Process Patent Protection via Analysis of Stable Isotope Ratios

Abstract

Process patent protection via the analysis of natural-abundance stable isotopes has been demonstrated as an approach to extend the effective life of bio/pharmaceutical patents. The high specificity of isotope ratio analysis compared to other approaches (for example, concentrations of organic impurities or trace metals) allows the isotopic analysis to differentiate processes that were not previously resolvable by less precise analytical methods. Here we summarize the rationale for, and some selected case studies of, this emerging field. We review: (i) the systematics of stable isotope chemistry, (ii) approaches to instrumental analysis of stable isotopes, (iii) the biogeochemical origin of stable isotopic fingerprints, (iv) equilibrium versus kinetic isotope effects on those fingerprints, (v) categories of application of process patent protection, and (vi) case histories of application. The three reviewed cases include one of nutraceutical false advertising, one of a small molecule antibiotic drug product infringement, and one of wrongful accusation of human drug product infringement, which protected these bio/pharmaceutical products against patent infringement. Finally, we briefly preview some new applications of stable isotopic analysis in the bio/pharmaceutical field including analysis of biologic drugs, continuous monitoring of drug reaction processes, and isotopically directed synthesis.