Towards in-house searching of Markush structures from patents

Most large pharmaceutical and biotechnology companies now use Oracle RDBMS chemistry data cartridges to manage databases of individual molecules for chemical structure searching. These systems are often linked to processes for new drug discovery and provide a common interface to a diverse range of specific structure databases. Recently some of these cartridges have been extended to handle Markush representations of un-enumerated combinatorial libraries alongside discrete molecules. An obvious extension would be to enable them to handle the Markush structures from chemical patents, though these have features and complexities not required for the representation of combinatorial libraries. The existing publicly available systems for handling patent Markush structures have changed little in the past 15 years and cannot easily be integrated with in-house systems; in-house access to chemical structures from patents is thus restricted at present to databases of specific molecules. A number of technical issues need to be tackled to enable the existing Markush-capable Oracle cartridges to handle data from patents, and several options are available for obtaining appropriate Markush structure databases for use with them. A demonstration system has been developed, using data from Thomson Reuters' World Patents Index Markush File, and Digital Chemistry's Oracle cartridge Torus. In-house access to patent Markush data could provide improved informatics support to the drug discovery process, both to enable patentability criteria to be added to computer-assisted drug design, and to expand the techniques available for data-mining in the patent literature.