ANTIBODIES TO OLANZAPINE AND USE THEREOF

• US 20190315885A1
• Filed: 06/17/2019
• Published: 10/17/2019
• Est. Priority Date: 08/21/2012
• Status: Active Grant

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Hryhorenko, Eric, Sankaran, Banumathi, DeCory, Thomas R., Tubbs, Theresa, Colt, Linda, Remmerie, Bart M., Salter, Rhys, Donahue, Matthew G., Gong, Yong
• Granted Patent: US 11,046,786 B2
• Time in Patent Office: Days
• CPC Class Codes: C07K 16/44 against material not provided for elsewhere , e.g. haptens, metals, DNA, RNA, amino acids
• CPC Class Codes: C07K 2317/54 F(ab')2
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/626 Diabody or triabody
• CPC Class Codes: G01N 2800/302 Schizophrenia
• CPC Class Codes: G01N 33/94 involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors

Abstract

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

Claims

1. An isolated antibody or a binding fragment thereof, which binds to olanzapine, comprising:

a) a light chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO;

11 and a heavy chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO;

12;

b) a light chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO;

15 and a heavy chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO;

16;

c) a light chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO;

31 and a heavy chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO;

32;

d) a light chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO;

35 and a heavy chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO;

36;

or

e) a light chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO;

39 and a heavy chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO;

40, and

wherein the antibody comprises the CDR1, CDR2, and CDR3 regions of the light chain variable region and the CDR1, CDR2, and CDR3 regions of the heavy chain variable region.

2. The isolated antibody of claim 1, comprising the light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:

11 and the heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO;

12.

3. The isolated antibody of claim 1, comprising the light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:

15 and the heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO;

16.

4. The isolated antibody of claim 1, comprising the light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:

31 and the heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO;

32.

5. The isolated antibody of claim 1, comprising the light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:

35 and the heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO;

36.

6. The isolated antibody of claim 1, comprising the light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:

39 and the heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO;

40.

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;

11;

b) a light chain CDR2 sequence comprising amino acid residues 70 to 76 of SEQ ID NO;

11;

c) a light chain CDR3 sequence comprising amino acid residues 109 to 117 of SEQ ID NO;

11;

d) a heavy chain CDR1 sequence comprising amino acid residues 45 to 54 of SEQ ID NO;

12;

e) a heavy chain CDR2 sequence comprising amino acid residues 69 to 85 of SEQ ID NO;

12; and

f) a heavy chain CDR3 sequence comprising amino acid residues 118 to 122 of SEQ ID NO;

12.

8. The isolated antibody of claim 1, comprising:

a) a light chain CDR1 sequence comprising amino acid residues 44 to 54 of SEQ ID NO;

15;

b) a light chain CDR2 sequence comprising amino acid residues 70 to 76 of SEQ ID NO;

15;

c) a light chain CDR3 sequence comprising amino acid residues 109 to 117 of SEQ ID NO;

15;

d) a heavy chain CDR1 sequence comprising amino acid residues 45 to 54 of SEQ ID NO;

16;

e) a heavy chain CDR2 sequence comprising amino acid residues 69 to 85 of SEQ ID NO;

16; and

f) a heavy chain CDR3 sequence comprising amino acid residues 118 to 122 of SEQ ID NO;

16.

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;

31;

b) a light chain CDR2 sequence comprising amino acid residues 70 to 76 of SEQ ID NO;

31;

c) a light chain CDR3 sequence comprising amino acid residues 109 to 117 of SEQ ID NO;

31;

d) a heavy chain CDR1 sequence comprising amino acid residues 44 to 54 of SEQ ID NO;

32;

e) a heavy chain CDR2 sequence comprising amino acid residues 69 to 84 of SEQ ID NO;

32; and

f) a heavy chain CDR3 sequence comprising amino acid residues 119 to 127 of SEQ ID NO;

32.

10. The antibody of claim 1, comprising:

a) a light chain CDR1 sequence comprising amino acid residues 44 to 54 of SEQ ID NO;

35;

b) a light chain CDR2 sequence comprising amino acid residues 70 to 76 of SEQ ID NO;

35;

c) a light chain CDR3 sequence comprising amino acid residues 109 to 117 of SEQ ID NO;

35;

d) a heavy chain CDR1 sequence comprising amino acid residues 45 to 54 of SEQ ID NO;

36;

e) a heavy chain CDR2 sequence comprising amino acid residues 69 to 87 of SEQ ID NO;

36; and

f) a heavy chain CDR3 sequence comprising amino acid residues 120 to 127 of SEQ ID NO;

36.

11. The isolated antibody of claim 1, comprising:

a) a light chain CDR1 sequence comprising amino acid residues 44 to 54 of SEQ ID NO;

39;

b) a light chain CDR2 sequence comprising amino acid residues 70 to 76 of SEQ ID NO;

39;

c) a light chain CDR3 sequence comprising amino acid residues 109 to 117 of SEQ ID NO;

39;

d) a heavy chain CDR1 sequence comprising amino acid residues 44 to 54 of SEQ ID NO;

40;

e) a heavy chain CDR2 sequence comprising amino acid residues 69 to 84 of SEQ ID NO;

40; and

f) a heavy chain CDR3 sequence comprising amino acid residues 120 to 127 of SEQ ID NO;

40.

12. 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.

13. The antibody of claim 1, wherein the antibody is a monoclonal antibody.

14. An assay kit comprising the antibody of claim 1.

15. 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.

16. The assay device of claim 15, wherein the assay device is a porous lateral flow assay device.

17. The assay device of claim 15, wherein the assay device is a non-porous lateral flow assay device.

18. A method of detecting olanzapine 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 olanzapine present in the sample form a labeled complex; and

(ii) detecting the labeled complex, thereby detecting olanzapine in the sample.

19. A competitive immunoassay method for detecting olanzapine in a sample, the method comprising:

(i) contacting the sample with the antibody of claim 1, and with olanzapine or a competitive binding partner of olanzapine, wherein one of the antibody and the olanzapine or competitive binding partner thereof is labeled with a detectable marker, wherein sample olanzapine competes with the olanzapine 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 olanzapine based on the amount of bound detectable marker.

20. The method of claim 18 or 19, further comprising detecting the presence of one or more analytes in addition to olanzapine.

21. The method of claim 20, wherein the one or more analytes are anti-psychotic drugs other than olanzapine.

22. The method of claim 21, wherein the anti-psychotic drugs other than olanzapine are selected from the group consisting of:

risperidone, paliperidone, quetiapine, aripiprazole, and metabolites thereof.

23. The method of claim 19, wherein the olanzapine or competitive binding partner thereof is labeled with the detectable marker.

24. The method of claim 19, wherein the antibody is labeled with a detectable marker.

25. The method of claim 16, wherein the immunoassay is performed on a lateral flow assay device and the sample is applied to the device.