Antibody to human il-1 beta

Abstract

The present invention relates to anti-IL-1 beta binding members and in particular to monovalent high potency IL-1 beta-binding antibody fragments being highly stable and soluble. Such binding members may be used in the treatment of inflammatory and other diseases as well as in diagnostics. Also provided are related nucleic acids, vectors, cells, and compositions.

1 - 29 . (canceled) 
     
     
         30 . A method of detecting the presence of IL-1 beta in a biological sample comprising the steps of:
 a. contacting said biological sample with an antibody against IL-1 beta, and   b. detecting whether a complex is formed with IL-1 beta.   wherein, the antibody comprises:   (i) the variable heavy chain (VH) CDR sequences CDR-H1, CDR-H2 or CDR-H3 as set forth in:
 SEQ ID NOS: 1, 2 and 3, respectively, and 
   (ii) the variable light chain (VL) CDR sequences CDR-L1, CDR-L2 or CDR-L3 as set forth in:
 SEQ ID NOS: 4, 5, 6, respectively. 
   
     
     
         31 . The method of  claim 30 , wherein the antibody having a potency (IC 50 ) with regard to inhibiting the biological effect of human IL-1 beta of lower than 50 pM as determined by inhibiting IL-1 beta stimulated release of IL-6 from human fibroblasts. 
     
     
         32 . The method of  claim 31 , wherein the IC 50  of the antibody is lower than about 30 pM. 
     
     
         33 . The method of  claim 31 , wherein the IC 50  of the antibody is lower than about 10 pM. 
     
     
         34 . The method of  claim 30 , wherein the antibody is a Fab, a Fab′, a scFv, or a Fv fragment. 
     
     
         35 . The method of  claim 30 , wherein the antibody is a full-length immunoglobulin or a bivalent antibody fragment. 
     
     
         36 . The method of  claim 30 , wherein the antibody comprises the light chain variable framework region FR-L1 of SEQ ID NO: 18, the light chain variable framework region FR-L2 of SEQ ID NO: 19, the light chain variable framework region FR-L3 of SEQ ID NO: 20 and/or the light chain variable framework region FR-L4 of SEQ ID NO: 21. 
     
     
         37 . The method of  claim 30 , wherein the antibody comprises the heavy chain variable framework region FR-H1 of SEQ ID NO: 22; the heavy chain variable framework region FR-H2 of SEQ ID NO: 23; the heavy chain variable framework region FR-H3 of SEQ ID NO: 24; and/or the heavy chain variable framework region FR-H4 of SEQ ID NO: 25. 
     
     
         38 . The method of  claim 30 , wherein the antibody comprises:
 a. a VH sequence of SEQ ID NO: 7; and   b. a VL sequence of SEQ ID NO: 8.   
     
     
         39 . The method of  claim 30 , wherein the antibody comprises the linker sequence of SEQ ID NO: 9. 
     
     
         40 . The method of  claim 30 , wherein the antibody comprises the sequence of SEQ ID NO: 10. 
     
     
         41 . The method of  claim 30 , wherein the antibody is humanized. 
     
     
         42 . The method of  claim 30 , wherein the antibody is cross-reactive with cynomolgus IL-1 beta, rhesus monkey IL-1 beta and/or rat IL-1 beta. 
     
     
         43 . The method of  claim 30 , being an in vitro or an in vivo method. 
     
     
         44 . The method of  claim 30 , wherein the biological sample is of human origin. 
     
     
         45 . The method of  claim 30 , wherein the biological sample is blood, urine, cerebrospinal fluid, biopsy, and/or lymph.