Bispecific HER2 and CD3 binding molecules
AssigneeMemorial Sloan Kettering Cancer Center
InventorsNai-Kong V. Cheung, Andres Lopez-Albaitero, Hong Xu
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Abstract
Provided herein are compositions, methods, and uses involving bispecific binding molecules that specifically bind to HER2, a receptor tyrosine kinase, and to CD3, a T cell receptor, and mediate T cell cytotoxicity for managing and treating disorders, such as cancer. Also provided herein are uses and methods for managing and treating HER2-related cancers.
Claims20
A bispecific binding molecule comprising a monoclonal antibody that is an immunoglobulin that binds to HER2, wherein said immunoglobulin is mutated in its Fc region to eliminate a glycosylation site, said immunoglobulin comprising two identical heavy chains and two identical light chains, said light chains being a first light chain and a second light chain, wherein the first light chain is fused to a first single chain variable fragment (scFv), via a peptide linker, to create a first light chain fusion polypeptide, and wherein the second light chain is fused to a second scFv, via a peptide linker, to create a second light chain fusion polypeptide, wherein the first and second scFv (i) are identical, and (ii) bind to CD3, wherein the first and second light chain fusion polypeptides are identical, and wherein the sequence of each heavy chain is SEQ ID NO:
- 27, wherein the sequence of the first light chain is SEQ ID NO:
- 25, and wherein the sequence of the first scFv is SEQ ID NO:
- 52.
A bispecific binding molecule comprising a heavy chain-aglycosylated monoclonal antibody that is an immunoglobulin that binds to HER2, said immunoglobulin comprising two identical heavy chains and two identical light chains, said light chains being a first light chain and a second light chain, wherein the first light chain is fused to a first single chain variable fragment (scFv), via a peptide linker, to create a first light chain fusion polypeptide, and wherein the second light chain is fused to a second scFv, via a peptide linker, to create a second light chain fusion polypeptide, wherein the first and second scFv (i) are identical, and (ii) bind to CD3, wherein the first and second light chain fusion polypeptides are identical, and wherein
- (a) the sequence of each heavy chain is any of SEQ ID NOs:
- 23, 27, 62 and 63;
- and
- (b) the sequence of the first light chain fusion polypeptide is any of SEQ ID NOs:
- 29, 34, 42-47, and 60.
A bispecific binding molecule comprising a heavy chain and a light chain fusion polypeptide, wherein the heavy chain comprises the sequence set forth in SEQ ID NO:
- 27 and the light chain fusion polypeptide comprises the sequence set forth in SEQ ID NO:
- 34.
Dependencies are inferred from the claim text.