AMD”) and diabetic macular edema (“DME”). As I noted above, I led the
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`scientific and clinical development of VEGF Trap-Eye, including overseeing the
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`clinical trial programs directed to AMD and DME, key portions of which are
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`briefly summarized below.
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`A.
`9.
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`Phase I AMD Clinical Trial – CLEAR-IT-1
`Regeneron conducted a Phase I clinical trial called CLEAR-IT-1 to
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`test the safety and tolerability of VEGF Trap-Eye in patients with AMD. Ex.1027.
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`In CLEAR-IT-1, a single intravitreal injection of 0.05, 0.15, 0.5, 1, 2, or 4 mg of
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`VEGF Trap-Eye was administered to 21 subjects with AMD. Ex.1027. The
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`CLEAR-IT-1 study detected improvements in both retinal and visual acuity in
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`patients with AMD following a single intravitreal injection of VEGF Trap-Eye. In
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`May 2006, Regeneron issued a press release announcing positive preliminary
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`results at a population level. Ex.1027.
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`B.
`10.
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`Phase I DME Clinical Trial – CLEAR-IT-DME
`In April 2006, Regeneron began its Phase I clinical trial, CLEAR-IT-
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`DME, to test the safety and tolerability of VEGF Trap-Eye in 5 subjects suffering
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`from DME. Ex.2012, 4. As shown in Exhibit 2012, which is a printout from
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`ClinicalTrials.gov summarizing the CLEAR-IT-DME protocol, each subject in the
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`study received a single 4 mg intravitreal injection of VEGF Trap-Eye. Ex.2012.
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`The single injection resulted in an increase in best corrected visual acuity (BCVA)
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`of 6 to 10 letters for 4 of the subjects. Ex.1030. The study also observed
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`regression in BCVA at 6 weeks. Ex.1009, 3.
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`Phase II AMD Clinical Trial – CLEAR-IT-2
`C.
`11. On May 1, 2006, Regeneron also announced the start of a Phase II
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`clinical trial. Ex.1027. The Phase II trial was called CLEAR-IT-2 and tested
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`dosing on a fixed interval followed by dosing on an as-needed (“PRN”) basis in
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`157 subjects. Ex.1009, 4. The fixed dosing period spanned the first 12 weeks—
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`subjects received either monthly doses of 0.5 mg or 2 mg of VEGF Trap-Eye for a
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`total of 4 injections (initial dose and weeks 4, 8, and 12) or quarterly doses of 0.5,
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`2, or 4 mg of VEGF Trap-Eye for a total of 2 injections (initial dose and week 12).
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`Ex.2004. After the fixed dosing period, the subjects were treated on an as-needed
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`basis with the same dose they received during the fixed dosing period. Ex.1009.
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`D.
`12.
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`Regeneron & Bayer Collaboration
`In October of 2006, while the CLEAR-IT-2 study was underway,
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`Regeneron entered into a collaboration with Bayer Schering Pharmaceuticals, now
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`called Bayer, for the global development and commercialization of VEGF Trap-
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`Eye. We decided to partner with Bayer because, at that time, Regeneron was still a
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`relatively small company and Bayer had the experience and resources needed to
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`execute and fund the global clinical trials that we wanted to pursue. To the
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`collaboration, Regeneron brought VEGF Trap-Eye, a clinically validated molecule,
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`as well as its extensive knowledge and experience in developing therapies for
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`diseases, including angiogenic eye disorders like AMD and DME.
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`13. Regeneron’s primary reason for collaborating with Bayer was to
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`ensure that we had the resources needed to commercialize a drug and compete
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`against more established companies like Genentech. This was very important
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`because in June 2006, Genentech had received the first approval of a biologic anti-
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`VEGF agent for ophthalmic use, Lucentis®, and we needed a better strategy and
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`more resources to compete with Genentech. We believed that combining
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`Regeneron’s scientific expertise regarding VEGF Trap-Eye with Bayer’s global
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`infrastructure and experience with commercializing drugs would maximize the
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`likelihood of succeeding commercially. Ex.2068. Under the terms of the
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`collaboration, Bayer agreed to an initial payment to Regeneron of $75M upfront
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`and then to share the global development costs in exchange for a share of profits
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`from any drug that ultimately became commercialized. Ex.2068.
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`several14.As part of the collaboration, Regeneron and Bayer established
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`joint committees to execute the global development ofVEGF Trap-Eye. Ex.2069.
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`I served as co-chair of the Joint Steering Committee (JSC), which included an
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`equal number of senior-level members from both companies and was responsible
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`for directing and supervising the collaboration. Ex.2069, 5-7. Various sub
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`committees-the joint development committee, the joint commercialization
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`committee, and the joint finance committee-were also established and reported to
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`the JSC. Ex.2069, 9. Typically, the sub-committees would prepare information,
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`presentations, and the like to share with the JSC, which made final decisions
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`relating to our development and commercialization efforts. Ex.2069, 4. Exhibit
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`2069, a November 8, 2006 PowerPoint presentation, further describes the JSC's
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`structure.
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`that I explained above,15.Consistent with the goal of the collaboration
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`we and Bayer understood that
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`Scientific Officer at the time, a position I continue to hold to this day,
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`. I was serving as Regeneron’s Chief
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`III. THE “2Q8” DOSING REGIMEN
`16.
`In my role as Chief Scientific Officer of Regeneron, I conceived of
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`the idea to test a VEGF Trap-Eye dosing regimen of 2 mg every 4 weeks for the
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`first three injections, followed by 2 mg every 8 weeks, for the treatment of
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`angiogenic eye disorders, including AMD and DME.
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`17. My idea was based on several sources of information, including
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`(1) the need to give patients results at least as good as with Lucentis® and, indeed,
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`to give patients a reason to choose VEGF Trap-Eye over Lucentis®, (2) recent
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`clinical trial results for extended dosing regimens of Lucentis®, (3) recent results
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`from Regeneron’s phase II CLEAR-IT 2 trial, and (4) careful weighing of the
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`potential advantages of less-frequent dosing against Regeneron’s aversion to the
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`risk of negative clinical trial results.
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`18.
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`I had the idea to try to determine the dosing interval at which
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`Lucentis® fails. This analysis is shown in Exhibit 2007, the February 16, 2007
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`presentation that I gave to Bayer at the kick-off meeting between Bayer and
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`Regeneron. Ex.2007, 46-47. At that time, recent data from a clinical trial of
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`Lucentis® for DME had shown that, when injections were administered monthly,
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`subjects gained visual acuity, but when they were dosed every two months,
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`patients would gain visual acuity in the first month after the injection and then lose
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`it over the second month after the injection. Ex.2007, 46-47. Likewise, a regimen
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`of three monthly doses followed by quarterly injections of Lucentis® failed to
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`improve or even maintain vision in subjects with AMD. Ex.2007, 46. From these
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`data, I determined that Lucentis® likely would fail to maintain gains in visual
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`acuity when dosed at two month or longer intervals. Ex.2007, 46-47.
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`19. By March 22, 2007, shortly after the kick-off meeting with Bayer, I
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`had received the interim results of the Phase II CLEAR-IT-2 trial for AMD.
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`Ex.2005; Ex.2006. Exhibits 2005 and 2006 are an email by myself and an
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`attachment summarizing those results, respectively. Ex.2005; Ex.2006. According
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`to the interim results, the CLEAR-IT-2 trial included two dosing intervals of
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`VEGF Trap-Eye for the first 12 weeks—monthly doses of 0.5, 2, or 4 mg for a
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`total of 4 treatments and quarterly doses of 0.5 or 2 mg for a total of 2 treatments.
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`Subjects in the quarterly dosing groups showed mean improvements in visual
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`acuity, but the gains were lower in these arms than in the monthly dosing arms.
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`Ex.2004, Ex.2006.
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`20. After I received the interim results of the CLEAR-IT-2 trial, I had the
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`idea to test 2 mg every 4 weeks for the first three injections, followed by 2 mg
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`every 8 weeks in a Phase III AMD trial.
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`23. My practice at that time was to study and understand the various
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`considerations relevant to the clinical design and protocol that we were working
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`towards, and I would have thoroughly discussed any of my ideas with the team
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`before making a final decision on clinical trial design. Thus, over the subsequent
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`weeks, my idea to test the 2 mg of VEGF Trap-Eye every 8 weeks following three
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`initial doses administered every 4 weeks was thoroughly discussed with the
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`internal members of the Regeneron team as well as with our collaborators at Bayer.
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`Ex.2008; Ex.2009; Ex.2075. Exhibits 2008, 2009, and 2075 are emails that I sent
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`or received documenting such discussions.
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`24. For the 2q8 dosing regimen, I believed that we should use a 2 mg dose
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`of VEGF Trap-Eye. Although we had the ability to dose up to 4 mg of VEGF
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`Trap-Eye in one dose, in my judgment, it was not clear that the higher 4 mg dose
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`could provide a clear benefit over the 2 mg dose. In addition, I knew that Phase III
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`trials sometimes reveal toxicities that smaller phase II trials do not detect. At the
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`time, we were very worried about an increased risk of intraocular toxicities and
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`inflammation, as well as systemic toxicities. Therefore, the lower, 2 mg dose was
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`the appropriate, more conservative, choice.
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`25. Ultimately, I concluded that an arm of the AMD Phase III clinical
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`trials (“VIEW trials”), and eventually an arm of the DME Phase II trial (“DA
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`VINCI trial”), should test multiple, “loading” doses administered every 4 weeks,
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`followed by “maintenance” doses, administered every 8 weeks. My rationale for
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`using multiple loading doses was that we had observed that monthly dosing could
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`produce gains in visual acuity, but that those visual acuity gains plateaued around
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`the third monthly injection. I also knew that dosing at intervals longer than one
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`month provided some benefit to visual acuity. My hope was that by pivoting to
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`dosing every 8 weeks after initial dosing every 4 weeks, we could achieve
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`significant benefits to visual acuity while also reducing the number of office visits
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`and intravitreal injections patients were required to receive. But at that time, it was
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`still unclear whether the dosing regimen that I envisioned would work.
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`26.
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`A. VIEW Trials and Results
`27. The VIEW trials were Phase III clinical trials designed to test the
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`efficacy of VEGF Trap-Eye in patients with AMD. In addition to conceiving of
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`the 2q8 dosing regimen, I played the leading role in designing the VIEW trials and
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`working with other investigators to carry them out and analyze the data.
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`28. As discussed above, I made the decision to test three, 2 mg VEGF
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`Trap-Eye loading doses administered every 4 weeks followed by 2 mg
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`maintenance doses of VEGF Trap-Eye administered every 8 weeks (the “2q8”
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`arm) in the VIEW trials. This was a new arm that was not previously tested in
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`either of the CLEAR-IT studies. In addition to this new arm, we included two of
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`the arms tested in CLEAR-IT-2, monthly dosing of 0.5 or 2 mg of VEGF Trap-
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`Eye. Ex.2011. According to the VIEW trials’ design, the results of the VEGF
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`Trap-Eye arms would be compared to 0.5 mg monthly Lucentis® (the “Rq4” arm).
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`Ex.2011. At the time I decided test the 2q8 dosing regimen, I was aware that the
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`VEGF Trap-Eye used in the VIEW trials would be formulated
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` Ex.2076, 76. And, given my earlier insight that Lucentis had failed to
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`sustain gains in visual acuity when dosed at longer intervals, I also made the
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`decision to measure maintenance of visual acuity and change in best corrected
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`visual acuity from baseline in the VIEW trials and to compare those results with
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`the Lucentis arm of those trials. Ex.2007, 46; Ex.2076, 4. I made the final
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`decision to proceed with the VIEW trials according to this design.
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`29. At the time I made the decision to test the 2q8 dosing regimen in the
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`VIEW trials and through to their completion,
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`30. The first VIEW trial, VIEW 1, included 1200 patients with AMD in
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`the United States and Canada and began dosing patients in August of 2007.
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`Ex.1015, 3. The second VIEW trial, VIEW 2, which enrolled patients in Europe,
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`Asia, Japan, and Latin America began dosing subjects in May 2008. Ex.1015, 3.
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`People with “[a]ctive ocular inflammation in either eye,” or an “[a]ctive ocular or
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`periocular infection in either eye” were excluded from the study. While Regeneron
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`executed the VIEW 1 study in the United States and Canada and Bayer executed
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`the VIEW 2 study abroad, I led the design and analysis plan for both VIEW trials.
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`Ex.1029. I did so with the help of personnel working at my direction to implement
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`all aspects of the trials, from inception through the completion of data analysis.
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`31. While both VIEW trials were two-year long studies, the primary
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`endpoints of the trials related to the gain and maintenance of visual acuity,
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`including as compared to Lucentis® at 52 weeks. Ex.1029, 1. We completed
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`collection of the 52-week data for both VIEW trials by around October 2010.
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`Ex.2037.
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`32. Once the results from the VIEW 1 and VIEW 2 trials were available,
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`personnel working at my direction prepared statistical analyses of the results. On
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`November 19, 2010, I received and reviewed Exhibit 2011, a PowerPoint file
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`summarizing the visual acuity results from each VIEW trial, which was attached to
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`Exhibit 2010, an email from one of my colleagues. Ex.2010; Ex.2011. I also
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`received Exhibits 2044 and 2045, an email and an attached draft press release that
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`summarized the same results on that day. Ex.2044, Ex.2045. On November 20,
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`2010, I requested, received, and reviewed a PowerPoint file (Exhibit 2043)
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`summarizing the combined visual acuity results from both VIEW trials, which was
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`attached to Exhibit 2042, an email from one of my colleagues. Ex.2042; Ex.2043.
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`33. The goal of the 2q8 VEGF Trap-Eye dosing regimen was to achieve
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`treatment comparable to Lucentis® on a fixed extended dosing interval. That was
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`one way we hoped to differentiate ourselves from Lucentis®. A different goal had
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`been better efficacy than Lucentis®, but we did not see that in the results when we
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`looked at the VIEW 1 and VIEW 2 results combined.
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`34. By at least November 20, 2010, I had reviewed the VIEW 1 and 2
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`results, and based on these clinical data, I recognized and appreciated that the 2q8
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`VEGF Trap-Eye dosing regimen had met that goal of comparable treatment to
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`Lucentis® on a fixed extended dosing interval for subjects with AMD at 52 weeks.
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`Specifically, I recognized and appreciated that the VIEW results indicated that the
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`dosing regimen was both (1) as effective in achieving a gain in visual acuity, and
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`(2) as effective in maintaining visual acuity, as monthly administration of 0.5 mg
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`of Lucentis® by intravitreal injection in human subjects with age-related macular
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`degeneration at 52 weeks following the initial dose:
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`VIEW 1 + VIEW 2
`Mean Changein Visual Acuity to 1 year
`Compared to Baseline
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`96.1%" 0.5q4
`95.3%"
`2q4
`95.3%" 2q8
`94.4% Rad
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`* Statistically
`non-inferior
`vs. Rq4
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`letters
`ETDRS
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`9.3 2q4
`8.7 Rq4
`8.4 298
`8.3 0.5q4
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`Week
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`LOCF; full analysis set; Rq4 n=595; 294 n=613; 0.5q4 n=597; 2q8 n=607
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`Ex.2043, 6.
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`VIEW 1 + VIEW 2
`Primary Endpoint: Maintenance of Vision
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` LOCF; per protocol set; Ra4 n=538; 2q4 n=559; 0.5q4 n=538; 2q8 n=535
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`ra
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`%Patients
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`Week
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`Ex.2043, 5.
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`I also recognized and appreciated that the 2q8 VEGF Trap-Eye dosing
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`regimen achieveda gain in visual acuity of 7.9 and 8.9 letters in VIEW 1 and 2,
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`respectively, that over 90% of patients lost fewer than 15 letters (1.e., “maintenance
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`of visual acuity”) at 52 weeks, and that these benefits were clinically equivalent
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`and statistically non-inferior to the 8.1 and 9.4 letters visual acuity gains and the
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`over 90% maintenance of visual acuity achieved with 0.5 mg monthly doses
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`Lucentis®:
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` Ex.2011, 4.
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`35. On November 22, 2010, Regeneron published a press release
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`announcing the positive 1-year results of the VIEW trials. Ex.1007. The
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`information in that press release related to the 2q8 dosing regimen used in the
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`VIEW trials and their results corresponds to the 1-year data of the VIEW trials that
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`I received on November 19, 2010. Ex.2010; Ex.2011. The 2q8 regimen and
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`results reported in the press release are my own work.
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`B. DA VINCI Trial and Results
`I also played a critical role in designing the Phase II DA VINCI trial
`36.
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`directed to testing VEGF Trap-Eye in subjects with DME and worked with others
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`to carry it out and analyze the data. Like the VIEW trials, the DA VINCI trial was
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`conducted in collaboration with Bayer, with the organizational structure described
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`above.
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`37.
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`I made the decision to test three 2 mg loading doses administered
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`every 4 weeks followed by 2 mg maintenance doses administered every 8 weeks
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`(the “2q8” arm) in the DA VINCI trial. Ex.2013. Exhibits 2039, 2040, and 2041,
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`an email, memo, and list of action items by myself, respectively,
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`
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`earlier insight that Lucentis had failed to sustain gains in visual acuity when dosed
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` Ex.2039; Ex.2040; Ex.2041. Given my
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`at longer intervals,
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`18
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`Samsung et al. v. Regeneron IPR2023-00884
`Regeneron Pharmaceuticals, Inc. Exhibit 2063 Page 19
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`. Ex.2048, 88. Regeneron followed
`
`
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`the same standard procedure for handling data that I described for the VIEW trials
`
`at the time I made the decision to test the 2q8 dosing regimen in the DA VINCI
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`trial and through its completion. I made the final decision to proceed with the
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`DA VINCI trial according to this design.
`
`38.
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`In December 2008, we began enrolling subjects with DME in the
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`Phase II DA VINCI clinical trial. Ex.2014, 2. Enrollment excluded people with
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`“ocular inflammation (including trace or above) in the study eye” and “evidence at
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`examination of infectious blepharitis, keratitis, scleritis, or conjunctivitis in either
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`eye or current treatment for serious systemic infection.” Ex.2048, 37-38.
`
`39.
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` The 221 subjects of the DA VINCI trial were randomly assigned to
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`one of five treatment arms—a laser photocoagulation arm, and four arms directed
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`to VEGF Trap-Eye: (1) 0.5 mg doses every 4 weeks, (2) 2 mg doses every 4
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`weeks, (3) three 2 mg loading doses administered every 4 weeks followed by 2 mg
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`maintenance doses administered every 8 weeks (the “2q8” arm), and (4) three 2 mg
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`doses every 4 weeks followed by as-needed dosing. Ex.2014.
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`40. As with the VIEW results,
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` On February 1 and 2, 2010, I received summaries
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`
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`ofthe 24-week data, includingstatistical analysesPo
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`pe The following day, I attended a meeting with other members of
`
`senior management at Regeneron to review and discuss the 24-weekinterim results
`
`of the DA VINCItrial. Ex.2017. Exhibits 2017, 2018, and 2019 are an email that
`
`I received and two attachments summarizing those data, respectively. Exhibit
`
`2035, likewise, is an email from myself attaching the 24-weekresults.
`
`41. Upon analyzing the 24-week DA VINCIresults, and at least by
`
`February 2, 2010, I recognized and appreciated that the 2qg8 VEGF Trap-Eye
`
`dosing regimen would beable to achieve significantly improved visual acuity in
`
`patients with DME comparedto baseline. Specifically, I recognized that
`
`administering the 2q8 VEGF Trap-Eyedosing regimenresulted in an improvement
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`of 9 or more letters in some DME patients as comparedto baseline at 24 weeks:
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` Ex.2019, 13.
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`42. On February 18, 2010, Regeneron released Exhibit 2020, a press
`
`release summarizing the 24-week interim results of the DA VINCI trial, including
`
`the visual acuity gains for the various dosing arms. Ex.2020. The 2q8 dosing
`
`regimen and visual acuity gains achieved by said dosing regimen that are described
`
`in the February 18, 2010 Press Release resulted from my work in designing the
`
`clinical trial and analysis plans. The clinical trial and analysis plans were executed
`
`by personnel working under my direction. In other words, I was responsible for
`
`the scientific aspects of the clinical trial and analysis plan, while administrative
`
`aspects of the clinical trials, such as the enrollment of patients and site selection,
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`were carried out by others.
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`
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`Regeneron Pharmaceuticals, Inc. Exhibit 2063 Page 22
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`43.
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` I understand that an abstract from the 2010 Association for Research
`
`in Vision and Ophthalmology (ARVO) conference has been filed as Exhibit 1010
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`in this proceeding. I have reviewed that abstract and I understand that it recites
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`some information about visual acuity gains observed at 24-weeks in the DA VINCI
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`trial. The submission of this abstract is consistent with Regeneron’s standard
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`practice of arranging for clinical investigators to submit abstracts and present
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`clinical trial results at scientific conferences. It was standard operating procedure
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`for me to review anything that would eventually publish, including abstracts.
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`44. Like the February 18, 2010 Press Release mentioned above, Exhibit
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`1010 recites data from the DA VINCI trial related to gains in visual acuity and the
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`change from baseline in central retinal thickness (CRT) at week 24 following
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`treatment. The information in Exhibit 1010 corresponds to the data described in
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`the internal summary of 24-week interim results of the DA VINCI trial emailed to
`
`me on February 1, 2010, as described above. Ex.2018, 19, 22-23. Thus, the visual
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`acuity gains (8.5+ letters) observed in subjects receiving the 2q8 dosing regimen in
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`the 2010 ARVO meeting abstract resulted from my work in designing the clinical
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`trial and analysis plans. The clinical trial and analysis plans were executed by
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`personnel working under my direction.
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`45. On December 1, 2010, the 1-year data for DA VINCI was ready for
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`cleaning, locking, and statistical analysis. Ex.2038, 2. By no later than December
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`
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`8, 2010, I received Exhibit 2015, a copy of the DA VINCI 1-year results, which
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`
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`was attached to Exhibit 2024, an email from one of my colleagues. Ex.2015;
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`Ex.2024.
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`46.
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` Upon review of the results, and at least by December 8, 2010, I
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`recognized and appreciated that the 24-week visual acuity gains could be sustained
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`over time using the 2q8 dosing regimen, as evidenced by the mean change in visual
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`acuity at 24-weeks (8.5 letters) versus at 52 weeks (9.7 letters):
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`
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` Ex.2015, 11.
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`47. On December 20, 2010, Regeneron published the 1-year results of the
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`Phase II DA VINCI trial in a press release. Ex.1006. The information in the
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`December 20, 2010 Press Release corresponds to the data included in the copy of
`23
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`Regeneron Pharmaceuticals, Inc. Exhibit 2063 Page 24
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`IPR2023-00884
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`the DA VINCI 1-year results that I received on December 8, 2010. Ex.2015;
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`
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`Ex.2024. The DA VINCI 1-year results resulted from my work in designing the
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`clinical trial, including my idea to test the 2q8 dosing regimen, and related analysis
`
`plans. The clinical trial and analysis plans were executed by people working under
`
`my direction.
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`24
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`I declare that all statements made herein of my own knowledgeare true and
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`that all statements made uponinformation and belief are believed to be true, and
`
`that these statements were made with knowledgethat willful false statements and
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`the like so made are punishable byfine or imprisonment, or both, under section
`
`1001 of Title 18 of the United States Code.
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`Dated:
`
`IY Ee Vaz
`
`
`“\
`%
`Vt
`George Yancopoulos, M.D., Ph.D.
`
`2a
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`IPR2023-00884
`Samsung etal. v. Regeneron
`Regeneron Pharmaceuticals, Inc. Exhibit2063
`Page 26
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`
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