Methods of treating chronic disorders with complement inhibitors

Abstract

In some aspects, the invention provides methods of treating a subject in need of treatment for a chronic complement-mediated disorder. In some aspects, the invention provides methods of treating a subject in need of treatment for a Th17-associated disorder. In some aspects, the invention provides methods of treating a subject in need of treatment for a chronic respiratory system disorder. In some aspects, the invention provides methods of administering a complement inhibitor to a subject. In some embodiments, a method of treating a subject comprises administering multiple doses of a complement inhibitor to the subject according to a dosing schedule that leverages the prolonged effect of complement inhibition in chronic respiratory disorders. In some embodiments, a subject has chronic obstructive pulmonary disease. In some embodiments, a subject has asthma.

1 .- 31 . (canceled) 
     
     
         32 . A method of treating a subject in need of treatment for a chronic complement-mediated disorder, the method comprising: (a) administering at least one dose of a complement inhibitor to the subject; and (b) monitoring the subject for a Th17 biomarker in the subject or in a sample obtained from the subject. 
     
     
         33 . The method of  claim 32 , further comprising: (c) administering at least one additional dose of the complement inhibitor to the subject. 
     
     
         34 . The method of  claim 32 , wherein step (b) comprises detecting a Th17 biomarker in the subject or in a sample obtained from the subject. 
     
     
         35 . The method of  claim 32 , wherein step (b) comprises detecting an increased level of the biomarker as compared to a reference, wherein the increased level indicates that the subject is in need of a dose of the complement inhibitor. 
     
     
         36 . The method of  claim 32 , wherein step (b) comprises detecting an increased level of the biomarker as compared to a reference, wherein the increased level indicates that the subject is in need of a dose of the complement inhibitor, and the method further comprises (c) administering at least one additional dose of the complement inhibitor to the subject. 
     
     
         37 . The method of  claim 32 , wherein step (b) comprises detecting an increased level of the biomarker as compared to a reference, wherein the increased level indicates that the subject is in need of a dose of the complement inhibitor, and the method further comprises (c) administering at least one additional dose of the complement inhibitor to the subject within a predetermined time of detecting the biomarker. 
     
     
         38 . The method of  claim 37 , wherein the predetermined time period is 1, 2, 3, 4, 5, 6, or 7 days or 2, 3, or 4 weeks. 
     
     
         39 .- 44 . (canceled) 
     
     
         45 . A pharmaceutical composition comprising a complement inhibitor and an anti-Th17 agent. 
     
     
         46 .- 48 . (canceled) 
     
     
         49 . A method of treating a complement-mediated disorder comprising administering the composition of  claim 45 , to a subject in need thereof. 
     
     
         50 . A method of treating a Th17-associated disorder comprising administering the composition of  claim 45  to a subject in need thereof. 
     
     
         51 .- 55 . (canceled) 
     
     
         56 . A method of treating a subject having or at risk of a complement-mediated disorder, the method comprising monitoring the subject for evidence of a DC-Th17-B-Ab-C-DC cycle and administering a complement inhibitor to the subject based at least in part on a result of said monitoring. 
     
     
         57 . The method of  claim 56 , further comprising administering an anti-Th17 agent to the subject. 
     
     
         58 .- 61 . (canceled) 
     
     
         62 . The method of  claim 56 , wherein the complement inhibitor inhibits C3 activity or C3 activation. 
     
     
         63 . The method of  claim 56 , wherein the complement inhibitor comprises a compstatin analog. 
     
     
         64 . The method of  claim 56 , wherein the anti-Th17 agent comprises an antibody, small molecule, aptamer, or polypeptide that binds to IL-43, IL-6, IL-21, IL-22, IL-17, or IL-23 or binds to receptor for any of the foregoing. 
     
     
         65 . The method of  claim 56 , wherein monitoring the subject for evidence of a DC-Th17-B-Ab-C-DC cycle comprises assessing a Th17-associated biomarker in the subject or in a sample obtained from the subject. 
     
     
         66 . The method of  claim 56 , wherein monitoring occurs approximately every 1-2 weeks, 2-4 weeks, or approximately every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months. 
     
     
         67 . The method of  claim 56 , comprising administering a complement inhibitor, anti-Th17 agent, or both, within no more than 1, 2, 3, 4, 5, 6, or 7 days or 2, 3, or 4 weeks of having detected evidence of a DC-Th17-B-Ab-C-DC cycle or increased level of a Th17-associated biomarker. 
     
     
         68 .- 70 . (canceled)