Anti mif antibodies

Abstract

The present invention relates to monoclonal antibodies and antigen-binding portions thereof that specifically bind to the C-terminal or the center region of macrophage migration inhibitory factor (MIF). These anti-MIF antibodies and antigen-binding portions thereof further inhibit human MIF biological function. The invention also relates to isolated heavy and light chain immunoglobulins derived from anti-MIF antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to a method of identifying anti-MIF antibodies, pharmaceutical compositions comprising these antibodies and a method of using these antibodies and compositions for the treatment of MIF-related conditions.

1 . A monoclonal antibody or an antigen-binding portion thereof that specifically binds to MIF and inhibits human MIF biological function, wherein said monoclonal antibody or antigen binding portion possesses at least one of the following properties:
 a) inhibits glucocorticoid overriding (GCO) activity;   b) inhibits proliferation of cancer cells or fibroblasts.   
     
     
         2 . (canceled) 
     
     
         3 . The monoclonal antibody or antigen-binding portion according to  claim 1 , wherein said antibody or antigen-binding portion binds human MIF with a K D  less than 500 nM. 
     
     
         4 . The monoclonal antibody or antigen-binding portion according to  claim 1 , wherein said antibody or said antigen-binding portion binds to active MIF. 
     
     
         5 . The monoclonal antibody according to  claim 1 , wherein said antibody is an IgG4 sub-format antibody. 
     
     
         6 . The monoclonal antibody according to  claim 5 , wherein said IgG4 sub-format has a single mutation, whereby the CPSC sub-sequence in the Fc region of IgG4 becomes CPPC. 
     
     
         7 . The monoclonal antibody or the antigen-binding portion according to  claim 1 , for use in treating an immunological disease, wherein said immunological disease is an inflammatory disease or a hyperproliferative disorder. 
     
     
         8 . A pharmaceutical composition, comprising the monoclonal antibody or the antigen-binding portion according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         9 . A method for treating an immunological disease selected from inflammatory disease or a hyperproliferative disorder in a subject, including a human, comprising the step of administering to said subject in need thereof a therapeutically effective amount of the monoclonal antibody or the antigen-binding portion according to  claim 1 , wherein said antibody or said antigen binding portion further inhibits human MIF biological function. 
     
     
         10 . An isolated cell line that produces the monoclonal antibody or the antigen-binding portion according to  claim 1 . 
     
     
         11 . An isolated nucleic acid molecule comprising a nucleotide sequence that encodes the heavy chain, or the light chain, of the monoclonal antibody or the antigen-binding portion according to  claim 1 . 
     
     
         12 . A vector comprising the nucleic acid molecule according to  claim 11 , wherein the vector optionally comprises an expression control sequence operably linked to said nucleic acid molecule. 
     
     
         13 . A host cell comprising the nucleic acid molecule according to  claim 11 . 
     
     
         14 . A host cell comprising a nucleic acid molecule encoding the heavy chain and a nucleic acid molecule encoding the light chain of the monoclonal antibody or the antigen-binding portion according to  claim 1 . 
     
     
         15 . A method of producing a monoclonal antibody or an antigen-binding portion thereof, comprising culturing the host cell according to  claim 14  under suitable conditions and recovering said antibody or antigen-binding portion thereof. 
     
     
         16 . A process for the identification of anti-MIF antibodies capable of inhibiting human MIF biological function and inducing a beneficial effect in an animal model by carrying out the following steps:
 a) selecting an antibody that binds to active MIF and does not bind to non-active MIF   b) testing said antibody in in-vitro assays   c) selecting an antibody, which inhibits GCO and/or cell proliferation.