AU2017200883B2 - Percutaneously deliverable heart valve including folded membrane cusps with integral leaflets - Google Patents

Abstract

PERCUTANEOUSLY DELIVERABLE HEART VALVE INCLUDING FOLDED MEMBRANE CUSPS WITH INTEGRAL LEAFLETS A transcatheter, percutaneously implantable, prosthetic heart valve is provided that comprises a lattice frame and two or more integrated cusp and leaflet folded structures attached to the lattice frame. The two or more integrated cusp and leaflet folded structures each comprise a flat sheet of biocompatible membrane that is folded to include a substantially conical shape according to a flat folding pattern. The substantially conical shape is further formed by joining apposing sides of the substantially conical shape along a seam. The two or more integrated cusp and leaflet folded structures are each attached along their respective seams to the lattice frame in a direction substantially parallel to an axis of the lattice frame. Embodiments of valves described herein have application within the entire vascular system.

Description

FERlT 1 WEOUSLY DELIVERABLE- ΗΕ\ΗΊ VMVE

INCLUDING FOLDS.D MLMBR Wl I I SFS IWH Ml GRU 11 UE I IS FIELD

The present invention relates to the field of medical devices, and more particularly, to 5 percutaeously deliverable heart valves.

BACKGROUND

The native heart valves, and in particular, the aortic valve, lias a complex geometry that endows. both ideal opening and closing geometries through an. anatomic joining of a tubular inflow structure of the left ventricular outflow tract -and an expansion of the valve sinuses above 10 the hinging point of the valve leaflets defined by the aortic valve annular ring, part of the fibrous “skeleton” of t he h eart

For the purposes of discussion and definition in. the ensuing descriptions, the “upper”, downstream outlet structure of the native aortic valve above its .hinging point contains three valve “cusps” of a generally spherical contour with central mobile portions termed. “leaflets” that 15 are induced by fluid pressure gradients to meet centrally to close and to move radially outward to open in. valve operation. The cusps am Anther continuous with downstream curved tissue walls meeting the tubular great vessel, 'the aorta, at the “sinotubular junction” Each, cusp and its upper, downstream extension above the level of leaflet closure (“coaptation”)' are a continuous structure of a generally spherical contour-and together define the envelope of the 20 “sinus of Valsalva. Typically, surgical prosthetic valves are implanted by excision of the diseased native wive leaflets at the level of the annular ring, and sumring of the prosthetic valve at tlrls point, thus replacing only the_; opening geometry of the. valve and leaving the outer structures of the cusps and the sinuses of Valsalva, the anatomy that confers proper closing geometry, generally irttaet.

Surgical valve prostheses are generally constructed as'analogs to this 'Central portion of the native valve geometry involved in the opening phase of the valve cycle. This approach: to modeling the replacement valve prosthesis is enabled by the nature, of th e surgical technique: ths replacement valve Is sutured into the valve seat under direct vision. In contrast, a percutaneous stent-mounted heart valve (“PHV”) [s typically a .construct in which the operating valve 30 membrane leaflets are mounted and confined within the. tubular envelope of a collapsible frame for effective .tansvascular -delivery.

.Further, in. order to preclude valve regurgitation, the base of each leaflet must lie in. exact apposition to the valve seat to form, a seal, a condition that is difficult to satisfy without implantation, under direct vision. Even then, since the diseased native valve would, not be 35 removed and its axial geometry is often distorted, it may not be possible to seal a. FHV exactly

2017200883 09 Feb 2017 trader any circumstances. Thus, a cylindrical cuff layer, interior or exterior to the frame, is usually employed th..' kk as a seat and pto\ 'des sonic latitude m the positioning and alignment of the PHV along tl i.o axes of slow, allowing for tc> ?>lu and ettcuue PHV wpiautanon and minimizing the risk of significant vatic 'oeam nation. Finally, the diseased native valve leaflets, 5 when pushed outward by the deployed PHV frame, .may themselves form a barrier separating the sinuses of Valsalva from the leaflets of the PHV, then disrupting the native closing geometry of the valve so that the sinuses are no longer continuous- with the pressurized space above the PHV leaflets.

Tn'v.' is-aies dm^rate some of the challenges to the formation of a PHV; that is, how to 10 confine operating leaflets within a partially sealed tubular structure while preserving ideal opening and closing valve behavior without the benefit of the natural mechanism of the sinuses of Valsalva in- a single valve and leaflet geometry, such as the separate and distinct upper and lower geometries of the native valve. As such, there is a need, .for additional devices, systems' and/or methods that address one. or -more of the problems or shortcomings noted above.

SUMMARY

It is to be understood that the present invention includes a variety of different versions or cmbo't'mmH. .nd this o mu arrant m be hnuri:n; m .·. l-inelfsHv l-.w Xu'n.uam provides .some general descriptions of some of the embodiments, bpt may also include some mom specific descriptions of other embodiments.

Two .goals of at least some embodiments of the present inventions are: (I) to maximizeeffective orifice area, and minimize opening pressure gradients through geometry that, mimics the natural form of inflow irito the valve ~~ the tubular ou tflo w tract Of the heart pumping chamber; arid (2) to minimize the inward tension, on the leaflet: co r*' s' res in the closed position through geometry that mimics the natural effect of rite sinuses of Valsalva - an effect that prevents downward displacement o f the leaflet free edges under closing pressure, thus distributing forcealong the lines of leaflet apposition rather, than tecusing it at the points of leaflet, attachment· to the frame,

The first of these goals dictates that the inflow .to the valve, similar to that of the natural aortic valve, encounters then outwardly displaces the most central portion of the leaflets, first, 30 with opening moving progressively outward along the surface of the leaflets. The second su ggests that the cross-sectional profile of the valve sinus/cusp termed in. its central portion. by the free edge of the leaflets, like that of the natural aortic valve, should be approximately elliptical, and that the eru.y>-«mon4 diameter of each cusp should progressively decrease below the plane of leaflet apposition, like that of the natural valve cusps. One or mote embodimenteof 35 the one or more present inventions answer the configuration ideals with a_; robust balance of

2017200883 09 Feb 2017 wo ιοί i-wm functional geometries for valve opening and closing.

The spl terical geometry of the native aortic valve leaflets is difficult to replicate. in a trsnscsfoefor valve. First, while thia shape is functionally robust in vivo, even if reproduced in some form it is not sailed to efficient radial comp? .w. typically required for collapse into a '«.hi η-, u <. n e ^s u , .tc nre ' i .wt. W .·. A JJo an *. -to w a ti Jnt o t tu.’.'s would develop in the leaflet surface that would, resolve, into irregalar folds with at least some ctreumferemial composure, thereby tfovarcmng the rrstlnfoon of the geometry on reopening at deployment. Second, tissue bioprosiheiic valve leaflets, if not actually constituted of the animal valve itself, are typically constructed of flat sheet tissue membrane from which rendering of .10 cusps with leaflets of a spherical contour would be difficult if not impossible without the use of taction force on the material, or extensive cutting and suturing of the leaflet cusp portion -— an impractical approach, and a threat to the material integrity of the ihin tissue membrane.

At least one embodiment of the one or more present inventions answers these challenges by employing corneal rather than spherical cusp geometry, thereby reproducing some benefits of 15 the latter with near-elliptical leaflet cross-section that progressively decreases moving proximal to t he plane of l eaflet apposition while being readily conformed on outward radial compression in the valve opening phase into a substantially flat folded construct against the interior tubular walls of the containing ffiime. This favorable resolution of the conical geometry in opening, phase expresses the openm c jciency of this valve des _ n with a large effective orifice area and' 20 low trahswalvnlar energy Ivxws In the closed positfou, the .fine edges of the separate leaflets- of the conical cusps meet in apportion, each cone acting as an independent valve;, pressure loadbearing is enhanced by the material, cOnrihuity of the cone structure with the inner appos ing wal l and outer'.wall of each cone being- pari of a single continuous membrane structure. Further, the conical cusps are particularly suited' for compression and containment within a. collapsible frame 25 for tanscatheter delivery.

In at least one embodiment,, a transcathetcrt pereutaneouSly implantable, bioprOsthetic heart valve having a lattice frame comprising 'a substantially tubular alloy metal mesh, and two. or mote valve cusps with leaflets mounted to the lattice frame, is provided. Farther, the cusps include a flat sheet of processed mammalian tissue membrane that is folded, into a sifostmfolly 30 conical shape according to a flat folding pattern, the substantially conical, shape is further formed by joining, opposing sides of the substantially' conical shape along a. seam th at is-oriented .along-a .longitudinal axis of (he substantially conical shape-. In at: least one embodiment, .the two or more cusps are attached along their seams, (which may- or may not include the apexes of the cusps), such as, by way of example and not. limitation, along rhe axial centerline of the outer 35 circumference of the cone, to an interior-portion, of the lattice fi-ame along an axial flow direction 3 wo £€1711820 ύ/084989

2017200883 09 Feb 2017 of the valve-and are further attached. along the distal, downstream, edge of the substantially conical shape along at least an outer half of the substantially conical shape’s edge. When the membrane valve leaflet is attached to the frame, its principal line of ^retirement along the axial centorline of the outer circumference of the cone is attached at a non-commissural seam or edge, 5 effecting a coaxial (to the flow axis) line of attachment at an area of the structure that advantageously bears load. thereby relieving, the commissural attachment of loads associated with the seettrement of the cusp structures to the frame. As such, the leaflet commissure attachments, thus located, at points where the leaflet membrane is continuous and uncut, advantageously need only bear the centripetal loads associated with the radially toward .10 movement and operation of the free edges of the leaflets.

to. at least one embodiment. a transcatheter, pereutaneously implantable, bioprostheticheart valve is provided wherein two distal, downstream, vertices of the flattened Cusp and leaflet structure are folded over .in a radially outward direction and .fixed to the .feme such that the vertex folds of neighboring leaflets are adjacent and define- an extent of leaflet apposition at the 15 points corresponding to leaflet commissures.

In at least one embodiment, a iranscatheter, percutaneously implantable, bioprosthetic· heart valve is provided wherein a vertex forming a proximal, upstream, apex of the substantially cortical shape is .folded over in a radially outward direction and affixed to an inner portion of the feme.

In at least one embodiment, a transcathtoer, percutaneously implantable, bioprosthetic heart valve is provided wherein the flat folding, pattern. is polygonal and. includes extending portions that, when.-the leaflet is mounted, extend cireumferehti-ally outward from: an axial line of attachment of ths leaflet to the fens so as to form, when joined and attached- to corresponding extending portions of neighboring leaflets, an integral, inner, luminal, ctre-rehferentlally partial 25 o:r complete sealing cuff to. at least one embodiment,, a trenscatheter, pereutaueouSly implantable, bioprosthetic heart valve is provided wherein a separate tubular sealing cuff of tissue membrane is attached to an outer, abhxmioto surface of the frame to form «.sealing cuff. In at least one emfedimont, the membrane sheet is a single layer of a substantially homogenous material. Tn at least one 30 embodiment, the .membrane sheet is an uhlaminated. sub <. toyer of material. In at least one embodiment, ths .membrane sheet is a single layer of material' that does not include any reinforcement, such as reinforcing fibers. In at least one embodiment, the membrane sheet is a single layer of treated pericardium tissue. In at least one embodiment, the membrane sheet is a. single layer of a synthetic film.

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Therefore, in accordance with st least one embodiment, a transcatheter, percutaneously implantable, prosthetic heart valve is provided, comprising:

a lattice frame; and two or more integrated cusp and leaflet folded structures attached to the lattice frame, the two or more integrated cusp and leaflet folded structures each comprising a .flat sheet of biocompatible membrane that is folded, to include a mobile leaflet layer and a cusp wall layer, wherein the cusp wall layer located, radially outside of the mobile leaflet layer, and wherein the cusp wall layer Is further formed by joining apposing sides of the cusp wall layer along a seam. In accordance with at least one embodiment, the two or more integrated cusp and leaflet folded structures are each attached' along their respective seams to the lattice frame, In accordance with at least one embodiment, foe seams are oriented in a direction substantially parallel to an axis of the lattice flame, in accordance with, at least one embodiment, foe flat sheet of biocompatible membrane forming H λ ad integrated cusp and leaflet folded structure .of the two-or more ”i crate»! v > p . e ic \ h'L,\ nut. , »- ω'ΊΝ.» i«.o > mw msCx »i ' Cvmtip » ib’v 15 membrane material.

In accordance with at least one embodiment, a transcatheter, percutaneously implantable, prosthetic heart valve is provided, comprising:

a lattice frame; and two or more integrated cusp and leaflet folded structures attached to the lattice bam®, the two or more integrated cusp and leaflet folded structures each comprising a Hat sheet of a biocompatible membrane, that is folded to include a valve- cusp according to a flat folding pattern,, .wherein the valve' cusp is fiirther formed by joining apposing sides of. the valve-cusp along a seam, and wherein the two'er more integrated cusp and leaflet folded structures' are each attached along their respective scams to the lattice'frame in .a. direction substantially parallel to .25 an axis of the lattice frame;. In aepordahee with at least one embodiment, two distal, downstream^ vertices of the. integrated cusp and leaflet folded, structure are. folded over-as vertex, folds in a radially outward direction and fixed to the lattice frame such that ths vertex folds of cireumfbrsntially adjacent leaflets are adjacent -and define a degree of leaflet apposition at the points cotrespoading to leaflet commissures. In aceotdaace with at least oae embodiment, the two distal, downstream* vertices, are fixed to foe lattice frame by 'attachment not along an alignment with the vertex folds. In accordance with at least one embodiment, a vertex, forming a proximal, up&teun, tip of the substantially conical shape is folded over in a radially outward, direction and attached to -an inner portion of the lattice frames In accordance with at least, one embodiment, foe flat folding pattern is polygonal and includes-extending portions font, when the cusp is mounted, extend circumferentially outward from an., axial line of attachment of the cusp

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2017200883 09 Feb 2017 to the frame .so as to form. when, joined and attached to corresponding. extending- portions of neighboring cusps, an integral, inner, luminal, drcwiifemntialiy complete sealing cuff. In accordance with at least one embodiment, the flat folding pattern is polygonal and includes extending portions that, when the two or more cusps are mourned, extend circumferentially 5 outward from an axial line of attachment of the cusp io the lattice frame so as to form, a circum.teretttia.Ily incomplete sealing cuff portion associated with css'' s. 'p. In accordance with at least one. embodiment, a separate tubular sealing cuff of biocompatible -membrane is attached to an outer, abluminal surface of the lattice frame to form a sealing cuff In accordance with at least one embodiment, the lattice frame is collapsible and expandable and comprises a metal .10 alloy substantially configured as tubular stent member. In accordance with at least one embodiment, the biocompatible membrane comprises processed-mammalian -pericardium tissue. In accordance with at least one embodiment, the bioeompatible membrane does not comprise a treated tissue. In accordance with at least one embodiment, the biocompatible membrane ‘Auto.-t e s.u lu .usotdaoc.· oith m -, is: < no smh<·ώηι?m, the sc.m,s iffhs two or more integrated cusp and leaflet folded stnsetures are each oriented along an axis of flow of the valve. In. accordance with at least one embodiment, the two or more integrated cusp and leaflet folded structures are each further attached-to a circumferential portion of the lattice frame along at least a portion, of their distal downstream, edges. In. accordance with at least one embodiment, the two or more integrated cusp and. leaflet, folded stractares are attached to the '20 lattice frame at least at a uoa-eommissural seam aligned -with an axial flow direction of the valve.

In accordance with at least one embodiment, s transeatheter, perctoancously implantable, prosthetic heart valve is provided, comprising:

a lattice frame; and .25 two or more integrated Cusp and leaflet structures attached to the lattice frarne, the two or .more integrated cusp and leaflet struetums each comprising a flat sheet of biocomparible membrane that is folded to-.include a mobile leaflet layer and a.Cusp wall layer, wherein with the mobile leaflet layer in a closed position a transverse cross-sectional area of a cusp-sinus space decreases monotonic-ally from a distal end to a pmximal end of the mobile leaflet, layer. In?

accordance.-with at feast one embodiment, the cusp wall layer is. located radially outside of the mobile- leaflet layer. In accordance with at least one embodiment, the easp wall layer is further .formed by joining apposing sides of the cusp wall layer along a. seam. In accordance with at least one embodiment, the inob-l·.' leaflet layer in. the dosed position a transverse cross-sectional, length of the mobile leaflet layer decreases monotonically from. a distal, end to a. proxima l end of the mobile leaflet layer. In accordance with at least one embodimen t, the mobile leaflet layer and

2017200883 09 Feb 2017 the cusp w't’l layer ofcseh integrated cusp and leaflet structure arc a single continuous piece of btocompai. ^e mcrabratK*.

At ku\; one wenbcm of the one or mote prewn; inxenhoits A si novel integrated cusp and leaflet structure that has application far a variety uses, including implantable valves other 5 than, prosthetic heart valves. Accordingly, in at: least one embodiment, and in subcombination,.

an integrated cusp and leaflet structure for attachment ta a lattice frame to form a valve confu nred for implantation in a vascular system of a patient is provided, the integrated cusp and f'uflc’ structure comprising:

a flat sheet of biocompatible membrane that is folded to include a mobile leaflet, layer 10 and a cusp wall layer, wherein the cusp wall layer is divided along a seam, and wherein the mobile leaflet layer is continuous and apposes the cusp wall layer when the integrated cusp and leaflet structure is pressed substantially flat. In accordance with at least one embodiment, the mobile leaflet layer and the cusp wall layer of the integrated, cusp and leaflet structure are a single continuous piece of biocompatible membrane. In. accordance with at least one .15 embodiment, the biocompatible membrane comprises a synthetic material. In accordance with at least one embodiment, the integrated cusp, and leaflet ..structure further comprises- at least one commissure tab. In. accordance with at: least one embodiment, the at least one. commissure tab is Configured for engaging a slot within, a member of the lattice frame.

One or more embodiments of the- one or more present inventions am also directed to 20 methods for forming the w_vn i.ve valves described herein, as well as Its component- elements.

Accordingly, a method ol f„< tning an integrated cusp and. leaflet folded structure for use in an implantable valve having-an axial flow direction is provided, comprising: folding a flat sheet of biocorapatible membrane to form an integrated cusp and leaflet folded structure according .to a. flat folding pattern, wherein said folding -includes making two diagonal folds in the flat sheet of 25 blocompatibie membrane,-the two diagonal folds separating a mobile leaflet layer from a cusp wall layer -of the integrated cusp and leaflet folded structure. In. accordance with, at least one embodiment,.the two diagonal folds are angled at between about 10 to 80 degress flora, the axial flow direction. In accordance with at least one embodiment, the method further comprises forming first and second cusp wall folds, wherein, the .cusp, wall layer is further formed by 30 joining apposing membrane portions adjacent the first and. second cusp wall, folds along a seam that is oriented substantially parallel with, the axial flow direction.

In addition to the foregoing, in accordance with at least one embodiment, a method of formrag a transcal heter,. percutaneo.nsly intplateable, prosthetic heart valve is provided, comprising: folding a plurality of integrated cusp and. leaflet .folded structures, each integrated cusp and leaflet folded structure of the plurality of integrated cusp and leaflet folded structures

304941211

511980AUPR

2017200883 14 Feb 2019 comprising a flat sheet of biocompatible membrane that is folded to form a cusp according to a flat folding pattern, wherein the cusp is further formed by joining apposing sides of the cusp along a seam; and attaching each integrated cusp and leaflet folded structure of the plurality of integrated cusp and leaflet folded structures to a lattice frame, wherein the two or more 5 integrated cusp and leaflet folded structures are each attached along their respective seams to the lattice frame in a direction substantially parallel to an axis of the lattice frame.

In one particular embodiment, the invention provides a transcatheter, implantable, prosthetic heart valve, comprising:

a lattice frame; and two or more integrated cusp and leaflet folded structures attached to the lattice frame, the two or more integrated cusp and leaflet folded structures each comprising a flat sheet of biocompatible membrane that has been folded to include a mobile leaflet section and a cusp wall section, wherein non-transverse diagonally oriented folds that are angled relative to an axial flow direction are located between the mobile leaflet section and the cusp wall section, wherein the cusp wall section is located radially outside of the mobile leaflet section, and wherein the cusp wall section includes a seam that joins apposing sides of the cusp wall section.

In a further particular embodiment the invention provides a method of forming an integrated cusp and leaflet folded structure for use in an implantable valve having an axial flow direction, comprising:

Ό folding a flat sheet of biocompatible membrane to form an integrated cusp and leaflet folded structure according to a flat folding pattern, wherein said folding includes making two diagonal folds in the flat sheet of biocompatible membrane, the two diagonal folds separating a mobile leaflet section from a cusp wall section of the integrated cusp and leaflet folded structure.

Various components are referred to herein as “operably associated.” As used herein, “operably associated” refers to components that are linked together in operable fashion, and encompasses embodiments in which components are linked directly, as well as embodiments in which additional components are placed between the two linked components.

As used herein, “at least one,” “one or more,” and “and/or” are open-ended expressions 30 that are both conjunctive and disjunctive in operation. For example, each of the expressions “at least one of A, B and C,” “at least one of A, B, or C,” “one or more of A, B, and C,” “one or more of A, B, or C” and “A, B, and/or C” means A alone, B alone, C alone, A and B together, A and C together, B and C together, or A, B and C together.

TIS511980AUPR

304270712

2017200883 21 Feb 2017

Various embodiments of the present inventions are set forth in the attached figures and in the Detailed Description as provided herein and as embodied by the claims. It should be understood, however, that this Summary does not contain all of the aspects and embodiments of 5 the one or more present inventions, is not meant to be limiting or restrictive in any manner, and that the invention(s) as disclosed herein is/are understood by those of ordinary skill in the art to encompass obvious improvements and modifications thereto.

Additional advantages of the present invention will become readily apparent from the following discussion, particularly when taken together with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

To further clarify the above and other advantages and features of the one or more present inventions, a more particular description of the one or more present inventions is rendered by reference to specific embodiments thereof which are illustrated in the appended drawings. It should be appreciated that these drawings depict only typical embodiments of the one or more 5 present inventions and are therefore not to be considered limiting of its scope. The one or more present inventions are described and explained with additional specificity and detail through the use of the accompanying drawings in which:

Fig. 1A is a plan view of a flat sheet membrane template for the formation of an integrated cusp and leaflet folded structure in accordance with at least one embodiment of the Ό one or more present inventions;

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2017200883 09 Feb 2017

Fig, IB is an oblique .-axial top. (distal) perspC'-tive νΰ~ν directed downward (proximal) and radially -outward of a -folded membrane sheet xflet cxceuhmt of the template 'foldings illustrated in Fig. I A, thereby yielding a completed imrgt.ded cusp >md leaflet folded structure;·

Fig. ] C is a side perspective view directed .radially outward of the inner aspect of an 5 initially folded version of the integrated cusp and leaflet template shown in .Fig. .1 A;

Fig. ID is an oblique axial top (distal) perspective view directed, downward (proximal) and. radially outward of a further partially folded version of the. integrated cusp and leaflet folded structure shown, in. Fig. IC;

Fig, IE is an another oblique axial top tdtstah perspective view directed downward 10 (proximal) and radially outward of a further partkdh folded version of the integrated cusp and leaflet folded structure shown in Fig. ID;

Fig. IF is a modified, version of the integrated cusp and leaflet folded structure shown in. Fig. IE;

Fig. IG is same structure and viewshown in. Fig. I E, along with a top (distal) cross15 w non > he tni a ' nm ol m >lw / mo o' a me m.A· \a xe a ckwe<’ ov?t pout mi.

Fig, 2 is a plan view of another flat sheet membrane template for the formation, of au integrated cusp and leaflet folded structure in accordance with at least one embodiment of the one or more prese.n inventfons;

Fig. 3 is a plan view of yet another flat sheet membrane template for the formation of an. '20 integrated cusp and leaflet folded structure tn accordan.ee with at least one embodiment of the mm or mow present bn cm tons;

Fig. 4 is a plan view of still yet another flat sheet membrane template for the formation of an integrated cusp and leaflet folded structure i.n accordance with, at least one embodiment of the one or more present inventions;

.25 Fig, 5A Is a plan, view of another flat sheet membrane template for the formation, of an integrated cusp and leaflet folded- structure in. .accordance with. at. least one. embodiment of foe one or more present inventions;

Fig. SB is an oblique axial top- (distal) perspective view directed, downward (proximal) and radially outward of a partially folded version of an. integrated: cusp and leaflet folded 30 structure prepared in. accordance with, .foe template shown in Fig. 5A;

Fig. 5C is an oblique axial top (distal) perspective view directed downward (proximal) and radially outward of a .forther partially folded version of the integrated cusp and leaflet folded structure shown in Fig. 513:

Fig, 5D is plan view of the inner (luminal) aspect of a completely folded version of foe structure of Fig. 5C, thereby yielding a completed integrated cusp and leaflet folded structure

2017200883 09 Feb 2017 prepaid in accm-dance with the template shown in Fig. 5.A (with, the exception of unfolded comnus'-.uc ubs\

Fig; 5F μβ·'λ5 a detail perspective view of a folded, commissure tab;

Fig. 5F shows a perspective view of the outer (abluminal) aspect of the device shown in 5 Fig. 513:.

Fig. 6 is a plan view: of yet another flat sheet membrane template for the formation of an. integrated cusp and leaflet folded structure in accordance with at least one embodiment of the .one or more present inventions;

Fig. 7 A is a plan view of still yet another .flat sheet membrane template for the formation 10 of an integrated cusp and ieaflet folded structure in. accordance with, at least one embodiment of the one or more present inventions;

Fig. 7B is an oblique axial too idistal) perspective view directed downward (proximal) and radially outward of a partially folded version of an mte^ated cusp and leaflet folded, structure prepared in accordance with the template stew» in Fig. 7 A;

Fig. 7C is an oblique axial top (distal) perspective view directed, downward, (proximal) and radially outward of a farther partially folded version of the integrated cusp and leaflet folded structure shown in Fig. 7B;

fog fo χ an .fofom ixi.d ίορ <,<bs\d) m ' χ. ra dmx fed ;<ra rac'd (p o< ce d) and radially outward of yet a further partially folded version of'the integrated cusp and leaflet 20 folded structure shoun in Fig. 7C;

Fig. 70 sbi’us » shallow oblique top perspective view of the-outer (abluminal) -aspect-of the partially folded uwp and leaflet structure of Fig. 7D:

Fig. 7F is. a plan view of'the inner' (luminal) aspect of a completely folded version of the' structure 'Of Fig. 713 yielding an integrated cusp and leaflet folded structure; prepared m 25 accordance with the template shown in Fig. 7A. (excepting that- the -'commissure tabs and apex are not yet folded, outward);

Fig. 7G is a side perspective view of the outer (sblunfotel) aspect -of the structure of Fig. 7F showing a completely folded vpmion of an. integrated, cusp and leaflet folded structure prepared, m accordance with. the template shown in Fig. 7A (excepting that the commissure tabs 30 and.apex am not yet folded eastward);

Fig. ? H i s a plan view of the inner -(luminal) aspect of a completely folded version of an .integrated cusp and leaflet.-folded structure prepared in accordance with the template shown in Fig. ?A;

2017200883 09 Feb 2017

Fig, 71 is a plan view of the outer (abiummal) aspect of a completely folded version of an integrated cusp and leaflet folded structure prepared in. accordance sth the template shown .in fog. 7A,

Fig, 7 J is an oblique top (distal.) perspective view of a completely folded version of an integrated cusp and leaflet folded structure prepared in accordance with the template Shown to. Fig. 7A;

Fig. 7K, is a top perspective, view directed downward:(proximal) into the cusp space of an integrated cusp and leaflet folded structure prepared in. accordance with the template shown in Fig. 7 A:

.10 Fig. FA is an oblique top t'distai) perspective view of an embodiment. of a lattice frame for mounting three of th-: smgh--mccv folded integrated cusp and leaflet structures as described herein:

Fig. FB is a side elevation view of the lattice frame shown in Fig. FA;

Fig. 8C is a. side elevation view of the lattice frame of Fig, F A with, a superimposed plan .15 view of the radially outer aspect of the completely folded -integrated, cusp and leaflet structure of Fig. Th

Fig. SD is an oblique axial (top/distal) perspective view'of'an assembled three-leaflet valve in accordance with at .least one embodiment;.

Figs. 9A and 9B are two different' oblique axial (top/distal.) perspective views of another 20 embodiment <»f a I ύ an; t<r mmsri nu th ee of the single-piece folded integrated cusp and leaflet streettne* that m-'ludc <w»nwi\' vw

Fig. 9U >s ... vev ρ<»<ριχ·η>' mow ot me lattice, frame shown in. Figs, 9A and 9B with a superimposed plan, view of the outer aspect .of the .completely folded integrated cusp and leaflet structure of Fig. 71;

.25 Fig, 9D is a side view of the: lattice frame shown in. Figs, 9 A and 9B with superimposed, views of the. outer aspect of two circumferentially adjacent completely folded integrated cusp and leaflet smatures; and.

Fig. 9E is an oblique axial (top/distal) perspective view of an assembled, three-teaflet valve comprising· the. lattice frame shown in Figs, 9A and 9B and three identical folded 30 integrated cusp and leaflet stmehaes.

The drawings are- not necessarily to scale,

DETAILED DESCRIPTION

One or more embodiments of the one or more inventions described herein include an implantable prosthetic heart valve having a frame and two or more susp and leaflet structures mounted to the frame. The frame preferably comprises ό lattice of substantially tubular alloy

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2017200883 09 Feb 2017 metal mesh. The cusp and leaflet structures include a membrane operable to open and close, thereby providing a functioning valve when mounted within. a frame. In at least one embodiment, the membrane preferably comprises a flat sheet of processed mammalian tissue membrane that is folded into a substantially conical..shape according to a flat folding- pattern.

In die ensuing descriptions and referenced figures it will be seen that, when applied to a dry sheet membrane, the folding initially results in a cusp shape of an inverted pyramid, with a rhomboid base. On relaxation of the folds as occurs naturally with a flexible and pliable membrane, especially when, the membrane is hydrated, the cusp -shape becomes substantially conical in. shape and will be described as such in the ensuing descriptions as it more closely .10 represents the embodiment o f the -cusp in operation of the valve.

Formation, of a valve'construct as described herein provides a. pereutaneously deliverable heart valve with a relatively small, diameter for transcatheter placement. That is, the substantially conical shape associated with the flat .folding, patterns used to form leaflets as described herein allow for construction of a valve that can be compressed prior to introduction to 15 a catheter to an advantageously small diameter, thereby facilitating transcsthctcr percutaneous delivery of the valve within a patient. The substantially conical shape is further formed by joining two axially oriented, sides of the substantially conical shape along a. seam that is oriented along a longitudinal axis of the substantially conical -shape. The two or more integrated cusp, and leaflet structures are affixed to an. interior portion of the lattice frame along an axial flow 20 direction of the valve and are further affixed' along the distal, downstream, edge of the substantially conical shape along at least'ah outer half of the substantially conical shape's edge.

One or more of the various embodiments described herein have -a number of different features and characteristics as compared to other commercially available prosthetic heart valves. For example, at least one embodiment of a transeatheter, pereuhmsously implantable, prosthetic .25 heart valve described below comprises a flat polygonal sheet membrane having more than four sides and which forms an integrated cusp and leaflet streeture.

In addition, at least one embodiment of a transcatheter, percutaneously Implantable, prosthetic heart valve described, below comprises integrated cusp and. leaflet structures that are attached, to a lattice frame at the circumferential penmeter locations corresponding to the 30 commissures. Al snch locations, the length of the seam that forms the common, line, of attachment of the cusp and in tegral leaflet to the frame is less than one-half to two-thirds of the axial length of the membrane portion o f the valve.

In. at least one embodiment of a transcatheter, percutaneously implantable, prosthetic .heart valve, when the valve is in the -open position, the mobile leaflet layer apposes or is geometrically tree to appose its full outward surface completely to the immediately radially

1.2

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2017200883 09 Feb 2017 located outward structure, such as at least one of the cusp-wall layer or interior -surface of the lattice frame. In at least one embodiment, in the closed position the transverse eross-sceiional length of the mobile leaflet layer and the cross-sectional area of the cu<« -anus space decreases monotonically from the distal end to proximal end of the membrane portion of the valve. (That is, generally the property of a cone as well, as an inverted pyramid,)

In at least one embodiment, the mobile leaflet layer and the immediately outward structure tor the full axial length of the leaflet (cusp -wall layer, frame, or other) are a single continuous piece of material.

In at least one embodiment, at the base of each cusp (that is, at the. most, proximal extern 10 of the leaflet), the circumferential extent of attachment of the membrane- to the frame is less than the circumferential extent of attachment of the membrane to the frame at the hsxd end of the cusp. In-addition,-at the base of each .cusp, the circumferential. extent of fransvas? «mat is, on a line or -on the plane of a cimumfere-ci d single-plane curve of .folding that, is generally perpendicular to the flow axis of the vahc> elding of the membrane to the frame is less than the .15 circumferential extent of transverse folding at the distal end of the cusp.

At .least one embodiment, a prosthetic valve described herein comprises an integrated cusp and leaflet structure wherein the apposing sides of the cusp are joined at one or more xs ' w.xl χ xs nx In < t c.,i >.> x' as flxx -' m dl io χ . <1 xem χ <,. Io, mJ o' him segments.

At least one embodiment of the one or more present invent ions does not include framex x ' x Hx x uh < x x ppf> Ϊ x iX'gU' 'gib. \Ot0’lli'x x X > > xup^'ii i'H ' >'!

more portions of the membrane sheet. Moreover, at least one embodiment of the one or more present inventions does net include any hardware shaping ferm. inward, of or attached to any •portion of the mobile leaflet portion of the membrane...

.25 In addition, at. least one embodiment of the. one or more present inventions does not utilize attachment of the- leaflet layer to the frame along the substantially complete circumferential distance separating the commissures at any point below (more proximal than) the commissure tabs.

At least one embodiment of the one or more present inventions does not include a 30 transverse ibid or reflection of the leaflet layer along the substantially complete circumferential distance separating the commissures at any point below (mom proximal than) the commissure tabs.

Wissndmis

For all embodiments presented herein it is to be understood feat a Anem.bnme” includes suitable materials for forming the cusps and leaflets. Accordingly, with regard to particular

2017200883 09 Feb 2017 material types that may be used to form foe membrane -sheet, in at least one embodiment the tn.nd η!·.-. shra. foirscre the tus? m Ltox. 'v: jo' .'λ> iL'\ u ece-puYC. x.'.gL' Lixci sheet o: but o itoe c I'm e s Ji <s v< rauonuL κ l.J n isue m ' ra biocompatible material, such as ePTFB. In at least one embodiment, the membrane sheet is made from a tissue preparation process that yields a leaflet material of suitable strength and durability for' use to a prosthetic traascafoeter deliverable heart valve. The content of WO 2011/109450A2 published on September 9,2011, is incorporated herein by reference. Although the .membrane sheet is preferably a single piece of material, a membrane sheet formed of a plurality of pieces of material may be -used,, such as two to- fifty or mote pieces of material that 10 are connected.

As used herein “proximal” means situated near or closer to foe upstream or flow inlet end of the valve, and “distal'’ means situated near or closer to the downstream or flow outlet end of the valve. This convention is further applied to. the description of the various folded structure elements (membrane sections, edge segments and fold, linos) that are termed “proximal” or 15 “distal” if the final, position or orientation of said element within the completed folded, structure satisfies the above definitions. Likewise, one.of said elements is termed, “axial”, “transverse” or “circumferential” to describe its position and orientation in the completed valve.

As used' .hemin, a “cusp” means that structural portion of a valve related, to a single leaflet that encompasses a space closed, toward the tower (proximal) direction and open to the 20 upper (distal) direction, formed by the joined and/or continuous structure's of foe. mobile leaflet portion on the radially inner side and the cusp wall, poruon on the radially outer side. The “cusp” in. the present invention is that Structure described as having, a substonua.Il.y conical shape.

As used herein, the mobile La,let i.ne”” or “leaflet” means that radially inward portion of foe cusp that mows during operation of the .valve,. For example, '-when the valve is closing the .25 mobile leaflet layer mo ves radially inward toward foe central' axis of the valve lumen. When the valve is opening, the mobile leaflet layer moves radially outward and way from the Central axis of the valve lumen.

As. used herein, the “cusp -wall layer” means a portion, of the cusp that resides radiallyoutward of the mobile leaflet layer. .In. some embodiments, a portion of the cusp wall layer 30 moves during operation -of the valve. In. other embodiments, the cusp- wall layer remains substantially -immobile during operation of the valve.

As used herein, lira. “cuff wall layer” means' a portion of foe, folded membrane -structure ran ra-lndb outxs nJ ->f ίχ·Α ;l·,' u^p JI : r.er .mJ mobs? ffJL- l«>;r and uber' present ix radially dnwst to the frame of the three layers comprising the mobile leaflet layer, the cusp wall layer, and the cuff wall layer. The cuff wail layer remains substantially immobile

2017200883 09 Feb 2017 during operation ol me valve.

A “frame” as used herein means a substantially tubular member tbit holds a plurality of cos is red Ci k':ukis Bx '1 <. <a\'\.imr>k-, -he fr,;o··.· mas lx a a -re iaif-cc Oi a \Hiι-re cut fc,‘to a single tubular piece of metal alley, that is both collapsible ami expandable

A Naive” as used herein means a frame with a pl urality of cusps and/or leaflets attached thereto. In the present invention each of said leaflets is an integral part of a folded membrane cusp structure, If a frame is used that is a metal lattice that is both collapsible and expandable, such a construct may be delivered through a catheter percutaneously to a target site within a patient, such as the aortic valve.

.10 As used herein, “cone” or “conical” means resembling a cone or -portion thereof st.some point in the practical use of the structure.

As used herein “substantially-conical” means resembling a cone or a -portion thereof at some point in foe practical use of foe structure with the specific property that the transverse (that is, on a plane'of section generally perpendicular to the axis of flow of the valve) cross-sectional 15 perimeter or area of said .structure in the operationally closed position decreases monotonicallymoving from the level of the leaflet apposition, to the proximal end of the valve.

As used herein, “two or mom leaflets,” “two or mom valve leaflets,” “a plurality of leaflets” or a similar term means: two, three, four, or mom valve leaflets. Accordingly, “a valve with two or mom leaflets” mcludes-a valve with two leaflets, a valve with three leaflets, a valve 20 with .four leaflets, and a valve with more than four leaflets.

As used hemin, a “folding” means the partition of a flat sheet section of material along a sharp line of folding or crease into subsections each lying on separate planes, but without interrup tion of material, continuity;

As used herein, a “complete folding'⁵ means folding (as above) wherein the: angular change of the planar axis at the line of folding is approximately IW degrees, such that the subsections lie w approximately parallel planes' and the subsections: are in. -approximate overlying-contact with each other at least at some point.

As used herein, a “cull?’ means that portion of-a valve structure that lies radially outward of the c usp wall portion that in some part circumferentially encompasses at least a portion of the 30 cusp structure and.sets to limit flow that may pass retrograde .around the cusp.

As used harem, ’'commissure⁵' means the site of union or junction between, adjacent cusps -and/or .leaflets, and by extension, collectively those -portions of the adjacent integrated cusp and leaflet structures that are coincident-at the union, or junction in the completed valve SirtiCk-re.

TIS511980AUPR

304270712

2017200883 21 Feb 2017

As used herein, an “integrated cusp and leaflet folded structure” means a membrane folded in accordance with one of the patterns described herein.

Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise”, “comprising”, and the like, are to be construed in an inclusive sense as 5 opposed to an exclusive or exhaustive sense, that is to say, in the sense of “including, but not limited to”.

Folded Valve Integrated Cusp and Leaflet - Folding Pattern No. 1

Referring generally to Figs. 1A-7K, each cusp embodiment of an integrated cusp and leaflet structure described herein is a substantially flattened cone collapsed along an axis 0 substantially perpendicular to its longitudinal axis. In one or more embodiments, the integrated cusp and leaflet structure, when being formed from a piece of membrane, is readily realized by folding a flat sheet of membrane from a closed polygon pattern. The pattern folding results in apposing seam lines aligned along their axial length. These are joined to close the cusp in the general shape of a cone with the joined seam forming the “spine” along which the cusp meets 5 the inner aspect of the tubular frame. It can be seen that, when formed of a dry sheet membrane, the pattern results initially in a cusp shape that is an inverted pyramid with a rhomboid base that, with a flexible, pliable membrane, is congruent to a substantially conical shape. On relaxation of the folds in practical use a substantially conical cusp is realized wherein the inner mobile operating portions of the leaflet are continuous with the outer portion that forms the integral wall Ό of the cusp sinus or pocket.

Referring now to Fig. 1A, a plan view of a rectangular flat sheet membrane template 100 is shown for the formation of a single-piece folded valve integrated cusp and leaflet. The plan view is shown with a view of that leaflet surface that faces radially inward once folded and mounted within a frame. Reference is also made to Fig. 1G, wherein a schematic of a valve in 25 distal axial view is shown, and wherein three cusps with integral leaflets are shown within the frame that collectively form the valve. As described and illustrated in the present application, alternate polygons and other closed shapes may be employed with alternate folding patterns to generate alternate shapes and functional features of the valve cusp and leaflet, and complete valve.

Referring again to Fig. 1A, and in accordance with at least one embodiment of the one or more present inventions, dotted lines 101, 116, 117, 126 and 127 represent the position of folds or creases applied to a piece of membrane to form a leaflet structure 130. More particularly, folding at lines 116, 126 and 101 is initiated inward (with convexity of the surface disposed radially inward toward the central axis of the valve lumen) while folds 117 and 127 are folded

TIS511980AUPR

304270712 initially outward (with convexity of surface disposed radially outward away from the central axis of the valve lumen). Since folding causes re-orientation of the various sections of the sheet template in relation to each other and to the valve geometry, final orientation of the fold lines within the structure on mounting and operation of the leaflets will not necessarily retain the same orientations as on initiation of the folds. The “inward” and “outward” conventions by this

2017200883 21 Feb 2017

16A

WO 301W29S3

2017200883 09 Feb 2017 definition will be followed throughout the descriptions of the various folded geometries presented herein.

Referring again to F?g 1A, a line of division by cutting is indicated at 102. Cutting at 102 results in opposing e<.te,ra 115 and 125 that will be separated by folding. The other free xL<> '* >< s'k>< . . ' < ,xle> s. ' iwto me cnent u on ax yes ,x the h>e '>

steps. Fold 101 defines the central axis of symmetry of the leaflet pattern, with die concave side of fold 101 facing radially -outward toward the frame and away from the central, axis of the valve lumen. Fold 101 assists In the:. maintenance of axial symmetry of the folded construct,, but is not nec-essaiy to leaflet function and is not retained in the final operational form of the valve. (See

Fig. 7A.)

Referring now to Fig, IB, an oblique axial fop (distal) perspective view of a substantially completed folded leaflet slructure 130 is shown. (Three completed folded cusp and leaflet structures 130 are typically mounted to a frame to form an operating heart, valve.)

The view of Fig. IB is directed, downward (proximally) and radially outward, with such view illustrating a substantially completed folded leaflet and cusp structure 1.3 ft that depicts-the reoriented segments and sections of Fig. 1A after execution of the template foldings. Segments

11.1 and 121 form, the left: and right halves of foe distal .free edge of the mobile operating portionof the leaflet. .Inward foldrag at 116 and 126 forms a second layer of membrane outward, of the first, with segments 112 and. .122 .forming the- distal free margin of the outer wall of the intern hod In radially flatted form of the -integrated cusp and' leaflet structure-(that lx, appu«\»m n'g the open -operating position of the leaflet), the segment III will appose tn 112, and 121 wih apprise to 122,

The left cusp wall section. 161 'is bounded by folds '116 and 117 and edge segment 11'2. The right cusp wall section 171 is bouhded by folds 126 and 127 and edge segment 122.

The left cuff wall section 118 is bounded by fold. '1.17 .and 'edge segments 113, 114 and.

115. The righi_: cuff wall section 128 is bounded by fold. 1.2? -and edge segments 123, 124 and 125. Inward folding at LI? and 127 cause these cuff wall sections 118 and 128 to position, outward of the cusp wall sections 161 and '171, respectively. In radially flatted form of the completed folded structure (again, approximating the open operating position of the leaflet), the edge .segment 113 will appose to 112, and etL e s' e stent 123 will appose to 122, FoIded.,y^aiye.,Fold.ingSggy.rafog.

Referring now to Figs. IC and l'D« oblique axial top (distal) perspective views: of a parts ally completed folded leaflet, and cusp are shown. The views provided by Figs, IC and LD am directed downward (pmx-imally) and radially, outward, with, such views depicting the 35 reoriented segments and sections of Fig. IA after partial execution of the template, fold ings.

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P€I7liS20117964989

2017200883 09 Feb 2017

Fig, 1C shows a perspective view of the inner aspect of the template 100 after initrf'cn of the foldings and cutting at 102 resulting in left and right cuff wall sections .118 a»d 2\ res;\-etueti I'u cat hoc ecg. s 115 and l.M at. scp.s.ated -done wnh ti-e ku sad oglu <. 1 wall sections .1 18 and 128 by outward folding at 11? and 127, respectively. Completed folding at

117 and 127 results in the cuff wall sections .1 IS and 128, respectively. Distally situated (with, respect to the blood flow direction) edge segments 113 and 123 of the cuff wal l sections 118 and 128, as well as proximally situated edge segments 115 and 125 of the cuff wall sections 118 and 128, are positioned transverse, and hr at least one embodiment, substantially perpendicular, to the central axis of the valve,

Fig, ID shows the cusp and leaflet structure 120 with the .folds 116, 126, .117 and .127 at an intermediate stage of completion. Triangular left and right mobile leaflet sections 119 and

129 respectively are bounded, by .folds 101. and 116 and free edge segment 111. on the left, and. folds 101 and .126 and fee edge segment 121 on the right. Folds .1.17 and 12? are then brought into apposition on the outward aspect of the integrated cusp and leaflet along a scam line 132 where the folds will be joined and attached to a frame to close the shape of the single-piece continuous conical integrated cusp, and leaflet.

Referring now to Figs, 1.E and IF, oblique axial top (distal) perspective views of a substantially completed folded cusp and leaflet are shown. The views provided by Figs, IE and. IF are directed downward (proximally) and radially outward, with such views depicting the 20 reoriented segmeuw and rceiious of Fig, IA after execution of the template foldings.

Fig : I the ι\Λ'> and leaflet folding substantially completed. forming the structure

130 with th? .on Ml h-rmed by the apposition of folds 117 and 127, thus forming a generally conical cusp and sinus space 1.31. The triangular corners formed at the distal ends of folds 11.6 and 126 am apposed to and attached to the caff wall sections 118 and. 128, respectively, .25 Between, adjacent cusp and leaflet structures in a multi-leaflet valve, the folded 'comers form the junction joining the adjacent free edges(121 of leaflet A to .111 of leafl et B, for example) of the mobile leaflet portions. When further attached to the circumferential valve frame, these corners tether the free edges of the mobile leaflet portions to the efreu referential inner boundary of the generally cylindrical valve frame, thus forming val ve leaflet commissures at each similar join.

Referring now to Fig. IF, a structur·' \ m-iar to that of Fig, IE is depicted, but with the cuff wall sections 11813 and 128.B reduced in circumferential extent from that of leaflet structure

130 shown in Fig. I E. More particularly, depending on the clinical application of the. valve, a fully circumferential, cuff nail may be un· rtAv’W;. and a valve with a limited cuff wall with, less tissue membrane mass may offer functional advantages.. Alternatively, an additional piece

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2017200883 09 Feb 2017 of membrane may be placed circumferentially around the rnttc? ablumioal. surface of the- valve flame to act as a sealing caff io form a barrier against valvular regurgitation.

Fc iiiiq <... to * m If > < * ' -'' /ίο > v qO ol i > ww <. v v< c J\' forms-the lower (proximal) end of the sera. 132. In at least one embodiment, the apex I >3 w 5 also attached to the circumferential boundary of the valve and valve flame.

Referring now to Fig. 1G, fo- c^'-e of reference the structure of Fig. IE is again, shown in Fig. IG-af t he top of the page, along vuth a top (distal) cross-section view of the distal end of a three-leaflet valve in the closed operating position. The three cusps with leaflets are shown residing within a. lattice frame in order to indicate the -configuration of elements between the .10 (hided integrated cusp and leaflet structure .130 and its disposition within a three-leaflet framemounted valve. Suture attachments are omitted for clarity.

For each folded integrated cusp and leaflet structure, ths outer axial seam .132 is aligned with one or more frame members 141 in. a manner to .pennit the attachment of the .folds .117 to 127, and to the coincident frame member by rhe same attachment, for example, by a single knot 15 or line of suture. Advantageously for this purpose, the .flame may preferentially contain axially oriented members that-align to the seam 132 for part or all of the full axial extent of the valve. Further, said axially oriented members may advantageously contain holes or notches for securing and tying suture, hi Fig. 1G at point A, an illustrated loop symbolizing a suture knot is shown to 20 demonstrate that a single knot may advantageously pass through or engage the frame member and the- six layers; that is, the mobile leaflet section, the cusp wall section, and. the cuff wall section, of each adjoining- cusp, and leaflet structure that are Com, ·<1,·:η :n this sue of the commissure.

Referring still io Fig. 1G, it can be seen that the folded Integrated cusp and leaflet 25 structure, When mounted within, the lattice frame- and placed in the -closed operating position, manifests the following configurations: (.1) the left leaflet free edge segment 1.1.1 is in each case apposed to the right leaflet free edge segment 12,1 of the adjacent leaflet; (2) the portions of the leaflets just proximal to the free edges, thus, are also apposed to form the contact seal that enables effective closing operation, thereby preventing valvular regurgitation; and (3) the distal 30 edges 112 and. 122 of the cusp wall sections are apposed to the distal edges of the cuff-wall sections 1:13 and 123, respectively.

Referring now to Fig,.2, and in. accordance with at least one- embodiment, a plan view of a flat-sheet nrem.brase template 200 that is polygonal rather than rectangular is shown. Template 35 200 contains folds 201, 2.16, 226, 21.7 and 227 that correspond to folds 101, 1.16, 126, .1.17 and

2017200883 09 Feb 2017 £€17682007084989

127. rcsp^.u-se g. and are disposed in like manner in folding execution, as are the segments enumerated The folding pattern is designed to form a longer cone of the same diameter, which achieves a more vliMallv disposed central point ot rabe leaflet coaptation, the mechanics of which are more tolerant of nrexsute loads. The pattern dimensions may be altered to suit the particular clinical application of the valve. The template examples disclosed, herein are for enablement purposes and shall, not be interpreted as limiting the scope of the claims. The example is shown for a cusp cone wail disposed at about a 60 degree angle to the horizontal (short a\>s! eft e generally cylindrical valve geometry, whereas that angle for ihe rectangular patient ot^{5 !}gs 1 x-fG was-about45 degrees.

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Referring now to Fig. 3, and. in accordance with, at least .-one embodiment, a plan view of template 300 is shown for a flat sheet membrane that contains the pattern. 200 of t-lg. 2 with, added sections that extend the- distal contour of the structure when completed in folding. More particularly, the free edge of the mobile leaflet section is extended distally with a section having 15 a -polygonal or curved free-edge in order to increase the contacting area of leaflet apposition in valve closing operation. Additionally, the distal, contour of the cusp wall sections and cuff wall sections 318 and 3.28 are extended by “tab” sections 31ST and 32HT. respectively. These added ’fob” extensions allow for increased area by which to mount the outer wall of the cusp and. leaflet assembly to the .feme-anti for elevating the cuff wall “above” (more distal to) the plane of 20 leaflet opposition, thereby also increasing the effective vdlume of the cusp in closing operation.

These-'“tab” ex tensions, being distally disposed after completion of folding and initial moutitiag within the lattice feme, dr a distal portion of them may optionally be folded radially outward along 312-313 and'322-323, for example, to wrap around the distal edge of the foams such that the “tab” extension areas 318T a»d.328T lie on the outer, abluminal aspect of the feme where, 25 when attached, to the frame, they potentially increase the strength, of the cusp attachment.

Referring still to Fig, 3. template 300 contains folds 301, 3.16, 326, 317 and 327 that correspond to folds 101,. 116,126, 117 and 1.27, respectively, and are. disposed in like manner to. folding execution, as are the edge segments similarly eimmerated, In addition to the tab features discussed m the preceding paragraph, as with template 200, template 300 is designed to forma 30 longer cone of the same diameter, which achieves a more distally disposed, central point of valve leaflet coaptation,. Again, the pattern dimensions may be altered to suit the particular clinical application of the valve. The example is shown for a cusp cone wall disposed at about a 60 degree angle to the horizontal. (short axis) of the generally cylindrical valve geometry.

2017200883 09 Feb 2017

WO

Referring now to Fig. 4, and in accordance with at least one embodimem, a plan view of pattern 400 is shown for a fiat sheet .membrane similar to pattern 300. except that the extension rah' weU->;:s 412’1 and 422'1' j*v Jist:d exomurae of the cusp u:fo only Th-s limitation reduces the double layer of membrane extension at the distal end of the completely 5 folded integrated cusp and leaflet, structure to -fogfo layer, thereby reducing the mass of membrane in the heart valve which, might othenuA· disadvantageously limit the efficiency of collapsing and compressing' the valve for use in the perentancous/transcathetcr delivery application.

In addition, at the lower (proximal) apex 433 of the cusp cone pattern the lower 10 (proximal) extent of the cuff wall sections 418 and 428 is limited so as to ’‘expose” the apex of the cone in the pattern. 'This feature allows, on the completely folded integrated cusp and leaflet structure, the transverse, radially outward folding of the tip of the cone-shaped cusp- at line 403 between points U and V. (See figures 7.) The folding of the apes wdaces the overall axial di J du u s ro .. ii ,* *' ,-J a,. k!'> in. tt'i < . v< a lei -.15 valve diameter.and frame length.

The'template 400 contains .folds 401, 416, 426,417 and 427 that correspond to folds 101, 116,126, '117 and 127, respectively, and are disposed in like manner in .folding execution, as are the edge segments similarly enumerated. Similar to templates 200 and 300 described above, template 400 dimensions may be altered, to suit the particular clinical application of'the valve. 20 The example is shown for a cusp cone wall disposed at about a 60 degree angle to the horizontal (short axis) of the generally cylindrical valve geometry.

Referring now to Figs, 5A.-5F, yet another embodiment of a template- pattern is illustrated, Referring- specifically now to Fig. 5A, a plan -view of template 500 is shown for a .25 flat sheet membrane. The template 500 contains folds 501, 516, 526, 517 and 527 that correspond to folds 101, 116,126,1.17 and 127, respectively, and ate disposed in like manner in. folding execution, as are' the edge segments similarly enumerated.

Template 300 illustrates a flat sheet membrane that is basically rectangular and is similar to. the upper (distal ) portion of template-100 of Figs, 1 A-1G, except that (a) the distal extension: 30 areas 512T and. 522T arc added at the letl and right margins of the template 500, and (b) the lower quadrants forming the cuff wait sections of the template 100 are truncated in template 500 to narrow cuff wall sections 51.8 and 528, the extent of which is defined by the length of cut 502. These limited interior cuff sections are still used for frame attachment along the central' seam. 532 of the -cusp and leaflet cone, and the distal extension sections 51.21’ and 522'1 are still used 35 for attachment of the. outer cusp wall to the distal edge of the frame.

2017200883 09 Feb 2017 wo

Referring still to Figs. 5A-5F, comer folds 505 and 506 are now described. For template 500, after folds 516 and 526 are executed by complete folding, segments 512 and 522 are apposed and aligned to segments 511 and 521, respectively, and overlapping layers (mobile leaflet layer and cusp wall layer) form, triangular comet sections at 562 and 572. Radially 5 outward folding of these comer sections at 505 and 506 define the axial extent of the leaflet commissures such that joining the corner sections of adjacent leaflet structures along corner folds 505 and 506 causes the leaflet apposition to be at least the length of 505 in axial extent at the radial margin of the leaflet. (See Fig. 9E that illustrates an embodiment of a valve comprising a fame 920 with a'plurality of integral cusp and leaflet structures 730 attached- to the 10 frame, Wherein the structures 730 include comer sections 762 and 772 corresponding to the corner sections 562 and 572 of template 500>) Additionally» these double-layer triangular corner sections 562 and 572 are used .for attachment of the commissures to the fame. The stent frame may optionally -contain a slot at this point, of attachment through which this triangular '“fab’’ section may be inserted .and attached on. the abl umma! surface of the -frame. (Again, see Fig, 15 9Ej

With specific reference- now to Fig. SB, a perspective view of the inner aspect (that is, a view directed radially outward) of an initially folded structure '510 folded according to template 500 is shown. The central frslding along 501 is initiated after cut 502 is executed as show». Foldings along 50 L 516, end 526 .are depicted as-initiated radially inward (out of the page) and' 20 foldings along 517 and 527 are depicted as initiated radially outward (into the page).

Figure 5C shows a steeply oblique perspective view of the folded integrated cusp and leaflet 520 at an imermedi ate .stage of Completion of the foldings. The view is directed from, the central axis outward and obliquely downward into the c usp space showing the forination of the' outer wall of the structure, that is, the cusp wail layer of the subject cusp. Folding along 5.17 and 25 527 acts to position the extension, sections 5 IB and 526 outward of the cusp wall sections: 561 and 571, respectively. Completion of .folding then will position, folds 517 and 527 in an axially aligned orientation in apposition to each other along their length. Folding along 516 and 526 acts to position the cusp wall sections 561 and 571 outward of the mobile leaflet sections 519 and 529, respectively. Completion, of folding, which radially collapses the folded flattened structure, 30 positions the cusp wall sections 56.1 and 571 in apposition to the mobile leaflet sections 519 and 529, respectively. In the final .folded configuration the structure embodies the integrated cusp and leaflet in the open operating position.

In addition, completed, folding at 516 and 526 nKo forms triangular two-layer sections,

562 and 572, respectively, that are designated as enmm-xMtre tabs”. These commissure tabs arc bounded by the comer folds 505 and 506, folds 516 and 326, and the free edges 511 and 521 of >7

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PCI711S20 07964989

2017200883 09 Feb 2017 the mobile leaflet sections 519 and 529, respectively; With .further reference to Figs. 50 end 5'E, these commissure tabs will be folded at 505 and 506 so as to .position both layers of the tabs oi os uJ fo fm uts > ac ‘ o'x 5r. m<^! '> · xnexeb, o 0; the to'<\ _ί;·ο fofe ctb tm J parallel to the central axis of the valve. With regard to a multi-leaflet valve, when, the cusp and leaflet structure is mounted within the frame, this folded commissure tab is aligned along fold 505 in apposition to fold 500 of an adjacent complementary commissure tab of an adjacent integrated cusp and leaflet structure. Thus mounted, the commissure tabs join the mobile leaflet layers and the cusp wall. layers, of adjacent folded cusp and leaflet structures along a line coincident to both 505 and 506 that forms a common seam for atta·'rment, such as by suturing 10 of the commissure tabs to each, other and to the frame -forming foe circumferential margin of the membrane portion of the folded cusp and leaflet structure.

Fig. 5D shows a plan view of the inner (luminal) aspect of the folded integrated cusp and leaflet structure 530 of template pattern 500-. Structure 53.0 is depicted, in a completed state of folding, excepting that the commissure tabs 562 and 572 are not yet folded outward, along fold .15 lines 505' and 506, respectively. The radially flattened form shown, gives the general configuration and orientation of the membrane segments and sections for the open operating position of the valve cusp and leaflet .

Still referring .to Fig. 5D, at the uppermost (distal.} portion of the cusp wall. .layer, the extension tabs 5.12T and 522T are projected above for distal to) the lines 512 and 522 (shown, hi 20 figures 5A and 58). respectively, that lie in apposition and alignment to the free- edges 5.11 arid 521, respectively, of the mobile leaflet-layer. A portion or all of these tabs 512T arid 522T may be optionally folded outward along 512 and 522, respectively, around the distal edge of the .frame.-to lie upon the outer (abtumihal-) surface of the frame 'where they may. be attached to both the 'frame' arid to the cusp wall sections (where the cusp wail sections am apposed to .the inner 25 surface of the finme) through, the interstices of the frame. This optional configuration provides for increased, strength of attachment for bearing downward (proximally directed) operational loads associated with the valve closing..

Completing the folding associated with template pattern. 500 places folds. 517 and 527 into axial alignment. Once in axial alignment, apposing, folds 517 'and 527 are joined along their 30 axial length to form the seam. 532 that closes the .-generally conical cusp- sfomrure with the extension sections 518 and 528 situated outward of the cusp wall sections 561 and 57.1, respectively The cusp wall sections 56'1 and.-571 are thus disposed outward of the mobile lea Oct s\!»wv 519 and 529, respectively, with the cusp wall sections ax ially and. cnvumfemnmdly apposed to the inner surfaces of the generally cylindrical frame.

Advantageously, for each, valve cusp and leaflet to be -mounted within, the frame may contain, an 2'3

2017200883 09 Feb 2017 element or elements that are axi aUv oriented and span a significant portion of the axial length of the frame, so as to align with the ream i'2 tor .muchmc: \u</ as b> suturing to the frame.

Pet'.rtmg ΟΟΆ m Fig 5l·', a past·;;; <.h.bid pe-siuesw. nv»' w shown of the commissure tab 57.2 configuration. of the completely folded integrated cusp -and leaflet structure .530, 5 \h. t <’ ae <J> <»' Lw <, < e n>'<e the x*> re hb ' 2 do > oe .._ fob

With reference now to Fig, 5F, a perspective view is shown of the outer (ablunnnal) aspect of the completely folded cusp and leaflet structure 530 (except that the triangular commissure tabs are not yet -folded) of template 500 in substantially flattened form. This view is complementary to Fig. 5.D that shows the inner aspect of the same structure 530. ’The central .10 seam 532 is seen- on the outer face of the cusp wall sections- 561 and 571 and is dcpicis d for purposes of illustration as partly separated with the extension sections 518 a nd 5 > uuompletcly flattened and. folds 517 and 527 hi close, but not hi the complete apposition and alignment that will form the final seam line 532 for attachment to the axially oriented frame members. The slight separation depicted between, folds 517 -and 527 exposes the cenwpomt of the mobile .15 leaflet free edge where the mobile leaflet free edge segments 511 and 521 meet as depicted behind the cusp wall, sections 561. and 571, respectively, in. this view.

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In. accordance with at least one embodiment,. Fig, 6 shows a plan view of another template 600 that is similar to template 500 except that the cusp cone wall angle-# exceeds- the 20 4S degrees of the generally rectangular template 500, and that the mobile leaflet sections are: extended by a polygonal or curved extension Section 604 of the free ed ge.

The change in cusp cone wall angle # afro results in changes in: the angle relating the lower (proximal) margins of the template and fold lines 6.17 and 627 to foe ren-er line of the template in order that when folding is completely executed, the fold lines' ol.7 and 627 and the :25 scam between them will be parallel to. the central axis, of the assembled: valve. Likewise, the further geometry of 'the cusp cone wall angle, will result in fold lines (optional) 613 and 623 and the long axes of extension tabs 612T and 622T being parallel to the transverse axis of the assembled valve.

The template 600 contains folds 601, 616. 626. 617, 627, optional folds 612 and 622, corner folds 605 and 606, and cut line 602 that correspond to folds 501., :5.16, 526, 517, 527, optional folds 512 and 52 2, earner .folds 505 and 506, and cut line 502, respectively. of template pattern 500 and are. disposed in like manner in folding execution, as are the template sections and edge segments similarly enumerated.

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2017200883 09 Feb 2017

Referring now to Figs. 7A-7F, still yet another embodinteni of a template pattern is illustrated Referring specifically now to Fig. 7A, a plan view of another xrnylate 700 is shown that i\ similar to template 600. but with a .section of the lower (proximal) midiine portion of the template cut away so as to expose the apex 733 of the triangular sections that, when, folded, will form the apex of the cone-shaped, cusp. .Effectively, the midline portions of the extension sections 718 and 728 are-removed in relation to template 600 to an extent determined by the desired length of the line segment U~V, which in turn determines the extent to which the-apex of the cone-shaped cusp may be truncated by folding at. IFV.

After the cusp and leaflet cone is formed by folding, the apex is folded radially outward at line U-V (703) to truncate the cone to reduce the overall length of the cusp and leaflet structure, allowing for increased cnsp/slntis volume for a given valve diameter and. frame length.

The template 700 contains folds 701, 71 6. 726, 717, 727, optional folds 712 and 722, and comer folds 705 and 706, that correspond to folds 601, 616. 626. 617, 627, optional folds 612 and 622, and corner fokfe 605 and 606,. respectively, of template 600 and are disposed in like manner in folding, execution, as are the template sections and edge segments similarly enumerated.

Fig. 713 shows a perspective view of the inner (luminal) aspect of the initially folded cusp and leaflet structure 7W of template 700 after initiation of the principal folds 716,. 726, 717, 727 and 701.....Inward folding along 701 assists in aligning the left and right sections of the structure, but is not necessary to the formation of the integrated cusp and leaflet folded' strueture or to the operation of'the valve. The disposition of the folds that converge at 'the' apex 733 of'the cusp can. be appreciated as later forming an overlapping two-layer triangular apex as the cusp wall sections 761 and 771 are folded outward along lines 716 and 726, respectively, so as to •position ths cusp wail sections 761 and 771 outward of, and in apposition to, the mobile'-leaflet sections 719 and 729, respectively.

Fig, 7C shows a steeply oblique perspective view of the folded integrated cusp and leaflet 720 at an intermediate stage of completion of the foldings. The View is directed from the central axis outward and obliquely downward, into .the cusp space showing the formation of the outer wall of the struc ture. Folding along 717 and 727 acts to position the extension sections 718 and 728 outward of the cusp wall sections· 76.1 and. 771., respectively. Completion of folding then will position folds 71? and 727 foan axially aligned orientation in apposition to each other along their length. Folding along 716 and 726 acts to position the cusp wall sections 761 and 771 emu md re > moh> e arafe x uotrt Ή a to 21 r.\,o c<o<- > ί won <*'ml'bn., uht, h radially collapses the folded flattened structure, positions the cusp wall, sections 761 and 771 m apposition to the mobile leaflet sections 719 and 729, respectively. In the final folded 25

2017200883 09 Feb 2017 configuration, the structure embodies the integrated cusp and. leaflet in the. open operating pGMRoit.

With reference to Fig. 7D, completed folding at. 716 and 726. also forms triangular twolayer sections, 762 .and. 772. respectively, that, are designated as “commissure tabs.” These commissure tabs are bounded by the comer folds 705 and 706. .folds 716 and 726, and the free edges 711 and 721 of the mobile- leaflet sections 719 and 729,.respectively. With further reference to Figs. 7D and 7E, those commissure tabs will be folded, at 705 and- 706 so as to position, both layers of the tabs outward of the cusp wall sections 761 and 771, respectively, with the folds 705 and 706 oriented parallel to the central axis of the valve. When the integrated cusp .10 and leaflet structure is mounted within-the flame, this folded commissure tab is aligned along fold 703 in apposition to fold 706 of an adjacent complementary commissure tab of an adjacent integrated cusp and leaflet structure of a .multi-leaflet valve. Thus mounted, the commissure tabs join, the mobile leaflet layers and the cusp wail layers of adjacent .folded cusp and. leaflet structures along a. line coincident to both 705 and 706 that forms- -a common, seam for 15 attachment, such as by suturing of foe commissure tabs to each other and. to- the frame forming the circumferential margin of the membrane portion of the. folded cusp and leaflet strucutre.

Fig. 7D shows a perspective view of the inner (luminal) aspect of the p..ird.Fdy folded integrated cusp and. valve structure 72() of template 700. integrated cusp and leaflet xlnicture 720 is depicted in nearly completed state-of folding, except that the commissure tab'* 762 «nd 20 772, as well as the cusp apex 733 are not yet folded, outward along fold lines 705, 706 and 703, respectively, and that the axial scam 732 is not yet formed by the appo- mon of the folds 717 and 727.

At the uppermost (distal) portion of the cusp wall layer, the extension tabs 712T and 722'T are projected above (or distal to) the lines 712 and 722 (shown in. Figs. 7A and 7B), All or 25 a portion of these tabs 712T and 722T .may 'be optionally folded outward along 712 and 722, respecti vely, around the distal edge of the frame to lie upon the outer (abtominal) surface of the frame 'where they may be attached to both the frame, and to the cusp wall sections (apposed to. the inner surface of the frame) through foe interstices of the. frame. This optional wnfiguratiop provides for increased strength of attachment for bearing downward (proximally directed). 30 operational loads associated with the. valve closing.

Completing the folding associated with template-pattern 700 places folds 71.7 and 727 into axial alignment. Once in axial alignment, apposing folds 717 and 727 are joined along their axial length to form foe seam 732 that closes-the generally-conical cusp structure with the extension sections 7.1 h and 728 situated outward of foe cusp wall sections 761 and 771, respectively, The cusp wall sections 761 and 771 then are disposed outward -of the mobile

2017200883 09 Feb 2017 k\iffo ,wcoons 719 and 729,. respectively, with the cusp wall scetfens axiaflv and eucumfoieutudly apposed to the inner surfaces of the generally sa'h'Chu· frame.

Adrau areraoh. t.> ntcgt.K.d ς,ΐχρ and i<-dc>l .-itucmu-b‘'>? wji'oU th;· de frame may contain an element or elements that are axially oriented, and span a Mgm’kant portion e^f the as al I 'n *' < the ^f , \ -e . - o .the . a tth the w - '2 ret <- \xhnur as b\ uru gio the frame.

Fig. 7E shows a shallow oblique top perspective view of the outer (abiuminal.) aspect of the partially folded cusp and leaflet structure 720 of template 700 (except that the triangular commissure tabs 762 and 772 and apex 733 are not yet .folded and that the axial seam 732 is not 10 yet joined). Tins view is complementary to Ftg. 7D that shows the inner aspect of the same structure 720, The central seam. 732 will be formed on the outer face of the cusp wall sections 761 and 771 as .folds 717 and 727 are brought together into apposition along the mi.dli.ne, with the extension sections 7.1 H and 728 thus also aligned. The outward (abhnninal) face of the mobile leaflet sections 719 and 729 are- shown between the yet separated folds 717 and 727 15 'before closure of the generally conical cusp along the outer scam 732.

Fig, 7F shows a plan, view of the inner (luminal) aspect of the folded integrated cusp and leaflet structure 720 of template pattern 700. Structure 720 is depicted in. a completed state of folding, orap u·,. ihm -he cumod\surc tabs A? and 772 not yet folded c-mward along fold lines 705 and *\> respectively, In addition, the apex 733 is. not folded outward. The radially 20 flattened form snown gives the general configuration and orientation of the membrane- linex-gnvus .mJ ure.d sw'wns tot the open operating position .of the valve cusp and leaflet.

At the uppermost (distal) portion of the cusp wall layer, the extension tabs 712T and 722T are-projected above (distal to) the lines 712 and 722 (.shown in Figs. 7A, 78 and 7G), respectively, befow (proximal to) which the cusp wall sections 761 and 771 lie in radial 25 apposition, to the nsobils leaflet sections 719 and 729. respectively, of the mobile leaflet layer.

These tabs 7I2T and 722T may be optionally folded outward, along 7.12 and 722, respectively, around : the distal edge of the frame to lie upon the-outer (ablummal) surface-of the flume where they may be attached to. both the frame and to the cusp-wall sections (apposed to foe inner surface of the frame) through foe interstices of the frame. This optional configuration provides 30 for increased strength of attachment for bearing downward (proximally directed) loads of valve closing.

Folding of the template positions folds 717 and. 727 into axial alignment, joined along their axial length, to form the seam, that closes- the generally conical cusp structure- with the extension, sections 718 and I¹- reflected outward of the cusp wall sections 761 and. 771, 35 respectively, The- cusp wall sections 761 and 771 then, are disposed outward of the mobile leaflet

2017200883 09 Feb 2017 sections 'fo and 729, respectively, with the cusp wall sections 761 and 771 axially and encumfoeutudly apposed to the inner surfaces of the -generally cylindrical frame. Adwmumcoufo, for each valve cusp and leaflet folded structure to be mounted within, the-frame may contain an element or elements that are axially oriented and span a significant portion of the 5 axial length of the frame, so as to align with the seam 732 for attachment as by suturing to the feme.

Fig. 7G show's a perspective view of the outer (abluminal) aspect of the completely folded cusp 'and leaflet structure 720 (except that the triangular commissure tabs 762 and 7'72 and apex 733 are not yet folded) of template 700, in nearly flattened form. This view is .10 complementary to Fig, 7F that shows the inner aspect of the same structure 720, The central, seam. 732 is seen on the outer face of the cusp wail sections 761 and 771 and is depicted for purposes of illustration as minimally separated with the extension, sections 718 and ”2f incompletely flattened and folds 717 and 727 in eflectively complete apposition and alignment that forms the feal scam line 732 for attachment to the axially oriented frame members. The 15 slight separation depicted: between folds 717 .and 727 exposes the centerpoint between the mobile leaflet free edge segments 711. and 721 depicted behind the cusp wall sections '761 and 771, respectively, in. this view.

Fig, 7.H shows a. plan view of the inner, aspect of the completely folded integrated cusp, and leaflet structure 730 of template 700. This.view ts subst mtially that of Fig. 7F except that '20 the triangular commissure tabs 762 and 7'72 are fold, d : ae w Ih outward of the cusp wall sections

76.1 and 771 afong corner folds 70'5 and 706,. w‘pxsrve.ly. Additionally, the apex (most prox-mai'» portion oi the eon,-shaped cusp is folded rapmltt ->-mxard along Aw fold hue 705 (between points U and V) to the position radially outward-of the.· joined extension sections 718 and 728 such that the apex point 733 then lies upon the seam line 732.

Fig, 71 shows a plan, view Of theradially outer aspect of the completely folded integrated, cusp and leaflet structure 730 of template 700, The outwardly folded, position of the triangular commissure tabs 762 and 772 can be seen -so that they lie in apposition, to the outer surface of the cusp wall sections 761 and 77I, respectively. While they may-attached in this position to the underlying cusp wall layer and to the frame, alternatively, the commissure tabs 762 and 772 may

F' g<warned to ροήν mo ,tth omo.wd ;<-uf o? '* e p;ge m tin, u u) m pasx ttb'itA a .ue- .>r space in the frame to be secured and attached to the outer (abluminal) surface of the feme.

Additionally, the apex (most proximal) portion of the cone-shaped cusp is folded radially outward- along the fold line 703 (bet ween, points U and V) to the position, radially outward of the joined extension, sections 718 and 728 such that the apex, point 733 then, lies upon the seam line 35 732.

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2017200883 09 Feb 2017

The apex portion of the cone-shaped cusp thus configured is to be attached in this position, as by -suturing and may be similarly attached into this posidon in the act of attaching or s^UiBUg : « port on ot ih. u>3kJ -..asp ,rc<l k«foy suneiu c <.> di. frame

In- Ί secs m o-ι i. rop peisprat'ra o?¹··. >>t\ .e ..o<npkie s fe-Ad nt J fo>r\d uwp 5 and leaflet -structure 730 with the view directed. radially outward and downward (proximal). The cusp and leaflet structure is shown -with the free edge of the moblie leaflet layer in the inward central position corresponding to the .substantially closed operating position of the valve leaflet

The commissure tabs 762 and 772 are depicted in radially aligned positions directed outward as would be required for passing them through slots or spaces in -a suitably designed 10 frame.

Fig, 7K. shows a top perspective view of the single-piece completely folded and formed cusp and leaflet structure 730 with the view directed downward (proximal) into the cusp-space. The cusp and leaflet structure is shown with the free edge- of the mobile leaflet layer sections 719 and 729 in the intermediate inward position corresponding to the partially closed operating 15 position of the valve leaflet.

The membrane structure is depicted with the free edges in a relaxed state corresponding to the typical behavior of tissue membranes when hydrated as when implanted in. the body.

The commissure tabs 762 and 772 are depicted in. radially aligned positions directed outward as would be required, for -passing them through slots or spaces in. a suitably designed ..0 frame.

Fig. 8A is--an. oblique top perspective view of a. metal Isttice frame 9W for mounting three of the single-piece folded integrated cusp and leaflet structures of the ensuing description in order to form a three-leaflet valve. The frame comprises a plurality of strut members 911 and 25 three axially oriented mounting bars 912 each with holes and/or slots for passing suture and/or portions of the folded membrane Structure, Each mounting 'bar 9.12 is to align with, and attach, to the axial outer seam of One single-piece completely folded and formed cusp and leaflet structure 730. The diameter D of the open ..frame, e.g., 19 - 35 mm naturally defines, the- deployed .and. operating- diameter of the valve assembly after implantation in the-body,· The strut members 911 30 are of specifi c length and orientation to permit radial collapse and. compression of the frame to a small diameter, e.g., 3-7 mm. The mounting bars 912 are near to equally spaced amend the circumferential course of the frame and the length L of the arc from the center of the mourning bar 912 to the center-of the closest mounting bar 912 is approximately equal to (pi χ ,p>'3. Thus defined, L also defines the 'transverse circumferential distance between, folds 705 and 706 , approximating the circumferential extent of the portions of the joined cusp wall sections 761 and

2017200883 09 Feb 2017

771 extending between 705 and 706 of the folded cusp and leaflet structure of appropriate size when mounted ithia'll v from.? 910,

Fig; ® she*', a sn.k pc· <.|'ectiv© view of the frame 910 with, the view centered on the axial mounti.u» ora Ή 2. The axial bars are shown with holes andfor slots for passing suture 5 and/or portions of the folded membrane structure to enable secure mounting of the folded cusp .rad te.ffi-A 'ray.-rar·? whhra lira frarn».·.

Fig. 8C shows a side view of the frame of'Fig. 8B with a superimposed plan view of the radially outer aspect of the completely folded integrated cusp and leaflet structure as depicted in Fig, 71, The cusp wall seam 732 is aligned upon the mner sur&ce of the mounting bar of the 10 frame and attached by sutures in this example. (Example suture locations are shown in Figs. 8C, 9C and 9D shown with an \T however, it is to be understood that the locations shown arc exemplary and not limiting.) As those skilled in the art will' appreciate, means other than sutures for attaching folded integrated cusp and leaflet structure to the .frame can be used.

The commissure tabs 762 and 772 arc folded flat against the outer surface of the cusp 15 wall layer along, corner folds 705 and 706 for mounting entirely within the frame 910. Each fold 705 then forms an axially oriented seam along its length with the complementary fold 796 of the adjacent folded cusp and leaflet structure 730. (Adjacent complementary commissure- tabs otwitote c<)ij i Sara ,-ram e> dvst rate m.Owd 1 \ Artrc. fo> w.raptey v,h ? Ae attaching to the radially overlying strut member 911 of the frame 910, and thereby affixes the '20 distal margins of the cusp -wall sections 761 and 77 .1 and the mobile leaflet sections- (obverse of this view) to the frame 910. The other suture points depicted attach, only the cusp wall layer 761+771 to the overlying frame strut members 91. L At no point within the interior operating volume of the 'Vahc w the mobile leaflet lay er 719+729 penetrated by suture. This-unintermpted continuity- of the operating leaflet material afforded, by the folded, design of the. integrated cusp 25 and leaflet structure endows the valve and its leaflets with strength:, durability and resistance to stress damage at; suture holes.

Fig. 8D shows an oblique axial (top/distal) perspective view of the. assembled threeleaflet valve comprising, the frame 910 and three identical folded integrated cusp and. leafletstructures 730A, 73® and 7300 attached within, the frame with the view centered.-on an axial 30 mounting bar 9I2A, The .suture attachments are omitted for clarity. The. cusp and 'leaflet structure 73OA nearest in view is seen within the frame 910, with. the. outer aspect of the seam. 732A, cuff wall extension sections 718A and 728A, -and cusp wall sections 76.IA and 77 iA viewed through the interspaces of the frame 910, The seam 73.2A is aligned to the -overlyingaxial mounting bar- 912A to which it is attached along its length. The inner (luminal)- aspect of 35 the seams 732B and 7326) and the cusp wail sections 761 Β, 77IB, 7610 and '7710 of the other

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2017200883 09 Feb 2017 two folded cusp and 'leaflet structures 7308 and 730C, respectively are seen on the for side of the view. The adjoined folded edges of the tw.-nd -raav portions of the commissure tsiw ''‘fl' «.\l ~O?C slw.n Hi the f<U ΧΚ'Λ :U pOsiBOO OppOMtC iO tBC .i usl SW :O: ;g tWi OF? A 'iW W)i view. The radially outward surface of the mobile leaflet sections 719A and 729A of the folded 5 cusp and leaflet structure 730A. is show in the near view. The distal free edges of all three mobile leaflets are shown tn the centrally apposed (coapted) .position corresponding to the closed operating position of the valve. Fig, fob also shows in-that aspect interior to the cusps, folds 7268 of'cusp and. leaflet structure 730.8 and 7.16C of eusp and leaflet structure 730(. as they form, the lower (proximal)-boundary of the valve cusps.

Slo'-.cJ I .r-ivc Frame fog ’> \ shows .oi oblique a\!«. ra>p d -ta '> pv >peeks. > cw <% name 9 m ci -i devgn to receive the commissure tabs 762 and 772 through slots 924 in slotted members 923 in order that the tabs are secured' and attached to the outer (foiranmal) aspect of the frame. This approach to mounting and attaching the commissure tabs enables the loading forces on the leaflet 15 commissures during valve operation to 'be advantageously distributed upon the frame slotted members .923 along their length rather than.-upon suture that', directly tethers the leaflets, thus greatly reducing the. risk of tearing of the material at points of suture penetration..The frame farther, comprises axial mounting bans 9.22 for mounting the central seams 732 joining, the cusp, wall, sections 761 and 771 along folds 717 and 727. The frame further comprises a plurality of 20 strut members 921 that otherwise form the metal lattice of the frame.

Each mounting bar 922 is fo align with and attach to the axial outer seam of one singlepiece completely· folded hud formed eusp and leaflet structure '730. The inner diameter D of the open flame, e.g., 19 - 35 mm naturally defines the-deployed and operating diameter of the valve assembly after implantation in the body. The strut members 921 are .Of specific length, and 25 orientation fo permit radial collapse and compression of the frame to a small, diameter, e.g., 3-7 mm. The mounting bats 922 are near to equally spaced, around the inner circumferential course of the frame. The length L of the arc along the inner circumference of the .frame .from the center of the mounting bar 922 to the center of the closest mount ing bar 922 is approximately equal to (pi x D)/3. Thus defined*. L also defines the transverse circumferential distance between, folds 30 705 and 706 , approximating- the circumferential extent of the portions of the joined, cusp-wall sections 76.1 and 771. extending between 705 and '706 of the folded cusp and leaflet structure of appropriate size when mounted within the.-frame 920.

The axial mounting bars 922 optionally contain, holes and/or slots to facilitate suture attachment of the .folded integrated cusp and. leaflet structures 730. 'The frame is -depicted in

Figs, 9A-9E as having axial mounting bars 922 each with a hole near the proximal end to

2017200883 09 Feb 2017

WO 2(H W2952 FClftiSWteWte) facilitate-suture attachment of the apical (most proximal) portion of the folded cusp and leaflet structure.

Fig; 9B shows, the metal lattice frame of Fig. 9A in the same -pa^pective, but with the view centered on the slotted frame- member 923.

Fig. 9C shows a side perspective view of the frame 920 centered on the axial mounting bar 922 with a superimposed plan, view of the outer aspect'of the completely folded integrated cusp and leaflet structure 730 (of Fig. 71) as mounted within the frame 920 to demonstrate the relationships between the two. An 'example suture pattern for attachment is shown. The cusp wall seam 732 is aligned upon the inner surface of the mounting bar 922 of the frame 920 and .10 attached by sutures 'in . - example.

The commissure tabs 762 -and 772 are to be understood as having been passed through the .frame slots 924 from within the central space of the frame to the outer (abluminal) side and folded along ^i>s aid 706, respectively onto the outer surface of rhe cusp and leaflet structure where they ate attached along their common length both to the frame members 923 and, through .15 the imc s»> a es of the frame 929, to the radially underlying outer aspect of the cusp wall sections 761 and 7'71, respectively. The adjacent eusp and leaflet structures of the three-leaflet valve are not shown, for clarity. The joining of adjacent commissure tabs at: the slotted members 923 is demonstrated in. Fig, 9ΓΧ

At the apical (most proximal) extent of the completely folded integrated cusp and leaflet '20 Structure 730, the apical portion folded radially outward along fold 793 is attached to the lower • mosi ram *< t o d ,<r flu <fl s Ot' ¹' 3 >i >' A> we < ; ό< re e < ra ilk axial mounting bar 922 facilitates suture attachment at this point.

Fig. 9D shows a side perspective view of the frame 920 centered bn the slotted: frame member 923AB with a- superimposed perspective view of the Outer aspect of two 25 circumferentially ..adjacent, completely folded integrated cusp and. leaflet structures 730A and, 7308 (of Fig. 71) to demonstrate their relationships as mounted within the frame 92(1, An. example suture pattern for attachment is shown. 'Suture attachment of the commissure folds '705 and. 706 at the level of the slot is notably absent, Rather, attachment of the bodies-of the commissure tabs 762A and. 772B to-the outer aspect of the frame at points removed from the 30 free edges and folds of the material avoids suture penetration- along the lines of traction in the slot and enhances the resistance of the structure to tearing at such suture attachments. The cusp wall searas 732A and 732B are aligned upon the inner surface of the mounting bam 922A and 9228. respectively of the frame 920 and attached by sutures in. this example.

The commissure tabs 762A and 7728 are to be understood as having been, passed 35 through, the frame slot 924 from within the central space of the frame to the outer (abiummal) 32

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2017200883 09 Feb 2017 side and folded along 705A and 7068, respectively onto the outer surface of the cusp and leaflet sfectere where they arc attached along their common length both to the frame member 923AB and, through the interspaces of the feme 920, to the radially underlying outer aspect of the cusp wall sections 76'lA.and 77¾ respectively.

Fig. 9B shows an. oblique axial (top/distal) perspective view of the assembled threeleaflet: valve comprising the feme 920 and three identical folded integrated cusp and leaflet structures 730A, 7308 and 730C attached, principally within the central space of the frame, but with the commissure tabs passed in complementary adjacent left-right pairs, 762A-772B, 76.2B772C and 762C-772A, through the slots 924A8, 924BC and 924CA, of slotted frame members 10 923 AB, 923BC, and 923CA, respectively, The view is centered on slotted member 923.AB, The suture attachments are omitted- for clarity.

The cusp and leaflet structure 730C farthest in view ix seen within the feme 920, with, the inner aspect of the seam 73 2C and cusp wal l sections 76 .1 C and 77'1 C in the far vi ew.. The cuff wall extension sections 71BC and 72 8C are depicted as folded onto the outer aspect of the 15 cusp wall sections 76IC and 77 .1C, respectively, but within the central space of the feme 920 and apposed to the inner .surface of the frame. The 'Inner (luminal) aspect of the seam 732C is shown aligned to the outwardly overlying axial mounting bar 922C to which it is attached along its length. The outer (abhmnnal) aspect of the top (most distal) portions of the seams 73.2A. and, 732B and the cusp wall sections 76.1 A and 77.1 B, of the other two folded cusp and leaflet '20 structures' 73QA and 7308 are also shown through the interspaces of the frame on either side of the near view.

The commissure tabs- 762A. and. 772B, aligned and. apposed along folds '70S A and 706B, respectively 'are shown centered in the near view in position Opposite to -the axial mounting bar 922C atid cusp wall seam 732C in the far view. The key mountfog configuration of the valve 25 commissures to the slotted feme -members is here demonstrated. The triangular commissure tabs are formed as a .result-of the folding of the membrane templ ate along folds 7 .16 and. 726, and are comprised of overlapping layers of the-cusp. wall-section and the mobile leaflet section. Thus, with passage of the commissure tabs from within the interior space, of the frame through the feme slots, 'both the cusp wall layer and the mobile leaflet layer arc carried together to the outer 30 -aspect of the., feme where they ate attached; In -addition, the. interior aspect of the commissure folds 706A of cusp and leaflet structure 730A and 705.B of cusp and leaflet structure 730B are shown where they mark the segment at: which .the commissure few ^SA and 762B -are passed through the feme slots 924CA and 924BC of slotted membc' V w A and 923BC, mspeettvely, and are tethered thereto.

3.3

WO 2(Η2ή)»32

2017200883 09 Feb 2017

The radially outward surface of foe mobile leaflet sections 719A, 2^UA of the folded cusp and leaflet structure 730A and sections 7I9B, 729B of the folded cusp and leaflet structure 730.8 arc shown on the left and right sides, respectively of the -scar v . (These labels omitted for clarity.)

The distal free edges of all three mobile leaflets are shown in the centrally apposed, (eoapted) position corresponding to the closed operating position of the valve I ig. 9E also shows in that aspect interior to the cusps, a -portion of folds 726A of cusp and ei H structure 730A and 716B of cusp and leaflet structure 730B as they form the lower (proximal) boundary of the valve cusps.

The template examples disclosed herein are provided for enabiemerit purposes and shall not be interpreted as limiting the scope of the claims. For example, angular whies shown and/or described herein are not to be interpreted as limiting the scope of a claim unless included in a gi ven claim.

As those skilled in the art will appreciate, circumference length varies with the diameter 15 circumscribed therein.. Accordingly, refinements in the valve manufacturing, process may address adjusting the length of the leaflet free edge to be slightly less than, the edge length of the cusp wall, i.e., less than the circumferential arc length between, the commissures. This adjustment depends upon the dimensions of a given valve in production, as well as the dimensions of the given valve’s component elements.

In still other embodiments- of the- otto or more present inventions, the percutaneously deliverable heart valve may Include various other configurations by using different variations of the polygon pattern, so as to Include, for example, -an. inner sealing cuff for the valve that is continuous and integral with the leaflet Structure itself In. yet other embodiments, the percutancously deliverable heart valve may include different con-figurations by adjusting the pattern and. foldingtechnique, such as the angle, of the cone and its surface area, or the extent of apposition between the leaflets may also be specified.

The present invention may.be- embodied in other specific forms without departing from its spirit or essential characteristics. The described embodiments: are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, 30 indicated by the appended, claims rather than by ihe foregoing description. All changes which come within, the meaning-and range of equivalency of the claims are to be- embraced within their scope.

The one or more present inventions-, in various embodimems, include components, methods, processes, systems and/or apparatus substantially as depicted and described, herein, including various embodiments, subcombinaiions, and subsets thereof. Those of skill in the art

TIS511980AUPR

304270712

2017200883 21 Feb 2017 will understand how to make and use the present invention after understanding the present disclosure.

The present invention, in various embodiments, includes providing devices and processes in the absence of items not depicted and/or described herein or in various 5 embodiments hereof, including in the absence of such items as may have been used in previous devices or processes (e.g., for improving performance, achieving ease and/or reducing cost of implementation).

The foregoing discussion of the invention has been presented for purposes of illustration and description. The foregoing is not intended to limit the invention to the form or forms 0 disclosed herein. In the foregoing Detailed Description for example, various features of the invention are grouped together in one or more embodiments for the purpose of streamlining the disclosure. This method of disclosure is not to be interpreted as reflecting an intention that the claimed invention requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects lie in less than all features of a single foregoing 5 disclosed embodiment. Thus, the following claims are hereby incorporated into this Detailed Description, with each claim standing on its own as a separate preferred embodiment of the invention.

Moreover, though the description of the invention has included description of one or more embodiments and certain variations and modifications, other variations and modifications Ό are within the scope of the invention (e.g., as may be within the skill and knowledge of those in the art, after understanding the present disclosure). It is intended to obtain rights which include alternative embodiments to the extent permitted, including alternate, interchangeable and/or equivalent structures, functions, ranges or steps to those claimed, whether or not such alternate, interchangeable and/or equivalent structures, functions, ranges or steps are disclosed herein, and 25 without intending to publicly dedicate any patentable subject matter.

The reference to any prior art in the specification is not, and should not be taken as, an acknowledgement or any form of suggestion that the prior art forms part of the common general knowledge in New Zealand.

Claims (11)

1. What is claimed is:

   1. A transcatheter, implantable, prosthetic heart valve, comprising:

   a lattice frame; and

   5 two or more integrated cusp and leaflet folded structures attached to the lattice frame, the two or more integrated cusp and leaflet folded structures each comprising a flat sheet of biocompatible membrane that has been folded to include a mobile leaflet section and a cusp wall section, wherein non-transverse diagonally oriented folds that are angled relative to an axial flow direction are located between the mobile leaflet section and the cusp wall section, wherein

   0 the cusp wall section is located radially outside of the mobile leaflet section, and wherein the cusp wall section includes a seam that joins apposing sides of the cusp wall section.
2. 2. The transcatheter, implantable, prosthetic heart valve of Claim 1, wherein the two or more integrated cusp and leaflet folded structures are each attached along their respective seams to the lattice frame.

   5
3. 3. The transcatheter, implantable, prosthetic heart valve of Claim 2, wherein the seams are oriented in a direction substantially parallel to an axis of the lattice frame.
4. 4. The transcatheter, implantable, prosthetic heart valve of Claim 1, wherein the flat sheet of biocompatible membrane forming at least one integrated cusp and leaflet folded structure of the two or more integrated cusp and leaflet folded structures comprises two or more

   20 pieces of biocompatible membrane material.
5. 5. The transcatheter, implantable, prosthetic heart valve of Claim 1, wherein the apposing sides of the cusp wall section include a left cusp wall portion and a right cusp wall portion, wherein a left cuff wall portion is continuous with the left cusp wall portion, and wherein a right cuff wall portion is continuous with the right cusp wall portion.

   25
6. 6. The transcatheter, implantable, prosthetic heart valve of Claim 5, wherein the left cuff wall portion and the right cuff wall portion of each of the two or more integrated cusp and leaflet folded structures are joined at the seam of each of the two or more integrated cusp and leaflet folded structures.

   304941211

   511980AUPR

   2017200883 14 Feb 2019
7. 7. The transcatheter, implantable prosthetic heart valve of Claim 5, wherein the left cuff wall portion and the right cuff wall portion reside radially exterior to the cusp wall section and the mobile leaflet section.
8. 8. The transcatheter, implantable, prosthetic heart valve of Claim 5, wherein the left 5 cuff wall portion and the right cuff wall portion reside radially interior of the lattice frame.
9. 9. A method of forming an integrated cusp and leaflet folded structure for use in an implantable valve having an axial flow direction, comprising:

   folding a flat sheet of biocompatible membrane to form an integrated cusp and leaflet folded structure according to a flat folding pattern, wherein said folding includes 0 making two diagonal folds in the flat sheet of biocompatible membrane, the two diagonal folds separating a mobile leaflet section from a cusp wall section of the integrated cusp and leaflet folded structure.
10. 10. The method of forming the integrated cusp and leaflet folded structure of Claim

    9, wherein said two diagonal folds are angled at between 10 to 80 degrees from the axial flow

    5 direction.
11. 11. The method of forming an integrated cusp and leaflet folded structure of Claim 9, further comprising forming first and second cusp wall folds, wherein the cusp wall section is further formed by joining apposing membrane portions adjacent the first and second cusp wall folds along a seam that is oriented substantially parallel with the axial flow direction.