Prosthetic valve with pivoting tissue anchor portions

Description

FIELD OF THE INVENTION

Some embodiments of the present invention relate in general to valve replacement. More specifically, some embodiments of the present invention relate to prosthetic valves for replacement of a cardiac valve.

BACKGROUND

Ischemic heart disease causes regurgitation of a heart valve by the combination of ischemic dysfunction of the papillary muscles, and the dilatation of the ventricle that is present in ischemic heart disease, with the subsequent displacement of the papillary muscles and the dilatation of the valve annulus.

Dilatation of the annulus of the valve prevents the valve leaflets from fully coapting when the valve is closed. Regurgitation of blood from the ventricle into the atrium results in increased total stroke volume and decreased cardiac output, and ultimate weakening of the ventricle secondary to a volume overload and a pressure overload of the atrium.

SUMMARY OF THE INVENTION

For some embodiments of the present invention, an implant is provided having a tubular portion, an upstream support portion and one or more flanges. The implant is percutaneously deliverable to a native heart valve in a compressed state, and is expandable at the native valve. The implant and its delivery system facilitate causing the upstream support portion and the flanges to protrude radially outward from the tubular portion without expanding the tubular portion. Expansion of the tubular portion brings the upstream support portion and the flanges closer together, for securing the implant at the native valve by sandwiching tissue of the native valve between the upstream support portion and the flanges.

In accordance with an embodiment of the present invention, an apparatus is provided for use with a native valve that is disposed between an atrium and a ventricle of a heart of a subject, the apparatus including: a valve frame, including a tubular portion that circumscribes a longitudinal axis of the valve frame so as to define a lumen along the axis, the tubular portion defining a plurality of valve-frame coupling elements disposed circumferentially around the longitudinal axis; a plurality of prosthetic leaflets, coupled to the frame, disposed within the lumen, and arranged to provide unidirectional flow of blood from an upstream end of the lumen to a downstream end of the lumen; an outer frame: including a ring defined by a pattern of alternating peaks and troughs, the peaks being longitudinally closer to the upstream end than to the downstream end, and the troughs being longitudinally closer to the downstream end than to the upstream end, and the pattern of the ring having an amplitude longitudinally between the peaks and the troughs, including a plurality of legs, each of the legs coupled to the ring at a respective trough, and shaped to define a plurality of outer-frame coupling elements, each of the outer-frame coupling elements (i) coupled to the ring at a respective peak, and (ii) fixed with respect to a respective valve-frame coupling element, and: the tubular portion has (i) a compressed state in which the tubular portion has a compressed diameter, and (ii) an expanded state in which the tubular portion has an expanded diameter that is greater than the compressed diameter, and the fixation of the outer-frame coupling elements to the valve-frame coupling elements is such that compression of the tubular portion from the expanded state toward the compressed state such that the valve-frame coupling elements pull the outer-frame coupling elements radially inward: (i) reduces a circumferential distance between each of the outer-frame coupling elements and its adjacent outer-frame coupling elements, and (ii) increases the amplitude of the pattern of the ring.

In an embodiment, the ring circumscribes the tubular portion.

In an embodiment, the valve-frame coupling elements are disposed circumferentially around the longitudinal axis between the upstream end and the downstream end but not at the upstream end nor at the downstream end.

In an embodiment, the upstream support portion includes one or more fabric pockets disposed circumferentially, each pocket of the one or more pockets having an opening that faces a downstream direction.

In an embodiment, the outer frame is coupled to the valve frame only via the fixation of the outer-frame coupling elements to the respective valve-frame coupling elements.

In an embodiment, the apparatus further includes an upstream support portion that includes a plurality of arms that extend radially from the tubular portion, and the upstream support portion has (i) a constrained-arm state, and (ii) a released-arm state in which the arms extend radially outward from the tubular portion, each leg has a tissue-engaging flange that has (i) a constrained-flange state, and (ii) a released-flange state in which the flange extends radially outward from the tubular portion, and the apparatus has an intermediate state in which (i) the tubular portion is in its compressed state, (ii) the upstream support portion is in its released-arm state, and (iii) the legs are in their released-flange state.

In an embodiment, the apparatus includes an implant that includes the valve frame, the leaflets, and the outer frame, and the apparatus further includes a tool: including a delivery capsule dimensioned (i) to house and retain the implant in a compressed state of the implant in which (a) the tubular portion is in its compressed state, (b) the upstream support portion is in its constrained-arm state, and (c) the legs are in their constrained-flange state, and (ii) to be advanced percutaneously to the heart of the subject while the implant is housed and in its compressed state, and operable from outside the subject to: transition the implant from its compressed state into the intermediate state while retaining the tubular portion in its compressed state, and subsequently, expand the tubular portion toward its expanded state.

In an embodiment, the tool is operable from outside the subject to transition the implant from its compressed state into the intermediate state by (i) releasing the legs into their released-flange state, while retaining the tubular portion in its compressed state, and (ii) subsequently, releasing the upstream support portion into its released-arm state, while retaining the tubular portion in its compressed state.

In an embodiment, the tool is operable from outside the subject to transition the implant from its compressed state into the intermediate state by (i) releasing the upstream support portion into its released-arm state, while retaining the tubular portion in its compressed state, and (ii) subsequently, releasing the legs into their released-flange state, while retaining the tubular portion in its compressed state.

In an embodiment, the fixation of the outer-frame coupling elements to the valve-frame coupling elements is such that, when the apparatus is in its intermediate state, expansion of the tubular portion from its compressed state toward its expanded state moves the flanges longitudinally away from the valve-frame coupling elements.

In an embodiment, the fixation of the outer-frame coupling elements to the valve-frame coupling elements is such that, when the apparatus is in its intermediate state, expansion of the tubular portion from a compressed state toward an expanded state reduces the amplitude of the pattern of the ring and passes the flanges between the arms.

In an embodiment, the upstream support portion further includes a covering that covers the arms to form an annular shape in the released-arm state, and, when the apparatus is in its intermediate state, expansion of the tubular portion from its compressed state toward its expanded state presses the flanges onto the covering.

In an embodiment, in the compressed state of the tubular portion, a downstream end of each leg of the tubular portion is longitudinally closer than the valve-frame coupling elements to the downstream end, and the flange of each leg is disposed longitudinally closer than the valve-frame coupling elements to the upstream end.

In an embodiment, in the expanded state of the tubular portion, the downstream end of each leg is longitudinally closer than the valve-frame coupling elements to the downstream end, and the flange of each leg is disposed longitudinally closer than the valve-frame coupling elements to the upstream end.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve of a heart of a subject is provided, the apparatus having an implant that includes: a valve frame that includes a tubular portion that circumscribes a longitudinal axis of the valve frame so as to define a lumen along the axis, the tubular portion having an upstream end, a downstream end, a longitudinal length therebetween, and a diameter transverse to the longitudinal axis; a valve member, coupled to the tubular portion, disposed within the lumen, and arranged to provide unidirectional upstream-to-downstream flow of blood through the lumen; an upstream support portion, coupled to the tubular portion; and an outer frame, coupled to the tubular portion, and including a tissue-engaging flange, and: the implant has a first state and a second state, in both the first state and the second state, (i) the upstream support portion extends radially outward from the tubular portion, and (ii) the tissue-engaging flange extends radially outward from the tubular portion, and the tubular portion, the upstream support portion, and the outer frame are arranged such that transitioning of the implant from the first state toward the second state: increases the diameter of the tubular portion by a diameter-increase amount, decreases the length of the tubular portion by a length-decrease amount, and moves the flange a longitudinal distance toward or toward-and-beyond the upstream support portion, the distance being greater than the length-decrease amount.

In an embodiment of the present invention, the tubular portion, the upstream support portion, and the outer frame may be arranged such that the longitudinal distance is more than 20 percent greater than the length-decrease amount.

In an embodiment, the tubular portion, the upstream support portion, and the outer frame may be arranged such that the longitudinal distance is more than 30 percent greater than the length-decrease amount.

In an embodiment, the tubular portion, the upstream support portion, and the outer frame may be arranged such that the longitudinal distance is more than 40 percent greater than the length-decrease amount.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve that is disposed between an atrium and a ventricle of a heart of a subject is provided, the apparatus including: a valve frame, including a tubular portion that circumscribes a longitudinal axis of the valve frame so as to define a lumen along the axis; a plurality of prosthetic leaflets, coupled to the frame, disposed within the lumen, and arranged to provide unidirectional flow of blood from an upstream end of the lumen to a downstream end of the lumen; an outer frame, including: a ring defined by a pattern of alternating peaks and troughs: the peaks being longitudinally closer than the troughs to the upstream end, the peaks being fixed to respective sites of the tubular portion at respective coupling points disposed circumferentially around the longitudinal axis, and the pattern of the ring having an amplitude longitudinally between the peaks and the troughs; and a plurality of legs, each of the legs coupled to the ring at a respective trough, and: the tubular portion has (i) a compressed state in which the tubular portion has a compressed diameter, and (ii) an expanded state in which the tubular portion has an expanded diameter that is greater than the compressed diameter, and the fixation of the peaks to the respective sites of the tubular portion is such that compression of the tubular portion from the expanded state toward the compressed state such that the respective sites of the tubular portion pull the peaks radially inward via radially-inward tension on the coupling points: (i) reduces a circumferential distance between each of the coupling points and its adjacent coupling points, and (ii) increases the amplitude of the pattern of the ring.

In an embodiment, the outer frame may be coupled to the valve frame only via the fixation of the peaks to the respective sites of the tubular portion at the respective coupling points.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve that is disposed between an atrium and a ventricle of a heart of a subject is provided, the apparatus including: a valve frame, including a tubular portion that circumscribes a longitudinal axis of the valve frame so as to define a lumen along the axis, the valve frame defining a plurality of valve-frame coupling elements disposed circumferentially around the longitudinal axis; a plurality of prosthetic leaflets, coupled to the frame, disposed within the lumen, and arranged to provide unidirectional flow of blood from an upstream end of the lumen to a downstream end of the lumen; an outer frame: including a ring defined by a pattern of alternating peaks and troughs, the peaks being longitudinally closer to the upstream end than to the downstream end, and the troughs being longitudinally closer to the downstream end than to the upstream end, and the pattern of the ring having an amplitude longitudinally between the peaks and the troughs, including a plurality of legs, each of the legs coupled to the ring at a respective trough, and shaped to define a plurality of outer-frame coupling elements, each of the outer-frame coupling elements (i) coupled to the ring at a respective peak, and (ii) fixed with respect to a respective valve-frame coupling element, and: the tubular portion has (i) a compressed state in which the tubular portion has a compressed diameter, and (ii) an expanded state in which the tubular portion has an expanded diameter that is greater than the compressed diameter, and the fixation of the outer-frame coupling elements with respect to the valve-frame coupling elements is such that compression of the tubular portion from the expanded state toward the compressed state (i) pulls the outer-frame coupling elements radially inward via radially-inward pulling of the valve-frame coupling elements on the outer-frame coupling elements, (ii) reduces a circumferential distance between each of the outer-frame coupling elements and its adjacent outer-frame coupling elements, and (iii) increases the amplitude of the pattern of the ring, without increasing a radial gap between the valve frame and the ring by more than 1.5 mm.

In an embodiment, the outer frame may be coupled to the valve frame only via the fixation of the outer-frame coupling elements to the respective valve-frame coupling elements.

There is further provided, in accordance with an embodiment of the present invention, an apparatus for use with a native valve that is disposed between an atrium and a ventricle of a heart of a subject is provided, the apparatus including: a valve frame, including a tubular portion that circumscribes a longitudinal axis of the valve frame so as to define a lumen along the axis; a plurality of prosthetic leaflets, coupled to the frame, disposed within the lumen, and arranged to provide unidirectional flow of blood from an upstream end of the lumen to a downstream end of the lumen; an outer frame, including: a ring defined by a pattern of alternating peaks and troughs: the peaks being longitudinally closer than the troughs to the upstream end, the peaks being fixed to respective sites of the tubular portion at respective coupling points disposed circumferentially around the longitudinal axis, and the pattern of the ring having an amplitude longitudinally between the peaks and the troughs; and a plurality of legs, each of the legs coupled to the ring at a respective trough, and: the tubular portion has (i) a compressed state in which the tubular portion has a compressed diameter, and (ii) an expanded state in which the tubular portion has an expanded diameter that is greater than the compressed diameter, and the fixation of the peaks to the respective sites of the tubular portion is such that compression of the tubular portion from the expanded state toward the compressed state (i) pulls the peaks radially inward via radially-inward pulling of the respective sites of the tubular portion on the peaks, (ii) reduces a circumferential distance between each of the coupling points and its adjacent coupling points, and (iii) increases the amplitude of the pattern of the ring, without increasing a radial gap between the valve frame and the ring by more than 1.5 mm.

In an embodiment, the outer frame may be coupled to the valve frame only via the fixation of the peaks to the respective sites of the tubular portion at the respective coupling points.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve disposed between an atrium and a ventricle of a heart of a subject is provided, the apparatus including: a valve frame, including a tubular portion that circumscribes a longitudinal axis of the valve frame so as to define a lumen along the axis, the tubular portion having an upstream end, a downstream end, and defining a plurality of valve-frame coupling elements disposed circumferentially around the longitudinal axis between the upstream end and the downstream end but not at the upstream end nor at the downstream end; a plurality of prosthetic leaflets, disposed within the lumen, and arranged to provide unidirectional flow of blood through the lumen; an outer frame: including a ring defined by a pattern of alternating peaks and troughs, the peaks being longitudinally closer to the upstream end than to the downstream end, and the troughs being longitudinally closer to the downstream end than to the upstream end, including a plurality of legs, each of the legs coupled to the ring at a respective trough, and shaped to define a plurality of outer-frame coupling elements, each of the outer-frame coupling elements (i) coupled to the ring at a respective peak, and (ii) fixed with respect to a respective valve-frame coupling element at a respective coupling point, and: the tubular portion has (i) a compressed state in which the tubular portion has a compressed diameter, and (ii) an expanded state in which the tubular portion has an expanded diameter that is greater than the compressed diameter, and expansion of the tubular portion from the compressed state toward the expanded state (i) increases a circumferential distance between each of the outer-frame coupling elements and its adjacent outer-frame coupling elements, and (ii) moves the plurality of legs in a longitudinally upstream direction with respect to the tubular portion.

In an embodiment, the outer frame may be coupled to the valve frame only via the fixation of the outer-frame coupling elements to the respective valve-frame coupling elements.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve disposed between an atrium and a ventricle of a heart of a subject is provided, the apparatus including: a valve frame, including a tubular portion that circumscribes a longitudinal axis of the valve frame so as to define a lumen along the axis, the tubular portion having an upstream end and a downstream end; a plurality of prosthetic leaflets, disposed within the lumen, and arranged to provide unidirectional flow of blood through the lumen; an outer frame, including: a ring defined by a pattern of alternating peaks and troughs: the peaks being longitudinally closer than the troughs to the upstream end, the peaks being fixed to respective sites of the tubular portion at respective coupling points disposed circumferentially around the longitudinal axis between the upstream end and the downstream end but not at the upstream end nor the downstream end; and a plurality of legs, each of the legs coupled to the ring at a respective trough, and: the tubular portion has (i) a compressed state in which the tubular portion has a compressed diameter, and (ii) an expanded state in which the tubular portion has an expanded diameter that is greater than the compressed diameter, and expansion of the tubular portion from the compressed state toward the expanded state (i) increases a circumferential distance between each of the coupling points and its adjacent coupling points, and (ii) moves the plurality of legs in a longitudinally upstream direction with respect to the tubular portion.

In an embodiment, the outer frame may be coupled to the valve frame only via the fixation of the peaks to the respective sites of the tubular portion at the respective coupling points.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve of a heart of a subject is provided, the apparatus including: a frame assembly, having an upstream end and a downstream end, and a central longitudinal axis therebetween, and including: a valve frame, including: a tubular portion having an upstream end and a downstream end, and shaped to define a lumen therebetween, and an upstream support portion, extending from the upstream end of the tubular portion; and at least one leg, coupled to the valve frame at a coupling point, and having a tissue-engaging flange; and a valve member disposed within the lumen, and configured to facilitate one-way liquid flow through the lumen from the upstream end of the tubular portion to the downstream end of the tubular portion, and the frame assembly: has a compressed state, for percutaneous delivery to the heart, in which the tubular portion has a compressed diameter, is biased to assume an expanded state in which the tubular portion has an expanded diameter that is greater than the compressed diameter, and is configured such that increasing the diameter of the tubular portion toward the expanded diameter causes longitudinal movement: of the upstream support portion toward the coupling point, and of the tissue-engaging flange away from the coupling point.

In an embodiment: the apparatus includes an implant that includes the frame assembly and the valve member, and the apparatus further includes a tool: including a delivery capsule dimensioned (i) to house and retain the implant in the compressed state, and (ii) to be advanced percutaneously to the heart of the subject while the implant is housed and in the compressed state, and operable from outside the subject to facilitate an increase of the diameter of the tubular portion from the compressed diameter toward the expanded diameter such that the increase of the diameter actuates longitudinal movement: of the upstream support portion toward the coupling point, and of the tissue-engaging flange away from the coupling point.

In an embodiment, the frame assembly may be configured such that increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state causes longitudinal movement of the upstream end of the tubular portion toward the coupling point.

In an embodiment, the coupling point is disposed closer to the downstream end of the frame assembly than are either the tissue-engaging flange or the upstream support portion.

In an embodiment, in the expanded state of the frame assembly, the leg extends away from the central longitudinal axis.

In an embodiment, the expanded state of the frame assembly may be a fully-expanded state of the frame assembly, the leg is expandable into an expanded state of the leg, independently of increasing the diameter of the tubular portion, and in the expanded state of the leg, the leg extends away from the central longitudinal axis.

In an embodiment, in the expanded state of the frame assembly, the leg extends away from the central longitudinal axis, and in the compressed state of the frame assembly, the leg is generally parallel with the central longitudinal axis.

In an embodiment, the frame assembly may be configured such that the longitudinal movement of the tissue-engaging flange away from the coupling point is a translational movement of the tissue-engaging flange that does not include rotation of the tissue-engaging flange.

In an embodiment, the frame assembly may be configured such that increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state causes 1-20 mm of longitudinal movement of the tissue-engaging flange away from the coupling point.

In an embodiment, the frame assembly may be configured such that increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state causes 1-20 mm of longitudinal movement of the upstream support portion toward the coupling point.

In an embodiment, the frame assembly may be configured such that increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state reduces a distance between the upstream support portion and the tissue-engaging flange by 5-30 mm.

In an embodiment, the frame assembly may be configured such that increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state moves the tissue-engaging flange longitudinally past the upstream support portion.

In an embodiment, the tubular portion may be defined by a plurality of cells of the valve frame, and increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state: includes (i) increasing a width, orthogonal to the longitudinal axis of the frame assembly, of each cell, and (ii) reducing a height, parallel with the longitudinal axis of the frame assembly, of each cell, and causes longitudinal movement of the upstream support portion toward the coupling point by reducing a height, parallel with the longitudinal axis of the frame assembly, of the tubular portion, by reducing the height of each cell.

In an embodiment, the leg is disposed on an outside of the tubular portion.

In an embodiment, the at least one leg includes a plurality of legs, the coupling point includes a plurality of coupling points, and the frame assembly includes a leg frame that circumscribes the tubular portion, includes the plurality of legs, and is coupled to the valve frame at the plurality of coupling points, such that the plurality of legs is distributed circumferentially around the tubular portion.

In an embodiment, the plurality of coupling points is disposed circumferentially around the frame assembly on a transverse plane that is orthogonal to the longitudinal axis of the frame assembly.

In an embodiment, the plurality of legs may be coupled to the valve frame via a plurality of struts, each strut having a first end that is coupled to a leg of the plurality of legs, and a second end that is coupled to a coupling point of the plurality of coupling points, in the compressed state of the frame assembly, being disposed at a first angle in which the first end is disposed closer to the downstream end of the frame assembly than is the second end, and being deflectable with respect to the coupling point of the plurality of coupling points, such that increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state causes the strut to deflect to a second angle in which the first end is disposed further from the downstream end of the frame assembly than is the first end in the compressed state of the frame assembly.

In an embodiment, the leg frame may be structured such that each leg of the plurality of legs is coupled to two struts of the plurality of struts, and two struts of the plurality of struts are coupled to each coupling point of the plurality of coupling points.

In an embodiment, the leg may be coupled to the valve frame via a strut, the strut having a first end that is coupled to the leg, and a second end that is coupled to the coupling point, in the compressed state of the frame assembly, being disposed at a first angle in which the first end is disposed closer to the downstream end of the frame assembly than is the second end, and being deflectable with respect to the coupling point, such that increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state causes the strut to deflect to a second angle in which the first end is disposed further from the downstream end of the frame assembly than is the first end in the compressed state of the frame assembly.

In an embodiment, the at least one leg includes at least a first leg and a second leg.

In an embodiment, the first leg and the second leg are both coupled to the valve frame at the coupling point.

In an embodiment, the first leg may be coupled to the coupling point via a respective first strut, and the second leg is coupled to the coupling point via a respective second strut.

In an embodiment, the first and second legs, the first and second struts, and the coupling point are arranged such that, in the expanded state of the frame assembly: the coupling point is disposed, circumferentially with respect to the tubular portion, between the first strut and the second strut, the first strut is disposed, circumferentially with respect to the tubular portion, between the coupling point and the first leg, and the second strut is disposed, circumferentially with respect to the tubular portion, between the coupling point and the second leg.

In an embodiment, the coupling point includes at least a first coupling point and a second coupling point.

In an embodiment, the leg is coupled to the valve frame at the first coupling point and at the second coupling point.

In an embodiment, the leg may be coupled to the first coupling point via a respective first strut, and to the second coupling point via a respective second strut.

In an embodiment, the first and second legs, the first and second struts, and the coupling point are arranged such that, in the expanded state of the frame assembly: the leg is disposed, circumferentially with respect to the tubular portion, between the first strut and the second strut, the first strut is disposed, circumferentially with respect to the tubular portion, between the leg and the first coupling point, and the second strut is disposed, circumferentially with respect to the tubular portion, between the leg and the second coupling point.

In an embodiment, in the expanded state of the frame assembly, the upstream support portion extends radially outward from the tubular portion.

In an embodiment, the expanded state of the frame assembly is a fully-expanded state of the frame assembly, the upstream support portion is expandable into an expanded state of the upstream support portion, independently of increasing the diameter of the tubular portion, and in the expanded state of the upstream support portion, the upstream support portion extends radially outward from the tubular portion.

In an embodiment, in the compressed state of the frame assembly, the upstream support portion is generally tubular, collinear with the tubular portion, and disposed around the central longitudinal axis.

In an embodiment, in the expanded state of the frame assembly, an inner region of the upstream support portion extends radially outward from the tubular portion at a first angle with respect to the tubular portion, and an outer region of the upstream support portion extends, from the inner region of the upstream support portion, further radially outward from the tubular portion at a second angle with respect to the tubular portion, the second angle being smaller than the first angle.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve of a heart of a subject is provided, the apparatus including a frame assembly, having an upstream end and a downstream end, and a central longitudinal axis therebetween, and including: an inner frame including an inner-frame tubular portion that circumscribes the central longitudinal axis, has an upstream end and a downstream end, and defines a channel therebetween, the inner frame defining a plurality of inner-frame couplings disposed circumferentially at a longitudinal location of the inner frame, an outer frame including an outer-frame tubular portion that coaxially circumscribes at least a portion of the inner-frame tubular portion, the outer frame defining a plurality of outer-frame couplings disposed circumferentially at a longitudinal location of the outer frame, and a plurality of connectors, each connector connecting a respective inner-frame coupling to a respective outer-frame coupling; a liner, disposed over at least part of the inner-frame tubular portion; and a plurality of prosthetic leaflets, coupled to the inner-frame tubular portion and disposed within the channel, and: the frame assembly: (i) is compressible by a radially-compressive force into a compressed state in which the inner frame is in a compressed state thereof and the outer frame is in a compressed state thereof, (ii) is configured, upon removal of the radially-compressive force, to automatically expand into an expanded state thereof in which the inner frame is in an expanded state thereof and the outer frame is in an expanded state thereof, in the expanded state of the frame assembly, the prosthetic leaflets are configured to facilitate one-way fluid flow, in a downstream direction, through the channel, and the connection of the inner-frame couplings to the respective outer-frame couplings is such that expansion of the frame assembly from the compressed state to the expanded state causes the inner-frame tubular portion to slide longitudinally in a downstream direction with respect to the outer-frame tubular portion.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve disposed between an atrium and a ventricle of a heart of a subject is provided, the apparatus including: a tubular portion, having an upstream portion that includes an upstream end, and a downstream portion that includes a downstream end, and shaped to define a lumen between the upstream portion and the downstream portion; a plurality of prosthetic leaflets, disposed within the lumen, and arranged to provide unidirectional flow of blood from the upstream portion to the downstream portion; an annular upstream support portion: having an inner portion that extends radially outward from the upstream portion, and including one or more fabric pockets disposed circumferentially around the inner portion, each pocket of the one or more pockets having an opening that faces a downstream direction.

In an embodiment, the upstream support portion includes (i) a plurality of arms that extend radially outward from the tubular portion, and (ii) a covering, disposed over the plurality of arms, each arm has (i) a radially-inner part at the inner portion of the upstream support portion, and (ii) a radially-outer part at the outer portion of the upstream support portion, at the inner portion of the upstream support portion, the covering is closely-fitted between the radially-inner parts of the arms, and at the outer portion of the upstream support portion, the pockets are formed by the covering being loosely-fitted between the radially-outer parts of the arms.

In an embodiment, the upstream support portion includes (i) a plurality of arms that extend radially outward from the tubular portion, and (ii) a covering, disposed over the plurality of arms, each arm has (i) a radially-inner part at the inner portion of the upstream support portion, and (ii) a radially-outer part at the outer portion of the upstream support portion, at the outer portion of the upstream support portion, the pockets are formed by each arm curving to form a hook shape.

In an embodiment, each pocket may be shaped and arranged to billow in response to perivalvular flow of blood in an upstream direction.

In an embodiment, the apparatus may be configured to be transluminally delivered to the heart and implanted at the native valve by expansion of the apparatus, such that the upstream support portion is disposed in the atrium and the tubular portion extends from the upstream support portion into the ventricle, and each pocket is shaped and arranged such that perivalvular flow of blood in an upstream direction presses the pocket against tissue of the atrium.

In accordance with an embodiment of the present invention, an apparatus is provided including a plurality of prosthetic valve leaflets; and a frame assembly, including: a tubular portion defined by a repeating pattern of cells, the tubular portion extending circumferentially around a longitudinal axis so as to define a longitudinal lumen, the prosthetic valve leaflets coupled to the inner frame and disposed within the lumen; an outer frame, including a plurality of legs, distributed circumferentially around the tubular portion, each leg having a tissue-engaging flange; an upstream support portion that includes a plurality of arms that extend radially outward from the tubular portion; and a plurality of appendages, each having a first end that defines a coupling element via which the tubular portion is coupled to the outer frame, and a second end; and the frame assembly defines a plurality of hubs, distributed circumferentially around the longitudinal axis on a plane that is transverse to the longitudinal axis, each hub defined by convergence and connection of, (i) two adjacent cells of the tubular portion, (ii) an arm of the plurality of arms, and (iii) an appendage of the plurality of appendages.

In an embodiment, each hub has six radiating spokes, two of the six spokes being part of a first cell of the two adjacent cells, two of the six spokes being part of a second cell of the two adjacent cells, one of the six spokes being the arm, and one of the six spokes being the second end of the appendage.

In an embodiment, the appendages are in-plane with the tubular portion.

In an embodiment, the appendages are in-plane with the outer frame.

In accordance with an embodiment of the present invention, a method for use with a native valve of a heart of a subject is provided, the method including percutaneously advancing to heart, an implant: including a valve frame, a valve member disposed within a lumen defined by the valve frame, and at least one leg, coupled to the valve frame at a coupling point, and having an upstream end, a downstream end, and a central longitudinal axis therebetween; positioning the implant within the heart such that a tissue-engaging flange of the leg is disposed downstream of the valve, and thereafter causing the flange to protrude radially outward from the axis; subsequently, while an upstream support portion of the valve frame is disposed upstream of the valve, causing the upstream support portion to protrude radially outward from the axis, such that tissue of the valve is disposed between the upstream support portion and the flange; and subsequently, sandwiching the tissue between the upstream support portion and the flange by reducing a distance between the upstream support portion and the flange by causing longitudinal movement (i) of the upstream support portion toward the coupling point, and (ii) of the tissue-engaging flange away from the coupling point.

In an embodiment, causing the longitudinal movement (i) of the upstream support portion toward the coupling point, and (ii) of the tissue-engaging flange away from the coupling point, includes causing the longitudinal movement by increasing a diameter of the lumen.

In accordance with an embodiment of the present invention, a method for use with a native valve of a heart of a subject is provided, the method including percutaneously advancing to heart, an implant: including a valve frame, a valve member disposed within a lumen defined by the valve frame, and at least one leg, coupled to the valve frame at a coupling point, and having an upstream end, a downstream end, and a central longitudinal axis therebetween; positioning the implant within the heart such that an upstream support portion of the valve frame is disposed upstream of the valve, and thereafter causing the upstream support portion to protrude radially outward from the axis; subsequently, while a tissue-engaging flange of the leg is disposed downstream of the valve, causing the tissue-engaging flange to protrude radially outward from the axis, such that tissue of the valve is disposed between the upstream support portion and the flange; and subsequently, sandwiching the tissue between the upstream support portion and the flange by reducing a distance between the upstream support portion and the flange by causing longitudinal movement (i) of the upstream support portion toward the coupling point, and (ii) of the tissue-engaging flange away from the coupling point.

In accordance with an embodiment of the present invention, a method for use with a native valve of a heart of a subject is provided, the method including: percutaneously advancing an implant to the heart, the implant having an upstream end, a downstream end, and a central longitudinal axis therebetween, and including a tubular portion, an upstream support portion, and a plurality of tissue-engaging flanges; positioning the implant within the heart such that the upstream support portion is disposed upstream of the valve, positioning the implant within the heart such that the tissue-engaging flanges are disposed downstream of the valve, without increasing a diameter of the tubular portion: causing the upstream support portion to extend radially outward from the axis so as to have a first support-portion span, and causing the flanges to extend radially outward from the axis so as to have a first flange span; and subsequently, causing the upstream support portion and the flanges move toward each other by at least 5 mm by increasing a diameter of the tubular portion such that: the upstream support portion extends radially outward so as to have a second support-portion span, the first support-portion span being at least 40 percent as great as the second support-portion span, and the flanges extend radially outward so as to have a second flange span, the first flange span being at least 30 percent as great as the second flange span.

There is further provided, in accordance with an application of the present invention, a method for use with a native valve of a heart of a subject, the method including: percutaneously advancing an implant to the heart, the implant: having an upstream end, a downstream end, and a central longitudinal axis therebetween, and including a tubular portion, an upstream support portion, and a plurality of tissue-engaging flanges; positioning the implant within the heart such that the upstream support portion is disposed upstream of the valve, positioning the implant within the heart such that the tissue-engaging flanges are disposed downstream of the valve, without increasing a diameter of the tubular portion: causing the upstream support portion to extend radially outward from the axis, and causing the flanges to extend radially outward from the axis so as to have a first flange span; and subsequently, by increasing a diameter of the tubular portion: causing the upstream support portion and the flanges move toward each other by at least 5 mm, causing the upstream support portion to move further radially outward from the axis, and causing each flange of the plurality of flanges to translate radially outward so as to have a second flange span that is greater than the first flange span.

The present invention will be more fully understood from the following detailed description of applications thereof, taken together with the drawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-B and 2A-E are schematic illustrations of an implant for use with a native valve of a heart of a subject, in accordance with some applications of the invention;

FIGS. 3A-C are schematic illustrations that show structural changes in a frame assembly during transitioning of the assembly between its compressed and expanded states, in accordance with some applications of the invention;

FIGS. 4A-F are schematic illustrations of implantation of the implant at the native valve, in accordance with some applications of the invention;

FIG. 5 is a schematic illustration of a step in the implantation of the implant, in accordance with some applications of the invention;

FIG. 6 is a schematic illustration of the implant, in accordance with some applications of the invention;

FIGS. 7A-B and 8A-B are schematic illustrations of frame assemblies of respective implants, in accordance with some applications of the invention; and

FIGS. 9A-C are schematic illustrations of an implant comprising a frame assembly, in accordance with some applications of the invention.

DETAILED DESCRIPTION OF EMBODIMENTS

Reference is made to FIGS. 1A-B and 2A-E, which are schematic illustrations of an implant 20 for use with a native valve of a heart of a subject, in accordance with some embodiments of the invention. Implant 20 comprises a frame assembly 22 (alternatively, “annular valve body 22”) that has an upstream end 24, a downstream end 26, and a central longitudinal axis ax1 therebetween. Annular valve body 22 comprises a valve frame 30 (alternatively “inner frame 30”) that comprises a tubular portion 32 that has an upstream end 34 and a downstream end 36, and is shaped to define a lumen 38 through the tubular portion from the upstream end to the downstream end. Tubular portion 32 circumscribes axis ax1, and thereby defines lumen 38 along the axis. Inner frame 30 further comprises an upstream support portion 40, extending from upstream end 34 of tubular portion 32. Annular valve body 22 further comprises at least one leg 50 (alternatively, “ventricular anchor support 50”), coupled to inner frame 30 at (e.g., via) a coupling point 52, and having a tissue-engaging flange 54 (alternatively, “ventricular anchoring leg 54”).

In some embodiments, and as described hereinbelow, ventricular anchor support 50 is part of an outer frame 60, and frames 30 and 60 define respective coupling elements 31 and 61, which are fixed with respect to each other at coupling points 52. As illustrated in FIG. 1A, inner frame 30 may be positioned at least partially within outer frame 60. In some embodiments, frames 30 and 60 are coupled to each other only at coupling points 52 (e.g., only via the fixation of coupling elements 31 and 61 with respect to each other).

Implant 20 further comprises a valve member 58 (e.g., one or more prosthetic leaflets) disposed within lumen 38, and configured to facilitate one-way liquid flow through the lumen from upstream end 34 to downstream end 36 (e.g., thereby defining the orientation of the upstream and downstream ends of tubular portion 32). FIG. 1A shows implant 20 in a fully-expanded state, in which annular valve body 22 is in a fully-expanded state. FIG. 1B shows an exploded view of annular valve body 22 in its fully-expanded state. FIGS. 2A-E show respective states of implant 20, which will be discussed in more detail hereinbelow with respect to the implantation of the implant and the anatomy in which the implant is implanted. FIG. 2A shows implant 20 in a compressed state (in which annular valve body 22 is in a compressed state constituting a delivery configuration), for percutaneous delivery of the implant to the heart of the subject. In some embodiments, in the compressed state, ventricular anchor support 50 (including ventricular anchoring leg 54 thereof) is in a constrained-leg state in which the ventricular anchoring leg is generally parallel with axis ax1. Further in some embodiments, in the compressed state, upstream support portion 40 is generally tubular, collinear with tubular portion 32 (e.g., extending collinearly from the tubular portion), and disposed around axis ax1.

FIG. 2B shows a state of implant 20 in which ventricular anchoring leg 54 of each ventricular anchor support 50 extends radially away from axis ax1 (e.g., radially away from tubular portion 32). FIG. 2C shows a state of implant 20 in which upstream-support portion 40 extends radially away from axis ax1 (and thereby radially away from tubular portion 32). In the states depicted in FIGS. 2B and 2C, annular valve body 22 is configured to remain compressed within the delivery configuration while ventricular anchoring legs 54 and upstream-support portion 40 (including atrial anchoring arms 46) deflect radially outwards into the deployed configuration. FIG. 2D shows a state of implant 20 in which both ventricular anchoring leg 54 and portion 40 extend away from axis ax1. In the fully-expanded state (FIGS. 1A-B) both upstream support portion 40 and ventricular anchoring leg 54 extend radially away from axis ax1. In some embodiments, annular valve body 22 is biased (e.g., shape-set) to assume its fully-expanded state, which is shown in FIG. 2E and which constitutes a deployed configuration. Transitioning of implant 20 between the respective states may be controlled by delivery apparatus, such as by constraining the implant in a compressed state within a delivery tube and/or against a control rod, and selectively releasing portions of the implant to allow them to expand.

In the compressed state of annular valve body 22, tubular portion 32 has a diameter d1, and in the expanded state, the tubular portion has a diameter d2 that is greater that diameter d1. For some embodiments, diameter d1 is 4-15 mm, (e.g., 5-11 mm) and diameter d2 is 20-50 mm, (e.g., 23-33 mm). Annular valve body 22 is configured such that increasing the diameter of tubular portion 32 (e.g., from d1 to d2) causes longitudinal movement of ventricular anchoring leg 54 away from coupling point 52. In the same way, reducing the diameter of tubular portion 32 (e.g., from d2 to d1) causes longitudinal movement of ventricular anchoring leg 54 toward coupling point 52. It is to be noted that the term “longitudinal movement” (including the specification and the claims) means movement parallel with central longitudinal axis ax1. Therefore longitudinal movement of ventricular anchoring leg 54 away from coupling point 52 means increasing a distance, measured parallel with longitudinal axis ax1, between ventricular anchoring leg 54 and coupling point 52. An example of such a configuration is described in more detail with respect to FIG. 3A.

Thus, expansion of tubular portion 32 from its compressed state toward its expanded state (i) increases a circumferential distance between each of coupling points 52 and its adjacent coupling points (e.g., between each of outer-frame coupling elements 61 and its adjacent outer-frame coupling elements) (e.g., from d8 to d9), and (ii) moves ventricular anchor support 50 in a longitudinally upstream direction with respect to the tubular portion. According to some embodiments, such as the embodiments depicted in FIGS. 1B and 3A, because a circumferential distance between adjacent coupling points 52 may be equal for all coupling points 52 (e.g., d8 or d9), a circumferential distance between adjacent legs 54 may also be equal for all ventricular anchoring legs 54, as each ventricular anchoring leg 54 is disposed between two adjacent coupling points 52. Thus, ventricular anchoring legs 54 may be configured to be spaced at a regular interval about a circumference of annular valve body 22.

In some embodiments, annular valve body 22 is configured such that increasing the diameter of tubular portion 32 also causes longitudinal movement of upstream support portion 40 toward coupling point 52, e.g., as described in more detail with respect to FIGS. 3B-C. In some embodiments, annular valve body 22 is configured such that increasing the diameter of tubular portion 32 also causes longitudinal movement of upstream end 34 of tubular portion 32 toward coupling point 52. In the same way, reducing the diameter of tubular portion 32 causes longitudinal movement of upstream end 34 away from coupling point 52.

For some embodiments, upstream support portion 40 comprises a plurality of atrial anchoring arms 46 that each extends radially outward from tubular portion 32 (e.g., from upstream end 34 of the tubular portion). Atrial anchoring arms 46 may be flexible. For some such embodiments, atrial anchoring arms 46 are coupled to tubular portion 32 such that each arm may deflect independently of adjacent atrial anchoring arms 46 during implantation (e.g., due to anatomical topography).

For some embodiments, upstream support portion 40 comprises a plurality of barbs 48 that extend out of a downstream surface of the upstream support portion. For example, each atrial anchoring arm 46 may comprise one or more of barbs 48. Barbs 48 press into tissue upstream of the native valve (e.g., into the valve annulus), thereby inhibiting downstream movement of implant 20 (in addition to inhibition of downstream movement provided by the geometry of upstream support portion 40).

One or more surfaces of annular valve body 22 are covered with a covering 23, which in some embodiments comprises a flexible sheet, such as a fabric, e.g., comprising polyester. In some embodiments, covering 23 covers at least part of tubular portion 32, in some embodiments lining an inner surface of the tubular portion, and thereby defining lumen 38.

Further in some embodiments, upstream support portion 40 is covered with covering 23, e.g., extending between atrial anchoring arms 46 to form an annular shape. It is hypothesized that this reduces a likelihood of paravalvular leakage. For such embodiments, excess covering 23 may be provided between atrial anchoring arms 46 of upstream support portion 40, so as to facilitate their independent movement. Although FIG. 1A shows covering 23 covering an upstream side of upstream support portion 40, the covering may additionally or alternatively cover the downstream side of the upstream support portion. For example, covering 23 may extend over the tips of atrial anchoring arms 46 and down the outside of the arms, or a separate piece of covering may be provided on the downstream side of the upstream support portion.

Alternatively, each atrial anchoring arm 46 may be individually covered in a sleeve of covering 23, thereby facilitating independent movement of the arms.

For some embodiments, at least a portion of ventricular anchor support 50 (e.g., ventricular anchoring legs 54 thereof) is covered with covering 23.

In some embodiments, annular valve body 22 comprises a plurality of ventricular anchor supports 50 (e.g., two or more ventricular anchor supports, e.g., 2-16 ventricular anchor supports, such as 4-12 ventricular anchor supports, such as 6-12 ventricular anchor supports), arranged circumferentially around inner frame 30 (e.g., around the outside of tubular portion 32). In some embodiments, annular valve body 22 comprises a plurality of coupling points 52 at which the ventricular anchor supports are coupled to inner frame 30.

As described in more detail hereinbelow (e.g., with reference to FIG. 3A), each ventricular anchor support 50 may be coupled to a coupling point 52 via a strut 70. For some embodiments, each ventricular anchor support 50 is coupled to a plurality of (e.g., two) coupling points 52 via a respective plurality of (e.g., two) struts 70. For some such embodiments, annular valve body 22 is arranged such that, in the expanded state of the annular valve body, ventricular anchor support 50 is disposed, circumferentially with respect to tubular portion 32, between two struts, and each of the two struts are disposed, circumferentially with respect to the tubular portion, between the ventricular anchor support and a respective coupling point 52.

For some embodiments, a plurality of (e.g., two) ventricular anchor supports 50 are coupled to each coupling point 52 via a respective plurality of (e.g., two) struts 70. For some such embodiments, annular valve body 22 is arranged such that, in the expanded state of the annular valve body, coupling point 52 is disposed, circumferentially with respect to tubular portion 32, between two struts 70, and each of the two struts are disposed, circumferentially with respect to the tubular portion, between the coupling point and a respective ventricular anchor support 50.

For some embodiments, annular valve body 22 comprises an outer frame (e.g., a leg frame) 60 that circumscribes tubular portion 32, comprises (or defines) the plurality of ventricular anchoring supports 50 and the plurality of struts 70, and is coupled to inner frame 30 at the plurality of coupling points 52, such that the plurality of ventricular anchoring supports are distributed circumferentially around the tubular portion. For such embodiments, outer frame 60 comprises a ring 66 that is defined by a pattern of alternating peaks 64 and troughs 62, and that in some embodiments circumscribes tubular portion 32. For example, the ring may comprise struts 70, extending between the peaks and troughs. Peaks 64 are longitudinally closer to upstream end 34 of tubular portion 32 than to downstream end 36, and troughs 62 are longitudinally closer to the downstream end than to the upstream end. (It is to be noted that throughout this patent application, including the specification and the claims, the term “longitudinally” means with respect to longitudinal axis ax1. For example, “longitudinally closer” means closer along axis ax1 (whether positioned on axis ax1 or lateral to axis ax1), and “longitudinal movement” means a change in position along axis ax1 (which may be in additional to movement toward or away from axis ax1). Therefore, peaks 64 are closer than troughs 62 to upstream end 34, and troughs 62 are closer than peaks 64 to downstream end 36. For embodiments in which frame 60 comprises ring 66, each ventricular anchor support 50 is coupled to the ring (or defined by frame 60) at a respective trough 62.

In the embodiment shown, the peaks and troughs are defined by ring 66 having a generally zig-zag shape. However, the scope of the invention includes ring 66 having another shape that defines peaks and troughs, such as a serpentine or sinusoid shape.

For embodiments in which annular valve body 22 has a plurality of coupling points 52, the coupling points (and therefore coupling elements 31 and 61) are disposed circumferentially around the annular valve body (e.g., around axis ax1), in some embodiments on a transverse plane that is orthogonal to axis ax1. This transverse plane is illustrated by the position of section A-A in FIG. 2B. Alternatively, coupling points 52 may be disposed at different longitudinal heights of annular valve body 22, e.g., such that different ventricular anchoring legs 54 are positioned and/or moved differently to others. In some embodiments, coupling points 52 (and therefore coupling elements 31 and 61) are disposed longitudinally between upstream end 24 and downstream end 26 of annular valve body 22, but not at either of these ends. Further in some embodiments, coupling points 52 are disposed longitudinally between upstream end 34 and downstream end 36 of tubular portion 32, but not at either of these ends. For example, the coupling points may be more than 3 mm (e.g., 4-10 mm) both from end 34 and from end 36. It is hypothesized that this advantageously positions the coupling points at a part of tubular portion 32 that is more rigid than end 34 or end 36.

It is to be noted that ventricular anchor support 50 may be expandable into its expanded state (e.g., a released-leg state) such that ventricular anchoring leg 54 extends away from axis ax1, independently of increasing the diameter of tubular portion 32 (e.g., as shown in FIGS. 2B & 2D). Similarly, upstream support portion 40 may be expandable into its expanded state (e.g., a released-arm state) such that it (e.g., arms 46 thereof) extends away from axis ax1, independently of increasing the diameter of tubular portion 32 (e.g., as shown in FIGS. 2C & 2D). The state shown in FIG. 2D may be considered to be an intermediate state. Therefore, implant 20 may be configured such that ventricular anchor supports 50 (e.g., ventricular anchoring legs 54 thereof) and upstream support portion 40 are expandable such that they both extend away from axis ax1, while retaining a distance d3 therebetween. This distance is subsequently reducible to a distance d4 by expanding tubular portion 32 (e.g., shown in FIG. 2E). By reducing distance d4 to distance d3, ventricular anchoring legs 54 and upstream support portion 40 (including atrial anchoring arms 46) are configured to apply opposing grasping forces upon tissue positioned therebetween, such as tissue of the native mitral valve.

For some embodiments, while tubular portion 32 remains in its compressed state, leg 54 can extend away from axis ax1 over 40 percent (e.g., 40-80 percent, such as 40-70 percent) of the distance that it extends from the axis subsequent to the expansion of the tubular portion. For example, for embodiments in which implant 20 comprises a leg 54 on opposing sides of the implant, a span d15 of the ventricular anchoring legs while tubular portion 32 is in its compressed state may be at least 40 percent (e.g., 40-80 percent, such as 40-70 percent) as great as a span d16 of the ventricular anchoring legs subsequent to the expansion of the tubular portion. For some embodiments, span d15 is greater than 15 mm and/or less than 50 mm (e.g., 20-30 mm). For some embodiments, span d16 is greater than 30 mm and/or less than 60 mm (e.g., 40-50 mm). It is to be noted that leg 54 is effectively fully expanded, with respect to other portions of ventricular anchor support 50 and/or with respect to tubular portion 32, before and after the expansion of the tubular portion.

Similarly, for some embodiments, while tubular portion 32 remains in its compressed state, upstream support portion 40 (e.g., arms 46) can extend away from axis ax1 over 30 percent (e.g., 30-70 percent) of the distance that it extends from the axis subsequent to the expansion of the tubular portion. That is, for some embodiments, a span d17 of the upstream support portion while tubular portion 32 is in its compressed state may be at least 30 percent (e.g., 30-70 percent) as great as a span d18 of the upstream support portion subsequent to the expansion of the tubular portion. For some embodiments, span d17 is greater than 16 mm (e.g., greater than 20 mm) and/or less than 50 mm (e.g., 30-40 mm). For some embodiments, span d18 is greater than 40 mm and/or less than 65 mm (e.g., 45-56 mm, such as 45-50 mm). It is to be noted that upstream support portion 40 is effectively fully expanded, with respect to tubular portion 32, before and after the expansion of the tubular portion.

It is to be noted that when tubular portion 32 is expanded, ventricular anchoring legs 54 may translate radially outward from span d15 to span d16 (e.g., without deflecting). In some embodiments, upstream support portion 40 behaves similarly (e.g., arms 46 translated radially outward from span d17 to span d18, e.g., without deflecting). That is, an orientation of each leg 54 and/or each arm 46 with respect to tubular portion 32 and/or axis ax1 may be the same in the state shown in FIG. 2D as it is in the state shown in FIG. 2E. Similarly, for some embodiments an orientation of each leg 54 with respect to upstream support portion 40 (e.g., with respect to one or more arms 46 thereof) is the same before and after expansion of tubular portion 32.

For some embodiments, increasing the diameter of tubular portion 32 from d1 to d2 causes greater than 1 mm and/or less than 20 mm (e.g., 1-20 mm, such as 1-10 mm or 5-20 mm) of longitudinal movement of leg 54 away from coupling point 52. For some embodiments, increasing the diameter of tubular portion 32 from d1 to d2 causes greater than 1 mm and/or less than 20 mm (e.g., 1-20 mm, such as 1-10 mm or 5-20 mm) of longitudinal movement of upstream support portion 40 toward coupling point 52. For some embodiments, distance d3 is 7-30 mm. For some embodiments, distance d4 is 0-15 mm (e.g., 2-15 mm). For some embodiments, increasing the diameter of tubular portion 32 from d1 to d2 reduces the distance between the upstream support portion and legs 54 by more than 5 mm and/or less than 30 mm, such as 5-30 mm (e.g., 10-30 mm, such as 10-20 mm or 20-30 mm). For some embodiments, the difference between d3 and d4 is generally equal to the difference between d1 and d2. For some embodiments, the difference between d3 and d4 is more than 1.2 and/or less than 3 times (e.g., 1.5-2.5 times, such as about 2 times) greater than the difference between d1 and d2.

For some embodiments, legs 54 curve such that a tip of each leg 54 is disposed at a shallower angle with respect to inner region 42 of upstream support portion 40, than are portions of ventricular anchor support 50 that are closer to downstream end 26 of annular valve body 22. For some such embodiments, a tip of each leg may be generally parallel with inner region 42. For some such embodiments, while tubular portion 32 is in its expanded state, a tip portion 55 of each leg 54 that extends from the tip of the leg at least 2 mm along the leg, is disposed within 2 mm of upstream support portion 40. Thus, for some embodiments, while tubular portion 32 is in its expanded state, for at least 5 percent (e.g., 5-8 percent, or at least 8 percent) of span 18 of upstream support portion 40, the upstream support portion is disposed within 2 mm of a leg 54.

For some embodiments, in the absence of any obstruction (such as tissue of the valve or covering 23) between leg 54 and upstream support portion 40, increasing the diameter of tubular portion 32 from d1 to d2 causes the leg 54 and the upstream support portion to move past each other (e.g., the leg 54 may move between arms 46 of the upstream support portion), such that the leg 54 is closer to the upstream end of implant 20 than is the upstream support portion, e.g., as shown hereinbelow for annular valve bodies 122 and 222, mutatis mutandis. (For embodiments in which upstream support portion 40 is covered by covering 23, legs 54 may not pass the covering. For example, in the absence of any obstruction, legs 54 may pass between arms 46, and press directly against covering 23.) It is hypothesized that for some embodiments this configuration applies greater force to the valve tissue being sandwiched, and thereby further facilitates anchoring of the implant. That is, for some embodiments, distance d3 is smaller than the sum of distance d5 and a distance d14 (described with reference to FIG. 3C). For some embodiments, increasing the diameter of tubular portion 32 from d1 to d2 advantageously causes legs 54 and upstream support portion 40 to move greater than 3 mm and/or less than 25 mm (e.g., greater than 5 mm and/or less than 15 mm, e.g., 5-10 mm, such as about 7 mm) with respect to each other (e.g., toward each other and then past each other).

In accordance with some embodiments of the present disclosure, and as depicted in FIGS. 4A-5, implant 20 (“prosthetic valve 20”) may be configured for implantation within a native valve, such as a native mitral valve. Prosthetic valve 20 may include annular valve body 22. As illustrated in FIGS. 1A and 2A-2E, a plurality of arms 46 (“atrial anchoring arms 46”) and a plurality of ventricular anchoring legs 54 may be configured to extend from annular valve body 22. Atrial anchoring arms 46 may include inner regions 42 (“inner portions 42”) and outer regions 44 (“outer portions 44”), with outer regions 44 positioned radially outward from inner regions 42. For example, inner regions 42 may be situated within inner radial halves of atrial anchoring arms 46, as illustrated in FIGS. 1A and 2D.

In some embodiments, atrial anchoring arms 46 and ventricular anchoring legs 54 may be configured to assume a delivery configuration (for example, as depicted in FIG. 2A). In the delivery configuration, atrial anchoring arms 46 and ventricular anchoring legs 54 may be arranged generally parallel with axis ax1. For example, atrial anchoring arms 46 and ventricular anchoring legs 54 may be radially constrained in the delivery configuration by a delivery device, such as delivery tool 89. Atrial anchoring arms 46 and ventricular anchoring legs 54 may also be configured to assume a deployed configuration (for example, as depicted in FIG. 2D). In the deployed configuration, atrial anchoring arms 46 and ventricular anchoring legs 54 may be released such that they deflect radially outward from axis ax1 and thus from the delivery configuration.

In some embodiments, and as depicted in FIGS. 2A, 2C, and 2E, for example, inner portions 42 of the atrial anchoring arms 46 may be configured as pivoting portions and may be configured to extend in different directions in the delivery and deployed configurations. Atrial anchoring arms 46, including inner portions 42, may be configured to extend in an atrial direction or, alternatively, in a non-ventricular direction when in the delivery configuration. The term “atrial direction” may refer to a direction extending upstream from prosthetic valve 20, towards an atrium of the heart. For example, in FIGS. 4A-4E, an “atrial direction” may refer to a direction extending upstream from the valve towards left atrium 6. The term “ventricular direction” may refer to a direction extending downstream from prosthetic valve 20, towards a ventricle of the heart. Thus, the term “non-ventricular direction” may refer to any direction which does not extend towards a ventricle of the heart; a “non-ventricular direction” may extend in an atrial direction, or it may extend laterally in a direction perpendicular to the ventricular direction. In some embodiments, an “atrial direction” may be angled radially inward or outward from prosthetic valve 20, so long as it also is angled upstream (towards an atrium) and not downstream (towards a ventricle); that is, an “atrial direction” need not necessarily be parallel to longitudinal axis ax1, although it may be parallel to longitudinal axis ax1 in some embodiments. Similarly, a “ventricular direction” may be angled radially inward or outward from prosthetic valve 20, so long as it also is angled downstream, towards a ventricle. For example, in FIGS. 4A-4F, a “ventricular direction” may refer to a direction extending downstream (downwards in FIGS. 4A-4F) from the valve towards the left ventricle. A “ventricular direction” need not necessarily be parallel to longitudinal axis ax1, although it may be parallel to longitudinal axis ax1 in some embodiments.

As described further below, inner portions 42 of the atrial anchoring arms may be configured to extend in a ventricular direction when the atrial anchoring arms 46 are in the deployed configuration. For example, inner portions 42 may deflect radially outward at an angle of 60-120 degrees (e.g., 70-110 degrees) with respect to axis ax1 when the atrial anchoring arms are in the deployed configuration. In some embodiments, inner portions 42 deflect by an angle greater than 90 degrees when transitioning from the delivery configuration to the deployed configuration; as a result, the inner portions 42 may extend in a ventricular direction (i.e. downstream towards a ventricle) when the atrial anchoring arms are in the deployed configuration.

In some embodiments, and as depicted in FIGS. 2A, 2C, and 2E, for example, outer portions 44 of the atrial anchoring arms 46 may be configured as upstanding portions and may be configured to extend in a non-ventricular direction when the atrial anchoring arms 46 are in both the delivery configuration and the deployed configuration. Atrial anchoring arms 46, including outer portions 44, may be arranged parallel to axis ax1 and may extend in an atrial direction when in the delivery configuration. As described further below, when atrial anchoring arms 46 transition into the deployed configuration, outer portions 44 may deflect radially outwards at an angle of 5-70 degrees with respect to axis ax1, thus continuing to extend in an atria direction, and thus also in a non-ventricular direction.

In some embodiments, as depicted in FIGS. 2A and 2B, for example, at least one ventricular anchoring leg 54 may be configured such that its entire length may extend in an atrial direction or, alternatively, in a non-ventricular direction in both the delivery configuration and the deployed configuration. With reference to FIGS. 3A-3C, the term “entire length” may refer to the length extending from a point of intersection between ventricular anchoring leg 54 and connectors 78, to the terminal end of ventricular anchoring leg 54. In the delivery configuration, the entire length of the at least one ventricular anchoring leg may be arranged parallel to axis ax1 and may extend upstream towards an atrium, that is, in an atrial direction. As explained further below, in some embodiments the entire length of the at least one ventricular anchoring leg may deflect radially outwards by less than 90 degrees with respect to longitudinal axis ax1 when transitioning from the delivery configuration to the deployed configuration. As a result, the entire length of the at least one ventricular anchoring leg may extend in an atrial direction and/or in a non-ventricular direction when in the deployed configuration.

In some embodiments, in the expanded state of annular valve body 22, upstream support portion 40 has an inner region (e.g., an inner ring) 42 that extends radially outward at a first angle with respect to axis ax1 (and in some embodiments with respect to tubular portion 32), and an outer region (e.g., an outer ring) 44 that extends, from the inner region, further radially outward from the tubular portion at a second angle with respect to the tubular portion, the second angle being smaller than the first angle. For example, for some embodiments inner region 42 extends radially outward at an angle alpha_1 of 60-120 degrees (e.g., 70-110 degrees) with respect to axis ax1, and outer region 44 extends radially outward at an angle alpha_2 of 5-70 degrees (e.g., 10-60 degrees) with respect to axis ax1. In some embodiments, such as the embodiments depicted in FIGS. 2A-2E, inner portions 42 may each be configured to deflect radially outward by the same angle with respect to longitudinal axis ax1 and outer portions 44 may each be configured to deflect radially outward by the same angle with respect to longitudinal axis ax1 such that the terminal ends of atrial anchoring arms 46 are substantially aligned in a common lateral plane when atrial anchoring arms 46 are in the deployed configuration (as depicted in FIGS. 2C and 2D).

It is to be noted that angles alpha_1 and alpha_2 are measured between the respective region support portion 40, and the portion of axis ax1 that extends in an upstream direction from the level of annular valve body 22 at which the respective region begins to extend radially outward.

For some embodiments in which implant 20 is configured to be placed at an atrioventricular valve (e.g., a mitral valve or a tricuspid valve) of the subject, region 42 is configured to be placed against the upstream surface of the annulus of the atrioventricular valve, and region 44 is configured to be placed against the walls of the atrium upstream of the valve.

For some embodiments, outer region 44 is more flexible than inner region 42. For example, and as shown, each arm 46 may have a different structure in region 44 than in region 42. It is hypothesized that the relative rigidity of region 42 provides resistance against ventricular migration of implant 20, while the relative flexibility of region 44 facilitates conformation of upstream support portion 40 to the atrial anatomy.

For some embodiments, two or more of arms 46 are connected by a connector (not shown), reducing the flexibility, and/or the independence of movement of the connected arms relative to each other. For some embodiments, arms 46 are connected in particular sectors of upstream support portion 40, thereby making these sectors more rigid than sectors in which the arms are not connected. For example, a relatively rigid sector may be provided to be placed against the posterior portion of the mitral annulus, and a relatively flexible sector may be provided to be placed against the anterior side of the mitral annulus, so as to reduce forces applied by upstream support portion 40 on the aortic sinus.

For some embodiments, and as shown, coupling points 52 are disposed closer to downstream end 26 of annular valve body 22 than are ventricular anchoring legs 54, or is upstream support portion 40.

As described in more detail with respect to FIGS. 4A-F, the movement of ventricular anchoring leg 54 away from coupling point 52 (and the typical movement of upstream support portion 40 toward the coupling point) facilitates the sandwiching of tissue of the native valve (e.g., leaflet and/or annulus tissue) between the ventricular anchoring leg 54 and the upstream support portion, thereby securing implant 20 at the native valve.

In some embodiments, in the compressed state of tubular portion 32, a downstream end of each ventricular anchor support 50 is longitudinally closer than valve-frame coupling elements 31 to downstream end 36, and ventricular anchoring leg 54 of each ventricular anchor support 50 is disposed longitudinally closer than the valve-frame coupling elements to upstream end 34. In some embodiments, this is also the case in the expanded state of tubular portion 32.

FIGS. 3A-C show structural changes in annular valve body 22 during transitioning of the annular valve body between its compressed and expanded states, in accordance with some embodiments of the invention. FIGS. 3A-C each show a portion of the annular valve body, the structural changes thereof being representative of the structural changes that occur in other portions of the annular valve body. FIG. 3A shows a ventricular anchor support 50 and struts 70 (e.g., a portion of outer frame 60), and illustrates the structural changes that occur around outer frame 60. FIG. 3B shows a portion of inner frame 30, and illustrates the structural changes that occur around the inner frame. FIG. 3C shows inner frame 30 as a whole. In each of FIGS. 3A-C, state (A) illustrates the structure while annular valve body 22 (and in particular tubular portion 32) is in its compressed state, and state (B) illustrates the structure while the annular valve body (and in particular tubular portion 32) is in its expanded state.

FIG. 3A shows structural changes in the coupling of ventricular anchoring supports 50 to coupling point 52 (e.g., structural changes of outer frame 60) during the transitioning of annular valve body 22 (and in particular tubular portion 32) between its compressed and expanded states. Each ventricular anchor support 50 is coupled to inner frame 30 via at least one strut 70, which connects the ventricular anchoring support to coupling point 52. In some embodiments, each ventricular anchor support 50 is coupled to inner frame 30 via a plurality of struts 70. A first end 72 of each strut 70 is coupled to ventricular anchor support 50, and a second end 74 of each strut is coupled to a coupling point 52. As described hereinabove, for embodiments in which frame 60 comprises ring 66, each ventricular anchor support 50 is coupled to the ring at a respective trough 62. Ring 66 may comprise struts 70, extending between the peaks and troughs, with each first end 72 at (or close to) a trough 62, and each second end 74 at (or close to) a peak 64.

In the compressed state of annular valve body 22 (and in particular of tubular portion 32), each strut 70 is disposed at a first angle in which first end 72 is disposed closer than second end 74 to the downstream end of the annular valve body. Expansion of annular valve body 22 (and in particular of tubular portion 32) toward its expanded state causes strut 70 to deflect to a second angle. This deflection moves first end 72 away from the downstream end of annular valve body 22. That is, in the expanded state of annular valve body 22, first end 72 is further from the downstream end of the annular valve body than it is when the annular valve body is in its compressed state. This movement is shown as a distance d5 between the position of end 72 in state (A) and its position in state (B). This movement causes the above-described movement of ventricular anchoring legs 54 away from coupling points 52. As shown, ventricular anchoring legs 54 in some embodiments move the same distance d5 in response to expansion of annular valve body 22.

For embodiments in which outer frame 60 comprises ring 66, the pattern of alternating peaks and troughs may be described as having an amplitude longitudinally between the peaks and troughs, i.e., measured parallel with central longitudinal axis ax1 of annular valve body 22, and the transition between the compressed and expanded states may be described as follows: In the compressed state of annular valve body 22 (and in particular of tubular portion 32), the pattern of ring 66 has an amplitude d20. In the expanded state annular valve body 22 (and in particular of tubular portion 32), the pattern of ring 66 has an amplitude d21 that is lower than amplitude d20. Because (i) it is at peaks 64 that ring 66 is coupled to inner frame 30 at coupling points 52, and (ii) it is at troughs 62 that ring 66 is coupled to ventricular anchoring supports 50, this reduction in the amplitude of the pattern of ring 66 moves ventricular anchoring supports 50 (e.g., ventricular anchoring legs 54 thereof) longitudinally further from the downstream end of the annular valve body. The magnitude of this longitudinal movement (e.g., the difference between magnitudes d20 and d21) is equal to d5.

In some embodiments, distance d5 is the same distance as the distance that ventricular anchoring leg 54 moves away from coupling point 52 during expansion of the annular valve body. That is, a distance between ventricular anchoring leg 54 and the portion of ventricular anchor support 50 that is coupled to strut 70, in some embodiments remains constant during expansion of the annular valve body. For some embodiments, the longitudinal movement of ventricular anchoring leg 54 away from coupling point 52 is a translational movement (e.g., a movement that does not include rotation or deflection of the ventricular anchoring leg 54).

For some embodiments, a distance d6, measured parallel to axis ax1 of annular valve body 22, between coupling point 52 and first end 72 of strut 70 while annular valve body 22 is in its compressed state, is 3-15 mm. For some embodiments, a distance d7, measured parallel to axis ax1, between coupling point 52 and first end 72 of strut 70 while annular valve body 22 is in its expanded state, is 1-5 mm (e.g., 1-4 mm).

For some embodiments, amplitude d20 is 2-10 mm (e.g., 4-7 mm). For some embodiments, amplitude d21 is 4-9 mm (e.g., 5-7 mm).

For some embodiments, and as shown, in the expanded state, first end 72 of strut 70 is disposed closer to the downstream end of annular valve body 22 than is coupling point 52. For some embodiments, in the expanded state, first end 72 of strut 70 is disposed further from the downstream end of annular valve body 22 than is coupling point 52.

For embodiments in which annular valve body 22 comprises a plurality of ventricular anchoring supports 50 and a plurality of coupling points 52 (e.g., for embodiments in which the annular valve body comprises outer frame 60) expansion of the annular valve body increases a circumferential distance between adjacent coupling points 52, and an increase in a circumferential distance between adjacent ventricular anchoring supports 50. FIG. 3A shows such an increase in the circumferential distance between adjacent coupling points 52, from a circumferential distance d8 in the compressed state to a circumferential distance d9 in the expanded state. For some embodiments, distance d8 is 1-6 mm. For some embodiments, distance d9 is 3-15 mm.

For some embodiments, in addition to being coupled via ring 66 (e.g., struts 70 thereof) ventricular anchoring supports 50 are also connected to each other via connectors 78. Connectors 78 allow the described movement of ventricular anchoring supports 50 during expansion of annular valve body 22, but in some embodiments stabilize ventricular anchoring supports 50 relative to each other while the annular valve body is in its expanded state. For example, connectors 78 may bend and/or deflect during expansion of the annular valve body. According to the embodiments depicted in FIGS. 1B and 3A, each ventricular anchoring leg 54 may extend from and be connected to a single portion of outer frame 60. Specifically, each ventricular anchoring leg 54 may connect to, and extend from, a point of intersection between ventricular anchoring leg 54 and connectors 78. In addition, no ventricular anchoring legs 54 share a connection point to outer frame 60. That is, each ventricular anchoring leg 54 may extend from a separate part of outer frame 60.

FIGS. 3B-C show structural changes in inner frame 30 during the transitioning of annular valve body 22 between its compressed and expanded states. Tubular portion 32 of inner frame 30 is defined by a plurality of cells 80, which are defined by the repeating pattern of the inner frame. When annular valve body 22 is expanded from its compressed state toward its expanded state, cells 80 (i) widen from a width d10 to a width d11 (measured orthogonal to axis ax1 of the annular valve body), and (ii) shorten from a height d12 to a height d13 (measured parallel to axis ax1 of the annular valve body). This shortening reduces the overall height (i.e., a longitudinal length between upstream end 34 and downstream end 36) of tubular portion 32 from a height d22 to a height d23, and thereby causes the above-described longitudinal movement of upstream support portion 40 toward coupling points 52 by a distance d14 (shown in FIG. 3C). For some embodiments, and as shown, coupling points 52 are disposed at the widest part of each cell. According to some embodiments, and as depicted in FIG. 3B, for example, because a circumferential distance between adjacent coupling elements 31 may be equal for all coupling elements 31 (e.g., d11), a circumferential distance between adjacent arms 46 (“atrial anchoring arms 46”) may also be equal for all atrial anchoring arms 46, as each anchoring arm 46 is disposed between two adjacent coupling elements 31. Thus, atrial anchoring arms 46 may be configured to be spaced at a regular interval about a circumference of annular valve body 22.

Due to the configurations described herein, the distance by which ventricular anchoring legs 54 move with respect to (e.g., toward, or toward-and-beyond) upstream support portion 40 (e.g., arms 46 thereof), may be greater than the reduction in the overall height of tubular portion 32 (e.g., more than 20 percent greater, such as more than 30 percent greater, such as more than 40 percent greater). That is, implant 20 comprises: a inner frame (30) that comprises a tubular portion (32) that circumscribes a longitudinal axis (ax1) of the inner frame so as to define a lumen (38) along the axis, the tubular portion having an upstream end (34), a downstream end (36), a longitudinal length therebetween, and a diameter (e.g., d1 or d2) transverse to the longitudinal axis; a valve member (58), coupled to the tubular portion, disposed within the lumen, and arranged to provide unidirectional upstream-to-downstream flow of blood through the lumen; an upstream support portion (40), coupled to the tubular portion; and an outer frame (60), coupled to the tubular portion, and comprising a ventricular anchoring leg (54), wherein: the implant has a first state (e.g., as shown in FIG. 2D and FIG. 4D) and a second state (e.g., as shown in FIG. 2E and FIG. 4E), in both the first state and the second state, (i) the upstream support portion extends radially outward from the tubular portion, and (ii) the ventricular anchoring leg 54 extends radially outward from the tubular portion, and the tubular portion, the upstream support portion, and the outer frame are arranged such that transitioning of the implant from the first state toward the second state: increases the diameter of the tubular portion by a diameter-increase amount (e.g., the difference between d1 and d2), decreases the length of the tubular portion by a length-decrease amount (e.g., the difference between d22 and d23), and moves the ventricular anchoring leg 54 a longitudinal distance with respect to (e.g., toward or toward-and-beyond) the upstream support portion (e.g., the difference between d3 and d4), this distance being greater than the length-decrease amount.

As shown in the figures, inner frame 30 may be coupled to outer frame 60 by coupling between (i) a valve-frame coupling element 31 defined by inner frame 30, and (ii) an outer-frame coupling element 61 defined by outer frame 60 (e.g., an outer-frame coupling element is coupled to end 74 of each strut). In some embodiments, elements 31 and 61 are fixed with respect to each other. Each coupling point 52 may be defined as the point at which a valve-frame coupling element and a corresponding outer-frame coupling element 61 are coupled (e.g., are fixed with respect to each other). For some embodiments, and as shown, elements 31 and 61 are eyelets configured to be coupled together by a connector, such as a pin or suture. For some embodiments, elements 31 and 61 are soldered or welded together.

In some embodiments, and as shown, valve-frame coupling elements 31 are defined by tubular portion 32, and are disposed circumferentially around central longitudinal axis ax1. Outer-frame coupling elements 61 are coupled to ring 66 (or defined by frame 60, such as by ring 66) at respective peaks 64.

As shown (e.g., in FIGS. 2A-E), inner frame 30 (e.g., tubular portion 32 thereof) and outer frame 60 (e.g., ring 66 thereof) are arranged in a close-fitting coaxial arrangement, in both the expanded and compressed states of annular valve body 22. Ignoring spaces due to the cellular structure of the frames, a radial gap d19 between inner frame 30 (e.g., tubular portion 32 thereof) and outer frame 60 (e.g., ring 66 thereof) may be less than 2 mm (e.g., less than 1 mm), in both the compressed and expanded states, and during the transition therebetween. This is facilitated by the coupling between frames 30 and 60, and the behavior, described hereinabove, of frame 60 in response to changes in the diameter of tubular portion 32 (e.g., rather than solely due to delivery techniques and/or tools). For some embodiments, more than 50 percent (e.g., more than 60 percent) of ring 66 is disposed within 2 mm of tubular portion 32 in both the compressed and expanded states, and during the transition therebetween. For some embodiments, more than 50 percent (e.g., more than 60 percent) of outer frame 60, except for ventricular anchoring legs 54, is disposed within 2 mm of tubular portion 32 in both the compressed and expanded states, and during the transition therebetween. In some embodiments in which annular valve body 22 and legs 54 (“ventricular anchoring legs 54”) are in a compressed state (a “delivery configuration”), as depicted in FIGS. 2A, 7A, and 8A, for example, at least one ventricular anchoring leg 54 may be configured such that its entire length is substantially flush with inner frame 30 due to the small distance d19 between inner frame 30 and outer frame 60, and due to the fact that anchoring legs 54 may be arranged generally parallel with axis ax1. As a result, the at least one ventricular anchoring leg 54 may be configured to abut a portion of inner frame 30.

The structural changes to annular valve body 22 (e.g., to outer frame 60 thereof) are described hereinabove as they occur during (e.g., as a result of) expansion of the annular valve body (in particular tubular portion 32 thereof). This is the natural way to describe these changes because, as described hereinbelow with respect to FIGS. 4A-6, annular valve body 22 is in its compressed state during percutaneous delivery to the implant site, and is subsequently expanded. However, the nature of implant 20 may be further understood by describing structural changes that occur during compression of the annular valve body (e.g., a transition from the expanded state in FIG. 2E to the intermediate state in FIG. 2D), in particular tubular portion 32 thereof (including if tubular portion 32 were compressed by application of compressive force to the tubular portion, and not to frame 60 except via the tubular portion pulling frame 60 radially inward). Such descriptions may also be relevant because implant 20 may be compressed (i.e., “crimped”) soon before its percutaneous delivery, and therefore these changes may occur while implant 20 is in the care of the operating physician.

For some embodiments, the fixation of peaks 64 to respective sites of tubular portion 32 is such that compression of the tubular portion from its expanded state toward its compressed state such that the respective sites of the tubular portion pull the peaks radially inward via radially-inward tension on coupling points 52: (i) reduces a circumferential distance between each of the coupling points and its adjacent coupling points (e.g., from d9 to d8), and (ii) increases the amplitude of the pattern of ring 66 (e.g., from d21 to d20).

For some embodiments, the fixation of outer-frame coupling elements 61 to valve-frame coupling elements 31 is such that compression of tubular portion 32 from its expanded state toward its compressed state such that the valve-frame coupling elements pull the outer-frame coupling elements radially inward: (i) reduces a circumferential distance between each of the outer-frame coupling elements and its adjacent outer-frame coupling elements (e.g., from d9 to d8), and (ii) increases the amplitude of the pattern of ring 66 (e.g., from d21 to d20).

For some embodiments, the fixation of peaks 64 to the respective sites of tubular portion 32 is such that compression of the tubular portion from its expanded state toward its compressed state (i) pulls the peaks radially inward via radially-inward pulling of the respective sites of the tubular portion on the peaks, (ii) reduces a circumferential distance between each of coupling points 52 and its adjacent coupling points (e.g., from d9 to d8), and (iii) increases the amplitude of the pattern of ring 66 (e.g., from d21 to d20), without increasing radial gap d19 between inner frame 30 (e.g., tubular portion 32 thereof) and the ring by more than 1.5 mm.

For some embodiments, the fixation of outer-frame coupling elements 61 with respect to valve-frame coupling elements 31 is such that compression of tubular portion 32 from its expanded state toward its compressed state (i) pulls outer-frame coupling elements 61 radially inward via radially-inward pulling of valve-frame coupling elements 31 on outer-frame coupling elements 61, (ii) reduces a circumferential distance between each of the outer-frame coupling elements and its adjacent outer-frame coupling elements (e.g., from d9 to d8), and (iii) increases the amplitude of the pattern of ring 66 (e.g., from d21 to d20), without increasing radial gap d19 between inner frame 30 (e.g., tubular portion 32 thereof) and the ring by more than 1.5 mm.

Reference is made to FIGS. 4A-F, which are schematic illustrations of implantation of implant 20 at a native valve 10 of a heart 4 of a subject, in accordance with some embodiments of the invention. Valve 10 is shown as a mitral valve of the subject, disposed between a left atrium 6 and a left ventricle 8 of the subject. However implant 20 may be implanted at another heart valve of the subject, mutatis mutandis. Similarly, although FIGS. 4A-F show implant 20 being delivered transseptally via a sheath 88, the implant may alternatively be delivered by any other suitable route, such as transatrially, or transapically.

Implant 20 is delivered, in its compressed state, to native valve 10 using a delivery tool 89 that is operable from outside the subject (FIG. 4A). In some embodiments, implant 20 is delivered within a delivery capsule 90 of tool 89, which retains the implant in its compressed state. A transseptal approach, such as a transfemoral approach, is shown. In some embodiments, implant 20 is positioned such that at least ventricular anchoring legs 54 are disposed downstream of the native valve (i.e., within ventricle 8). At this stage, annular valve body 22 of implant 20 is as shown in FIG. 2A.

Subsequently, ventricular anchoring legs 54 are allowed to protrude radially outward, as described hereinabove, e.g., by releasing them from capsule 90 (FIG. 4B). For example, and as shown, capsule 90 may comprise a distal capsule-portion 92 and a proximal capsule-portion 94, and the distal capsule-portion may be moved distally with respect to implant 20, so as to expose ventricular anchoring legs 54. At this stage, annular valve body 22 of implant 20 is as shown in FIG. 2B.

Subsequently, implant 20 is moved upstream, such that upstream support portion 40, in its compressed state, is disposed upstream of leaflets 12 (i.e., within atrium 6). For some embodiments, the upstream movement of implant 20 causes ventricular anchoring legs 54 to engage leaflets 12. However, because of the relatively large distance d3 provided by implant 20 (described hereinabove), for some embodiments it is not necessary to move the implant so far upstream that ventricular anchoring legs 54 tightly engage leaflets 12 and/or pull the leaflets upstream of the valve annulus. Upstream support portion 40 is then allowed to expand such that it protrudes radially outward, as described hereinabove, e.g., by releasing it from capsule 90 (FIG. 4D). For example, and as shown, proximal capsule-portion 94 may be moved proximally with respect to implant 20, so as to expose upstream support portion 40. At this stage, annular valve body 22 of implant 20 is as shown in FIG. 2D, in which: (i) distance d3 exists between upstream support portion 40 and ventricular anchoring legs 54, (ii) the ventricular anchoring legs have span d15, (iii) the upstream support portion has span d17, and (iv) tubular portion 32 has diameter d1.

In some embodiments, expansion of annular valve body 22 is inhibited by distal capsule-portion 92 (e.g., by inhibiting expansion of tubular portion 32), and/or by another portion of delivery tool 89 (e.g., a portion of the delivery tool that is disposed within lumen 38).

Subsequently, implant 20 is allowed to expand toward its expanded state, such that tubular portion 32 widens to diameter d2, and the distance between upstream support portion 40 and ventricular anchoring legs 54 reduces to distance d4 (FIG. 4E). This sandwiches tissue of valve 10 (in some embodiments including annular tissue and/or leaflets 12) between upstream support portion 40 and ventricular anchoring legs 54, thereby securing implant 20 at the valve. FIG. 4F shows delivery capsule 90 having been removed from the body of the subject, leaving implant 20 in place at valve 10.

As described hereinabove, implant 20 is configured such that when tubular portion 32 is expanded, ventricular anchoring legs 54 and upstream support portion 40 move a relatively large distance toward each other. This enables distance d3 to be relatively large, while distance d4 is sufficiently small to provide effective anchoring. As also described hereinabove, implant 20 is configured such that ventricular anchoring legs 54 and upstream support portion 40 can extend radially outward a relatively large distance while tubular portion 32 remains compressed. It is hypothesized that for some embodiments, these configurations (independently and/or together) facilitate effective anchoring of implant 20, by facilitating placement of a relatively large proportion of valve tissue (e.g., leaflets 12) between the ventricular anchoring legs 54 and the upstream support portion prior to expanding tubular portion 32 and sandwiching the valve tissue.

It is further hypothesized that the relatively great radially-outward extension of ventricular anchoring legs 54 and upstream support portion 40 prior to expansion of tubular portion 32, further facilitates the anchoring/sandwiching step by reducing radially-outward pushing of the valve tissue (e.g., leaflets 12) during the expansion of the tubular portion, and thereby increasing the amount of valve tissue that is sandwiched.

It is yet further hypothesized that this configuration of implant 20 facilitates identifying correct positioning of the implant (i.e., with upstream support portion 40 upstream of leaflets 12 and ventricular anchoring legs 54 downstream of the leaflets) prior to expanding tubular portion 32 and sandwiching the valve tissue.

As shown in FIG. 1A, for some embodiments, in the expanded state of annular valve body 22, implant 20 defines a toroidal space 49 between ventricular anchoring legs 54 and upstream support portion 40 (e.g., a space that is wider than distance d4). For example, space 49 may have a generally triangular cross-section. It is hypothesized that for some such embodiments, in addition to sandwiching tissue of the native valve between upstream support portion 40 and ventricular anchoring legs 54 (e.g., the tips of the legs), space 49 advantageously promotes tissue growth therewithin (e.g., between leaflet tissue and covering 23), which over time further secures implant 20 within the native valve.

Reference is now made to FIG. 5, which is a schematic illustration of a step in the implantation of implant 20, in accordance with some embodiments of the invention. Whereas FIGS. 4A-F show an implantation technique in which ventricular anchoring legs 54 are expanded prior to upstream support portion 40, for some embodiments the upstream support portion is expanded prior to the ventricular anchoring legs 54. FIG. 5 shows a step in such an embodiment.

Reference is again made to FIGS. 2A-5. As noted hereinabove, implant 20 may be implanted by causing ventricular anchoring legs 54 to radially protrude before causing upstream support portion 40 to radially protrude, or may be implanted by causing the upstream support portion to protrude before causing the ventricular anchoring legs 54 to protrude. For some embodiments, implant 20 is thereby configured to be deliverable in a downstream direction (e.g., transseptally, as shown, or transapically) or in an upstream direction (e.g., transapically or via the aortic valve). Thus, for some embodiments, an operating physician may decide which delivery route is preferable for a given application (e.g., for a given subject, and/or based on available equipment and/or expertise), and implant 20 is responsively prepared for the chosen delivery route (e.g., by loading the implant into an appropriate delivery tool).

It is to be noted that for some embodiments, downstream delivery of implant 20 may be performed by expanding ventricular anchoring legs 54 first (e.g., as shown in FIGS. 4A-F) or by expanding upstream support portion 40 first (e.g., as shown in FIG. 5). Similarly, for some embodiments upstream delivery of implant 20 may be performed by upstream support portion 40 first, or by expanding ventricular anchoring legs 54 first.

Reference is now made to FIG. 6, which is a schematic illustration of implant 20, in the state and position shown in FIG. 4D, in accordance with some embodiments of the invention. For some embodiments, while implant 20 is in the state and position shown in FIG. 4D, leaflets 12 of valve 10 are able to move, at least in part in response to beating of the heart. Frame (A) shows leaflets 12 during ventricular systole, and frame (B) shows the leaflets during ventricular diastole. For some such embodiments, blood is thereby able to flow from atrium 6 to ventricle 8, between leaflets 12 and implant 20. It is hypothesized that this advantageously facilitates a more relaxed implantation procedure, e.g., facilitating retaining of implant 20 in this state and position for a duration of greater than 8 minutes. During this time, imaging techniques may be used to verify the position of implant 20, and/or positioning of leaflets 12 between upstream support portion 40 and legs 54.

Reference is made to FIGS. 7A-B and 8A-B, which are schematic illustrations of annular valve bodies 122 and 222 of respective implants, in accordance with some embodiments of the invention. Except where noted otherwise, annular valve bodies 122 and 222 are in some embodiments identical to annular valve body 22, mutatis mutandis. Elements of annular valve bodies 122 and 222 share the name of corresponding elements of annular valve body 22. Additionally, except where noted otherwise, the implants to which annular valve bodies 122 and 222 belong are similar to implant 20, mutatis mutandis.

Annular valve body 122 comprises (i) a inner frame 130 that comprises a tubular portion 132 and an upstream support portion 140 that in some embodiments comprises a plurality of arms 146, and (ii) an outer frame (e.g., a leg frame) 160 that circumscribes the inner frame, and comprises a plurality of ventricular anchoring supports 150 that each comprise a ventricular anchoring leg 154. In some embodiments, ventricular anchoring leg 154 may include an opening therein, such as near its terminal end, as depicted in FIGS. 7A-8B, for example. In some embodiments, outer frame 160 comprises a ring 166 to which ventricular anchoring supports 150 are coupled. Ring 166 is defined by a pattern of alternating peaks and troughs, the peaks being fixed to frame 130 at respective coupling points 152, e.g., as described hereinabove for annular valve body 22, mutatis mutandis.

Annular valve body 222 comprises (i) a inner frame 230 that comprises a tubular portion 232 and an upstream support portion 240 that in some embodiments comprises a plurality of arms 246, and (ii) an outer frame (e.g., a leg frame) 260 that circumscribes the inner frame, and comprises a plurality of ventricular anchoring supports 250 that each comprise a ventricular anchoring leg 254. In some embodiments, outer frame 260 comprises a ring 266 to which ventricular anchoring supports 250 are coupled. Ring 266 is defined by a pattern of alternating peaks and troughs, the peaks being fixed to frame 230 at respective coupling points 252, e.g., as described hereinabove for annular valve body 22, mutatis mutandis.

Whereas arms 46 of annular valve body 22 are shown as extending from upstream end 34 of tubular portion 32, arms 146 and 246 of annular valve bodies 122 and 222, respectively, extend from sites further downstream. (This difference may also be made to annular valve body 22, mutatis mutandis.) Tubular portions 32, 132 and 232 are each defined by a repeating pattern of cells that extends around the central longitudinal axis. In some embodiments, and as shown, tubular portions 32, 132 and 232 are each defined by two stacked, tessellating rows of cells. In the expanded state of each tubular portion, these cells may be narrower at their upstream and downstream extremities than midway between these extremities. For example, and as shown, the cells may be roughly diamond or astroid in shape. In annular valve body 22, each arm 46 is attached to and extends from a site 35 that is at the upstream extremity of cells of the upstream row. In contrast, in annular valve bodies 122 and 222, each arm 146 or 246 is attached to and extends from a site 135 (annular valve body 122) or 235 (annular valve body 222) that is at the connection between two adjacent cells of the upstream row (alternatively described as being at the upstream extremity of cells of the downstream row).

It is hypothesized by the inventors that this lower position of the arms, while maintaining the length of the lumen of the tubular portion, advantageously reduces the distance that the tubular portion (i.e., the downstream end thereof) extends into the ventricle of the subject, and thereby reduces a likelihood of inhibiting blood flow out of the ventricle through the left ventricular outflow tract. It is further hypothesized that this position of the arms reduces radial compression of the tubular portion by movement of the heart, due to greater rigidity of the tubular portion at sites 135 and 235 (which is supported by two adjacent cells) than at site 35 (which is supported by only one cell).

As shown, in the expanded state of annular valve bodies 22, 122 and 222, the ventricular anchoring supports (50, 150 and 250, respectively) are circumferentially staggered with the arms of the upstream support portion (46, 146 and 246, respectively). This allows the ventricular anchoring supports to move in an upstream direction between the arms during expansion of the tubular portion (32, 132 and 232, respectively), facilitating application of greater sandwiching force on tissue of the native valve. The lower position of the arms of annular valve bodies 122 and 222 includes circumferentially shifting the position of the arms by the width of half a cell. In order to maintain the circumferential staggering of the atrial anchoring arms 46, 146, 246 and ventricular anchoring legs 54, 154, 254, rings 166 and 266 (and thereby ventricular anchoring supports 150 and 250) are circumferentially shifted correspondingly. As a result, whereas the peaks of ring 66 generally align with connections between adjacent cells of the downstream row of cells of tubular portion 32 (and are fixed to these sites), the peaks of rings 166 and 266 are generally aligned midway between these sites (i.e., at spaces of the cellular structure of the tubular portion). An appendages 168 (for annular valve body 122) or 268 (for annular valve body 222) facilitate fixing of the peak with respect to the tubular structure.

For annular valve body 122, appendages 168 are defined by inner frame 130 (e.g., by tubular portion 132 thereof) and extend (in a downstream direction) to the peaks of ring 166, to which they are fixed. For example, each appendage 168 may define a valve-frame coupling element 131 that is fixed to a respective outer-frame coupling element 161 defined by outer frame 260. In some embodiments, appendages 168 extend from sites 135. In some embodiments, appendages 168 are integral with tubular portion 132 and/or in-plane with the tubular portion (e.g., are part of its tubular shape).

For annular valve body 222, appendages 268 are defined by outer frame 260, and extend (e.g., in an upstream direction) from the peaks of ring 266. In some embodiments, appendages 268 extend to sites 235, to which they are fixed. For example, each appendage 268 may define an outer-frame coupling element 261 that is fixed to a respective valve-frame coupling element 231 defined by inner frame 230 (e.g., by tubular portion 232 thereof). In some embodiments, appendages 268 are integral with outer frame 260 and/or in-plane with adjacent portions of outer frame 260, such as ring 266.

Therefore, annular valve body 122 defines a hub at site 135, and annular valve body 222 defines a hub at site 235. For some embodiments, apparatus therefore comprises: a plurality of prosthetic valve leaflets; and a annular valve body, comprising: a tubular portion (132 or 232) defined by a repeating pattern of cells, the tubular portion extending circumferentially around longitudinal axis ax1 so as to define a longitudinal lumen, the prosthetic valve leaflets coupled to the inner frame and disposed within the lumen; an outer frame (160 or 260), comprising a plurality of ventricular anchoring supports (150 or 250), distributed circumferentially around the tubular portion, each support having a ventricular anchoring leg (154 or 254); an upstream support portion (140 or 240) that comprises a plurality of arms (146 or 246) that extend radially outward from the tubular portion; and a plurality of appendages (168 or 268), each having a first end that defines a coupling element (161 or 261) via which the tubular portion is coupled to the outer frame, and a second end; wherein the annular valve body defines a plurality of hubs (135 or 235), distributed circumferentially around the longitudinal axis on a plane that is transverse to longitudinal axis ax1, each hub defined by convergence and connection of, (i) two adjacent cells of the tubular portion, (ii) an arm of the plurality of arms, and (iii) an appendage of the plurality of appendages.

Reference is made to FIGS. 9A-C, which are schematic illustrations of an implant 320 comprising a annular valve body 322, in accordance with some embodiments of the invention. Except where noted otherwise, annular valve body 322 is identical to annular valve body 122, and implant 300 is identical to the implant to which annular valve body 122 belongs, mutatis mutandis. FIG. 9A is a side-view of implant 320, and FIG. 9B is an isometric bottom-view of the implant.

Annular valve body 122 comprises (i) a inner frame 330 that comprises a tubular portion 332 and an upstream support portion 340 that in some embodiments comprises a plurality of arms 346, and (ii) an outer frame (e.g., a leg frame) 360 that circumscribes the inner frame, and comprises a plurality of ventricular anchoring supports 350 that each comprise a ventricular anchoring leg 354. In some embodiments, outer frame 360 comprises a ring 366 to which ventricular anchoring supports 350 are coupled. Ring 366 is defined by a pattern of alternating peaks and troughs, the peaks being fixed to frame 330 at respective coupling points 352, e.g., as described hereinabove for annular valve body 22 and/or annular valve body 122, mutatis mutandis.

Annular valve body 322 comprises an annular upstream support portion 340 that has an inner portion 342 that extends radially outward from the upstream portion (e.g., the upstream end) of tubular portion 332. Upstream support portion 340 further comprises one or more fabric pockets 344 disposed circumferentially around inner portion 342, each pocket of the one or more pockets having an opening that faces a downstream direction (i.e., generally toward the downstream end of implant 320). In the figures, upstream support portion 340 has a single toroidal pocket 344 that extends circumferentially around inner portion 342.

In some embodiments, a covering 323 (e.g., similar to covering 23, described hereinabove, mutatis mutandis) is disposed over arms 346, thereby forming pocket 344. Further in some embodiments, arms 346 are shaped to form pocket 344 from covering 323. For example, and as shown, arms 346 may curve to form a hook-shape.

For some embodiments, portion 340 has a plurality of separate pockets 344, e.g., separated at arms 346. For some such embodiments, covering 323 is loosely-fitted (e.g., baggy) between radially-outward parts of arms 346, e.g., compared to inner portion 342, in which the covering is more closely-fitted between radially-inward parts of the arms.

FIG. 9C shows implant 320 implanted at native valve 10. Pocket 344 may be shaped and arranged to billow in response to perivalvular flow 302 of blood in an upstream direction. If ventricular systole forces blood in ventricle 8 between implant 320 and native valve 10, that blood inflates pocket 344 and presses it (e.g., covering 323 and/or the radially-outward part of arm 346) against tissue of atrium 6 (e.g., against the atrial wall), thereby increasing sealing responsively. It is hypothesized by the inventors that the shape and orientation of pocket 344 (e.g., the hook-shape of arms 346) facilitates this pressing radially-outward in response to the pocket's receipt of upstream-flowing blood.

Pocket(s) 344 may be used in combination with any of the implants described herein, mutatis mutandis.

Reference is again made to FIGS. 1A-9C. It is to be noted that unless specifically stated otherwise, the term “radially outward” (e.g., used to describe upstream support portion 40 and ventricular anchoring legs 54) means portions of the element are disposed progressively further outward from a central point (such as longitudinal axis ax1 or tubular portion 32), but does not necessarily mean disposed at 90 degrees with respect to longitudinal axis ax1. For example, ventricular anchoring legs 54 may extend radially outward at 90 degrees with respect to longitudinal axis ax1, but may alternatively extend radially outward at a shallower angle with respect to the longitudinal axis.

It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description.

Claims

1. A prosthetic heart valve, comprising: an annular valve body having a lumen extending between an upstream end of the annular valve body and a downstream end of the annular valve body;a plurality of atrial anchors extending from the annular valve body, each atrial anchor having a proximal end secured to the annular valve body and a terminal end opposite from the proximal end; anda plurality of ventricular anchors extending from the annular valve body, each ventricular anchor having a proximal end secured to the annular valve body and a terminal end opposite from the proximal end, whereinthe prosthetic heart valve is configured to be arranged in: a delivery configuration in which the atrial anchors and ventricular anchors are configured to be contained at least partially within a delivery device and are arranged in respective delivery positions, anda deployed-anchor configuration in which the atrial anchors and the ventricular anchors move radially outward from their respective delivery positions,at least one atrial anchor includes a pivoting portion configured to extend from the annular valve body in an upstream direction when the prosthetic heart valve is in the delivery configuration and to extend from the annular valve body in a downstream direction when the prosthetic heart valve is in the deployed-anchor configuration, anda first portion of at least one ventricular anchor is configured to abut the annular valve body when the prosthetic heart valve is in the delivery configuration and a second portion of the at least one ventricular anchor is configured to be situated upstream from at least part of the pivoting portion of the at least one atrial anchor when the prosthetic heart valve is in the deployed-anchor configuration.
2. The prosthetic heart valve of claim 1, wherein the at least one atrial anchor and the at least one ventricular anchor are configured to extend from the annular valve body in an upstream direction parallel to a longitudinal axis of the annular valve body when the prosthetic heart valve is in the delivery configuration.
3. The prosthetic heart valve of claim 1, wherein the first portion of the at least one ventricular anchor is arranged between the second portion and the proximal end of the at least one ventricular anchor.
4. The prosthetic heart valve of claim 1, wherein the terminal end of the at least one atrial anchor is configured to be situated at a position upstream and radially-outward from the pivoting portion of the at least one atrial anchor, relative to a longitudinal axis of the annular valve body, when the prosthetic heart valve is in the deployed-anchor configuration.
5. The prosthetic heart valve of claim 1, wherein the prosthetic heart valve is additionally configured to be arranged in a fully-expanded configuration, the annular valve body having a larger diameter when the prosthetic heart valve is in the fully-expanded configuration than when the prosthetic heart valve is in the delivery and deployed-anchor configurations.
6. The prosthetic heart valve of claim 5, wherein the diameter of the annular valve body remains constant when the prosthetic heart valve transitions from the delivery configuration to the deployed-anchor configuration.
7. The prosthetic heart valve of claim 5, wherein the pivoting portion of the at least one atrial anchor is configured to extend from the annular valve body in a downstream direction when the prosthetic heart valve is in the fully-expanded configuration, andthe terminal end of the at least one atrial anchor is configured to be situated radially-outward from the pivoting portion of the at least one atrial anchor, relative to a longitudinal axis of the annular valve body, when the prosthetic heart valve is in the fully-expanded configuration.
8. The prosthetic heart valve of claim 1, wherein the at least one atrial anchor includes an upstanding portion configured to extend in an upstream direction when the prosthetic heart valve is in the deployed-anchor configuration, the upstanding portion including the terminal end of the at least one atrial anchor.
9. The prosthetic heart valve of claim 1, wherein the annular valve body comprises: an annular outer frame; andan inner frame positioned at least partially within the annular outer frame, whereinthe plurality of ventricular anchors extend from the annular outer frame and the plurality of atrial anchors extend from the inner frame.
10. The prosthetic heart valve of claim 9, wherein the portion of the at least one ventricular anchor is configured to abut a portion of the inner frame when the prosthetic heart valve is in the delivery configuration.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No. 15/995,725, filed Jun. 1, 2018, which issued as U.S. Pat. No. 10,682,227 on Jun. 16, 2020, which is a continuation of U.S. patent application Ser. No. 15/682,789, filed Aug. 22, 2017, which issued as U.S. Pat. No. 10,449,047 on Oct. 22, 2019, which is a continuation of U.S. patent application Ser. No. 15/541,783, filed Jul. 6, 2017, which issued as U.S. Pat. No. 9,974,651 on May 22, 2018, which is a U.S. national stage entry under 35 U.S.C. § 371 of International Application No. PCT/IL2016/050125, filed Feb. 3, 2016, which claims priority from U.S. Provisional Patent Application No. 62/112,343, filed Feb. 5, 2015, all of which are hereby incorporated by reference in their entirety. U.S. patent application Ser. No. 15/995,725 also claims priority from U.S. Provisional Patent Application No. 62/560,384, filed Sep. 19, 2017, which is hereby incorporated by reference in its entirety.

US Referenced Citations (1141)

Number	Name	Date	Kind
3874388	King et al.	Apr 1975	A
4222126	Boretos et al.	Sep 1980	A
4261342	Aranguren	Apr 1981	A
4275469	Gabbay	Jun 1981	A
4340091	Skelton et al.	Jul 1982	A
4423525	Vallana et al.	Jan 1984	A
4853986	Allen	Aug 1989	A
4892541	Alonso	Jan 1990	A
4972494	White et al.	Nov 1990	A
4994077	Dobben	Feb 1991	A
5078739	Martin	Jan 1992	A
5108420	Marks	Apr 1992	A
5314473	Godin	May 1994	A
5332402	Teitelbaum	Jul 1994	A
5397351	Pavenik et al.	Mar 1995	A
5405378	Strecker	Apr 1995	A
5443500	Sigwart	Aug 1995	A
5473812	Morris et al.	Dec 1995	A
5607444	Lam	Mar 1997	A
5607470	Milo	Mar 1997	A
5647857	Anderson et al.	Jul 1997	A
5702397	Goble et al.	Dec 1997	A
5713948	Uflacker	Feb 1998	A
5716417	Girard et al.	Feb 1998	A
5741297	Simon	Apr 1998	A
5765682	Bley et al.	Jun 1998	A
5776140	Cottone	Jul 1998	A
5868777	Lam	Feb 1999	A
5873906	Lau et al.	Feb 1999	A
5954766	Zadno-Azizi et al.	Sep 1999	A
5957949	Leonhardt et al.	Sep 1999	A
5961549	Nguyen et al.	Oct 1999	A
5980565	Jayaraman	Nov 1999	A
6010530	Goicoechea	Jan 2000	A
6019787	Richard et al.	Feb 2000	A
6042607	Williamson, IV	Mar 2000	A
6059827	Fenton	May 2000	A
6074417	Peredo	Jun 2000	A
6113612	Swanson et al.	Sep 2000	A
6120534	Ruiz	Sep 2000	A
6126686	Badylak et al.	Oct 2000	A
6152937	Peterson et al.	Nov 2000	A
6165183	Kuehn et al.	Dec 2000	A
6165210	Lau et al.	Dec 2000	A
6187020	Zegdi et al.	Feb 2001	B1
6193745	Fogarty et al.	Feb 2001	B1
6254609	Vrba et al.	Jul 2001	B1
6264700	Kilcoyne et al.	Jul 2001	B1
6287339	Vasquez et al.	Sep 2001	B1
6312465	Griffin et al.	Nov 2001	B1
6332893	Mortier et al.	Dec 2001	B1
6334873	Lane et al.	Jan 2002	B1
6346074	Roth	Feb 2002	B1
6350278	Lenker et al.	Feb 2002	B1
6352561	Leopold et al.	Mar 2002	B1
6391036	Berg et al.	May 2002	B1
6402780	Williamson, IV	Jun 2002	B2
6409755	Vrba	Jun 2002	B1
6419696	Ortiz et al.	Jul 2002	B1
6428550	Vargas et al.	Aug 2002	B1
6440164	Dimatteo et al.	Aug 2002	B1
6454799	Schreck	Sep 2002	B1
6458153	Bailey et al.	Oct 2002	B1
6482228	Norred	Nov 2002	B1
6511491	Grudem et al.	Jan 2003	B2
6530952	Vesely	Mar 2003	B2
6540782	Snyders	Apr 2003	B1
6551350	Thornton et al.	Apr 2003	B1
6558396	Inoue	May 2003	B1
6558418	Carpentier et al.	May 2003	B2
6569196	Vesely	May 2003	B1
6602263	Swanson et al.	Aug 2003	B1
6616675	Evard et al.	Sep 2003	B1
6652556	VanTessel et al.	Nov 2003	B1
6669724	Park et al.	Dec 2003	B2
6682558	Tu et al.	Jan 2004	B2
6699256	Logan et al.	Mar 2004	B1
6716244	Klaco	Apr 2004	B2
6719781	Kim	Apr 2004	B1
6719788	Cox	Apr 2004	B2
6730118	Spenser et al.	May 2004	B2
6733525	Yang et al.	May 2004	B2
6752813	Goldfarb et al.	Jun 2004	B2
6755857	Peterson et al.	Jun 2004	B2
6764518	Godin	Jul 2004	B2
6767362	Schreck	Jul 2004	B2
6797002	Spence et al.	Sep 2004	B2
6821297	Snyders	Nov 2004	B2
6830585	Artof et al.	Dec 2004	B1
6830638	Boylan et al.	Dec 2004	B2
6893460	Spenser et al.	May 2005	B2
6926715	Hauck et al.	Aug 2005	B1
6960217	Bolduc	Nov 2005	B2
6964684	Ortiz et al.	Nov 2005	B2
6974476	McGuckin et al.	Dec 2005	B2
7011681	Vesely	Mar 2006	B2
7018406	Seguin et al.	Mar 2006	B2
7041132	Quijano et al.	May 2006	B2
7074236	Rabkin et al.	Jul 2006	B2
7077861	Spence	Jul 2006	B2
7101395	Tremulis et al.	Sep 2006	B2
7101396	Artof et al.	Sep 2006	B2
7137184	Schreck	Nov 2006	B2
7172625	Shu et al.	Feb 2007	B2
7175656	Khairkhahan	Feb 2007	B2
7198646	Figulla et al.	Apr 2007	B2
7201772	Schwammenthal	Apr 2007	B2
7226467	Lucatero et al.	Jun 2007	B2
7226477	Cox	Jun 2007	B2
7261686	Couvillon, Jr.	Aug 2007	B2
7288097	Séguin	Oct 2007	B2
7288111	Holloway et al.	Oct 2007	B1
7316716	Egan	Jan 2008	B2
7329279	Haug et al.	Feb 2008	B2
7335213	Hyde et al.	Feb 2008	B1
7351256	Hojeibane et al.	Apr 2008	B2
7374573	Gabbay	May 2008	B2
7377938	Sarac et al.	May 2008	B2
7381218	Schreck	Jun 2008	B2
7381219	Salahieh et al.	Jun 2008	B2
7404824	Webler et al.	Jul 2008	B1
7422603	Lane	Sep 2008	B2
7429269	Schwammenthal	Sep 2008	B2
7442204	Schwammenthal	Oct 2008	B2
7445630	Lashinski et al.	Nov 2008	B2
7455677	Vargas et al.	Nov 2008	B2
7455688	Furst et al.	Nov 2008	B2
7462162	Phan et al.	Dec 2008	B2
7481838	Carpentier et al.	Jan 2009	B2
7510575	Spenser et al.	Mar 2009	B2
7513909	Lane et al.	Apr 2009	B2
7524331	Birdsall	Apr 2009	B2
7527646	Rahdert et al.	May 2009	B2
7556632	Zadno	Jul 2009	B2
7556646	Yang et al.	Jul 2009	B2
7563267	Goldfarb et al.	Jul 2009	B2
7563273	Goldfarb et al.	Jul 2009	B2
7582111	Krolik et al.	Sep 2009	B2
7585321	Cribier	Sep 2009	B2
7597711	Drews et al.	Oct 2009	B2
7608091	Goldfarb et al.	Oct 2009	B2
7611534	Kapadia et al.	Nov 2009	B2
7621948	Hermann et al.	Nov 2009	B2
7625403	Krivoruchko	Dec 2009	B2
7632302	Vreeman et al.	Dec 2009	B2
7635329	Goldfarb et al.	Dec 2009	B2
7648528	Styrc	Jan 2010	B2
7655015	Goldfarb et al.	Feb 2010	B2
7682380	Thornton et al.	Mar 2010	B2
7708775	Rowe et al.	May 2010	B2
7717952	Case et al.	May 2010	B2
7717955	Lane et al.	May 2010	B2
7731741	Eidenschink	Jun 2010	B2
7736388	Goldfarb et al.	Jun 2010	B2
7748389	Salahieh et al.	Jul 2010	B2
7753922	Starksen	Jul 2010	B2
7753949	Lamphere et al.	Jul 2010	B2
7758595	Allen et al.	Jul 2010	B2
7758632	Hojeibane et al.	Jul 2010	B2
7758640	Vesely	Jul 2010	B2
7771467	Svensson	Aug 2010	B2
7771469	Liddicoat	Aug 2010	B2
7776083	Vesely	Aug 2010	B2
7780726	Seguin	Aug 2010	B2
7785341	Forster et al.	Aug 2010	B2
7799069	Bailey et al.	Sep 2010	B2
7803181	Furst et al.	Sep 2010	B2
7811296	Goldfarb et al.	Oct 2010	B2
7811316	Kalmann et al.	Oct 2010	B2
7824442	Salahieh et al.	Nov 2010	B2
7837645	Bessler et al.	Nov 2010	B2
7837727	Goetz et al.	Nov 2010	B2
7842081	Yadin	Nov 2010	B2
7850725	Vardi et al.	Dec 2010	B2
7871432	Bergin	Jan 2011	B2
7871436	Ryan et al.	Jan 2011	B2
7887583	Macoviak	Feb 2011	B2
7892281	Seguin et al.	Feb 2011	B2
7896915	Guyenot et al.	Mar 2011	B2
7914544	Nguyen et al.	Mar 2011	B2
7914569	Nguyen et al.	Mar 2011	B2
7927370	Webler et al.	Apr 2011	B2
7942927	Kaye et al.	May 2011	B2
7947072	Yang et al.	May 2011	B2
7947075	Goetz et al.	May 2011	B2
7955375	Agnew	Jun 2011	B2
7955377	Melsheimer	Jun 2011	B2
7955384	Rafiee et al.	Jun 2011	B2
7959666	Salahieh et al.	Jun 2011	B2
7959672	Salahieh et al.	Jun 2011	B2
7967833	Sterman et al.	Jun 2011	B2
7967857	Lane	Jun 2011	B2
7981151	Rowe	Jul 2011	B2
7981153	Fogarty et al.	Jul 2011	B2
7992567	Hirotsuka et al.	Aug 2011	B2
7993393	Carpentier et al.	Aug 2011	B2
8002825	Letac et al.	Aug 2011	B2
8002826	Seguin	Aug 2011	B2
8016877	Seguin et al.	Sep 2011	B2
8016882	Macoviak	Sep 2011	B2
8021420	Dolan	Sep 2011	B2
8021421	Fogarty et al.	Sep 2011	B2
8025695	Fogarty et al.	Sep 2011	B2
8029518	Goldfarb et al.	Oct 2011	B2
8029557	Sobrino-Serrano et al.	Oct 2011	B2
8029564	Johnson et al.	Oct 2011	B2
8034104	Carpentier et al.	Oct 2011	B2
8038720	Wallace et al.	Oct 2011	B2
8043360	McNamara et al.	Oct 2011	B2
8048138	Sulivan et al.	Nov 2011	B2
8048140	Purdy	Nov 2011	B2
8048153	Salahieh et al.	Nov 2011	B2
8052592	Goldfarb et al.	Nov 2011	B2
8052741	Bruszewski et al.	Nov 2011	B2
8052749	Salahieh et al.	Nov 2011	B2
8057493	Goldfarb et al.	Nov 2011	B2
8057532	Hoffman	Nov 2011	B2
8057540	Letac et al.	Nov 2011	B2
8062355	Figulla et al.	Nov 2011	B2
8062359	Marquez et al.	Nov 2011	B2
8070708	Rottenberg et al.	Dec 2011	B2
8070800	Lock et al.	Dec 2011	B2
8070802	Lamphere et al.	Dec 2011	B2
8070804	Hyde	Dec 2011	B2
8075611	Milwee et al.	Dec 2011	B2
8080054	Rowe	Dec 2011	B2
8083793	Lane et al.	Dec 2011	B2
D652927	Braido et al.	Jan 2012	S
D653341	Braido et al.	Jan 2012	S
8092518	Schreck	Jan 2012	B2
8092520	Quadri	Jan 2012	B2
8092521	Figulla et al.	Jan 2012	B2
8105377	Liddicoat	Jan 2012	B2
8109996	Stacchino et al.	Feb 2012	B2
8118866	Herrmann et al.	Feb 2012	B2
8133270	Kheradvar et al.	Mar 2012	B2
8136218	Millwee et al.	Mar 2012	B2
8137398	Tuval et al.	Mar 2012	B2
8142492	Forster et al.	Mar 2012	B2
8142494	Rahdert et al.	Mar 2012	B2
8142496	Berreklouw	Mar 2012	B2
8142497	Friedman	Mar 2012	B2
8147504	Ino et al.	Apr 2012	B2
8157852	Bloom et al.	Apr 2012	B2
8157853	Laske et al.	Apr 2012	B2
8157860	McNamara et al.	Apr 2012	B2
8163008	Wilson et al.	Apr 2012	B2
8163014	Lane et al.	Apr 2012	B2
D660433	Braido et al.	May 2012	S
D660967	Braido et al.	May 2012	S
8167894	Miles et al.	May 2012	B2
8167932	Bourang et al.	May 2012	B2
8167935	McGuckin, Jr. et al.	May 2012	B2
8172896	McNamara et al.	May 2012	B2
8172898	Alferness et al.	May 2012	B2
8177836	Lee et al.	May 2012	B2
8182528	Salahieh et al.	May 2012	B2
8211169	Lane et al.	Jul 2012	B2
8216256	Raschdorf, Jr. et al.	Jul 2012	B2
8216301	Bonhoeffer et al.	Jul 2012	B2
8221492	Case et al.	Jul 2012	B2
8221493	Boyle et al.	Jul 2012	B2
8226710	Nguyen et al.	Jul 2012	B2
8231670	Salahieh et al.	Jul 2012	B2
8236045	Benichou et al.	Aug 2012	B2
8236049	Rowe et al.	Aug 2012	B2
8252042	McNamara et al.	Aug 2012	B2
8252051	Chau et al.	Aug 2012	B2
8252052	Salahieh et al.	Aug 2012	B2
8257390	Carley et al.	Sep 2012	B2
8267988	Hamer et al.	Sep 2012	B2
8277501	Chalekian et al.	Oct 2012	B2
8287591	Keidar et al.	Oct 2012	B2
8298280	Yadin et al.	Oct 2012	B2
8303653	Bonhoeffer et al.	Nov 2012	B2
8308798	Pintor et al.	Nov 2012	B2
8313525	Tuval et al.	Nov 2012	B2
8317853	Agnew	Nov 2012	B2
8317855	Gregorich et al.	Nov 2012	B2
8323335	Rowe et al.	Dec 2012	B2
8328868	Paul et al.	Dec 2012	B2
8337541	Quadri et al.	Dec 2012	B2
8343174	Goldfarb et al.	Jan 2013	B2
8343213	Salahieh et al.	Jan 2013	B2
8348999	Kheradvar et al.	Jan 2013	B2
8366767	Zhang	Feb 2013	B2
8372140	Hoffman et al.	Feb 2013	B2
8377119	Drews et al.	Feb 2013	B2
8398708	Meiri et al.	Mar 2013	B2
8403981	Forster et al.	Mar 2013	B2
8403983	Quadri et al.	Mar 2013	B2
8408214	Spenser	Apr 2013	B2
8414644	Quadri et al.	Apr 2013	B2
8425593	Braido et al.	Apr 2013	B2
8430934	Das	Apr 2013	B2
8444689	Zhang	May 2013	B2
8449599	Chau et al.	May 2013	B2
8449625	Campbell et al.	May 2013	B2
8454686	Alkhatib	Jun 2013	B2
8460365	Haverkost et al.	Jun 2013	B2
8474460	Barrett et al.	Jul 2013	B2
8500821	Sobrino-Serrano et al.	Aug 2013	B2
8512400	Tran et al.	Aug 2013	B2
8539662	Stacchino et al.	Sep 2013	B2
8540767	Zhang	Sep 2013	B2
8545544	Spenser et al.	Oct 2013	B2
8551160	Figulla et al.	Oct 2013	B2
8551161	Dolan	Oct 2013	B2
8562672	Bonhoeffer et al.	Oct 2013	B2
8568475	Nguyen et al.	Oct 2013	B2
8579964	Lane et al.	Nov 2013	B2
8579965	Bonhoeffer et al.	Nov 2013	B2
8585755	Chau et al.	Nov 2013	B2
8585756	Bonhoeffer et al.	Nov 2013	B2
8591460	Wilson et al.	Nov 2013	B2
8591570	Revuelta et al.	Nov 2013	B2
8623075	Murray et al.	Jan 2014	B2
8623080	Fogarty et al.	Jan 2014	B2
8628569	Benichou et al.	Jan 2014	B2
8628570	Seguin	Jan 2014	B2
8628571	Hacohen et al.	Jan 2014	B1
8652203	Quadri et al.	Feb 2014	B2
8652204	Quill et al.	Feb 2014	B2
8657872	Seguin	Feb 2014	B2
8663322	Keranen	Mar 2014	B2
8673020	Sobrino-Serrano et al.	Mar 2014	B2
8679174	Ottma et al.	Mar 2014	B2
8685086	Navia et al.	Apr 2014	B2
8696742	Pintor et al.	Apr 2014	B2
8728155	Montorfano et al.	May 2014	B2
8734507	Keranen	May 2014	B2
8747460	Tuval et al.	Jun 2014	B2
8771345	Tuval et al.	Jul 2014	B2
8784472	Eidenschink	Jul 2014	B2
8784479	Antonsson et al.	Jul 2014	B2
8784481	Alkhatib et al.	Jul 2014	B2
8795355	Alkhatib	Aug 2014	B2
8795356	Quadri et al.	Aug 2014	B2
8795357	Yohanan et al.	Aug 2014	B2
8801776	House et al.	Aug 2014	B2
8808366	Braido et al.	Aug 2014	B2
8840663	Salahieh et al.	Sep 2014	B2
8840664	Karapetian et al.	Sep 2014	B2
8845722	Gabbay	Sep 2014	B2
8852261	White	Oct 2014	B2
8852272	Gross et al.	Oct 2014	B2
8870948	Erzberger et al.	Oct 2014	B1
8870949	Rowe	Oct 2014	B2
8870950	Hacohen	Oct 2014	B2
8876800	Behan	Nov 2014	B2
8894702	Quadri et al.	Nov 2014	B2
8900294	Paniagua et al.	Dec 2014	B2
8900295	Migliazza et al.	Dec 2014	B2
8906083	Obermiller et al.	Dec 2014	B2
8911455	Quadri et al.	Dec 2014	B2
8911489	Ben-Muvhar	Dec 2014	B2
8911493	Rowe et al.	Dec 2014	B2
8932343	Alkhatib et al.	Jan 2015	B2
8945177	Dell et al.	Feb 2015	B2
8961595	Alkhatib	Feb 2015	B2
8979922	Jayasinghe et al.	Mar 2015	B2
8986370	Annest	Mar 2015	B2
8986373	Chau et al.	Mar 2015	B2
8986375	Garde et al.	Mar 2015	B2
8992599	Thubrikar et al.	Mar 2015	B2
8992604	Gross et al.	Mar 2015	B2
8992608	Haug et al.	Mar 2015	B2
8998982	Richter et al.	Apr 2015	B2
9005273	Salahieh et al.	Apr 2015	B2
9011468	Ketai et al.	Apr 2015	B2
9011527	Li et al.	Apr 2015	B2
9017399	Gross et al.	Apr 2015	B2
D730520	Braido et al.	May 2015	S
D730521	Braido et al.	May 2015	S
9023100	Quadri et al.	May 2015	B2
9034032	McLean et al.	May 2015	B2
9034033	McLean et al.	May 2015	B2
9039757	McLean et al.	May 2015	B2
D732666	Nguyen et al.	Jun 2015	S
9050188	Schweich et al.	Jun 2015	B2
9060858	Thornton et al.	Jun 2015	B2
9072603	Tuval et al.	Jul 2015	B2
9084676	Chau et al.	Jul 2015	B2
9095434	Rowe	Aug 2015	B2
9119719	Zipory et al.	Sep 2015	B2
9125738	Figulla et al.	Sep 2015	B2
9125740	Morriss et al.	Sep 2015	B2
9132006	Spenser et al.	Sep 2015	B2
9132009	Hacohen et al.	Sep 2015	B2
9138312	Tuval et al.	Sep 2015	B2
9155619	Liu et al.	Oct 2015	B2
9173659	Bodewadt et al.	Nov 2015	B2
9173738	Murray et al.	Nov 2015	B2
9180009	Majkrzak et al.	Nov 2015	B2
9220594	Braido et al.	Dec 2015	B2
9226820	Braido et al.	Jan 2016	B2
9226839	Kariniemi et al.	Jan 2016	B1
9232995	Kovalsky et al.	Jan 2016	B2
9241790	Lane et al.	Jan 2016	B2
9241791	Braido et al.	Jan 2016	B2
9241792	Benichou et al.	Jan 2016	B2
9241794	Braido et al.	Jan 2016	B2
9248014	Lane et al.	Feb 2016	B2
9277994	Miller et al.	Mar 2016	B2
9289290	Alkhatib et al.	Mar 2016	B2
9289291	Gorman et al.	Mar 2016	B2
9295550	Nguyen et al.	Mar 2016	B2
9295551	Straubinger et al.	Mar 2016	B2
9295552	McLean et al.	Mar 2016	B2
9301836	Buchbinder et al.	Apr 2016	B2
9320591	Bolduc	Apr 2016	B2
D755384	Pesce et al.	May 2016	S
9326852	Spenser	May 2016	B2
9345573	Nyuli et al.	May 2016	B2
9358107	Nguyen et al.	Jun 2016	B2
9387078	Gross et al.	Jul 2016	B2
9393110	Levi et al.	Jul 2016	B2
9421098	Gifford et al.	Aug 2016	B2
9427303	Liddy et al.	Aug 2016	B2
9427316	Schweich, Jr. et al.	Aug 2016	B2
9439757	Wallace et al.	Sep 2016	B2
9445893	Vaturi	Sep 2016	B2
9463102	Kelly	Oct 2016	B2
9474638	Robinson et al.	Oct 2016	B2
9480559	Vidlund et al.	Nov 2016	B2
9492273	Wallace et al.	Nov 2016	B2
9498314	Behan	Nov 2016	B2
9498332	Hacohen et al.	Nov 2016	B2
9532870	Cooper et al.	Jan 2017	B2
9554897	Lane et al.	Jan 2017	B2
9554899	Granada et al.	Jan 2017	B2
9561103	Granada et al.	Feb 2017	B2
9566152	Schweich et al.	Feb 2017	B2
9572665	Lane et al.	Feb 2017	B2
9597182	Straubinger et al.	Mar 2017	B2
9629716	Seguin	Apr 2017	B2
9662203	Sheahan et al.	May 2017	B2
9681952	Hacohen et al.	Jun 2017	B2
9717591	Chau et al.	Aug 2017	B2
9743932	Amplatz et al.	Aug 2017	B2
9763657	Hacohen et al.	Sep 2017	B2
9770256	Cohen et al.	Sep 2017	B2
D800908	Hariton et al.	Oct 2017	S
9788941	Hacohen	Oct 2017	B2
9895226	Harari et al.	Feb 2018	B1
10010414	Cooper et al.	Jul 2018	B2
10076415	Metchik et al.	Sep 2018	B1
10105222	Metchik et al.	Oct 2018	B1
10111751	Metchik et al.	Oct 2018	B1
10123873	Metchik et al.	Nov 2018	B1
10130475	Metchik et al.	Nov 2018	B1
10136993	Metchik et al.	Nov 2018	B1
10149761	Granada et al.	Dec 2018	B2
10154906	Granada et al.	Dec 2018	B2
10159570	Metchik et al.	Dec 2018	B1
10182908	Tubishevitz et al.	Jan 2019	B2
10226341	Gross et al.	Mar 2019	B2
10231837	Metchik et al.	Mar 2019	B1
10238493	Metchik et al.	Mar 2019	B1
10245143	Gross et al.	Apr 2019	B2
10245144	Metchik et al.	Apr 2019	B1
10292816	Raanani et al.	May 2019	B2
10299927	McLean et al.	May 2019	B2
10321995	Christianson et al.	Jun 2019	B1
10322020	Lam et al.	Jun 2019	B2
10327895	Lozonschi et al.	Jun 2019	B2
10335278	McLean et al.	Jul 2019	B2
10357360	Hariton et al.	Jul 2019	B2
10376361	Gross et al.	Aug 2019	B2
10390952	Hariton et al.	Aug 2019	B2
10426610	Hariton et al.	Oct 2019	B2
10463487	Hariton et al.	Nov 2019	B2
10463488	Hariton et al.	Nov 2019	B2
10507105	Hariton et al.	Dec 2019	B2
10507108	Delgado et al.	Dec 2019	B2
10507109	Metchik et al.	Dec 2019	B2
10512456	Hacohen et al.	Dec 2019	B2
10517719	Miller et al.	Dec 2019	B2
10524792	Hernandez et al.	Jan 2020	B2
10524903	Hariton et al.	Jan 2020	B2
10531872	Hacohen et al.	Jan 2020	B2
10548731	Lashinski et al.	Feb 2020	B2
10575948	Iamberger et al.	Mar 2020	B2
10595992	Chambers	Mar 2020	B2
10595997	Metchik et al.	Mar 2020	B2
10610358	Vidlund et al.	Apr 2020	B2
10631871	Goldfarb et al.	Apr 2020	B2
10646342	Marr et al.	May 2020	B1
10667908	Hariton et al.	Jun 2020	B2
10667912	Dixon et al.	Jun 2020	B2
10682227	Hariton et al.	Jun 2020	B2
10695177	Hariton et al.	Jun 2020	B2
10702385	Hacohen	Jul 2020	B2
10722360	Hariton et al.	Jul 2020	B2
10758342	Chau et al.	Sep 2020	B2
10758344	Hariton et al.	Sep 2020	B2
10799345	Hariton et al.	Oct 2020	B2
10813760	Metchik et al.	Oct 2020	B2
10820998	Marr et al.	Nov 2020	B2
10842627	Delgado et al.	Nov 2020	B2
10849748	Hariton et al.	Dec 2020	B2
10856972	Hariton et al.	Dec 2020	B2
10856975	Hariton et al.	Dec 2020	B2
10856978	Straubinger et al.	Dec 2020	B2
10864078	Hariton et al.	Dec 2020	B2
10874514	Dixon et al.	Dec 2020	B2
10881511	Hariton et al.	Jan 2021	B2
10888422	Hariton et al.	Jan 2021	B2
10888425	Delgado et al.	Jan 2021	B2
10888644	Ratz et al.	Jan 2021	B2
10905548	Hariton et al.	Feb 2021	B2
10905549	Hariton et al.	Feb 2021	B2
10905552	Dixon et al.	Feb 2021	B2
10905554	Cao	Feb 2021	B2
10918483	Metchik et al.	Feb 2021	B2
10925595	Hacohen et al.	Feb 2021	B2
10925732	Delgado et al.	Feb 2021	B2
10945843	Delgado et al.	Mar 2021	B2
10945844	McCann et al.	Mar 2021	B2
10959846	Marr et al.	Mar 2021	B2
10973636	Hariton et al.	Apr 2021	B2
10993809	McCann et al.	May 2021	B2
11065114	Raanani et al.	Jul 2021	B2
11083582	McCann et al.	Aug 2021	B2
11147672	McCann et al.	Oct 2021	B2
11179240	Delgado et al.	Nov 2021	B2
11291545	Hacohen	Apr 2022	B2
11291546	Gross et al.	Apr 2022	B2
11291547	Gross et al.	Apr 2022	B2
11304806	Hariton et al.	Apr 2022	B2
11389297	Franklin et al.	Jul 2022	B2
20010005787	Oz et al.	Jun 2001	A1
20010021872	Bailey et al.	Sep 2001	A1
20010056295	Solem	Dec 2001	A1
20020013571	Goldfarb et al.	Jan 2002	A1
20020032481	Gabbay	Mar 2002	A1
20020099436	Thornton et al.	Jul 2002	A1
20020151970	Garrison et al.	Oct 2002	A1
20020177894	Acosta et al.	Nov 2002	A1
20030036791	Bonhoeffer et al.	Feb 2003	A1
20030050694	Yang et al.	Mar 2003	A1
20030060875	Wittens	Mar 2003	A1
20030069635	Cartledge	Apr 2003	A1
20030074052	Besselink	Apr 2003	A1
20030074059	Nguyen et al.	Apr 2003	A1
20030083742	Spence et al.	May 2003	A1
20030105519	Fasol et al.	Jun 2003	A1
20030158578	Pantages et al.	Aug 2003	A1
20040010272	Manetakis et al.	Jan 2004	A1
20040030382	St. Goar et al.	Feb 2004	A1
20040039414	Carley et al.	Feb 2004	A1
20040093060	Seguin et al.	May 2004	A1
20040122503	Campbell et al.	Jun 2004	A1
20040122514	Fogarty et al.	Jun 2004	A1
20040133267	Lane	Jul 2004	A1
20040143315	Bruun et al.	Jul 2004	A1
20040176839	Huynh et al.	Sep 2004	A1
20040186558	Pavcnik et al.	Sep 2004	A1
20040186565	Schreck	Sep 2004	A1
20040186566	Hindrichs et al.	Sep 2004	A1
20040210244	Vargas et al.	Oct 2004	A1
20040210304	Seguin et al.	Oct 2004	A1
20040220593	Greenhalgh	Nov 2004	A1
20040225354	Allen et al.	Nov 2004	A1
20040236354	Seguin	Nov 2004	A1
20040249433	Freitag	Dec 2004	A1
20040260389	Case et al.	Dec 2004	A1
20040260394	Douk et al.	Dec 2004	A1
20050004668	Aklog et al.	Jan 2005	A1
20050021056	St. Goar et al.	Jan 2005	A1
20050027348	Case et al.	Feb 2005	A1
20050038494	Eidenschink	Feb 2005	A1
20050055086	Stobie	Mar 2005	A1
20050075731	Artof et al.	Apr 2005	A1
20050080430	Wright et al.	Apr 2005	A1
20050080474	Andreas et al.	Apr 2005	A1
20050085900	Case et al.	Apr 2005	A1
20050137681	Shoemaker et al.	Jun 2005	A1
20050137686	Salahieh et al.	Jun 2005	A1
20050137688	Salahieh et al.	Jun 2005	A1
20050137689	Salahieh et al.	Jun 2005	A1
20050137690	Salahieh et al.	Jun 2005	A1
20050137691	Salahieh et al.	Jun 2005	A1
20050137692	Haug et al.	Jun 2005	A1
20050137693	Haug et al.	Jun 2005	A1
20050137695	Salahieh et al.	Jun 2005	A1
20050137697	Salahieh et al.	Jun 2005	A1
20050137699	Salahieh et al.	Jun 2005	A1
20050143809	Salahieh et al.	Jun 2005	A1
20050154443	Linder et al.	Jul 2005	A1
20050182483	Osborne et al.	Aug 2005	A1
20050182486	Gabbay	Aug 2005	A1
20050197695	Stacchino et al.	Sep 2005	A1
20050203549	Realyvasquez	Sep 2005	A1
20050203618	Sharkawy et al.	Sep 2005	A1
20050216079	MaCoviak	Sep 2005	A1
20050234508	Cummins et al.	Oct 2005	A1
20050240200	Bergheim	Oct 2005	A1
20050251251	Cribier	Nov 2005	A1
20050256566	Gabbay	Nov 2005	A1
20050267573	Macoviak et al.	Dec 2005	A9
20060004439	Spenser et al.	Jan 2006	A1
20060004469	Sokel	Jan 2006	A1
20060015171	Armstrong	Jan 2006	A1
20060020275	Goldfarb et al.	Jan 2006	A1
20060020327	Lashinski et al.	Jan 2006	A1
20060020333	Lashinski et al.	Jan 2006	A1
20060041189	Vancaillie	Feb 2006	A1
20060052867	Revuelta et al.	Mar 2006	A1
20060089627	Bumett et al.	Apr 2006	A1
20060111773	Rittgers et al.	May 2006	A1
20060135964	Vesley	Jun 2006	A1
20060161250	Shaw	Jul 2006	A1
20060047297	Case	Aug 2006	A1
20060178700	Quinn	Aug 2006	A1
20060178740	Stacchino et al.	Aug 2006	A1
20060184203	Martin et al.	Aug 2006	A1
20060190036	Wendel et al.	Aug 2006	A1
20060190038	Carley et al.	Aug 2006	A1
20060195183	Navia et al.	Aug 2006	A1
20060195184	Lane et al.	Aug 2006	A1
20060201519	Frazier et al.	Sep 2006	A1
20060212111	Case et al.	Sep 2006	A1
20060216404	Seyler et al.	Sep 2006	A1
20060229708	Powell et al.	Oct 2006	A1
20060241656	Starksen et al.	Oct 2006	A1
20060241748	Lee et al.	Oct 2006	A1
20060247680	Amplatz et al.	Nov 2006	A1
20060253191	Salahieh et al.	Nov 2006	A1
20060259136	Nguyen et al.	Nov 2006	A1
20060259137	Artof et al.	Nov 2006	A1
20060271166	Thill et al.	Nov 2006	A1
20060271171	McQuinn et al.	Nov 2006	A1
20060282150	Olson et al.	Dec 2006	A1
20060287719	Rowe et al.	Dec 2006	A1
20070016286	Herrmann et al.	Jan 2007	A1
20070016288	Gurskis et al.	Jan 2007	A1
20070027528	Agnew	Feb 2007	A1
20070027549	Godin	Feb 2007	A1
20070038293	St. Goar et al.	Feb 2007	A1
20070038295	Case et al.	Feb 2007	A1
20070043435	Seguin et al.	Feb 2007	A1
20070055340	Pryor	Mar 2007	A1
20070056346	Spenser et al.	Mar 2007	A1
20070078510	Ryan	Apr 2007	A1
20070112422	Dehdashtian	May 2007	A1
20070118151	Davidson	May 2007	A1
20070162103	Case et al.	Jul 2007	A1
20070162107	Haug et al.	Jul 2007	A1
20070162111	Fukamachi et al.	Jul 2007	A1
20070173932	Cali et al.	Jul 2007	A1
20070197858	Goldfarb et al.	Aug 2007	A1
20070198077	Cully et al.	Aug 2007	A1
20070198097	Zegdi	Aug 2007	A1
20070213810	Newhauser et al.	Sep 2007	A1
20070213813	Von Segesser et al.	Sep 2007	A1
20070219630	Chu	Sep 2007	A1
20070225759	Thommen et al.	Sep 2007	A1
20070225760	Moszner et al.	Sep 2007	A1
20070233186	Meng	Oct 2007	A1
20070233237	Krivoruchko	Oct 2007	A1
20070239272	Navia et al.	Oct 2007	A1
20070239273	Allen	Oct 2007	A1
20070244546	Francis	Oct 2007	A1
20070255400	Parravicini et al.	Nov 2007	A1
20080004688	Spenser et al.	Jan 2008	A1
20080004697	Lichtenstein et al.	Jan 2008	A1
20080051703	Thornton et al.	Feb 2008	A1
20080065011	Marchand et al.	Mar 2008	A1
20080065204	Macoviak et al.	Mar 2008	A1
20080071361	Tuval et al.	Mar 2008	A1
20080071363	Tuval et al.	Mar 2008	A1
20080071366	Tuval et al.	Mar 2008	A1
20080071369	Tuval et al.	Mar 2008	A1
20080077235	Kirson	Mar 2008	A1
20080082083	Forde et al.	Apr 2008	A1
20080082166	Styrc et al.	Apr 2008	A1
20080086164	Rowe et al.	Apr 2008	A1
20080086204	Rankin	Apr 2008	A1
20080091261	Long et al.	Apr 2008	A1
20080097595	Gabbay	Apr 2008	A1
20080132989	Snow et al.	Jun 2008	A1
20080140003	Bei et al.	Jun 2008	A1
20080147182	Righini et al.	Jun 2008	A1
20080161910	Revuelta et al.	Jul 2008	A1
20080167705	Agnew	Jul 2008	A1
20080167714	St. Goar et al.	Jul 2008	A1
20080188929	Schreck	Aug 2008	A1
20080195200	Vidlund et al.	Aug 2008	A1
20080200980	Robin et al.	Aug 2008	A1
20080208328	Antocci et al.	Aug 2008	A1
20080208332	Lamphere et al.	Aug 2008	A1
20080221672	Lamphere et al.	Sep 2008	A1
20080234814	Salahieh et al.	Sep 2008	A1
20080243245	Thambar et al.	Oct 2008	A1
20080255580	Hoffman et al.	Oct 2008	A1
20080262609	Gross et al.	Oct 2008	A1
20080269879	Sathe et al.	Oct 2008	A1
20080281411	Bereklouw	Nov 2008	A1
20080294234	Hartley et al.	Nov 2008	A1
20090005863	Goetz et al.	Jan 2009	A1
20090054969	Salahieh et al.	Feb 2009	A1
20090082844	Zacharias et al.	Mar 2009	A1
20090088836	Bishop et al.	Apr 2009	A1
20090099650	Bolduc et al.	Apr 2009	A1
20090105794	Ziarno et al.	Apr 2009	A1
20090112159	Slattery et al.	Apr 2009	A1
20090125098	Chuter	May 2009	A1
20090157175	Benichou	Jun 2009	A1
20090163934	Raschdorf, Jr. et al.	Jun 2009	A1
20090171363	Chocron	Jul 2009	A1
20090177278	Spence	Jul 2009	A1
20090210052	Forster et al.	Aug 2009	A1
20090222081	Linder et al.	Sep 2009	A1
20090240320	Tuval et al.	Sep 2009	A1
20090248143	Laham	Oct 2009	A1
20090259306	Rowe	Oct 2009	A1
20090264994	Saadat	Oct 2009	A1
20090276040	Rowe et al.	Nov 2009	A1
20090281619	Le et al.	Nov 2009	A1
20090287304	Dahlgren et al.	Nov 2009	A1
20090299449	Styre	Dec 2009	A1
20090306768	Quardi	Dec 2009	A1
20090319037	Rowe et al.	Dec 2009	A1
20100022823	Goldfarb et al.	Jan 2010	A1
20100023117	Yoganathan et al.	Jan 2010	A1
20100023120	Holecek et al.	Jan 2010	A1
20100036479	Hill et al.	Feb 2010	A1
20100049313	Alon et al.	Feb 2010	A1
20100076548	Konno	Mar 2010	A1
20100100167	Bortlein et al.	Apr 2010	A1
20100114299	Ben-Muvhar et al.	May 2010	A1
20100131054	Toval et al.	May 2010	A1
20100137979	Tuval et al.	Jun 2010	A1
20100160958	Clark	Jun 2010	A1
20100161036	Pintor et al.	Jun 2010	A1
20100161042	Maisano et al.	Jun 2010	A1
20100174363	Castro	Jul 2010	A1
20100179643	Shalev	Jul 2010	A1
20100179648	Richter et al.	Jul 2010	A1
20100179649	Richter et al.	Jul 2010	A1
20100185277	Braido et al.	Jul 2010	A1
20100217382	Chau et al.	Aug 2010	A1
20100222810	DeBeer et al.	Sep 2010	A1
20100228285	Miles et al.	Sep 2010	A1
20100234940	Dolan	Sep 2010	A1
20100249908	Chau et al.	Sep 2010	A1
20100249917	Zhang	Sep 2010	A1
20100256737	Pollock et al.	Oct 2010	A1
20100262232	Annest	Oct 2010	A1
20100280603	Maisano et al.	Nov 2010	A1
20100280606	Naor	Nov 2010	A1
20100312333	Navia	Dec 2010	A1
20100324595	Linder et al.	Dec 2010	A1
20100331971	Keranen et al.	Dec 2010	A1
20110004227	Goldfarb et al.	Jan 2011	A1
20110004296	Lutter et al.	Jan 2011	A1
20110004299	Navia et al.	Jan 2011	A1
20110015729	Jimenez et al.	Jan 2011	A1
20110015731	Carpentier et al.	Jan 2011	A1
20110022165	Oba et al.	Jan 2011	A1
20110178597	Navia et al.	Jan 2011	A9
20110029072	Gabbay	Feb 2011	A1
20110040374	Goetz et al.	Feb 2011	A1
20110040375	Letac et al.	Feb 2011	A1
20110046662	Moszner et al.	Feb 2011	A1
20110054466	Rothstein et al.	Mar 2011	A1
20110054596	Taylor	Mar 2011	A1
20110054598	Johnson	Mar 2011	A1
20110066233	Thornton et al.	Mar 2011	A1
20110071626	Wright et al.	Mar 2011	A1
20110077730	Fentster	Mar 2011	A1
20110082538	Dahlgren et al.	Apr 2011	A1
20110087322	Letac et al.	Apr 2011	A1
20110093063	Schreck	Apr 2011	A1
20110098525	Kermode et al.	Apr 2011	A1
20110106247	Miller et al.	May 2011	A1
20110112625	Ben-Muvhar et al.	May 2011	A1
20110112632	Chau et al.	May 2011	A1
20110118830	Liddicoat et al.	May 2011	A1
20110125257	Seguin et al.	May 2011	A1
20110125258	Centola	May 2011	A1
20110137326	Bachman	Jun 2011	A1
20110137397	Chao et al.	Jun 2011	A1
20110137409	Yang et al.	Jun 2011	A1
20110137410	Hacohen	Jun 2011	A1
20110144742	Madrid et al.	Jun 2011	A1
20110166636	Rowe	Jul 2011	A1
20110172784	Richter	Jul 2011	A1
20110184510	Maisano et al.	Jul 2011	A1
20110190877	Lane et al.	Aug 2011	A1
20110190879	Bobo et al.	Aug 2011	A1
20110202076	Richter	Aug 2011	A1
20110208283	Rust	Aug 2011	A1
20110208293	Tabor	Aug 2011	A1
20110208298	Tuval et al.	Aug 2011	A1
20110213461	Seguin et al.	Sep 2011	A1
20110218619	Benichou et al.	Sep 2011	A1
20110218620	Meiri et al.	Sep 2011	A1
20110224785	Hacohen	Sep 2011	A1
20110238159	Guyenot et al.	Sep 2011	A1
20110245911	Quill et al.	Oct 2011	A1
20110245917	Savage et al.	Oct 2011	A1
20110251675	Dwork	Oct 2011	A1
20110251676	Sweeney et al.	Oct 2011	A1
20110251678	Eidenschink et al.	Oct 2011	A1
20110251679	Weimeyer et al.	Oct 2011	A1
20110251680	Tran et al.	Oct 2011	A1
20110251682	Murray, III et al.	Oct 2011	A1
20110251683	Tabor	Oct 2011	A1
20110257721	Tabor	Oct 2011	A1
20110257729	Spenser et al.	Oct 2011	A1
20110257736	Marquez et al.	Oct 2011	A1
20110257737	Fogarty et al.	Oct 2011	A1
20110264191	Rothstein	Oct 2011	A1
20110264196	Savage et al.	Oct 2011	A1
20110264198	Murray, III et al.	Oct 2011	A1
20110264199	Tran et al.	Oct 2011	A1
20110264200	Tran et al.	Oct 2011	A1
20110264201	Yeung	Oct 2011	A1
20110264202	Murray, III et al.	Oct 2011	A1
20110264203	Dwork et al.	Oct 2011	A1
20110264206	Tabor	Oct 2011	A1
20110264208	Duffy	Oct 2011	A1
20110270276	Rothstein et al.	Nov 2011	A1
20110271967	Mortier et al.	Nov 2011	A1
20110282438	Drews et al.	Nov 2011	A1
20110282439	Thill et al.	Nov 2011	A1
20110282440	Cao	Nov 2011	A1
20110283514	Fogarty et al.	Nov 2011	A1
20110288634	Tuval et al.	Nov 2011	A1
20110295363	Girard et al.	Dec 2011	A1
20110301688	Dolan	Dec 2011	A1
20110301698	Miller et al.	Dec 2011	A1
20110301701	Padala et al.	Dec 2011	A1
20110301702	Rust et al.	Dec 2011	A1
20110306916	Nitzan et al.	Dec 2011	A1
20110307049	Kao	Dec 2011	A1
20110313452	Carley et al.	Dec 2011	A1
20110313515	Quadri et al.	Dec 2011	A1
20110319989	Lane et al.	Dec 2011	A1
20110319991	Hariton et al.	Dec 2011	A1
20120010694	Lutter et al.	Jan 2012	A1
20120016468	Robin et al.	Jan 2012	A1
20120022629	Perera et al.	Jan 2012	A1
20120022633	Olson et al.	Jan 2012	A1
20120022637	Ben-Movhar et al.	Jan 2012	A1
20120022639	Hacohen et al.	Jan 2012	A1
20120022640	Gross et al.	Jan 2012	A1
20120035703	Lutter et al.	Feb 2012	A1
20120035713	Lutter et al.	Feb 2012	A1
20120035722	Tuval et al.	Feb 2012	A1
20120041547	Duffy et al.	Feb 2012	A1
20120041551	Spenser et al.	Feb 2012	A1
20120046738	Lau et al.	Feb 2012	A1
20120046742	Toval et al.	Feb 2012	A1
20120053676	Ku et al.	Mar 2012	A1
20120053682	Kovalsky et al.	Mar 2012	A1
20120053688	Fogarty et al.	Mar 2012	A1
20120059454	Millwee et al.	Mar 2012	A1
20120059458	Buchbinder	Mar 2012	A1
20120065464	Ellis et al.	Mar 2012	A1
20120078237	Wang et al.	Mar 2012	A1
20120078353	Quadri et al.	Mar 2012	A1
20120078357	Conklin	Mar 2012	A1
20120083832	Delaloye et al.	Apr 2012	A1
20120083839	Letac et al.	Apr 2012	A1
20120083879	Eberhardt et al.	Apr 2012	A1
20120089223	Nguyen et al.	Apr 2012	A1
20120101570	Tuval et al.	Apr 2012	A1
20120101571	Thambar et al.	Apr 2012	A1
20120101572	Kovalsky et al.	Apr 2012	A1
20120123511	Brown	May 2012	A1
20120123529	Levi et al.	May 2012	A1
20120123530	Carpentier et al.	May 2012	A1
20120130473	Norris et al.	May 2012	A1
20120130474	Buckley	May 2012	A1
20120130475	Shaw	May 2012	A1
20120136434	Carpentier et al.	May 2012	A1
20120150218	Sandgren et al.	Jun 2012	A1
20120165915	Melsheimer et al.	Jun 2012	A1
20120165930	Gifford, III et al.	Jun 2012	A1
20120179244	Schankereli et al.	Jul 2012	A1
20120197292	Chin-Chen et al.	Aug 2012	A1
20120277845	Bowe	Nov 2012	A1
20120283824	Lutter et al.	Nov 2012	A1
20120290062	McNamara et al.	Nov 2012	A1
20120296360	Norris et al.	Nov 2012	A1
20120296418	Bonyuet et al.	Nov 2012	A1
20120300063	Majkrzak et al.	Nov 2012	A1
20120310328	Olson et al.	Dec 2012	A1
20120323316	Chau et al.	Dec 2012	A1
20120330408	Hillukka et al.	Dec 2012	A1
20130006347	McHugo	Jan 2013	A1
20130018450	Hunt	Jan 2013	A1
20130018458	Yohanan et al.	Jan 2013	A1
20130030519	Tran et al.	Jan 2013	A1
20130035759	Gross et al.	Feb 2013	A1
20130041204	Heilman et al.	Feb 2013	A1
20130041451	Patterson et al.	Feb 2013	A1
20130046373	Cartledge et al.	Feb 2013	A1
20130066341	Ketai et al.	Mar 2013	A1
20130066342	Dell et al.	Mar 2013	A1
20130116780	Miller et al.	May 2013	A1
20130123896	Bloss et al.	May 2013	A1
20130123900	Eblacas et al.	May 2013	A1
20130144381	Quadri et al.	Jun 2013	A1
20130150945	Crawford et al.	Jun 2013	A1
20130150956	Yohanan et al.	Jun 2013	A1
20130158647	Norris et al.	Jun 2013	A1
20130166017	Cartledge et al.	Jun 2013	A1
20130166022	Conklin	Jun 2013	A1
20130172978	Vidlund et al.	Jul 2013	A1
20130172992	Gross et al.	Jul 2013	A1
20130178930	Straubinger et al.	Jul 2013	A1
20130190861	Chau et al.	Jul 2013	A1
20130211501	Buckley et al.	Aug 2013	A1
20130245742	Norris	Sep 2013	A1
20130253643	Rolando et al.	Sep 2013	A1
20130261737	Costello	Oct 2013	A1
20130261738	Clague et al.	Oct 2013	A1
20130274870	Lombardi et al.	Oct 2013	A1
20130282059	Ketai et al.	Oct 2013	A1
20130289711	Liddy et al.	Oct 2013	A1
20130289740	Liddy et al.	Oct 2013	A1
20130297013	Klima et al.	Nov 2013	A1
20130304197	Buchbinder et al.	Nov 2013	A1
20130304200	McLean et al.	Nov 2013	A1
20130310928	Morriss et al.	Nov 2013	A1
20130325114	McLean et al.	Dec 2013	A1
20130331929	Mitra et al.	Dec 2013	A1
20140000112	Braido et al.	Jan 2014	A1
20140005767	Glazier et al.	Jan 2014	A1
20140005778	Buchbinder et al.	Jan 2014	A1
20140018911	Zhou et al.	Jan 2014	A1
20140018915	Biadillah et al.	Jan 2014	A1
20140031928	Murphy et al.	Jan 2014	A1
20140046430	Shaw	Feb 2014	A1
20140052237	Lane et al.	Feb 2014	A1
20140067050	Costello et al.	Mar 2014	A1
20140067054	Chau et al.	Mar 2014	A1
20140081376	Burkart et al.	Mar 2014	A1
20140106951	Brandon	Apr 2014	A1
20140120287	Jacoby et al.	May 2014	A1
20140121763	Duffy et al.	May 2014	A1
20140135894	Norris et al.	May 2014	A1
20140135895	Andress et al.	May 2014	A1
20140142681	Norris	May 2014	A1
20140142688	Duffy et al.	May 2014	A1
20140148891	Johnson	May 2014	A1
20140163690	White	Jun 2014	A1
20140172069	Roeder et al.	Jun 2014	A1
20140172077	Bruchman et al.	Jun 2014	A1
20140172082	Bruchman et al.	Jun 2014	A1
20140188210	Beard et al.	Jul 2014	A1
20140188221	Chung et al.	Jul 2014	A1
20140194981	Menk et al.	Jul 2014	A1
20140194983	Kovalsky et al.	Jul 2014	A1
20140207231	Hacohen et al.	Jul 2014	A1
20140214157	Börtlein et al.	Jul 2014	A1
20140214159	Vidlund et al.	Jul 2014	A1
20140222136	Geist et al.	Aug 2014	A1
20140222142	Kovalsky et al.	Aug 2014	A1
20140236287	Clague et al.	Aug 2014	A1
20140236289	Alkhatib	Aug 2014	A1
20140249622	Carmi et al.	Sep 2014	A1
20140257461	Robinson et al.	Sep 2014	A1
20140257467	Lane et al.	Sep 2014	A1
20140257475	Gross et al.	Sep 2014	A1
20140257476	Montorfano et al.	Sep 2014	A1
20140277358	Slazas	Sep 2014	A1
20140277409	Bortlein et al.	Sep 2014	A1
20140277411	Bortlein et al.	Sep 2014	A1
20140277412	Börtlein et al.	Sep 2014	A1
20140277418	Miller	Sep 2014	A1
20140277422	Ratz et al.	Sep 2014	A1
20140277427	Ratz et al.	Sep 2014	A1
20140296962	Cartledge et al.	Oct 2014	A1
20140296969	Tegels et al.	Oct 2014	A1
20140324164	Gross et al.	Oct 2014	A1
20140331475	Duffy et al.	Nov 2014	A1
20140343670	Bakis et al.	Nov 2014	A1
20140358222	Gorman, III et al.	Dec 2014	A1
20140358224	Tegels et al.	Dec 2014	A1
20140379065	Johnson et al.	Dec 2014	A1
20140379074	Spence et al.	Dec 2014	A1
20140379076	Vidlund et al.	Dec 2014	A1
20150018944	O'Connell et al.	Jan 2015	A1
20150032205	Matheny	Jan 2015	A1
20150045880	Hacohen	Feb 2015	A1
20150045881	Lim	Feb 2015	A1
20150094802	Buchbinder et al.	Apr 2015	A1
20150119970	Nakayama et al.	Apr 2015	A1
20150127097	Neumann et al.	May 2015	A1
20150142100	Morriss et al.	May 2015	A1
20150142103	Vidlund	May 2015	A1
20150157457	Hacohen	Jun 2015	A1
20150157458	Thambar et al.	Jun 2015	A1
20150173896	Richter et al.	Jun 2015	A1
20150173897	Raanani et al.	Jun 2015	A1
20150196390	Ma et al.	Jul 2015	A1
20150196393	Vidlund et al.	Jul 2015	A1
20150216661	Hacohen et al.	Aug 2015	A1
20150238313	Spence et al.	Aug 2015	A1
20150245934	Lombardi et al.	Sep 2015	A1
20150250588	Yang et al.	Sep 2015	A1
20150272730	Melnick et al.	Oct 2015	A1
20150272731	Racchini et al.	Oct 2015	A1
20150272734	Sheps et al.	Oct 2015	A1
20150305903	Kitaoka	Oct 2015	A1
20150320556	Levi et al.	Nov 2015	A1
20150327994	Morriss et al.	Nov 2015	A1
20150328000	Ratz et al.	Nov 2015	A1
20150335429	Morriss et al.	Nov 2015	A1
20150342736	Rabito et al.	Dec 2015	A1
20150351903	Morriss et al.	Dec 2015	A1
20150351904	Cooper et al.	Dec 2015	A1
20150351906	Hammer et al.	Dec 2015	A1
20150359629	Ganesan et al.	Dec 2015	A1
20160030169	Shahriari	Feb 2016	A1
20160030171	Quijano et al.	Feb 2016	A1
20160089482	Siegenthaler	Mar 2016	A1
20160095700	Righini	Apr 2016	A1
20160100939	Armstrong et al.	Apr 2016	A1
20160106539	Buchbinder et al.	Apr 2016	A1
20160113765	Ganesan et al.	Apr 2016	A1
20160113766	Ganesan et al.	Apr 2016	A1
20160113768	Ganesan et al.	Apr 2016	A1
20160158497	Tran et al.	Jun 2016	A1
20160175095	Dienno et al.	Jun 2016	A1
20160184098	Vaturi	Jun 2016	A1
20160213473	Hacohen et al.	Jul 2016	A1
20160220367	Barrett	Aug 2016	A1
20160242902	Morriss et al.	Aug 2016	A1
20160270911	Ganesan et al.	Sep 2016	A1
20160296330	Hacohen	Oct 2016	A1
20160310268	Oba et al.	Oct 2016	A1
20160310274	Gross et al.	Oct 2016	A1
20160317301	Quadri et al.	Nov 2016	A1
20160317305	Pelled et al.	Nov 2016	A1
20160324633	Gross et al.	Nov 2016	A1
20160324635	Vidlund et al.	Nov 2016	A1
20160324640	Gifford et al.	Nov 2016	A1
20160331525	Straubinger et al.	Nov 2016	A1
20160331526	Schweich et al.	Nov 2016	A1
20160338706	Rowe	Nov 2016	A1
20160367360	Cartledge et al.	Dec 2016	A1
20160367368	Vidlund et al.	Dec 2016	A1
20160374802	Levi et al.	Dec 2016	A1
20170042678	Ganesan et al.	Feb 2017	A1
20170049435	Sauer et al.	Feb 2017	A1
20170056166	Ratz et al.	Mar 2017	A1
20170056171	Cooper et al.	Mar 2017	A1
20170065407	Hacohen et al.	Mar 2017	A1
20170065411	Grundeman et al.	Mar 2017	A1
20170100236	Robertson et al.	Apr 2017	A1
20170128205	Tamir et al.	May 2017	A1
20170135816	Lashinski et al.	May 2017	A1
20170189174	Braido et al.	Jul 2017	A1
20170196688	Christianson et al.	Jul 2017	A1
20170196692	Kirk et al.	Jul 2017	A1
20170209264	Chau et al.	Jul 2017	A1
20170216026	Quill et al.	Aug 2017	A1
20170224323	Rowe et al.	Aug 2017	A1
20170231757	Gassler	Aug 2017	A1
20170231759	Geist et al.	Aug 2017	A1
20170231760	Lane et al.	Aug 2017	A1
20170239048	Goldfarb et al.	Aug 2017	A1
20170325948	Wallace et al.	Nov 2017	A1
20170333183	Backus	Nov 2017	A1
20170333187	Hariton et al.	Nov 2017	A1
20180000580	Wallace et al.	Jan 2018	A1
20180014930	Hariton et al.	Jan 2018	A1
20180021129	Peterson et al.	Jan 2018	A1
20180028215	Cohen	Feb 2018	A1
20180049873	Manash et al.	Feb 2018	A1
20180055630	Patel et al.	Mar 2018	A1
20180098850	Rafiee et al.	Apr 2018	A1
20180116790	Ratz et al.	May 2018	A1
20180116843	Schreck et al.	May 2018	A1
20180125644	Conklin	May 2018	A1
20180132999	Perouse	May 2018	A1
20180153689	Maimon et al.	Jun 2018	A1
20180161159	Lee et al.	Jun 2018	A1
20180206983	Noe et al.	Jul 2018	A1
20180214263	Rolando et al.	Aug 2018	A1
20180243086	Barbarino et al.	Aug 2018	A1
20180250126	O'Connor et al.	Sep 2018	A1
20180250147	Syed	Sep 2018	A1
20180296333	Dixon et al.	Oct 2018	A1
20180296336	Cooper et al.	Oct 2018	A1
20180325671	Abunassar et al.	Nov 2018	A1
20180344457	Gross et al.	Dec 2018	A1
20180344490	Fox et al.	Dec 2018	A1
20180353294	Calomeni et al.	Dec 2018	A1
20180360457	Ellis et al.	Dec 2018	A1
20190000613	Delgado et al.	Jan 2019	A1
20190015200	Delgado et al.	Jan 2019	A1
20190021852	Delgado et al.	Jan 2019	A1
20190053896	Adamek-Bowers et al.	Feb 2019	A1
20190060060	Chau et al.	Feb 2019	A1
20190060068	Cope et al.	Feb 2019	A1
20190060070	Groothuis et al.	Feb 2019	A1
20190069997	Ratz et al.	Mar 2019	A1
20190083261	Perszyk et al.	Mar 2019	A1
20190105153	Barash et al.	Apr 2019	A1
20190117391	Humair	Apr 2019	A1
20190175339	Vidlund	Jun 2019	A1
20190183639	Moore	Jun 2019	A1
20190192295	Spence et al.	Jun 2019	A1
20190336280	Naor et al.	Nov 2019	A1
20190350701	Adamek-Bowers et al.	Nov 2019	A1
20190365530	Hoang et al.	Dec 2019	A1
20190388218	Vidlund et al.	Dec 2019	A1
20190388220	Vidlund et al.	Dec 2019	A1
20200000449	Goldfarb et al.	Jan 2020	A1
20200000579	Manash et al.	Jan 2020	A1
20200015964	Noe et al.	Jan 2020	A1
20200030098	Delgado et al.	Jan 2020	A1
20200054335	Hernandez et al.	Feb 2020	A1
20200060818	Geist et al.	Feb 2020	A1
20200113677	McCann et al.	Apr 2020	A1
20200113689	McCann et al.	Apr 2020	A1
20200113692	McCann et al.	Apr 2020	A1
20200138567	Marr et al.	May 2020	A1
20200163761	Hariton et al.	May 2020	A1
20200214832	Metchik et al.	Jul 2020	A1
20200237512	McCann et al.	Jul 2020	A1
20200246136	Marr et al.	Aug 2020	A1
20200246140	Hariton et al.	Aug 2020	A1
20200253600	Darabian	Aug 2020	A1
20200261094	Goldfarb et al.	Aug 2020	A1
20200315786	Metchik et al.	Oct 2020	A1
20200337842	Metchik et al.	Oct 2020	A1
20210085455	Bateman et al.	Mar 2021	A1
20210093449	Hariton et al.	Apr 2021	A1
20210106419	Abunassar	Apr 2021	A1
20210113331	Quadri et al.	Apr 2021	A1
20210137680	Kizuka et al.	May 2021	A1
20210259835	Tyler, II et al.	Aug 2021	A1
20220000612	Hacohen	Jan 2022	A1

Foreign Referenced Citations (95)

Number	Date	Country
2822801	Aug 2006	CA
103974674	Aug 2014	CN
0170262	Feb 1986	EP
1264582	Dec 2002	EP
1264582	Dec 2002	EP
1637092	Mar 2006	EP
2 446 915	May 2012	EP
2349124	Oct 2018	EP
3583922	Dec 2019	EP
3270825	Apr 2020	EP
2485795	Sep 2020	EP
1999030647	Jun 1999	WO
2000-047139	Aug 2000	WO
2001-062189	Aug 2001	WO
WO 2003020179	Mar 2003	WO
03028558	Apr 2003	WO
WO 2004028399	Apr 2004	WO
2004108191	Dec 2004	WO
WO 2006007389	Jan 2006	WO
06054930	May 2006	WO
2006070372	Jul 2006	WO
2006089236	Aug 2006	WO
WO 2006086434	Aug 2006	WO
WO 2006116558	Nov 2006	WO
WO 2006128193	Nov 2006	WO
WO 2007047488	Apr 2007	WO
2007059252	May 2007	WO
08013915	Jan 2008	WO
WO 2008029296	Mar 2008	WO
2008070797	Jun 2008	WO
2008103722	Aug 2008	WO
09033469	Mar 2009	WO
09053497	Apr 2009	WO
2009091509	Jul 2009	WO
WO 2009091509	Jul 2009	WO
2010006627	Jan 2010	WO
WO 2010006627	Jan 2010	WO
WO 2010027485	Mar 2010	WO
WO 2010045297	Apr 2010	WO
WO 2010057262	May 2010	WO
2010073246	Jul 2010	WO
2010081033	Jul 2010	WO
2011069048	Jun 2011	WO
WO 2011069048	Jun 2011	WO
2011089601	Jul 2011	WO
2011106137	Sep 2011	WO
2011111047	Sep 2011	WO
0187190	Nov 2011	WO
2011137531	Nov 2011	WO
2011-143263	Nov 2011	WO
WO 2011144351	Nov 2011	WO
2011154942	Dec 2011	WO
2012011108	Jan 2012	WO
2012024428	Feb 2012	WO
2012036740	Mar 2012	WO
WO 2012036740	Mar 2012	WO
WO 2012048035	Apr 2012	WO
2012127309	Sep 2012	WO
2012177942	Dec 2012	WO
2013021374	Feb 2013	WO
2013021375	Feb 2013	WO
2013021384	Feb 2013	WO
WO 2013059747	Apr 2013	WO
WO 2013072496	May 2013	WO
2013078497	Jun 2013	WO
WO 2013078497	Jun 2013	WO
WO 2013114214	Aug 2013	WO
2013128436	Sep 2013	WO
WO 2013175468	Nov 2013	WO
2014022124	Feb 2014	WO
2014076696	May 2014	WO
2014115149	Jul 2014	WO
2014121280	Aug 2014	WO
2014145338	Sep 2014	WO
WO 2014144937	Sep 2014	WO
WO 2014164364	Oct 2014	WO
2015173794	Nov 2015	WO
2016016899	Feb 2016	WO
2016093877	Jun 2016	WO
WO 2016098104	Jun 2016	WO
2016125160	Aug 2016	WO
WO 2016150806	Sep 2016	WO
WO 2018025260	Feb 2018	WO
WO 2018029680	Feb 2018	WO
WO 2018039631	Mar 2018	WO
WO 2018106837	Jun 2018	WO
WO 2018112429	Jun 2018	WO
WO 2018118717	Jun 2018	WO
WO 2018131042	Jul 2018	WO
WO 2018131043	Jul 2018	WO
WO 2019027507	Feb 2019	WO
WO 2019195860	Oct 2019	WO
WO 2020167677	Aug 2020	WO
2021156866	Aug 2021	WO
2021186424	Sep 2021	WO

Non-Patent Literature Citations (159)

Entry
IPR2021-00383 Final Written Decision dated Jul. 18, 2022.
IPR2021-01051 Preliminary Guidance Patent Owner's Motion to Amend dated Jun. 24, 2022.
Ex Parte Quayle dated May 2, 2022, which issued during the prosecution of U.S. Appl. No. 16/879,952.
An International Search Report and a Written Opinion both dated May 3, 2022, which issued during the prosecution of Applicant's PCT/IL2021/051433.
An Office Action together with an English Summary dated May 7, 2022 which issued during the prosecution of Chinese Patent Application No. 201880058940.2.
Notice of Allowance dated May 4, 2022, which issued during the prosecution of U.S. Appl. No. 16/680,739.
An Office Action dated Jun. 28, 2022, which issued during the prosecution of U.S. Appl. No. 16/135,969.
An Office Action dated Jul. 8, 2022, which issued during the prosecution of U.S. Appl. No. 16/144,054.
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Exhibit 2009: Percutaneous Mitral Leaflet Repair: MitraClip Therapy for Mitral Regurgitation (Aug. 17, 2012) (8 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Exhibit 2010: Deposition of Dr. Ivan Vesely, Ph.D. (Sep. 27, 2021) (170 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Exhibit 2014: Second Declaration of Dr. Michael Sacks (Oct. 13, 2021) (28 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Patent Owner's Contingent Motion to Amend Under 37 C.F.R. § 42.121 (Oct. 13, 2021) (35 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Patent Owner's Response Pursuant to 37 C.F.R. § 42.120 (Oct. 13, 2021) (75 pages).
Fann, James I. et al., Beating Heart Catheter-Based Edge-to-Edge Mitral Valve Procedure in a Porcine Model: Efficacy and Healing Response, 110 Circulation, Aug. 2004, at 988 (6 pages).
Feldman, Ted et al., Percutaneous Mitral Repair With the MitraClip System: Safety and Midterm Durability in the Initial Everest Cohort, 54 J. Am. Coll. Cardiology, Aug. 2009, at 686 (9 pages).
Feldman, Ted et al., Percutaneous Mitral Valve Repair Using the Edge-to-Edge Technique: Six-Month Results of the Everest Phase I Clinical Trial, 46 J. Am. Coll. Cardiology, Dec. 2005, at 3134 (7 pages).
Maisano, Francesco et al., The Evolution From Surgery to Percutaneous Mitral Valve Interventions: The Role of the Edge-to-Edge Technique, 58 J. Am. Coll. Cardiology, Nov. 201 1, at 2174 (9 pages).
An Office Action dated Jan. 26, 2022, which issued during the prosecution of U.S. Appl. No. 16/888,210.
Notice of Allowance dated Jan. 31, 2022, which issued during the prosecution of U.S. Appl. No. 17/479,418.
An Office Action dated Mar. 18, 2022, which issued during the prosecution of U.S. Appl. No. 16/746,489.
Notice of Allowance dated Mar. 22, 2022, which issued during the prosecution of U.S. Appl. No. 17/366,711.
Notice of Allowance dated Mar. 4, 2022, which issued during the prosecution of U.S. Appl. No. 16/768,909.
An Office Action dated Dec. 9, 2021, which issued during the prosecution of U.S. Appl. No. 16/135,969.
An Office Action dated Jan. 24, 2022, which issued during the prosecution of U.S. Appl. No. 16/135,466.
An Office Action dated Apr. 11, 2022, which issued during the prosecution of U.S. Appl. No. 17/473,472.
IPR2021-00383 Preliminary Guidance dated Jan. 31, 2022.
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Paper 10: Decision Granting Institution Of Inter Partes Review (Dec. 10, 2021) (42 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Petitioners' Opposition to Patent Owner's Contingent Motion to Amend (Jan. 5, 2022) (32 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Petitioners' Reply to Patent Owner's Response (Jan. 5, 2022) (41 pages).
International Search Report dated May 30, 2016, by the European Patent Office in PCT/IL2016/050125 (6 pages).
Written Opinion of the International Searching Authority issued by the European Patent Office in PCT/IL2016/050125 (7 pages).
European Search Report dated Jun. 29, 2017, which issued during the prosecution of Applicant's European App. No. 11809374.9.
An Invitation to pay additional fees dated Sep. 29, 2017, which issued during the prosecution of Applicant's PCT/IL2017/050873.
An Office Action dated Oct. 23, 2017, which issued during the prosecution of U.S. Appl. No. 14/763,004.
An Office Action dated Jan. 17, 2018, which issued during the prosecution of U.S. Appl. No. 14/763,004.
An Office Action dated Dec. 7, 2017, which issued during the prosecution of U.S. Appl. No. 15/213,791.
An Office Action dated Feb. 8, 2018, which issued during the prosecution of U.S. Appl. No. 15/213,791.
An Office Action dated Feb. 2, 2018, which issued during the prosecution of U.S. Appl. No. 15/329,920.
An Office Action dated Feb. 7, 2018, which issued during the prosecution of U.S. Appl. No. 15/197,069.
An Invitation to pay additional fees dated Jan. 2, 2018, which issued during the prosecution of Applicant's PCT/IL2017/050849.
An Office Action dated Nov. 23, 2012, which issued during the prosecution of U.S. Appl. No. 13/033,852.
An Office Action dated Dec. 31, 2012, which issued during the prosecution of U.S. Appl. No. 13/044,694.
An Office Action dated Feb. 6, 2013, which issued during the prosecution of U.S. Appl. No. 13/412,814.
Langer F et al., “Ring plus String: Papillary muscle repositioning as an adjunctive repair technique for ischemic mitral regurgitation,” J Thorac Cardiovasc Surg 133:247-9, Jan. 2007.
Langer F et al., “Ring+String: Successful repair technique for ischemic mitral regurgitation with severe leaflet tethering,” Circulation 120[suppl 1]: S85-S91, Sep. 2009.
“Transcatheter Valve-in-Valve Implantation for Failed Bioprosthetic Heart Valves”, J Webb et al., Circulation. Apr. 2010; 121: 1848-1857.
Jansen, J., Willeke, S., Reul, H. and Rum, G. (1992), Detachable Shape-Memory Sewing Ring for Heart Valves. Artificial Organs, 16:294-297. 1992 (an abstract).
Alexander S. Geha, et al., Replacement of degenerated mitral and aortic bioprostheses without explanation Ann Thorac Surg. Jun. 2001; 72:1509-1514.
An International Search Report and a Written Opinion both dated Oct. 13, 2011 which issued during the prosecution of Applicant's PCT/IL11/00231.
An Office Action dated Jul. 1, 2016, which issued during the prosecution of U.S. Appl. No. 14/161,921.
An International Search Report and a Written Opinion both dated Dec. 5, 2011, which issued during the prosecution of Applicant's PCT/IL11/00582.
An Office Action dated May 29, 2012, which issued during the prosecution of U.S. Appl. No. 12/840,463.
U.S. Appl. No. 61/555,160, filed Nov. 3, 2011.
U.S. Appl. No. 61/525,281, filed Aug. 19, 2011.
U.S. Appl. No. 61/537,276, filed Sep. 21, 2011.
U.S. Appl. No. 61/515,372, filed Aug. 5, 2011.
U.S. Appl. No. 61/492.449, filed Jun. 2, 2011.
U.S. Appl. No. 61/588,892, filed Jan. 20, 2012.
An International Search Report and a Written Opinion both dated Feb. 6, 2013, which issued during the prosecution of Applicant's PCT/IL12/00292.
An International Search Report and a Written Opinion both dated Feb. 6, 2013, which issued during the prosecution of Applicant's PCT/IL12/00293.
An Office Action dated Nov. 28, 2012, which issued during the prosecution of U.S. Appl. No. 12/961,721.
An Office Action dated Feb. 15, 2013, which issued during the prosecution of U.S. Appl. No. 12/840,463.
An Office Action dated Feb. 10, 2014, which issued during the prosecution of U.S. Appl. No. 13/033,852.
An Office Action dated Sep. 19, 2014, which issued during the prosecution of U.S. Appl. No. 13/044,694.
An International Search Report and a Written Opinion both dated Sep. 4, 2014, which issued during the prosecution of Applicant's PCT/IL2014/050087.
Invitation to Pay Additional Fees dated Jun. 12, 2014 PCT/IL2014/050087.
An Office Action dated Jun. 17, 2014, which issued during the prosecution of U.S. Appl. No. 12/961,721.
An Office Action dated Jul. 3, 2014, which issued during the prosecution of U.S. Appl. No. 13/033,852.
An Office Action dated May 23, 2014, which issued during the prosecution of U.S. Appl. No. 13/412,814.
Dominique Himbert; Mitral Regurgitation and Stenosis from Bioprosthesis and Annuloplasty Failure: Transcatheter approaches and outcomes, 24 pages Oct. 28, 2013.
An International Search Report and a Written Opinion both dated Mar. 17, 2014 which issued during the prosecution of Applicant's PCT/IL2013/050937.
An International Preliminary Report on Patentabilty dated Dec. 2, 2013, which issued during the prosecution of Applicant's PCT/IL11/00582.
An Office Action dated Sep. 12, 2013, which issued during the prosecution of U.S. Appl. No. 13/412,814.
An Office Action dated Aug. 2, 2013, which issued during the prosecution of U.S. Appl. No. 13/033,852.
An International Preliminary Report on patentabilty dated Sep. 11, 2012, which issued during the prosecution of Applicant's PCT/IL2011/000231.
An Office Action dated Jul. 2, 2014, which issued during the prosecution of U.S. Appl. No. 13/811,308.
An Office Action dated Jan. 20, 2016, which issued during the prosecution of U.S. Appl. No. 14/161,921.
An Office Action dated Jul. 23, 2013, which issued during the prosecution of U.S. Appl. No. 12/961,721.
An Office Action dated Jul. 18, 2013, which issued during the prosecution of U.S. Appl. No. 13/044,694.
An Office Action dated Nov. 8, 2013, which issued during the prosecution of U.S. Appl. No. 12/840,463.
An Office Action dated Jun. 4, 2014, which issued during the prosecution of U.S. Appl. No. 12/840,463.
An Office Action dated Aug. 13, 2012, which issued during the prosecution of U.S. Appl. No. 13/044,694.
An Office Action dated Jul. 2, 2012, which issued during the prosecution of U.S. Appl. No. 13/033,852.
An Office Action dated Feb. 3, 2014, which issued during the prosecution of U.S. Appl. No. 13/811,308.
An International Preliminary Report on patentabilty dated Feb. 11, 2014, which issued during the prosecution of Applicant's PCT/IL12/00292.
An International Preliminary Report on patentabilty dated Feb. 11, 2014, which issued during the prosecution of Applicant's PCT/IL12/00293.
A Notice of Allowance dated Aug. 15, 2014, which issued during the prosecution of U.S. Appl. No. 13/412,814.
An Office Action dated Aug. 14, 2012, which issued during the prosecution of U.S. Appl. No. 12/961,721.
U.S. Appl. No. 61/283,819, filed Dec. 8, 2009.
Notice of Allowance dated Sep. 29, 2016, which issued during the prosecution of U.S. Appl. No. 14/442,541.
U.S. Appl. No. 61/756,034, filed Jan. 24, 2013.
U.S. Appl. No. 61/756,049, filed Jan. 24, 2013.
Notice of Allowance dated Jul. 1, 2016, which issued during the prosecution of U.S. Appl. No. 14/442,541.
An Office Action dated Mar. 25, 2015, which issued during the prosecution of U.S. Appl. No. 12/840,463.
Notice of Allowance dated May 5, 2015, which issued during the prosecution of U.S. Appl. No. 12/840,463.
Georg Lutter, MD, et al; “Percutaneous Valve Replacement: Current State and Future Prospects”, The Annals of Thoracic Surgery ; vol. 78, pp. 2199-2206; Dec. 2004.
An Office Action dated Dec. 10, 2015, which issued during the prosecution of U.S. Appl. No. 14/237,258.
An International Preliminary Report on Patentability dated Jul. 28, 2015, which issued during the prosecution of Applicant's PCT/IL2014/050087.
An Office Action dated Nov. 27, 2015, which issued during the prosecution of U.S. Appl. No. 14/626,267.
An Office Action dated Jan. 21, 2016, which issued during the prosecution of U.S. Appl. No. 14/237,264.
An Office Action dated Apr. 13, 2016, which issued during the prosecution of U.S. Appl. No. 14/626,267.
An International Search Report and a Written Opinion both dated May 30, 2016, which issued during the prosecution of Applicant's PCT/IL2016/050125.
An Office Action dated Sep. 26, 2016, which issued during the prosecution of U.S. Appl. No. 14/763,004.
An Office Action dated Jan. 18, 2017, which issued during the prosecution of U.S. Appl. No. 14/626,267.
An Office Action dated Feb. 7, 2017, which issued during the prosecution of U.S. Appl. No. 14/689,608.
An Office Action dated Feb. 8, 2017, which issued during the prosecution of UK Patent Application No. 1613219.3.
An Office Action together dated Feb. 10, 2017, which issued during the prosecution of European Patent Application No. 12821522.5.
An International Search Report and a Written Opinion both dated Oct. 27, 2015, which issued during the prosecution of Applicant's PCT/IL2015/050792.
European Search Report dated Feb. 18, 2015, which issued during the prosecution of Applicant's European App No. 12821522.5.
Saturn Project—a novel solution for transcatheter heart valve replacement specifically designed to address clinical therapeutic needs on mitral valve: Dec. 2016.
Righini presentation EuroPCR May 2015 (Saturn)—(downloaded from: https://www.pcronline.com/Cases-resourcesimages/Resources/Course-videos-slides/2015/Cardiovascularinnovation-pipeline-Mitral-and-tricuspid-valve-interventions).
An International Preliminary Report on Patentability dated Jan. 31, 2017, which issued during the prosecution of Applicant's PCT/IL2015/050792.
An Office Action dated Jan. 30, 2015, which issued during the prosecution of UK Patent Application No. 1413474.6.
An International Preliminary Report on Patentability dated May 19, 2015, which issued during the prosecution of Applicant's PCT/IL2013/050937.
Dusan Pavcnik, MD, PhD2, et al; “Development and Initial Experimental Evaluation of a Prosthetic Aortic Valve for Transcatheter Placement”, Cardiovascular Radiology. Radiology Apr. 1992, vol. 183, pp. 151-154.
Notice of Allowance dated Oct. 16, 2013, which issued during the prosecution of U.S. Appl. No. 13/675,119.
Notice of Allowance dated Feb. 11, 2015, which issued during the prosecution of U.S. Appl. No. 13/033,852.
Notice of Allowance dated Mar. 10, 2015, which issued during the prosecution of U.S. Appl. No. 13/811,308.
An Office Action dated Aug. 28, 2015, which issued during the prosecution of U.S. Appl. No. 14/237,264.
Notice of Allowance dated Apr. 8, 2016, which issued during the prosecution of U.S. Appl. No. 14/237,258.
Notice of Allowance dated May 10, 2016, which issued during the prosecution of U.S. Appl. No. 14/237,258.
Notice of Allowance dated May 20, 2016, which issued during the prosecution of U.S. Appl. No. 14/237,258.
An Office Action dated Jun. 30, 2015, which issued during the prosecution of U.S. Appl. No. 14/522,987.
An Office Action dated Feb. 25, 2016, which issued during the prosecution of U.S. Appl. No. 14/522,987.
Notice of Allowance dated Dec. 13, 2013, which issued during the prosecution of U.S. Appl. No. 13/675,119.
An International Preliminary Report on Patentability dated Aug. 8, 2017, which issued during the prosecution of Applicant's PCT/IL2016/050125.
Maisano (2015) TCR presentation re Cardiovalve.
Sündermann, Simon H. et al., Feasibility of the Engager™ aortic transcatheter valve system using a flexible over-the-wire design, 42 European Journal of Cardio-Thoracic Surgery, Jun. 27, 2012, at e48 (5 pages).
Symetis S.A., Clinical Investigation Plan for Acurate Neo™ TA Delivery System, Protocol Jan. 2015, ver. 2, ClinicalTrials.gov Identifier NCT02950428, Sep. 8, 2015 (76 pages).
Tchetche, Didier et al., New-generation TAVI devices: description and specifications, 10 EuroIntervention (Supplement), Sep. 2014, at U90 (11 pages).
Ando, Tomo et al., Iatrogenic Ventricular Septal Defect Following Transcatheter Aortic Valve Replacement: A Systematic Review, 25 Heart, Lung, and Circulation 968-74 (Apr. 22, 2016) (7 pages).
Batista, Randas J. V. et al., Partial Left Ventriculectomy to Treat End-Stage Heart Disease, 64 Annals Thoracic Surgery 634-38 (1997) (5 pages).
Beall, Jr., Arthur C. et al., Clinical Experience with a Dacron Velour-Covered Teflon-Disc Mitral-Valve Prosthesis, 5 Annals Thoracic Surgery 402-10 (1968) (9 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Exhibit 1014: Transcript of proceedings held May 20, 2021 (May 26, 2021) (21 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Exhibit 1015: Facilitate, Merriam-Webster.com, https://www. www.merriam-webster.com/dictionary/facilitate (accessed May 27, 2021) (5 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Paper 12: Petitioners' Authorized Reply to Patent Owner's Preliminary Response (May 27, 2021) (9 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Paper 13: Patent Owner's Authorized Surreply to Petitioner's Reply to Patent Owner's Preliminary Response (Jun. 4, 2021) (8 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Paper 16: Institution Decision (Jul. 20, 2021) (51 pages).
Fucci, Carlo et al., Improved Results with Mitral Valve Repair Using New Surgical Techniques, 9 Eur. J. Cardiothoracic Surgery 621-27 (1995) (7 pages).
Maisano, Francesco et al., The Edge-To-Edge Technique: A Simplified Method to Correct Mitral Insufficiency, 13 Eur. J. Cardiothoracic Surgery 240-46 (1998) (7 pages).
Poirier, Nancy et al., A Novel Repair for Patients with Atrioventricular Septal Defect Requiring Reoperation for Left Atrioventricular Valve Regurgitation, 18 Eur. J. Cardiothoracic Surgery 54-61 (2000) (8 pages).
Stone, Gregg W. et al., Clinical Trial Design Principles and Endpoint Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 1: Clinical Trial Design Principles, 66 J. Am. C. Cardiology 278-307 (2015) (30 pages).
Urena, Marina et al., Transseptal Transcatheter Mitral Valve Replacement Using Balloon-Expandable Transcatheter Heart Valves, JACC: Cardiovascular Interventions 1905-19 (2017) (15 pages).
An Office Action dated Mar. 3, 2023, which issued during the prosecution of European Patent Application No. 17751143.3.
An Office Action dated Mar. 20, 2023, which issued during the prosecution of U.S. Appl. No. 17/181,722.
An Office Action dated Jul. 27, 2022, which issued during the prosecution of U.S. Appl. No. 16/881,350.
An Office Action dated Sep. 21, 2022, which issued during the prosecution of U.S. Appl. No. 16/776,581.
An Office Action dated Jul. 20, 2022, which issued during the prosecution of U.S. Appl. No. 17/101,787.
An Office Action dated Sep. 16, 2022, which issued during the prosecution of U.S. Appl. No. 16/135,466.
An Office Action dated Aug. 1, 2022, which issued during the prosecution of European Patent Application No. 18826823.9.
European Search Report dated Sep. 6, 2022 which issued during the prosecution of Applicant's European App No. 22161862.2.
IPR2021-01051 Petitioners' Reply to Preliminary Guidance dated Aug. 2, 2022.
IPR2021-01051 Patent Owner's Sur-Reply to Petitioners' Reply to Preliminary Guidance dated Aug. 23, 2022.
An Office Action dated Aug. 5, 2022, which issued during the prosecution of U.S. Appl. No. 16/760,147.
Office Action dated Nov. 28, 2022 issued by the United States Patent Office in U.S. Appl. No. 17/141,853.
U.S. Appl. No. 15/995,725, filed Jun. 1, 2018, published as 2018/0271655, issued as U.S. Pat. No. 10,682,227.
U.S. Appl. No. 15/682,789, filed Aug. 22, 2017, published as 2017/0367823, issued as U.S. Pat. No. 10,449,047.
U.S. Appl. No. 15/541,783, filed Jul. 6, 2017, published as 2018/0014930, issued as U.S. Pat. No. 9,974,651.
U.S. Appl. No. 62/112,343, filed Feb. 5, 2015.

Related Publications (1)

	Number	Date	Country
	20200297486 A1	Sep 2020	US

Provisional Applications (2)

	Number	Date	Country
	62112343	Feb 2015	US
	62560384	Sep 2017	US

Continuations (3)

	Number	Date	Country
Parent	15995725	Jun 2018	US
Child	16896858		US
Parent	15682789	Aug 2017	US
Child	15995725		US
Parent	15541783		US
Child	15682789		US

Prosthetic valve with pivoting tissue anchor portions

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