# US 10,500,251 B2 · Compositions and methods for inhibiting intercellular interactions > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,500,251 B2 - Document ID: US10500251B2 - Status: Granted - Kind: B2 - Application number: 16/108,621 - Filed: 2018-08-22 - Published: 2018-12-13 - Granted: 2019-12-10 - Earliest claimed: 2013-11-26 - Assignees: Lubris LLC - Applicants: Lubris LLC - Inventors: Gregory D. Jay; Tannin Schmidt; Benjamin Sullivan - Web page: https://patentgrep.com/patent/US10500251B2 ## CPC - A61K 38/1709: {from mammals} - A01N 1/146: Non-refrigerated containers specially adapted for transporting or storing living parts whilst preserving - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 47/02: Inorganic compounds - A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 9/14: Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers - A61P 11/00: Drugs for disorders of the respiratory system - A61P 13/00: Drugs for disorders of the urinary system - A61P 17/00: Drugs for dermatological disorders - A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like - A61P 19/00: Drugs for skeletal disorders - A61P 19/02: for joint disorders, e.g. arthritis, arthrosis - A61P 19/04: for non-specific disorders of the connective tissue - A61P 27/06: Antiglaucoma agents or miotics - A61P 35/04: specific for metastasis - A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract 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. ## Claims ### Claim 1 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. ### Claim 2 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. ### Claim 3 (depends on 1) The method of claim 1, wherein the cells are neoplastic cells or leukocytes. ### Claim 4 (depends on 1) The method of claim 1, wherein the cells are cancer cells. ### Claim 5 (depends on 4) The method of claim 4, wherein the cancer cells are prostate cancer cells, breast cancer cells, lung cancer cells, or ovarian cancer cells. ### Claim 6 (depends on 1) The method of claim 1, wherein the PRG4 is administered to provide a dose of between 0.3 mg/kg and 3.0 mg/kg of PRG4 in said patient. ### Claim 7 (depends on 1) The method of claim 1, wherein the injection is a systemic intravenous injection or a localized injection at the site of the cells. ### Claim 8 (depends on 1) The method of claim 1, wherein the extravasation of cells reduced or inhibited is metastasis of cancer cells to bone, lymph, lungs, brain, or liver. ### Claim 9 (depends on 4) The method of claim 4, wherein administration of PRG4 occurs in conjunction with surgical, chemotherapy, or radiation treatment for the cancer. ### Claim 10 (depends on 2) The method of claim 2, wherein the cells are neoplastic cells or leukocytes. ### Claim 11 (depends on 2) The method of claim 2, wherein the cells are cancer cells. ### Claim 12 (depends on 11) The method of claim 11, wherein the cancer cells are prostate cancer cells, breast cancer cells, lung cancer cells, or ovarian cancer cells. ### Claim 13 (depends on 2) The method of claim 2, wherein the PRG4 is administered to provide a dose of between 0.3 mg/kg and 3.0 mg/kg of PRG4 in said patient. ### Claim 14 (depends on 2) The method of claim 2, wherein the injection is a systemic intravenous injection or a localized injection at the site of the cells. ### Claim 15 (depends on 2) The method of claim 2, wherein the extravasation of cells reduced or inhibited is metastasis of cancer cells to bone, lymph, lungs, brain, or liver. ### Claim 16 (depends on 15) The method of claim 15, wherein administration of PRG4 occurs in conjunction with surgical, chemotherapy, or radiation treatment for the cancer.