Bispecific antibodies and methods of using the same

An isolated bispecific antibody comprising an IL-17A/F binding entity and an IL-23 binding entity, wherein the IL-23 binding entity comprises two pairs of immunoglobulin chains, each pair having one light and one heavy chain, which IL-23 light chain variable domain comprises a CDR1 having the amino acid sequence of SEQ ID NO:22, a CDR2 having the amino acid sequence of SEQ ID NO:23, and a CDR3 having the amino acid sequence of SEQ ID NO:24, and IL-23 heavy chain variable domain comprises a CDR1 having the amino acid sequence of SEQ ID NO:19, a CDR2 having the amino acid sequence of SEQ ID NO:20, and a CDR3 having the amino acid sequence of SEQ ID NO:21, and wherein the IL-17A/F binding entity comprises two Fab fragments linked to the C-terminus of the IL-23 heavy chain.

An isolated bispecific antibody comprising an IL-17A/F binding entity and an IL-23 binding entity, wherein the IL-17A/F binding entity comprises a light chain comprising the amino acid sequence of SEQ ID NO:17 and a heavy chain comprising the amino acid sequence of SEQ ID NO:81, and the IL-23 binding entity comprises a light chain comprising the amino acid sequence of SEQ ID NO:17 and a heavy chain comprising the amino acid sequence of SEQ ID NO:61.

An isolated bispecific antibody comprising a first binding entity and a second binding entity wherein the first binding entity is an antibody comprising two pairs of immunoglobulin chains;

• the second binding entity is a Fv unit comprising a heavy chain variable domain and a light chain variable domain, wherein the Fv unit of the second binding entity is positioned between and linked to the Fab region and the hinge region of the antibody of the first binding entity.

An isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds to IL-17A (SEQ ID NO:2) and IL-17F (SEQ ID NO:4) comprising a heavy chain variable domain and a light chain variable domain, wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:13 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:9.

An isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds to IL-23p19 (SEQ ID NO:6) comprising a heavy chain variable domain and a light chain variable domain, wherein the heavy chain variable domain comprises a CDR1 having the amino acid sequence of SEQ ID NO:19, a CDR2 having the amino acid sequence of SEQ ID NO:20, and a CDR3 having the amino acid sequence of SEQ ID NO:21;

• and wherein the light chain variable domain comprises a CDR1 having the amino acid sequence of SEQ ID NO:22, a CDR2 having the amino acid sequence of SEQ ID NO:23, and a CDR3 having the sequence of SEQ ID NO:24.

An isolated bispecific antibody comprising a first binding entity and a second binding entity wherein the first binding entity is an antibody comprising two pairs of immunoglobulin chains and the second binding entity comprises a single domain antibody, wherein the single domain antibody of the second binding entity is positioned between and linked to the CH1 region of the Fab fragment and the hinge of the first binding entity.

An isolated antibody or antigen-binding fragment thereof which specifically binds IL-23p19, wherein the antibody or antigen-binding fragment binds a discontinuous epitope on IL-23p19 comprising a first epitope and a second epitope, wherein the first epitope consists of at least one of amino acid residues 33-59 of SEQ ID NO:6 and the second epitope consists of at least one of amino acid residues 89-125 of SEQ ID NO:6.

An isolated IL-17A/F binding entity which specifically binds IL-17A at an epitope comprising at least amino acid residue 108 (Tyr) of SEQ ID NO:2, wherein the IL-17A/F binding entity is a monoclonal antibody or antigen-binding fragment thereof.