`
`
`
`
`
`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.
`
`
`PETITIONERS’ REPLY
`
`IN SUPPORT OF INTER PARTES REVIEW OF
`
`U.S. PATENT NO. 8,992,608
`
`
`
`
`
`

`

`I.
`
`II.
`
`TABLE OF CONTENTS
`
`IPR2017-00060
`
`Page
`
`OVERVIEW OF REPLY ................................................................................ 1
`
`CLAIMS 1-4 ARE OBVIOUS OVER SPENSER IN VIEW OF
`ELLIOT (GROUND 7), THORNTON (GROUND 8), AND COOK
`(GROUND 9) ................................................................................................... 2
`
`A.
`
`B.
`
`Spenser Discloses Nearly Every Feature of Claim 1 .................. 3
`
`Spenser’s Purportedly Missing Features Are Taught by
`Elliot, Thornton, and Cook ......................................................... 6
`
`
`C. A POSITA Would Have Been Motivated to Combine
`Spenser’s Teachings With Those of Elliot, Thornton,
`and Cook ................................................................................... 11
`
`III. PO’S RELIANCE ON SECONDARY CONSIDERATIONS OF
`NON-OBVIOUSNESS IS FLAWED ........................................................... 17
`
`A.
`
`Secondary Considerations Are PO’s Initial Production
`Burden ....................................................................................... 18
`
`
`B.
`
`
`C.
`
`PO Failed to Establish a Nexus Between the Claimed
`Invention and S3 ....................................................................... 19
`
`Even if PO Had Established a Nexus, Secondary
`Considerations Do Not Render the ’608 Non-Obvious ............ 23
`
`IV. DR. BULLER IS A QUALIFIED THV EXPERT, AND HIS
`EXPERT OPINIONS (UNLIKE PO’S) DESERVE SIGNIFICANT
`WEIGHT ........................................................................................................ 27
`
`V.
`
`CONCLUSION .............................................................................................. 29
`
`
`
`
`
`
`
`
`ii
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`IPR2017-00060
`
`EXHIBIT LIST
`
`EXHIBIT 1001 U.S. Patent No. 8,992,608 to Haug et al.
`EXHIBIT 1002
`File History of U.S. Application No. 12/492,512
`EXHIBIT 1003 WO 98/29057 to Cribier et al.
`EXHIBIT 1004 WO 03/047468 to Spenser et al.
`EXHIBIT 1005 U.S. Patent App. Pub. No. 2003/0236567 to Elliot
`EXHIBIT 1006 U.S. Patent App. Pub. No. 2004/0082989 to Cook et al.
`EXHIBIT 1007 Declaration of Dr. Nigel Buller
`EXHIBIT 1008 Alain Cribier et al., “Early experience with percutaneous
`transcatheter implantation of heart valve prosthesis for the
`treatment of end-stage inoperable patients with calcific aortic
`stenosis,” J. Am. Coll. Cardiol., 43(4): 698-703 (2004).
`EXHIBIT 1009 U.S. Patent App. Pub. No. 2001/0039450 to Pavcnik et al.
`EXHIBIT 1010 U.S. Patent App. Pub. No. 2004/0033364 to Spiridigliozzi et al.
`EXHIBIT 1011 U.S. Patent No. 3,365,728 to Edwards
`EXHIBIT 1012 Charles T. Dotter, “Transluminally-Placed Coilspring
`Endarterial Tube Grafts,” Investigative Radiology, 329-32
`(1969).
`Frank Ing, “Stents: What’s Available to the Pediatric
`Interventional Cardiologist?” Catheterization and Cardiovascular
`Interventions 57:274-386 (2002).
`EXHIBIT 1014 U.S. Patent No. 6,206,911 to Milo
`EXHIBIT 1015
`Excerpts from Vossoughi et al., Stent Graft Update (2000)
`EXHIBIT 1016
`Excerpts from Dolmatch et al., Stent Grafts: Current Clinical
`Practice (1999)
`EXHIBIT 1017 Andersen et al., “Transluminal implantation of artificial heart
`valves. Description of a new expandable aortic valve and initial
`results with implantation by catheter technique in closed chest
`pigs,” European Heart Journal, 13:704-08 (1992).
`EXHIBIT 1018 U.S. Patent No. 5,411,552 to Andersen et al.
`EXHIBIT 1019 U.S. Patent No. 6,015,431 to Thornton et al.
`EXHIBIT 1020 U.S. Patent App. Pub. No. 2001/0021872 to Bailey et al.
`EXHIBIT 1021 U.S. Patent No. 6,352,554 to De Paulis
`
`EXHIBIT 1013
`
`
`
`iii
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`

`

`IPR2017-00060
`
`European Patent 2 749 254 B1 to Salahieh et al.
`EXHIBIT 1022
`EXHIBIT 1023 American Heritage College Dictionary, 4th Ed. 2002 (definition
`of “flaps”)
`EXHIBIT 1024 Merriam-Webster’s Collegiate Dictionary, 10th ed. (2001)
`(definitions of “flaps” and “pleats”)
`EXHIBIT 1025 Charles S. Thompson et al., “Endoluminal stent grafting of the
`thoracic aorta: Initial experience with the Gore Excluder,”
`Journal of Vascular Surgery, 1163-70 (June 2002).
`EXHIBIT 1026 Gore Excluder Instructions for Use (2002)
`EXHIBIT 1027 U.S. Patent No. 5,957,949 to Leonhardt et al.
`EXHIBIT 1028 Assignment record for U.S. Patent App. Pub. No. 2003/0236567
`to Elliot
`Lawrence et al., “Percutaneous Endovascular Graft:
`Experimental Evaluation,” Radiology, 163(2): 357-60 (May
`1987).
`European Patent 2 926 766 B1 to Salahieh et al.
`Boston Scientific’s August 24, 2016 Response in Opposition
`Proceedings of EP 2 749 254 B1
`Boston Scientific’s August 24, 2016 Reply in German
`Infringement Proceeding 4a O 137/15
`U.S. Patent No. 5,855,601 to Bessler et al.
`U.S. Patent No. 5,476,506 to Lunn
`Supplemental Declaration of Nigel. P. Buller, M.D.
`Approved Judgment, Edwards Lifesciences, Inc. v. Boston
`Scientific Scimed, Inc., HC-2015-004574 dated March 3, 2017
`Judgment, CoreValve Inc. v. Edwards Lifesciences AG et al., HC
`07 C01243 dated January 9, 2009
`Approved Judgment, Edwards Lifesciences AG v. Cook Biotech
`Inc., HC08 C 00934 dated June 12, 2009
`Memorandum, Edwards Lifesciences AG et al. v. CoreValve,
`Inc. et al., C.A. No. 08-91 (GMS) dated February 1, 2011
`Plaintiffs’ Opening Brief in Support of Their Motion for
`Enhanced Damages Pursuant to 35 U.S.C. § 284, Edwards
`Lifesciences LLC, et al. v. Medtronic CoreValve LLC, et al. C.A.
`12-023 (GMS) dated March 24, 2014
`Vossoughi et al. (Eds.), Stent Graft Update, Medical and
`Engineering Publishers Inc. (2000)
`
`EXHIBIT 1029
`
`Exhibit 1030
`Exhibit 1031
`
`Exhibit 1032
`
`Exhibit 1033
`Exhibit 1034
`Exhibit 1035
`Exhibit 1036
`
`Exhibit 1037
`
`Exhibit 1038
`
`Exhibit 1039
`
`Exhibit 1040
`
`Exhibit 1041
`
`
`
`iv
`
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`

`IPR2017-00060
`
`Dolmatch et al. (Eds.), Stent-Grafts Current Clinical Practice,
`Thieme (2000)
`Deposition Transcript of Stephen J.D. Brecker, M.D. (Sept. 1,
`2017)
`Deposition Transcript of Andrew J. Manganaro, M.D. (Sept. 15,
`2017)
`Reply Declaration of Nigel P. Buller, M.D.
`Declaration of Larry Lee Wood
`Curriculum Vitae of Larry Lee Wood
`Shuren, Life-Saving, Smart Regulation on Behalf of Patients with
`Aortic Stenosis, FDA Voice (June 16, 2014)
`Edwards Endovascular HVT – Patriot Technical Design Review
`Proof of Concept & Selection of 1st Generation Valve dated June
`11, 2003
`Rowe, Stanton, “History of Sapien and the Future of THV”
`[EDWARDS 02433143-211]
`Boston Scientific’s 2016 Annual Report
`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)
`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)
`Zaman et al., Incidence and Predictors of Permanent Pacemaker
`Implantation Following Treatment with the Repositionable
`Lotus™ Transcatheter Aortic Valve, Catheterization and
`Cardiovascular Interventions (2016)
`August 18, 2016 Letter from B. Zuckerman to J. Mazzarella re:
`P130009/S057
`Medtronic CoreValve™ Evolut™ R System First TAVI to
`Receive CE Mark for Intermediate Risk Aortic Stenosis Patients,
`Medtronic Press Release (August 1, 2016)
`Medtronic Expands TAVR Access to More Patients With
`Symptomatic, Severe Aortic Stenosis Upon Intermediate Risk
`FDA Approval, Medtronic Press Release (July 10, 2017)
`Boston Scientific Receives CE Mark for Lotus™ Valve System,
`Boston Scientific Press Release (October 28, 2013)
`
`v
`
`Exhibit 1042
`
`Exhibit 1043
`
`Exhibit 1044
`
`Exhibit 1045
`Exhibit 1046
`Exhibit 1047
`Exhibit 1048
`
`Exhibit 1049
`
`Exhibit 1050
`
`Exhibit 1051
`Exhibit 1052
`
`Exhibit 1053
`
`Exhibit 1054
`
`Exhibit 1055
`
`Exhibit 1056
`
`Exhibit 1057
`
`Exhibit 1058
`
`
`
`

`

`Exhibit 1059
`Exhibit 1060
`
`Exhibit 1061
`Exhibit 1062
`Exhibit 1063
`Exhibit 1064
`
`Exhibit 1065
`
`Exhibit 1066
`
`Exhibit 1067
`
`Exhibit 1068
`Exhibit 1069
`
`Exhibit 1070
`
`Exhibit 1071
`
`Exhibit 1072
`
`Exhibit 1073
`
`Exhibit 1074
`
`IPR2017-00060
`
`WO 2005/102015 to Bergheim et al.
`Jayalath, R.W. et al., “Aortic Calcification,” Eur. J. Vasc.
`Endovasc. Surg., Vol. 30, 476-488 (2005)
`Compilation of Pictures of PVT Prototype Designs
`Engineering Drawings, S3 External Skirt
`Engineering Drawings, S3 Internal Skirt
`Brecker Deposition Exhibit 1, Excerpts from Textbook of
`Interventional Cardiology, 2d Ed. (1994)
`U.S. Patent App. No. 13/290,369 Prosecution History,
`Examiner’s Answering Brief to Appeal (Mar. 12, 2015)
`U.S. Patent App. No. 13/290,369 Prosecution History, PTAB
`Appeal Decision (June 2, 2017)
`Declaration of Professor Stephen J.D. Brecker in Support of
`Boston Scientific’s Reply Claim Construction Brief (D.I. 109 in
`Boston Scientific Corp. v. Edwards Lifesciences Corp., C.A. No.
`16-275 (SLR) (SRF) (D. Del.))
`Lotus Valve FDA Recall Notice
`Edwards Lifesciences LLC’s and Edwards Lifesciences PVT,
`Inc.’s Reply Claim Construction Brief Regarding U.S. Patent
`Nos. 7,510,575, 9,168,133, and 9,339,383 (D.I. 106 in Boston
`Scientific Corp. v. Edwards Lifesciences Corp., C.A. No. 16-275
`(SLR) (SRF) (D. Del.))
`Roy, David et al., “Transcatheter Aortic Valve Implantation for
`Pure Severe Native Aortic Valve Regurgitation,” JACC, Vol.
`16(15), 1577-84 (2013)
`J.A. Southard, M.D., TAVR: It’s a Career, Not Just a Procedure!
`(May 5, 2012) available at
`www.ucdmc.ucdavis.edu/internalmedicine/cardio/pdf/Symposiu
`m%202012/TAVR%20Talk.pdf
`H.B. Riberio et al., Balloon-Expandable Prostheses for
`Transcatheter Aortic Valve Replacement, 56 Progress in
`Cardiovascular Diseases 583 (2014)
`“Centera: Novel Transcatheter Heart Valve Shows Promise in
`Aortic Stenosis,” EuroPCR Meeting News (May 26, 2017)
`Edwards Lifesciences Press Release: “Edwards’ Novel Self-
`Expanding Transcatheter Heart Valve Demonstrates Excellent
`Early Patient Outcomes” (May 17, 2017)
`
`
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`

`IPR2017-00060
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`“Edwards’ Self-Expanding Transcatheter Heart Valve
`Demonstrates Excellent Early Patient Outcomes,” DAIC (May
`24, 2017)
`Declaration of Gregory S. Cordrey
`
`Exhibit 1075
`
`Exhibit 1076
`
`
`
`
`
`
`
`
`vii
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`

`

`IPR2017-00060
`
`I.
`
`OVERVIEW OF REPLY
`
`The ’608 Patent (“’608”) did not invent THVs, first identify the problem of
`
`PVL, or invent the use of fabric seals on THVs to prevent or minimize PVL—and
`
`Patent Owner’s (“PO”) Response does not argue otherwise. PO further concedes
`
`the primary Spenser reference on which review was instituted (Grounds 7-9)
`
`discloses almost every element of independent Claim 1 of the ’608, including a
`
`THV having a “fabric seal [that] extends from the distal end of the replacement
`
`valve and back proximally over the expandable anchor”—the addition during
`
`prosecution on which allowance was based. (EX1002, 358; EX1004, 21, 24).
`
`As to the elements purportedly missing from Spenser—“flaps that extend
`
`into spaces formed by native valve leaflets” (Claim 1) and “pockets” (Claims 2-
`
`3)—PO’s attempt to distinguish secondary references disclosing these elements
`
`(Elliot, Thorton and Cook) fails. PO bases its purported distinction on unclaimed
`
`requirements, arguing these references pertain only to “preventing leaks between
`
`the grafts and healthy aortic tissue,” while, according to PO, the claims require
`
`that the flaps “fill gaps formed by diseased and calcified native leaflets.”1
`
`(Response, 3; EX1043, 82:23-83:3; EX1044, 60:5-13). Even if the claims
`
`included this limitation (they don’t), as with Spenser and the ’608 these
`
`references expressly disclose using fabric seals to prevent leakage between the
`
`1
`All emphasis is added unless noted.
`
`
`
`1
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`

`

`IPR2017-00060
`
`prosthesis and calcified tissue. See infra, § II(B). Moreover, PO concedes
`
`Petitioners’ secondary references disclose fabric seals with “pockets” as in
`
`Claims 2-3. And PO does not dispute that the “flaps” and “pockets” features
`
`were deemed an obvious design choice by the Patent Office. (EX1002, 352-53).2
`
`PO’s further arguments—that hypothesized secondary considerations
`
`overcome this art and render Claims 1-4 non-obvious, and that the fully-qualified
`
`and-supported opinions of Petitioners’ expert, Dr. Buller, should be ignored—are
`
`similarly baseless.3 For the reasons herein, as well as those in the Petition and
`
`cited exhibits, which stand unrebutted, Claims 1-4 of the ’608 should be found
`
`unpatentable.
`
`II. CLAIMS 1-4 ARE OBVIOUS OVER SPENSER IN VIEW OF ELLIOT
`(GROUND 7), THORNTON (GROUND 8), AND COOK (GROUND 9)
`
`PO’s arguments about combining Spenser with Elliot, Thornton, and Cook
`
`are factually unsupported and contradicted by the prior art’s explicit teachings; are
`
`
`2
`Applying the same art relied upon by the ’608’s Examiner, the Board
`
`recently affirmed an obviousness rejection of a “pleated seal” in PO’s related
`
`application, No. 13/290,369. (EX1065, ¶ 8; EX1066, 7).
`
`3
`
`As explained below, PO fails to establish that Petitioners' SAPIEN 3 (“S3”)
`
`product practices, and thus has a nexus to, the Challenged Claims.
`
`
`
`2
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`IPR2017-00060
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`based on purported distinctions that are unclaimed; and are contradicted by PO’s
`
`own expert’s statements here and in the District of Delaware.
`
`A.
`
`Spenser Discloses Nearly Every Feature of Claim 1
`
`PO does not dispute that “Spenser discloses each element of Claims 1-4 of
`
`the ’608 patent except for the ‘flaps’ and ‘pockets’ limitations ….” (Response, 39
`
`(citing Petition, 66, 71)).4
`
`PO instead argues Spenser’s teachings are inconsistent with using “flaps” as
`
`claimed by the ’608 because “the cuff portion is depicted as having no slack,” and
`
`modifying Spenser to include slack is “contrary to the express teachings of
`
`Spenser” as it would “render the cuff unable to enhance stability.” (See, e.g.,
`
`Response, 27-31). Not so.
`
`First, Spenser’s cited statements about “slack” relate only to the valve
`
`portions (i.e., the commissures) attached to the three support beams “at the
`
`support beams,” not the remaining valve portions extending between the support
`
`beams, or the portion of the cuff extending along the outside of the anchor.
`
`4
`In the related Delaware litigation the Court adopted PO’s proposals and
`
`defined “flaps” as “[f]abric projecting from the anchor” and “pockets” as
`
`“[c]avities formed by the fabric seal,” (EX2032, 3)–constructions broader than
`
`Petitioners’ proposals. If adopted here, the Challenged Claims would be
`
`unpatentable for at least the same reasons already presented.
`
`
`
`3
`
`

`

`IPR2017-00060
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`(EX1004, 23). Directly contradicting PO, Spenser references the portion of the
`
`cuff on the outside of the anchor as “slack wall”: “[t]o prevent leakage from the
`
`inlet it is optionally possible to roll up some slack wall of the inlet over the edge of
`
`the frame ….” (EX1004, 21).
`
`Second, the use of “slack” in Spenser’s cuff and using the cuff to enhance
`
`valve stability are not incompatible. (Cf., e.g., Response, 27-31). Confusing the
`
`issue, PO’s expert interprets Spenser’s reference to “stability” to mean prevention
`
`of valve migration, (EX1043, 69:10-13), when it refers, instead, to the stability of
`
`the device’s construction. (Petition, 68; EX1007, ¶ 178; EX1004, 22 (“floating
`
`supports … enhance the stability of the device”; “a cuff portion … to enhance the
`
`stability”), 23; EX1045, ¶ 28). Spenser discloses use of an additional second stent
`
`or hooks to prevent migration, not the cuff. (EX1004, 30-31, 36-37; EX1045,
`
`¶ 28). Furthermore, both kinds of “stability” can be achieved with slack material.
`
`Indeed, PO’s argument about device migration resulting from slack is
`
`inconsistent with the ’608’s own recognition that “[a]n improved seal is expected
`
`to reduce paravalvular leakage, as well as migration of the anchor over time.”
`
`(EX1001, 13:48-50; EX1045, ¶ 29). This makes sense—a POSITA would have
`
`understood that a fabric seal with excess fabric has a greater surface area, resulting
`
`in more contact and friction with the native leaflets, in turn providing improved
`
`stability. (EX1045, ¶ 30 (citing EX1059 (Bergheim), 12 (“The cuff may also
`
`
`
`4
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`

`

`IPR2017-00060
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`prevent migration of the valve as the friction between the valve device and the
`
`surrounding is increased.”))).
`
`As to the construction’s stability, any points of attachment of the valve to the
`
`anchor will enhance stability, regardless of whether the cuff also includes “slack.”
`
`(EX1004, 35 (“[t]he fixed attachment of the valve leaflets to the support frame …
`
`renders it greater stability”)). Pavcnik, among others, further confirms that an
`
`external THV seal can include both portions stably connected to the anchor and
`
`“slack” portions for sealing:
`
`
`
`(EX1009, Fig. 27, ¶ [0074] (detailing a covering “sutured into place” that “can also
`
`form a corner flap” for sealing); see also Petition, 23-24).
`
`Third, Spenser teaches that “[p]referably cuff portion 21 of valve material 28
`
`is attached to support beams 23.” (EX1004, 22). This means the cuff can be
`
`attached to anchor portions subject to dimensional changes, suggesting the use of
`
`
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`5
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`

`

`IPR2017-00060
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`slack material to accommodate these changes. (See Petition, 22; EX1004, 22, 43;
`
`EX2028, 184:23-190:3; EX1044, 59:7-11; EX1043, 67:20-24; EX1045, ¶¶ 31-39).
`
`Fourth, in the counterpart litigation, Petitioners counterclaimed with Spenser
`
`patents5 sharing specifications identical to Spenser here. Applying the Phillips
`
`standard narrower than the BRI applicable here, the Court rejected PO’s argument
`
`that the annular cuff disclosed by Spenser is limited to a cuff that is tight and flush
`
`against the support frame. (EX2032, 6; EX1069, 12-14).
`
`For each of these reasons, Spenser does not exclude, much less teach away,
`
`from the use of slack material in the cuff. (Cf. Response, 3-4, 27-29, 31, 34, 37).
`
`B.
`
`Spenser’s Purportedly Missing Features Are Taught by Elliot,
`Thornton, and Cook
`
`PO’s arguments concerning Elliot, Thornton, and Cook rest on fundamental
`
`misconceptions: (1) that “healthy” tissue surrounding aneurysms is free of
`
`calcification; and (2) that the disclosed flaps cannot extend into spaces formed by
`
`native leaflets. Both are false.
`
`First, PO erroneously argues Elliot, Thornton, and Cook can only address
`
`leaks along “healthy” tissue, not calcified tissue. (E.g., Response, 24). But
`
`“healthy” does not mean free of calcification; PO’s own expert concedes it simply
`
`refers to tissue that is not part of the aneurysm. (EX1043, 70:7-71:4). Indeed, PO
`
`
`5
`U.S. 7,510,575; 9,168,133; and 9,339,383.
`
`
`
`6
`
`

`

`IPR2017-00060
`
`ignores Elliot’s and Thornton’s confirmation that this “healthy” tissue can be
`
`calcified, (EX1019, 30:27-36; EX1005, ¶ [0004]), which PO’s experts also
`
`concede. (EX2079, ¶ 47; EX2080, ¶ 59; EX1043, 70:7-71:4; EX1044, 86:4-9; see
`
`also EX2028, 119:21-125:7; EX1045, ¶¶ 40-47).
`
`Further belying PO’s misplaced focus on TAVR and aortic calcification
`
`(Response, 6-11), the Challenged Claims are not limited to aortic replacement, or
`
`to treating aortic calcification. (EX1001, Claims 1-4; EX1043, 82:23-83:10
`
`(Brecker admitting he interpreted claims to require calcification), 89:5-90:9;
`
`EX1044, 33:2-14, 34:17-35:3, 40:3-11, 60:1-13 (Manganaro admitting same)).
`
`Indeed, ’608 states “[v]alve replacement may be indicated when there is a
`
`narrowing of the native heart valve, commonly referred to as stenosis, or when the
`
`native valve leaks or regurgitates.” (EX1001, 1:29-31; EX1043, 46:2-8; EX1044,
`
`34:4-15 (confirming “stenosis” broadly means “narrowing,” and does not
`
`necessarily include calcification)). This is echoed in Claim 1, which refers only to
`
`“spaces formed by native valve leaflets,” not “spaces formed by diseased, calcified
`
`native valve leaflets” as PO argues. (Response, 33). PO’s expert agrees Claim 1
`
`covers “pure” aortic regurgitation, where the leaflets have no calcification.
`
`(EX1043, 42:11-20; 44:8-45:18, 90:14-91:13; see also EX1070 (Brecker’s “pure”
`
`regurgitation publication)).
`
`
`
`7
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`

`IPR2017-00060
`
`Second, PO erroneously argues Petitioners’ combinations fail to disclose a
`
`“bunched up” “fabric seal” that “in the deployed state . . . comprises flaps that
`
`extend into spaces formed by native valve leaflets.” (Response, 39, 42, 45;
`
`EX2080, §VII; EX2079, ¶¶ 50, 59, 62; EX1044, 59:21-25 (Manganaro admitting
`
`he read the claims to require bunching up)).6 But Claims 1-4 do not require a
`
`“bunched up” seal, or any degree of foreshortening. (EX1043, 83:12-85:9; see
`
`also Petition, 33 (flaps could be pre-formed); EX1045, ¶ 32).
`
`Moreover, Elliot, Thornton, and Cook each disclose “flaps” designed to
`
`extend into and conform to the surrounding tissue. (Petition, 57-64, 71-73):
`
` Elliot discloses that “[i]rregularities and/or wall displacement … can
`
`be responded to by the skirt 16 in minimizing endoleaks about the
`
`prosthesis 10.” (EX1005, ¶ [00024]);
`
` Thornton discloses that “flange (26) may engage a radially confining
`
`endolumenal wall … [and] enhance the reduction of flow around
`
`tubular member ….” (EX1019, 7:31-42); and
`
`
`6
`PO’s identification of “flaps that extend into spaces formed by native valve
`
`leaflets” as the only missing feature in Petitioners’ combinations is an implicit
`
`admission that each of Elliot, Thornton, and Cook discloses “pockets” as claimed.
`
`(See also EX2079, ¶¶ 46, 52, 58).
`
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` Cook discloses an “external sealing zone configured to engage the
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`walls of the vessel to facilitate sealing ….” (EX1006, Claim 7).
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`Each disclosure confirms that the seals would extend into spaces formed by the
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`native leaflets (which may or may not be calcified in Claim 1).7 (See also Petition,
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`70 (citing earlier discussion of Hemobahn graft and Leonhardt patent, both
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`confirming fabric seals will conform to, and extend into spaces formed by,
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`surrounding tissue); EX1007, ¶¶ 59, 74). These seals would do so even if
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`compressed tightly between an anchor and a calcified aortic annulus, which PO
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`assumes for its argument. (Response, 41, 44, 46).8 Even the seal described and
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`claimed in the ’608 is “compressed tightly” between the anchor and surrounding
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`annulus, yet it purportedly remains capable of extending into spaces formed by the
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`native valve leaflets. (EX1001, Fig. 34; EX1043, 88:3-19). Moreover, the nearly
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`These references’ teachings are not limited to stent grafts. (EX1007, n.1,
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`n.2, n.3). Even if they were, attacking these references individually on the basis
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`that they don’t disclose a valve is improper. (Paper 7, 12).
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`PO’s experts conditionally argue Elliot, Thornton, and Cook do not teach
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`seals that would extend into spaces formed by native leaflets “if deployed in a
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`diseased and calcified aortic valve,” (EX2079, ¶¶ 45, 51, 57), and “if [it] were
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`compressed tightly between a TAVR anchor and the hard, calcified aortic
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`annulus.” (EX2080, ¶¶ 62, 67).
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`identical structure taught by these references and ’608 Figure 34 also belies any
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`suggestion this structure would not function the same way as claimed:
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`(Compare Ex. 1001, Fig. 34, with Ex. 1005, Fig. 5b, Ex. 1006, Fig. 6, & Ex. 1019,
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`Fig. 1 (highlighting added); see also Petition, 58).
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`PO also ignores its expert’s, Dr. Brecker’s, admission in sworn testimony
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`that only a projection the size of a wrinkle is needed to form the claimed “flaps that
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`extend into spaces formed by native valve leaflets.” EX1067, 6 (“these gaps [in
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`native valve leaflets] vary from patient to patient and there could be a patient in
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`which the gaps were very small and only a ‘wrinkle’ in the fabric would suffice to
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`extend into the gap”). There can be no dispute that the flaps in each of Elliot,
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`Thornton, and Cook are more than mere wrinkles in the graft, and would thus, by
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`Brecker’s own admission, extend into spaces formed by the native valve leaflets.
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`Thornton, for example, explicitly references the formation of longitudinal wrinkles
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`in the graft, and teaches that its seal extends radially beyond those wrinkles in
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`order to prevent formation of leakage paths along the graft. (EX1019, 10:13-30;
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`see also EX1005, ¶ [0029]; EX1006, ¶ [0026]).
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`Finally, in arguing the “conical” cuffs/projections of Elliot, Thornton, and
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`Cook are not “flaps” (Response, 40, 43, 45), PO appears to suggest a single
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`cuff/projection cannot form “flaps,” plural. This ignores that Elliot, Thornton, and
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`Cook each disclose multiple cuffs/projections, which form “flaps,” (see, e.g.,
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`Petition, 12-15), and also ignores ’608’s Figure 34, which purportedly shows a
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`single cuff with “flaps.” (EX1001, 14:21-29). Moreover, in single-cuff
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`embodiments, the cuff “projects” from the anchor, which is all that would be
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`required under the District Court’s “flaps” construction advocated by PO.
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`C. A POSITA Would Have Been Motivated to Combine Spenser’s
`Teachings With Those of Elliot, Thornton, and Cook
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`PO argues there is no motivation for Petitioners’ combinations because
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`(1) none purportedly recognized the PVL problem with THVs, and (2) even if a
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`POSITA recognized the problem, they would not combine these references
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`because they “address vastly different problems.” (Response, 23-24, 32-33, 35-
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`36). PO is wrong on both counts: (1) PVL was a recognized problem since the
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`advent of surgical heart valves in the 1960s and early development of THVs in the
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`1990s, (Petition, 3-5; EX1043, 72:23-76:22, 77:9-79:16; EX1064, 1271), and
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`(2) PO’s assertion of “vastly different problems” rests on its erroneous and
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`unclaimed distinction between calcified leaflets and “healthy” tissue surrounding
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`an aneurysm, supra 6-7.
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`Beyond PO’s flawed analysis, there are numerous reasons a POSITA would
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`have been motivated to combine the teachings of Spenser with those of Elliot,
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`Thornton, or Cook.
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`First, that PVL was known and addressed in the surgical valve context
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`would motivate a POSITA to address it in THV designs. Contrary to Dr. Brecker’s
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`assertion that sewing rings in surgical heart valves were “never considered …
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`‘sealing’ ring[s]” (EX2080, 8), the first surgical valve patent cited in the Petition
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`(from 1968) is titled “Upholstered Heart Valve Having a Sealing Ring …,” and
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`details that the sealing ring conforms to irregularities in surrounding tissue.
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`(Petition, 4; see also EX1011, 1:13-16). Moreover, PVL in surgical valves did not
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`occur “only in the rarest of circumstances” as Dr. Manganaro suggests (EX2079,
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`10); PO’s own evidence and expert confirm PVL was identified after surgical
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`valve implants in as many as 47% of patients. (EX2004, 1; see also EX1043,
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`72:23-76:22 (agreeing that PVL is a known problem with surgical heart valve
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`replacement)).
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`Second, contrary to PO’s assertion that the ’608 “identified the problem of
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`PVL” (Response, 2), THV-specific literature recognized long before ’608’s
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`purported priority date that designs should address PVL. Dr. Cribier’s 2004
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`publication disclosed that “severe paravalvular aortic regurgitation might impair
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`long-term clinical outcomes after [THV] [] implantation.” (Petition, 59 (citing
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`EX1008)). And, as PO’s expert conceded, the 1994 Textbook of Interventional
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`Cardiology recognized PVL among the problems associated with surgical valves,
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`concluding “[t]he designer of any percutaneously placed valve will need to
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`consider these issues during its design and development in order to minimize these
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`problems.” (EX1064, 1271; EX1043, 72:16-77:14). Knowing this, a POSITA
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`would have been motivated to combine the teachings of Spenser and Elliot,
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`Thornton, or Cook in an effort to reduce PVL.
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`PO further points to a June 2004 patent (U.S. Patent No. 7,276,078), which
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`says Spenser “do[es] not address leaks that can occur around the implanted valve,”
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`but then highlights a series of PVL solutions for THVs substantially similar to
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`those disclosed in Spenser. (Response, 22 (referencing EX2030)). Even if its
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`characterization of Spenser were correct,9 this highlights that skilled artisans
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`around the time of ’608’s purported priority date were aware of PVL issues and
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`motivated to employ solutions, even solutions increasing the device’s profile. (See,
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`e.g., EX2030, 4:39-45; EX1043, 80:6-24 (acknowledging ’078 solutions increase
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`profile)).
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`Third, even if the “spaces formed by native valve leaflets” of Claims 1-4
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`were limited to calcified aortic leaflets as PO suggests (Response, 3), both Elliot
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`and Thornton, as well as PO’s experts, confirm the “healthy” tissue surrounding
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`Whether or not Spenser’s inventors (or the subset of them named on the
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`’078) believed Spenser addressed PVL is irrelevant; the proper analysis is through
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`the eyes of a POSITA as of June 2004. Arkie Lures, Inc. v. Gene Larew Tackle,
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`Inc., 119 F.3d 953, 956 (Fed. Cir. 1997) (obviousness evaluated through eyes of
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`POSITA, not inventor); (EX1007, ¶¶ 178, 180). And PO’s experts concede that,
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`even with a tight fitting seal around a THV (not required by Spenser), there would
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`still be a reduction in PVL. (EX2080, 31 (disputing only whether this would
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`“significantly reduce or prevent PVL.”); EX1043, 94:20-95:24 (Brecker admitting
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`Medtronic Evolut Pro device—which he characterized as having “a tightly fitting
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`external wrap”—has “significantly less” PVL (EX2080, ¶ 54)); EX1044, 75:1-5
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`(Manganaro admitting Spenser’s cuff will prevent PVL depending upon degree of
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`calcification)).
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`aneurysms may be calcified. Supra 6-7. Thus, a POSITA would have been
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`motivated to combine these teachings with Spenser for a THV implanted in a
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`calcified, aortic annulus to prevent/reduce PVL. A POSITA likewise would have
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`been motivated to combine these references where the native leaflets are free of
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`calcification.
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`Fourth, Spenser discloses a desire to enhance its THV’s sealing properties
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`(Petition, 22), disclosing, e.g., “a rolled sleeve, which enhances the sealing of the
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`device at the valve inlet.” (Id., 70 (quoting EX1004, 24)). Thus, even Spenser
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`alone provides motivation to combine its teachings with others to improve its
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`sealing function.
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`Fifth, the Patent Office, including the Board, has now twice concluded a
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`POSITA would be motivated to incorporate “flaps”/“pleats” in a THV seal as “an
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`obvious alternative design choice.” (See Petition, 37-38; supra n.2). This is no
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`surprise given that modifying Spenser requires nothing more than adapting the
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`fabric seal in view of express teachings directed to fabric seals in the same field
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`and for the same end result of sealing the prosthesis to the surrounding tissue.
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`(See, e.g., supra § II(B); EX1044, 42:17-21 (confirming stent grafts are relevant to
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`subject matter of ’608)). Moreover, a POSITA would have recognized that
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`Petitioners’ combinations would work as expected to produce a fabric seal with
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`“flaps” “extend[ing] into spaces formed by the native valve leaflets” and
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`“pockets”—as the Petition explains (Petition, 59, 61, 64, 71-73), the combinations
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`are nothing more than the arrangement of known elements, each performing its
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`same, known function to yield the expected result of a THV with a fabric seal
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`having “flaps” and “pockets” that reduces the risk of PVL. (Petition, 60, 61, 64,
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`71-73); see also KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
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`Sixth, the cited success of th