US 12,485,186 B2
Antibody-mediated conditioning with immunosuppression to enable allogeneic transplantation
Derrick J. Rossi, Newton, MA (US); Agnieszka D. Czechowicz, Irvine, CA (US); Philip M. Murphy, Rockville, MD (US); and Zhanzhuo Li, North Potomac, MD (US)
Assigned to The Children's Medical Center Corporation, Boston, MA (US); and The United States of America, as Represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US)
Appl. No. 16/498,572
Filed by THE CHILDREN'S MEDICAL CENTER CORPORATION, Boston, MA (US); and THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES, Bethesda, MD (US)
PCT Filed Mar. 29, 2018, PCT No. PCT/US2018/025044
§ 371(c)(1), (2) Date Sep. 27, 2019,
PCT Pub. No. WO2018/183613, PCT Pub. Date Oct. 4, 2018.
Claims priority of provisional application 62/479,772, filed on Mar. 31, 2017.
Prior Publication US 2020/0188527 A1, Jun. 18, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/68 (2017.01); A61K 35/12 (2015.01); A61K 35/28 (2015.01); A61K 39/00 (2006.01); A61K 39/395 (2006.01); A61K 45/06 (2006.01); A61P 37/06 (2006.01)
CPC A61K 47/6849 (2017.08) [A61K 35/28 (2013.01); A61K 39/3955 (2013.01); A61K 45/06 (2013.01); A61K 47/6825 (2017.08); A61P 37/06 (2018.01); A61K 2035/124 (2013.01); A61K 2039/505 (2013.01)] 2 Claims
 
1. A method of tolerizing a patient to a recombinant formulation, the method comprising:
administering to the patient a CD117 antibody or antibody fragment with specific binding affinity to a protein displayed at the HSC surface, said antibody or antibody fragment being coupled with a toxin;
administering to the patient gene-modified autologous HSCs that give rise to cells which are tolerant to a recombinant formulation;
administering to the patient the recombinant formulation; and
administering to the patient a medicament selected from the group consisting of a T-cell depleting or inhibiting antibody or antibody fragment, natural killer (NK) cell depleting or inhibiting antibody or fragment, immunosuppressive drug, and any combination thereof, wherein the medicament is administered during a time period selected from the group consisting of: prior to the administration of the HSC-depleting composition; during administration of the HSC-depleting composition; after the administration of the HSC-depleting composition, but before the administration of the gene-modified autologous HSCs; during administration of the gene-modified autologous HSCs; after the administration of the gene-modified autologous HSCs; after the administration of the recombinant formulation; and any combination thereof.