Methods for inhibiting angiogenesis in a subject in need thereof

Inventors

Demopulos, Gregory A. • Schwaeble, Hans-Wilhelm • Dudler, Thomas • Tjoelker, Larry

Assignees

University of Leicester • Omeros Corp

Abstract

In one aspect, the present invention provides methods for preventing, treating, reverting and/or delaying angiogenesis in a mammalian subject suffering from, or at risk for developing, an angiogenesis-dependent disease or condition, comprising administering to the subject an amount of a MASP-2 inhibitory agent effective to inhibit angiogenesis. In some embodiments of these aspects of the invention, the MASP-2 inhibitory agent is a MASP-2 antibody or fragment thereof.

Core Innovation

The invention relates to inhibiting angiogenesis by inhibiting MASP-2 activity in a mammalian subject. It uses a MASP-2 inhibitory agent administered in an amount effective to inhibit angiogenesis, including a MASP-2 inhibitory monoclonal antibody or a fragment thereof. The approach also includes RNA-based expression inhibition of MASP-2, including ribozymes targeting MASP-2 mRNA and antisense/ribozyme constructs, as MASP-2 inhibitory agents.

The invention relates to inhibiting lectin pathway complement activation by targeting MASP-2. MASP-2 is positioned as a lectin-pathway-specific therapeutic target, and inhibition of MASP-2 prevents or reduces complement activation associated with the lectin pathway while preserving C1q-dependent classical pathway activity. The document links MASP-2 inhibition to reduction of C4 cleavage and C4b deposition, formation of the C3 convertase (C4b2a), and downstream steps in complement activation including formation of the C5 convertase and the membrane attack complex (MAC/C5b-9).

The document further describes pharmaceutical compositions and delivery and dosing approaches for MASP-2 inhibitory agents, including pharmaceutically acceptable carriers and multiple delivery vehicles. It also describes determining tolerable dosing using animal models, including NOAEL and MED, and indicates combination administration with anti-angiogenic agents and anti-cancer/chemotherapeutic agents. The stated purpose is preventing or treating angiogenesis-dependent diseases by inhibiting angiogenesis, and MASP-2 inhibitory agents include MASP-2 inhibitory monoclonal antibodies, such as OMS646, and related forms including fragments, peptides, small molecules, or expression inhibitors.

Claims Coverage

The identified independent claims cover treatment of angiogenesis-dependent benign tumors by administering a MASP-2 inhibitory agent effective to inhibit angiogenesis, with the agent defined as a MASP-2 inhibitory monoclonal antibody or fragment comprising specified heavy- and light-chain variable regions. Three inventive features are consistently identified across the inputs.

Overall, the claim coverage is directed to inhibiting angiogenesis in mammalian subjects with angiogenesis-dependent benign tumors by administering a MASP-2 inhibitory monoclonal antibody or antigen-binding fragment defined by specified heavy- and light-chain variable regions, with dependent language specifying multiple administration routes for the composition.

Stated Advantages

Documented Applications