Antibodies to quetiapine haptens and use thereof

Abstract

Disclosed is an antibody which binds to quetiapine, which can be used to detect quetiapine 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 quetiapine, including multiplex detection of aripiprazole, olanzapine, quetiapine, and risperidone in a single lateral flow assay device.

1 - 14 . (canceled) 
     
     
         15 . An isolated antibody or a binding fragment thereof, which specifically binds to quetiapine, and is generated in response to a conjugate of a compound of Formula I: 
       
         
           
           
               
               
           
         
         wherein: 
       
       R 1 H, 
       
         
           
           
               
               
           
         
       
       R 2 H, 
       R 3 H, 
       
         
           
           
               
               
           
         
       
       m is 1, 2, 3, 4, or 5, and 
       n is 1, 2, 3, 4, or 5,
 wherein either R 1  or R 2  is H, and both R 1  and R 2  may not simultaneously be H, and 
 wherein the immunogenic carrier is conjugated to the compound of Formula I at R 1  when R 1  is not H, or at R 2  when R 2  is not H. 
 
     
     
         16 . The isolated antibody or the binding fragment of  claim 15 , wherein
 R 1 H, or   
       
         
           
           
               
               
           
         
       
       and
 R 2  is H, or 
 
       
         
           
           
               
               
           
         
       
     
     
         17 . The isolated antibody or the binding fragment of  claim 15 , wherein R 1  is H, or 
       
         
           
           
               
               
           
         
       
       and
 R 2  is H, or 
 
       
         
           
           
               
               
           
         
       
     
     
         18 . The isolated antibody or the binding fragment of  claim 16 , wherein the compound of Formula I is selected from a group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         19 . The isolated antibody or the binding fragment of  claim 15 , wherein the compound is N-((4-(Dibenzo[b,f][1,4]thiazepin-11-yl)-1-(2-(2-hydroxyethoxy)ethyl)piperazin-2-yl)methyl)-2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetamide. 
     
     
         20 . The isolated antibody or the binding fragment of  claim 15 , wherein the compound is 2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-((11-(4-(2-(2-hydroxyethoxy)ethyl)piperazin-1-yl)dibenzo[b,f][1,4]thiazepin-3-yl)methyl)acetamide. 
     
     
         21 . The isolated antibody or the binding fragment of  claim 15 , wherein the immunogenic carrier is a protein. 
     
     
         22 . The isolated antibody or the binding fragment of  claim 21 , wherein the protein is selected from a group consisting of keyhole limpet hemocyanin, bovine thyroglobulin, and ovalbumin. 
     
     
         23 . The isolated antibody or the binding fragment of  claim 21 , wherein the immunogenic carrier is a thiol-activated protein. 
     
     
         24 . The isolated antibody or the binding fragment of  claim 23 , wherein the thiol-activated protein comprises a nucleophilic sulfhydryl group. 
     
     
         25 . The isolated antibody or the binding fragment of  claim 15 , wherein the conjugate is selected from a group consisting of:
 N-((4-(dibenzo[b,f][1,4]thiazepin-11-yl)-1-(2-(2-hydroxyethoxy)ethyl)piperazin-2-yl)methyl)-2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetamide-bovine thyroglobulin-conjugate,   2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-((11-(4-(2-(2-hydroxyethoxy)ethyl)piperazin-1-yl)dibenzo[b,f][1,4]thiazepin-3-yl)methyl)acetamide-bovine thyroglobulin-conjugate,   N-((4-(dibenzo[b,f][1,4]thiazepin-11-yl)-1-(2-(2-hydroxyethoxy)ethyl)piperazin-2-yl)methyl)-2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetamide-keyhole limpet hemocyanin-conjugate, and   2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-((11-(4-(2-(2-hydroxyethoxy)ethyl)piperazin-1-yl)dibenzo[b,f][1,4]thiazepin-3-yl)methyl)acetamide-keyhole limpet hemocyanin-conjugate.   
     
     
         26 . The isolated antibody or the binding fragment of  claim 15 , wherein the binding fragment is selected from the group of fragments consisting Fv, F(ab′), F(ab′)2, scFv, minibody and diabody fragments. 
     
     
         27 . The isolated antibody or the binding fragment of  claim 15 , wherein the antibody is a monoclonal antibody. 
     
     
         28 . An assay kit comprising the antibody or the binding fragment thereof of  claim 15 . 
     
     
         29 . An assay device comprising the antibody or the binding fragment thereof of  claim 15 . 
     
     
         30 . The assay device of  claim 25 , wherein the device is a lateral flow assay device. 
     
     
         31 . A method of detecting quetiapine in a sample comprising
 (a) contacting a sample with the antibody or the binding fragment thereof of  claim 15  labeled with a detectable marker, wherein the labeled antibody or the labeled binding fragment and quetiapine present in the sample form a labeled complex; and   (b) detecting the labeled complex so as to detect quetiapine in the sample.   
     
     
         32 . A competitive immunoassay method for detecting quetiapine in a sample comprising:
 (a) contacting a sample with the antibody or the binding fragment thereof of  claim 15 , and with quetiapine or a competitive binding partner of quetiapine, wherein one of the antibody or the binding fragment thereof and the quetiapine or the competitive binding partner thereof is labeled with a detectable marker, and wherein quetiapine in the sample competes with the quetiapine or competitive binding partner thereof for binding to the antibody or the binding fragment thereof; and   (b) detecting the label so as to detect quetiapine in the sample.   
     
     
         33 . The method of  claim 32 , wherein the quetiapine or competitive binding partner thereof is labeled with the detectable marker. 
     
     
         34 . The method of  claim 32 , wherein the antibody or the binding fragment thereof is labeled with a detectable marker.