US 12,459,983 B2
Engineered immune cells with receptor signal strength modulated by a hinge
Alexander Kamb, Agoura Hills, CA (US)
Assigned to A2 BIOTHERAPEUTICS, INC., Agoura Hills, CA (US)
Filed by A2 BIOTHERAPEUTICS, INC., Agoura Hills, CA (US)
Filed on Apr. 30, 2024, as Appl. No. 18/650,881.
Application 18/650,881 is a continuation of application No. 17/480,490, filed on Sep. 21, 2021, granted, now 12,012,612.
Claims priority of provisional application 63/081,256, filed on Sep. 21, 2020.
Claims priority of provisional application 63/081,237, filed on Sep. 21, 2020.
Claims priority of provisional application 63/081,248, filed on Sep. 21, 2020.
Claims priority of provisional application 63/081,242, filed on Sep. 21, 2020.
Claims priority of provisional application 63/081,258, filed on Sep. 21, 2020.
Claims priority of provisional application 63/081,231, filed on Sep. 21, 2020.
Claims priority of provisional application 63/081,229, filed on Sep. 21, 2020.
Claims priority of provisional application 63/081,250, filed on Sep. 21, 2020.
Prior Publication US 2024/0294870 A1, Sep. 5, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 14/725 (2006.01); A61K 35/17 (2015.01); A61K 40/11 (2025.01); A61K 40/31 (2025.01); A61K 40/32 (2025.01); A61K 40/42 (2025.01); C07K 14/47 (2006.01); C12N 5/0783 (2010.01); C12N 15/85 (2006.01)
CPC C07K 14/7051 (2013.01) [A61K 35/17 (2013.01); A61K 40/11 (2025.01); A61K 40/31 (2025.01); A61K 40/32 (2025.01); A61K 40/4204 (2025.01); A61K 40/4268 (2025.01); A61K 40/4269 (2025.01); C07K 14/4702 (2013.01); C12N 5/0637 (2013.01); C12N 15/85 (2013.01); C07K 2317/53 (2013.01); C07K 2317/622 (2013.01); C07K 2319/03 (2013.01); C07K 2319/715 (2013.01); C12N 2510/00 (2013.01)] 10 Claims
 
1. A method of producing an engineered immune cell, the method comprising:
determining a strength of a blocking signal sent from a cell surface blocking receptor on an engineered immune cell at least in-part due to a length of a hinge of the cell surface blocking receptor, said receptor expressed from one or more engineered polynucleotide in the engineered cell, wherein longer hinge lengths impart an increased blocking signal strengths for the cell surface blocking receptor;
wherein the hinge is of a known length and comprises a peptide derived from leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) of between 10 and 64 amino acids in length; and
introducing the one or more polynucleotide into a cell thereby producing an engineered immune cell that expresses the cell surface blocking receptor and a cell surface activating receptor that sends an activating signal that the promotes a cytotoxic response is inhibited by the blocking signal and the cell surface blocking receptor with a known hinge length.