Targeted apheresis for the treatment of rheumatoid arthritis and immune disorders

Abstract

This invention uses “Targeted Apheresis” to treat patients with Rheumatoid Arthritis and other autoimmune and inflammatory disorders. “Targeted Apheresis” is a process whereby only the pathogenic and pro-inflammatory elements associated with the disease symptoms are simultaneously and selectively removed from the blood by passing the blood through an extracorporeal affinity device containing selective binding agents. Removal of these pathogenic and pro-inflammatory elements will ameliorate the symptoms of autoimmune disease and may prolong the period of disease remission.

What is claimed is: 
     
         1 . A means of selectively removing pathological, pro-inflammatory and disease inciting factors from the blood of patients with rheumatoid arthritis and other autoimmune diseases using targeted apheresis. 
     
     
         2 . According to  claim 1  the targeted apheresis process for treating RA patients employs an extracorporeal affinity device containing two or more immobilized binding agents selected from the list of: “altered IgG” agarose beads, “altered IgG” binding agent agarose beads; TNF-alpha binding agent agarose beads, and IL-1 binding agent agarose beads. 
     
     
         3 . According to  claim 2  an affinity device composed of a chamber with an inlet and an outlet aperture and top and bottom filters containing within two or more layers of immobilized binding agents conjugated to agarose beads. Each layer is separated from the other by filters that allow through passage of plasma through the device. Each compartment contains a specific binding layer selected from the list of: “altered IgG” agarose beads, “altered IgG” binding agent agarose beads; TNF-alpha binding agent agarose beads, and IL-1 binding agent agarose beads. 
     
     
         4 . According to  claim 2  an affinity device composed of a chamber with an inlet and an outlet aperture and top and bottom filters containing within a single mixed bed of two or more different immobilized binding agents conjugated to agarose beads selected from the list of: “altered IgG” agarose beads, “altered IgG” binding agent agarose beads; TNF alpha binding agent agarose beads, and IL-1 binding agent agarose beads. 
     
     
         5 . According to  claims 2  the “altered IgG” is prepared from heat-denatured purified human IgG. 
     
     
         6 . According to  claims 2  the “altered IgG” binding agent is either an anti-“altered IgG” polyclonal antibody prepared in immunized animals; or an anti-“altered IgG” monoclonal antibody prepared in murine:human or human:human hybridomas; or purified human IgM rheumatoid factor obtained from patients with RA; or an anti-“altered IgG” aptamer prepared using the SELEX method. 
     
     
         7 . According to  claims 2  the TNF-alpha binding agent is either an anti-TNF-alpha polyclonal antibody prepared in immunized animals; or an anti-TNF-alpha monoclonal antibody prepared in murine:human or human:human hybridomas; or a recombinant human TNF receptor protein prepared using genetic engineering techniques; or an anti-TNF-alpha aptamer prepared using the SELEX method. 
     
     
         8 . According to  claim 2  the IL-1 binding agent is either an anti-IL-1 polyclonal antibody prepared in immunized animals; or an anti-IL-1 monoclonal antibody prepared in murine:human or human:human hybridomas; or a recombinant human IL-1 receptor protein prepared using genetic engineering techniques; or an anti-IL-1 aptamer prepared using the SELEX method. 
     
     
         9 . According to  claim 2  the binding agents are immobilized by chemically conjugating them to an insoluble support matrix such as cross-linked agarose beads. 
     
     
         10 . A method of targeted apheresis for treating patients with systemic lupus erythematosus (SLE) using an extracorporeal affinity device containing two or more immobilized binding agents selected from the list of: immobilized nuclear extract agarose beads; “altered IgG” binding agent agarose beads; TNF-alpha binding agent agarose beads, and IL-1 binding agent agarose beads. 
     
     
         11 . A method of targeted apheresis for treating patients with myasthenia gravis (MG) using an extracorporeal affinity device containing two or more immobilized binding agents selected from the list of: immobilized anti-acetylcholine antibody binding agent agarose beads; immobilized TNF-alpha binding agent agarose beads; and immobilized IL-1 binding agent agarose beads. 
     
     
         12 . According to  claim 11  the anti-acetylcholine antibody binding agent is either immobilized acetylcholine receptor agarose beads, or immobilized receptor mimetic peptide agarose beads, or immobilized receptor mimetic aptamer agarose beads; 
     
     
         13 . A method of targeted apheresis for treating osteoarthritis patients using an extracorporeal affinity device containing two or more immobilized binding agents selected from the list of: “altered IgG” agarose beads, “altered IgG” binding agent agarose beads; TNF-alpha binding agent agarose beads, and IL-1 binding agent agarose beads.