Monoclonal antibodies to type i interferon receptor

Abstract

Anti-IFNAR1 monoclonal antibodies with neutralizing activities against the anti-viral cytopathic effects of various type I interferons are provided.

1 - 10 . (canceled)  
     
     
         11 . An anti-IFNAR1 monoclonal antibody that 
 a) inhibits the anti-viral activity of a first type I interferon selected from the group consisting of IFN-α1, IFN-α2/1, IFN-α2, IFN-α5, and IFN-α8;    b) does not inhibit the anti-viral activity of IFN-β.    
     
     
         12 . The monoclonal antibody of  claim 11  that binds to one or more amino acids in situ in the sequence of amino acids 244-249 of IFNAR1 having the amino acid sequence of SEQ ID NO:22.  
     
     
         13 . The monoclonal antibody of  claim 12 , wherein the monoclonal antibody does not bind to one or more amino acids in situ in the sequence of amino acids 291-298 of IFNAR1 having the amino acid sequence of SEQ ID NO:22.  
     
     
         14 . The monoclonal antibody of  claim 12 , wherein the monoclonal antibody binds to amino acid 249 of IFNAR1 in situ having the amino acid sequence of SEQ ID NO:22.  
     
     
         15 . The monoclonal antibody of  claim 14 , wherein the monoclonal antibody binds to amino acids 291 and 296 of IFNAR1 in situ having the amino acid sequence of SEQ ID NO:22.  
     
     
         16 . The monoclonal antibody of  claim 11 , wherein the monoclonal antibody does not bind to one or more amino acids 244-249 of IFNAR1 having the amino acid sequence of SEQ ID NO:22.  
     
     
         17 . The monoclonal antibody of  claim 16 , wherein the monoclonal antibody recognizes a conformational epitope of IFNAR1.  
     
     
         18 . The monoclonal antibody of  claim 11 , wherein the first type I interferon is IFN-α8.  
     
     
         19 . The monoclonal antibody of  claim 11 , wherein the monoclonal antibody inhibits the anti-viral activity of type I interferons IFN-α2, IFN-α5, and IFN-α8.  
     
     
         20 . The monoclonal antibody of  claim 11 , wherein the monoclonal antibody exhibits an EC 50  of up to or about 1 μg/ml against the anti-viral activity of the first type I interferon.  
     
     
         21 . The monoclonal antibody of  claim 11 , wherein the monoclonal antibody exhibits an EC 50  of up to or about 10 μg/ml against the anti-viral activity of the first type I interferon.  
     
     
         22 . The monoclonal antibody of  claim 11 , wherein the monoclonal antibody exhibits an EC 50  of up to or about 20 μg/ml against the anti-viral activity of the first type I interferon.  
     
     
         23 . The monoclonal antibody of  claim 11 , wherein the monoclonal antibody exhibits an EC 50  of up to or about 50 μg/ml against the anti-viral activity of the first type I interferon.  
     
     
         24 . The monoclonal anti-IFNAR1 antibody of  claim 11  having the heavy chain CDRs of the monoclonal antibody 2E1, ATCC Deposit No. HB12133, 4A7, ATCC Deposit No. HB12132, or 5H8, ATCC Deposit No. HB12129, respectively.  
     
     
         25 . The monoclonal antibody of  claim 24  which is humanized.  
     
     
         26 . A method for treatment of an immune-mediated or autoimmune disorder comprising administering a therapeutically effective amount of an anti-IFNAR1 monoclonal antibody of  claim 25  to a mammal.  
     
     
         27 . The method of  claim 26 , wherein the autoimmune disorder is selected from the group consisting of insulin-dependent diabetes mellitus, noninsulin-dependent diabetes mellitus, systemic lupus erythematosis, rheumatoid arthritis, and combinations thereof.  
     
     
         28 . The method of  claim 27 , wherein the autoimmune disorder is insulin-dependent diabetes mellitus.  
     
     
         29 . The method of  claim 28 , wherein the immune-mediated disorder is graft rejection or graft versus host disease.  
     
     
         30 . The method of  claim 29 , wherein the anti-IFNAR1 monoclonal antibody is administered prior to transplantation surgery.  
     
     
         31 . The method of  claim 29 , wherein the anti-IFNAR1 monoclonal antibody is administered post-transplant surgery.  
     
     
         32 . A method for detecting IFNAR1 comprising: 
 a) contacting an isolated cell with an anti-IFNAR1 monoclonal antibody of  claim 11;  and    b) detecting IFNAR1 expression in said cell.    
     
     
         33 . A hybridoma cell line producing an anti-IFNAR1 monoclonal antibody of  claim 11 .  
     
     
         34 . The hybridoma cell line of  claim 33 , wherein the hybridoma cell line is ATCC HB 12132, ATCC HB 12133, or ATCC HB 12129.  
     
     
         35 . The monoclonal antibody produced by a hybridoma having Deposit No. ATCC HB 12129, Deposit No. ATCC HB 12133, or Deposit No. ATCC HB 12132.