US 12,227,551 B2
Membrane bound IL12 compositions and methods for tunable regulation
Michelle Lynn Ols, Northborough, MA (US); Vipin Suri, Belmont, MA (US); Dexue Sun, Cambridge, MA (US); Dan Jun Li, Cambridge, MA (US); Dhruv Kam Sethi, Westwood, MA (US); Abhishek Kulkarni, Brookline, MA (US); Benjamin J. Primack, Brookline, MA (US); and James Storer, Medford, MA (US)
Assigned to OBSIDIAN THERAPEUTICS, INC., Cambridge, MA (US)
Appl. No. 17/413,512
Filed by Obsidian Therapeutics, Inc., Cambridge, MA (US)
PCT Filed Dec. 11, 2019, PCT No. PCT/US2019/065810
§ 371(c)(1), (2) Date Jun. 11, 2021,
PCT Pub. No. WO2020/123716, PCT Pub. Date Jun. 18, 2020.
Claims priority of provisional application 62/860,386, filed on Jun. 12, 2019.
Claims priority of provisional application 62/815,408, filed on Mar. 8, 2019.
Claims priority of provisional application 62/777,900, filed on Dec. 11, 2018.
Prior Publication US 2022/0056092 A1, Feb. 24, 2022
Int. Cl. C07K 14/54 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); C07K 14/725 (2006.01); C07K 16/28 (2006.01)
CPC C07K 14/5434 (2013.01) [A61K 39/4611 (2023.05); A61K 39/4631 (2023.05); A61K 39/464412 (2023.05); A61K 39/46444 (2023.05); A61P 35/00 (2018.01); C07K 14/7051 (2013.01); C07K 16/2803 (2013.01); A61K 2239/31 (2023.05); A61K 2239/38 (2023.05); A61K 2239/48 (2023.05); C07K 2317/622 (2013.01); C07K 2319/03 (2013.01); C07K 2319/20 (2013.01); C07K 2319/33 (2013.01)] 18 Claims
 
1. A modified cell comprising an effector module, wherein said effector module comprises:
(a) a payload of interest, said payload comprising a membrane-associated Interleukin 12 (IL12),
wherein the membrane-associated IL12 is a fusion protein comprising IL12 subunit beta (p40), IL 12 subunit alpha (p35), at least one linker, and a transmembrane domain; and
(b) a stimulus response element (SRE) comprising a region of Human phosphodiesterase 5 (hPDE5) corresponding to amino acids 535-860 of SEQ ID NO:1, wherein the region further comprises mutation R732L, and wherein the SRE is responsive to or interacts with at least one stimulus.