It is estimated at least 50 per cent of all drugs, including chemotherapeutic agents and a wide variety of over-the-counter medications, are metabolised by the CYP3A4 enzyme. Individuals with a reduced ability to metabolise these drugs may be exposed to higher levels of the drug, placing them at risk for adverse drug reactions.
The allowed patent, "Methods for Evaluating the Ability to Metabolise Pharmaceuticals," describes the selection of chemotherapeutic agents based on the presence or absence of this variant, which is commonly called CYP3A4*1B. The patent also describes how a mutation in the GSTM1 gene affects drug metabolism.
In addition to the pharmacogenetic uses described above, the CYP3A4*1B variant may also be useful in identifying individuals at risk for prostate and breast cancer. An earlier related patent, "Isolated CYP3A4 Nucleic Acid Molecules and Detection Methods," describes the discovery of the CYP3A4*1B variant and its detection.
This patent details a method that allowed information to be gathered for better prediction of drug interactions, and effective dose for an individual. Nucleic acids that comprise the polymorphic sequences, identified in the human CYP3A4 gene, are used in screening assays, and for genotyping individuals.
The genotyping information is used to predict the rate of metabolism for CYP3A4 substrates, and the effect that CYP3A4 modulators will have on such metabolism.
The granting of the patent by the US Patent and Trademark Office is just one step closer to a field of the drug industry that some analysts reckon is the future of drug development. Pharmacogenetics is the linkage between an individual's genotype and that individual's ability to metabolise or react to a therapeutic agent.
Differences in metabolism or target sensitivity can lead to severe toxicity or therapeutic failure by altering the relation between bioactive dose and blood concentration of the drug. Relationships between polymorphisms in metabolic enzymes or drug targets and both response and toxicity can be used to optimise therapeutic dose administration.
In this case, genetic polymorphisms are identified in the human CYP3A4 gene. Nucleic acids comprising the polymorphic sequences are used to screen patients for altered metabolism for CYP3A4 substrates, potential drug-drug interactions, and adverse/side effects, as well as diseases that result from environmental or occupational exposure to toxins. The nucleic acids are used to establish animal, cell culture and in vitro cell-free models for drug metabolism.
"This is a significant addition to our intellectual property estate covering key drug-response markers because such a large number of important drugs are metabolised by CYP3A4," notes Kevin Rakin, president and chief executive officer of Genaissance.
"The clinical utility would be to appropriately dose medications that could cause harm if not fully metabolised, especially in the elderly or in cases where patients are receiving multiple drugs," he added.
Rakin added that the company's CYP3A4*1B assay technology may ultimately be incorporated in a simple DNA test that would provide potentially valuable prescribing information to physicians.