Antibodies to aripiprazole and use thereof
Disclosed is an antibody which binds to aripiprazole, which can be used to detect aripiprazole 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 aripiprazole, including multiplex detection of aripiprazole, olanzapine, quetiapine, and risperidone in a single lateral flow assay device.
1. An isolated antibody or a binding fragment thereof, which binds to aripiprazole, comprising:
a) a light chain variable region consisting of SEQ ID NO:43 and a heavy chain variable region consisting of SEQ ID NO:44;
b) a light chain variable region consisting of SEQ ID NO:47 and a heavy chain variable region consisting of SEQ ID NO:48;
c) a light chain variable region consisting of SEQ ID NO:51 and a heavy chain variable region consisting of SEQ ID NO:52; or
d) a light chain variable region consisting of SEQ ID NO:55 and a heavy chain variable region consisting of SEQ ID NO:56.
2. The isolated antibody of claim 1 , comprising the light chain variable region consisting of SEQ ID NO:43 and the heavy chain variable region consisting of SEQ ID NO:44.
3. The isolated antibody of claim 1 , comprising the light chain variable region consisting of SEQ ID NO:47 and the heavy chain variable region consisting of SEQ ID NO:48.
4. The isolated antibody of claim 1 , comprising the light chain variable region consisting of SEQ ID NO:51 and the heavy chain variable region consisting of SEQ ID NO:52.
5. The isolated antibody of claim 1 , comprising the light chain variable region consisting of SEQ ID NO:55 and the heavy chain variable region consisting of SEQ ID NO:56.
6. The isolated antibody of claim 1 , comprising:
a) a light chain CDR1 sequence comprising amino acid residues 46 to 55 of SEQ ID NO:43;
b) a light chain CDR2 sequence comprising amino acid residues 71 to 77 of SEQ ID NO:43;
c) a light chain CDR3 sequence comprising amino acid residues 110 to 118 of SEQ ID NO:43;
d) a heavy chain CDR1 sequence comprising amino acid residues 45 to 54 of SEQ ID NO:44;
e) a heavy chain CDR2 sequence comprising amino acid residues 69 to 85 of SEQ ID NO:44; and
f) a heavy chain CDR3 sequence comprising amino acid residues 118 to 125 of SEQ ID NO:44.
7. The isolated antibody of claim 1 , comprising:
a) a light chain CDR1 sequence comprising amino acid residues 44 to 54 of SEQ ID NO:47;
b) a light chain CDR2 sequence comprising amino acid residues 70 to 76 of SEQ ID NO:47;
c) a light chain CDR3 sequence comprising amino acid residues 109 to 117 of SEQ ID NO:47;
d) a heavy chain CDR1 sequence comprising amino acid residues 45 to 54 of SEQ ID NO:48;
e) a heavy chain CDR2 sequence comprising amino acid residues 69 to 85 of SEQ ID NO:48; and
f) a heavy chain CDR3 sequence comprising amino acid residues 118 to 126 of SEQ ID NO:48.
8. The isolated antibody of claim 1 , comprising:
a) a light chain CDR1 sequence comprising amino acid residues 44 to 58 of SEQ ID NO:51;
b) a light chain CDR2 sequence comprising amino acid residues 74 to 80 of SEQ ID NO:51;
c) a light chain CDR3 sequence comprising amino acid residues 113 to 121 of SEQ ID NO:51;
d) a heavy chain CDR1 sequence comprising amino acid residues 45 to 54 of SEQ ID NO:52;
e) a heavy chain CDR2 sequence comprising amino acid residues 69 to 85 of SEQ ID NO:52; and
f) a heavy chain CDR3 sequence comprising amino acid residues 118 to 130 of SEQ ID NO:52.
9. The isolated antibody of claim 1 , comprising:
a) a light chain CDR1 sequence comprising amino acid residues 44 to 54 of SEQ ID NO:55;
b) a light chain CDR2 sequence comprising amino acid residues 70 to 76 of SEQ ID NO:55;
c) a light chain CDR3 sequence comprising amino acid residues 109 to 117 of SEQ ID NO:55;
d) a heavy chain CDR1 sequence comprising amino acid residues 45 to 54 of SEQ ID NO:56;
e) a heavy chain CDR2 sequence comprising amino acid residues 69 to 85 of SEQ ID NO:56; and
f) a heavy chain CDR3 sequence comprising amino acid residues 118 to 122 of SEQ ID NO:56.
10. The isolated antibody of claim 1 , wherein the antibody binding fragment is selected from the group of fragments consisting of Fv, F(ab′), F(ab′)2, scFv, minibody and diabody fragments.
11. The isolated antibody of claim 1 , wherein the isolated antibody is a monoclonal antibody.
12. An assay kit comprising the antibody of claim 1 .
13. An assay device comprising a lateral flow assay device and the antibody of claim 1 , wherein the antibody is disposed on the lateral flow assay device.
14. The assay device of claim 13 , wherein the assay device is a porous lateral flow assay device.
15. The assay device of claim 13 , wherein the assay device is a non-porous lateral flow assay device.
16. A method of detecting aripiprazole in a sample, the method comprising:
(i) contacting the sample with the antibody of claim 1 labeled with a detectable marker, wherein the labeled antibody and aripiprazole present in the sample form a labeled complex; and
(ii) detecting the labeled complex, thereby detecting aripiprazole in the sample.
17. A competitive immunoassay method for detecting aripiprazole in a sample, the method comprising:
(i) contacting the sample with the antibody of claim 1 , and with aripiprazole or a competitive binding partner of aripiprazole, wherein one of the antibody and the aripiprazole or competitive binding partner thereof is labeled with a detectable marker, and wherein sample aripiprazole competes with the aripiprazole or competitive binding partner thereof for binding to the antibody to form a complex;
(ii) detecting the amount of the detectable marker bound to the complex; and
(iii) determining the amount of sample aripiprazole based on the amount of bound detectable marker.
18. The method of claim 16 or 17 , further comprising detecting the presence of one or more analytes in addition to aripiprazole.
19. The method of claim 18 , wherein the one or more analytes are anti-psychotic drugs other than aripiprazole.
20. The method of claim 19 , wherein the anti-psychotic drugs other than aripiprazole are selected from the group consisting of: risperidone, paliperidone, quetiapine, olanzapine, and metabolites thereof.
21. The method of claim 17 , wherein the aripiprazole or competitive binding partner thereof is labeled with the detectable marker.
22. The method of claim 17 , wherein the antibody is labeled with a detectable marker.
23. The method of claim 17 , wherein the immunoassay is performed on a lateral flow assay device and the sample is applied to the device.