Bispecific antigen binding constructs targeting HER2
AssigneeZymeworks BC Inc.
InventorsNina E. Weisser, Gordon Yiu Kon Ng, Grant Raymond Wickman, Surjit Bhimarao Dixit, Eric Escobar-Cabrera, Mario Sanches
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Abstract
Provided herein are biparatopic antigen-binding constructs that specifically bind HER2. The biparatopic antigen-binding constructs comprise one antigen-binding moiety that binds to ECD2 of HER2, a second antigen-binding moiety that binds to ECD4 of HER2, and an Fc. At least one of the antigen-binding moieties is an scFv. The biparatopic antigen-binding constructs can be used in the treatment of cancer.
Claims23
An isolated antigen binding construct comprising:
- (a) a first antigen-binding polypeptide construct which specifically binds a HER2 (human epidermal growth factor receptor 2) ECD2 (extracellular domain 2) antigen on a HER2-expressing cell, wherein the first antigen binding polypeptide construct comprises a first heavy chain variable region (VH1) and a first light chain variable region (VL1), wherein the VH1 comprises the sequence shown in SEQ ID NO:99 and the VL1 comprises the sequence shown in SEQ ID NO:71;
- and
- (b) a second antigen binding polypeptide construct which specifically binds a HER2 ECD4 (extracellular domain 4) antigen on a HER2-expressing cell, wherein the second antigen binding polypeptide construct comprises a second heavy chain variable domain (VH2) and a second light chain variable domain (VL2), wherein the VH2 comprises the sequence shown in SEQ ID NO:
- 305 and the VL2 comprises the sequence shown in SEQ ID NO:297, and wherein the second antigen binding polypeptide construct is operably linked to the first antigen binding polypeptide construct.
An isolated polynucleotide or set of isolated polynucleotides that encode(s):
- (a) a first antigen-binding polypeptide construct which specifically binds a HER2 (human epidermal growth factor receptor 2) ECD2 (extracellular domain 2) antigen on a HER2-expressing cell, wherein the first antigen binding polypeptide construct comprises a first heavy chain variable region (VH1) and a first light chain variable region (VL1), wherein the VH1 comprises the sequence shown in SEQ ID NO:99 and the VL1 comprises the sequence shown in SEQ ID NO:71;
- and
- (b) a second antigen binding polypeptide construct which specifically binds a HER2 ECD4 (extracellular domain 4) antigen on a HER2-expressing cell, wherein the second antigen binding polypeptide construct comprises a second heavy chain variable domain (VH2) and a second light chain variable domain (VL2), wherein the VH2 comprises the sequence shown in SEQ ID NO:305 and the VL2 comprises the sequence shown in SEQ ID NO:297.
A vector or set of vectors comprising an isolated polynucleotide or set of isolated polynucleotides that encode(s):
- (a) a first antigen-binding polypeptide construct which specifically binds a HER2 (human epidermal growth factor receptor 2) ECD2 (extracellular domain 2) antigen on a HER2-expressing cell, wherein the first antigen binding polypeptide construct comprises a first heavy chain variable region (VH1) and a first light chain variable region (VL1), wherein the VH1 comprises the sequence shown in SEQ ID NO:99 and the VL1 comprises the sequence shown in SEQ ID NO:71;
- and
- (b) a second antigen binding polypeptide construct which specifically binds a HER2 ECD4 (extracellular domain 4) antigen on a HER2-expressing cell, wherein the second antigen binding polypeptide construct comprises a second heavy chain variable domain (VH2) and a second light chain variable domain (VL2), wherein the VH2 comprises the sequence shown in SEQ ID NO:305 and the VL2 comprises the sequence shown in SEQ ID NO:297.
Dependencies are inferred from the claim text.