US 12,377,119 B2
Natural killer cells
Matthew J. Fuchter, London (GB); Amaia Uriz Huarte, London (GB); and Hugh J. M. Brady, London (GB)
Assigned to IMPERIAL COLLEGE INNOVATIONS LIMITED, London (GB)
Appl. No. 17/255,091
Filed by IMPERIAL COLLEGE INNOVATIONS LIMITED, London (GB)
PCT Filed Jun. 26, 2019, PCT No. PCT/GB2019/051803
§ 371(c)(1), (2) Date Dec. 22, 2020,
PCT Pub. No. WO2020/002911, PCT Pub. Date Jan. 2, 2020.
Claims priority of application No. 1810486 (GB), filed on Jun. 26, 2018.
Prior Publication US 2022/0073880 A1, Mar. 10, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 35/17 (2025.01); A61K 31/47 (2006.01); C07D 217/26 (2006.01); C07D 405/06 (2006.01); C07D 409/06 (2006.01); C07D 413/06 (2006.01); C07D 417/06 (2006.01); C12N 5/0783 (2010.01)
CPC A61K 35/17 (2013.01) [A61K 31/47 (2013.01); C07D 217/26 (2013.01); C07D 405/06 (2013.01); C07D 409/06 (2013.01); C07D 413/06 (2013.01); C07D 417/06 (2013.01); C12N 5/0646 (2013.01); C12N 2501/125 (2013.01); C12N 2501/2307 (2013.01); C12N 2501/2315 (2013.01); C12N 2501/26 (2013.01); C12N 2501/42 (2013.01); C12N 2501/999 (2013.01); C12N 2506/11 (2013.01)] 22 Claims
 
1. An ex vivo method for expanding an NK cell population, comprising the steps of:
a) culturing an haematopoietic progenitor cell (HPC) comprising sample obtained from an individual;
b) contacting said sample with a compound that inhibits the action of REV-ERB; and
c) expanding said cells in vitro to produce an NK cell population;
wherein the compound has formula (I):

OG Complex Work Unit Chemistry
where: custom character represents bonds that are all either present or absent;
R1 is selected from C1-6 hydrocarbyl, and is optionally substituted with one or more groups independently selected from C1-4 hydrocarbyl, —OR′, —OC(O)R′, —C(O)OR′, —SR′, —S(O)R′, —S(O)2R′, —NR′2, —NR′C(O)R′, —C(O)NR′2, —CN, —NO2, -Ph, —CF3 and halogen;
R2 is selected from 5-10 membered heterocyclyl rings and C1-6 hydrocarbyl, and is optionally substituted with one or more groups independently selected from C1-4 hydrocarbyl, —OR′, —OC(O)R′, —C(O)OR′, —SR′, —S(O)R′, —S(O)2R′, —NR′2, —NR′C(O)R′, —C(O)NR′2, —CN, —NO2, -Ph, —CF3 and halogen;
X is selected from —O— and —NR′— or is absent;
Y is selected from —C(O)— or —CR′2—;
Z is selected from —O— and —NR′— or is absent;
each Ra is independently selected from H, C1-4 hydrocarbyl, —OR′, —OC(O)R′, —C(O)OR′, —SR′, —S(O)R′, —S(O)2R′, —NR′2, —NR′C(O)R′, —C(O)NR′2, —CN, —NO2, -Ph, —CF3 and halogen;
each Rb is independently selected from H, C1-4 hydrocarbyl and —OR′;
Rc is selected from H and C1-4 hydrocarbyl; and
each R′ is independently selected from H, C1-4 hydrocarbyl and -Ph;
or a pharmaceutically acceptable salt thereof, provided that the compound is not:

OG Complex Work Unit Chemistry