Humaneered anti-factor B antibody

摘要

This invention relates to humaneered anti-factor B antibodies and antigen-binding fragments thereof with reduced immunogenicity. The humaneered anti-factor B antibodies and antigen-binding fragments thereof are derived from murine monoclonal antibody 1379, which binds factor B in the third short consensus repeat (“SCR”) domain and selectively inhibits activation of the alternative complement pathway by preventing formation of the C3bBb complex. The invention also relates to methods of treating diseases or disorders in which activation of the alternative complement pathway plays a role, and methods of selectively inhibiting activation of the alternative complement pathway in an individual in need thereof.

主权项

1. A method of reducing airway hyperresponsiveness (AHR) or airway inflammation comprising administering a composition comprising an engineered human anti-factor B antibody or antigen-binding fragment thereof and a pharmaceutically acceptable carrier to an individual in need thereof, wherein the engineered human anti-factor B antibody or antigen-binding fragment thereof comprises:
a) a VK-region comprising the amino acid sequence of SEQ ID NO:16 and a VH-region comprising the amino acid sequence of SEQ ID NO:17; b) a VK-region comprising the amino acid sequence of SEQ ID NO:18 and a VH-region comprising the amino acid sequence of SEQ ID NO:19; c) a VK-region comprising the amino acid sequence of SEQ ID NO:20 and a VH-region comprising the amino acid sequence of SEQ ID NO:21; d) a VK-region comprising the amino acid sequence of SEQ ID NO:16 and a VH-region comprising the amino acid sequence of SEQ ID NO:35; e) a VK-region comprising the amino acid sequence of SEQ ID NO:18 and a VH-region comprising the amino acid sequence of SEQ ID NO:36; or f) a VK-region comprising the amino acid sequence of SEQ ID NO:20 and a VH-region comprising the amino acid sequence of SEQ ID NO:37, wherein the antigen-binding fragment is selected from the group consisting of Fab', (Fab')2 Fv, scFv, and diabodies and wherein the engineered human anti-factor B antibody or antigen-binding fragment thereof reduces C3bBb complex formation in the individual.