Local complement inhibition for treatment of complement-mediated disorders

Abstract

The present invention features the local administration of complement inhibitors for treatment of complement-mediated disorders. In certain embodiments the invention features inhibiting activation of one or more locally produced complement proteins. The invention provides sustained release formulations and devices comprising a complement inhibitor and methods of use thereof.

1 . A method of treating a complement-mediated disorder comprising the step of: administering a complement inhibitor directly to an extravascular location that is a site of local complement activation in said disorder. 
     
     
         2 .- 6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein said complement inhibitor inhibits cleavage of a complement component selected from the group consisting of: C3, C5, and factor B. 
     
     
         8 . The method of  claim 1 , wherein said complement inhibitor binds to a complement component selected from the group consisting of: C3, C5, factor B, and factor D. 
     
     
         9 . The method of  claim 1 , wherein said complement inhibitor is a peptide, small molecule, or aptamer. 
     
     
         10 . The method of  claim 1 , wherein said complement inhibitor is an antibody. 
     
     
         11 . The method of  claim 1 , wherein said complement inhibitor is a compstatin analog. 
     
     
         12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein said extravascular location is within a joint. 
     
     
         14 . The method of  claim 1 , wherein said extravascular location is within the spinal canal. 
     
     
         15 . The method of  claim 1 , wherein said extravascular location is on or in the skin. 
     
     
         16 .- 18 . (canceled) 
     
     
         19 . The method of  claim 1 , wherein said effective amount has essentially no effect on systemic complement activation when administered at said extravascular location. 
     
     
         20 .- 55 . (canceled) 
     
     
         56 . A method of treating a complement-mediated disorder of the nervous system comprising administering a complement inhibitor to a region of the nervous system by a route selected from the group consisting of: intrathecal, intranasal, and by local injection into a nerve sheath. 
     
     
         57 . The method of  claim 56 , wherein said complement inhibitor is a peptide or antibody that binds to a locally produced soluble complement protein. 
     
     
         58 . The method of  claim 56 , wherein said complement inhibitor is a compstatin analog. 
     
     
         59 .- 63 . (canceled) 
     
     
         64 . A method of treating a skin condition comprising administering a complement inhibitor directly to the skin, wherein said complement inhibitor is administered in an amount effective to inhibit activation of a locally produced soluble complement component or in an amount effective to inhibit local activation of complement and is not sufficient to significantly inhibit systemic complement activation when administered directly to the skin. 
     
     
         65 . The method of  claim 64 , wherein said complement inhibitor is a compstatin analog. 
     
     
         66 . (canceled) 
     
     
         67 . The method of  claim 64 , wherein said skin condition is selected from the group consisting of: psoriasis, pemphigus, scleroderma, and lupus. 
     
     
         68 . The method of  claim 64 , wherein said complement inhibitor is administered as a component of a cream, paste, ointment, gel, or lotion. 
     
     
         69 .- 104 . (canceled) 
     
     
         105 . A method of treating an ocular disorder characterized by macular degeneration and/or inflammation comprising administering an effective amount of an anti-TNFα agent to a subject in need thereof. 
     
     
         106 . The method of  claim 105 , wherein the anti-TNFα agent comprises an antibody or soluble TNF receptor. 
     
     
         107 . The method of  claim 105 , wherein the anti-TNFα agent is locally administered to the eye. 
     
     
         108 . The method of  claim 105 , wherein the ocular disorder is AMD, diabetic retinopathy, uveitis, or glaucoma. 
     
     
         109 .- 127 . (canceled)