Despite an understanding of the pharmacological basis of cocaine abuse there is no effective pharmacotherapy, suggesting that pharmacotherapy may be impractical. An alternative approach is to: develop an immunotherapy that directly targets cocaine. We have generated a fully human anti-cocaine monoclonal antibody (mAb) with high affinity (Kd = 4 nM) for cocaine and selectivity over cocaine's inactive metabolites. This is a unique product. The immunogenicity of foreign proteins such as mouse mAbs is the major factor compromising the safety and efficacy of immunotherapeutic agents. The fully human sequence of our anti-cocaine mAb should be safe for repeated treatments in patients. In addition, the human sequence should confer long-term efficacy. Anti-cocaine mAbs do not cross the blood-brain-barrier but bind to cocaine in the peripheral circulation thereby sequestering cocaine in the periphery. Consequently, the anti-cocaine antibodies reduce all the central effects of cocaine. Accomplishing the aims of the proposed studies will advance this potential immunotherapeutic agent towards clinical trials by providing the initial indications of efficacy required for an IND application to the FDA. Prevention of relapse in cocaine abusers is the proposed primary indication of our human anti-cocaine mAbs.
The aim of this Phase I Fast-Track application is to add value to our immunotherapeutic agent by demonstrating the in vivo efficacy of the human anti-cocaine mAb. Efficacy will be defined as the ability to alter the pharmacokinetics of cocaine in vivo as measured by the ability to decrease the brain concentrations and increase the plasma concentrations of cocaine in mice. After successful completion of proposed Phase 1 milestones, Phase 2 studies will be implemented that will determine the stoichiometric relationship between cocaine and anti-cocaine mAb necessary to confer efficacy and will further determine efficacy of the anti-cocaine mAb in an animal model of cocaine abuse. A safe and effective passive immunotherapy for the treatment of cocaine abuse will be a valuable and unique product.
