This paper describes a new type of mitochondrial mutation. During germination of ascospores the mutants are blocked at the first budding stage and consequently die. However, vegetative growth on nonfermentable carbon sources and respiration are close to normal. The spores of the mutants which (like the wild type) contain very low amounts of mitochondrial cytochromes, do not synthesize cytochromes b and aa3 during germination.The mutants show a pleiotropic phenotype during the vegetative phase: they lack carbon catabolite repression of cytochromes on media containing 10% glucose. We discuss here the hypothesis that the mutation is located in a regulatory region on the mitochondrial genome which is needed for the reinitiation of mitochondrial genetic activity during germination of ascospores.
Patent applications provide unique opportunities for landscaping ongoing medical innovation. In this analysis of drug repurposing patent applications published under the international Patent Convention Treaty during the years 2011-2014, we discuss what categories in the World Health Organization's International Classification of Diseases provide drugs and drug candidates for potential second medical uses, and how these proposed repurposed uses relate to each other and the original ones. Also discussed are the geographic origin of the patent assignees and their type and size. Beyond the expected interactions within the field of neuropsychiatry, frequent secondary use claims for oncology compounds to treat noninfectious respiratory diseases, and for cardiovascular compounds to treat neurological conditions, were unexpected findings derived from the repurposing heatmap. The relative absence of repurposing claims to treat parasitic or tropical diseases contrasts sharply with the broad attention this segment receives in the peer-reviewed literature. Equally notable are the dominance of universities and small pharmaceutical companies; a focus of large multinational companies to repurpose their own compounds; and the leading role of European-centered entities among the assignees. We believe that this investigation represents the first comprehensive cross-sectional attempt at mapping drug repurposing patterns across therapeutic fields, and could provide important clues that complement those obtained from the peer-reviewed literature.
We have used a focused and comprehensive ophthalmology patent database to characterize the international patenting landscape dedicated to the pharmacological treatment of cataract, corneal opacities and dystrophies, and complicated refractive errors. A total of 201 disclosures related to cataract or corneal clouding (published between 1982 and 2011), and 99 documents (published between 1991 and 2011) related to refractive or geometry errors were identified. Current applications for the treatment or prevention of primary cataract have ceased to address diabetic cataract specifically through the inhibition of glycation-specific mechanisms. The most innovative approaches for pharmacotherapy of the lens focus on phase separation inhibitors, modulators of the TGF-β pathway, and matrix metalloproteinase inhibition. Patenting for the prevention of secondary cataracts as a delayed complication of intraocular lens insertion follows similar routes. For keratoconus, progressive myopia and Avellino corneal dystrophy, the focus remains on efficiently stabilizing the corrected shape of the cornea in the course of orthokeratology treatments. We expect future patenting in the fields of our investigation to concentrate more heavily on molecular medicine, in close lockstep with biotechnology and genetic testing.
We are currently building a database of all patent documents that contain substantial information related to pharmacology, drug delivery, tissue technology, and molecular diagnostics in ophthalmology. The goal is to establish a 'patentome', a body of cleaned and annotated data where all text-based, chemistry and pharmacology information can be accessed and mined in its context. We provide metrics on patent convention treaty documents, which demonstrate that ocular-related patenting has shown stronger growth than general patent cooperation treaty patenting during the past 25 years, and, while the majority of applications of this type have always provided substantial biological data, both data support and objections by patent examiners have been increasing since 2006-2007. Separately, we present a case study of chemistry information extraction from patents published during the 1950s and 1970s, which reveal compounds with corneal anesthesia potential that were never published in the peer-reviewed literature.
Patent applications provide unique opportunities for landscaping ongoing medical innovation. In this analysis of drug repurposing patent applications published under the international Patent Convention Treaty during the years 2011-2014, we discuss what categories in the World Health Organization's International Classification of Diseases provide drugs and drug candidates for potential second medical uses, and how these proposed repurposed uses relate to each other and the original ones. Also discussed are the geographic origin of the patent assignees and their type and size. Beyond the expected interactions within the field of neuropsychiatry, frequent secondary use claims for oncology compounds to treat noninfectious respiratory diseases, and for cardiovascular compounds to treat neurological conditions, were unexpected findings derived from the repurposing heatmap. The relative absence of repurposing claims to treat parasitic or tropical diseases contrasts sharply with the broad attention this segment receives in the peer-reviewed literature. Equally notable are the dominance of universities and small pharmaceutical companies; a focus of large multinational companies to repurpose their own compounds; and the leading role of Europeancentered entities among the assignees. We believe that this investigation represents the first comprehensive cross-sectional attempt at mapping drug repurposing patterns across therapeutic fields, and could provide important clues that complement those obtained from the peer-reviewed literature.
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