Neutralising Antibody Molecules having Specificity for Human IL-17

Abstract

The invention relates to an antibody molecule having specificity for antigenic determinants of IL-17, therapeutic uses of the antibody molecule and methods for producing said antibody molecule.

1 . (canceled) 
     
     
         2 . A method of treating an IL-17 mediated pathological condition in a mammal comprising the step of administering to the mammal a therapeutically effective amount of a pharmaceutical composition comprising a neutralising antibody having specificity for human IL-17, wherein a variable domain of a heavy chain comprises at least one CDR having a sequence selected from SEQ ID NO:5 for CDR-H1, SEQ ID NO:6 for CDR-H2, and SEQ ID NO:7 for CDR-H3 and wherein a light chain comprises SEQ ID NO:13. 
     
     
         3 . The method of  claim 2 , wherein the neutralising antibody comprises a light chain and a heavy chain, wherein a variable domain of the heavy chain comprises SEQ ID NO:5 for CDR-H1, SEQ ID NO:6 for CDR-H2, and SEQ ID NO:7 for CDR-H3, and a variable domain of the light chain comprises SEQ ID NO:8 for CDR-L1, SEQ ID NO:9 for CDR-L2, and SEQ ID NO:10 for CDR-L3 to human IL-17. 
     
     
         4 . The method of  claim 2 , wherein the neutralising antibody comprises a heavy chain and a light chain, wherein a variable domain of the heavy chain comprises the sequence gH11 (SEQ ID NO:11) and a variable domain of the light chain comprises the sequence gL3 (SEQ ID NO: 13). 
     
     
         5 . The method of  claim 2 , wherein the neutralising antibody comprises a heavy chain comprising sequence given in SEQ ID NO:16 and a light chain comprising sequence given in SEQ ID NO:18. 
     
     
         6 . The method of  claim 2 , wherein the neutralising antibody comprises a light chain and a heavy chain wherein the heavy chain comprises SEQ ID NO:11. 
     
     
         7 . The method of  claim 2 , wherein the neutralising antibody binds to the same epitope as an antibody in which a variable domain of a heavy chain comprises sequence gH11 (SEQ ID NO:11) and a variable domain of a light chain comprises the sequence gL3 (SEQ ID NO: 13). 
     
     
         8 . The method of  claim 2 , wherein the neutralising antibody binds to a same epitope as an antibody comprising a light chain and a heavy chain, wherein a variable domain of the heavy chain comprises SEQ ID NO:5 for CDR-H1, SEQ ID NO:6 for CDR-H2, and SEQ ID NO:7 for CDR-H3 and wherein a variable domain of the light chain comprises SEQ ID NO:8 for CDRL1, SEQ ID NO:9 for CDR-L2, and SEQ ID NO:10 for CDR-L3 to human IL-17. 
     
     
         9 . The method of  claim 2 , wherein the neutralising antibody cross-blocks binding of an antibody in which a variable domain of a heavy chain comprises sequence gH11 (SEQ ID NO: 11) and a variable domain of a light chain comprises sequence gL3 (SEQ ID NO: 13) to human IL-17. 
     
     
         10 . The method of  claim 2 , wherein the neutralising antibody cross-blocks binding of an antibody in which a variable domain of a heavy chain comprises SEQ ID NO:5 for CDR-H1, SEQ ID NO:6 for CDR-H2, and SEQ ID NO:7 for CDR-H3 and wherein a variable domain of a light chain comprises SEQ ID NO:8 for CDRL1, SEQ ID NO:9 for CDR-L2, and SEQ ID NO:10 for CDR-L3 to human IL-17. 
     
     
         11 . The method of  claim 2 , wherein the neutralising antibody is cross-blocked from binding human IL-17 by the antibody in which the variable domain of the heavy chain comprises the sequence gH11 (SEQ ID NO: 11) and the variable domain of the light chain comprises the sequence gL3 (SEQ ID NO: 13) to human IL-17. 
     
     
         12 . The method of  claim 2 , wherein the neutralising antibody affinity for human IL-17 is between 100 pM and 400 pM. 
     
     
         13 . The method of  claim 2 , wherein the neutralising antibody affinity for human IL-17 is less than 500 pM. 
     
     
         14 . The method of  claim 2 , wherein one or more effector or reporter molecules are attached to the neutralising antibody. 
     
     
         15 . The method of  claim 2 , wherein the pharmaceutical composition further comprises one or more of a pharmaceutically acceptable excipient, diluent or carrier. 
     
     
         16 . The method of  claim 2 , wherein the IL-17 mediated pathological condition is associated with an increased level of IL-17. 
     
     
         17 . The method of  claim 2 , wherein the IL-17 mediated pathological condition is an infection comprising viral, bacterial, fungal or parasitic infection, endotoxic shock associated with infection, arthritis, rheumatoid arthritis, asthma, pelvic inflammatory disease, Alzheimer's disease, Crohn' s disease, inflammatory bowel disease, ulcerative colitis, Peyronie's disease, coeliac disease, gallbladder disease, Pilonidal disease, peritonitis, psoriasis, vasculitis, surgical adhesions, stroke, Type I Diabetes, Lyme arthritis, meningoencephalitis, immune mediated inflammatory disorders of the central and peripheral nervous system such as multiple sclerosis and Guillain-Barr syndrome, other autoimmune disorders, pancreatitis, trauma, surgery, graft-versus-host disease, transplant rejection, cancer comprising solid tumours comprising melanomas, hepatoblastomas, sarcomas, squamous cell carcinomas, transitional cell cancers, ovarian cancers and hematologic malignancies and in particular acute myelogenous leukaemia, chronic myelogenous leukemia, gastric cancer and colon cancer, heart disease comprising ischaemic diseases, wherein the diseases comprise myocardial infarction or atherosclerosis, intravascular coagulation, bone resorption, osteoporosis, periodontitis, hypochlorhydia, pain, rheumatoid arthritis, multiple sclerosis, inflammatory disease, autoimmune disease or cancer. 
     
     
         18 . A kit comprising the pharmaceutical composition of  claim 2  and instructions for use. 
     
     
         19 . A method of treating an IL-17 mediated pathological condition in a mammal comprising the step of administering to the mammal a therapeutically effective amount of a pharmaceutical composition comprising a neutralising antibody having specificity for human IL-17, wherein the neutralising antibody binds to a same epitope as an antibody in which a variable domain of a heavy chain comprises sequence gH11 (SEQ ID NO:11) and a variable domain of a light chain comprises sequence gL3 (SEQ ID NO: 13).