Monoclonal antibody inhibitor of factor xiia

A method of treating a disease associated with contact system activation, the method comprising administering to a subject in need thereof a monoclonal antibody that binds to active Factor XII (FXIIa) and does not bind to Factor XII (FXII);

• wherein the antibody comprises a heavy chain comprising a heavy chain variable region that comprises a complementarity determining region 1 (CDR1), a complementarity determining region 2 (CDR2), and a complementarity determining region 3 (CDR3), and
• wherein the heavy chain CDR1 comprises the formula X1YX3MX5 (SEQ ID NO:
• 117), in which:
• X1 is selected from the group consisting of amino acids R, Q, W, H, F, P, M, and N;
• X3 is selected from the group consisting of amino acids I, V, T, H, S, and N;
• and
• X5 is selected from the group consisting of amino acids H, G, V, A, R, Q, Y, L, N, and S;
• wherein the heavy chain CDR2 comprises the formula X1IX3PSGX7X8TX10YX12DSVKG, (SEQ ID NO:
• 118), in which:
• X1 is selected from the group consisting of amino acids S, R, V, Y, and G,
• X3 is selected from the group consisting of amino acids Y, W, V and S;
• X7 is selected from the group consisting of amino acids G and S;
• X8 is selected from the group consisting of amino acids V, K, M, N, L, F, A, I, S, H, and R;
• X10 is selected from the group consisting of amino acids K, R, T, Q, S, N, H, and L;
• and
• X12 is selected from the group consisting of amino acids A and T;
• and/or
• wherein the heavy chain CDR3 comprises an amino acid sequence selected from the group consisting of QRYRGPKYYYYMDV (SEQ ID NO:
• 111), QRYRGPKYYYYMDA (SEQ ID NO:
• 112), and QRYRGPRYYYYIDA (SEQ ID NO:
• 113).