Patent Landscape of Helminth Vaccines and Related Technologies

Executive Summary This report focuses on patent landscape analysis of technologies related to vaccines targeting parasitic worms, also known as helminths. These technologies include methods of formulating vaccines, methods of producing of subunits, the composition of complete vaccines, and other technologies that have the potential to aid in a global response to this pathogen. The purpose of this patent landscape study was to search, identify, and categorize patent documents that are relevant to the development of vaccines that can efficiently promote the development of protective immunity against helminths. The search strategy used keywords which the team felt would be general enough to capture (or “recall”) the majority of patent documents which were directed toward vaccines against helminths. After extensive searching of patent literature databases, approximately 2847 publications were identified and collapsed to about 446 INPADOC families. Relevant patent families, almost half of the total relevant families (210 being total number of relevant families), were then identified and sorted into the categories of trematodes, cestodes, nematodes or nonspecific helminth. The 210 patent families that were divided into these four major categories were then further divided into sub categories relating to common fields of technology (e.g. DNA vaccine, vaccine formulations, methods to produce subunits) This sorting process increased the precision of the result set. The four major categories (cestodes, nematodes, trematodes, and non specific applications) as well as the overall data set of the 210 relevant family members were subjected to a range of analytics in order to extract as much information as possible from the dataset. First, patent landscape maps were generated to assess the accuracy of the sorting procedure and to reveal the relationships between the various technologies that are involved in creating an effective vaccine. Then, filings trends are analyzed for the overall dataset of the 210 relevant families as well as by the categories of trematodes, cestodes, and nematodes. The country of origin each member of the 210 relevant families was determined, and the range of distribution to other jurisdictions was assessed. Filings were also analyzed by year, by assignee. Finally, the various patent classification systems were mapped to find which particular classes tend to hold helminth vaccine-related technologies. Besides the keywords developed during the searches and the landscape map generation, the classifications represent an alternate way for further researchers to identify emerging helminth vaccine technologies. The analysis included creation of a map of keywords describing the relationship of the various technologies involved in the development of helminth vaccines. The map has regions corresponding to plasmids and other gene based technologies used in DNA vaccines for Japonicum Schistosoma. Important technologies listed on the map include the use of reverse genetics to create reassorted viruses targeted for the use in veterinary applications. Additionally, the map suggests that numerous subunits exist for use in vaccines targeting cestodes, trematodes, and nematodes. Another major finding was that the number of patent documents related to helminths being published has been steadily increasing in the last decade, as shown in the figure below. Until the early-1990s, there were only a few helminth vaccine related patent documents being published each year. The number of publications increased noticeably when TRIPS took effect, resulting in publication of patent applications. However, since 2006 the number of vaccine publications has exploded. In the years 2011 and 2012, about 23 references disclosing parasitic worm vaccine technologies were published each year. Thus, interest in developing new and more efficacious helminth vaccines has been growing in recent years. The origin of the vaccine-related inventions was also analyzed. The team determined the country in which the priority application was filed, which was taken as an indication of the country where the invention was made or where the inventors intended to practice the invention. By far, most of the relevant families originated with patent applications filed in the United States and China. Other prominent priority countries were the United Kingdom, Japan, Brazil, Australia and France. Countries with the most filings were also analyzed. Countries that were heavily targeted for patent filings included the United States, Australia, Canada, and New Zealand. Top assignees for these families were mostly large pharmaceutical companies, with the majority of patent families coming from Heska, followed by Merck & Co., Institute Pasteur, AusBiotech Biotechnology, and Biological Sciences Research Council. Lastly, the jurisdictions were inventors have sought protection for their vaccine technologies were determined, and the number of patent families filing in a given country is plotted on the world map shown (Fig. 25). The United States, Canada, Australia, Japan, New Zealand and France have the highest level of filings, followed by Germany, Brazil, India, United Kingdom and Spain. However, although there are a significant number of filings in Brazil, the remainder of Central and South America has only sparse filings. Of concern, with the exception of South Africa, few other African nations have a significant number of filings. In summary, the goal of this report is to provide a knowledge resource for making informed policy decisions and for creating strategic plans concerning the assembly of vaccines targeting highly prevalent helminth infections. The ITTI team has defined the current state of the art of technologies involved in the manufacture of helminth vaccines, and the important assignees, inventors, and countries have been identified. This document should aid in evaluating the current state of vaccines technologies targeting helminths and the potential outgrows of these technological fields. Furthermore, as this report illustrates, the steady increase in helminth patenting, expanded diversity of assignees and greater global filings, indicates that intellectual property protection does not inhibit the development of crucial innovations for this class of neglected diseases, but, on the contrary, appears to be a driver of accelerated research and development

Bidirectional Pressure-Regulator System

A bidirectional pressure-regulator system has been devised for use in a regenerative fuel cell system. The bidirectional pressure-regulator acts as a back-pressure regulator as gas flows through the bidirectional pressure-regulator in one direction. Later, the flow of gas goes through the regulator in the opposite direction and the bidirectional pressure-regulator operates as a pressure- reducing pressure regulator. In the regenerative fuel cell system, there are two such bidirectional regulators, one for the hydrogen gas and another for the oxygen gas. The flow of gases goes from the regenerative fuel cell system to the gas storage tanks when energy is being stored, and reverses direction, flowing from the storage tanks to the regenerative fuel cell system when the stored energy is being withdrawn from the regenerative fuel cell system. Having a single bidirectional regulator replaces two unidirectional regulators, plumbing, and multiple valves needed to reverse the flow direction. The term "bidirectional" refers to both the bidirectional nature of the gas flows and capability of each pressure regulator to control the pressure on either its upstream or downstream side, regardless of the direction of flow

PhoSim-NIRCam: Photon-by-photon image simulations of the James Webb Space Telescope's Near-Infrared Camera

Recent instrumentation projects have allocated resources to develop codes for simulating astronomical images. Novel physics-based models are essential for understanding telescope, instrument, and environmental systematics in observations. A deep understanding of these systematics is especially important in the context of weak gravitational lensing, galaxy morphology, and other sensitive measurements. In this work, we present an adaptation of a physics-based ab initio image simulator: The Photon Simulator (PhoSim). We modify PhoSim for use with the Near-Infrared Camera (NIRCam) -- the primary imaging instrument aboard the James Webb Space Telescope (JWST). This photon Monte Carlo code replicates the observational catalog, telescope and camera optics, detector physics, and readout modes/electronics. Importantly, PhoSim-NIRCam simulates both geometric aberration and diffraction across the field of view. Full field- and wavelength-dependent point spread functions are presented. Simulated images of an extragalactic field are presented. Extensive validation is planned during in-orbit commissioning

Sequence validation of candidates for selectively important genes in sunflower

Analyses aimed at identifying genes that have been targeted by past selection provide a powerful means for investigating the molecular basis of adaptive differentiation. In the case of crop plants, such studies have the potential to not only shed light on important evolutionary processes, but also to identify genes of agronomic interest. In this study, we test for evidence of positive selection at the DNA sequence level in a set of candidate genes previously identified in a genome-wide scan for genotypic evidence of selection during the evolution of cultivated sunflower. In the majority of cases, we were able to confirm the effects of selection in shaping diversity at these loci. Notably, the genes that were found to be under selection via our sequence-based analyses were devoid of variation in the cultivated sunflower gene pool. This result confirms a possible strategy for streamlining the search for adaptively-important loci process by pre-screening the derived population to identify the strongest candidates before sequencing them in the ancestral population

The decline of laparoscopic sterilisation

Female sterilisation is an extensively used method of contraception all over the world but there appears to be a decline in the performance of this procedure in Ireland. There also appears to be an increased uptake of safe, long-acting contraceptive alternatives. We set out to establish the extent of the decline of laparoscopic sterilisation and to explore possible explanations. Data for female sterilisation from Ireland was obtained from the Hospital In-Patient Enquiry Scheme (HIPE) section of the Economic and Social Research Institute for the years 1999 to 2004. Recent sales figures for long acting reversible contraceptives, specifically the levo-norgestrel-loaded intrauterine system (LNG-IUS) (Mirena) and the etonogestrel implant (Implanon) were also obtained. Laparoscopic tubal ligations reduced from 2,566(1999) to 910 (2004). In the corresponding period the use of Mirena coils increased from 4,840 (1999) to 17,077 (2004)

Pleasant emotions widen thought-action repertoires, develop long-term resources, and improve reaction time performance: A multi-study examination of the Broaden-and-Build theory among athletes

The authors investigated relationships between emotions, coping, and resilience across two studies. In Study 1a, 319 athletes completed dispositional questionnaires relating to the aforementioned constructs. In Study 1b, 126 athletes from Study 1a repeated the same questionnaires 6months later. In Study 2, 21 athletes were randomly allocated to an emotional (e.g., pleasant or unpleasant emotions) or control group and undertook a laboratory-based reaction-time task across three time points. Questionnaires and salivary cortisol samples were collected before and after each performance with imagery-based emotional manipulations engendered during the second testing session. Partial longitudinal evidence of the broaden-and-build effects of pleasant emotions was found. Pleasant emotions may undo lingering cognitive resource losses incurred from previous unpleasant emotional experiences. In Study 2, pleasant and unpleasant emotions had an immediate and sustained psychophysiological and performance impact. Taken together, this research supports the application of broaden-and-build theory in framing emotional interventions for athletes

Stress appraisals influence athletic performance and psychophysiological response during 16.1 km cycling time trials

Objectives: We examined how stress appraisals were associated with emotions, coping behaviours, as well as subjective and objective measures of performance.Design: Prospective field- and laboratory-based studies.Methods: In Study 1, 192 athletes completed process-oriented psychometrics pertaining to the aforementioned constructs throughout a sporting competition. Study 2 utilised an experimental design to assess the causal influence of stress appraisals on performance, cortisol, and psychological variables. Thirty gender-matched athletes were randomly assigned to either a stress appraisal (e.g., challenge, threat, benefit, or harm/loss) or the control group. Participants completed three 16.1km cycling time trials (TT) on a cycle ergometer, with their appropriate stress appraisal engendered via falsified performance feedback throughout the final TT. Salivary cortisol samples and psychometrics (e.g., appraisals, emotions, and coping) were collected before and after each TT.Results: The results of Study 1 revealed a sequential link between challenge stress appraisals and perceived goal attainment via pleasant emotions and task-oriented coping behaviours. Threat stress appraisals inversely related to goal attainment via unpleasant emotions and both distraction- and disengagement-oriented coping. In Study 2, no significant psychophysiological or performance differences were found across genders. The temporal orientation of stress appraisals influenced objective cycling TT performance. Benefit and harm/loss stress appraisals significantly facilitated or inhibited performance, respectively. Cortisol spikes were observed in the stress appraisal group’s threat, challenge, and benefit, with a decline detected within the harm/loss group. Whilst the process of winning is physiologically stressful, the fear of defeat may be more stressful than losing itself. Conclusion: Stress appraisals influence subjective and objective performance, as well as neuroendocrine and psychological responses to stress. Stress Appraisals Influence Athletic Performance and Psych

A target enrichment method for gathering phylogenetic information from hundreds of loci: An example from the Compositae.

UnlabelledPremise of the studyThe Compositae (Asteraceae) are a large and diverse family of plants, and the most comprehensive phylogeny to date is a meta-tree based on 10 chloroplast loci that has several major unresolved nodes. We describe the development of an approach that enables the rapid sequencing of large numbers of orthologous nuclear loci to facilitate efficient phylogenomic analyses. •Methods and resultsWe designed a set of sequence capture probes that target conserved orthologous sequences in the Compositae. We also developed a bioinformatic and phylogenetic workflow for processing and analyzing the resulting data. Application of our approach to 15 species from across the Compositae resulted in the production of phylogenetically informative sequence data from 763 loci and the successful reconstruction of known phylogenetic relationships across the family. •ConclusionsThese methods should be of great use to members of the broader Compositae community, and the general approach should also be of use to researchers studying other families