Antigen-binding proteins and related methods of use
AssigneeGritstone Bio, Inc.
InventorsGodfrey Jonah Anderson Rainey, Karin Jooss, Roman Yelensky, Wade Blair, Heungnam Kim, Christine Janson, Anne Van Abbema, Isaac J. Rondon
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Abstract
Provided herein are antigen binding proteins (ABPs) that bind HLA-PEPTIDE targets. Also disclosed are methods for identifying the HLA-PEPTIDE targets and methods of treating cancers and other diseases using the disclosed ABPs.
Claims27
An isolated antigen binding protein (ABP) comprising a first scFv and a second scFv which each specifically bind a 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 scFv and a —CH2-CH3;
- (b) a second polypeptide comprising, in an N→C direction, the second scFv, a VH domain of the Fab, a CH1 domain of the Fab, and a —CH2-CH3;
- and
- (c) a third polypeptide comprising, in an N→C direction, a VL domain of the Fab and a CL domain of the Fab;
- wherein:
- the target antigen is a human leukocyte antigen (HLA)-PEPTIDE target comprising HLA subtype A*02:01 and a peptide comprising the sequence AIFPGAVPAA (SEQ ID NO:
- 42);
- and
- the first scFv and the second scFv each comprise a variable heavy chain (VH) sequence comprising the sequence set forth in SEQ ID NO:37 or SEQ ID NO:39, and a variable light chain (VL) sequence comprising the sequence set forth in SEQ ID NO:2.
An isolated antigen binding protein (ABP) comprising a first scFv and a second scFv which each specifically bind a 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 scFv and a —CH2-CH3;
- (b) a second polypeptide comprising, in an N→C direction, the second scFv, a VH domain of the Fab, a CH1 domain of the Fab, and a —CH2-CH3;
- and
- (c) a third polypeptide comprising, in an N→C direction, a VL domain of the Fab and a CL domain of the Fab;
- wherein:
- the target antigen is a human leukocyte antigen (HLA)-PEPTIDE target comprising HLA subtype A*02:01 and a peptide comprising the sequence AIFPGAVPAA (SEQ ID NO:
- 42);
- and
- the first scFv and the second scFv each comprise:
- (i) a variable heavy chain (VH) sequence comprising complementarity-determining regions (CDR) H1 (CDR-H1), CDR-H2, and CDR-H3 comprising the sequences set forth in SEQ ID NOs 16, 22, and 27 respectively, and a variable light chain (VL) sequence comprising CDR-L1, CDR-L2, and CDR-L3 comprising the sequences set forth in SEQ ID NOs 28, 30, and 32, respectively;
- or
- (ii) a variable heavy chain (VH) sequence comprising complementarity-determining regions (CDR) H1 (CDR-H1), CDR-H2, and CDR-H3 comprising the sequences set forth in SEQ ID NOs 16, 25, and 36 respectively, and a variable light chain (VL) sequence comprising CDR-L1, CDR-L2, and CDR-L3 comprising the sequences set forth in SEQ ID NOs 28, 30, and 32, respectively.
Dependencies are inferred from the claim text.