Antigen-based heteropolymers and method for treating autoimmune diseases using the same

Abstract

Constructs consisting of antigen-based heteropolymers (AHP's) are provided. The antigen-based heteropolymers comprise at least one monoclonal antibody specific for binding to complement receptor (CR1) site on a human or non-human primate erythrocyte, and the anti-CR1 monoclonal antibody is crosslinked to an antigen specific for a target pathogenic autoantibody. Further provided is a method for treating autoimmune diseases in human or non-human primates using the AHP.

What is claimed is:  
     
         1 . An antigen-based heteropolymer (AHP) complex comprising a monoclonal antibody specific for binding to complement receptor (CR1) site on a primate erythrocyte, wherein said monoclonal antibody is crosslinked to an antigen specific for a target pathogenic antibody or autoantibody.  
     
     
         2 . The AHP of  claim 1 , wherein the monoclonal antibodies are selected from the group consisting of 1B4, HB8592, and 7G9.  
     
     
         3 . The AHP of  claim 1 , wherein the target antibody or autoantibody is selected from the group consisting of antibodies or autoantibodies to the following antigens: factor VIII, muscle acetylcholine receptor, cardiolipin, platelet associated proteins, antigens associated with Sjogren's Syndrome, double stranded deoxyribonucleic acid (dsDNA), and single stranded DNA (ssDNA).  
     
     
         4 . The AHP of  claim 1 , wherein said antigen is selected from the group consisting of factor VIII, muscle acetylcholine receptor, cardiolipin, platelet associated proteins, antigens associated with Sjogren's Syndrome, double stranded deoxyribonucleic acid (dsDNA), and single stranded DNA (ssDNA).  
     
     
         5 . An AHP cocktail, comprising at least two AHP's wherein said AHP comprises a monoclonal antibody specific for binding to complement receptor (CR1) site on a primate erythrocyte, and wherein said monoclonal antibody is crosslinked to an antigen specific for a target pathogenic antibody or autoantibody.  
     
     
         6 . A method for treating an autoimmune disease comprising the steps of: 
 1administering to a human or non-human primate a clinically effective amount of an AHP, said AHP comprising a monoclonal antibody specific for complement receptor (CR1) site on a primate erythrocyte, and wherein said monoclonal antibody is crosslinked to an antigen which is specific for a target pathogenic antibody or autoantibody;    2 ) allowing said AHP to bind to at least one competing CR1 site and to said pathogenic antibody or autoantibody; and    3) permitting said bound AHP to be cleared from circulation of said human or non-human primate.    
     
     
         7 . The method of  claim 6 , wherein the monoclonal antibody is selected from the group consisting of 1B4, HB8592, and 7G9.  
     
     
         8 . The AHP of  claim 6 , wherein the target antibody or autoantibody is selected from the group consisting of antibodies or autoantibodies to the following antigens: factor VIII, muscle acetylcholine receptor, cardiolipin, platelet associated proteins, antigens associated with Sjogren's Syndrome, double stranded deoxyribonucleic acid (dsDNA), and single stranded DNA (ssDNA).  
     
     
         9 . The AHP of  claim 6 , wherein said antigen is selected from the group consisting of factor VIII, muscle acetylcholine receptor, cardiolipin, platelet associated proteins, antigens associated with Sjogren's Syndrome, double stranded deoxyribonucleic acid (dsDNA), and single stranded DNA (ssDNA).  
     
     
         10 . The method of  claim 6 , wherein the AHP is administered intravenously to a human or non-human primate in a clinically effective amount.  
     
     
         11 . The method of  claim 10 , wherein said AHP is administered intravenously to a human in a clinically effective amount of 1-10 mg.  
     
     
         12 . The method of  claim 6 , wherein said administration of said clinically effective amount of AHP is repeated until the pathogenic antibody or autoantibody is completely cleared from circulation of said human or non-human primate.  
     
     
         13 . The method of  claim 6 , wherein said target pathogenic antibody or autoantibody is cleared from a circulatory system of a primate and said primate erythrocyte is recirculated through the circulatory system.  
     
     
         14 . A method for treating an autoimmune disease comprising the steps of: 
 1administering to a human or non-human primate an effective amount of an AHP cocktail comprising at least two AHP's, wherein each AHP comprises a monoclonal antibody specific for complement receptor (CR1) site on a primate erythrocyte, and wherein said monoclonal antibody is crosslinked to an antigen which is specific for a target pathogenic antibody or autoantibody;    2 ) allowing said AHP cocktail to bind to at least one competing CR1 site and to said pathogenic antibody or autoantibody; and    3) permitting said bound AHP cocktail to be cleared from circulation of said human or non-human primate.    
     
     
         15 . A method for treating an autoimmune disease comprising the steps of: 
 1franking human or non-human primate erythrocytes with an AHP, said AHP comprising a monoclonal antibody specific for complement receptor (CR1) site on a primate erythrocyte, and wherein said monoclonal antibody is crosslinked to an antigen which is specific for a target pathogenic antibody or autoantibody;    2 ) administering to a human or non-human primate a clinically effective amount of the AHP-franked erythrocytes;    3) allowing said franked AHP to bind to said pathogenic antibody or autoantibody; and    4) permitting said bound AHP to be cleared from circulation of said human or non-human primate.