WO 2007/138572
`
`31
`
`PCT /IL2007 /000615
`
`Extension of tubular wall 74 has allowed ring-shaped component 78 to tilt in a
`
`manner that equalizes the unequal pull of chordae 46 and 48 so that coaptation surface
`
`42 is maintained.
`
`In embodiments, (seen Figure 18C) wall 74 is substantially non-stretchable
`
`5
`
`and ring-shaped component 78 extends into lumen 88 by anywhere from 5 to 15
`
`millimeters.
`
`In embodiments (as discussed with reference to Figure 15), the proximal end
`
`of the tubular wall is trimmable, that is, can be shortened by a desired extent without
`
`adversely affecting the functioning of the tubular implant. In embodiments, prior to
`
`IO
`
`attachment of the proximal end of the tubular wall to the vicinity of the cardiac
`
`annulus, the proximal portion of the tubular wall is trimmed so that the height of
`
`leaflet coaptation surface 42 is set to between 10 and 15 millimeters, ensuring that
`
`leaflets 38 and 40 will properly coapt and that regurgitation through leaflets 38 and 40
`
`will not recur, even in the face of post-operative remodeling of ventricular wall 82
`
`15
`
`(Figure 16) and the pull of papillary muscles 44.
`
`In embodiments, the tubular wall of an implant is secured to the vicinity of the
`
`cardiac valve annulus at a location along the wall to provide a desired degree of
`
`leaflet coaptation, and subsequently excess tubular wall that extends into the atrium is
`
`trimmed.
`
`20
`
`In exemplary embodiments, tubular implant 72 is provided in various sizes
`
`and shapes that depend, inter alia, on the diameter and/or shape of mitral valve
`
`annulus 34 (Figure 16) and/or the valve periphery edge 70 and whether there is a
`
`necessity to alter the shape of mitral valve 26 and/or leaflets 38 and 40.
`
`As a non-limiting example, the surgeon may choose a tubular implant having a
`
`25
`
`diameter of proximal end 76 of 28 millimeters. In a tubular implant 72 having a
`
`tubular wall 74 that is substantially parallel to a longitudinal axis passing through
`
`lumen 88, ring 78 will have an effective orifice area of 480 millimeters2.
`
`In some instances, the surgeon opts to reduce the native diameter of valve
`
`periphery edge 70 in order to increase coaptation of leaflets 38 and 40. In some
`
`30
`
`embodiments, tubular wall 74 is sloped along its entire outer surface, thereby reducing
`
`the cross section oflumen 88 of the tubular implant at ring-shaped component 78.
`
`As a non-limiting example, the surgeon may choose a tubular implant having a
`
`tubular wall diameter of 28 millimeters at proximal end 76 while lumen 88 of the
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 801 of 1441
`
`

`

`WO 2007/138572
`
`32
`
`PCT /IL2007 /000615
`
`tubular implant, as measured at ring-shaped component 78, has a smaller diameter,
`thereby reducing effective orifice area to 466 millimeters2
`Upon attachment of mitral valve 26, the diameter of valve periphery edge 70 will be
`
`, as seen in Figure 18A.
`
`reduced, thereby increasing coaptation ofleaflets 38 and 40.
`
`5
`
`In other embodiments, as seen in Figure 18B, a side of tubular -wall 90 1s
`
`sloped with respect to a proximal portion 76 while opposite wall side 92 is
`
`substantially parallel to a luminal axis 94, thereby reducing and offsetting ring-shaped
`
`component 78 and leaflets 38 and 40.
`
`In other embodiments (e.g., 18C), a ring-shaped component 78 projects
`
`10
`
`radially inward into lumen 88, thereby providing a lip or ledge for attachment
`
`components such as sutures 64, so the attachment of a mitral valve 26 to ring-shaped
`
`component 78 is within lumen 88.
`
`Alternatively, ring-shaped component 78 comprises a flexible distal lip 96, as
`
`seen in Figure 18D, that deflects into lumen 88 dm)ng securing, and retracts out of
`
`15
`
`lumen 88 following attachment to the tubular implant.
`
`In other embodiments, a ring-shaped component 78 includes a projection 98
`
`that projects radially outward from tubular wall 74, as seen in Figure 19A, to enhance
`
`the ease of placing securing components such as sutures.
`
`In still other embodiments, a ring-shaped component 78 includes a bend 100,
`
`20
`
`as seen in Figure 19B, for example: to compensate for tenting of either leaflet 38 or
`
`leaflet 40.
`
`Many different configurations of a ring-shaped component 78 may be
`
`conceived by one skilled in the art upon perusal of the description herein.
`
`There are many configurations of materials, material properties and
`
`25
`
`attachment methods between a tubular wall 74 and a ring-shaped component 78 which
`
`may be conceived by one skilled in the art upon perusal of the description herein.
`
`Described above have been ring-shaped components that are substantially
`
`uniform, that is the extent of rigidity or flexibility, was well as other properties 1s
`
`substantially at all locations about the ring-shaped component.
`
`30
`
`In embodiments, the ring-shaped component comprises at least two sectors, a
`
`first sector and a second sector more flexible than the first sector. In embodiments, the
`
`first sector is substantially rigid. In embodiments, the first sector is substantially
`
`flexible and the second sector is even more flexible. Such a configuration is known,
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 802 of 1441
`
`

`

`WO 2007/138572
`
`33
`
`PCT /IL2007 /000615
`
`for example, in the field of annuloplasty, where it is known that a sector of a ring
`
`close to an anterior leaflet 38 is preferably more flexible than a sector of a ring close
`
`to a posterior leaflet 40. For example, in Figure 19C, ring 78 comprises two sectors: a
`
`rigid sector 102, for example comprising a solid metal; and a more flexible sector 104,
`
`5
`
`for example comprising a metal mesh. Many combinations of material properties and
`
`configurations that are optionally used in a ring such as 78 may be conceived by one
`
`skilled in the art upon perusal of the description herein. In some embodiments, such as
`
`in Figure 19D, ring 78 is of a uniformly flexible material.
`
`In embodiments, following full excision of mitral valve 26 from valve annulus
`
`IO
`
`34, a properly configured stapler is used to attach the valve to a ring-shaped
`
`component 78. For example, a Proximate Prolapse and Hemorrhoids (PPH) Stapler by
`
`Johnson and Johnson (not shown) may be used to staple a valve periphery edge 70 to
`
`a ring-shaped component 78.
`
`When ring 78 is substantially ~)Val (Figure 20B), the stapler gently bends oval
`
`15
`
`. ring-shaped component 78 into a circle (Figure 20C) during stapling. Upon removal
`
`of the stapler, oval ring 78 returns to oval shape (Figure 20B). To allow oval-to(cid:173)
`
`circular-to-oval transposition, such a ring-shaped component 78 optionally comprises
`
`a semi-rigid material, for example a metal mesh.
`
`20
`
`In embodiments, a cardiac valve is secured inside the lumen of a tubular wall
`
`as depicted in Figure 17B and 17D. In embodiments, the cardiac valve is secured over
`
`a distal end of the tubular implant as depicted in Figure 19A. In embodiments, the
`
`cardiac valve is secured abutting against a distal end of the tubular implant as depicted
`
`in Figures 17 A, l 7C, 18A, 18B, 18C, 18D, 19B, l 9C, 19D, 20A and 20C
`
`25
`
`In embodiments, a cardiac valve 26 is secured to the tubular wall 74, as
`
`depicted in Figure 21, for example with sutures 64.
`
`In embodiments, the proximal portion 76 of a tubular wall 74 is attached to the
`
`inner rim of the cardiac valve annulus 34, as depicted in Figure 15 or Figure 20A. As
`
`depicted in Figures 22A and 22C, in embodiments the proximal portion of the tubular
`
`30 wall 74 is attached above the inner rim of the cardiac valve annulus 34 so that at least
`
`a portion of the implant is located over the inner rim of the cardiac annulus 34, for
`
`example to a portion of an inner wall of the atrium 24 above the cardiac annulus 34
`
`(Figure 22A) or to a ring-shaped component 106 (such as a prior art annuloplasty
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 803 of 1441
`
`

`

`WO 2007/138572
`
`34
`
`PCT /IL2007 /000615
`
`ring) located above the inner rim of the cardiac valve annulus 34 (Figure 22C). In
`
`embodiments, the proximal portion 76 of the tubular wall 74 of the tubular implant is
`
`attached below the inner rim of the cardiac valve annulus 34, Figure 22B.
`
`As discussed hereinabove, many different shapes of ring-shaped components
`
`5
`
`78 are suitable for implementing the teachings of the present invention. In addition to
`
`the above, in Figure 23A is depicted a ring-shaped component having a rectangular
`
`cross-section that describes an ellipse. In Figure 23B is depicted a ring-shaped
`
`component having a circular cross-section that describes a circle that is bent and is not
`
`flat. In Figure 23C is depicted a flat ring-shaped component having an L-shaped
`
`10
`
`cross-section that describes a circle.
`
`In embodiments, the cross-sectional area of the lumen at the proximal end is
`
`substantially equal to the cross-sectional area of the lumen at the distal end, for
`
`example, as depicted in Figures 17 A-1 ?D. In embodiments, the cross-sectional area of
`
`the lumen at the proxjmal end is greater than the cross-sectional area of the lumen at
`
`15
`
`the distal end, as depicted in Figures 18A and 18B.
`
`In embodiments, such as depicted in Figure 17D, secured to the luminal
`
`surface (in non-depicted embodiments, secured to the outer surface) of the tubular
`
`wall (fashioned of woven polyester) is a series of rings or hoops 110 (e.g., of rigid
`
`titanium or nitinol wire) as reinforcement components, arranged coaxially with the
`
`20
`
`axis tubular wall. The series of loops provide the tubular wall with radial rigidity and
`
`also allow axial bendability without kinking or folding that would otherwise obstruct
`
`the lumen of the tubular wall. In embodiments, the rings flexibly elastic so as to
`
`provide a radial flexibility, that is allow elastic radial deformation without changing
`
`circumference or allowing collapse of the lumen. In Figure 17C, reinforcement
`
`25
`
`component 108 is a conical section helical spring.
`
`Embodiments, such as depicted in Figure 17E, are provided with a conical
`
`section helical spring 108 (e.g., of titanium or nitinol wire) as a reinforcement
`
`component encased within tubular wall 74. Tubular wall 74 comprises two layers 74a
`
`and 74b of serous tissue (peritoneum) with the respective basement layers facing each
`
`30
`
`other and sandwiching helical spring 108 therebetween, mutually secured with
`
`biological glue or other suitable adhesive. In such a way, the smooth serous layer of
`
`the serous tissue face outward in contact with blood while the tough basement layers
`
`hold helical spring 108. Helical spring 108 is sandwiched and glued between the
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 804 of 1441
`
`

`

`WO 2007/138572
`
`35
`
`PCT /IL2007 /000615
`
`serous layers when slightly lengthened and released only when dry so as to bias the
`
`entire construct to a shortened configuration, substantially pleating the serous tissue.
`
`In such a way, helical spring 108 provides, in part, not only radial flexibility as
`
`described above, but also both axial extensibility and axial bendability to the tubular
`
`5
`
`wall. Secured to the distal end of tubular wall 74 (by sutures) and engaging of the end
`
`of helical spring 108 is a slightly flexible and piercable ring-shaped component 78 of
`
`titanium mesh.
`
`In most of the embodiments discussed above, the teachings of the present
`
`invention have been discussed where a mitral valve is relocated by implantation of a
`
`10
`
`cylindrical tubular implant where the distal end and the proximal end of the tubular
`
`wall are substantially of similar size and shape. In embodiments, implants having
`
`tubular walls with other shapes are implanted including tubular implants that are
`
`frustoconical ( distal and proximal ends are not parallel).
`
`In embodiments where the teachings of the present invention are applied to
`
`15
`
`augmenting the tissue surrounding a mitral valve it is important that subsequent to
`
`deployment of the implant, the mitral valve has a rnitral lumen large enough to allow
`
`passage of sufficient blood. It is important to note that a person weighing between 60
`
`and 100 kg has a usual cardiac output of about 4 to 6 l blood / minute and about 15 l
`
`blood / minute during maximum effort. It is known that a mitral valve lumen having a
`
`20
`
`diameter of at least about 28 mm diameter is needed to transfer 15 l blood minute
`
`without undue stress. Thus, generally it is desirable that the implant be configured so
`
`that the diameter of the mitral valve lumen subsequent to implantation be at least
`
`about 28 nun in diameter. For example, in embodiments the edge of the implant to
`
`which the valve edge is secured is at least about 28 mm in diameter.
`
`25
`
`In the embodiments described above, the cardiac ( e.g., mitral) valve is first
`
`detached from the respective annulus, and then secured to an edge of an implant of the
`
`present invention. In embodiments, a cardiac valve is first secured to an edge of an
`
`implant and then detached from the respective annulus.
`
`In the embodiments described above, the cardiac (e.g., mitral) valve is
`
`30
`
`detached from the respective annulus substantially intact as a complete functioning
`
`unit where the leaflets of the valve are mutually associated through commissures of
`
`the valve as depicted in Figure 11. Such embodiments are exceptionally simple to
`
`implement. In embodiments, the cardiac valve is detached not intact, for example,
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 805 of 1441
`
`

`

`WO 2007/138572
`
`36
`
`PCT /IL2007 /000615
`
`each leaflet separately. In such embodiments, for example, each leaflet is secured to
`
`the edge of the implant separately. Such embodiments allow repair or replacement of
`
`a damaged leaflet.
`
`When implementing the teachings of the present inventions, the membranes of
`
`5
`
`an annuloplasty apparatus or the walls of a cardiac valve augmenting implants,
`
`whether as sheets with holes, annuli, tubes or other, may comprise any suitable
`
`material or combination of materials, whether synthetic or biological. Preferably at
`
`least one material from which an implant is fashioned is impermeable to prevent the
`
`flow of blood through the implant once implanted. Typically, the thickness of the
`
`l 0
`
`tubular wall is at least 0.05 millimeter at least about 0.1 millimeter and even at least
`
`about 0.2 millimeter. Typically, the thickness of the tubular wall is no more than
`
`about 2 millimeter, no more than about l millimeter and even no more than about 0.5
`
`millimeter.
`
`Typical synthetic materials suitable for fashioning a membrane of an
`
`15
`
`annuloplasty apparatus or a wall of a cardiac valve augmenting implant of the present
`
`invention
`
`include but are not
`
`limited to fluorinated hydrocarbons such as
`
`polytetrafluoroethylene, urethane, elastomer, polyamide, polyethylene, polyester (e.g.,
`
`Dacron®), silicon rubber and titanium mesh.
`
`Sources of typical biological materials suitable for fashioning a membrane of
`
`20
`
`an annuloplasty apparatus of a wall of a cardiac valve augmenting implant of the
`
`present invention include but are not limited to materials from a human source, an
`
`equine source, a porcine source or a bovine source. In embodiments, biological
`
`materials used for fashioning an implant of the present invention include but are not
`
`limited to autologous tissue, homologous tissue and heterologous tissue. Specific
`
`25
`
`examples include venous tissue, arterial tissue, serous tissue, dura mater, pleura,
`
`peritoneum, pericardium and aortic leaflet. In embodiments, the tissue is toughened,
`
`for example by crosslinking in the usual way.
`
`The present invention also provides for the manufacture of implants such as
`
`annuloplasty apparatus and cardiac valve augmenting implants such as described
`
`30
`
`herein. Thus according to the teachings of the present invention there is also provided
`
`for the use of a sheet of an implantable material ( as described hereinabove) for the
`
`manufacture of a cardiac valve augmenting implant, the implant including a wall
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 806 of 1441
`
`

`

`WO 2007/138572
`
`37
`
`PCT /IL2007 /000615
`
`comprising the material, the wall delimited by two edges each having a shape of a
`
`closed curve and defining a lumen.
`
`In embodiments, the wall is substantially annular. In embodiments, a first edge
`
`is a periphery of the wall and a second edge is a periphery of the hole of the wall.
`
`5
`
`In embodiments, the wall is substantially tubular. In embodiments, a first edge
`
`is a periphery of a proximal end of the wall and a second edge is a periphery of a
`
`distal end of the wall.
`
`In embodiments, the second edge is configured to be secured to an excised
`
`cardiac valve and a first edge is configured to be secured to a mitral valve seat, e.g., in
`
`l 0
`
`proximity of a mitral valve annulus.
`
`According to the teachings of the present invention there is also provided a
`
`method of producing a cardiac implant, comprising: a) providing a sheet of
`
`implantable material (as described hereinabove); and b) fashioning the material in the
`
`shape of a wall of the cardiac implant, the wall delimited by two edges each having a
`
`15
`
`shape of a closed curve and defining a lumen.
`
`In embodiments, the wall is substantially annular. In embodiments, a first edge
`
`is a periphery of the wall and a second edge is a periphery of the hole of the wall.
`
`In embodiments, the wall is substantially tubular. In embodiments, a first edge
`
`is a periphery of a proximal end of the wall and a second edge is a periphery of a
`
`20
`
`distal end of the wall.
`
`In embodiments, the second edge is configured to be secured to an excised
`
`cardiac valve and a first edge is configured to be secured to a mitral valve seat.
`
`While the description of methods and apparatus of the invention have been
`
`directed to restoring proper function to mitral valves, it will be clear to those familiar
`
`25 with the art, that the methods and apparatus are also applicable to restoring proper
`
`function to a tricuspid valve (not shown), in some cases with minor modification
`
`which one skilled in the art is able to formulate upon perusal of the specification.
`
`Further, while the description of methods and apparatus were directed to
`
`improperly functioning mitral valves with dysfunction of papillary muscle wall, it will
`
`30
`
`be clear to those familiar with the art, that the methods and apparatus are also
`
`applicable to any disorder causing improper closure of mitral valve including, inter
`
`alia: mitral valve prolapse;
`
`rheumatic heart disease; mitral annular calcification;
`
`cardiac tumors; congenital defects; endocarditis; atherosclerosis; hypertension; left
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 807 of 1441
`
`

`

`WO 2007/138572
`
`38
`
`PCT /IL2007 /000615
`
`ventricular enlargement; connective tissue disorders such as Marfan's syndrome; and
`
`untreated syphilis.
`
`The various embodiments of the present invention, especially the methods of
`
`augmenting tissue, have been described herein primarily with reference to treatment
`
`5
`
`of living human subjects. It is understood, however, that embodiments of the present
`
`invention are performed for the veterinary treatment of a non-human mammal,
`
`especially horses, cats, dogs, cows and pigs.
`
`The various embodiments of the present invention, especially the methods of
`
`augmenting tissue, have been described herein primarily with reference to treatment
`
`10
`
`of living subjects. It is understood that application of the present invention for training
`
`and educational purposes (as opposed to treating a condition) falls within the scope of
`
`the claims, whether on a living non-human subject or on a dead subject, whether on a
`
`human cadaver or on a non-human body, whether on an isolated cardiac valve, or on a
`
`valve in a heart isolated (at least partially) from a body, or on a body.
`
`15
`
`It is appreciated that certain features of the invention, which are, for clarity,
`
`described in the context of separate embodiments, may also be provided in
`
`combination in a single embodiment. Conversely, various features of the invention,
`
`which are, for brevity, described in the context of a single embodiment, may also be
`
`provided separately or in any suitable subcombination.
`
`20
`
`Although the invention has been described m conjunction with specific
`
`embodiments thereof, it is evident that many alternatives, modifications and variations
`
`will be apparent to those skilled in the art. Accordingly, it is intended to embrace all
`
`such alternatives, modifications and variations that fall within the spirit and broad
`
`scope of the appended claims. All publications, patents and patent applications
`
`25 mentioned in this specification are herein incorporated in their entirety by reference
`
`into the specification, to the same extent as if each individual publication, patent or
`
`patent application was specifically and individually indicated to be incorporated
`
`herein by reference. In addition, citation or identification of any reference in this
`
`application shall not be construed as an admission that such reference is available as
`
`30
`
`prior art to the present invention.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 808 of 1441
`
`

`

`WO 2007/138572
`
`39
`
`PCT /IL2007 /000615
`
`WHAT IS CLAIMED IS:
`
`I.
`
`An annuloplasty apparatus comprising:
`
`a) a substantially complete ring defining a ring lumen having:
`
`an inner portion configured to be operatively associated with a lumen
`
`of an in vivo cardiac valve;
`
`an outer portion configured to be operatively associated with a
`
`periphery of said lumen of said cardiac valve; and
`
`b) a membrane functionally associated with said ring, said membrane at least
`
`partially covering said ring lumen around the entire periphery of said ring
`
`lumen in a plane substantially parallel to a plane passing radially through said
`
`ring.
`
`2.
`
`The apparatus according to claim I, wherein said membrane is
`
`provided with a membrane opening through said ring lumen.
`
`3.
`
`The apparatus according to claim 2, wherein said membrane opening is
`
`located substantially in the center of said ring lumen.
`
`4.
`
`The apparatus according to claim 2, wherein said membrane opening is
`
`located off-center of said ring lumen.
`
`5.
`
`The apparatus according to claim 2, wherein said membrane opening
`
`has an area of at least about 10% of the area of said ring lumen.
`
`6.
`
`The apparatus according to claim 1, wherein at least a portion of said
`
`ring includes a portion being substantially covered by said membrane.
`
`7.
`
`The apparatus according to claim I, wherein said membrane is at least
`
`about 0.2 millimeters thick.
`
`8.
`
`The apparatus according to claim 1, wherein said membrane is no more
`
`than about 0.5 millimeters thick.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 809 of 1441
`
`

`

`WO 2007/138572
`
`40
`
`PCT /IL2007 /000615
`
`9.
`
`The apparatus according to claim 1, wherein said ring has height of no
`
`more than about 5.0 millimeters.
`
`10.
`
`The apparatus according to claim 1, wherein said ring has height of at
`
`least about 1.0 millimeter.
`
`11.
`
`A method for performing an annuloplasty procedure m a heart,
`
`comprising:
`
`a) providing a substantially continuous ring defining a ring lumen and
`
`functionally associating a membrane to said ring so that said membrane covers
`
`a portion of said ring lumen;
`
`b) detaching at least a portion of a first cardiac valve leaflet from a periphery
`
`of a lumen of an in vivo cardiac valve, said valve including at least two
`
`cardiac valve leaflets extending from said periphery of said cardiac valve;
`
`c) securing said continuous ring to said periphery of said cardiac valve lumen;
`
`and
`
`d) attaching a detached edge of said cardiac valve leaflet to said membrane
`
`thereby restoring valve function by increasing the dimensions of said leaflet.
`
`12.
`
`The method according to claim 11, further comprising:
`
`e) modifying said membrane to decrease said covered portion of said ring
`
`lumen; and
`
`13.
`
`The method according to claim 11, said membrane at least partially
`
`covering said ring lumen around the entire periphery of said ring lumen in a plane
`
`substantially parallel to a plane passing radially through said ring.
`
`14.
`
`The method according to claim 11, wherein said leaflet is detached
`
`from said periphery substantially entirely.
`
`15.
`
`The method according to claim 11, wherein said attaching of said
`
`detached edge of said leaflet is proximate to a luminal edge of said membrane.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 810 of 1441
`
`

`

`WO 2007/138572
`
`41
`
`PCT /IL2007 /000615
`
`16.
`
`The method according to claim 11, wherein prior to said attaching of
`
`said detached edge of said first leaflet, said membrane is cut so as to expose a second
`
`of said cardiac leaflets.
`
`1 7.
`
`The method according to claim 11, wherein said membrane is shaped
`
`to cover said second cardiac leaflet.
`
`18.
`
`A method of augmenting the tissue surrounding a cardiac valve,
`
`comprising:
`
`a) excising leaflets of a cardiac valve with an incision having a shape of a
`
`closed curve so as to define a valve seat edge of said incision and a valve
`
`periphery edge of said incision;
`b) providing an implant including a wall, the wall delimited by two edges each
`in the shape of a closed curve and defining a lumen as a cardiac valve
`
`augmenting implant;
`
`c) securing a first portion of said implant to said valve seat edge at a plurality
`
`of locations; and
`
`d) securing a second portion of said implant to said valve periphery edge at a
`
`plurality of locations,
`
`thereby augmenting a surface area of tissue surrounding said cardiac valve with said
`
`implant.
`
`19.
`
`The method of claim 18, wherein said implant is substantially annular
`
`having an outer periphery and a hole defining said lumen, wherein said first portion is
`
`nearer to said outer periphery than to a periphery of said hole and wherein said second
`
`portion is nearer to said periphery of said hole than to said outer periphery.
`
`20.
`
`The method of claim 18, wherein said implant is substantially tubular
`
`having a distal end and a proximal end, wherein said first portion is nearer to said
`
`proximal end than to said distal end and wherein said second portion is nearer to said
`
`distal end than to said proximal end.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 811 of 1441
`
`

`

`WO 2007/138572
`
`42
`
`PCT /IL2007 /000615
`
`21.
`
`The method of claim 18, wherein said securing said first portion of
`
`said implant to said valve seat edge around a plurality of locations of said proximal
`
`overlap region is performed substantially simultaneously for said plurality of
`
`locations.
`
`22.
`
`The method of claim 18, wherein:
`
`said excising;
`
`said placing said implant to define said proximal overlap zone; and
`
`said securing said first portion of said implant to said valve seat edge
`
`are substantially simultaneous.
`
`23.
`
`The method of claim 18, wherein said relocation of said cardiac valve
`
`improves coaptation of leaflets of said cardiac valve.
`
`24.
`
`A cardiac valve augmenting implant comprising:
`
`a) a substantially tubular wall defining a lumen, comprising a proximal portion
`
`with a proximal end, a distal portion with a distal end, an outer surface and a
`
`luminal surface; and
`
`b) associated with said distal end, a ring-shaped component thicker in the
`
`radial direction than said wall
`
`configured for implantation in a mammalian heart.
`
`25.
`
`The implant of claim 24, wherein said proximal portion of said tubular
`
`wall is configured for attachment to a cardiac valve annulus.
`
`26.
`
`The implant of claim 24, wherein said ring-shaped component 1s
`
`configured for attachment of the periphery of a cardiac valve.
`
`27.
`
`The implant according to claim 24, wherein said proximal portion of
`
`said tubular wall is radially expandable.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 812 of 1441
`
`

`

`WO 2007/138572
`
`43
`
`PCT /IL2007 /000615
`
`28.
`
`The implant according to claim 24, wherein said tubular wall is axially
`
`bendable.
`
`29.
`
`The implant according to claim 24, wherein said tubular wall is axially
`
`extensible.
`
`30.
`
`The implant according to claim 24, wherein said tubular wall 1s
`
`substantially radially non-expandable.
`
`31.
`
`The implant according to claim 24, wherein said tubular wall 1s
`
`substantially radially non-collapsible.
`
`32.
`
`The implant of claim 24, further comprising at least one reinforcement
`
`component functionally associated with said tubular wall.
`
`33.
`
`A method for relocating a cardiac valve distally to a cardiac valve
`
`annulus, the method comprising:
`
`a) providing a substantially tubular implant comprising a substantially tubular
`
`wall defining a lumen, said apparatus having a proximal portion and a distal
`
`portion;
`
`b) detaching a cardiac valve from a cardiac valve annulus located between an
`
`atrium and a ventricle of a subject;
`
`c) securing said cardiac valve to said distal portion of said tubular implant; and
`
`d) securing said proximal portion of said tubular implant in the proximity of
`
`said cardiac valve annulus so that said valve is distal to said valve annulus,
`
`thereby providing fluid communication between said atrium and said ventricle
`
`through said lumen and through said cardiac valve.
`
`34.
`
`The method according to claim 33, wherein said cardiac valve 1s
`
`detached substantially intact.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 813 of 1441
`
`

`

`WO 2007/138572
`
`44
`
`PCT /IL2007 /000615
`
`35.
`
`The use of a sheet of implantable material for the manufacture of a
`
`cardiac valve augmenting implant, said implant including a wall comprising said
`
`material, said wall delimited by two edges each having a shape of a closed curve and
`
`defining a lumen.
`
`36.
`
`The use of claim 35, wherein said wall is substantially annular.
`
`37.
`
`The use of claim 36, wherein a first said edge is a periphery of said
`
`wall and a second said edge is a periphery of a hole of said wall.
`
`38.
`
`The use of claim 35, wherein said wall is substantially tubular.
`
`39.
`The use of claim 38, wherein a first said edge is a periphery of a
`proximal end of said wall and a second said edge is a periphery of a distal end of said
`wall.
`
`40.
`
`The use of claim 35, wherein a second said edge is configured to be
`
`secured to an excised cardiac valve and a first said edge is configured to be secured to
`
`a mitral valve seat.
`
`41.
`
`A method of producing a cardiac implant, comprising:
`
`a) providing an sheet of implantable material; and
`
`b) fashioning said material in the shape of a wall of the cardiac implant, said
`
`wall delimited by two edges each having a shape of a closed curve and
`
`defining a lumen.
`
`42.
`
`The method of claim 41, wherein said wall is substantially annular.
`
`43.
`
`The method of claim 42, wherein a first said edge is a periphery of said
`
`wall and a second said edge is a periphery of a hole of said wall.
`
`44.
`
`The method of claim 41, wherein said wall is substantially tubular.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 814 of 1441
`
`

`

`WO 2007/138572
`
`45
`
`PCT /IL2007 /000615
`
`45.
`
`The method of claim 44, wherein a first said edge is a periphery of a
`
`proximal end of said wall and a second said edge is a periphery of a distal end of said
`
`wall.
`
`46.
`
`The method of claim 41, wherein a second said edge is configured to
`
`be secured to an excised cardiac valve and a first said edge is configured to be secured
`
`to a mitral valve seat.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 815 of 1441
`
`

`

`WO 2007/138572
`
`PCT /IL2007 /000615
`
`1/25
`
`14
`
`10
`
`Fig. 1 (Prior Art)
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 816 of 1441
`
`

`

`Q g
`~ N
`
`Q
`
`(/1
`i,(cid:173)
`~
`Q
`Q
`
`Fig. 2b (Prior Art)
`
`("".l
`"d
`
`N
`-..J
`(JI
`00
`(,;,i
`i,(cid:173)
`~
`Q
`Q
`N
`0
`~
`
`~ CJ'I
`
`:\.~--33
`
`40
`
`34 \
`
`24
`
`26
`
`/10
`
`Fig. 2a (Prior Art)
`
`26
`)
`
`34
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 817 of 1441
`
`

`

`Q g
`~ N
`
`Q
`
`(/1
`i,(cid:173)
`~
`Q
`Q
`
`("".l
`"d
`
`N
`-..J
`(JI
`00
`(,;,i
`i,(cid:173)
`~
`Q
`Q
`N
`0
`~
`
`CJ'1
`~
`w
`
`5° Fig. 3b (Prior Art)
`)
`
`Fig. 3a (Prior Art)
`
`40
`
`34 \
`
`24
`
`26
`
`26
`)
`
`34
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 818 of 1441
`
`

`

`WO 2007/138572
`
`PCT /IL2007 /000615
`
`4/25
`
`36
`
`'
`
`26
`
`/
`
`,,
`
`52
`
`34
`
`Fig. 4
`
`Edwards Lifesciences Corporation, et al. Exhi