University of California

The Schepens Eye Research Institute, Inc.

Lubris LLC

Tannin Avery Schmidt

Benjamin D Sullivan

David A Sullivan

Gregory D Jay

Edward R Truitt, Iii

Jawed Fareed

Roman Krawetz

Khaled Elsaid

Disclosed herein are methods of using PRG4 glycoprotein, also known as lubricin, to reduce, inhibit, or down-regulate pro-inflammatory pathways in patients at risk of or suffering from an inflammatory response or allergy symptom through CD44 antagonization, regulating pro-inflammatory cytokine production, inhibiting NF-&#x3ba;B translocation and/or facilitating removal of inflammation-inducing cellular or matrix debris or allergens.

Use of PRG4 as an anti-inflammatory agent

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 intravazation, inhibits sticking of macrophages and platelets, and/or serves as a substitute or mimic of native glycocalyx.

Compositions and methods for inhibiting intercellular interactions

Disclosed are new recombinant isoforms of human-like lubricin or PRG4 glycoprotein having outstanding lubrication properties and a novel glycosylation pattern, and methods for their manufacture at high levels enabling commercial production.

Recombinant lubricin composition

Disclosed are mixed solutions of PRG4 and hyaluronic acids having controlled, enhanced rheological properties adapted for various particular medical and cosmetic uses. Such solutions combine the solution-based lubrication ability of HA and the boundary-based lubricating effects of lubricin. Being more viscous, the solutions when used for joint viscosupplementation enhance both the duration of the HA within the joint capsule (in vivo half-life) and enhance the cushioning effects of the HA, as well as improve both solution and boundary mode lubrication mechanisms.

Control of rheological properties of mixed hyaluronate/lubricin solutions

The present invention provides a pharmaceutical composition, and methods of use thereof, for treating ocular boundary deficiency, symptoms associated therewith, or an undesired condition that is associated with or causes ocular boundary deficiency at the ocular surface. The pharmaceutical composition of the present invention comprises a human PRG4 protein, a lubricant fragment, homolog, or isoform thereof, suspended in an ophthalmically acceptable balanced salt solution. The pharmaceutical composition of the present invention may also comprise one or more ophthalmically acceptable agents selected from the group consisting of an ophthalmically acceptable demulcent, excipient, astringent, vasoconstrictor, emollient, sodium hyaluronate, hyaluronic acid, and surface active phospholipids, in a pharmaceutically acceptable carrier for topical administration.

Compositions for treating dry eye disease

The present invention provides a pharmaceutical composition, and methods of use thereof, for treating ocular boundary deficiency, symptoms associated therewith, or an undesired condition that is associated with or causes discomfort at the ocular surface. The pharmaceutical composition of the present invention comprises a human PRG4 protein, or a lubricating fragment thereof, suspended in an ophthalmically acceptable vehicle. The pharmaceutical composition of the present invention may also comprise one or more ophthalmically acceptable agents selected from the group consisting of an ophthalmically acceptable demulcent, excipient, astringent, vasoconstrictor, emollient, sodium hyaluronate, hyaluronic acid, and surface active phospholipids, in a pharmaceutically acceptable carrier for topical administration.

Method for therapeutic replenishment and enrichment of ocular surface lubrication

Provided herein are ophthalmically acceptable pharmaceutical compositions comprising PRG4 or lubricant fragments and a PRG4 inducing compound. The PRG4 inducing compound in the pharmaceutical composition of the present invention upregulates PRG4 expression and localization in the ocular surface for efficient surface boundary lubrication. In some instances, pharmaceutical compositions described herein are utilized for treating ophthalmic conditions, e.g., ocular boundary deficiency and symptoms associated therewith.

Therapeutic modulation of ocular surface lubrication

The present invention provides a pharmaceutical composition, and methods of use thereof, for treating ocular boundary deficiency, symptoms associated therewith, or undesired condition that is associated with or causes ocular boundary deficiency at the ocular surface. The pharmaceutical composition of the present invention comprises a human PRG4 protein, a lubricant fragment, homolog, or isoform thereof, suspended in an ophthalmically acceptable balanced salt solution. The pharmaceutical composition of the present invention may also comprise one or more ophthalmically acceptable agents selected from the group consisting of an ophthalmically acceptable demulcent, excipient, astringent, vasoconstrictor, emollient, sodium hyaluronate, hyaluronic acid, and surface active phospholipids, in a pharmaceutically acceptable carrier for topical administration.

Provided herein are ophthalmically acceptable pharmaceutical compositions comprising a PRG4 inducing compound in combination with PRG4 (including a lubricant fragments, homologs, or isoforms thereof), and methods of using the same. The PRG4 inducing compound in the pharmaceutical composition of the present invention upregulates PRG4 expression and localization in the ocular surface for efficient surface boundary lubrication. In some instances, pharmaceutical compositions described herein are utilized for treating ophthalmic conditions, e.g., ocular boundary deficiency and symptoms associated therewith.

The present invention provides an ophthalmic device, and method of use thereof, for an individual wearing an ophthalmic lens to increase ocular surface boundary lubrication. The invention device comprises an ophthalmic lens and a sacrificial mechanism disposed on the ophthalmic lens, wherein the sacrificial mechanism comprises a plurality of surface bound receptors, such as PRG4, hyaluronic acid, and DNA aptamers, that reversibly bound to a lubricating composition comprising a gel forming agent, a surfactant, or a combination thereof, effectively inhibiting or preventing protein and lipid adsorption on the surface of the lens, and mitigate shear stress and reduce the friction between the lens and the ocular surface of the individual in need.

Ophthalmic device, and method of use thereof, for increasing ocular boundary lubrication

An ophthalmic composition, and methods of use thereof, including for treating ocular boundary deficiency, symptoms associated therewith, or undesired condition that is associated with or causes ocular boundary deficiency at the ocular surface or for the treatment or care of ophthalmic devices. The ophthalmic composition comprises a human PRG4 protein, a lubricant fragment, homolog, or isoform thereof, suspended in an ophthalmically acceptable balanced salt solution. The ophthalmic composition may also comprise one or more ophthalmically acceptable agents.

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Calgary, Canada

Tannin Avery Schmidt