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US 11,952,681 B2Granted
Masked activatable CD137 antibodies
AssigneeAdagene Inc.
InventorsPeter Peizhi Luo, Fangyong Du
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Abstract
Provided herein are libraries containing synthetic polynucleotides that encode activatable binding polypeptides. Further provided herein are activatable binding polypeptides and polypeptide libraries containing such activatable binding polypeptides. Also provided herein are vectors, vector libraries, cells, kits, and methods of making and using activatable polypeptide libraries.
Claims43
An activatable antibody comprising:
- a first polypeptide comprising, from N-terminus to C-terminus, a masking moiety (MM), a cleavable moiety (CM), and a target binding moiety (TBM),
- wherein the MM comprises an amino acid sequence selected from the group consisting of SEQ ID NOS:
- 79-85;
- wherein the CM comprises at least a first cleavage site and a first flexible linker (L1);
- and
- wherein:
- a) the TBM comprises an antibody light chain variable region (VL), and the activatable antibody further comprises a second polypeptide comprising an antibody heavy chain variable region (VH);
- b) the TBM comprises an antibody heavy chain variable region (VH), and the activatable antibody further comprises a second polypeptide comprising an antibody light chain variable region (VL);
- c) the TBM comprises from the N-terminus to the C-terminus, an antibody light chain variable region (VL) and an antibody heavy chain variable region (VH);
- or
- d) the TBM comprises from the N-terminus to the C-terminus, an antibody heavy chain variable region (VH) and an antibody light chain variable region (VL);
- wherein:
- (i) the VH comprises an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 65, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 66, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 67;
- and
- (ii) the VL comprises an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 68, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 69, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 70;
- and
- wherein the activatable antibody binds to human CD137 via the VH and the VL when the CM is cleaved.
20 more elements
An activatable antibody comprising:
- a first polypeptide comprising, from N-terminus to C-terminus, a masking moiety (MM), a cleavable moiety (CM), and an antibody light chain variable region (VL), and
- a second polypeptide comprising an antibody heavy chain variable region (VH);
- wherein the MM comprises an amino acid sequence selected from the group consisting of SEQ ID NOS:
- 79-85;
- wherein the CM comprises at least a first cleavage site and a first flexible linker (L1);
- wherein:
- (i) the VH comprises an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
- 65, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
- 66, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
- 67;
- and
- (ii) the VL comprises an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
- 68, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
- 69, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
- 70;
- and
- wherein the activatable antibody binds to human CD137 via the VH and the VL when the CM is cleaved.
14 more elements
Dependencies are inferred from the claim text.