Methods of Treatment Using Anti-IL-17A/F Antibodies

Abstract

The invention relates to therapeutic uses of antibody molecules having specificity for antigenic determinants of both IL-17A and IL-17F in the treatment of dermatological and rheumatological diseases, such as psoriasis, psoriatic arthritis and axial spondyloarthritis.

1 . A method of treating psoriatic arthritis in a human comprising the step of administering to the human a neutralizing antibody which binds human IL-17A and human IL-17F. 
     
     
         2 . The method of  claim 1 , wherein the antibody specifically binds
 (a) an epitope of human IL-17F, the epitope comprising one or more residues selected from ARG47, ARG73, LEU75 and ILE86 of SEQ ID NO: 27; and/or   (b) epitope of human IL-17A, the epitope comprising one or more residues selected from TYR44, ASN45, ARG46, TRP51, ASN52, HIS54 and ASP84 of SEQ ID NO: 28.   
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the antibody binds to the same epitope on human IL-17A, human IL-17F, or IL-17 A/F heterodimer as a neutralising antibody that has a heavy chain comprising the sequence given in SEQ ID NO: 11 and a light chain comprising the sequence given in SEQ ID NO: 10. 
     
     
         5 . The method of  claim 1 , wherein the antibody cross-blocks a neutralising antibody that has a heavy chain comprising the sequence given in SEQ ID NO: 11 and a light chain comprising the sequence given in SEQ ID NO: 10 and binds human IL-1 7A and human IL-1 7F. 
     
     
         6 . The method of  claim 1 , wherein the antibody comprises a light chain variable domain and a heavy chain variable domain, wherein the variable domain of the light chain comprises the sequence given in SEQ ID NO:10. 
     
     
         7 . The method of  claim 1 , wherein the antibody is bimekizumab. 
     
     
         8 . The method of any one of  claims 1  through  7 , wherein the antibody is administered as a pharmaceutical composition. 
     
     
         9 . The method of any one of  claims 1  through  8 , wherein the antibody is administered subcutaneously. 
     
     
         10 . The method of any one of  claims 1  through  8 , wherein the antibody is administered intravenously. 
     
     
         11 . The method of  claim 1 , wherein the human
 (a) has a diagnosis of adult-onset psoriatic arthritis;   (b) has active arthritis;   (c) has active psoriatic lesions or a history of psoriatic lesions; and/or   (d) is an inadequate responder to at least one non-biologic disease-modifying antirheumatic drug (“DMARD”) and/or one approved biologic DMARD.   
     
     
         12 - 17 . (canceled) 
     
     
         18 . A method of treating psoriatic arthritis in a human concurrently treated with methotrexate comprising the step of administering to the human a neutralizing antibody which binds human IL-17A and human IL-17F. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 1 , wherein the antibody is administered in an amount that is effective to provide an ACR20 response at week 8, an ACR50 response at week 8, or an ACR70 response at week 8 in a population of patients in need of treatment. 
     
     
         21 - 22 . (canceled) 
     
     
         23 . The method of  claim 1 , wherein the antibody is administered in an amount that is effective to provide a PASI50 response at week 8, a PASI75 response at week 8, or a PASI90 response at week 8. 
     
     
         24 .- 30 . (canceled) 
     
     
         31 . A method of reducing joint effects in a human comprising the step of administering to the human a neutralizing antibody which binds human IL-17A and human IL-17F. 
     
     
         32 . (canceled) 
     
     
         33 . A method of reducing psoriasis and reducing joint effects in a human comprising the step of administering to the human a neutralizing antibody which binds human IL-17A and human IL-17F. 
     
     
         34 . The method of  claim 33 , wherein the psoriasis is plaque psoriasis. 
     
     
         35 . (canceled) 
     
     
         36 . A method of treating psoriatic arthritis in a human, comprising the step of administering to the human at least one dose of a neutralizing antibody which binds human IL-17A and human IL-17F. 
     
     
         37 . A method of treating rheumatoid arthritis in a human comprising the step of administering to the human a neutralizing antibody which binds human IL-17A and human IL-17F. 
     
     
         38 . The method of  claim 37 , wherein the human has a diagnosis of adult-onset rheumatoid arthritis. 
     
     
         39 - 41 . (canceled) 
     
     
         42 . The method of  claim 37 , wherein the human
 (a) has active arthritis; and/or   (b) is an inadequate responder to at least one non-biologic disease-modifying antirheumatic drug (“DMARD”) and/or one approved biologic DMARD.   
     
     
         43 . (canceled) 
     
     
         44 . A method of treating rheumatoid arthritis in a human concurrently treated with methotrexate comprising the step of administering to the human a neutralizing antibody which binds human IL-17A and human IL-17F. 
     
     
         45 - 58 . (canceled) 
     
     
         59 . The method of  claim 1 , wherein the method comprises administering a dose comprising between 40 and 640 mg of the antibody. 
     
     
         60 - 71 . (canceled) 
     
     
         72 . The method of  claim 1 , comprising administering to the human a loading dose of the neutralizing antibody followed by at least one maintenance dose of the antibody. 
     
     
         73 - 82 . (canceled) 
     
     
         83 . The method of treating psoriatic arthritis of  claim 1  wherein the method comprises administering (a) 16 mg of antibody every four weeks, (b) 160 mg of antibody every four weeks, (b) 320 mg loading dose of antibody followed by a maintenance dose of 160 mg of antibody every four weeks, or (d) 320 mg of antibody every four weeks. 
     
     
         84 - 112 . (canceled) 
     
     
         113 . A method of treating ankylosing spondylitis in a human comprising the step of administering to the human a neutralizing antibody which binds human IL-17A and human IL-17F. 
     
     
         114 - 124 . (canceled)