US 11,839,647 B2
Methods for inducing partial apoptosis using caspase polypeptides
Kevin Slawin, Houston, TX (US); David Michael Spencer, Frisco, TX (US); and Aaron Edward Foster, Houston, TX (US)
Assigned to Bellicum Pharmaceuticals, Inc., Houstin, TX (US)
Filed by Bellicum Pharmaceuticals, Inc., Houston, TX (US)
Filed on Jan. 3, 2020, as Appl. No. 16/734,104.
Application 16/734,104 is a division of application No. 15/888,948, filed on Feb. 5, 2018, granted, now 10,525,110.
Application 15/888,948 is a continuation of application No. 14/296,404, filed on Jun. 4, 2014, granted, now 9,913,882, issued on Mar. 13, 2018.
Claims priority of provisional application 61/949,847, filed on Mar. 7, 2014.
Claims priority of provisional application 61/831,428, filed on Jun. 5, 2013.
Prior Publication US 2020/0230216 A1, Jul. 23, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 38/48 (2006.01); A61K 38/16 (2006.01); C12N 9/64 (2006.01); C12N 5/00 (2006.01); A61K 35/17 (2015.01); A61K 38/17 (2006.01); A61K 48/00 (2006.01); A61K 35/28 (2015.01); A61K 35/30 (2015.01); A61K 35/545 (2015.01); A61K 39/00 (2006.01)
CPC A61K 38/4873 (2013.01) [A61K 35/17 (2013.01); A61K 35/28 (2013.01); A61K 35/30 (2013.01); A61K 35/545 (2013.01); A61K 38/16 (2013.01); A61K 38/177 (2013.01); A61K 39/0005 (2013.01); A61K 48/005 (2013.01); C12N 5/0081 (2013.01); C12N 5/0087 (2013.01); C12N 9/6472 (2013.01); C12N 2501/48 (2013.01); C12N 2510/00 (2013.01)] 25 Claims
 
1. A method of controlling survival of transplanted T cells in a subject, comprising administering a multimeric ligand to a human subject to whom T cells have been administered, wherein the T cells have been transduced or transfected with:
a) a first nucleic acid that encodes a chimeric polypeptide comprising a multimerization region and a caspase-9 polypeptide or a modified caspase-9 polypeptide, wherein the caspase-9 polypeptide or the modified caspase-9 polypeptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 9; and
b) a second nucleic acid that encodes a chimeric antigen receptor;
wherein the multimeric ligand binds to the multimerization region in an amount effective to kill less than 80% of transplanted T cells that express the caspase-9 polypeptide or the modified caspase-9 polypeptide; and
wherein at least 1×106 transduced or transfected T cells are administered to the subject.