Antigen-binding proteins

An antigen-binding protein comprising a protein scaffold which is linked to one or more epitope-binding domains wherein the antigen-binding protein has at least two antigen binding sites at least one of which is from an epitope binding domain and at least one of which is from a paired VH/VL domain wherein the epitope binding domain is linked to the protein scaffold by a linker selected from those set out in SEQ ID NO:

• 53 to 60, SEQ ID NO:62-72, SEQ ID NO:74, SEQ ID NO:76-78, SEQ ID NO:112-114, or combinations or multiples of such linkers.

The antigen-binding protein according to any preceding claim wherein at least one epitope binding domain is an immunoglobulin single variable domain.

The antigen-binding protein of any preceding claim wherein the antigen binding protein has specificity for more than one antigen.

The antigen-binding protein according to any preceding claim wherein the first binding site has specificity for a first epitope on an antigen and the second binding site has specificity for a second epitope on the same antigen.

The antigen-binding protein according to any preceding claim wherein the antigen-binding protein is capable of binding IL-13.

The antigen-binding protein according to any preceding claim wherein the antigen-binding protein is capable of binding two or more antigens selected from IL-13, IL-5, and IL-4.

The antigen-binding protein according to any preceding claim wherein the antigen-binding protein is capable of binding two or more antigens selected from VEGF, IGF-1R and EGFR,

The antigen-binding protein according to any preceding claim wherein the antigen-binding protein is capable of binding TNFα.

The antigen-binding protein according to any preceding claim wherein the protein scaffold is an Ig scaffold.

The antigen-binding protein according to any preceding claim wherein the protein scaffold comprises a monovalent antibody.

The antigen-binding protein according to any preceding claim which comprises four domain antibodies.

The antigen-binding protein according to any preceding claim wherein at least two of the antigen binding sites have specificity for the same antigen.

The antigen-binding protein according to any preceding claim wherein at least one of the epitope binding domains binds human serum albumin.

The antigen-binding protein according to any preceding claim comprising an epitope binding domain attached to the Ig scaffold at the N-terminus of the light chain.

The antigen-binding protein according to any preceding claim for use in medicine.

The antigen-binding protein according to any preceding claim for the treatment of cancer or inflammatory diseases such as asthma, rheumatoid arthritis or osteoarthritis.

A recombinant transformed or transfected host cell comprising one or more polynucleotide sequences encoding a heavy chain and a light chain of an antigen binding protein of any preceding claim.

A method for improving the potency of an epitope binding domain when attached to a protein scaffold, which epitope binding domain has reduced potency when attached directly to a protein scaffold without a linker, compared with its potency as a naked epitope binding domain, comprising the step of adding a peptide linker between the protein scaffold and the eptiope binding domain wherein the peptide linker comprises at least 10 amino acids