IP Library Granted Patent US 7,148,024
Granted Patent B2
US 7,148,024 · App. 11/225,613 · Granted Dec 12, 2006

Busulfan immunoassay

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Quick Facts
Patent No.
US 7,148,024
App. No.
11/225,613
Granted
Dec 12, 2006
Kind
B2
Abstract

Novel conjugates of busulfan and novel busulfan immunogens derived from α-substituted derivatives of busulfan and antibodies generated by these busulfan linked immunogens are useful in immunoassays for the quantification and monitoring of busulfan in biological fluids.

Claims (54)

1. An immunoassay for detecting busulfan in a sample comprising providing a mixture of a sample, containing an antibody selectively reactive with busulfan and not substantially cross-reactive with tetramethylene sulfone, tetrahydrothiophene and tetrahydrothiophene-3-ol-1,1-dioxide and a conjugate of a carrier with a compound of the formula:

wherein A is lower alkylene;

X′ is a functional linking group;

Y is an organic spacing group;

X is a terminal functional group capable of binding to a carrier;

p and z are independent integers of from 0 to 1;

or a compound of the formula

wherein A′ is lower alkylene or lower alkenylene;

X′, Y, X and z are as above

or mixtures thereof,

causing the busulfan in the sample and said conjugate to bind with said antibody and thereafter measuring the amount of said conjugate in said mixture which is bound or unbound to said antibody whereby the presence of busulfan in the sample can be determined.

2. The process of claim 1 , wherein the sample is a human sample.

3. The immunoassay of claim 2 , wherein said antibody is generated from an immunogen comprising an immunogenic polymer linked to a compound of the formula:

wherein A is lower alkylene;

X′ is a functional linking group;

Y is an organic spacing group;

X″ is a terminal functional group capable of binding to a

immunogenic polymer;

p and z are independent integers of from 0 to 1; or a compound of the formula

wherein A′ is lower alkylene or lower alkenylene;

X′, Y, X″, p and z are as above and mixtures thereof.

4. The immunoassay of claim 2 , wherein the antibody or the conjugate is attached to a solid support.

5. The immunoassay of claim 4 , wherein the solid support is microtiter plates.

6. The immunoassay of claim 4 , wherein the solid support is nanoparticles.

7. The immunoassay of claim 1 , wherein said compound which forms said conjugates is

wherein A, X′, Y, X, p and z are as above.

8. The immunoassay of claim 7 , wherein X is

and R 3 is hydrogen or taken together with its attached oxygen chain forms a reactive ester.

9. The immunoassay of claim 8 , wherein z is 0 and p is 1.

10. The immunoassay of claim 9 , wherein A is —(CH 2 ) v — and v is 1 or 2.

11. The immunogen of claim 10 , wherein v is 2.

12. The immunoassay of claim 1 , wherein said compound which forms said conjugates is

wherein A′, X′, Y, X and z are as above.

13. The immunoassay of claim 12 , wherein X is

and R 3 is hydrogen or taken together with its attached oxygen chain forms a reactive ester.

14. The immunoassay of claim 13 wherein z is 0 and p is 1.

15. The immunoassay of claim 14 , wherein A′ is —CH═CH—.

16. A kit for determining the presence of busulfan in a patient sample comprising reagents in separate containers, one of the reagents being a conjugate of a carrier with a compound selected from the groups consisting of compounds of the formula:

wherein A is lower alkylene;

X′ is a functional linking group;

Y is an organic spacing group;

X is a terminal functional group capable of binding to a carrier;

p and z are independent integers from 0 to 1; or a compound of the formula

wherein A′ is lower alkyl or lower alkenylene;

X′, Y, X and z are as above

or mixtures thereof; and the second container containing an antibody substantially selectively reactive with busulfan and not substantially cross-reactive to tetramethylene sulfone, tetrahydrothiophen and tetrahydrothiophene-3-ol-1,1 dioxide.

17. The kit of claim 16 , wherein said conjugate is present in a predetermined amount in said first container.

18. The kit of claim 17 , wherein said kit is used to determine the amount of busulfan in said sample.

19. The immunoassay of claim 12 , wherein said compound which forms the immunogens has the formula

wherein A is lower alkylene;

X′ is a functional linking group;

Y is an organic spacing group;

X″ is a terminal functional group capable of binding to a immunogenic polymer; and

p and z are independent integers of from 0 to 1.

Assignments (2)
SECURITY INTEREST Recorded Nov 17, 2015
From: SALADAX BIOMEDICAL, INC.
To: SHANGHAI FOSUN PHARMACEUTICAL (GROUP) CO., LTD.
Reel/Frame 037126/0733 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 13, 2005
From: SALAMONE, SALVATORE J.; COURTNEY, JODI BLAKE; HE, SHU
To: SALADAX BIOMEDICAL INC.
Reel/Frame 016984/0642 →