US 12,221,465 B2
Signaling and antigen-presenting bifunctional receptors (SABR)
Alok V Joglekar, Pasadena, CA (US); Michael T Leonard, Pasadena, CA (US); Michael T Bethune, Pasadena, CA (US); and David Baltimore, Pasadena, CA (US)
Assigned to California Institute of Technology, Pasadena, CA (US)
Filed by California Institute of Technology, Pasadena, CA (US)
Filed on Sep. 5, 2018, as Appl. No. 16/122,562.
Claims priority of provisional application 62/554,652, filed on Sep. 6, 2017.
Prior Publication US 2019/0201443 A1, Jul. 4, 2019
Int. Cl. C07K 14/705 (2006.01); A61K 39/00 (2006.01); A61P 37/00 (2006.01); C07K 14/725 (2006.01); C07K 14/74 (2006.01); C12N 5/0783 (2010.01); C40B 40/02 (2006.01); G01N 33/566 (2006.01); G01N 33/68 (2006.01); A61K 38/00 (2006.01)
CPC C07K 14/7051 (2013.01) [A61K 39/4611 (2023.05); A61K 39/4615 (2023.05); A61K 39/4621 (2023.05); A61K 39/4622 (2023.05); A61K 39/4632 (2023.05); A61K 39/46433 (2023.05); A61K 39/464401 (2023.05); A61K 39/464488 (2023.05); A61K 39/464491 (2023.05); A61K 39/464838 (2023.05); A61P 37/00 (2018.01); C07K 14/705 (2013.01); C07K 14/70539 (2013.01); C12N 5/0636 (2013.01); C40B 40/02 (2013.01); G01N 33/566 (2013.01); G01N 33/68 (2013.01); A61K 38/00 (2013.01); C07K 2319/03 (2013.01); C07K 2319/70 (2013.01); G01N 2333/7051 (2013.01)] 10 Claims
OG exemplary drawing
 
1. A signaling and antigen-presenting bifunctional receptor (SABR) comprising:
an antigen presenting domain comprising a binding domain of a major histocompatibility complex (MHC) molecule, a peptide epitope covalently linked to the binding domain of the MHC molecule for extracellular presentation of the peptide epitope to a first cell expressing at least one antigen receptor, and a transmembrane domain;
one or more linkers; and
a signal transduction domain fused to the antigen presenting domain, wherein the SABR is made by a method comprising expressing, in a second cell that is an isolated cell, a nucleic acid sequence encoding the antigen presenting domain, the signal transduction domain, and the one or more linkers, and
wherein the peptide epitope is synthesized and cloned, from pooled single stranded oligonucleotide libraries, into the nucleic acid sequence,
wherein the transmembrane domain comprises a transmembrane domain from one or more of 4-1BB (CD137), CD28, CD27, DAP10, ICOS, OX40, PD1, CTLA4, TIM3, CD3zeta, Notch, synNotch, CD79A, CD79B, CD72, CD22, CD5, CD19, CD45, IL2, IL4, EPO, GM-CSF, JAK-STAT, CCL10, a G protein coupled receptor, a receptor of the TNF Receptor superfamily, a NK cell receptor, a Fc receptor, a toll-like receptor, a RIG-I-like receptor, a NOD-like receptor, or a MHC molecule, and
wherein the signal transduction domain comprises an intracellular signaling domain of CD137, CD27, DAP10, ICOS, OX40, PD1, CTLA4, TIM3, an IL2, an IL4, an EPO, a GM-CSF, JAK-STAT, a CCL10, a G protein coupled receptor, or a receptor of the TNF Receptor superfamily, or a fragment thereof.