US 11,744,861 B2
Compositions and methods for selective elimination and replacement of hematopoietic stem cells
Eric M. Ostertag, San Diego, CA (US); Devon Shedlock, San Diego, CA (US); and Julian David Down, San Diego, CA (US)
Assigned to Poseida Therapeutics, Inc., San Diego, CA (US)
Appl. No. 16/493,853
Filed by Poseida Therapeutics, Inc., San Diego, CA (US)
PCT Filed Mar. 13, 2018, PCT No. PCT/US2018/022169
§ 371(c)(1), (2) Date Sep. 13, 2019,
PCT Pub. No. WO2018/169948, PCT Pub. Date Sep. 20, 2018.
Claims priority of provisional application 62/596,062, filed on Dec. 7, 2017.
Claims priority of provisional application 62/470,814, filed on Mar. 13, 2017.
Prior Publication US 2020/0078402 A1, Mar. 12, 2020
Int. Cl. A61K 35/17 (2015.01); A61K 9/00 (2006.01); A61K 31/664 (2006.01); A61K 31/7076 (2006.01); A61K 35/28 (2015.01); A61K 38/17 (2006.01); A61K 38/19 (2006.01); A61K 38/48 (2006.01); A61K 38/52 (2006.01); A61K 39/39 (2006.01); A61K 39/395 (2006.01); A61K 45/06 (2006.01); C12N 5/0783 (2010.01); C12N 9/12 (2006.01); C12N 9/22 (2006.01); C12N 15/11 (2006.01)
CPC A61K 35/17 (2013.01) [A61K 9/0019 (2013.01); A61K 9/0085 (2013.01); A61K 31/664 (2013.01); A61K 31/7076 (2013.01); A61K 35/28 (2013.01); A61K 38/177 (2013.01); A61K 38/1774 (2013.01); A61K 38/193 (2013.01); A61K 38/4873 (2013.01); A61K 38/52 (2013.01); A61K 39/39 (2013.01); A61K 39/3955 (2013.01); A61K 45/06 (2013.01); C12N 5/0636 (2013.01); C12N 9/1241 (2013.01); C12N 9/22 (2013.01); C12N 15/11 (2013.01); C12Y 207/07 (2013.01); C12Y 304/22062 (2013.01); C12Y 502/01008 (2013.01); C12N 2310/20 (2017.05); C12N 2510/00 (2013.01); C12N 2800/80 (2013.01)] 19 Claims
 
1. A method of eliminating at least one target hematopoietic stem cell (HSC) in a subject, comprising administering to the subject an effective amount of a composition comprising a plurality of T-cells that express at least one chimeric ligand receptor (CLR) that specifically binds to c-KIT,
wherein the specific binding of the at least one CLR to c-KIT activates the T-cell,
wherein the activated T-cell induces death of the at least one target HSC, and
wherein the at least one CLR comprises:
(a) an ectodomain comprising
i) a signal peptide comprising a human CD8α signal peptide;
ii) a scFv comprising the amino acid sequence of SEQ ID NO: 73; and
iii) a hinge domain comprising a human CD8α hinge domain;
(b) a transmembrane domain comprising a human CD8α transmembrane domain;
(c) a co-stimulatory domain comprising a human 4-1BB costimulatory domain; and
(d) a endodomain comprising a human CD3ζ endodomain.