Use of IL-23 and IL-17 antagonists to treat autoimmune ocular inflammatory disease

Abstract

Novel methods and drug products for treating autoimmune ocular inflammatory disease are disclosed, which involve administration of agents that antagonize one or both of IL-17 and IL-23 activity.

1 . A method of treating a patient with an autoimmune ocular inflammatory disease (AOID), comprising administering to the patient an IL-17 antagonist. 
     
     
         2 . The method of  claim 1 , wherein the patient has been diagnosed as having an ocular inflammation of putative autoimmune etiology. 
     
     
         3 . The method of  claim 1 , wherein a specified dose of the IL-17 antagonist is administered at a specified interval during a first treatment period. 
     
     
         4 . The method of  claim 3 , wherein the first treatment period ends after disappearance of one or more symptoms of the AOID. 
     
     
         5 . The method of  claim 4 , wherein the first treatment period ends within 30 days after disappearance of all symptoms of the AOID. 
     
     
         6 . The method of  claim 4 , wherein the dose of the IL-17 antagonist administered is gradually reduced during a second treatment period that begins upon the end of the first treatment period. 
     
     
         7 . The method of  claim 6 , wherein the duration of the second treatment period is at least one year. 
     
     
         8 . The method of  claim 1 , wherein the IL-17 antagonist is a monoclonal antibody or a monoclonal antibody fragment. 
     
     
         9 . The method of  claim 8 , wherein the IL-17 antagonist is a humanized monoclonal antibody or a fully human monoclonal antibody. 
     
     
         10 . The method of  claim 8 , wherein the IL-17 antagonist is a humanized monoclonal antibody fragment or a fully human monoclonal antibody fragment. 
     
     
         11 . The method of  claim 8 , wherein the monoclonal antibody or monoclonal antibody fragment is pegylated. 
     
     
         12 . The method of  claim 8 , wherein the monoclonal antibody or monoclonal antibody fragment binds to and inhibits the activity of IL-17. 
     
     
         13 . The method of  claim 8 , wherein the monoclonal antibody or monoclonal antibody fragment binds to and inhibits the activity of IL-17RA or IL-17RC. 
     
     
         14 . The method of  claim 1 , wherein the IL-17 antagonist is a bispecific antibody or bispecific antibody fragment that binds to and inhibits the activity of
 a) IL-17 and IL-23p19; or   b) IL-17 and IL-23R.   
     
     
         15 . The method of  claim 3 , further comprising administering an IL-23 antagonist to the patient during the first treatment period. 
     
     
         16 . The method of  claim 15 , wherein a specified dose of the IL-23 antagonist is administered at a specified interval during the first treatment period. 
     
     
         17 . The method of  claim 16 , wherein the first treatment period ends after disappearance of one or more symptoms of the AOID. 
     
     
         18 . The method of  claim 16 , wherein the first treatment period ends within 30 days after disappearance of all symptoms of the AOID. 
     
     
         19 . The method of  claim 18 , wherein the dose of each of the IL-17 antagonist and the IL-23 antagonist is gradually reduced during a second treatment period that begins upon the end of the first treatment period. 
     
     
         20 . The method of  claim 18 , wherein the dose of the IL-17 antagonist is gradually reduced during a second treatment period that begins upon the end of the first treatment period, and wherein the dose of the IL-23 antagonist administered during the second treatment period is the same as the dose administered in the first treatment period, and wherein the second treatment period ends when therapy with the IL-17 antagonist is stopped. 
     
     
         21 . The method of  claim 20 , wherein the duration of the second treatment period is between one month and three months. 
     
     
         22 . The method of  claim 20 , further comprising administering the IL-23 antagonist during a third treatment period that begins upon the end of the second treatment period. 
     
     
         23 . The method of  claim 22 , wherein the duration of the third treatment period is between six months and twelve months. 
     
     
         24 . The method of  claim 22 , wherein the dose of the IL-23 antagonist is gradually reduced during the third treatment period. 
     
     
         25 . The method of  claim 15 , wherein the IL-23 antagonist is a monoclonal antibody or a monoclonal antibody fragment. 
     
     
         26 . The method of  claim 25 , wherein the IL-23 antagonist is a humanized monoclonal antibody or a fully human monoclonal antibody. 
     
     
         27 . The method of  claim 25 , wherein the IL-23 antagonist is a humanized monoclonal antibody fragment or a fully human monoclonal antibody fragment. 
     
     
         28 . The method of  claim 25 , wherein the monoclonal antibody or monoclonal antibody fragment is pegylated. 
     
     
         29 . The method of  claim 25 , wherein the IL-23 antagonist binds to and inhibits the activity of IL-23p19. 
     
     
         30 . The method of  claim 25 , wherein the IL-23 antagonist binds to and inhibits the activity of IL-23R. 
     
     
         31 . The method of  claim 1 , wherein the AOID is uveitis. 
     
     
         32 . The method of  claim 1 , further comprising administering a therapeutic agent that does not antagonize IL-17 or IL-23 activity, wherein the therapeutic agent is capable of alleviating at least one symptom of the AOID or at least one side effect of the IL-17 antagonist. 
     
     
         33 . The method of  claim 32 , wherein the therapeutic agent is capable of alleviating at least one symptom of the AOID and is a steroid, a non-steroidal anti-inflammatory or a TNF inhibitor. 
     
     
         34 . A method of prophylactically treating a patient who is diagnosed as being susceptible for an autoimmune ocular inflammatory disease (AOID), the method comprising administering to the patient an antagonist selected from the group consisting of an IL-23 antagonist, an IL-17 antagonist and an antagonist of both IL-17 and IL-23. 
     
     
         35 . The method of  claim 34 , wherein the susceptibility diagnosis is based on the patient having a previous incident of ocular inflammation. 
     
     
         36 . The method of  claim 34 , wherein the susceptibility diagnosis is based on the patient having a systemic autoimmune disease. 
     
     
         37 . The method of  claim 36 , wherein the antagonist is a monoclonal antibody or a monoclonal antibody fragment. 
     
     
         38 . The method of  claim 37 , wherein the antagonist is a humanized monoclonal antibody or a fully human monoclonal antibody. 
     
     
         39 . The method of  claim 37 , wherein the antagonist is a humanized monoclonal antibody fragment or a fully human monoclonal antibody fragment. 
     
     
         40 . The method of  claim 37 , wherein the antibody or antibody fragment is pegylated. 
     
     
         41 . The method of  claim 37 , wherein the monoclonal antibody or monoclonal antibody fragment binds to and inhibits the activity of IL-23p19 or IL-23R. 
     
     
         42 . The method of  claim 41 , wherein the monoclonal antibody or monoclonal antibody fragment binds to and inhibits the activity of IL-23p19. 
     
     
         43 . The method of  claim 37 , wherein the monoclonal antibody or monoclonal antibody fragment binds to and inhibits the activity of IL-17 or IL-17RA. 
     
     
         44 . The method of  claim 43 , wherein the monoclonal antibody or monoclonal antibody fragment binds to and inhibits the activity of IL-17. 
     
     
         45 . The method of  claim 34 , wherein a specified dose of the antagonist is administered at a specified interval during a first treatment period. 
     
     
         46 . The method of  claim 45 , wherein the duration of the first treatment period is between three months and two years. 
     
     
         47 . The method of  claim 46 , wherein the duration of the first treatment period is between six months and one year. 
     
     
         48 . The method of  claim 45 , wherein the dose of the antagonist is gradually reduced during a second treatment period that begins upon the end of the first treatment period. 
     
     
         49 . The method of  claim 48 , wherein the duration of the second treatment period is between one month and six months. 
     
     
         50 . A method of treating a patient for an autoimmune ocular inflammatory disease (AOID), comprising administering to the patient an IL-23 antagonist. 
     
     
         51 . The method of  claim 50 , wherein the IL-23 antagonist is a monoclonal antibody or a monoclonal antibody fragment that binds to and inhibits the activity of IL-23p19 or IL-23R. 
     
     
         52 . The method of  claim 50 , wherein a specified dose of the IL-23 antagonist is administered at a specified interval during a first treatment period. 
     
     
         53 . The method of  claim 52 , wherein the duration of the first treatment period is between three months and two years. 
     
     
         54 . The method of  claim 52 , wherein the duration of the first treatment period is between six months and one year. 
     
     
         55 . The method of  claim 52 , wherein the dose of the IL-23 antagonist is gradually reduced during a second treatment period that begins upon the end of the first treatment period. 
     
     
         56 . The method of  claim 52 , wherein the AOID is uveitis. 
     
     
         57 . A manufactured drug product for treating an autoimmune inflammatory disease (AOID), which comprises
 (a) a first pharmaceutical formulation comprising an IL-17 antagonist; and   (b) a second pharmaceutical formulation comprising an IL-23 antagonist.   
     
     
         58 . The manufactured drug product of  claim 57 , which further comprises instructions for administering the pharmaceutical formulations according to the method of any of  claims 15  to  24 . 
     
     
         59 . The manufactured drug product of  claim 58 , wherein the IL-17 antagonist is a monoclonal antibody or monoclonal antibody fragment binds to and inhibits the activity of IL-17 or IL-17RA and the a monoclonal antibody or a monoclonal antibody fragment that binds to and inhibits the activity of IL-23p19 or IL-23R.