Multispecific fusion proteins targeting angiogenic and inflammatory factors

Abstract

A fusion protein or an antigen-binding fragment or domain thereof comprises a binding construct targeting and being capable of binding at least one of the VEGF family members, IL-6 or IL-6R, and Ang-2. The antibody fusion protein comprises, as binding components, a pair of heavy chain and light chain of a VEGF antibody, a pair of heavy chain and light chain of an IL-6 or IL-6R antibody, and a single domain antibody or binding polypeptide directed against Ang-2 that is linked to each of the VEGF antibody and the IL-6 or IL-6R antibody, wherein the constant domains of the VEGF antibody and the IL-6 or IL-6R antibody are modified to enhance the formation of the fusion protein. The fusion protein is useful in treating or controlling an ocular or systemic disease, condition, or disorder that has etiology in at least one of aberrant angiogenesis (including excessive angiogenesis), increased vascular leakage, and inflammation.