IPR2017-0060
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`____________
`
`EDWARDS LIFESCIENCES CORPORATION, EDWARDS LIFESCIENCES LLC,
`AND EDWARDS LIFESCIENCES AG
`Petitioners
`
`v .
`
`BOSTON SCIENTIFIC SCIMED, INC.
`Patent Owner
`
`____________
`
` Case IPR2017-00060
`Patent 8,992,608
`____________
`
`Before the Honorable NEIL T. POWELL, JAMES A. TARTAL, and
`ROBERT L. KINDER, Administrative Patent Judges.
`
`DECLARATION OF LARRY WOOD
`
`
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 1 of 31
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`TABLE OF CONTENTS
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`IPR2017-0060
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`INTRODUCTION AND QUALIFICATIONS .............................................. 1
`I.
`LEGAL STANDARDS AND MATERIALS CONSIDERED....................... 4
`II.
`III. RESPONSE TO OPINIONS REGARDING ASSERTED
`SECONDARY CONSIDERATIONS OF NON-OBVIOUSNESS ................ 5
`A.
`Failure of Others (P.O. Response pp. 58-63) ........................................ 7
`B.
`Long-Felt Need (P.O. Response pp. 63-64) ...................................... 14
`C.
`Copying (P.O. Response pp. 64-66) ................................................... 17
`D.
`Industry Praise (P.O. Response pp. 66-69) ......................................... 19
`E.
`Unexpected Results (P.O. Response pp. 69-70) ................................. 20
`F.
`Commercial Success (P.O. Response pp. 70-72) ............................... 21
`IV. CONCLUSION ............................................................................................. 26
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 2 of 31
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`IPR2017-0060
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`List of Materials Cited
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`Petitioner’s Exhibits:
`Exhibit 1048, Shuren, Life-Saving, Smart Regulation on Behalf of Patients with Aortic
`Stenosis, FDA Voice dated June 16, 2014
`Exhibit 1049, Edwards Endovascular HVT – Patriot Technical Design Review Proof of
`Concept & Selection of 1st Generation Valve dated June 11, 2003
`Exhibit 1050, History of Sapien and the Future of THV
`Exhibit 1051, Boston Scientific’s 2016 Annual Report
`Exhibit 1052, Freeman et al., First-in-Man Transfemoral Transcatheter Aortic Valve
`Replacement with the 29 mm Edwards SAPIEN XT Valve, Catheterization and
`Cardiovascular Interventions, 82:664-70 (2013)
`Exhibit 1053, Wiegerinck et al., An Up-to-date Overview of the Most Recent
`Transcatheter Implantable Aortic Valve Prostheses, Expert Review of Medical
`Devices, 31-45 (2016)
`Exhibit 1054, Zaman et al., Incidence and Predictors of Permanent Pacemaker
`Implantation Following Treatment with the Repositionable Lotus™
`Transcatheter Aortic Valve, Catheterization and Cardiovascular Interventions
`(2016)
`Exhibit 1055, August 18, 2016 Letter from B. Zuckerman to J. Mazzarella re:
`P130009/S057
`Exhibit 1056, Medtronic CoreValve™ Evolut™ R System First TAVI to Receive CE
`Mark for Intermediate Risk Aortic Stenosis Patients, Medtronic Press Release
`(August 1, 2016)
`Exhibit 1057, Medtronic Expands TAVR Access to More Patients With Symptomatic,
`Severe Aortic Stenosis Upon Intermediate Risk FDA Approval, Medtronic Press
`Release (July 10, 2017)
`Exhibit 1058, Boston Scientific Receives CE Mark for Lotus™ Valve System, Boston
`Scientific Press Release (October 28, 2013)
`Exhibit 1073, “Centera: Novel Transcatheter Heart Valve Shows Promise in Aortic
`Stenosis,” EuroPCR Meeting News (May 26, 2017)
`Exhibit 1074, Edwards Lifesciences Press Release: “Edwards’ Novel Self-Expanding
`Transcatheter Heart Valve Demonstrates Excellent Early Patient Outcomes”
`(May 17, 2017)
`Exhibit 1075, “Edwards’ Self-Expanding Transcatheter Heart Valve Demonstrates
`Excellent Early Patient Outcomes,” DAIC (May 24, 2017)
`
`
`Patent Owner Exhibits:
`Exhibit 2002, Press Release: FDA approves expanded indication for two transcatheter
`heart valves for patients at intermediate risk for death or complications
`associated with open-heart surgery, FDA 8/18/2016
`Exhibit 2003, Thourani, V. H., et al., Transcatheter aortic valve replacement versus
`surgical valve replacement in intermediate-risk patients : a propensity score
`analysis, The Lancet, Apr. 3, 2016
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 3 of 31
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`IPR2017-0060
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`Exhibit 2015, Press Release: Edwards Lifesciences Receives CE Mark for Edwards
`SAPIEN Transcatheter Heart Valve, Edwards Lifesciences (Sept. 5, 2007)
`Exhibit 2017, SAPIEN XT Valve Product Overview, Edwards Lifesciences
`Exhibit 2018, Ramin S. Hastings & Isaac George, The Sapien 3 Valve, Cardiac
`Interventions Today, Mar./Apr. 2016
`Exhibit 2020, Press Release: Edwards Lifesciences Receives FDA Approval for First
`Catheter-Based Aortic Heart Valve in the U.S., Edwards Lifesciences (Nov. 2,
`2011)
`Exhibit 2021, Press Release: Edwards Lifesciences Launching Sapien XT Valve In
`The U.S., Edwards Lifesciences (June 16, 2014)
`Exhibit 2031, Slide Deck titled “SAPIEN 3 26mm CDR Nov 2010” (EDWARDS
`01933840-939)
`Exhibit 2047, “FACT SHEET: Cribier-Edwards Percutaneous Aortic Heart Valve,”
`Edwards Lifesciences
`Exhibit 2051, Martin B. Leon slide deck titled “A Randomized Evaluation of the
`SAPIEN XT Transcatheter Valve System in Patients with Aortic Stenosis Who
`Are Not Candidates for Surgery: PARTNER II, Inoperable Cohort,” dated
`March 10, 2013
`Exhibit 2059, Tae-Hyun Yang et al., Incidence and Severity of Paravalvular Aortic
`Regurgitation With Multidetector Computed Tomography Nominal Area
`Oversizing or Undersizing After Transcatheter Heart Valve Replacement With
`the Sapien 3, 8 JACC: Cardiovascular Interventions 462 (2015)
`Exhibit 2062, Freek Nijhoff et al., Transcatheter Aortic Valve Implantation With the
`New Balloon-Expandable Sapien 3 Versus Sapien XT Valve System,
`Circulation: Cardiovascular Interventions, June 1, 2015
`Exhibit 2063, Document titled “Journey to S3,” dated May 8, 2016 (EDWARDS
`02399064-68)
`Exhibit 2072, Matthew J. Czarny & Jon R. Resar, Diagnosis and Management of
`Valvular Aortic Stenosis, Clinical Medicine Insights: Cardiology 2014:8(S1),
`15-24
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`iii
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 4 of 31
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`IPR2017-0060
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`I, Larry Wood, declare as follows:
`
`1.
`
`I am over the age of eighteen (18) and otherwise competent to make
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`this Declaration.
`
`2.
`
`I understand that this Declaration is being submitted in connection
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`with Edwards’1 reply in support of inter partes review (“IPR”) of U.S. Patent No.
`
`8,992,608 (the “’608 Patent”).
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`3.
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`As I explain in detail below, I am an employee of Edwards. I have
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`not been compensated separately for my efforts in connection with the preparation of
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`this Declaration, but have instead continued to receive my usual salary, including with
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`respect to periods of time during which I worked on this Declaration. My regular
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`Edwards compensation is in no way contingent on the results of these or any other
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`proceedings.
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`4.
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`I am making this Declaration based upon my own personal
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`knowledge (except where otherwise indicated), and I am competent and prepared to
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`testify regarding the contents of this Declaration.
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`I.
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`INTRODUCTION AND QUALIFICATIONS
`5.
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`I am currently the Corporate Vice President, Transcatheter Heart
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`Valves, at Edwards Lifesciences, a position I have held since 2007. In that capacity, I
`
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`1 “Edwards” refers collectively to Edwards Lifesciences Corporation, Edwards
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`Lifesciences LLC, and Edwards Lifesciences AG.
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`1
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 5 of 31
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`IPR2017-0060
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`have had responsibility for a number of projects relating to transcatheter heart valves at
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`Edwards, including R&D, operations, marketing, and commercial and clinical
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`development. Prior to 2007, I held a number of other positions at Edwards, including
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`in connection with the research and development of Edwards’ transcatheter heart valve
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`(“THV”) programs and in connection with Edwards’ commercial surgical heart valves.
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`The Edwards SAPIEN transcatheter heart valve, Edwards SAPIEN XT transcatheter
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`heart valve, and Edwards SAPIEN 3 (“S3”) transcatheter heart valve were all
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`commercialized and marketed during my tenure and under my leadership, along with
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`the leadership of several of my colleagues at Edwards. Between my time at Edwards
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`and my prior experience at Baxter International (a predecessor to Edwards), I have
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`decades of experience in the medical device industry, with over 20 years of experience
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`in prosthetic heart valves dating back to the early 1990s.
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`6.
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`I am frequently invited to speak at medical device and cardiology
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`conferences and other professional gatherings, and have delivered many presentations
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`over the years to interventional cardiologists, cardiac surgeons, and others interested in
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`transcatheter heart valve technology, including other industry executives. My
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`presentations have covered such subjects as Edwards’ clinical results, innovations in
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`Edwards’ transcatheter heart valves, and the transcatheter heart valve industry as a
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`whole, including trends and commercial outlook. As Edwards helped to pioneer the
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`transcatheter aortic valve replacement (“TAVR”) industry, it is fair to say that I have
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`been involved in the TAVR industry from its beginning.
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`2
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 6 of 31
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`7.
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`I have an undergraduate degree in business and an M.B.A. A copy
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`of my c.v. is attached as Exhibit 1047.
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`8.
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`I have been asked to review that portion of the Patent Owner’s
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`Response entitled “Objective Indicia of Non-Obviousness Establish That Claims 1-4
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`Are Not Invalid Under 35 U.S.C. § 103(a),” which begins on page 47 of the Patent
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`Owner’s Response (Paper No. 22, “P.O. Response”), and, within that section, to focus
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`on point heading VI.C.2, “Objective Indicia of Non-Obviousness,” which spans pages
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`58 through 72 of the Patent Owner’s Response. In sum, and at a high level, the Patent
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`Owner relies on the success of Edwards’ S3 valve (both on its own and as compared to
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`the Edwards SAPIEN and SAPIEN XT valves) and statements made regarding S3 as
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`allegedly supporting the non-obviousness of the ’608 patent. As the person responsible
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`for much of the commercialization and marketing of Edwards’ S3 valve, and as an
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`expert in the commercial TAVR industry as a whole,2 I am intimately familiar with the
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`commercial success of the S3, how it and Edwards’ prior devices have been received in
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`the commercial market, and how the commercial TAVR industry has functioned in the
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`period of time covered by the Patent Owner’s statements concerning the argued
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`2 For clarity, my expertise is in the field of the commercialization and marketing of
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`THV devices. As explained above, I have developed that expertise through long
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`involvement in the industry, building on my educational background in business.
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`3
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 7 of 31
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`IPR2017-0060
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`“secondary considerations.” As a result, I am qualified to respond to the Patent
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`Owner’s arguments, many of which are factually flawed.
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`9.
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`I am aware that Edwards’ expert, Dr. Nigel Buller, is also
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`submitting a declaration in support of Edwards’ Reply to the Patent Owner’s Response,
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`which I understand includes an analysis rebutting Patent Owner’s unsupported
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`allegation that S3 infringes Claims 1-3 of the ’608 patent. Although I have been and
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`am currently involved in transcatheter heart valve design, I do not attempt to address
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`the subjects covered by Dr. Buller.
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`II. LEGAL STANDARDS AND MATERIALS CONSIDERED
`10.
`I am not an attorney, and I do not intend to express any opinion
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`regarding patent law. But for purposes of understanding the context of the Patent
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`Owner’s arguments regarding secondary considerations, I have had the following legal
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`concepts explained to me:
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`11.
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`I understand that a patent can be held invalid as “obvious,” and that
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`a patent is invalid as obvious under 35 U.S.C. § 103 only if “the differences between
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`the claimed invention and the prior art are such that the claimed invention as a whole
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`would have been obvious before the effective filing date of the claimed invention to a
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`person having ordinary skill in the art to which the claimed invention pertains.” I
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`understand that in arguing against the obviousness of its ’608 Patent, the Patent Owner
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`has stated that certain “secondary considerations” of non-obviousness point to the non-
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`obviousness of the patent. (P.O. Response at 49.) I understand that the question of
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 8 of 31
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`obviousness can sometimes turn in part upon secondary considerations of non-
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`obviousness, which I understand are also sometimes called objective indicia of non-
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`obviousness.
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`12.
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`In terms of arguments here about secondary considerations of non-
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`obviousness, the Patent Owner has focused on assertions of (1) failure of others, (2)
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`long-felt need, (3), copying, (4) industry praise, (5) unexpected results, and (6)
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`commercial success.
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`13. Regarding commercial success, I understand that there is a “nexus”
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`between the commercial success of the product and the claimed, novel features of the
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`invention when the success is due to that feature.
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`14. A list of the materials that I have considered is included above,
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`supra pages ii-iii. Except as noted in my declaration, I am personally familiar with the
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`documents on which I rely; such scientific publications, FDA commentary, industry
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`press releases, and regulatory approvals are indeed all documents of the type that I
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`consult on a regular basis in my work in the field. The exhibit copies included in
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`Edwards’ Reply to the Patent Owner’s Response are each authentic copies of the
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`documents they purport to be.
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`III. RESPONSE TO OPINIONS REGARDING ASSERTED SECONDARY
`CONSIDERATIONS OF NON-OBVIOUSNESS
`15. Before responding to specific individual points raised by the Patent
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`Owner, I first note my strong disagreement with the entire underlying premise of
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 9 of 31
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`Patent Owner’s analysis—the assertion that Edwards’ S3 device practices Claims 1-3
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`of the ’608 patent. To be clear, I am not offering an opinion regarding the Patent
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`Owner’s efforts to match up the claim elements of the ’608 patent to the S3, which I
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`understand Dr. Buller has done. What I can say is that Boston Scientific Corporation
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`and Boston Scientific Scimed, Inc. (“Boston Scientific”) have accused S3 of infringing
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`the ’608 patent in litigation pending in the District of Delaware, and that Edwards
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`vigorously denies that S3 infringes. Trial in that case is set for 2018, and so there has
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`been no decision regarding whether Boston Scientific will prevail on its argument that
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`S3 infringes. Therefore, while I respond to the Patent Owner’s comments regarding S3
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`below, in doing so I do not agree that S3 practices the ’608 patent.
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`16. On a related issue, I also note that the Patent Owner does not seek
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`to rely on any alleged success by or statements concerning its own transcatheter heart
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`valve, the Lotus device, yet on page 65 of the Patent Owner’s Response, the Patent
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`Owner briefly states that the Lotus embodies the claimed invention of the ’608 patent.
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`I do not know whether it is in fact the case that the Lotus embodies the invention of
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`’608 patent, but even assuming for the sake of argument that it does, I note that one
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`possible reason for the Patent Owner’s failure to point to its own product in its
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`secondary considerations argument is the lack of commercial success of the Lotus. I
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`am familiar with the attempted commercialization of the Lotus as a result of my job
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`responsibilities at Edwards. As I explain below, the lack of success of the Lotus
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`device—even before it was globally recalled—confirms that the success of Edwards’
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 10 of 31
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`S3 cannot be attributed to the single feature that the Patent Owner focuses on here,
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`namely, the outer skirt.
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`17. For convenience, I have organized my testimony to correspond to
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`the order in which the Patent Owner raised arguments about secondary considerations
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`in its Response.
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`A.
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`Failure of Others (P.O. Response pp. 58-63)
`18.
`I do not agree with the premise from which the Patent Owner
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`begins this section, namely, Patent Owner’s argument that Edwards and others
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`“struggled unsuccessfully for years [] before and after the priority date of the ‘608
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`patent [] to find a solution to PVL.” (P.O. Response at 58.) The fact that Edwards did
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`not include an outer skirt on the first two generations of its valves does not mean that
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`Edwards was “struggl[ing] unsuccessfully” to hit upon that solution, or other solutions
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`to paravalvular leak (“PVL”). To the contrary, Edwards long ago developed an outer
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`skirt for use on a THV, and also long ago began implementing other solutions to
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`reduce PVL.
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`19. By way of background, in January of 2004, Edwards completed the
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`acquisition of Percutaneous Valve Technologies, Inc. (“PVT”), the company that
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`created the valve used in the first human transcatheter aortic valve replacement,
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`performed by Dr. Alain Cribier in April 2002. Dr. Cribier was a co-founder of PVT. I
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`understand that Dr. Buller has explained some of the details of PVT’s and Dr. Cribier’s
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`work in his prior declaration. I had been working on Edwards’ own transcatheter heart
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 11 of 31
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`valve project prior to the PVT acquisition, and began working with PVT heart valves
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`essentially as soon as the PVT acquisition was completed. As one of the Patent
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`Owner’s exhibits lays out (P.O. Ex. 2047), the valve developed by PVT was called the
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`Cribier-Edwards Percutaneous Aortic Heart Valve in the early clinical trials; the valve
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`that was ultimately approved was known as the SAPIEN valve. On September 5,
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`2007, Edwards received CE Mark approval for European commercial sales of the
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`SAPIEN valve. (P.O. Ex. 2015.) Edwards received U.S. FDA approval for the
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`SAPIEN valve on November 2, 2011 (P.O. Ex. 2020)—the first FDA approval for a
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`catheter-based aortic heart valve in the U.S.
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`20. To put this approval in context, prior to the U.S. approval of the
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`Edwards SAPIEN device, U.S. patients who were considered by their physician to be
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`inoperable for open-heart surgery aortic valve replacement had no options, and many
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`of those patients would unfortunately go on to die. As a senior FDA administrator
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`explained on the occasion of the approval of SAPIEN XT, prior to the introduction of
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`transcatheter heart valve technology, up to fifty percent of patients suffering from
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`aortic valve stenosis would not survive two years after the onset of symptoms without
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`open-heart surgery, a procedure too risky for many of these patients to tolerate. (Ex.
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`1048 (Shuren, Life-Saving, Smart Regulation on Behalf of Patients with Aortic
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`Stenosis, FDA Voice dated June 16, 2014).) After the approval of the SAPIEN valve,
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`many of these patients could be saved, and go on to live for many additional years.
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`Indeed, the success of the original SAPIEN device has widely been credited with
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 12 of 31
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`helping to create the entire TAVR industry and with revolutionizing the treatment of
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`patients with aortic stenosis. (See, e.g., P.O. Ex. 2072 at 6-8.) Thus, the SAPIEN
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`valve was an enormous success, not a failure as Patent Owner suggests (cf. P.O.
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`Response at 61). The follow-up to the SAPIEN, the SAPIEN XT, continued to build
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`on that success. (See P.O. Ex. 2021.) Many lives were saved because of these
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`devices. See, e.g., P.O. Ex. 2072 at 6-8; Ex. 1048.)
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`21. The Patent Owner appears to be suggesting from the fact that the
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`SAPIEN and SAPIEN XT did not include an outer fabric skirt that Edwards had failed
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`to develop such a skirt or had failed to address PVL in any way. (See P. O. Response
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`at 62.) The Patent Owner is mistaken. Both PVT and Edwards (prior to its acquisition
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`of PVT) had developed the idea of including fabric on the outside of a transcatheter
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`heart valve for sealing purposes prior to the asserted June 2004 priority date of the ’608
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`patent.
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`22. Edwards’ own program, which existed prior to the PVT acquisition,
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`was named “Patriot,” and I was heavily involved. I attach here as Exhibit 1049 a copy
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`of a document generated during that program dated June 11, 2003, produced by
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`Edwards in the District Court litigation at Bates number EDWARDS 01016212-314.3
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`I am personally familiar with the work discussed in this document.
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`3 Documents bearing “EDWARDS” Bates numbers were produced from Edwards’
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`files by Edwards.
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 13 of 31
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`23.
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 14 of 31
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`simply is not true that Edwards previously failed to develop “a fabric seal disposed
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`around the exterior of the stent” as Patent Owner contends. (P.O. Response at 60.)
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`24. As I mentioned above, I also began working with the PVT valve as
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`soon as the acquisition was completed. Through that work, I became aware that PVT
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`also had considered including loose fabric on the outside of its early transcatheter heart
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`valves. A copy of a presentation given at Edwards by Stanton Rowe (one of PVT’s co-
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`founders) that covers some of PVT’s early work is attached as Exhibit 1050, produced
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`in the District Court litigation at Bates number EDWARDS 02433143-211.
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`25. That Edwards did not include an outer fabric skirt on its first two
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`commercial valves therefore is not evidence of anyone failing to develop the idea. It
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`was not a matter of whether we could add a second skirt to SAPIEN or SAPIEN XT, as
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`we surely could have based upon our prior development work.
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 15 of 31
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`26.
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`Indeed, the entire premise from which the Patent Owner proceeds—
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`asserting that Edwards must have “failed” to come up with a particular feature solely
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`because earlier FDA-approved devices did not include that feature—makes no sense.
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`Commercializing any medical device is a complicated process, filled with trade-offs.
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`In this case, the Edwards SAPIEN device was the first device of its type ever approved
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`in the U.S. (see P.O. Ex. 2020), such that there was no clear paradigm for how to
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`secure FDA approval, or avoid undue delay in the approval process. SAPIEN XT was
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`approved in the U.S. less than three years after SAPIEN was approved (P.O. Ex. 2021),
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`and indeed, the approval process for SAPIEN XT had begun before SAPIEN was
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`approved. I have never seen any study or article positing that SAPIEN or SAPIEN XT
`
`could have been approved on those timelines if they had included additional or
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`different features, regardless of how easy those features were to design or add, and I do
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`not see any such evidence in the Patent Owner’s Response. I therefore do not believe
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`that any assumptions the Patent Owner has made regarding the reasons for the lack of
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`an outer skirt are justified. Furthermore, as I explain below in the section on “long-felt
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`need” (see infra Section III.B), there were other successful strategies being employed
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`to address PVL with both SAPIEN and SAPIEN XT.
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`27.
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`I also note that although it is apparently the Patent Owner’s position
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`that their Lotus valve embodies the invention of the ’608 patent and has a feature
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`specifically designed to address PVL, the Lotus still is not FDA-approved for sale in
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 16 of 31
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`the United States, for reasons that appear to be entirely unrelated to the seal feature.4
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`In my opinion, this provides further evidence underscoring that the Patent Owner has
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`no basis to suspect that whether particular FDA-approved devices possess a particular
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`feature somehow reflects whether the industry had “failed” to come up with a given
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`solution.
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`28.
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`I also feel compelled to respond to statements in the Patent Owner’s
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`Response such as “The studies cited above suggest that Petitioner’s failure to include a
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`fabric skirt in its earlier-generation TAVR devices resulted in the premature deaths of
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`many patients.” (P.O. Response at 62.) I am not aware of a single doctor, statistician,
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`or other scientist who has ever made the assertion the Patent Owner makes or who has
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`performed an analysis that could support such an assertion, and indeed, the Patent
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`Owner does not point to any publication or other presentation in support of this bald
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`statement. To the contrary, SAPIEN and SAPIEN XT are widely regarded as having
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`saved many lives, as Patent Owner’s own evidence indicates. (See, e.g., P.O. 2051 at 3
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`(“In the PARTNER I randomized trials, patients with symptomatic severe aortic
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`stenosis, treated using the balloon-expandable SAPIEN transcatheter heart valve
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`system, had reduced mortality compared with standard therapy in patients who could
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`4 This has been reported in, among other places, Boston Scientific’s Annual Report
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`for 2016 (at p. 22); for convenience, excerpts of that document are attached here as
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`Exhibit 1051.
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 17 of 31
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`not undergo surgery. . . .”). In my position, I frequently analyze study data, and I am
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`familiar with the many different ways in which raw data and results can be analyzed,
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`both soundly and unsoundly. Using the outcome of a study about the S3 valve to
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`conclude (without making any calculations or adjustments) that earlier-generation
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`valves led to premature deaths is not a sound analysis. A true statistical analysis might,
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`for example, need to adjust for any differences in patient populations, as the first
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`patients to receive transcatheter heart valves were often extremely ill, more so than was
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`the case with later trials. And as I note above, the FDA approval process was not
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`predictable, particularly in the early days of TAVR. The SAPIEN and SAPIEN XT
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`saved many lives. It is entirely possible that even an easily-added feature could have
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`set back the time of the approval of SAPIEN or SAPIEN XT substantially, during
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`which period of delay patients who in fact received life-saving replacement valves
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`might have died. I see no portion of the Patent Owner’s Response that even attempts
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`to grapple with these types of issues.
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`B.
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`Long-Felt Need (P.O. Response pp. 63-64)
`29.
`I am informed that the secondary consideration addressed by the
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`Patent Owner under the heading of “long-felt need” is more completely described as a
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`long-felt and unresolved need. It is not true, as Patent Owner contends (P.O. Response
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`at 64), that paravalvular leakage (PVL) was unresolved. As is made clear in some of
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`the presentations on which the Patent Owner itself relies, close to 40% of patients who
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`received either a SAPIEN or SAPIEN XT showed either no PVL or only trace PVL at
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 18 of 31
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`1 year (P.O. Ex. 2051 at p.38 (SAPIEN = 38.2%, SAPIEN XT = 40.0%), and very few
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`patients suffered severe paravalvular leakage. (Id.) Indeed, one existing solution that
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`reduced PVL was to size the valve correctly—that is, to pick a valve size that was the
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`best match for the patient’s native anatomy to avoid creating leakage paths. At
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`Edwards, we recognized this very early on. For example, the Patriot document that I
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`referred to above reflects Edwards’ understanding as of June 2003 that “[p]roper sizing
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`is critical determinant for avoiding paravalvular leakage” and “[p]rosthesis sizing
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`remains critical to preventing PV leak.” (Ex. 1049 at 39, 41 (EDWARDS 01016250,
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`01016252).) Thus, in developing additional valve sizes for approval and eventual use,
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`we were in fact directly addressing PVL. For this reason, SAPIEN XT was offered in
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`multiple sizes. (Ex. 1052 (Freeman et al., First-in-Man Transfemoral Transcatheter
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`Aortic Valve Replacement with the 29 mm Edwards SAPIEN XT Valve, Catheterization
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`and Cardiovascular Interventions, 82:664-70 (2013)) at 667; see also P.O. Ex. 2017.)
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`So, for example, it was noted that for patients with larger vasculature, the 29mm valve
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`allowed for “a reduction in paravalvular leak, which has been associated with valve
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`undersizing.” (Ex. 1052 at 669.)
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`30.
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` Relatedly, the availability of additional sizes allowed physicians
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`not only to avoid putting in an undersized valve, but also allowed them to “oversize”
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`the valve implanted. An oversized valve is one that is slightly larger, when fully
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`expanded, than the patient’s native annulus. Implanting such an oversized valve acts to
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`reduce PVL. (See P.O. Ex. 2059 (Yang et al., Incidence and Severity of Paravalvular
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 19 of 31
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`Aortic Regurgitation With Multidetector Computed Tomography Nominal Area
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`Oversizing or Undersizing After Transcatheter Heart Valve Replacement With the
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`Sapien 3, 8 JACC: Cardiovascular Interventions 462 (2015)).) Another way in which
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`PVL was successfully addressed prior to S3 was through ensuring that the valves were
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`placed correctly, as correct placement acts to reduce PVL. (P.O. Ex. 2059 at 463.)
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`And finally, improvements in imaging allowed for both better determination of the size
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`of the patient’s anatomy and better visualization of the placement of the device,
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`leading to reduced PVL. (See Ex. 1053 (Wiegerinck et al., An Up-to-date Overview of
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`the Most Recent Transcatheter Implantable Aortic Valve Prostheses, Expert Review of
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`Medical Devices, 31-45 (2016)) at 38 (“Prevention of paravalvular leakage has been
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`achieved by optimal sizing using CT imaging.”).)
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`31. The Patent Owner’s Response implies that none of these other PVL
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`solutions worked. (P.O. Response at 60-61, 64.) But that is simply not true, as the
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`evidence that I discuss above and other evidence demonstrates. (See, e.g., P.O. Ex.
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`2003 at 7 (“The SAPIEN 3 valve combined with improved MDCT valve sizing and
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`more precise valve positioning techniques might be responsible for the reduction of
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`moderate or severe paravalvular regurgitation to sufficiently low levels that treatment
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`of lower-risk patients should no longer be discouraged.”) (emphasis added).)
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`32.
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`I also note that to my knowledge, the valve that has demonstrated
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`the lowest rates of PVL to date is a valve without an outer skirt. Data recently reported
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`at the 2017 EuroPCR conference regarding the Edwards CENTERA valve—which
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`Edwards Lifescience Corporation, et al. Exhibit 1046, p. 20 of 31
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`does not have an outer skirt (see photo contained in Ex. 1075)—indicates that the
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`CENTERA had excellent clinical outcomes and only a low 0.6 percent rate of
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`moderate paravalvular leak, with no severe paravalvular leak. (See Exs. 1073, 1074,
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`1075.) Yet the Patent Owner makes no mention of CENTERA at all.
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`33.
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`In sum, the fact that some PVL solutions (such as fabric disposed
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`around the exterior of the stent) were not implemented in each and every FDA-
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`approved THV does not mean that these solutions were not recognized or that other
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`solutions failed to address PVL.
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`C. Copying (P.O. Response pp. 64-66)
`34. The Patent Owner’s Response misstates the factual record
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`concerning Edwards’ efforts in several ways. First,
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` That early work also disproves the
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`Patent Owner’s theory that Edwards copied the outer skirt on the S3 from the Lotus.
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`We did not—w