Patent ID: 11905328
Assignee: IMMATICS BIOTECHNOLOGIES GMBH
Field: Biotechnology (Chemistry)
Classification: CPC C | IPC C

Claim 0:
1. A dual specificity polypeptide molecule comprising:
a first polypeptide chain and a second polypeptide chain,
wherein the first polypeptide chain has an N-terminus and a C-terminus and comprises
a first binding region of a variable domain of an antibody (VD1) that specifically binds to a cell surface antigen of a human immune effector cell, and
a first binding region of a variable domain of a TCR (VR1) that specifically binds to an MHC-associated peptide epitope, and
a first linker (LINK1) connecting the domains;

wherein the second polypeptide chain has an N-terminus and a C-terminus and comprises
a second binding region of a variable domain of a TCR (VR2) that specifically binds to an MHC-associated peptide epitope, and
a second binding region of a variable domain of an antibody (VD2) that specifically binds to a cell surface antigen of a human immune effector cell, and
a second linker (LINK2) connecting the domains;

wherein the VR1 comprises a TCR Vα domain or a TCR Vβ domain,
wherein the VR2 comprises a TCR Vα domain or a TCR Vβ domain,
wherein, when the VR1 comprises a TCR Vα domain, the VR2 comprises a TCR Vβ domain, and, when the VR2 comprises a TCR Vα domain, the VR1 comprises a TCR Vβ domain, wherein the VR1 and the VR2 associate to form a second binding site that specifically binds an MHC-associated peptide epitope,
wherein the VD1 comprises an antibody VH domain or an antibody VL domain,
wherein the VD2 comprises an antibody VH domain or an antibody VL domain,
wherein, when the VD1 comprises an antibody VH domain, the VD2 comprises an antibody VL domain, and, when the VD1 comprises an antibody VL domain, the VD2 comprises an antibody VH domain, wherein the VD1 and VD2 associate to form a first binding site that binds a cell surface antigen of a human immune effector cell;
wherein
the order of the binding regions in the first polypeptide chain from the N-terminus to the C-terminus direction is Vα-LINK1-VH and the order of the binding regions in the second polypeptide chain from the N-terminus to the C-terminus direction is VL-LINK2-Vβ, or
the order of the binding regions in the first polypeptide chain from the N-terminus to the C-terminus direction is VH-LINK1-Vβ and the order of the binding regions in the second polypeptide chain from the N-terminus to the C-terminus direction is Vα-LINK2-VL, or
the order of the binding regions in the first polypeptide chain from the N-terminus to the C-terminus direction is Vβ-LINK1-VH and the order of the binding regions in the second polypeptide chain from the N-terminus to the C-terminus direction is VL-LINK2-Vα, or
the order of the binding regions in the first polypeptide chain from the N-terminus to the C-terminus direction is VH-LINK1-Vα and the order of the binding regions in the second polypeptide chain from the N-terminus to the C-terminus direction is Vβ-LINK2-VL and

wherein the two polypeptide chains are each fused to (i) a human IgG hinge domain or dimerizing portion thereof, (ii) a human IgG Fc domain or dimerizing portion thereof, or (iii) to both (i) and (ii);
wherein the two polypeptide chains are connected by covalent, non-covalent bonds, or both between the hinge domains, between the Fc domains, or between both the hinge domains and the Fc domains; and
wherein the dual specificity polypeptide molecule is capable of simultaneously binding the cell surface molecule and the MHC-associated peptide epitope.