Binding members-513

Abstract

This invention relates to binding members, especially antibody molecules, specific for interleukin 1 receptor 1 (IL-1R1). For example, isolated binding members specific for IL-1R1 which competes with IL-1 and IL-1Ra for binding to IL-1R1 and binds Il-1R1 with a K D of 10 pM or less when measured by Kinexa™. The binding members are useful for, inter alia, treatment of disorders mediated by IL-1R1 including rheumatoid arthritis, asthma and chronic obstructive pulmonary disease (COPD).

1 - 25 . (canceled) 
     
     
         26 . An isolated antibody or fragment thereof specific for IL-R11 comprising a set of CDRs: HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 wherein:
 HCDR1 has the amino acid sequence of SEQ. ID. NO: 63;   HCDR2 has the amino acid sequence of SEQ. ID. NO: 64;   HCDR3 has the amino acid sequence of SEQ. ID. NO: 65;   LCDR1 has the amino acid sequence of SEQ. ID. NO: 68;   LCDR2 has the amino acid sequence of SEQ. ID. NO: 69;   LCDR3 has the amino acid sequence of SEQ. ID. NO: 70.   
     
     
         27 . An isolated antibody or fragment thereof specific for IL-1R1 which binds the same epitope as the isolated antibody of  claim 26 , wherein the epitope is comprised within one or more of the following sequences of IL-1R1: (i) N123-V134; (ii) L140-K157; and/or (iii) K178-R180 of SEQ. ID. NO: 137. 
     
     
         28 . An isolated antibody or fragment thereof specific for IL-1R1 according to  claim 27  which binds a discontinuous epitope comprised within the following sequences of IL-1R: (i) N123-V134; (ii) L140-K157; and (iii) K178-R180 of SEQ. ID. NO:137. 
     
     
         29 . The isolated antibody according to  claim 26 , wherein the antibody is a monoclonal antibody, a human antibody, a chimeric antibody, a bi-specific antibody, a multi-specific antibody, or an antibody fragment thereof. 
     
     
         30 . The antibody fragment of  claim 29 , wherein the antibody fragment is a Fab fragment, a Fab′ fragment, a F(ab′)2 fragment, a Fv fragment, a diabody, a triabody, a tetrabody, a minibody, a disulphide stabilized variable region (dsFv) or a single chain antibody molecule. 
     
     
         31 . An isolated antibody or fragment thereof that binds IL-1R1, comprising a heavy chain variable region (VH) comprising SEQ ID NO: 62 and a light chain variable region (VL) comprising SEQ ID NO: 67. 
     
     
         32 . An isolated antibody or fragment thereof that binds IL-1R1 at the same epitope as the antibody of  claim 31 , wherein the epitope comprises one or more of the following sequences of IL-1R1: (i) N123-V134; (ii) L140-K157; and/or (iii) K178-R180 of SEQ ID NO: 137. 
     
     
         33 . The isolated antibody or fragment thereof of  claim 32  which binds a discontinuous epitope comprising the following sequences of IL-1R1: (i) N123-V134; (ii) L140-K157; and (iii) K178-R180 of SEQ ID NO: 137. 
     
     
         34 . The antibody of  claim 31 , wherein the antibody is a monoclonal antibody, a human antibody, a chimeric antibody, a bi-specific antibody, a multi-specific antibody, or an antibody fragment thereof. 
     
     
         35 . The antibody fragment of  claim 34 , wherein the antibody fragment is a Fab fragment, a Fab′ fragment, a F(ab′)2 fragment, a Fv fragment, a diabody, a triabody, a tetrabody, a minibody, a disulphide stabilized variable region (dsFv) or a single chain antibody molecule. 
     
     
         36 . A method for treating or preventing a condition associated with IL-1R1 in a patient, comprising administering to a patient in need thereof an effective amount of the antibody or fragment thereof of  claim 26 . 
     
     
         37 . The method of  claim 36 , wherein the condition is selected from the group consisting of rheumatoid arthritis, osteoarthritis, asthma, chronic obstructive pulmonary disease, psoriasis, allergic rhinitis, HIV, solid tumors, leukaemia, Alzheimer's disease, type II diabetes, ischaemic disease and atherosclerosis. 
     
     
         38 . A method for treating or preventing a condition associated with IL-1R1 in a patient, comprising administering to a patient in need thereof an effective amount of the antibody or fragment thereof of  claim 31 . 
     
     
         39 . The method of  claim 38 , wherein the condition is selected from the group consisting of rheumatoid arthritis, osteoarthritis, asthma, chronic obstructive pulmonary disease, psoriasis, allergic rhinitis, HIV, solid tumors, leukaemia, Alzheimer's disease, type II diabetes, ischaemic disease and atherosclerosis.