# US 10,478,459 B2 · Compositions and methods for cell transplantation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,478,459 B2 - Document ID: US10478459B2 - Status: Granted - Kind: B2 - Application number: 15/687,340 - Filed: 2017-08-25 - Published: 2017-12-14 - Granted: 2019-11-19 - Earliest claimed: 2012-01-25 - Assignees: Université Catholique De Louvain - Applicants: Université Catholique De Louvain - Inventors: Xavier Stephenne; Etienne Sokal; Mustapha Najimi; Stéphane Eeckhoudt; Cédric Hermans - Web page: https://patentgrep.com/patent/US10478459B2 ## CPC - A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells - A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol - A61K 31/727: Heparin; Heparan - A61K 31/737: Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate (A61K31/727 takes precedence) - A61K 35/407: Liver; Hepatocytes - A61K 38/55: Protease inhibitors - A61K 38/58: from leeches, e.g. hirudin, eglin - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics - A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to compositions and methods for cell transplantation. In particular, the present invention provides a composition with procoagulant cells and at least one factor Xa inhibitor, preferably rivaroxaban, as well as at least one thrombin inhibitor, preferably bivalirudin. ## Claims ### Claim 1 A combination comprising: a liquid cell suspension comprising adult liver-derived progenitor or stem cells and at least one factor Xa inhibitor which is a direct or indirect factor Xa inhibitor and is not an antithrombin activator, and at least one thrombin inhibitor. ### Claim 2 (depends on 1) The combination according to claim 1, wherein the factor Xa inhibitor is a direct factor Xa inhibitor. ### Claim 3 (depends on 2) The combination according to claim 2, wherein the direct factor Xa inhibitor is selected from the group consisting of rivaroxaban, apixaban, betrixaban, edoxaban, otamixaban, YM466, DX9065a, razaxaban, darexaban, letaxaban, LY517717, GW813893, YM-60828, eribaxaban, JTV-803, KFA-144, DPC-423, RPR-209685, MCM-09, and antistasin, preferably wherein the direct factor Xa inhibitor is rivaroxaban. ### Claim 4 (depends on 1) The combination according to claim 1, wherein the adult liver-derived progenitor or stem cells are human adult-derived liver progenitor or stem cells which express alpha-smooth muscle actin (ASMA) and albumin (ALB) and do not express cytokeratin-19 (CK-19), or are a non-oval adult human liver pluripotent progenitor cell line which expresses hepatic cell markers and which is capable of differentiating into mature liver cells, insulin-producing cells, osteogenic cells and epithelial cells, or are a non-oval adult human liver pluripotent progenitor cell line which expresses hepatic cell markers and which is capable of differentiating into mature liver cells, insulin-producing cells, osteogenic cells and endothelial cells. ### Claim 5 (depends on 1) The combination according to claim 1, wherein the cells express tissue factor, preferably wherein the cells express tissue factor constitutively. ### Claim 6 (depends on 1) The combination according to claim 1, wherein the cells: Are primary cells; or Are a cell line; or Have been subjected to storage, such as to cryopreservation, and/or to proliferation or passaging; or Are induced to express one or more proteins; or Are stably or transiently transformed with a nucleic acid. ### Claim 7 (depends on 1) The combination according to claim 1 for separate, simultaneous or sequential in any order administration of the liquid cell suspension and the at least one thrombin inhibitor, optionally in combination with one or more pharmaceutically acceptable excipients. ### Claim 8 (depends on 1) The combination according to claim 1, wherein the thrombin inhibitor is selected from the group consisting of bivalirudin, hirudin, lepirudin, desirudin, argatroban, melagatran, ximelagatran, and dabigatran; preferably selected from the group consisting of bivalirudin and hirudin; more preferably bivalirudin. ### Claim 9 (depends on 1) The combination according to claim 1, wherein said suspension are for administration via injection; preferably via localised injection, systemic injection, intrasplenic injection, injection to a portal vein, injection to liver pulp, or parenteral administration. ### Claim 10 (depends on 1) The combination according to claim 1, wherein said cells are at a concentration of between 104/ml to 108/ml in the liquid cell suspension. ### Claim 11 (depends on 1) The combination according to claim 1 further comprising an immunosuppressive agent. ### Claim 12 (depends on 1) A pharmaceutical composition comprising the combination according to claim 1 and one or more pharmaceutically acceptable excipients. ### Claim 13 (depends on 12) A pharmaceutical composition according to claim 12, wherein the pharmaceutical composition is liquid, and the cells are present in the pharmaceutical composition at a concentration between 104/ml to 108/ml, preferably between 105/ml to 107/ml, more preferably between 1×106/ml and 1×107/ml, or 5×106/ml. ### Claim 14 (depends on 1) The combination according to claim 1 for use as a medicament. ### Claim 15 (depends on 1) A kit of parts or an article of manufacture comprising the combination according to claim 1 and optionally comprising one or more pharmaceutically acceptable excipients. ### Claim 16 A kit of parts or an article of manufacture comprising: a liquid cell suspension 1 comprising adult liver-derived progenitor or stem cells and at least one factor Xa inhibitor which is a direct or indirect factor Xa inhibitor and is not an antithrombin activator, and at least one thrombin inhibitor. ### Claim 17 (depends on 16) The kit of parts or article of manufacture according to claim 16, wherein the liquid cell suspension is configured for separate, simultaneous or sequential in any order administration with the at least one thrombin inhibitor. ### Claim 18 (depends on 16) The kit of parts or article of manufacture according to claim 16, wherein the at least one thrombin inhibitor is included in an aqueous solution. ### Claim 19 (depends on 16) The kit of parts or article of manufacture according to claim 16, wherein the at least one thrombin inhibitor is selected from the group consisting of bivalirudin, hirudin, lepirudin, desirudin, argatroban, melagatran, ximelagatran, and dabigatran; preferably selected from the group consisting of bivalirudin and hirudin; more preferably bivalirudin. ### Claim 20 (depends on 16) The kit of parts or article of manufacture according to claim 16, further comprising one or more pharmaceutically acceptable excipients. ### Claim 21 (depends on 16) The kit of parts or article of manufacture according to claim 16, wherein the liquid cell suspension and the at least one thrombin inhibitor are in separate containers. ### Claim 22 (depends on 16) The kit of parts or article of manufacture according to claim 16, wherein the liquid cell suspension and the at least one thrombin inhibitor are admixed.