Multivalent antibody constructs
View Patent ↗The present invention relates to a multivalent F v antibody construct having at least four variable domains which are linked with each over via the peptide linkers 1, 2 and 3. The invention also concerns expression plasmids which code for such an F v antibody construct and a method of producing the F v antibody constructs as well as their use.
1. A bivalent monomeric F v antibody formed by one single-chain F v monomer having four variable domains, wherein said four variable domains are V H -A, V L -B, V H -B and V L -A, wherein V H -A and V L -A are V H and V L domains of an antibody specific for antigen A, respectively, and V H -B and V L -B are V H and V L domains of an antibody specific for antigen B, respectively; V H -A is linked to V L -B by peptide linker 1, V L -B is linked to V H -B by peptide linker 2 and V H -B is linked to V L -A by peptide linker 3; said peptide linker 1 and said peptide linker 3 are a peptide bond or have 1 to about 10 amino acids; and said peptide linker 2 has about 10 to about 30 amino acids; V H -A and V L -A associate intramolecularly to form a binding site for antigen A; and V L -B and V H -B associate intramolecularly to form a binding site for antigen B.
2. The F v antibody of claim 1 , wherein said peptide linker has 2 have 11 to about 20 amino acids.
3. The F v antibody of claim 1 , wherein said peptide linker has 2 have 15 to 20 amino acids.
4. The F v antibody of claim 1 , wherein said peptide linker 2 is (G 4 S) 4 (SEQ ID NO: 14).
5. The F v antibody of claim 1 , wherein said peptide linker 1 and said peptide linker 3 have the amino acid sequence GG.
6. The F v antibody of claim 1 , wherein said peptide linker 1 and said peptide linker 3 have the same amino acid sequence.
7. The F v antibody of claim 1 , wherein said antibody is monospecific.
8. The F v antibody of claim 1 , wherein said antibody is bispecific.
9. The F v antibody of claim 1 , wherein said antibody is specific for an antigen selected from the group consisting of CD3 and CD19.
10. The F v antibody of claim 9 , wherein said antibody is specific for CD3 and CD19.
11. A composition comprising said F v antibody of claim 1 for diagnosis and/or treatment of diseases.