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

• US 6,669,937 B2
• Filed: 04/20/2001
• Issued: 12/30/2003
• Est. Priority Date: 04/20/2000
• Status: Expired due to Term

• 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
• Primary Examiner(s): CEPERLEY, MARY
• Application Number:
  US09/839,549
• Publication Number:
  US 20010051158A1
• Time in Patent Office: 984 Days
• Field of Search: 530/388.9, 530/389.8, 424/141.1, 424/142.1
• 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 class or stimulant or hallucinogenic drug of abuse comprising d-methamphetamine, d-amphetamine, (+/−

) 3,4-methylenedioxymethamphetamine, and (+/−

) 3,4-methylenedioxyamphetamine, wherein said monoclonal antibody is generated by a hapten comprising (S)- or (R)-3-(5′

-Carboxypentyloxy) methamphetamine hydrochloride.

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 selected from the group consisting of d-methamphetamine, d-amphetamine, (+/−

) 3,4-methylenedioxymethamphetamine, and (+/−

) 3,4-methylenedioxyamphetamine.

4. An antibody fragment that specifically recognizes a class of stimulant or hallucinogenic drug of abuse comprising d-methamphetamine, d-amphetamine, (+/−

) 3,4-methylenedioxymethamphetamine, and (+/−

) 3,4-methylenedioxyamphetamine, wherein said antibody fragment is part of a monoclonal antibody generated by a hapten comprising (S)- or (R)-3-(5′

-Carboxypentyloxy) methamphetamine hydrochloride.

5. The antibody fragment of claim 4, wherein said antibody fragment is of murine origin.

6. The antibody fragment of claim 4, wherein said antibody fragment is of human origin or contains portions of a human antibody.

9. A method of treating stimulant or hallucinogenic drug abuse and/or overdose, comprising the step of administering a pharmacological effective dose of the antibody 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 selected from the group consisting of d-methamphetamine, d-amphetamine, (+/−

) 3,4-methylenedioxymethamphetamine, and (+/−

) 3,4-methylenedioxyamphetamine.