Method for evaluating therapeutic efficacy

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...

Reexamination Certificate

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C435S007200, C435S007210, C436S501000

Reexamination Certificate

active

06875576

ABSTRACT:
The present invention relates to in vitro methods for evaluating compounds that better correlate with therapeutic efficiency than evaluating compounds based on potency alone. In general, the inventive method comprises: (i) determining a potency value for a compound against its target receptor; (ii) determining a desensitization value for the compound against its target receptor; and (iii) comparing the potency value with the desensitization value. If the desired action of a compound is as a receptor agonist, then the compound's desensitization value should be larger than the compound's potency value. This ensures that the concentration of a compound required for potency will not also cause the receptor to desensitize at the same time, thus in an essence nullifying the desired effect. The inventive methods are used to evaluate novel motilide compounds as well as ABT-229 and EM-574, two motilide compounds for which clinical trials have been initiated.

REFERENCES:
patent: 4677097 (1987-06-01), Omura et al.
patent: 5854407 (1998-12-01), Harada et al.
patent: WO 9313780 (1993-07-01), None
Feighner et al. Receptor for Motilin Identified in the Human Gastrointestinal System, SCIENCE 284:2184-2188, Jun. 25, 1999.*
Riccobene et al. Modeling Activation and Desentization of G-protein Coupled Receptors Provides Insight into Ligand Efficacy. J. Theor. Biol. 200:207-222, 1999.

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