METHAMPHETAMINE-LIKE HAPTEN COMPOUNDS, LINKERS, CARRIERS AND COMPOSITIONS AND USES THEREOF

• US 20070238653A1
• Filed: 04/09/2007
• Published: 10/11/2007
• 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: Abraham, Philip, Carroll, Frank, Owens, Samuel
• Granted Patent: US 7,632,929 B2
• Time in Patent Office: Days
• US Class Current: 530/403
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• 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'
• CPC Class Codes: G01N 33/946 CNS-stimulants, e.g. cocaine, amphetamines
• CPC Class Codes: Y10S 436/823 Immunogenic carrier or carrier per se
• CPC Class Codes: Y10S 436/901 Drugs of abuse, e.g. narcotics, amphetamine
• CPC Class Codes: Y10T 436/173845 Amine and quaternary ammonium

Abstract

The invention generally relates to hapten compounds comprising either (+) methamphetamine or (+) amphetamine conjugated to a linker. Generally speaking, hapten compounds of the invention may be used to elicit an immune response to one or more of (+) methamphetamine, (+) amphetamine, or (+) MDMA.

Claims

1. A compound comprising formula (I):

2. The compound of claim 1, wherein L is from about 5 to about 10 atoms in length.

3. The compound of claim 1, wherein L is selected from the group consisting of:

(CH₂)_m, wherein m is an integer between 5 and 10 and O(CH₂)_m, wherein m is an integer between 5 and 9.

4. The compound of claim 3, wherein L is (CH₂)₁₀ or O(CH₂)₉.

5. The compound of claim 1, wherein L is attached to the benzene ring at a position selected from the group consisting of ortho, meta, and para.

6. The compound of claim 1, wherein the compound comprises formula (II):

7. The compound of claim 6, wherein the X is a protein selected from the group consisting of KLH, ovalbumin, BSA, cationized BSA, thyroglobulin, a bacterial toxin and a bacterial toxoid.

8. The compound of claim 7, wherein R₃ is selected from the group consisting of (CH₂)₄ and (CH₂)₄NHCO(CH₂)₅.

9. The compound of claim 8, wherein L is from about 5 to 10 atoms in length, and is attached to the benzene ring at a position selected from the group consisting of para and meta;

and n is greater than or equal to 2.

10. The compound of claim 6, wherein L is (CH₂)₁₀ or O(CH₂)₉.

11. The compound of claim 1, wherein the compound comprises formula (III):

12. The compound of claim 11, wherein R₂ is oxygen.

13. The compound of claim 12, wherein L is (CH₂)_m, wherein m is an integer between 5 and 9.

14. The compound of claim 13, wherein L (CH₂)₉.

15. The compound of claim 9, wherein the compound comprises formula (IV):

16. The compound of claim 15, wherein the X is a protein selected from the group consisting of KLH, ovalbumin, BSA, cationized BSA, thyroglobulin, a bacterial toxin or a bacterial toxoid.

17. The compound of claim 16, wherein R₃ is selected from the group consisting of (CH₂)₄ and (CH₂)₄NHCO(CH₂)₅.

18. The compound of claim 17, wherein L is from about 5 to 9 atoms in length, and is attached to the benzene ring at a position selected from the group consisting of para and meta;

and n is an integer greater than or equal to 2.

19. The compound of claim 18, wherein L is (CH₂)₉.

20. A composition comprising a compound selected from the group consisting of a compound of formula (I), a compound of formula (II), a compound of formula (III), and a compound of formula (IV).

21. The composition of claim 20, further comprising an adjuvant.

22. The composition of claim 21, wherein the adjuvant is pharmaceutically acceptable for use in a human subject.

23. The composition of claim 21, wherein the adjuvant is selected from the group consisting of alum, TiterMax Gold, Ribi, ASO4, Freund'"'"'s complete adjuvant, and Freund'"'"'s incomplete adjuvant.

24. The composition of claim 21, further comprising a pharmaceutically acceptable carrier.

25. The composition of claim 21, wherein the pharmaceutically acceptable carrier is a bacterial toxin or a bacterial toxoid.

26. The composition of claim 21, further comprising a pharmaceutically acceptable excipient.

27. A method for eliciting an immune response in a subject, the method comprising administering the composition of claim 20 to the subject.

28. The method of claim 27, wherein the subject is selected from the group consisting of a rodent, a non-human primate, and a human.

32. A method of treating drug addiction, the method comprising eliciting an immune response in a drug-addicted subject by administering the composition of claim 20 to the subject, wherein the immune response decreases the concentration of (+)methamphetamine, (+)amphetamine, or (+)MDMA in the brain of the subject.

29. A method for generating specific antibodies for a compound selected from the group consisting of a compound of formula (I), a compound of formula (II), a compound of formula (III), a compound of formula (IV);

the method comprising administering the compound to a subject.

30. The method of claim 29, wherein the subject is selected from the group consisting of a rodent, a non-human primate, and a human.

31. The method of claim 29, wherein the specific antibodies decrease the concentration of (+)methamphetamine, (+)amphetamine, or (+)MDMA in the brain of the subject.