Back to results
US 12,269,859 B2Granted
Synthetic immune receptors and methods of use thereof
AssigneeAngeles Therapeutics, Inc.
InventorPreet M. Chaudhary
Life of this patent
Estimating the term…
Abstract
The disclosure provides synthetic immune receptors (SIRs), nucleic acids encoding the SIRs, methods of making and using the SIRs, in, for example, adoptive cell therapy.
Claims23
An at least one recombinant polynucleotide encoding a synthetic immune receptor (SIR), wherein the SIR comprises a heterodimer of two T-cell receptor (TCR) constant chains selected from (a)(i) and (a)(ii), (a)(i) and (a)(iii), (a)(iv) and (a)(ii), (a)(iv) and (a)(iii), and (a)(v) and (a)(vi) below, wherein the TCR constant chains of the encoded SIR comprise:
- (a) an amino acid sequence selected from the group consisting of:
- (i) an amino acid sequence that is at least 85% identical to SEQ ID NO:3010 and has one or more mutations at positions 10, 15, 45, 48, 61, 91, 92, 93, and/or 94;
- (ii) an amino acid sequence that is at least 85% identical to SEQ ID NO:3024 and has one or more mutations at positions 15, 17, 18, 22, 57, 59, 77, 79, 133, 136 and/or 139;
- (iii) an amino acid sequence that is at least 85% identical to SEQ ID NO:
- 3025 and has one or more mutations at position 15, 17, 18, 22, 57, 59, 77, 79, 133, 136 and/or 139;
- (iv) an amino acid sequence that is at least 85% identical to SEQ ID NO:
- 3046, 3047 or 3048;
- (v) an amino acid sequence that is at least 90% identical to SEQ ID NO:3049;
- or
- (vi) an amino acid sequence that is at least 85% identical to SEQ ID NO:
- 3051 or 3052;
- and
- (b) an optional linker;
- and
- (c) one or more non-natural TCR antigen binding domain(s) linked to (a) selected from the group consisting of:
- (1) an antibody;
- (2) an antibody fragment selected from the group consisting of a Fv, a Fab, and a (Fab′)2;
- (3) a heavy chain variable region of an antibody (vH domain) and a light chain variable region of an antibody (vL domain) specific for a target antigen, such that one of said vH and vL domains is attached to a first of said two TCR constant chains of (a) and the other of said vH and vL domains is attached to a second of said TCR constant chains of (a);
- (4) a single chain variable fragment (scFv);
- (5) a single domain antibody (SDAB);
- (6) a camelid VHH domain;
- (7) a monomeric variable region of an antibody;
- (8) a non-immunoglobulin antigen binding scaffold selected from the group consisting of a DARPIN, an affibody, an affilin, an adnectin, an affitin, an obody, a repebody, a fynomer, an alphabody, an avimer, an atrimer, a centyrin, a pronectin, an anticalin, a kunitz domain, an Armadillo repeat protein and a functional fragment thereof;
- (9) a receptor or a fragment thereof;
- (10) a ligand or a fragment thereof;
- and
- (11) an autoantigen or a fragment thereof.
24 more elements
An isolated synthetic immune receptor (SIR) polypeptide heterodimer wherein SIR polypeptide heterodimer comprises two T-cell receptor (TCR) constant chains selected from (a)(i) and (a)(ii), (a)(i) and (a)(iii), (a)(iv) and (a)(ii), (a)(iv) and (a)(iii), and (a)(v) and (a)(vi) below, wherein the TCR constant chains comprise:
- (a) an amino acid sequence selected from the group consisting of:
- (i) an amino acid sequence that is at least 85% identical to SEQ ID NO:3010 and has one or more mutations at positions 10, 15, 45, 48, 61, 91, 92, 93, and/or 94;
- (ii) an amino acid sequence that is at least 85% identical to SEQ ID NO:3024 and has one or more mutations at positions 15, 17, 18, 22, 57, 59, 77, 79, 133, 136 and/or 139;
- (iii) an amino acid sequence that is at least 85% identical to SEQ ID NO:
- 3025 and has one or more mutations at position 15, 17, 18, 22, 57, 59, 77, 79, 133, 136 and/or 139;
- (iv) an amino acid sequence that is at least 85% identical to SEQ ID NO:
- 3046, 3047 or 3048;
- (v) an amino acid sequence that is at least 90% identical to SEQ ID NO:3049;
- (vi) an amino acid sequence that is at least 85% identical to SEQ ID NO:
- 3051 or 3052;
- and
- (b) an optional linker;
- and
- (c) one or more non-natural TCR antigen binding domain(s) linked to (a) selected from the group consisting of:
- (1) an antibody;
- (2) an antibody fragment selected from the group consisting of a Fv, a Fab, and a (Fab′)2;
- (3) a heavy chain variable region of an antibody (vH domain) and a light chain variable region of an antibody (vL domain) specific for a target antigen, such that one of said vH and vL domains is attached to a first of said two TCR constant chains of (a) and the other of said vH and vL domains is attached to a second of said TCR constant chains of (a);
- (4) a single chain variable fragment (scFv);
- (5) a single domain antibody (SDAB);
- (6) a camelid VHH domain;
- (7) a monomeric variable region of an antibody;
- (8) a non-immunoglobulin antigen binding scaffold selected from the group consisting of a DARPIN, an affibody, an affilin, an adnectin, an affitin, an obody, a repebody, a fynomer, an alphabody, an avimer, an atrimer, a centyrin, a pronectin, an anticalin, a kunitz domain, an Armadillo repeat protein and a functional fragment thereof;
- (9) a receptor or a fragment thereof;
- (10) a ligand or a fragment thereof, and;
- (11) an autoantigen or a fragment thereof.
22 more elements
Dependencies are inferred from the claim text.