Smith & Nephew Ex. 1016
`IPR Petition - USP 8,377,129
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`WO 02/22014 A1
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`Published:
`— with international search report
`— before the expiration of the time limit for amending the
`claims and to be republished in the event of receipt of
`amendments
`
`For two-letter codes and other abbreviations, refer to the "Guid-
`ance Notes on Codes andAbbreviations " appearing at the begin-
`ning ofeach regular issue ofthe PCT Gazette.
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`WO 02/22014
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`PCT/US01/28680
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`ASSESSING THE CONDITION OF A JOINT AND
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`DEVISING TREATMENT
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`This invention was supported in part by a National Institute of Health Grant No. PAR—97—
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`014, and the government may have rights in this invention.
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`BACKGROUND OF THE INVENTION
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`FIELD OF INVENTION
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`This invention relates to assessing the condition of a joint and the use of the assessment in
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`aiding in prevention of damage to the joint or treatment of diseased cartilage in the joint.
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`BACKGROUND
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`Osteoarthritis is the most common condition to affect human joints as well as a ‘
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`frequent cause of locomotor pain and disability. More particularly, osteoarthritis (OA) of
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`the knee occurs in a substantial portion of the population over the age of fifty.
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`In spite of its societal
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`impact and prevalence, however,
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`there is a paucity of
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`information on the factors that cause osteoarthritis to progress more rapidly in some
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`individuals and not in others. Previously considered a “wear and tear” degenerative disease
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`with little opportunity for therapeutic intervention, osteoarthritis is now increasingly viewed
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`as a dynamic process with potential for new pharmacologic and surgical
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`treatment
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`modalites such as cartilage transplantation, osteochondral allo- or autografting, osteotomies
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`and tibial corticotomies with angular distraction.
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`However, the appropriate deployment and selection of treatment interventions for
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`0A is dependent on the development of better methods for the assessment of the condition
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`30
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`of a patient’s joint and the degeneration process.
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`There is, therefore, a need for improved methods for examining the factors that
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`influence as well as quantification of the progression of the disease.
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`Magnetic resonance imaging (MRI) is an accurate non-invasive imaging technique
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`for visualization of articular cartilage in osteoarthritis, particularly in knees. However,
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`current MRI techniques camiot provide information on the relationship between the location
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`of the cartilage loss and variations in the load bearing areas during the walking cycle. This
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`information is important since it has been shown that dynamic loads during walking are
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`related to the progression of knee OA. Thus, the ability to locate cartilage defects or areas of
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`cartilage thinning relative to the load bearing areas of the knee could be valuable in
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`evaluating factors influencing the progression of osteoarthritis.
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`SUMMARY OF THE INVENTION
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`This invention relates to assessing the condition of a joint of a mammal, particularly
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`a human subject, using the assessment to treat and monitor the subject as needed for
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`cartilage degeneration problems. While the numerous aspects of the invention are useful for
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`joints generally, they are particularly suited for dealing with the human knee. Some aspects
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`related the static images and degeneration patterns of a cartilage, while others relate to the
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`interaction of such images and patterns to provide a better means of assessing the condition
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`of a cartilage.
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`One aspect of this invention is a method for assessing the condition of a cartilage.
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`The method comprises obtaining an image of a cartilage, (preferably a magnetic resonance
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`image), converting the image to a three—dimensional degeneration pattern, and evaluating
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`the degree of degeneration in a volume of interest of the cartilage. By performing this
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`method at an initial time T, and a later time T2, one can determine the change in the volume
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`of interest and evaluate what steps to take for treatment.
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`Another aspect of this invention is a method of estimating the loss of cartilage in a
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`joint. The method comprises obtaining a three-dimensional map of the cartilage at an initial
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`time and calculating the thickness or regional volume of a region thought to contain
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`degenerated cartilage so mapped at the initial time, obtaining a three-dimensional map of
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`the cartilage at a later time, and calculating the thickness or regional Volume of the region
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`thought to contain degenerated cartilage so mapped at the later time, and determining the
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`loss in thickness or regional volume of the cartilage between the later and initial times. The
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`3D map may be a thickness map, a biochemical map or a combination.
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`Another aspect of the invention is a method for assessing the condition of cartilage
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`in a joint of a human, which method comprises electronically transferring an electronically-
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`generated image of a cartilage of the joint from a transferring device to a receiving device
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`located distant from the transferring device; receiving the transferred image at the distant
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`location; converting the transferred image to a degeneration pattern of the cartilage; and
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`transmitting the degeneration pattern to a site for analysis.
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`Another aspect of the invention is a method for determining the volume of cartilage
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`loss in a region of a cartilage defect of a cartilage in joint of a mammal. The method
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`comprises (a) determining the thickness, DN, of the normal cartilage near the cartilage
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`defect; (b) obtaining the thickness of the cartilage defect, DD, of the region; (c) subtracting
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`DD from DN to give the thickness of the cartilage loss, DL; and (d) multiplying the DL value
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`times the area of the cartilage defect, AD, to give the volume of cartilage loss.
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`Still another aspect of the invention is a method of estimating the change of a region
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`of cartilage in a joint of a mammal over time. The method comprises (a) estimating the
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`Width or area or volume of a region of cartilage at an initial time T1, (b) estimating the
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`width or area or volume of the region of cartilage at a later time T2, and (c) determining the
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`change in the width or area or volume of the region of cartilage between the initial and the
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`later times.
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`Still another aspect of the invention is a method of estimating the loss of cartilage in
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`a joint. The method comprises (a) defining a 3D object coordinate system of the joint at an
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`initial time, T1; (b) identifying a region of a cartilage defect within the 3D object coordinate
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`system; (c) defining a volume of interest around thevregion of the cartilage defect whereby
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`the Volume of interest is larger than the region of cartilage defect, but does not encompass
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`the entire articular cartilage; (d) defining the 3D object coordinate system of the joint at a
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`second timepoint, T2; (e) placing the identically-sized volume of interest into the 3D object
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`coordinate system at timepoint T2 using the object coordinates of the volume of interest at
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`timepoint T1; (1) and measuring any differences in cartilage volume within the volume of
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`interest between timepoints T1 and T2.
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`Another aspect of this invention is a method for providing a biochemically—based
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`map of joint cartilage.
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`The method comprises measuring a detectable biochemical
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`component throughout the cartilage, determining the relative amounts of the biochemical
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`component throughout the cartilage; mapping the amounts of the biochemical component
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`through the cartilage; and determining the areas of cartilage deficit by identifying the areas
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`having an altered amount of the biochemical component present.
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`Once a map is obtained, it can be used in assessing the condition of a cartilage at an
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`initial time and over a time period. Thus, the biochemical map may be used in the method
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`aspects of the invention in a manner similar to the cartilage thickness map.
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`Another aspect of this invention is a method for assessing the condition of cartilage
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`in a joint from a distant location. The method comprises electronically transferring an
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`electronically-generated image of a cartilage of the joint from a transferring device to a
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`receiving device located distant from the transferring device;
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`receiving the transferred
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`image at the distant location; converting the transferred image to a degeneration pattern of
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`the cartilage; and transmitting the degeneration pattern to a site for analysis.
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`Another aspect of the invention is a kit for aiding in assessing the condition of
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`cartilage in a joint of a mammal, which kit comprises a software program, which when
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`installed and executed on a computer reads a cartilage degeneration pattern presented in a
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`standard graphics format and produces a computer readout showing a cartilage thickness
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`map of the degenerated cartilage.
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`Another aspect of this invention is a method for assessing the condition of a
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`subject’s cartilage in a joint,
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`the method comprises obtaining a three dimensional
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`biochemical representation of the cartilage, obtaining a morphological representation of the
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`cartilage, and merging the two representations, and simultaneously displaying the merged
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`representations on a medium. The merged representations are then used to assess the
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`condition of a cartilage, estimate the loss of cartilage in a joint, determining the volume of
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`cartilage loss in a region of cartilage defect, or estimating the change of a region of cartilage
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`at a particular point in time or over a period of time.
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`A method for correlating cartilage image data, bone image data, and opto-electrical
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`image data for the assessment of the condition of a joint, which method comprises (a)
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`obtaining the bone image data of the joint with a set of skin reference markers positioned in
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`externally near the joint, (b) obtaining the opto-electrical image data of the joint with a set
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`of skin reference markers positioned in the same manner as (a), and (c) using the skin
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`reference markers to correlate the images obtained in (a) and (b) with each other, wherein
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`each skin reference marker is detectable in the bone data and the opto~electrical data. The
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`method also can be used to further evaluate cartilage image data that is obtained using a
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`similarly positioned set of skin reference markers.
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`Another aspect of the invention is a skin reference marker that comprises (a) a
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`material detectable by an imaging technique; (b) a container for holding the material, (c) a
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`material that causes the container to adhere to the skin of a human, and (d) a reflective
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`material placed on the surface of the container.
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`Another aspect of the invention is a biochemical map of a cartilage that comprises a
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`three-dimensional representation of the distribution of the amount of the biochemical
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`component throughout the cartilage.
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`Another aspect of the invention is a method for providing a biochemically—based
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`map of joint cartilage of a mammal, wherein the joint comprises cartilage and associated
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`bones on either side of the joint, which method comprises (a) measuring a detectable
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`biochemical component throug