# US 9,750,767 B2 · IL-18 inhibition for promotion of early hematopoietic progenitor expansion > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,750,767 B2 - Document ID: US9750767B2 - Status: Granted - Kind: B2 - Application number: 14/760,076 - Filed: 2014-01-14 - Published: 2016-02-04 - Granted: 2017-09-05 - Earliest claimed: 2013-01-14 - Assignees: The General Hospital Corporation; President and Fellows of Harvard College - Applicants: The General Hospital Corporation; President and Fellows of Harvard College - Inventors: David T. Scadden; Lev Silberstein; Peter Kharchenko - Web page: https://patentgrep.com/patent/US9750767B2 ## CPC - A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells - A61K 38/1709: {from mammals} - A61K 38/20: Interleukins [IL] - A61P 7/00: Drugs for disorders of the blood or the extracellular fluid - A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells} - 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 Disclosed herein are methods for enhancing hematopoietic reconstitution of a subject. One method involves administering a therapeutically effective amount of an inhibitor of IL-18 to a recipient subject and also administering hematopoietic stem/progenitor cells to the subject. Another method involves administering an inhibitor of IL-18 to a donor prior to harvest of hematopoietic stem/progenitor cells. Pharmaceutical compositions relating to the methods are also described. ## Claims ### Claim 1 A method for enhancing hematopoietic reconstitution of a subject in need thereof comprising: a) administering to the subject hematopoietic stem/progenitor cells (HSPC) obtained from the blood, placenta or umbilical cord of a donor; and b) administering to the subject a therapeutically effective amount of an inhibitor of interleukin 18 (IL-18) to thereby inhibit IL-18 interaction with IL-18R molecules present on the HSPC administered in step a). ### Claim 2 (depends on 1) The method of claim 1, wherein administering step b) is by a route selected from the group consisting of enteral and parenteral. ### Claim 3 (depends on 2) The method of claim 2, wherein administering step b) is performed immediately after administering step a). ### Claim 4 (depends on 2) The method of claim 2, wherein administering step b) is performed prior to and immediately after administering step a). ### Claim 5 (depends on 1) The method of claim 1, wherein the inhibitor of IL-18 is administered to the subject over a period of time from about 1 day to 100 days directly after administration of the HSPCs. ### Claim 6 (depends on 5) The method of claim 5, wherein the period is from about 1 day to about 21 days directly after administration of the HSPCs. ### Claim 7 (depends on 5) The method of claim 5, wherein the period is from about 1 day to about 5 days directly after administration of the HSPCs. ### Claim 8 (depends on 5) The method of claim 5, wherein the period is about 5 days directly after administration of the HSPCs. ### Claim 9 (depends on 1) The method of claim 1, wherein the HSPCs are allogenic. ### Claim 10 (depends on 1) The method of claim 1, wherein the HSPCs are autologous. ### Claim 11 (depends on 1) The method of claim 1 wherein the HSPC are obtained from a donor subject treated with an inhibitor of IL-18 prior to harvest of the HSPCs to thereby expand early hematopoietic progenitor cells in the HSPCs. ### Claim 12 (depends on 11) The method of claim 11, wherein the treatment of the donor subject is by administration of the inhibitor of IL-18 to the donor subject by a method selected from the group consisting of enteral and parenteral. ### Claim 13 (depends on 1) The method of claim 1, wherein the inhibitor of IL-18 is selected from the group consisting of IL-18 binding protein, an antibody against IL-18, an antibody against an IL-18 receptor subunits, an inhibitor of the IL-18 signaling pathway, an antagonist of IL-18 which competes with IL-18 and blocks the IL-18 receptor, an inhibitor of caspase-1 (ICE), an IL-18 isoform, an IL-18 mutein, an IL-18 fused protein, an IL-18 functional derivative, an IL-18 active fraction, and an IL-18 circularly permutated derivative thereof inhibiting the biological activity of IL-18. ### Claim 14 A method for enhanced hematopoietic reconstitution in a subject in need thereof comprising administering to the subject hematopoietic stem/progenitor cells (HSPC) obtained from a donor subject, wherein the donor subject was treated with an inhibitor of interleukin 18 (IL-18) to thereby expand early hematopoietic progenitor cells prior to harvest of the HSPCs from the donor. ### Claim 15 (depends on 14) The method of claim 14, wherein the donor subject is treated with the inhibitor of IL-18 for a period of from about 1 day to about 10 days directly prior to harvest of the HSPCs. ### Claim 16 (depends on 15) The method of claim 15, wherein the period is from about 1 day to about 5 days directly prior to harvest of the HSPCs. ### Claim 17 (depends on 15) The method of claim 15, wherein the period is about 5 days directly prior to harvest of the HSPCs. ### Claim 18 (depends on 14) The method of claim 14, wherein the HSPCs are obtained from bone marrow, blood, placenta, or umbilical cord of the donor. ### Claim 19 (depends on 14) The method of claim 14, wherein the inhibitor of IL-18 is selected from the group consisting of IL-18 binding protein, an antibody against IL-18, an antibody against an IL-18 receptor subunits, an inhibitor of the IL-18 signaling pathway, an antagonist of IL-18 which competes with IL-18 and blocks the IL-18 receptor, an inhibitor of caspase-1 (ICE), an IL-18 isoform, an IL-18 mutein, an IL-18 fused protein, an IL-18 functional derivative, an IL-18 active fraction, and an IL-18 circularly permutated derivative thereof inhibiting the biological activity of IL-18. ### Claim 20 A method for enhancing hematopoietic reconstitution of a subject in need thereof comprising: a) administering to the subject autologous hematopoietic stem/progenitor cells (HSPC); and b) administering to the subject a therapeutically effective amount of an inhibitor of interleukin 18 (IL-18) to thereby inhibit IL-18 interaction with IL-18R molecules present on the HSPC administered in step a).