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Abstract

Most drugs act by being either agonists or antagonists at receptors that respond to chemical messengers such as neurotransmitters. An agonist binds to the receptor and produces an effect within the cell. An antagonist may bind to the same receptor, but does not produce a response, instead it blocks that receptor to a natural agonist. A partial agonist can produce an effect within a cell that is not maximal and then block the receptor to a full agonist. Antagonism may be competitive and reversed by higher concentrations of agonist. Insurmountable antagonists bind strongly to the receptor and are not reversed by additional agonist. Pharmacological receptors can be divided into four superfamilies: ligand-gated ion channels, G-protein coupled receptor, direct enzyme-linked receptors, and intracellular receptors affecting gene transcription.

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Amidst the controversy about promoting innovation through patents while maintaining access to medicines, India's 2005 Patents (Amendment) Act on patent layering offers a novel attempt at entering a middle path. Genuine advance is to be filtered from “evergreening” by requiring new forms of known substances to display enhanced therapeutic efficacy in order to be patentable. For this purpose, substance derivatives are presumed to be the same as the original known substance. While this heightened patentability standard for incremental innovation has been widely discussed from economic, political and legal standpoints, it has not yet been fully considered on natural scientific grounds. In this article, the Sec. 3(d) criteria “enhanced therapeutic efficacy” and the negative presumption on substance derivatives will be explored on the scientific basis of drug development in order to assess the regime's efficiency. This analysis reveals that “therapeutic” and “efficacy” are not entirely suitable as patentability criteria, while the presumption may entail undesired effects. Section 3(d) as it stands offers a novel approach to limiting evergreening and endorsing some incremental innovation, but much can be gained from a closer congruence between natural and legal scientific terminology in the pharmaceutical patenting context. A few interpretive adaptations are proposed to further fine-tune it to this end. © 2015, Max Planck Institute for Innovation and Competition, Munich.
How drugs act: molecular aspects
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