Given the need for further improvements in anti-cocaine vaccination strategies, a chimeric hapten (GNET) was developed that combines chemically-stable structural features from steady-state haptens with the hydrolytic functionality present in transition-state mimetic haptens. Additionally, as a further investigation into the generation of an improved bifunctional antibody pool, sequential vaccination with steady-state and transition-state mimetic haptens was undertaken. While GNET induced the formation of catalytically-active antibodies, it did not improve overall behavioral efficacy. In contrast, the resulting pool of antibodies from GNE/GNT co-administration demonstrated intermediate efficacy as compared to antibodies developed from either hapten alone. Overall, improved antibody catalytic efficiency appears necessary to achieve the synergistic benefits of combining cocaine hydrolysis with peripheral sequestration.

01 Apr 2008·Journal of the American Chemical SocietyQ1 · CHEMISTRY

Modeling the Catalysis of Anti-Cocaine Catalytic Antibody: Competing Reaction Pathways and Free Energy Barriers

Q1 · CHEMISTRY

Article

Author: Zhan, Chang-Guo ; Pan, Yongmei ; Gao, Daquan

The competing reaction pathways and the corresponding free energy barriers for cocaine hydrolysis catalyzed by an anti-cocaine catalytic antibody, mAb15A10, were studied by using a novel computational strategy based on the binding free energy calculations on the antibody binding with cocaine and transition states. The calculated binding free energies were used to evaluate the free energy barrier shift from the cocaine hydrolysis in water to the antibody-catalyzed cocaine hydrolysis for each reaction pathway. The free energy barriers for the antibody-catalyzed cocaine hydrolysis were predicted to be the corresponding free energy barriers for the cocaine hydrolysis in water plus the calculated free energy barrier shifts. The calculated free energy barrier shift of -6.87 kcal/mol from the dominant reaction pathway of the cocaine benzoyl ester hydrolysis in water to the dominant reaction pathway of the antibody-catalyzed cocaine hydrolysis is in good agreement with the experimentally derived free energy barrier shift of -5.93 kcal/mol. The calculated mutation-caused shifts of the free energy barrier are also reasonably close to the available experimental activity data. The good agreement suggests that the protocol for calculating the free energy barrier shift from the cocaine hydrolysis in water to the antibody-catalyzed cocaine hydrolysis may be used in future rational design of possible high-activity mutants of the antibody as anti-cocaine therapeutics. The general strategy of the free energy barrier shift calculation may also be valuable in studying a variety of chemical reactions catalyzed by other antibodies or proteins through noncovalent bonding interactions with the substrates.

01 Jul 2003·Journal of Pharmacy and PharmacologyQ3 · MEDICINE

Controlled release of anti-cocaine catalytic antibody from biodegradable polymer microspheres

Q3 · MEDICINE

Article

Author: Homayoun, P ; Landry, D ; Komiskey, H ; Mandal, T

AbstractRecent reports have shown that anti-cocaine catalytic monoclonal antibody 15A10 reduces the toxic effect of cocaine by increasing its breakdown to systemically inert products ecgonine methylester and benzoic acid. This study reports the microencapsulation of antibody 15A10 using biodegradable poly (lactic-glycolic) acid (PLGA) by double emulsion technique. Formulation parameters such as protein loading, polymer molecular weight and the presence of zinc carbonate were studied for their effects on in-vitro release of antibody from microspheres. The initial burst release was decreased by the reduction of the protein (as % of total ingredients) in the formulation. Although changing the polymer molecular weight did not cause a reduction in initial burst release, it was effective in improving the release rate. The inclusion of zinc carbonate in microsphere preparation resulted in increase in initial burst release. An in-vivo study in mice revealed the presence of antibody in blood up to ten days following subcutaneous injections. These data demonstrate a potential for a sustained-release formulation of monoclonal antibody 15A10 for treatment of cocaine addiction.

100 Deals associated with MAb 15a10 (Columbia)

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Indication	Highest Phase	Country/Location	Organization	Date
Cocaine-Related Disorders	Discovery	United States	MedImmune LLC	-
Cocaine-Related Disorders	Discovery	United States	MEDITE Cancer Diagnostics, Inc.	-
Cocaine-Related Disorders	Discovery	United States	The Trustees of Columbia University in The City of New York	-
Poisoning	Discovery	United States	MEDITE Cancer Diagnostics, Inc.	-
Poisoning	Discovery	United States	The Trustees of Columbia University in The City of New York	-
Poisoning	Discovery	United States	MedImmune LLC	-

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