Antibodies to paliperidone haptens and use thereof

Abstract

Disclosed is an antibody which binds to paliperidone, which can be used to detect paliperidone in a sample such as in a competitive immunoassay method. The antibody can be used in a lateral flow assay device for point-of-care detection of paliperidone, including multiplex detection of aripiprazole, olanzapine, quetiapine, risperidone and paliperidone in a single lateral flow assay device.

What is claimed is: 
     
         1 . A method of detecting paliperidone in a sample, the method comprising:
 (i) generating an antibody or a binding fragment thereof that binds to paliperidone in response to a conjugate of a compound of Formula I and an immunogenic carrier,   
       
         
           
           
               
               
           
         
         wherein 
         L 1  is OC(O)(CH 2 ) n , or O(CH 2 ) n ; 
         wherein n is 2 or 3; 
         L 2  is NHC(O), 
       
       
         
           
           
               
               
           
         
       
       or absent;
 L 3  is (CH 2 )mCO 2 H, or 
 
       
         
           
           
               
               
           
         
         wherein m is 0, 1, 2, or 3; provided that m may only be 0 if L 2  is absent, and further provided that when L 2  is absent L 3  is 
       
       
         
           
           
               
               
           
         
         (ii) contacting a sample with the antibody or binding fragment thereof labeled with a detectable marker, wherein the labeled antibody or binding fragment and paliperidone present in the sample form a labeled complex; and 
         (iii) detecting the labeled complex so as to detect paliperidone in the sample. 
       
     
     
         2 . A competitive immunoassay method for detecting paliperidone in a sample, the method comprising:
 (i) generating an antibody or a binding fragment thereof that binds to paliperidone in response to a conjugate of a compound of Formula I and an immunogenic carrier,   
       
         
           
           
               
               
           
         
         wherein 
         L 1  is OC(O)(CH 2 ) n , or O(CH 2 ) n ; 
         wherein n is 2 or 3; 
         L 2  is NHC(O), 
       
       
         
           
           
               
               
           
         
       
       or absent;
 L 3  is (CH 2 )mCO 2 H, or 
 
       
         
           
           
               
               
           
         
         wherein m is 0, 1, 2, or 3; provided that m may only be 0 if L 2  is absent, and further provided that when L 2  is absent L 3  is 
       
       
         
           
           
               
               
           
         
         (ii) contacting a sample with the antibody or binding fragment thereof, and with paliperidone or a competitive binding partner of paliperidone, wherein one of the antibody or binding fragment thereof and the paliperidone or competitive binding partner thereof is labeled with a detectable marker, and wherein sample paliperidone competes with the paliperidone or competitive binding partner thereof for binding to the antibody; and 
         (ii) detecting the label so as to detect sample paliperidone. 
       
     
     
         3 . The method of  claim 2 , wherein the paliperidone or competitive binding partner thereof is labeled with the detectable marker. 
     
     
         4 . The method of  claim 2 , wherein the antibody is labeled with a detectable marker. 
     
     
         5 . The method of  claim 2 , wherein the immunoassay is performed on a lateral flow assay device and the sample is applied to the device. 
     
     
         6 . The method of  claim 1 , further comprising detecting the presence of one or more analytes in addition to paliperidone. 
     
     
         7 . The method of  claim 6 , wherein the one or more analytes are anti-psychotic drugs other than paliperidone. 
     
     
         8 . The method of  claim 7 , wherein the anti-psychotic drugs other than paliperidone are selected from the group consisting of: risperidone, aripiprazole, quetiapine, olanzapine, and metabolites thereof. 
     
     
         9 . The method of  claim 1 , wherein the detection of paliperidone is an indication of patient adherence with prescribed paliperidone therapy. 
     
     
         10 . The method of  claim 1 , wherein the detection of paliperidone is used to determine whether a patient should be converted from an oral paliperidone regimen to an injectable anti-psychotic regimen. 
     
     
         11 . The method of  claim 1 , wherein the detection of paliperidone is used to determine if the dose level or dosing interval of oral or injectable paliperidone should be increased or decreased to ensure attainment or maintenance of efficacious or safe drug levels. 
     
     
         12 . The method of  claim 1 , wherein the detection of paliperidone is an aid in the initiation of paliperidone therapy by providing evidence of the attainment of minimum pK levels. 
     
     
         13 . The method of  claim 1 , wherein the detection of paliperidone is used to determine bioequivalence of paliperidone in multiple formulations or from multiple sources. 
     
     
         14 . The method of  claim 1 , wherein the detection of paliperidone is used to assess the impact of polypharmacy and potential drug-drug interactions. 
     
     
         15 . The method of  claim 1 , wherein the detection of paliperidone is an indication that a patient should be excluded from or included into a clinical trial and is an aid in the subsequent monitoring of adherence to clinical trial medication requirements. 
     
     
         16 . The method of  claim 2 , further comprising detecting the presence of one or more analytes in addition to paliperidone. 
     
     
         17 . The method of  claim 16 , wherein the one or more analytes are anti-psychotic drugs other than paliperidone. 
     
     
         18 . The method of  claim 17 , wherein the anti-psychotic drugs other than paliperidone are selected from the group consisting of: risperidone, aripiprazole, quetiapine, olanzapine, and metabolites thereof. 
     
     
         19 . The method of  claim 2 , wherein the detection of paliperidone is an indication of patient adherence with prescribed paliperidone therapy. 
     
     
         20 . The method of  claim 2 , wherein the detection of paliperidone is used to determine whether a patient should be converted from an oral paliperidone regimen to an injectable anti-psychotic regimen. 
     
     
         21 . The method of  claim 2 , wherein the detection of paliperidone is used to determine if the dose level or dosing interval of oral or injectable paliperidone should be increased or decreased to ensure attainment or maintenance of efficacious or safe drug levels. 
     
     
         22 . The method of  claim 2 , wherein the detection of paliperidone is an aid in the initiation of paliperidone therapy by providing evidence of the attainment of minimum pK levels. 
     
     
         23 . The method of  claim 2 , wherein the detection of paliperidone is used to determine bioequivalence of paliperidone in multiple formulations or from multiple sources. 
     
     
         24 . The method of  claim 2 , wherein the detection of paliperidone is used to assess the impact of polypharmacy and potential drug-drug interactions. 
     
     
         25 . The method of  claim 2 , wherein the detection of paliperidone is an indication that a patient should be excluded from or included into a clinical trial and is an aid in the subsequent monitoring of adherence to clinical trial medication requirements.