Alternative pathway specific antibodies for treating arthritis
A method of selecting a genus of therapeutic antibodies includes selecting antibodies with the following criteria; a) do inhibit cell lysis under conditions wherein the alternative pathway is isolated from the classical pathway; and b) do not inhibit cell lysis under conditions wherein the classical pathway is isolated from the alternative pathway; and c) do not inhibit cell lysis under conditions wherein the classical pathway and alternative pathway are active; and d) do inhibit C3b produced exclusively by the alternative pathway.
1. A method of selecting a genus of therapeutic antibodies, the method comprising:
a) determining whether an antibody inhibits alternative pathway complement activation but not classical pathway complement activation or classical pathway initiated amplification of the alternative pathway by assaying the antibody for its ability to:
i) inhibit cell lysis under conditions wherein the alternative pathway is isolated from the classical pathway;
ii) not inhibit cell lysis under conditions wherein the classical pathway is isolated from the alternative pathway; and
iii) not inhibit cell lysis under conditions wherein the classical pathway activates the alternative pathway; and
b) determining whether the antibody inhibits C3b produced exclusively by the alternative pathway;
c) and selecting an antibody which meets steps (a) and (b) above;
wherein the selected antibodies bind to a component of Alternative Pathway C3 Convertase, which have the specific characteristic of selectively inhibiting C3a, C5a, C3b, C5b, and C5b-9 produced exclusively by the alternative pathway, without inhibiting any of the classical pathway's ability to produce C3a, C5a, C3b, C5b, and C5b-9 at levels sufficient to maintain normal host defense.
2. The method of claim 1 , wherein the antibody binds to P, Bb, C3b, or Ba.