Multi-specific antibodies and methods of use
AssigneeGritstone Bio, Inc.
InventorsIsaac J. RONDON, Christine JANSON, Manankumar Anilkumar SHAH, Karin JOOSS
Life of this patent
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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.
Claims31
1-95. (canceled)
An isolated antigen binding protein (ABP) that comprises a first antigen binding region (ABR) and a second ABR which each specifically bind a first target antigen, a Fab that specifically binds CD3, and an Fc domain, wherein the ABP comprises:
- (a) a first polypeptide comprising, in an N→C direction, the first ABR-a first hinge-a first CH2-CH3;
- (b) a second polypeptide comprising, 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-a second CH2-CH3;
- and
- (c) a third polypeptide comprising, 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-a VH domain;
- the VH domain of the first ABR is attached to the VL domain of the first ABR via a first linker;
- the VH domain of the second ABR is attached to the VL domain of the second ABR via a second linker;
- the first linker and second linker are each about 5-15 amino acids in length;
- 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);
- the VH of the first and second ABRs comprises the sequence set forth in SEQ ID NO:
- 6;
- and
- the VL of the first and second ABRs comprises the sequence set forth in SEQ ID NO:4.
An isolated antigen binding protein (ABP) that comprises a first antigen binding region (ABR) and a second ABR which each specifically bind a first target antigen, a Fab that specifically binds CD3, and an Fc domain, wherein the ABP comprises:
- (a) a first polypeptide comprising, in an N→C direction, the first ABR-a first hinge-a first CH2-CH3;
- (b) a second polypeptide comprising, 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-a second CH2-CH3;
- and
- (c) a third polypeptide comprising, 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-a VH domain;
- the VH domain of the first ABR is attached to the VL domain of the first ABR via a first linker;
- the VH domain of the second ABR is attached to the VL domain of the second ABR via a second linker;
- the first linker and second linker are each about 5-15 amino acids in length;
- 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
- the VH domains of the first and second ABRs each comprise complementarity-determining regions (CDR) H1 (CDR-H1), CDR-H2, and CDR-H3 comprising the sequences set forth in SEQ ID NOS:18, 19, and 20, respectively, and the VL domains of the first and second ABRs each comprise CDR-L1, CDR-L2, and CDR-L3 comprising the sequences set forth in SEQ ID NOS:21, 22, and 23, respectively.
An isolated antigen binding protein (ABP) that comprises a first antigen binding region (ABR) and a second ABR which each specifically bind a first target antigen, a Fab that specifically binds CD3, and an Fc domain, wherein the ABP comprises:
- (a) a first polypeptide comprising, in an N→C direction, the first ABR-a first hinge-a first CH2-CH3;
- (b) a second polypeptide comprising, 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-a second CH2-CH3;
- and
- (c) a third polypeptide comprising, 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-a VH domain;
- the VH domain of the first ABR is attached to the VL domain of the first ABR via a first linker;
- the VH domain of the second ABR is attached to the VL domain of the second ABR via a second linker;
- the first linker and second linker comprise
- (i) a (GS)n sequence, wherein n is 1, 2, 3, 4, 5, 6, or 7;
- (ii) a (GGS)n sequence, wherein n is 1, 2, 3, 4, or 5;
- (iii) a (GGGS)n sequence, wherein n is 1, 2, or 3;
- (iv) a (GGSG)n sequence, wherein n is 1, 2, or 3;
- (v) a (GGSGG)n sequence, wherein n is 1, 2, or 3;
- or
- (vi) a (GGGGS)n sequence, wherein n is 1, 2, or 3
- 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);
- the VH of the first and second ABRs comprises the sequence set forth in SEQ ID NO:
- 6;
- and
- the VL of the first and second ABRs comprises the sequence set forth in SEQ ID NO:4.
Dependencies are inferred from the claim text.