Monoclonal antibody antagonists for treating medical problems associated with d-amphetamine-like drugs

• US 20010051158A1
• Filed: 04/20/2001
• Published: 12/13/2001
• Est. Priority Date: 04/20/2000
• Status: Active Grant

• Current Assignee: Bioventures, LLC
• Original Assignee: The Board of Trustees of the University of Arkansas (University of Arkansas System)
• Inventors: Carroll, Frank Ivy, Owens, Samuel M., Abraham, Philip
• Granted Patent: US 6,669,937 B2
• Time in Patent Office: Days
• US Class Current: 424/142.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: C07B 2200/07 Optical isomers
• CPC Class Codes: C07C 217/60 linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
• CPC Class Codes: C07C 233/18 having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• CPC Class Codes: C07K 16/44 against material not provided for elsewhere , e.g. haptens, metals, DNA, RNA, amino acids
• CPC Class Codes: C07K 2317/55 Fab or Fab'

Abstract

The invention includes synthetic immunochemical haptens for the generation of antibodies, the antibodies, and the medical treatment applications for using the antibodies. The antibodies are designed to recognize the common molecular features of d-methamphetamine-like abused stimulants, and will have insignificant cross-reactivity with endogenous substrates (e.g. dopamine) or over-the-counter medications (e.g. 1-methamphetamine, pseudoephedrine, phenylpropanolamine and ephedrine). These monoclonal antibodies and their antigen binding fragments are useful in treatment plans for recovering addicts, in emergency room settings for rapidly reversing a drug overdose, in protection of fetuses or fetus from drug-abusing pregnant mothers or in a psychiatric setting to reduce the exacerbation of psychotic disorders caused by stimulant drugs.

Claims

1. A monoclonal antibody that specifically recognizes a stimulant or hallucinogenic drug of abuse or a metabolite thereof, wherein said drug of abuse or its metabolite is selected from the group consisting of d-methamphetamine, d-amphetamine, (+/−

) 3,4-methylenedioxymethamphetamine, (+) 3,4-methylenedioxyamphetamine and structural-related analogs of these compounds.

2. The monoclonal antibody of

claim 1

, wherein said antibody is of murine origin.

3. The monoclonal antibody of

claim 1

, wherein said antibody is of human origin or contains portions of a human antibody

7. A method of treating stimulant or hallucinogenic drug abuse and/or overdose, comprising the step of administering a pharmacological effective dose of the monoclonal antibody of

claim 1

to an individual in need of such treatment.

8. The method of

claim 7

, wherein said stimulant or hallucinogenic drug is d-methamphetamine, d-amphetamine, (+/−

) 3,4-methylenedioxymethamphetamine, (+/−

) 3,4-methylenedioxyamphetamine and structural-related analogs of these compounds.

4. An antigen binding fragment that specifically recognizes a stimulant or hallucinogenic drug of abuse or a metabolite thereof, wherein said drug of abuse or its metabolite is selected from the group consisting of d-methamphetamine, d-amphetamine, (+/−

) 3,4-methylenedioxymethamphetamine, (+) 3,4-methylenedioxyamphetamine and structural-related analogs of these compounds.

5. The antigen binding fragment of

claim 4

, wherein said antigen binding fragment is of murine origin.

6. The antigen binding fragment of

claim 4

, wherein said antigen binding fragment is of human origin or contains portions of a human antibody.

9. A method of treating stimulant drug abuse and/or overdose, comprising the step of administering a pharmacological effective dose of the antigen binding fragment of

claim 4

to an individual in need of such treatment.

10. The method of

claim 9

, wherein said stimulant or hallucinogenic drug is d-methamphetamine, d-amphetamine, (+/−

) 3,4-methylenedioxymethamphetamine, (+/−

) 3,4-methylenedioxyamphetamine and structural-related analogs of these compounds.

11. A compound with the structure of

12. A method of generating a class-specific monoclonal antibody that recognizes methamphetamine-like stimulants, comprising the step of:

immunizing animals with the compound of

claim 11

;

generating antibody-secreting hybridomas from the spleen cells of said animals; and

screening the specificity of the antibodies, wherein antibody showing cross-reactivity to methamphetamine-like stimulants indicates the generation of methamphetamine-like stimulants-specific antibody.

13. A compound with the structure of

14. The compound of

claim 13

, wherein R is O(CH₂)_XCOOH, and X is from 2 to 9.

15. The compound of

claim 13

, wherein R is OCH₂CH═

CH(CH2)_XCOOH, and X is from 1 to 6.

16. The compound of

claim 13

, wherein R is OCH₂C═

C(CH2)_XCOOH, and X is from 1 to 6.

17. The compound of

claim 13

, wherein R is O(CH₂)_XO(CH₂)_YCOOH, and X is from 2 to 4, Y is from 1 to 5.

18. The compound of

claim 13

, wherein R is O(CH₂)_XNR1(CH₂)_YCOOH, X is from 2 to 3, Y is from 1 to 5, and R1 is alkyl 1-5 carbon.

19. The compound of

claim 13

, wherein R is S(CH₂)_XCOOH, and X is from 2 to 9.

20. The compound of

claim 13

, wherein R is SCH₂CH═

CH(CH2)_XCOOH, and X is from 1 to 6.

21. The compound of

claim 13

, wherein R is SCH₂C═

C(CH2)_XCOOH, and X is from 1 to 6.

22. The compound of

claim 13

, wherein R is S(CH₂)_XO(CH2)_YCOOH, and X is from 2 to 4, Y is from 1 to 5.

23. The compound of

claim 13

, wherein R is S(CH₂)_XNR1(CH2)_YCOOH, X is from 2 to 3, Y is from 1 to 5, and R1 is alkyl 1-5 carbon.

24. The compound of

claim 13

, wherein R is (CH₂)_XCOOH, and X is from 3 to 8.

25. The compound of

claim 13

, wherein R is (CH2)_XCH═

CHCOOH, and X is from 2 to 7.

26. The compound of

claim 13

, wherein R is (CH2)_XC═

CCOOH, and X is from 2 to 7.

27. The compound of

claim 13

, wherein R is CH═

CH(CH2)_XCOOH, and X is from 1 to 6.

28. The compound of

claim 13

, wherein R is C═

C(CH2)_XCOOH, and X is from 1 to 6.

29. The compound of

claim 13

, further comprises of a hydrocarbon structure R1 attached to R, wherein R1 is selected from the group consisting of —

CH₂CH₂CN,