Alternative pathway specific antibodies for treating arthritis

Abstract

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 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;   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 method is applied to antibodies targeting P. 
     
     
         3 . An antibody selected by the method of  claim 1 . 
     
     
         4 . The antibody of  claim 3 , comprising: a light chain variable domain that includes the amino acid sequences of the three CDRs in SEQ ID NO: 1 or SEQ ID NO: 5, and a heavy chain variable domain that includes the amino acid sequences of the three CDRs in SEQ ID NO: 33, wherein the antibody binds to P. 
     
     
         5 . The antibody of  claim 3 , comprising: a light chain variable domain that includes the amino acid sequences of the three CDRs in SEQ ID NO: 9, and a heavy chain variable domain that includes the amino acid sequences of the three CDRs in SEQ ID NO: 37, wherein the antibody binds to P. 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . The antibody of  claim 3 , upon administration to blood of a subject inhibiting monocyte activation, neutrophil activation, platelet activation, basophil activation, and mast cell activation and the resulting production of inflammatory molecules. 
     
     
         12 . The antibody of  claim 3 , upon administration to blood of a subject inhibiting leukocyte-platelet conjugates. 
     
     
         13 . The antibody of  claim 3 , upon administration to blood of a subject inhibiting cellular production and release of inflammatory cytokines. 
     
     
         14 . The antibody of  claim 3 , upon administration to blood of a subject inhibiting cellular production and release of IL-1, TNF-α, neutrophil elastase. 
     
     
         15 . A method of using the antibody of  claim 3 , comprising administering to a subject a therapeutically effective amount of the antibody and thereby preventing or ameliorating tissue damage caused by alternative complement pathway induced inflammation. 
     
     
         16 . The method of  claim 15  wherein the tissue damage is cartilage degradation, loss of cartilage, pannus formation, bone loss, synovitis, osteophyte formation, or swelling. 
     
     
         17 . The method of  claim 15  wherein the tissue damage is associated with loss of joint mobility, pain, adult or juvenile rheumatoid arthritis, osteoarthritis, or mixed connective tissue disease. 
     
     
         18 . The method of  claim 15  wherein the subject is at a heightened risk of infection, suffering from an active infection, or known to have undergone previous unsuccessful treatments involving the administration of other antibody therapy or therapies. 
     
     
         19 . The method of  claim 15 , comprising administering to the subject a therapeutically effective amount of the antibody and thereby treating or preventing arthritis or arthritic conditions. 
     
     
         20 . The method of  claim 19  wherein the arthritic condition is osteoarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, arthritis-related joint instability, or an arthritis related autoimmune disorder. 
     
     
         21 . A method of treating or preventing arthritis or arthritic conditions in a subject, the method comprising: administering to the subject a therapeutically effective amount of an antibody that specifically binds to a component of Alternative Pathway C3 Convertase, inhibits alternative pathway activation, and does not inhibit alternative pathway activation. 
     
     
         22 . The method of  claim 21 , the antibody specifically binding to P. 
     
     
         23 . The method of  claim 21 , the antibody comprising: a light chain variable domain that includes the amino acid sequences of the three CDRs in SEQ ID NO: 1 or SEQ ID NO: 5, and a heavy chain variable domain that includes the amino acid sequences of the three CDRs in SEQ ID NO: 33, wherein the antibody binds to P. 
     
     
         24 . The method of  claim 21 , the antibody comprising: a light chain variable domain that includes the amino acid sequences of the three CDRs in SEQ ID NO: 9, and a heavy chain variable domain that includes the amino acid sequences of the three CDRs in SEQ ID NO: 37, wherein the antibody binds to P. 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled)