Gamma-1 And Gamma-3 Anti-Human CD23 Monoclonal Antibodies And Use Thereof As Therapeutics

Abstract

Monoclonal antibodies which specifically bind human CD23, the low affinity receptor for IgE (FceRII/CD23), and contain either a human gamma-1 or human gamma-3 constant domain, are disclosed. The antibodies are useful for modulating or inhibiting induced IgE expression. Accordingly, they have practical utility in the treatment or prophylaxis of disease conditions wherein inhibition of induced IgE production is therapeutically desirable, including allergic conditions, autoimmune diseases and inflammatory diseases.

1 . An anti-human CD23 monoclonal antibody comprising a constant region that binds to human Fc gamma receptors and inhibits IgE expression.  
     
     
         2 . The anti-human CD23 monoclonal antibody of  claim 1 , which comprises a primate antigen binding portion.  
     
     
         3 . The anti-human CD23 monoclonal antibody of  claim 1 , which is either a human gamma-1 or a human gamma-3 monoclonal antibody.  
     
     
         4 . The anti-human CD23 monoclonal antibody of  claim 1 , which comprises a rodent antigen binding portion.  
     
     
         5 . The anti-human CD23 antibody of  claim 1 , which is a humanized antibody.  
     
     
         6 . The anti-human CD23 monoclonal antibody of  claim 1 , which inhibits IgE expression in vitro.  
     
     
         7 . The anti-human CD23 monoclonal antibody of  claim 6 , which inhibits IL-4 induced IgE expression by B cells in vitro.  
     
     
         8 . The anti-human CD23 monoclonal antibody of  claim 1 , which inhibits IL-4 induced IgE expression in vivo.  
     
     
         9 . The anti-human CD23 monoclonal antibody of  claim 1 , having a binding affinity ranging from 0.01 nM to 1000 nM.  
     
     
         10 . The anti-human CD23 monoclonal antibody of  claim 1 , having a CD23 binding affinity of at least 5 nM.  
     
     
         11 . The anti-human CD23 monoclonal antibody of  claim 9 , having a CD23 binding affinity of at least 100 nM.  
     
     
         12 . The anti-human CD23 antibody of  claim 1 , wherein the variable domains are derived from 5E8, 6G5 or 2C8.  
     
     
         13 . The anti-human CD23 antibody of  claim 1 , which is capable of inhibiting the binding of monoclonal anti-human CD23 antibody 5E8 or 6G5 to CD23.  
     
     
         14 . A pharmaceutical composition containing an anti-human CD23 antibody according to  claim 1 .  
     
     
         15 - 24 . (canceled)  
     
     
         25 . The anti-human CD23 antibody of  claim 12 , which is capable of inhibiting the binding of monoclonal anti-human CD23 antibody 5E8 to CD23.  
     
     
         26 . A method of treating or preventing a disease condition wherein inhibition of IgE is therapeutically or prophylactically beneficial comprising administering an effective amount of an antibody according to  claim 1 .  
     
     
         27 - 34 . (canceled)  
     
     
         35 . The method of  claim 26 , wherein the disease condition is an allergic disorder, an autoimmune disease or an inflammatory disease.  
     
     
         36 - 37 . (canceled)  
     
     
         38 . The anti-human CD23 monoclonal antibody of  claim 3 , which is a human gamma-1 monoclonal antibody.  
     
     
         39 . The anti-human CD23 monoclonal antibody of  claim 3 , which is a human gamma-3 monoclonal antibody.