IP Library › Granted Patent US 7,371,829
Granted Patent B2
US 7,371,829 · App. 10/355,348 · Granted May 13, 2008

Haptens, immunogens, antibodies and conjugates to ketamine and its metabolites

View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 7,371,829
App. No.
10/355,348
Granted
May 13, 2008
Kind
B2
Abstract

The invention provides haptens, immunogens comprising such haptens coupled to an antigenicity-conferring carrier material, conjugates comprising such haptens bonded to a labelling agent as well as, antibodies raised against such immunogens and capable of binding with ketamine and its primary metabolite, norketamine.

Claims (84)

1. An antibody for use in a method for detecting ketamine and norketamine, said antibody possessing a cross-reactivity of 100-175% for norketamine and a cross-reactivity of 100% for ketamine, wherein said antibody is raised against an immunogen comprising a norketamine hapten, wherein said norketamine hapten is derivatised with a crosslinker at the nitrogen of the norketamine, wherein the norketamine hapten has the following structural formula:

wherein R is a bivalent link and X is a terminal group, wherein R is an alkylene moiety; and X is selected from the group comprising a carboxylic acid or an ester thereof, an amine, a maleimide, a halocarboxylic acid or an ester thereof, an aldehyde, a dithiopyridyl moiety, a vinylsulphone moiety or a thiocarboxylic acid or an ester thereof and said antibody binds at least one structural epitope of each of norketamine and ketamine.

2. The antibody of claim 1 , wherein the structural epitope is an arylcyclohexanone moiety.

3. The antibody of claim 2 , wherein the structural epitope is a chlorophenylcyclohexanone moiety.

4. A process of preparing the antibody of claim 1 , the process comprising the steps of:

immunizing an animal by repeated administration of an immunogen comprising a norketamine hapten wherein said norketamine hapten is derivatised with a crosslinker at the nitrogen of the norketamine, wherein the norketamine hapten has the following structural formula:

wherein R is a bivalent link and X is a terminal group, wherein R is an alkylene moiety; and X is selected from the group comprising a carboxylic acid or an ester thereof, an amine, a maleimide, a halocarboxylic acid or an ester thereof, an aldehyde, a dithiopyridyl moiety, a vinylsulphone moiety or a thiocarboxylic acid or an ester thereof; and

collecting the resulting serum from the immunized animal.

5. A process of preparing the antibody of claim 1 , the process comprising the steps of:

immunizing a vertebrate animal by repeated administration of an immunogen comprising a norketamine hapten wherein said norketamine hapten is derivatised with a crosslinker at the nitrogen of the norketamine, wherein the norketamine hapten has the following structural formula:

wherein R is a bivalent link and X is a terminal group, wherein R is an alkylene moiety; and X is selected from the group comprising a carboxylic acid or an ester thereof, an amine, a maleimide, a halocarboxylic acid or an ester thereof, an aldehyde, a dithiopyridyl moiety, a vinylsulphone moiety or a thiocarboxylic acid or an ester thereof; and

collecting the resulting serum from the immunized animal.

6. A process of preparing the antibody of claim 1 , the process comprising the steps of:

immunizing a mammalian animal by repeated administration of an immunogen comprising a norketamine hapten wherein said norketamine hapten is derivatised with a crosslinker at the nitrogen of the norketamine, wherein the norketamine hapten has the following structural formula:

wherein R is a bivalent link and X is a terminal group, wherein R is an alkylene moiety; and X is selected from the group comprising a carboxylic acid or an ester thereof, an amine, a maleimide, a halocarboxylic acid or an ester thereof, an aldehyde, a dithiopyridyl moiety, a vinylsulphone moiety or a thiocarboxylic acid or an ester thereof; and

collecting the resulting serum from the immunized animal.

7. A method for detecting ketamine and norketamine in a sample, the method comprising;

contacting the sample with at least one conjugate comprising a norketamine hapten covalently bonded to a detectable labelling agent, wherein said norketamine hapten is derivatised with a crosslinker at the nitrogen of the norketamine, wherein the norketamine hapten has the following structural formula:

wherein R is a bivalent link and X is a terminal group, wherein R is an alkylene moiety; and X is selected from the group comprising a carboxylic acid or an ester thereof, an amine, a maleimide, a halocarboxylic acid or an ester thereof, an aldehyde, a dithiopyridyl moiety, a vinylsulphone moiety or a thiocarboxylic acid or an ester thereof and at least one antibody of claim 1 ;

detecting bound conjugate; and

deducing from a calibration curve the presence of ketamine and norketamine in the sample.

8. A method for detecting ketamine and norketamine in a sample, the method comprising:

contacting the sample with at least one conjugate comprising a norketamine hapten covalently bonded to a detectable labelling agent, wherein said norketamine hapten is derivatised with a crosslinker at the nitrogen of the norketamine, wherein the norketamine hapten has the following structural formula:

wherein R is a bivalent link and X is a terminal group, wherein R is an alkylene moiety; and X is selected from the group comprising a carboxylic acid or an ester thereof, an amine, a maleimide, a halocarboxylic acid or an ester thereof, an aldehyde, a dithiopyridyl moiety, a vinylsulphone moiety or a thiocarboxylic acid or an ester thereof and at least one antibody of claim 2 ;

detecting bound conjugate; and

deducing from a calibration curve the presence of ketamine and norketamine in the sample.

9. A method for detecting ketamine and norketamine in a sample, the method comprising:

contacting the sample with at least one conjugate comprising a norketamine hapten covalently bonded to a detectable labelling agent, wherein said norketamine hapten is derivatised with a crosslinker at the nitrogen of the norketamine, wherein the norketamine hapten has the following structural formula:

wherein R is a bivalent link and X is a terminal group, wherein R is an alkylene moiety; and X is selected from the group comprising a carboxylic acid or an ester thereof, an amine, a maleimide, a halocarboxylic acid or an ester thereof, an aldehyde, a dithiopyridyl moiety, a vinylsulphone moiety or a thiocarboxylic acid or an ester thereof and at least one antibody of claim 3 ;

detecting bound conjugate; and

deducing from a calibration curve the presence of ketamine and norketamine in the sample.

10. A kit for use in a method for detecting ketamine and norketamine, the kit comprising:

at least one conjugate comprising a norketamine hapten covalently bonded to a detectable labelling agent, wherein said norketamine hapten is derivatised with a crosslinker at the nitrogen of the norketamine, wherein the norketamine hapten has the following structural formula:

wherein R is a bivalent link and X is a terminal group, wherein R is an alkylene moiety; and X is selected from the group comprising a carboxylic acid or an ester thereof, an amine, a maleimide, a halocarboxylic acid or an ester thereof, an aldehyde, a dithiopyridyl moiety, a vinylsulphone moiety or a thiocarboxylic acid or an ester thereof; and

at least one antibody of claim 1 .

11. A kit for use in a method for detecting ketamine and norketamine, the kit comprising:

at least one conjugate comprising a norketamine hapten covalently bonded to a detectable labelling agent, wherein said norketamine hapten is derivatised with a crosslinker at the nitrogen of the norketamine, wherein the norketamine hapten has the following structural formula:

wherein R is a bivalent link and X is a terminal group, wherein R is an alkylene moiety; and X is selected from the group comprising a carboxylic acid or an ester thereof, an amine, a maleimide, a halocarboxylic acid or an ester thereof, an aldehyde, a dithiopyridyl moiety, a vinylsulphone moiety or a thiocarboxylic acid or an ester thereof; and at least one antibody of claim 2 .

12. A kit for use in a method for detecting ketamine and norketamine, the kit comprising:

at least one conjugate comprising a norketamine hapten covalently bonded to a detectable labelling agent, wherein said norketamine hapten is derivatised with a crosslinker at the nitrogen of the norketamine, wherein the norketamine hapten has the following structural formula:

wherein R is a bivalent link and X is a terminal group, wherein R is an alkylene moiety; and X is selected from the group comprising a carboxylic acid or an ester thereof, an amine, a maleimide, a halocarboxylic acid or an ester thereof, an aldehyde, a dithiopyridyl moiety, a vinylsulphone moiety or a thiocarboxylic acid or an ester thereof; and

at least one antibody of claim 3 .

13. The method of claim 7 , wherein said sample is a biological fluid.

14. The antibody of claim 1 , wherein said antibody is polyclonal.

15. An antibody for use in a method of detecting ketamine and norketamine, said antibody possessing a cross-reactivity of 100-175% for norketamine and a cross-reactivity of 100% for ketamine, wherein said antibody is raised against an immunogen comprising a norketamine hapten wherein said norketamine hapten is coupled to an antigenicity-conferring carrier material, wherein said norketamine hapten is derivatised with a crosslinker at the nitrogen of the norketamine, wherein the norketamine hapten has the following structural formula:

wherein R is a bivalent link and X is a terminal group, wherein R is an alkylene moiety; and X is selected from the group comprising a carboxylic acid or an ester thereof, an amine, a maleimide, a halocarboxylic acid or an ester thereof, an aldehyde, a dithiopyridyl moiety, a vinylsulphone moiety or a thiocarboxylic acid or an ester thereof, wherein said antibody binds at least one structural epitope of each of norketamine and ketamine.

16. A method for detecting ketamine and norketamine in a sample, the method comprising:

contacting the sample with at least one conjugate comprising a norketamine hapten covalently bonded to a detectable labelling agent, wherein said norketamine hapten is derivatised with a crosslinker at the nitrogen of the norketamine, wherein the norketamine hapten has the following structural formula:

wherein R is a bivalent link and X is a terminal group, wherein R is an alkylene moiety; and X is

selected from the group comprising a carboxylic acid or an ester thereof, an amine, a maleimide, a halocarboxylic acid or an ester thereof, an aldehyde, a dithiopyridyl moiety, a vinylsulphone moiety or a thiocarboxylic acid or an ester thereof and at least one antibody of claim 15 ;

detecting bound conjugate; and

deducing from a calibration curve the presence of ketamine and norketamine in the sample.

17. A kit for use in a method for detecting ketamine and norketamine, the kit comprising:

at least one conjugate comprising a norketamine hapten covalently bonded to a detectable labelling agent, wherein said norketamine hapten is derivatised with a crosslinker at the nitrogen of the norketamine, wherein the norketamine hapten has the following structural formula:

wherein R is a bivalent link and X is a terminal group, wherein R is an alkylene moiety; and X is selected from the group comprising a carboxylic acid or an ester thereof, an amine, a maleimide, a halocarboxylic acid or an ester thereof, an aldehyde, a dithiopyridyl moiety, a vinylsulphone moiety or a thiocarboxylic acid or an ester thereof, wherein the norketamine hapten is prepared by reacting norketamine with an X-R—leaving group; and

at least one antibody of claim 15 .

18. A method for detecting ketamine and norketamine in a sample, the method comprising:

contacting the sample with at least one conjugate comprising a norketamine hapten covalently bonded, via a crosslinker, to a detectable labelling agent, wherein said norketamine hapten is derivatised with the crosslinker at the nitrogen of the norketamine, and at least one antibody of claim 1 ;

detecting bound conjugate; and

deducing from a calibration curve the presence of ketamine and norketamine in the sample.

19. A method for detecting ketamine and norketamine in a sample, the method comprising:

contacting the sample with at least one conjugate comprising a norketamine hapten covalently bonded, via a crosslinker, to a detectable labelling agent, wherein said norketamine hapten is derivatised with the crosslinker at the nitrogen of the norketamine, and at least one antibody of claim 2 ;

detecting bound conjugate; and

deducing from a calibration curve the presence of ketamine and norketamine in the sample.

20. A method for detecting ketamine and norketamine in a sample, the method comprising:

contacting the sample with at least one conjugate comprising a norketamine hapten covalently bonded, via a crosslinker, to a detectable labelling agent, wherein said norketamine hapten is derivatised with the crosslinker at the nitrogen of the norketamine, and at least one antibody of claim 3 ;

detecting bound conjugate; and

deducing from a calibration curve the presence of ketamine and norketamine in the sample.

21. A kit for use in a method for detecting ketamine and norketamine, the kit comprising:

at least one conjugate comprising a norketamine hapten covalently bonded, via a crosslinker, to a detectable labelling agent, wherein said norketamine hapten is derivatised with the crosslinker at the nitrogen of the norketamine; and

at least one antibody of claim 1 .

22. A kit for use in a method for detecting ketamine and norketamine, the kit comprising:

at least one conjugate comprising a norketamine hapten covalently bonded, via a crosslinker, to a detectable labelling agent, wherein said norketamine hapten is derivatised with the crosslinker at the nitrogen of the norketamine; and

at least one antibody of claim 2 .

23. A kit for use in a method for detecting ketamine and norketamine, the kit comprising:

at least one conjugate comprising a norketamine hapten covalently bonded, via a crosslinker, to a detectable labelling agent, wherein said norketamine hapten is derivatised with the crosslinker at the nitrogen of the norketamine; and

at least one antibody of claim 3 .

24. A method for detecting ketamine and norketamine in a sample, the method comprising:

contacting the sample with at least one conjugate comprising a norketamine hapten covalently bonded, via a crosslinker, to a detectable labelling agent, wherein said norketamine hapten is derivatised with the crosslinker at the nitrogen of the norketamine, and at least one antibody of claim 15 ;

detecting bound conjugate; and

deducing from a calibration curve the presence of ketamine and norketamine in the sample.

25. A kit for use in a method for detecting ketamine and norketamine, the kit comprising:

at least one conjugate comprising a norketamine hapten covalently bonded, via a crosslinker, to a detectable labelling agent, wherein said norketamine hapten is derivatised with the crosslinker at the nitrogen of the norketamine; and

at least one antibody of claim 15 .

Assignments (2)
CORRECTIVE ASSIGNMENT TO CORRECT THE NATURE OF CONVENYANCE PREVIOUSLY RECORDED AT REEL: 055950 FRAME: 0471. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Apr 20, 2021
From: RANDOX LABORATORIES LIMITED
To: NORTHERN BANK LIMITED
Reel/Frame 056210/0055 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 15, 2021
From: RANDOX LABORATORIES LIMITED
To: NORTHERN BANK LIMITED
Reel/Frame 055950/0471 →