Anti-interferon-alpha antibodies

Abstract

The present invention relates generally to the generation and characterization of neutralizing anti-IFN-α monoclonal antibodies with broad reactivity against various IFN-α subtypes. The invention further relates to the use of such anti-IFN-α antibodies in the diagnosis and treatment of disorders associated with increased expression of TUN-α, in particular, autoimmune disorders such as insulin-dependent diabetes mellitus (IDDM) and systemic lupus erythematosus (SLE).

1 . An anti-IFN-α monoclonal antibody which binds to and neutralizes a biological activity of at least IFN-α subtypes, IFN-α1, IFN-α2, IFN-α4, IFN-α5, IFN-α8, IFN-α10, and IFN-α21. 
     
     
         2 - 19 . (canceled) 
     
     
         20 . An anti-IFN-α antibody light chain or a fragment thereof, comprising the following CDR's:
 (a) L1 of the formula RASQSVSTSSYSYMH (SEQ ID NO: 7); 
 (b) L2 of the formula YASNLES (SEQ ID NO: 8); and 
 (c) L3 of the formula QHSWGIPRTF (SEQ ID NO: 9). 
 
     
     
         21 . (canceled) 
     
     
         22 . An anti-IFN-α antibody heavy chain or a fragment thereof, comprising the following CDR's:
 (a) H1 of the formula GYTFTEYIIH (SEQ ID NO: 10); 
 (b) H2 of the formula SINPDYDITNYNQRFKG (SEQ ID NO: 11); and 
 (c) H3 of the formula WISDFFDY (SEQ ID NO: 12). 
 
     
     
         23 . (canceled) 
     
     
         24 . An anti-IFN-α antibody comprising
 (A) at least one light chain or a fragment thereof, comprising the following CDR's:
 (a) L1 of the formula RASQSVSTSSYSYMH (SEQ ID NO: 7); 
 (b) L2 of the formula YASNLES (SEQ ID NO: 8); and 
 (c) L3 of the formula QHSWGIPRTF (SEQ ID NO: 9); and 
 
 (B) at least one heavy chain or a fragment thereof, comprising the following CDR's:
 (a) H1 of the formula GYTFTEYIIH (SEQ ID NO: 10); 
 (b) H2 of the formula SINPDYDITNYNQRFKG (SEQ ID NO: 11); and 
 (c) H3 of the formula WISDFFDY (SEQ ID NO: 12). 
 
 
     
     
         25 - 30 . (canceled) 
     
     
         31 . An isolated nucleic acid molecule encoding an antibody of  claim 1 . 
     
     
         32 - 33 . (canceled) 
     
     
         34 . An isolated nucleic acid molecule encoding an antibody of  claim 24 . 
     
     
         35 . An isolated nucleic acid molecule encoding an antibody light chain or light chain fragment of  claim 20 . 
     
     
         36 . An isolated nucleic acid molecule encoding an antibody heavy chain or heavy chain fragment of  claim 22 . 
     
     
         37 . An isolated nucleic acid molecule comprising the light chain polypeptide-encoding nucleic acid sequence of the vector deposited with ATCC on Jan. 9, 2001 and having accession No. PTA-2882. 
     
     
         38 . An isolated nucleic acid molecule comprising the heavy chain polypeptide-encoding nucleic acid sequence of the vector deposited with ATCC on Jan. 9, 2001 and having accession No. PTA-2881. 
     
     
         39 . A vector comprising a nucleic acid molecule according to  claim 31 . 
     
     
         40 . A host cell transformed with a nucleic acid molecule according to  claim 31 . 
     
     
         41 . A method of producing the antibody of  claim 1  comprising culturing a host cell comprising a nucleic acid sequence encoding the antibody under conditions wherein the nucleic acid sequence is expressed to produce the antibody. 
     
     
         42 . A hybridoma cell line comprising a nucleic acid molecule according to  claim 31 . 
     
     
         43 . A hybridoma cell line deposited with ATCC on Jan. 18, 2001 and having accession No. PTA-2917. 
     
     
         44 . An antibody produced by the hybridoma cell line of  claim 42 . 
     
     
         45 . A pharmaceutical composition comprising an effective amount of the antibody of  claim 1  in admixture with a pharmaceutically acceptable carrier. 
     
     
         46 - 47 . (canceled) 
     
     
         48 . A pharmaceutical composition comprising an effective amount of the antibody of  claim 24  in admixture with a pharmaceutically acceptable carrier. 
     
     
         49 . A method for diagnosing a condition associated with the expression of IFN-α in a cell, comprising contacting said cell with an anti-IFN-α antibody of  claim 1 , and detecting the presence of IFN-α. 
     
     
         50 . A method for the treatment of a disease or condition associated with the expression of IFN-α in a patient, comprising administering to said patient an effective amount of an anti-IFN-α antibody of  claim 1 . 
     
     
         51 - 54 . (canceled)