Antibody-nanoparticle conjugates for the treatment of drug abuse
The present invention generally relates to an antibody composition including antibodies conjugated to nanoparticles. The antibody composition may be used in methods to treat drug use, drug addiction, and effects of drug use.
1. A method of antagonizing the effects of amphetamine and amphetamine-like compounds in a subject, the method comprising administering to the subject an antibody composition comprising:
a. a single chain antibody that binds an amphetamine compound;
b. a nanoparticle, wherein the nanoparticle is a PEG modified poly(amidoamine) PAMAM dendrimer wherein the dendrimer conjugates two or more single chain antibody fragments and resulting dendribodies are multivalent; and,
c. a crosslinker
wherein the antibody composition antagonizes the effects of the amphetamine compound by binding the compound and maintaining the compound in the serum at higher concentrations relative to a corresponding unconjugated antibody, wherein the antibody composition has a longer in vivo serum half-life when compared to a composition comprising a corresponding unconjugated single chain antibody and wherein the antibody composition still displays at least 30% binding activity in the subject at 72 hours after administration, when compared to binding activity of the antibody composition at 1 minute after administration.
2. The method of claim 1 , wherein the subject is selected from the group comprising a rodent, a non-human primate, and a human.
3. The method of claim 1 , wherein the amphetamine-like compound is selected from the group consisting of (+)amphetamine, (+)methamphetamine, (+)3,4-methylenedioxymethamphetamine, and combinations thereof.
4. The method of claim 1 , wherein the single chain antibody does not include an FcRn binding site.
5. The method of claim 1 , wherein the single chain antibody does not include an effector region.
6. The method of claim 1 , wherein the single chain antibody comprises a terminal cysteine.
7. The method of claim 1 , wherein the single chain antibody is conjugated to the nanoparticle via the crosslinker.
8. The method of claim 1 , wherein a plurality of single chain antibodies are conjugated to a single nanoparticle.