US 12,152,080 B2
Compositions and methods for non-myeloablative conditioning
David T. Scadden, Weston, MA (US); Rahul Palchaudhuri, Cambridge, MA (US); Derrick J. Rossi, Newton, MA (US); and Agnieszka D. Czechowicz, Boston, MA (US)
Assigned to President and Fellows of Harvard College, Cambridge, MA (US); The General Hospital Corporation, Boston, MA (US); and The Children's Medical Center Corporation, Boston, MA (US)
Filed by President and Fellows of Harvard College, Cambridge, MA (US); The General Hospital Corporation, Boston, MA (US); and The Children's Medical Center Corporation, Boston, MA (US)
Filed on Dec. 29, 2020, as Appl. No. 17/137,337.
Application 17/137,337 is a continuation of application No. 16/726,803, filed on Dec. 24, 2019, granted, now 10,906,980.
Application 16/726,803 is a continuation of application No. 16/205,205, filed on Nov. 29, 2018, granted, now 10,570,207, issued on Feb. 25, 2020.
Application 16/205,205 is a continuation of application No. 15/148,837, filed on May 6, 2016, granted, now 10,280,225, issued on May 7, 2019.
Application 15/148,837 is a continuation of application No. PCT/US2016/026276, filed on Apr. 6, 2016.
Claims priority of provisional application 62/239,573, filed on Oct. 9, 2015.
Claims priority of provisional application 62/221,595, filed on Sep. 21, 2015.
Claims priority of provisional application 62/220,204, filed on Sep. 17, 2015.
Claims priority of provisional application 62/143,642, filed on Apr. 6, 2015.
Prior Publication US 2021/0388094 A1, Dec. 16, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); A61K 35/14 (2015.01); A61K 35/28 (2015.01); A61K 38/16 (2006.01); A61K 47/68 (2017.01); C07K 4/04 (2006.01); G01N 33/50 (2006.01); G01N 33/569 (2006.01); G01N 33/574 (2006.01)
CPC C07K 16/2866 (2013.01) [A61K 35/28 (2013.01); A61K 38/164 (2013.01); A61K 38/168 (2013.01); A61K 47/6825 (2017.08); A61K 47/6849 (2017.08); A61K 47/6898 (2017.08); C07K 4/04 (2013.01); C07K 16/289 (2013.01); G01N 33/50 (2013.01); G01N 33/56966 (2013.01); G01N 33/57407 (2013.01); G01N 33/57434 (2013.01)] 49 Claims
 
1. A method of conditioning a human subject having a hemoglobinopathy for hematopoietic stem cell transplantation, the method comprising administering to a human subject an amount of an immunotoxin effective to condition the human subject for hematopoietic stem cell engraftment by selectively depleting endogenous hematopoietic stem cells in the human subject,
wherein the immunotoxin comprises an antibody, or an antigen-binding fragment thereof, conjugated to a toxin, wherein the immunotoxin selectively binds to the endogenous hematopoietic stem cells, wherein the immunotoxin is internalized by the endogenous hematopoietic stem cells, wherein the immunotoxin is capable of conditioning an immunocompetent subject, and wherein the method does not induce life-threatening anemia in the human subject prior to transplantation of hematopoietic stem cells.