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US 12,643,949 B2Granted
Multi-specific antibodies and methods of use
AssigneeGritstone Bio, Inc.
InventorsIsaac J. Rondon, Christine Janson, Manankumar Anilkumar Shah, Karin Jooss
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Abstract
Provided herein are multispecific antigen binding proteins that selectively bind a particular KKLC-1 (CT-83) shared antigen and CD3, as well as related methods, kits, and compositions. Included herein are multispecific antigen binding proteins with a circularized conformation.
Claims18
An isolated antigen binding protein (ABP) that comprises:
- a first antigen binding region (ABR) and a second ABR that each specifically bind a first target antigen, a Fab that specifically binds a second target antigen CD3, and an Fc domain, wherein the ABP comprises a first polypeptide, a second polypeptide, and a third polypeptide;
- wherein the first polypeptide comprises, in an N→C direction, the first ABR-a first hinge-CH2-CH3;
- wherein the second polypeptide comprises, in an N→C direction, the second ABR-a variable heavy chain (VH) domain of the Fab-a CH1 domain of the Fab-a second hinge-CH2-CH3;
- wherein the third polypeptide comprises, in an N→C direction, a variable light chain (VL) domain of the Fab-a CL domain of the Fab;
- wherein the first ABR and second ABR each comprise, in an N→C direction:
- (i) a VH domain-a VL domain or (ii) a VL domain-VH domain;
- wherein the VH domain of the first ABR is attached to the VL domain of the first ABR via a first linker;
- wherein the VH domain of the second ABR is attached to the VL domain of the second ABR via a second linker;
- wherein the first linker and second linker are each about 5-15 amino acids in length;
- and
- wherein the first target antigen is an HLA-PEPTIDE target comprising an HLA-restricted peptide complexed with an HLA Class I molecule, wherein the HLA Class I molecule is HLA subtype HLA-A*01:01 and the HLA-restricted peptide comprises the sequence NTDNNLAVY (SEQ ID NO:
- 214);
- and
- wherein the VH domains of the first and second ABRs each comprise complementarity-determining regions (CDR)-H1, CDR-H2, and CDR-H3 comprising the sequences set forth in SEQ ID NOS:
- 18, 19, and 20, respectively and wherein the VL comprises CDR-L1, CDR-L2, and CDR-L3 comprising the sequences set forth in SEQ ID NOS:
- 21, 22, and 23, respectively.
13 more elements
Dependencies are inferred from the claim text.