Interferon alpha antibodies and their uses

Abstract

The present invention provides isolated anti-interferon alpha monoclonal antibodies, particularly human monoclonal antibodies, that inhibit the biological activity of multiple interferon (IFN) alpha subtypes but do not substantially inhibit the biological activity of IFN alpha 21 or the biological activity of either IFN beta or IFN omega. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting the biological activity of IFN alpha using the antibodies of the invention, as well as methods of treating disease or disorders mediated by IFN alpha, such as autoimmune diseases, transplant rejection and graft versus host disease, by administering the antibodies of the invention.

What is claimed is: 
     
         1 . An isolated anti-interferon alpha monoclonal antibody, or antigen binding portion thereof, comprising a heavy chain variable region comprising CDR1, CDR2, and CDR3 domains and a light chain variable region comprising CDR1, CDR2, and CDR3 domains, wherein: (a) the heavy chain variable region CDR3 domain comprises an amino acid sequence selected from the group consisting of amino acid sequences of SEQ ID NOs: 7, 8 and 9, and conservative modifications thereof; and (b) the light chain variable region CDR3 domain comprises an amino acid sequence selected from the group consisting of amino acid sequence of SEQ ID NOs: 16, 17 and 18, and conservative modifications thereof. 
     
     
         2 . The antibody of  claim 1 , wherein the heavy chain variable region CDR2 domain comprises an amino acid sequence selected from the group consisting of amino acid sequences of SEQ ID NOs: 4, 5 and 6, and conservative modifications thereof; and the light chain variable region CDR2 domain comprises an amino acid sequence selected from the group consisting of amino acid sequences of SEQ ID NOs: 13, 14 and 15, and conservative modifications thereof. 
     
     
         3 . The antibody of  claim 2 , wherein the heavy chain variable region CDR1 domain comprises an amino acid sequence selected from the group consisting of amino acid sequences of SEQ ID NOs: 1, 2 and 3, and conservative modifications thereof; and the light chain variable region CDR1 domain comprises an amino acid sequence selected from the group consisting of amino acid sequences of SEQ ID NOs: 10, 11 and 12, and conservative modifications thereof. 
     
     
         4 . An isolated anti-interferon alpha monoclonal antibody, or antigen binding portion thereof, comprising a heavy chain variable region and a light chain variable region, wherein: (a) the heavy chain variable region comprises an amino acid sequence that is at least 90% homologous to an amino acid sequence selected from the group consisting of SEQ ID NOs: 19, 20 and 21; and (b) the light chain variable region comprises an amino acid sequence that is at least 90% homologous to an amino acid sequence selected from the group consisting of SEQ ID NOs: 22, 23 and 24. 
     
     
         5 . An isolated anti-interferon alpha monoclonal antibody, or antigen binding portion thereof comprising: (a) a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 19, 20 and 21; and (b) a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 22, 23 and 24. 
     
     
         6 . The antibody of  claim 5 , which comprises: (a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 20; and (b) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 23. 
     
     
         7 . The antibody of  claim 5 , which comprises: (a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 21; and (b) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 24. 
     
     
         8 . A composition comprising the antibody, or antigen-binding portion thereof, of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         9 . An immunoconjugate comprising the antibody, or antigen-binding portion thereof, of  claim 1 , linked to a therapeutic agent. 
     
     
         10 . The immunoconjugate of  claim 9 , wherein the therapeutic agent is a cytotoxin or a radioactive isotope. 
     
     
         11 . A method of treating an interferon alpha-mediated disease or disorder in a subject in need of treatment comprising administering to the subject the antibody, or antigen-binding portion thereof, of  claim 1 , such that the interferon-alpha mediated disease in the subject is treated. 
     
     
         12 . The method of  claim 11 , wherein the disease or disorder is selected from the group consisting of multiple sclerosis, inflammatory bowel disease, insulin dependent diabetes mellitus, psoriasis, autoimmune thyroiditis, rheumatoid arthritis, glomerulonephritis, transplant rejection and graft versus host disease.