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`Smith & Nephew Ex. 1021
`IPR Petition - USP 8,657,827
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`METHODS To IMPROVE CARTILAGE REPAIR SYSTEMS
`
`PROVISIONAL PATENT APPLICATION
`ATTORNEY DOCKET NO.: OA-002.00us
`
`
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`Background:
`
`A large number of cartilage repair systems are currently being developed. These cartilage
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`repair systems include cartilage or cartilage—like material grown out of stem cells, fetal
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`cells or adult cartilage cells. Other cartilage repair systems include non—human material
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`with elastic and biomechanical properties similar to cartilage. Again other cartilage repair
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`systems include a scaffold for ingrowth of cartilage cells.
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`One of the biggest challenges for all of these cartilage repair systems is the integration of
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`the cartilage replacement material with the surrounding cartilage of the patient. This
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`integration can be extremely difficult due to differences in thickness and curvature
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`between the surrounding cartilage or the underlying subchondral bone and the cartilage
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`replacement material.
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`The present invention provides for methods and devices that improve and facilitate the
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`integration between the cartilage replacement system and the surrounding cartilage.
`
`Definitions:
`
`A cartilage repair system is a system to repair,
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`to replace or to regenerate articular
`
`cartilage. Cartilage repair systems include autologous chondrocyte transplantation,
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`osteochondral allografting, osteochondral autografting,
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`tibial corticotomy, femoral or
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`tibial osteotomy. Cartilage repair systems include also treatment with cartilage or bone
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`tissue grown ex vivo, stem cells, cartilage material grown with use of stem cells, fetal
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`cells or immature or mature cartilage cells, an artificial non—human material, an agent that
`stimulates repair of diseased cartilage tissue, an agent that protects diseased cartilage
`tissue and that protects adjacent normal cartilage tissue. Cartilage repair systems include
`also treatment with a cartilage tissue transplant, a cartilage tissue graft, a cartilage tissue
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`implant, a cartilage tissue scaffold, or any other cartilage tissue replacement or
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`regenerating material.
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`A cartilage replacement or regenerating material includes cartilage or bone tissue grown
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`ex vivo, stem cells, cartilage material grown out of stem cells, fetal cells or immature or
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`mature cartilage cells, an artificial non-human material, a cartilage tissue transplant, a
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`cartilage tissue graft, a cartilage tissue implant, a cartilage tissue scaffold, or a cartilage
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`tissue regenerating material.
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`An imaging test includes X-ray based techniques such as conventional film based x-ray
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`films, digital
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`x—ray
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`images,
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`single and dual x-ray absorptiometry,
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`radiographic
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`absorptiometry, ultrasound including broadband ultrasound attenuation measurement and
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`speed of sound measurements, computed tomography, nuclear scintigraphy, SPECT,
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`positron emission tomography and MRI. The imaging test can be used to obtain certain
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`morphological information about one or several tissues such as bone including bone
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`mineral density and curvature of the subchondral bone, cartilage including biochemical
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`composition of cartilage, cartilage thickness, cartilage volume, cartilage curvature,
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`marrow including marrow composition, synovium including synovial inflammation, lean
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`and fatty tissue, and thickness, dimensions and volume of soft and hard tissues. The
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`imaging test can be performed with use of a contrast agent, such as Gd—DTPA in the case
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`of MRI.
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`
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`Arthritis is a condition that
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`is characterized by progressive deterioration of joints.
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`Arthritis encompasses a group of different diseases including osteoarthritis, rheumatoid
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`arthritis, seronegative spondyloarthropathies and posttraumatic joint deformity.
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`Detailed Description of the Invention:
`
`The current invention provides for methods and devices that improve the integration of
`
`cartilage replacement or regenerating materials.
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`In one embodiment of the invention, the thickness of the normal or only mildly diseased
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`cartilage surrounding a cartilage defect can be measured. This thickness measurement can
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`be obtained at a single point, more preferably two points, even more preferably 4 or 6
`points, and even more preferably all around the defect. Similarly, the curvature of the
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`articular surface can be measured. This curvature measurement can be obtained in one
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`direction, preferably in two directions, and, even more preferably, in three dimensions. At
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`least one, preferably two or more of these measurements can then be used to shape the
`cartilage replacement or regenerating material.
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`Said thickness and curvature measurements can be obtained with use of an imaging test
`or they can be obtained intraoperatively during arthroscopy or open arthrotomy.
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`In one embodiment of the invention, said thickness and curvature information is used to
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`shape a base material on which a cartilage replacement or regenerating material can be
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`applied. For example, fetal cartilage cells can be applied to said base material and can be
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`grown on the base material until the thickness of the cartilage surrounding the cartilage
`defect has been reached. If different sections of the cartilage replacement or regenerating
`material require different thicknesses,
`this can be achieved by means of mechanical
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`abrasion, laser abrasion or ablation, radiofrequency treatment, cryoablation, variations in
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`exposure time and concentration of nutrients or growth factors and any other means
`suitable for influencing or changing cartilage thickness. In this fashion,
`the cartilage
`replacement or regenerating material will have a curvature that will fit into the cartilage
`defect, that will follow the contour and shape of the articular surface, and that will match
`the thickness of the surrounding cartilage. The cartilage replacement or regenerating
`material can then be implanted into the area of the defect. Said implantation can be
`performed with the cartilage replacement or regenerating material still attached to the
`base material or removed from the base material. The base material can be a plastic, a
`tissue scaffold, a bone replacement material, e.g. a hydroxyapatite, a bioresorbable
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`material, or any other material
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`suitable for growing a cartilage replacement or
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`regenerating material on it.
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`In another embodiment of the invention, a container can be formed using the thickness
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`and curvature information obtained from the joint and from the cartilage defect. More
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`specifically,
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`the inside of the container can be shaped to follow the measurements
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`obtained from the cartilage defect. The container can be filled with a cartilage
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`replacement or regenerating material. Said cartilage replacement or regenerating material,
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`can, for example, consist of a collagen material or a plastic or a bioresorbable material or
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`a tissue scaffold that subsequently hardens inside the container thereby exactly following
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`the contour of the inside of the container. Said cartilage regenerating or replacement
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`material can also consist of a suspension of stem cells or fetal or immature or mature
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`cartilage cells that subsequently develop to more mature cartilage inside the container.
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`Said development can be enhanced with use of certain tissue nutrients and growth factors.
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`Once the cartilage replacement or regenerating material inside the container has reached a
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`certain level of maturity, for example a certain level of hardness and elasticity,
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`the
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`container can be removed and the cartilage replacement or regenerating material can be
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`implanted.
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`In another embodiment of the invention, an existing cartilage replacement or regenerating
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`material can be shaped to fit into a cartilage defect. Said shaping is achieved with use of
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`at least one or more of said measurements obtained in and around the cartilage defect.
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`Said shaping can be performed with mechanical means, for example by abrading portions
`of the cartilage replacement or regenerating material that are thicker than the cartilage
`surrounding the defect. Said shaping can also be achieved with use of laser ablation or
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`radiofrequency ablation. Said shaping can also be achieved with use of enzymatic
`digestion. If enzymatic digestion is used, certain sections of the cartilage replacement or
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`regenerating material can be exposed to higher doses of the enzyme or can be exposed
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`longer as a means of achieving different thicknesses and curvatures of the cartilage
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`replacement or regenerating material in different sections of said material.
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`In another embodiment of the invention, the biochemical composition of the cartilage
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`surrounding a defect can be assessed prior to implantation of a cartilage replacement or
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`cartilage regenerating material. Said biochemical composition of
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`said cartilage
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`surrounding said cartilage defect can be assessed with use of tissue sampling with
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`subsequent
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`chemical
`
`analysis. Said biochemical
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`composition of
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`said cartilage
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`surrounding said cartilage defect can also be assessed with use of an imaging test. Said
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`imaging test can be an MRI scan with use of Gd-DTPA or other contrast agents enabling
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`estimation of glycosaminoglycan content. The cartilage replacement or regenerating
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`material can then be grown in a manner to achieve a biochemical composition similar to
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`that of the cartilage surrounding the implantation site. Said biochemical composition of
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`said cartilage replacement or regenerating material can, for example, be influenced by
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`controlling concentrations and exposure times of certain nutrients and growth factors.
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`
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`I claim:
`
`
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`A method to improve integration of a cartilage replacement or regenerating
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`material comprising
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`a. measuring the thickness of
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`the cartilage surrounding the intended
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`implantation site
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`b. measuring the curvature of
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`the cartilage surrounding the intended
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`implantation site or inside the cartilage defect
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`c.
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`shaping the cartilage replacement or regenerating material so that it will fit
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`into the intended implantation site and align with the surrounding
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`cartilage,
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`whereby said fitting and aligning will improve postoperative joint congruity.
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`The method of claim 1, whereby said thickness of said cartilage surrounding
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`said implantation site and said curvature of said cartilage surrounding said
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`intended implantation site or
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`inside said cartilage defect
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`is measured
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`intraoperatively during arthroscopy or arthotomy.
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`The method of claims 1 and 2, whereby said cartilage replacement or
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`regenerating material is shaped intraoperatively using said cartilage thickness
`
`and said cartilage curvature measurements.
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`The method of claim 3, whereby said shaping is performed using mechanical
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`abrasion.
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`The method of claim 3, whereby said shaping is performed with use of a laser.
`
`The method of claim 3, whereby said shaping is performed with use of a
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`radiofrequency probe.
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`The method of claim 3, whereby said shaping is performed with use of
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`cryoablation.
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`The method of claim 3, whereby said shaping is performed with use of a
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`enzymatic digestion.
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`The method of claims 1 and 2, whereby said measurements of said cartilage
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`thickness and said cartilage curvature are used to grow a cartilage replacement
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`or regenerating material ex Vivo.
`
`10.
`
`The method of claim 9, whereby said cartilage replacement or regenerating
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`material is grown and shaped until it will fit into the cartilage defect and until
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`its thickness is similar to that of the surrounding cartilage.
`
`
`11.
`
`A method to generate a cartilage replacement or regenerating material
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`comprising
`
`a.
`
`b.
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`selecting a thickness for the cartilage replacement or regenerating material
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`selecting a curvature or a shape for
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`the cartilage replacement or
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`regenerating material
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`c. producing said cartilage replacement or regenerating material using said
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`thickness and using said curvature,
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`whereby producing said cartilage replacement or regenerating material with
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`said thickness and said curvature helps improve postoperative joint congruity.
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`The method of claim 11, wherein said selecting of said thickness of said
`
`cartilage replacement or regenerating material
`
`is done with use of an
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`intraoperative measurement.
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`The method of claim 11, wherein said selecting of said curvature or said shape
`
`of said cartilage replacement or regenerating material is done with use of an
`
`intraoperative measurement.
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`The method of claim 11, wherein, said cartilage replacement or regenerating
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`material is produced intraoperatively using said thickness and said curvature
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`measurements.
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`The method of claim 14, wherein said cartilage replacement or regenerating
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`material is shaped with use of mechanical abrasion in order to achieve a
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`thickness and a curvature similar to said thickness and said curvature
`measurements.
`
`12.
`
`13.
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`14.
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`15.
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`16.
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`The method of claim 14, wherein said cartilage replacement or regenerating
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`material is shaped with use of a laser probe in order to achieve a thickness and
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`a curvature similar to said thickness and said curvature measurements.
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`17.
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`The method of claim 14, wherein said cartilage replacement or regenerating
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`material is shaped with use of a radiofrequency probe in order to achieve a
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`thickness and a curvature similar
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`to said thickness and said curvature
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`measurements.
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`18.
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`The method of claim 14, wherein said cartilage replacement or regenerating
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`material is shaped with use of cryoablation in order to achieve a thickness and
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`a curvature similar to said thickness and said curvature measurements.
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`19.
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`The method of claim 14, wherein said cartilage replacement or regenerating
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`material
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`is shaped with use of enzymatic digestion in order to achieve a
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`thickness and a curvature similar to said thickness and said curvature
`
`measurements.
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`20.
`
`The method of claim 11, wherein said selecting of said thickness of said
`
`cartilage replacement or regenerating material is done with use of an imaging
`test.
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`21.
`
`The method of claim 11, wherein said selecting of said curvature or said shape
`
`of said cartilage replacement or regenerating material is done with use of an
`
`imaging test.
`
`22.
`
`23.
`
`24.
`
`25.
`
`26.
`
`27.
`
`The method of claims 20 and 21, wherein said imaging test is an ultrasound.
`
`The method of claims 20 and 21, wherein said imaging test is an MRI.
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`The method of claims 20 and 21, wherein said imaging test is a CT scan.
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`The method of claims 20 and 21, wherein said imaging test is an X—ray
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`obtained with x-ray dye.
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`The method of claims 20 and 21, wherein said imaging test is fluoroscopy.
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`The method of claims
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`11—13, wherein said cartilage replacement or
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`regenerating material is produced postoperatively using said thickness and
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`said curvature measurements.
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`28.
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`The method of claims 11, 20 and 21, wherein said cartilage replacement or
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`regenerating material
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`is produced with use of said thickness and said
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`curvature measurements obtained with use of said imaging test.
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`29.
`
`The method of claim 11, wherein said cartilage replacement or regenerating
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`material is produced on a base material.
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`30.
`
`The method of claim 29, wherein said base material has a curvature or shape
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`similar to said curvature or said shape obtained during said intraoperative
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`measurement or obtained with use of said imaging test.
`
`31.
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`The method of claim 29, wherein said cartilage replacement or regenerating
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`material
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`is grown on said base material until
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`it has
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`reached said
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`intraoperatively measured thickness or said thickness measured with said
`
`imaging test.
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`32.
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`The method of claim 29, wherein the thickness of said cartilage replacement
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`or
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`repair material
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`is adjusted to match said intraoperatively measured
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`thickness or said thickness measured with said imaging test.
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`33.
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`The method of claim 32, wherein said adjusting is performed with use of
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`mechanical abrasion.
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`34.
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`The method of claim 32, wherein said adjusting is performed with use of a
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`laser probe.
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`35.
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`The method of claim 32, wherein said adjusting is performed with use of a
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`radiofrequency probe.
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`36.
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`The method of claim 32, wherein said adjusting is performed with use of
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`cryoablation.
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`37.
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`The method of claim 32, wherein said adjusting is performed with use of
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`enzymatic digestion.
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`38.
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`The method of claim 32, wherein said adjusting is performed by controlling
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`exposure times of the cartilage replacement or regenerating material
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`to
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`nutrients and growth factors.
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`39.
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`The method of claim 32, wherein said adjusting is performed by controlling
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`concentrations of nutrients and growth factors.
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`40.
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`The method of claims 33—39, wherein said adjusting is done differently in
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`different regions of the cartilage replacement or regenerating material as a
`
`means of achieving an optimal fit with the implantation site.
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`
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`3; isional Patent
`
`OA-002.00us
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`DECLARATION AND CORRESPONDENCE ADDRESS
`
`As a below named inventor, I hereby declare that:
`
`
`
`My residence, post office address and citizenship are as stated next to my name.
`
`I believe I am the original, first and sole inventor (if only one name is listed
`below) or an original inventor (if plural names are listed below) of the subject matter
`which is claimed and for which a provisional patent is sought on the invention entitled:
`
`METHODS TO IMPROVE CARTILAGE REPAIR SYSTEMS
`
`the specification of which:
`
`[] is attached hereto.
`
`[X] was filed on May 25, 2001, and identified as Docket No. OA—002.00us.
`[] was filed on , as Application Serial number
`
`I hereby state that I reviewed and understand the contents of the above-identified
`specification, including the claims, as amended by any amendment referred to above.
`I acknowledge the duty to disclose information which is material to the
`examination of this application in accordance with Title 37, Code of Federal Regulations,
`Section 1.56(a).
`
`I hereby claim foreign priority benefits under Title 35, United States Code,
`Section 119 of any foreign application(s) for patent or inventor’s certificate listed below
`and have also identified below any foreign application for patent or inventor’s certificate
`having a filing date before that of the application on which priority is claimed:
`
`Prior Foreign Applicationg S) (Country) (Number) (Day/Month/Year Filed) Priority Claimed
`
`I hereby claim the benefit under Title 35, United States Code, Section 120 of any
`United States Application(s) listed below and, insofar as the subject matter of each of the
`claims of this application is not disclosed in the prior United States application in the
`manner provided by the first paragraph of Title 35, United States Code, Section 112, I
`acknowledge the duty to disclose material information as defined in Title 37, Code of
`Federal Regulations, Section 1.56(a) which occurred between the filing date of the prior
`application and the national or PCT international filing date of this application.
`
`Application Serial No.
`
`Filing Date
`
`Status Pending
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`I further direct that correspondence concerning this application be directed to:
`
`Philipp Lang, MD.
`3677 Highland Ave.
`Redwood City, CA 94062
`
`(650)-261-1898
`
`I hereby declare that all statements made herein of my own knowledge are true
`and that all statements made on information and belief are believed to be true; and further
`that these statements were made with the knowledge that willful false statements and the
`like so made are punishable by fine or imprisonment, or both, under Section 1001 of Title
`18 of the United States Code and that such willful false statements may jeopardize the
`validity the application or any patent issued thereon.
`
`
`
`Full name of sole or first inve
`
`Inventor’s signature
`
`/
`
`
`
`Residence:
`
`Redwood ity, California, USA
`
`Citizen:
`
`Germany
`
`Post Office Address:
`
`3677 Highland Ave.
`Redwood City, CA 94062
`
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`ATTORNEY DOCKET NO.: OA-002.00us
`
`TITLE: Methods to Impove Cartilage Repair Systems
`
`VERIFIED STATEMENT CLAIMING SMALL ENTITY STATUS
`
`37 CFR 1.27(b) AS AN INDIVIDUAL
`
`I hereby declare that I am Philipp Lang, German Citizen and Resident of 3677 Highland Avenue,
`Redwood City, CA 94062 (herein referred to as “Lang”).
`
`I hereby declare that any and all rights under contract or law have been conveyed to and remain with
`Lang with regard to the invention:
`
`ENTITLED “METHODS TO IMPROVE CARTILAGE REPAIR SYSTEMS”
`
`by inventor Philipp Lang
`
`described in docket no. OA—002.00us, filed May 25, 2001.
`
`
`
`Address: ————___._________—_________
`
`[ ] INDIVIDUAL [ ] SMALL BUSINESS CONCERN [ ] NONPROFIT ORGANIZATION
`
`I acknowledge the duty to file, in this application or patent, notification of any change in status
`resulting in loss of entitlement to small entity status prior to paying, or at the time of paying, the
`earliest of the issue fee or any maintenance fee due after the date on which status as a small entity is no
`longer appropriate.
`(37 CFR 1.28(b))
`
`I hereby declare that all statements made herein of my own knowledge are true and that all statements
`made on information and belief are believed to be true; and further that these statements were made
`with the knowledge that willful false statements and the like so made are punishable by fine or
`imprisonment, or both, under section 1001 of Title 18 of the United States Code, and that such willful
`false statements may jeopardize the validity of the application, any patent issuing thereon, or any patent
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`on which this verified statement is directed.
`
`Name:
`
`Address:
`
`Signature:
`
`
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