Methods of treating lupus based on antibody affinity and screening methods and compositions for use thereof

Abstract

The invention provides methods identifying individuals suitable for treatment for lupus and methods of monitoring treatment, based on measuring antibody affinities, as well as of treating lupus based on measuring antibody affinities. The treatment entails administration of a conjugate comprising a non-immunogenic valency platform molecule and at least two double stranded DNA epitopes, such as DNA molecules, which bind to anti-DNA antibodies from the patient.

1 . A method of treating systemic lupus erythematosus (SLE) in an individual, comprising administering to the individual a conjugate comprising (a) a non-immunogenic valency platform molecule and (b) two or more double stranded DNA (dsDNA) epitopes which specifically bind to an antibody from the individual which specifically binds to double stranded DNA, wherein affinity of the dsDNA epitope for the antibody from the individual is used as a basis for selecting the individual to receive or continue to receive the treatment.  
     
     
         2 . The method of  claim 1 , wherein the dsDNA epitopes are polynucleotides.  
     
     
         3 . The method of  claim 2 , wherein the polynucleotides are double stranded DNA.  
     
     
         4 . A method of treating SLE in an individual, comprising administering to the individual a conjugate comprising (a) a non-immunogenic valency platform molecule and (b) two or more polynucleotides which specifically bind to an antibody from the individual which specifically binds to double stranded DNA, said polynucleotide consisting essentially of the sequence 5′-GTGTGTGTGTGTGTGTGTGT-3′, wherein the apparent equilibrium dissociation constant (K D ′) for the polynucleotide with respect to the antibody from the individual before or upon initiation of treatment is less than about 1.0 mg IgG per ml, and wherein said K D ′ value or a functional equivalent thereof is used as a basis for selecting the individual to receive the treatment.  
     
     
         5 . The method of  claim 4 , wherein the K D ′ is less than about 0.8.  
     
     
         6 . The method of  claim 4 , wherein the K D ′ is less than about 0.5.  
     
     
         7 . The method of  claim 4 , wherein the K D ′ is less than about 0.2.  
     
     
         8 . The method of  claim 4 , wherein the platform molecule is  
       
         
           
           
               
               
           
         
         wherein PN is the polynucleotide.  
       
     
     
         9 . The method of  claim 5 , wherein the polynucleotide consists of the sequence 5′-GTGTGTGTGTGTGTGTGTGT-3′.  
     
     
         10 . The method of  claim 9 , wherein the platform molecule is  
       
         
           
           
               
               
           
         
         wherein PN is the polynucleotide.  
       
     
     
         11 . The method of  claim 9 , wherein the K D ′ is less than about 0.5.  
     
     
         12 . A method of treating SLE in an individual comprising: 
 (a) assessing affinity of an anti-double stranded DNA antibody from the individual with respect to a dsDNA epitope which is to be used in treatment, wherein the individual is selected for treatment based on said antibody affinity; and    (b) administering to said selected individual a conjugate comprising (a) a non-immunogenic valency platform molecule and (b) two or more of the dsDNA epitopes.    
     
     
         13 . The method of  claim 12 , wherein the dsDNA epitope is a polynucleotide.  
     
     
         14 . The method of  claim 13 , wherein the polynucleotide is double stranded DNA.  
     
     
         15 - 64 . (canceled)