Assessment of the significance of patent-derived information for the early identification of compound–target interaction hypotheses

Abstract

BackgroundPatents are an important source of information for effective decision making in drug discovery. Encouragingly, freely accessible patent-chemistry databases are now in the public domain. However, at present there is still a wide gap between relatively low coverage-high quality manually-curated data sources and high coverage data sources that use text mining and automated extraction of chemical structures. To secure much needed funding for further research and an improved infrastructure, hard evidence is required to demonstrate the significance of patent-derived information in drug discovery. Surprisingly little such evidence has been reported so far. To address this, the present study attempts to quantify the relevance of patents for formulating and substantiating hypotheses for compound–target interactions.ResultsA manually-curated set of 130 compound–target interaction pairs annotated with what are considered to be the earliest patent and publication has been produced. The analysis of this set revealed that in stark contrast to what has been reported for novel chemical structures, only about 10% of the compound–target interaction pairs could be found in publications in the scientific literature within one year of being reported in patents. The average delay across all interaction pairs is close to 4 years. In an attempt to benchmark current capabilities, it was also examined how much of the benefit of using patent-derived information can be retained when a bioannotated version of SureChEMBL is used as secondary source for the patent literature. Encouragingly, this approach found the patents in the annotated set for 72% of the compound–target interaction pairs. Similarly, the effect of using the bioactivity database ChEMBL as secondary source for the scientific literature was studied. Here, the publications from the annotated set were only found for 46% of the compound–target interaction pairs.ConclusionPatent-derived information is a significant enabler for formulating compound–target interaction hypotheses even in cases where the respective interaction is later reported in the scientific literature. The findings of this study clearly highlight the significance of future investments in the development and provision of databases and tools that will allow scientists to search patent information in a comprehensive, reliable, and efficient manner.Electronic supplementary materialThe online version of this article (doi:10.1186/s13321-017-0214-2) contains supplementary material, which is available to authorized users.

Identification of the Core Chemical Structure in SureChEMBL Patents

“…Pharmacological patents are a key source of information in drug discovery as they offer early access to novel chemical space of biological relevance. Motivated by the competitiveness of the business sector, the patent system encourages the constant discovery and disclosure of new active structures, often poorly covered in the scientific literature . In this respect, a recent comparison between patent-derived and literature-extracted data revealed that, from the 15.4 million chemical structures available in all large patent-derived chemical sources, only 0.5 million were found to be present also in literature-derived databases, and when comparing the deposition date in patents of these 0.5 million molecules with their corresponding publication date in scholarly literature, an average lag time of four years was observed, with delays going up to six years for its final storage in publicly available sources such as ChEMBL .…”

“…Motivated by the competitiveness of the business sector, the patent system encourages the constant discovery and disclosure of new active structures, often poorly covered in the scientific literature . In this respect, a recent comparison between patent-derived and literature-extracted data revealed that, from the 15.4 million chemical structures available in all large patent-derived chemical sources, only 0.5 million were found to be present also in literature-derived databases, and when comparing the deposition date in patents of these 0.5 million molecules with their corresponding publication date in scholarly literature, an average lag time of four years was observed, with delays going up to six years for its final storage in publicly available sources such as ChEMBL . Therefore, there is a need for an early, more complete and accurate open access to molecules exemplified in pharmacological patents.…”

Innovation in Small-Molecule-Druggable Chemical Space: Where are the Initial Modulators of New Targets Published?

“…Additionally, a previous study analyzed a small number of protein modulators and considered the delay of the publication of these annotations in scientific literature after having been published in a patent. In this study, the authors found that on average there is a four year delay between publishing a patent to the scientific literature for compound–target interactions, which also highlights the need for scientists to be able to search patents reliably …”

“…In this study, the authors found that on average there is a four year delay between publishing a patent to the scientific literature for compound−target interactions, which also highlights the need for scientists to be able to search patents reliably. 6 The main objective of this study is to try to understand where pharmaceutical innovations in the form of new modulators of protein targets are reported as a function of time. For achieving this, we investigated whether the first bioactive compound (a compound that has been shown to have activity on a particular target) for a novel target tends to be primarily published in either patents or scientific literature.…”

Illuminating the Druggable Genome through Patent Bioactivity Data

“…For example, in a 2009 paper the authors found that just 6% of compounds in patents also appeared in the scientific literature in one of the commercial sources included in their study (GVKBIO) 7 . A later study reported that only 10% of a set of compound-target pairs could be found in literature publications within one year of being reported in patents, and that on average data appears 3 to 4 years earlier in patents than in the scientific literature 8 . For compounds that progress into clinical trials and are ultimately approved, the gap between publication of the patent and publication of the compound in the medicinal chemistry literature can be even longer 6 .…”