Recent Patents on Biotechnology - Volume 15, Issue 1, 2021

Background: Argentina has progressed with industrialization in comparison to other Latin American countries and this process had a direct impact on the innovative capacity of the national economy. A constant search for market leadership, including the dentistry field and dental materials, stimulates the industries to launch new products daily. Inventions related to health researches are mostly protected by patents as intellectual property. A patent landscape analysis through searches in patent banks is a tool used to identify trends in different areas of innovations. Objective: This study aims to identify and evaluate the scenario of research, development and innovation of dental products in Argentina by a technological prospecting based on patents. Methods: A survey of patent documents was conducted by searching for deposited and granted patents of dental products. The search was carried out during January 2020 in the patent database of the National Institute of Industrial Property of Argentina (INPI-AR). The terms “dentistry”, “buccal”, “dental” and “oral” were used to select the titles and abstracts of patent application reports. The information extracted from patent reports was organized in tables and Figs using Fig.Pad Prism 6 software to evaluate the applications. Results: A total of 363 patents were published from 1989 to 2016, mainly by international industries, 93.3% as patent invention and 3.0% as utility model applications on dentistry. Only two patents (0.5%) were deposited by universities, as the University of Melbourne (Patent number 20060102378) and Universidad Nacional del Nordeste (Patent number 20140104149), among which only the last one is national. Among the deposits, only 6.6% were granted; mostly were in force, denied or lost. According to the specialties, most patents were related to compositions (64.7%) and personal products (21.7%), also on dentistry/cariology (6.33%) and prostheses/implants (4.68%). Conclusion: In general, we find that most patent applications are related to the preventive area, personal products and compositions for formulations. Few dental patents deposits are currently available in Argentina, suggesting that the importation of products into the area remains large, which can make dental products more expensive. It is important to invest in technology-based companies to promote increased economic activity, being a consequence of an investment in knowledge creation and intellectual property to the Dentistry area.

Background: Coronaviruses have caused outbreaks of respiratory disease since the beginning of the 21^st century, representing a significant threat to public health. Together, the severe acute respiratory syndrome coronavirus (SARS-CoV), the respiratory syndrome coronavirus (MERS-CoV), and, more recently, the novel coronavirus (SARS-CoV-2) have caused a large number of deaths around the world. Thus, investments in research and the development of strategies aimed at diagnosing, treating, and preventing these infections are urgently needed. Objective: The objective of this study was to analyze the patents that address pathogenic coronaviruses in Google Patents databases in the last year (2019-2020). Methods: The search strategy was carried out in April 2020, based on the keywords “SARS”, “SARS-CoV”, “MERS”, “MERS-CoV”, “SARS-CoV-2” and “COVID-19. Out of the patents examined, 25 were selected for a short description in this study. Results: A total of 191 patents were analyzed, 149 of which were related to SARS-CoV, and 29 and 12 were related to MERS-CoV and SARS- CoV2, respectively. The patents addressed the issues of diagnosis, therapeutic agents, prevention and control, along with other applications. Conclusion: Several promising strategies have been documented in intellectual property databases favoring the need for further studies on the pathogenesis and optimization of the diagnosis and therapeutic treatment for these emerging infections.

Bacteriophages are bacterio-specific viruses that constitute the main portion of the environment. Bacteriophages inject their genome into the targeted bacterial cells and some of them can disrupt the metabolism of bacteria and cause bacterial cell disintegration. The application of bacteriophages to kill bacteria is known as bacteriophage therapy. Since bacteriophages target bacteria and are strain-specific, every bacteriophage/bacterial host pair is unique. They are believed to cause no harm to humans. An additional advantage of the strain-specific nature of bacteriophages is that they do not disrupt the beneficial natural flora in the body. Bacteriophage therapy in the West is not a recognized medicine at this time, and no products are registered. Some clinicians are turning to bacteriophage therapy for the treatment of antibiotic-resistant infections. Lack of adverse effects makes bacteriophage therapy ideal for use. Funding research, media attention, and the increased publication of articles helped in a widespread understanding of its therapeutic potential. The first prerequisite for the use of bacteriophage therapy is simply the availability of bacteriophages for treatment, which is often complicated at this stage of bacteriophage production. This includes providing access to all biologically active bacteriophages against the bacterial isolate of the patient and meeting regulatory criteria of purity, traceability, and characterization. A monophage preparation, which is a single bacteriophage, or a phage cocktail, which consists of a number of combined bacteriophages against one or more bacterial species may be used. Accordingly, the antibiotic resistance crisis brought back bacteriophage therapy as a potential complementary or alternative treatment. Bacteriophages are promising cheap antibacterials.

Background: The immediate automatic systemic monitoring and reporting of adverse drug reactions, improving the efficacy is the utmost need of the medical informatics community. The venturing of advanced digital technologies into the health sector has opened new avenues for rapid monitoring. In recent years, data shared through social media, mobile apps, and other social websites has increased manifolds requiring data mining techniques. Objective: The objective of this report is to highlight the role of advanced technologies together with the traditional methods to proactively aid in the early detection of adverse drug reactions concerned with drug safety and pharmacovigilance. Methods: A thorough search was conducted on papers and patents regarding pharmacovigilance. All articles with respect to the relevant subject were explored and mined from public repositories such as Pubmed, Google Scholar, Springer, ScienceDirect (Elsevier), Web of Science, etc. Results: The European Union’s Innovative Medicines Initiative WEB-RADR project has emphasized the development of mobile applications and social media data for reporting adverse effects. Only relevant data has to be captured through the data mining algorithms (DMAs) as it plays an important role in timely prediction of risk with high accuracy using two popular approaches; the frequentist and Bayesian approach. Pharmacovigilance at the pre-marketing stage is useful for the prediction of adverse drug reactions in the early developmental stage of a drug. Later, post-marketing safety reports and clinical data reports are important to be monitored through electronic health records, prescription-event monitoring, spontaneous reporting databases, etc. Conclusion: The advanced technologies supplemented with traditional technologies are the need of the hour for evaluating a product’s risk profile and reducing risk in population especially with comorbid conditions and on concomitant medications.

Background: Microorganisms can migrate from the external environment to the patient’s organism through the insertion of catheters. Despite being indispensable medical device, the catheter surface can be colonized by microorganisms and become a starting point for biofilm formation. Therefore, new technologies are being developed in order to modify surfaces to prevent the adhesion and survival of microorganisms. Patents with the use of DMPEI have been filed. Objective: In the present work, we coated latex catheter surfaces with 2 mg mL-1 DMPEI in different solvents, evaluated the wettability of the surface and the anti- biofilm activity of the coated catheter against Escherichia coli, Staphylococcus aureus, and Candida albicans. Methods: We coated the inner and outer catheter surfaces with 2 mg mL-1 of DMPEI solubilized in butanol, dimethylformamide, and cyclohexanone and the surfaces were analyzed visually. Contact angle measurement allowed the analysis of the wettability of the surfaces. The CFU mL-1 count evaluated E. coli, S. aureus, and C. albicans adhesion onto the control and treated surfaces. Results: The contact angle decreased from 50.48º to 46.93º on the inner surface and from 55.83º to 50.91º on the outer surface of latex catheters coated with DMPEI. The catheter coated with DMPEI showed anti-biofilm activity of 83%, 88%, and 93% on the inner surface and 100%, 92%, and 86% on the outer surface for E. coli, S. aureus, and C. albicans, respectively. Conclusion: Latex catheter coated with DMPEI efficiently impaired the biofilm formation both on the outer and inner surfaces, showing a potential antimicrobial activity along with a high anti-biofilm activity for medical devices.

Background: Human MxA gene is related to the class of interferon (IFN)-stimulated genes (ISGs) that plays a role in antiviral resistance. Objective: Implementation of standard curves obtained from designing a procedure for data processing in relative qPCR between MxA expression and interferon’s antiviral activity (IU/ml). These standard curves can be used to detect the antiviral activity of any new compound rapidly and safely. Methods: To detect the optimum incubation time for maximum MxA gene expression in human peripheral blood mononuclear cells (PBMC), the isolated human PBMCs (1x106 cells) were incubated with a concentration of 1000 IU/ml of each IFN at different time intervals; 2 h, 4 h, 6 h, and 24 h post-treatment. A standard curve was performed for each IFN (α, β, and γ) at different concentrations (250, 500, 750, 1000, 1500, and 2000 IU/ml). Results: As observed at 4 h incubation time of 1000 IU/ml concentration, IFN-γ provided a higher expression of MxA compared to IFN-α and IFN-β. Correlation analyses between IFN-α and IFN-β, IFN-β and IFN-γ were non-significant. However, there was a significant correlation between IFN-α and IFN-γ (p<0.01). Receiver operator characteristic (ROC) analysis revealed that cut-off values of IFN- γ, IFN-β, and IFN-α were 58.14 > 7.31 and > 3.33, respectively. Conclusions: The relative expression of MxA is a biomarker for IFN-α, β, and γ, especially IFN-α. It has compiled and validated a standard curve-based protocol for PCR data processing. It shows that the standard curve is an easy alternative tool to assess antiviral activity. We revised all patents relating to the antiviral assays of the used interferons.

Background: Commercial poultry farming is expanding every day and contributing to the provision of affordable and high-quality protein. However, this sector is confronted with many diseases of which coccidiosis is among the most important. There are many registered patents affirming the health benefits of Garcinia kola in poultry. Objective: Evaluation of in vitro anticoccidial activities of the extracts and fractions of Garcinia kola against Eimeria tenella oocyst was carried out. Methods: Fresh seeds of G. kola were collected, dried under shade at room temperature, and pulverized using a mortar and a pestle. The powder was exhaustively extracted with a soxhlet apparatus using 70% methanol, and the crude methanol extract (CME) was concentrated to dryness using a rotary evaporator. The CME was further partitioned using butanol, ethylacetate, and n-hexane. The CME, butanol fraction (BTF), ethylacetate fraction (EAF), and hexane fraction (HXF) were concentrated in vacuo and tested for the presence of phytochemical constituents using standard procedures. Similarly, the CME, butanol, ethyl acetate, and hexane fractions were evaluated in vitro for oocyst sporulation inhibition. Results: Phytochemical analysis revealed the presence of cardiac glycosides, saponins, carbohydrates, steroids/triterpenes, tannins, flavonoids, and alkaloids in the CME and BTF. The EAF contains all the metabolites mentioned except saponins. Similarly, HXF contains only cardiac glycosides, tannins, and steroids/ triterpenes. The CME and BTF caused a concentration-dependent increase in the inhibition of sporulation of unsporulated oocysts of E. tenella. In the acute toxicity studies, the CME did not produce any toxic effect or mortality at doses between 10 and 5000 mg/kg. The CME was then considered safe, and the LD50 was assumed to be >5000 mg/kg. Conclusion: The data obtained in this study suggested that the crude methanol extract (CME) of G. kola could be an appreciable beneficial effect as an anticoccidial agent against Eimeria tenella oocyst.