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AssigneeLubris LLC
InventorsGregory D. Jay, Tannin Schmidt, Benjamin Sullivan
Estimating the term…
Disclosed are compositions and methods involving the use of PRG4 protein, also known as lubricin, to mechanically inhibit biological processes involving cell motility and adhesion. The methods and compositions may be used to develop a variety of specific therapies and compositions, often exploited through surgical procedures, where development of the pathology involves one or more of the following modes of action: 1) the passage of cells from one body compartment to another, 2) adherence of macrophages to substrates such as fibrin or exposed extra cellular matrix, 3) binding of platelets to fibrin, or 4) failure of function of the glycocalyx on exposed epithelial cell surfaces, e.g., within the vasculature. In these instances PRG4 glycoprotein adheres to extracellular matrix or cell surfaces and presents a glycol-surface of polysaccharide which blocks the mechanisms of cell motility, extravasation, or intravasation, inhibits sticking of macrophages and platelets, and/or serves as a substitute or mimic of native glycocalyx.
A method of reducing or inhibiting extravasation of cells from the circulatory system of a patient in need thereof comprising administering by injection directly or indirectly to the vascular system a composition comprising a physiologically compatible vehicle and PRG4 in an amount sufficient to contact PRG4 with an activated epithelial cell surface of the vasculature to produce a PRG4 film associated with at least a portion of the surface thereby to present a boundary lubricant layer effective at reducing or inhibiting the process of extravasation.
The method of inhibiting or reducing intravasation of cells from an extravascular compartment to the circulatory system of a patient comprising administering by injection directly or indirectly to the extravascular compartment a composition comprising a physiologically compatible vehicle and PRG4 in an amount sufficient to contact PRG4 with the cells or cell-surrounding matrix to produce a PRG4 film associated with the surface or the matrix thereby to present an boundary lubricant layer effective at reducing or inhibiting the native process of cell motility or intravasation.
A method of maintaining or improving circulatory system function and health comprising administering by injection directly or indirectly to the circulatory system a maintenance concentration of a composition comprising a physiologically compatible vehicle and PRG4 in an amount sufficient to form a boundary lubrication film of PRG4 at a stressed endothelial surface or plaque within the vascular system.
A method of inhibiting or reducing vascular thrombus formation comprising administering by injection directly or indirectly to the circulatory system a maintenance concentration of a composition comprising a physiologically compatible vehicle and PRG4 in an amount sufficient to form a boundary lubrication film of PRG4 on fibrin and/or platelets present therein.
A method of reducing or inhibiting vascular restenosis after an intravascular procedure comprising administering by injection to the circulatory system of a patient systemically or locally at the site of the procedure a composition comprising PRG4 and a physiologically compatible vehicle in an amount sufficient to form a boundary lubricating film of PRG4 at an endothelial surface at said site within the vascular system.
A method of treating a surgical incision in a patient to maintain patency of the incision and inhibit fibrosis at the site of the incision comprising administering PRG4 in a physiologically compatible vehicle to a surface at the site of the incision, whereby the lubricin prevents adherence of macrophages to the site of surgical incision, thereby inhibiting fibrosis.
A method of treating, preventing, or slowing the progress of fibrosis of an organ or tissue comprising administering to a patient suffering from or at risk of fibrosis PRG4 in a physiologically compatible vehicle directly or indirectly to a site having or at risk of fibrosis, whereby the PRG4 inhibits adherence of macrophages at the site, thereby preventing or slowing progression of the fibrosis.
Use of PRG4 in the preparation of a medicament for inhibiting extravasation of cells from the circulatory system of a patient to produce a PRG4 film associated with at least a portion of the surface of the vasculature thereby to present a boundary lubricant layer effective at inhibiting the process of extravasation.
Use of PRG4 in the preparation of a medicament for inhibiting intravasation of cells from an extravascular compartment to the circulatory system of a patient and to contact PRG4 with the cells or cell-surrounding matrix to produce a PRG4 film associated with the surface or the matrix thereby to present a boundary lubricant layer effective at inhibiting the native process of cell motility or intravasation.
Use of PRG4 in the preparation of a medicament for maintaining circulatory system function and health and to form a boundary lubrication film of PRG4 at a stressed endothelial surface or plaque within the vascular system.
Use of PRG4 in the preparation of a medicament for inhibiting vascular thrombus formation and to form a boundary lubrication film of PRG4 on fibrin and/or platelets present within the vascular system.
Use of PRG4 in the preparation of a medicament for reducing vascular restenosis after an intravascular procedure to form a boundary lubricating film of PRG4 at an endothelial surface at the surgical site within the vascular system.
Use of PRG4 in the preparation of a medicament for treating a patient having a surgical incision to maintain patency of the incision and prevent fibrosis at the site of the incision.
Use of PRG4 in the preparation of a medicament for treatment of fibrosis of an organ or tissue.
Use of PRG4 as an anticoagulant.
A container for housing a blood sample comprising a coating of PRG4.
A method of inhibiting in a mammal transient binding interactions between a motile cell and a tissue, the method comprising the step of applying PRG4 to the surface of the motile cell or of the tissue in an amount sufficient to provide a coating which inhibits transient attractive interactions between the cell and the tissue so as to inhibit motility of the cell through, within, or across the surface of the tissue.
Dependencies are inferred from the claim text.