Use of interleukin-4 antagonists and compositions thereof

Abstract

Methods for treating medical conditions induced by interleukin-4 involve administering an IL-4 antagonist to a patient afflicted with such a condition. Suitable IL-4 antagonists include, but are not limited to, IL-4 receptors (such as a soluble human IL-4 receptor), antibodies that bind IL-4, antibodies that bind IL-4R, IL-4 muteins that bind to IL-4R but do not induce a biological response, molecules that inhibit IL-4-induced signal transduction, and other compounds that inhibit a biological effect that results from the binding of IL-4 to a cell surface IL-4R. Particular antibodies provided herein include human monoclonal antibodies generated by procedures involving immunization of transgenic mice. Such human antibodies may be raised against human IL-4 receptor. Certain of the antibodies inhibit both IL-4-induced and IL-13-induced biological activities.

What is claimed is: 
     
         1 . A method of reducing interleukin-4 receptor (IL-4R)-dependent signaling in a subject, comprising administering to said subject an effective amount of an isolated anti-IL-4R antibody, wherein:
 a. the light chain variable domain of said isolated IL-4R antibody comprises the CDR1, 2, and 3 sequences of SEQ ID NO:14 and the heavy chain variable domain of said isolated IL-4R antibody comprises the CDR1, 2, and 3 sequences of SEQ ID NO:16; or   b. the light chain variable domain of said isolated IL-4R antibody comprises the CDR1, 2, and 3 sequences of SEQ ID NO:18 and the heavy chain variable domain of said isolated IL-4R antibody comprises the CDR1, 2, and 3 sequences of SEQ ID NO:20; or   c. the light chain variable domain of said isolated IL-4R antibody comprises the CDR1, 2, and 3 sequences of SEQ ID NO:22 and the heavy chain variable domain of said isolated IL-4R antibody comprises the CDR1, 2, and 3 sequences of SEQ ID NO:24.   
     
     
         2 . The method of  claim 1 , wherein said method suppresses a TH2-type immune response. 
     
     
         3 . The method of  claim 1 , wherein said subject has, or is at risk of developing, a condition responsive to inhibition of IL-4R signaling. 
     
     
         4 . The method of  claim 3 , wherein said condition is an inflammatory condition. 
     
     
         5 . The method of  claim 3 , wherein said condition is an IgE mediated condition. 
     
     
         6 . The method of  claim 3 , wherein said condition is an allergic condition. 
     
     
         7 . The method of  claim 3 , wherein said condition is a condition in which IL-4 mediated epithelial barrier disruption plays a role. 
     
     
         8 . The method of  claim 3 , wherein said condition is asthma, COPD, pulmonary fibrosis, septic arthritis, or atopic dermatitis.