Bispecific binding proteins that bind CD40 and mesothelin
The present disclosure provides bispecific proteins that bind to two antigens, as well as their compositions, uses, and methods of making.
1. A bispecific binding protein capable of binding CD40 and capable of binding mesothelin, comprising two polypeptides of formula (II):
scFv X —H—Fc—L—scFv Y (II),
wherein
L is a polypeptide linker,
H is a hinge region,
Fc comprises CH2 and CH3 regions of an immunoglobulin,
scFv X and ScFv Y are each independently a single chain variable fragment,
scFv X specifically binds a first antigen,
scFv Y specifically binds a second antigen, and
one of the two antigens is CD40 and the other is mesothelin; and
wherein the scFv that binds CD40 comprises a V H having a CDR-H1 according to SEQ ID NO:25, a CDR-H2 according to SEQ ID NO:26, and a CDR-H3 according to SEQ ID NO:27, and a V L having a CDR-L1 according to SEQ ID NO:55, a CDR-L2 according to SEQ ID NO:56, and a CDR-L3 according to SEQ ID NO:57; and
wherein the scFv that binds mesothelin comprises a V H having a CDR-H1 according to SEQ ID NO:241, a CDR-H2 according to SEQ ID NO:242, and a CDR-H3 according to SEQ ID NO:243, and a V L having a CDR-L1 according to SEQ ID NO:244, a CDR-L2 according to SEQ ID NO:245, and a CDR-L3 according to SEQ ID NO:246.
2. The bispecific binding protein of claim 1 , wherein the scFv that binds CD40 comprises a V H according to SEQ ID NO:17 and a V L according to SEQ ID NO:44.
3. The bispecific binding protein of claim 1 , wherein the scFv that binds mesothelin comprises a V H according to SEQ ID NO:120 and a V L according to SEQ ID NO:137.
4. The bispecific binding protein of claim 1 , wherein the scFv that binds CD40 comprises a V H according to SEQ ID NO:17 and a V L according to SEQ ID NO:44, and wherein the scFv that binds mesothelin comprises a V H according to SEQ ID NO:120 and a V L according to SEQ ID NO:137.
5. The bispecific binding protein of claim 1 , wherein the two polypeptides each comprise the amino acid sequence of SEQ ID NO:406.
6. A pharmaceutical composition comprising a bispecific binding protein of claim 5 , and a pharmaceutically acceptable carrier.
7. A bispecific binding protein capable of binding CD40 and capable of binding mesothelin, comprising two polypeptides of formula (III):
Fab—H—Fc—L—scFv Y (III),
wherein
L is a polypeptide linker,
H is a hinge region,
Fc comprises CH2 and CH3 regions of an immunoglobulin,
Fab is a fragment antigen-binding region,
scFv Y is a single chain variable fragment,
Fab specifically binds a first antigen,
scFv Y specifically binds a second antigen, and
the first antigen is mesothelin and the second antigen is CD40; and
wherein the scFv that binds CD40 comprises a V H having a CDR-H1 according to SEQ ID NO:25, a CDR-H2 according to SEQ ID NO:26, and a CDR-H3 according to SEQ ID NO:27, and a V L having a CDR-L1 according to SEQ ID NO:55, a CDR-L2 according to SEQ ID NO:56, and a CDR-L3 according to SEQ ID NO:57; and
wherein the scFv that binds mesothelin comprises a V H having a CDR-H1 according to SEQ ID NO:241, a CDR-H2 according to SEQ ID NO:242, and a CDR-H3 according to SEQ ID NO:243, and a V L having a CDR-L1 according to SEQ ID NO:244, a CDR-L2 according to SEQ ID NO:245, and a CDR-L3 according to SEQ ID NO:246.
8. A pharmaceutical composition comprising a bispecific binding protein of claim 7 , and a pharmaceutically acceptable carrier.
9. The bispecific binding protein of claim 1 , wherein the first antigen is CD40 and the second antigen is mesothelin.
10. The bispecific binding protein of claim 1 , wherein the first antigen is mesothelin and the second antigen is CD40.