Injectable combination therapy for eye disorders

Abstract

The present invention provides composition, methods, and articles of manufacture for treating an eye disorder, e.g., a disorder characterized by macular degeneration, choroidal neovascularization, or retinal neovascularization. One method of the invention comprises the step of: administering first and second therapeutic agents to the subject's eye in a single procedure, wherein the first therapeutic agent provides rapid improvement in the condition of the subject's eye and the second therapeutic agent is administered as a sustained release formulation of the second therapeutic agent. For example, the first and second therapeutic agents are administered by intravitreal injection. The first therapeutic agent may be dissolved in a liquid medium located in the syringe and the sustained formulation of the second therapeutic agent may comprise an ocular implant or plurality of particles located in the needle. The therapeutic agents may be selected from the group consisting of angiogenesis inhibitors and complement inhibitors.

1 . A method of treating an eye disorder characterized by macular degeneration, choroidal neovascularization, or retinal neovascularization, the method comprising a step of:
 administering to an eye of a patient who has received anti-VEGF therapy characterized by administration of a plurality of doses of an anti-VEGF agent, which doses are separated from one another by a first dosing interval, a combination therapy regimen according to which the anti-VEGF agent is administered in combination with a compstatin analog or an antibody that binds to C3, C5, factor B, or factor D, and doses of the anti-VEGF agent are separated from one another by a second dosing interval that is longer than the first dosing interval.   
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the anti-VEGF agent and the compstatin analog or antibody that binds to C3, C5, factor B, or factor D are administered in a single procedure. 
     
     
         4 . The method of  claim 1 , wherein the anti-VEGF agent and compstatin analog or antibody that binds to C3, C5, factor B, or factor D are injected into the vitreous of the subject's eye. 
     
     
         5 . The method of  claim 3 , wherein the procedure is an injection procedure in which, prior to administration, the anti-VEGF agent is contained in a syringe and a sustained release formulation comprising the compstatin analog or antibody that binds to C3, C5, factor B, or factor D is contained in a needle attached to the syringe. 
     
     
         6 . The method of  claim 5 , wherein the anti-VEGF agent is dissolved in a liquid medium located in the syringe and the sustained release formulation of the compstatin analog or antibody that binds to C3, C5, factor B, or factor D comprises an ocular implant located in the needle. 
     
     
         7 .- 9 . (canceled) 
     
     
         10 . The method of  claim 1 , wherein the anti-VEGF agent is selected from the group consisting of bevacizumab, ranibizumab, a fusion protein containing extracellular domains of two VEGF receptors connected to the Fc region of an antibody, and pegaptanib. 
     
     
         11 .- 17 . (canceled) 
     
     
         18 . The method of  claim 1 , wherein the anti-VEGF agent is dissolved or suspended in a liquid medium prior to administration. 
     
     
         19 . The method of  claim 1 , wherein the compstatin analog or antibody that binds to C3, C5, factor B, or factor D is administered as a component of a sustained release formulation that comprises an ocular implant. 
     
     
         20 . The method of  claim 1 , wherein the compstatin analog or antibody that binds to C3, C5, factor B, or factor D is administered as a component of a sustained release formulation that comprises a polymeric material. 
     
     
         21 . The method of  claim 20 , wherein the polymeric material is biodegradable. 
     
     
         22 . The method of  claim 20 , wherein the polymeric material is selected from the group consisting of: poly-lactic acid (PLA), poly-glycolic acid (PGA), poly-lactide-co-glycolide (PLGA), poly(phosphazine), poly (phosphate ester), polycaprolactones, polyanhydrides, ethylene vinyl acetate, polyorthoesters, polyethers, poly (beta amino esters), copolymers containing monomeric subunits found in any of the foregoing polymers, collagen, albumin, chitosan, alginate, hyaluronic acid, and mixtures of any of the foregoing polymers. 
     
     
         23 . The method of  claim 1 , wherein the compstatin analog or antibody that binds to C3, C5, factor B, or factor D is administered as a component of a sustained release formulation that comprises nanoparticles, microparticles, dendrimers, or liposomes. 
     
     
         24 . The method of  claim 1 , wherein the compstatin analog or antibody that binds to C3, C5, factor B, or factor D is administered as a component of a sustained release formulation that comprises a solid or semi-solid material that entraps or encapsulates compstatin analog or antibody that binds to C3, C5, factor B, or factor D. 
     
     
         25 . The method of  claim 1 , wherein the compstatin analog or antibody that binds to C3, C5, factor B, or factor D is administered as a component of a sustained release formulation that comprises an inactive material to which the compstatin analog or antibody that binds to C3, C5, factor B, or factor D is covalently attached. 
     
     
         26 . The method of  claim 1 , wherein the anti-VEGF agent is administered in soluble or particulate form in a liquid medium and the compstatin analog or antibody that binds to C3, C5, factor B, or factor D is administered in or attached to a solid or semi-solid matrix. 
     
     
         27 . (canceled) 
     
     
         28 . The method of  claim 1 , wherein administering the compstatin analog or antibody that binds to C3, C5, factor B, or factor D prolongs the time interval during which the subject experiences improvement in the condition of the subject's eye relative to the time interval during which the subject would have experienced improvement if the anti-VEGF agent had been administered as sole therapy. 
     
     
         29 . The method of  claim 1 , wherein the eye disorder is exudative age-related macular degeneration. 
     
     
         30 . The method of  claim 1 , wherein the subject has experienced a perceptible deterioration in the condition of the subject's eye within the two weeks preceding administration of the anti-VEGF agent and compstatin analog or antibody that binds to C3, C5, factor B, or factor D. 
     
     
         31 .- 40 . (canceled) 
     
     
         41 . The method of  claim 19 , wherein the compstatin analog is released from the ocular implant so as to maintain a therapeutic level in the subject's eye over a period of at least 3 months. 
     
     
         42 .- 65 . (canceled)