= ffi
`
`a,
`
`C
`
`�
`� Manuel R. ValclLfeel, Esq.
`
`oJOS-579-0812
`email: Valca.n:clm@gtlaw.com
`
`VIA EXPRESS MAil,
`
`A TT O A Ni YS A T 1. A "C'
`
`o�[f��f�o
`1����,u
`
`JuJy 9, 2004
`
`Commissioner for Patents
`P.O. Box 1450
`
`Alexandria, Virginia 22313-1450
`
`
`
`CO TINUATlON-IN-PART UTO..lTY PA TENT APPLICA TlON
`
`Sir:
`
`INVENTORS: Paniagua, et al.
`
`Transmitted herewith for filing is the continuation-in-part patent application of:
`
`TRANSMITIAL
`
`
`
`
`
`FOR: Percutaneously implantable replacement heart valve device and method of making same.
`
`Enclosed are:
`
`1. 34 pages of specification, claims, abstract.
`
`2. 12 pages of figur es.
`l.136(a) with respect to application
`3. Petition for extension of time under 37 CFR
`
`
`
`(to which the enclosed application is a continuation·in part).
`
`serial no. 10/037,266,
`4. Postage paid retwn postcard.
`
`(33 claims, including one
`g fee of $545.00 for this application
`
`Please charg
`e the filin
`), the petition fee of
`
`excess independent claim
`
`
`$210.00 for the petition for extension of time with
`t Account
`
`
`
`
`respect to application serial no. I0/037 266 and any other required charges to Deposi
`No. 50-1792. A duplicate of this letter is enclosed for charging purposes.
`
`
`-Provisional Patent
`The enclosed application is a continuation-in-part of U.S. Non
`ary 4, 2002. A Declaration and Power of
`Application Serial No. 10/037
`,266 filed on Janu
`
`
`ty starus and an Information Disclosure Statement were filed in
`Attorney, claim for small enti
`rporated into the present
`
`
`connection with Application Serial No. I 0/037
`,266, and are inco
`ty status.
`y this reference. The A
`application b
`pplicants claim small enti
`
`GRtf.NAEllG THAURIG, P.A.
`
`1221 8HICKELL AVF.NUE MIAMI, f'LORIOA 33131
`305-579-0500 FAX 305-579-0717 www.g1law.com
`EW l'ORK WASlll CTO • o.c. TLA 'TA PHILAO£LPHIA TnONS COHN H CHICAGO HosTO PH
`
`
`f'ORT LAUDERDALE BOCA RATO WEST PALll BEACH 0RLA 'DO TALLAHASSE
`
`Of:NIX WlLMINGTO. Los ANt;f;L£S DENVER
`
`II I
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 1 of 1441
`
`

`

`Commissioner for Patents
`July 9, 2004
`Page2
`
`Please direct all communications regarding the foregoing to the undersigned.
`
`Respectfully submitted,
`
`GREENBERG TRAURIG, P.A.
`
`~v~
`
`M uel R. Valcarcel
`R
`stration No. 41,360
`
`MRV/kfh
`
`Enclosures
`
`\\MIA-SRVOl\1570118v01
`
`Express Mail Mailing Label No. ER940080602US
`
`GREENBERG TRAURIG, P.A.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 2 of 1441
`
`

`

`O')
`
`.....
`.....
`c.o
`0
`--.J
`O')
`~ o - C
`0 -.s::-_¢
`~ Manuel R. Valcarcel, Esq.
`O 305-579-0812
`email: Valcarcelrn@gtlaw.com
`
`ATTORNEYS AT LAW
`
`~~[[~~[~~
`l~~~~I~
`
`July 9, 2004
`
`VIA EXPRESS MAIL
`
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, Virginia 22313-1450
`
`CONTINUATION-IN-PART UTILITY PATENT APPLICATION
`TRANSMITTAL
`
`Sir:
`
`Transmitted herewith for filing is the continuation-in-part patent application of:
`Paniagua, et al.
`INVENTORS:
`
`FOR: Percutaneously implantable replacement heart valve device and method of making same.
`
`Enclosed are:
`
`1.
`2.
`3.
`
`4.
`
`34 pages of specification, claims, abstract.
`12 pages of figures.
`Petition for extension of time under 37 CFR l.136(a) with respect to application
`serial no. 10/037,266, (to which the enclosed application is a continuation in part).
`Postage paid return postcard.
`
`Please charge the filing fee of $545.00 for this application (33 claims, including one
`excess independent claim), the petition fee of $210.00 for the petition for extension of time with
`respect to application serial no. 10/037,266 and any other required charges to Deposit Account
`No. 50-1792. A duplicate of this letter is enclosed for charging purposes.
`
`The enclosed application is a continuation-in-part of U.S. Non-Provisional Patent
`Application Serial No. 10/037,266 filed on January 4, 2002. A Declaration and Power of
`Attorney, claim for small entity status and an Information Disclosure Statement were filed in
`connection with Application Serial No. 10/037,266, and are incorporated into the present
`application by this reference. The Applicants claim small entity status.
`
`1221 BRICKELL AVENUE MIAMI, FLORIDA 33131
`305-579-0500 FAX 305-579-0717 www.gtlaw.com
`MIAMI NEW YORK WASHINGTON, D.C. ATLANTA PHILADELPHIA TYSONS CORNER CHICAGO BOSTON PHOENIX WILMINGTON Los ANGELES DENVER
`
`FORT LAUDERDALE BOCA RATON WEST PALM BEACH ORLANDO TALLAHASSEE
`
`GREENBERG TRAURIG, P.A.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 3 of 1441
`
`

`

`Commissioner for Patents
`July 9, 2004
`Page2
`
`Please direct all communications regarding the foregoing to the undersigned.
`
`Respectfully submitted,
`
`GREENBERG TRAURIG, P.A.
`
`~v~
`
`M uel R. Valcarcel
`R
`stration No. 41,360
`
`MRV/kfh
`
`Enclosures
`
`\\MIA-SRVOl\1570118v01
`
`Express Mail Mailing Label No. ER940080602US
`
`GREENBERG TRAURIG, P.A.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 4 of 1441
`
`

`

`Docket No. 51458.010100
`
`CONTINUATION IN PART
`
`NON-PROVISIONAL PATENT
`APPLICATION
`
`SPECIFICATION
`
`TO WHOM IT MAY CONCERN:
`
`BE IT KNOWN THAT WE, David Paniagua, Eduardo lnduni, Carlos Mejia, Francisco
`
`Lopez and R. David Fish, have invented a new and useful percutaneously implantable
`
`replacement heart valve device and method of making same, of which the following is
`
`the Specification.
`
`CONTINUITY INFORMATION
`
`This Application is a continuation in part of U.S. non-provisional patent application serial
`
`number 10/037 ,266 filed on January 4, 2002. The Applicants hereby claim the benefit
`
`under 35 U.S.C. §120 based on said application.
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 5 of 1441
`
`

`

`BACKGROUND OF THE INVENTION
`
`[0001] 1.
`
`Field of the Invention
`
`The present invention is in the field of heart valve replacement. More
`
`specifically,
`
`the present invention
`
`is directed
`
`to a percutaneously
`
`implantable
`
`replacement heart valve and method of making same.
`
`[0002] 2.
`
`Description of Related Art
`
`There have been numerous efforts in the field of heart valve replacement to
`
`improve both the durability and effectiveness of replacement heart valves as well as the
`
`ease of implantation. A brief description of heart valves and heart function follows to
`
`provide relevant background for the present invention.
`
`[0003] There are four valves in the heart that serve to direct the flow of blood through
`
`the two sides of the heart in a forward direction. On the left (systemic) side of the heart
`
`are: 1) the mitral valve, located between the left atrium and the left ventricle, and 2) the
`
`aortic valve, located between the left ventricle and the aorta. These two valves direct
`
`oxygenated blood coming from the lungs through the left side of the heart into the aorta
`
`for distribution to the body. On the right (pulmonary) side of the heart are: 1) the
`
`tricuspid valve, located between the right atrium and the right ventricle, and 2) the
`
`pulmonary valve, located between the right ventricle and the pulmonary artery. These
`
`two valves direct de--oxygenated blood coming from the body through the right side of
`
`the heart into the pulmonary artery for distribution to the lungs, where it again becomes
`
`re-oxygenated to begin the circuit anew.
`
`[0004] Heart valves are passive structures that simply open and close in response to
`
`differential pressures on either side of the particular valve. They consist of moveable
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 6 of 1441
`
`

`

`"leaflets" that are designed simply to open and close in response to differential
`
`pressures on either side of the valve's leaflets. The mitral valve has two leaflets and the
`
`tricuspid valve has three. The aortic and pulmonary valves are referred to as "semilunar
`
`valves" because of the unique appearance of their leaflets, which are more aptly termed
`
`"cusps" and are shaped somewhat like a half-moon. The aortic and pulmonary valves
`
`each have three cusps.
`
`[0005] In general, the components of heart valves include the valve annulus, which will
`
`remain as a roughly circular open ring after the leaflets of a diseased or damaged valve
`
`have been removed; leaflets or cusps; papillary muscles which are attached at their
`
`bases to the interior surface of the left or right ventricular wall; and multiple chordae
`
`tendineae, which couple the valve leaflets or cusps to the papillary muscles. There is
`
`no one-to-one chordal connection between the leaflets and the papillary muscles;
`
`instead, numerous chordae are present, and chordae from each papillary muscle attach
`
`to both of the valve leaflets.
`
`[0006] When the left ventricular wall relaxes so that the ventricular chamber enlarges
`
`and draws in blood, the leaflets of the mitral valve separate and the valve opens.
`
`Oxygenated blood flows in a downward direction through the valve, to fill the expanding
`
`ventricular cavity. Once the left ventricular cavity has filled, the left ventricle contracts,
`
`causing a rapid rise in the left ventricular cavitary pressure. This causes the mitral valve
`
`to close while the aortic valve opens, allowing the oxygenated blood to be ejected from
`
`the left ventricle into the aorta. The chordae tendineae of the mitral valve prevent the
`
`mitral leaflets from prolapsing back into the left atrium when the left ventricular chamber
`
`contracts.
`
`3
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 7 of 1441
`
`

`

`[0007] The three leaflets, chordae tendineae, and papillary muscles of the tricuspid
`
`valve function in a similar manner, in response to the filling of the right ventricle and its
`
`subsequent contraction. The cusps of the aortic valve also respond passively to
`
`pressure differentials between the left ventricle and the aorta. When the left ventricle
`
`contracts, the aortic valve cusps open to allow the flow of oxygenated blood from the left
`
`ventricle into the aorta. When the left ventricle relaxes, the aortic valve cusps
`
`reapproximate to prevent the blood which has entered the aorta from leaking
`
`(regurgitating) back into the left ventricle. The pulmonary valve cusps respond
`
`passively in the same manner in response to relaxation and contraction of the right
`
`ventricle in moving de-oxygenated blood into the pulmonary artery and thence to the
`
`lungs for re-oxygenation. Neither of these semilunar valves has associated chordae
`
`tendineae or papillary muscles.
`
`[0008] Problems that can develop with heart valves consist of stenosis, in which a valve
`
`does not open properly, and/or insufficiency, also called regurgitation, in which a valve
`
`does not close properly. In addition to stenosis and insufficiency of heart valves, heart
`
`valves may need to be surgically repaired or replaced due to certain types of bacterial
`
`or fungal infections in which the valve may continue to function normally, but
`
`nevertheless harbors an overgrowth of bacteria (vegetation) on the leaflets of the valve
`
`that may embolize and lodge downstream in a vital artery.
`
`If such vegetations are on
`
`the valves of the left side (i.e., the systemic circulation side} of the heart, embolization
`
`may occur, resulting in sudden loss of the blood supply to the affected body organ and
`
`immediate malfunction of that organ. The organ most commonly affected by such
`
`embolization is the brain, in which case the patient suffers a stroke. Thus, surgical
`
`4
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 8 of 1441
`
`

`

`replacement of either the mitral or aortic valve (left-sided heart valves) may be
`
`necessary for this problem even though neither stenosis nor insufficiency of either valve
`
`is present. Likewise, bacterial or fungal vegetations on the tricuspid valve may
`
`embolize to the lungs resulting in a lung abscess and therefore, may require
`
`replacement of the tricuspid valve even though no tricuspid valve stenosis or
`
`insufficiency is present.
`
`[0009] These problems are treated by surgical repair of valves, although often the
`
`valves are too diseased to repair and must be replaced.
`
`If a heart valve must be
`
`replaced, there are currently several options available, and the choice of a particular
`
`type of artificial valve depends on factors such as the location of the valve, the age and
`
`other specifics of the patient, and the surgeon's experiences and preferences. Currently
`
`in the United States over 100,000 defective heart valves are replaced annually, at an
`
`approximate cost of $30-50,000 per procedure, and thus it would be desirable if heart
`
`valves could be replaced using minimally invasive techniques and without having to
`
`repeat the procedure within a matter of years due to the lack of durability of the
`
`replacement heart valve. It would be especially advantageous if a defective heart valve
`
`could be removed via an endovascular procedure, that is, a procedure where the
`
`invasion into the body is through a blood vessel such as the femoral artery. The
`
`procedure is then carried out percutaneously and transluminally using the vascular
`
`system to convey appropriate devices to the position in the body wherein it is desired to
`
`carry out the desired procedure. An example of such a procedure would be
`
`angioplasty, wherein a catheter carrying a small balloon at its distal end is manipulated
`
`through the body's vessels to a point where there is a blockage in a vessel. The balloon
`
`5
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 9 of 1441
`
`

`

`is expanded to create an opening in the blockage, and then the balloon is deflated and
`
`the catheter and balloon are removed from the vessel.
`
`[001 0] Endovascular procedures have substantial benefits both from the standpoint of
`
`health and safety as well as cost. Such procedures require minimal invasion of the
`
`human body, and there is consequently considerable reduction and in some instances
`
`even elimination, of the use of a general anesthesia and much shorter hospital stays.
`
`[0011] Replacement heart valves can be categorized as either artificial mechanical
`
`valves, transplanted valves and tissue valves. Replacement heart valves are designed
`
`to optimize hemodynamic performance, thrombogenicity and durability. Another factor
`
`taken into consideration is the relative ease of surgical implantation.
`
`[0012) Mechanical valves are typically constructed from nonbiological materials such as
`
`plastics, metals and other artificial materials which, while durable, are expensive and
`
`prone to blood clotting which increases the risk of an embolism. Anticoagulants taken
`
`to help against blood clotting can further complicate the patient's health due to
`
`increased risks for hemorrhages.
`
`[0013] Transplanted valves are natural valves taken from cadavers. These valves are
`
`typically removed and frozen in liquid nitrogen, and are stored for later use. They are
`
`typically fixed in glutaraldehyde to eliminate antigenicity and are sutured in place,
`
`typically with a stent.
`
`[0014] Artificial tissue valves are valves constructed from animal tissue, such as bovine
`
`or porcine tissue. Efforts have also been made at using tissue from the patient for
`
`which the valve will be constructed.
`
`6
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 10 of 1441
`
`

`

`[0015] Most tissue valves are constructed by sewing the leaflets of pig aortic valves to a
`
`stent to hold the leaflets in proper position, or by constructing valve leaflets from the
`
`pericardia! sac of cows or pigs and sewing them to a stent. The porcine or bovine
`
`tissue is chemically treated to alleviate any antigenicity. The pericardium is a
`
`membrane that surrounds the heart and isolates it from the rest of the chest wall
`
`structures. The pericardium is a thin and very slippery, which makes it difficult for
`
`suturing in a millimetricly precise way. The method of making the replacement heart
`
`valve of the present invention solves this problem through a process that includes
`
`drying and compressing the pericardium using photo-mechanical compression in such a
`
`way that makes it possible to handle and fold the material more easily.
`
`[0016] For example, one prior replacement heart valve requires each sculpted leaflet to
`
`be trimmed in a way that forms an extended flap, which becomes a relatively narrow
`
`strand of tissue near its tip. The tip of each pericardia! tissue strand is sutured directly
`
`to a papillary muscle, causing the strand to mimic a chordae tendineae. Each strand
`
`extends from the center of a leaflet in the valve, and each strand is sutured directly to
`
`either an anterior and posterior papillary muscle. This requires each leaflet to be
`
`positioned directly over a papillary muscle. This effectively rotates the leaflets of the
`
`valve about 90 degrees as compared to the leaflets of a native valve. The line of
`
`commissure between the leaflets, when they are pressed together during systole, will
`
`bisect (at a perpendicular angle) an imaginary line that crosses the peaks of the two
`
`papillary muscles, instead of lying roughly along that line as oocurs in a native valve.
`
`[0017] A different approach to creating artificial tissue valves is described in U.S. Patent
`
`Nos. 5,163,955 to Calvin, et al. and 5,571,174 and 5,653,749 to Love. Using a cutting
`
`7
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 11 of 1441
`
`

`

`die, the pericardia! tissue is cut into a carefully defined geometric shape, treated with
`
`glutaraldehyde, then clamped in a sandwich-fashion between two stent components.
`
`This creates a tri-leaflet valve that resembles an aortic or pulmonary valve, having
`
`semilunar-type cusps rather than atrioventricular-type leaflets.
`
`(0018] U.S. Patent No. 3,671,979 to Moulopoulos describes an endovascularly inserted
`
`conical shaped umbrella-like valve positioned and held in place by an elongated
`
`mounting catheter at a supra-annular site to the aortic valve in a nearby arterial vessel.
`
`The conical end points toward the malfunctioning aortic valve and the umbrella's distal
`
`ends open up against the aorta wall with reverse blood flow, thereby preventing
`
`regurgitation.
`
`(0019] U.S. Patent No. 4,056,854 to Boretos describes an endovascularly inserted,
`
`catheter mounted, supra-annular valve in which the circular frame abuts the wall of the
`
`artery and attached flaps of flexible membrane extend distally in the vasculature. The
`
`flaps lie against the artery wall during forward flow, and close inward towards the central
`
`catheter to prevent regurgitation during reverse blood flow. The Boretos valve was
`
`designed to be positioned against the artery wall during forward flow, as compared to
`
`the mid-center position of the Moulopoulos valve, to reduce the stagnation of blood flow
`
`and consequent thrombus and embolic formation expected from a valve at mid-center
`
`position.
`
`(0020] The main advantage of tissue valves is that they do not cause blood clots to form
`
`as readily as do the mechanical valves, and therefore, they do not absolutely require
`
`systemic anticoagulation. The major disadvantage of tissue valves is that they lack the
`
`long-term durability of mechanical valves. Tissue valves have a significant failure rate,
`
`8
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 12 of 1441
`
`

`

`usually within ten years following implantation. One cause of these failures is believed
`
`to be the chemical treatment of the animal tissue that prevents it from being antigenic to
`
`the patient. In addition, the presence of extensive suturing prevents the artificial tissue
`
`valve from being anatomically accurate in comparison to a normal heart valve, even in
`
`the aortic valve position.
`
`(0021) A shortcoming of prior artificial tissue valves has been the inability to effectively
`
`simulate the exact anatomy of a native heart valve. Although transplanted human or
`
`porcine aortic valves have the gross appearance of native aortic valves, the fixation
`
`process (freezing with liquid nitrogen, and chemical treatment, respectively) alters the
`
`histologic characteristics of the valve tissue. Porcine and bovine pericardia! valves not
`
`only require chemical preparation (usually involving fixation with glutaraldehyde ), but the
`
`leaflets must be sutured to cloth-covered stents in order to hold the leaflets in position
`
`for proper opening and closing of the valve. Additionally, the leaflets of most such
`
`tissue valves are constructed by cutting or suturing the tissue material, resulting in
`
`leaflets that do not duplicate the form and function of a real valve and are more
`
`susceptible to failure.
`
`SUMMARY OF THE INVENTION
`
`(0022) The present invention is a replacement heart valve device and method of making
`
`same. The replacement heart valve device, in a preferred embodiment, comprises a
`
`stent made of stainless steel or self-expanding nitinol and a completely newly designed
`
`artificial biological tissue valve disposed within the inner space of the stent. The cusp or
`
`leaflet portion of the valve means is formed by folding of the pericardium material
`
`preferably used to create the valve without cutting of slits to form leaflets or suturing or
`
`9
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 13 of 1441
`
`

`

`otherwise affixing of separate leaflet portions. Other forms of .tissue and suitable
`
`synthetic materials can also be used for the valve, formed in a sheet of starting material.
`
`The folded design provides a number of advantages over prior designs, including
`
`improved resistance to tearing at suture lines. The cusps/leaflets open in response to
`
`blood flow in one direction and close in response to blood flow in the opposite direction.
`
`Preferably the tubular portion of the valve means contains the same number of cusps as
`
`the native valve being replaced, in substantially the same size and configuration. The
`
`outer surface of the valve means is attached to the stent member.
`
`[0023] The replacement heart valve device is preferably implanted using a delivery
`
`system having a central part which consists of a flexible hollow tube catheter that allows
`
`a metallic guide wire to be advanced inside it. The stented valve is collapsed over the
`
`central tube and it is covered by a movable sheath. The sheath keeps the stented valve
`
`in the collapsed position. Once the cover sheath is moved backwards, the stented
`
`valve can be deployed. The endovascular stented-valve, in a preferred embodiment, is
`
`a glutaraldehyde fixed mammal pericardium or synthetic biocompatible material which
`
`has two or three cusps that open distally to permit unidirectional blood flow. The stent
`
`can either be self-expanding or the stent can be expandable through use of a balloon
`
`catheter.
`
`[0024] The present invention also comprises a method of making a replacement heart
`
`valve device.
`
`In order to make the valve, the pericardium starting material is isolated
`
`and all the fat tissue and extra fibers are removed. The biological membrane material is
`
`cleaned by mechanical separation of unwanted layers using hydromechanical force
`
`means. Once the pericardium is completely clean, the material is dried in order to make
`
`10
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 14 of 1441
`
`

`

`it easier to handle and fold. Preferably, this drying is done by exposing the
`
`biocompatible membrane material to photo-mechanical compression to remove all lipids
`
`from the pericardium or other biocompatible membrane material and to cause protein
`
`denaturalization, transforming the material into a stronger and more homogeneous
`
`surface. The valve is formed by taking a flat sheet of the material and folding in such a
`
`way that forms a three-leaflet or other number of leaflet valve. Then it is placed in a
`
`sequence of solutions, one of isopropyl alcohol of about 70-100%, one of ethanol of
`
`about 70-100%, one of glycerol and one of gluteraldehyde, preferably at a concentration
`
`of about 0.07-25% for approximately 36 hours. The material is dried in order to make it
`
`easier to handle and fold. Preferably this drying is done by exposing the biocompatible
`
`membrane material to light and then mechanically compressing the material to cause
`
`protein denaturation. This results in material that is stronger and more homogeneous.
`
`The valve is formed by taking a flat sheet of bovine pericardium and folding it in such a
`
`way that forms a three-leaflet valve. The valve can also be made in the same manner
`
`from fresh, cryopreserved or glutaraldehyde fixed allografts or xenografts or synthetic
`
`non-biological, non-thrombogenic material. The folding of the pericardium material to
`
`create the cusps or leaflets reduces the extent of suturing otherwise required, and
`
`resembles the natural form and function of the valve leaflets. The cleaning, pressing
`
`and drying technique used to create the valve material makes the folding more
`
`practicable. The valve is rehydrated after being formed. The method of the present
`
`invention also greatly reduces the risk of tearing of the cusps or leaflets, since they are
`
`formed by folding a single uncut portion of material forming the valve rather than being
`
`attached by suturing.
`
`11
`
`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 15 of 1441
`
`

`

`[0025] Once the endovascular implantation of the prosthetic valve device is completed
`
`in the host, the function of the prosthetic valve device can be monitored by the same
`
`methods as used to monitor valve replacements done by open heart surgery. Routine
`
`physical examination, periodic echocardiography or angiography can be performed. In
`
`contrast to open heart surgery, however, the host requires a short recovery period and
`
`can return home within one day of the endovascular procedure. The replacement heart
`
`valve device of the present invention can be used in any patient where bioprosthetic
`
`valves are indicated, namely elderly patients with cardiac valve diseases, and patients
`
`unable to tolerate open heart procedures or life-long anticoagulation medication and
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`treatment. The present invention can be practiced in applications with respect to each
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`of the heart's valves.
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`BRIEF DESCRIPTION OF THE DRAWINGS
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`(0026] Fig. 1 depicts a side perspective view of the replacement heart valve device of
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`the present invention in one embodiment with the valve in the closed position.
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`(0027] Fig. 2 depicts the folds which form the leaflets or cusps of the replacement heart
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`valve of the present invention in one embodiment.
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`(0028) Figs. 3A and 38 depict a preferred procedure for folding the pericardium tissue
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`starting material to create the replacement heart valve of the present invention.
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`(0029] Fig. 4 depicts a side perspective view of the replacement heart valve device of
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`the present invention in one embodiment represented as if implanted within an artery.
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`(0030) Fig. 5 depicts a side view of one embodiment of the replacement heart valve
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`device of the present invention mounted within a self-expanding stent, with the stent in
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`the expanded position.
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`12
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`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 16 of 1441
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`(0031) Fig. 6 depicts a side perspective view of one embodiment of the replacement
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`heart valve device of the present invention mounted within a self-expanding stent in the
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`collapsed position.
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`(0032) Fig. 7 depicts the suture points of one embodiment of the replacement heart
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`valve device of the present invention.
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`(0033) Fig. 8 depicts the implantation/delivery system used with the present invention in
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`a preferred embodiment.
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`[0034) Figs. 9A, 98 and 9C depicts a representation of a sheet of biocompatible valve
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`material showing preferred folds.
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`DESCRIPTION OF A PREFERRED EMBODIMENT
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`(0034) The present invention comprises a percutaneously implantable replacement
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`heart valve and a method for making same. The artificial heart valve device of the
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`present invention is capable of exhibiting a variable diameter between a compressed or
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`collapsed position and an expanded position. A preferred embodiment of the
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`replacement heart valve device according to the present invention is set forth in FIG. 5.
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`The replacement heart valve device comprises a stent member 100 and a flexible valve
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`means 200. The stent member 100 is preferably self-expanding, although balloon(cid:173)
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`expandable stents can be used as well, and has a first polygonal shape in its
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`compressed or collapsed configuration and a second, larger polygonal shape in its
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`expanded configuration. Referring to FIG. 1, the valve means 200 comprises a
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`generally tubular portion 210 and, preferably, a peripheral upstanding cusp or leaflet
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`portion 220. The valve means 200 is disposed within the cylindrical stent member 100
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`with the tubular portion 210 transverse of and at some acute angle relative to the stent
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`13
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`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 17 of 1441
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`walls. The diameter of the tubular portion 210 is substantially the same as the inside
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`diameter of the stent member in its initial expanded configuration. The peripheral
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`upstanding cusp or leaflet portion 220 is disposed on valve means 200 substantially
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`parallel to the walls of the stent member similar to a cuff on a shirt. The cusp or leaflet
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`portion 220 of the valve means 200 is generally tubular in shape and comprises three
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`leaflets 221, 222 and 223 as shown, although it is understood that there could be from
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`two to four leaflets. The tubular portion of the valve means 200 is attached .to the stent
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`member 100 by a plurality of sutures 300, as depicted in FIG. 7.
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`[0035] The leaflet portion 220 of the valve means 200 extends across or transverse of
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`the cylindrical stent 100. The leaflets 221, 222 and 223 are the actual valve and allow
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`for one-way flow of blood. The leaflet portion 220 as connected to the rest of the valve
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`resembles the cuff of a shirt. FIG. 9 depicts the folds preferred for valve cusp and
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`leaflet formation involving three leaflets. The configuration of the stent member 100 and
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`the flexible, resilient material of construction allows the valve to collapse into a relatively
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`small cylinder as seen in FIG. 6. The replacement heart valve will not stay in its
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`collapsed configuration without being restrained. Once the restraint is removed, the
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`self-expanding stent member 100 will cause the artificial heart valve to take its
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`expand.ed configuration, as seen in FIG. 5.
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`Stent Member
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`[0036] The stent member 100 preferably comprises a self-expanding nickel-titanium
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`alloy stent, also called "nitinol," in a sine wave-like configuration as shown in FIG. 5. An
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`enlarged view of a preferred embodiment of the stent member for use in the
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`replacement heart valve of the invention is depicted in FIG. 5. The stent member 100
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`14
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`Edwards Lifesciences Corporation, et al. Exhibit 1016, p. 18 of 1441
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`

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`includes a length of wire 110 formed in a closed zigzag configuration. The wire can be
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`a single piece, stamped or extruded, or it could be formed by welding the free ends
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`together. The straight sections of the stent member 100 are joined by bends. The stent
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`is readily compressible to a small cylindrical shape as depicted in FIGS. 6 and 8, and
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`r~siliently self-expandable to the shape shown in FIG. 5.
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`[0037) The stent member 100 of the artificial heart valve device of the present invention
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`may be made from various metal alloys, titanium, titanium alloy, nitinol, stainless steel,
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`or other resilient, flexible non-toxic, non-thrombogenic, physiologically acceptable and
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`biocompatible materials. The configuration may be the zigzag configuration shown or a
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`sine wave configuration, mesh configuration or a similar configuration which will allow
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`the stent to be readily collapsible and self-expandable. When a zigzag or sine wave
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`configured stent member is used, the diameter of the wire from which the stent is made
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`is preferably from about 0.010 to 0.035 inches and still, preferably from about 0.012 to
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`0.025 inches. The diameter of the stent member will be from about 1.5 to 3.5 cm,
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`preferably from about 1.75 to 3.00 cm, and the length of the stent member will be from
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`about 1.0 to 10 cm, preferably from about 1.1 to 5 cm.
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`[0038) The stent used in a preferred embodiment of the present invention is fabricated
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`from a "shaped memory" alloy, nitinol, which is composed of nickel and titanium. Nitinol
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`wire is first fashioned into the desired shape for the device and then the device is heat
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`annealed. A meshwork of nitinol wire of approximately 0.008 inch gauge is formed into
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`a tubular structure with a minimum central diameter of 20 min to make the stent. Away
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`fro