A significant limitation of numerous current genetic engineering therapy approaches is their limited control over the strength, timing, or cellular context of their therapeutic effect. Synthetic gene/genetic circuits are synthetic biology approaches that can control the generation, transformation, or depletion of a specific DNA, RNA, or protein and provide precise control over gene expression and cellular behavior. They can be designed to perform logical operations by carefully selecting promoters, repressors, and other genetic components. Patent search was performed in Espacenet, resulting in 38 selected patents with 15 most frequent international classifications. Patent embodiments were categorized into applications for the delivery of therapeutic molecules, treatment of infectious diseases, treatment of cancer, treatment of bleeding, and treatment of metabolic disorders. The logic gates of selected genetic circuits are described to comprehensively demonstrate their therapeutic applications. Synthetic gene circuits can be customized for precise control of therapeutic interventions, leading to personalized therapies that respond specifically to individual patient needs, enhancing treatment efficacy and minimizing side effects. They can be highly sensitive biosensors that provide real-time therapy by accurate monitoring various biomarkers or pathogens and appropriately synthesizing a therapeutic molecule. Synthetic gene circuits may also lead to the development of advanced regenerative therapies and to implantable biodevices that produce on-demand bioactive molecules. However, this technology faces challenges for commercial profitability. The genetic circuit designs need adjustments for specific applications, and may have disadvantages like toxicity from multiple regulators, homologous recombination, context dependency, resource overuse, and environmental variability.

BACKGROUND: Decompressive craniectomy (DC) is a widely used procedure to alleviate high intracranial pressure. Multidisciplinary teams have designed and implemented external medical prototypes to improve patient life quality and avoid complications following DC in patients awaiting cranioplasty (CP), including 3D printing and plaster prototypes when available.
OBJECTIVE: This scoping review aims to understand the extent and type of evidence about innovative external prototypes for patients who undergo DC while awaiting CP.
METHODS: This scoping review will use the Joanna Briggs Institute methodology for scoping reviews. This scoping review will include noninvasive medical devices for adult patients who undergo DC while waiting for CP. The search strategy will be implemented in MEDLINE, Embase, Web of Science, Scielo, Scopus, and the World Health Organization (WHO) Global Health Index Medicus. Patent documents were also allocated in Espacenet, Google Patents, and the World Intellectual Property Organization (WIPO) database.
RESULTS: This scoping review is not subject to ethical approval as there will be no involvement of patients. The dissemination plan includes publishing the review findings in a peer-reviewed journal and presenting results at conferences that engage the most pertinent stakeholders in innovation and neurosurgery.
CONCLUSIONS: This scoping review will serve as a baseline to provide evidence for multidisciplinary teams currently designing these noninvasive innovations to reduce the risk of associated complications after DC, hoping that more cost-effective models can be implemented, especially in low- and middle-income countries.
UNASSIGNED: DERR1-10.2196/50647.

Due to the great interest in ovarian cryopreservation and, consequently conservation and restoration of female fertility in the last decades, different vitrification procedures (vitrification devices or solutions) have been developed, patented, and used both for academic research purposes and for clinical use. Therefore, the present study aimed to provide a systematic review and meta-analysis of data obtained from the application of different patented and non-patented vitrification devices and solutions in different countries. For this purpose, relevant observational studies published between the years 2000 to 2021 were selected to verify the efficiency of ovarian vitrification processes on parameters such as morphology, viability, and apoptosis in preantral ovarian follicles after transplantation or in vitro culture. Our research revealed that, although several countries were considered in the study, the United States and Japan were the countries that registered the most processes, and 22 and 16 vitrification devices and solutions out of a total of 51, respectively were patented. Sixty-two non-patented processes were also considered in the study in all countries. We also observed that transplantation and in vitro ovarian culture were the techniques predominantly used to evaluate the efficiency of the devices and vitrification solutions, respectively. In conclusion, this review showed that patented or non-patented protocols available in the literature are able to successfully preserve preantral follicles present in ovarian tissue. Despite the satisfactory results reported so far, adjustments in ovarian vitrification protocols in order to minimize cryoinjuries to the follicles remain one of the goals of cryopreservation and preservation of the female reproductive function. We found that vitrification alters the morphology and viability, and offers risks leading in some cases to follicular apoptosis. However, adjustments to current protocols to develop an optimal procedure can minimize damage by not compromising follicular development after vitrification/warming.

BACKGROUND: Morus nigra L. is a plant with significant potential for drug development due to the presence of numerous bioactive compounds in its various parts.
OBJECTIVE: This article aims to compile the technological perspectives of Morus nigra L. towards drug development and therapeutic indications based on registered patents in databases.
METHODS: The study analyzed patents published within the last five years, focusing on products derived from different parts of the Morus nigra L. plant. Patent databases such as the European Patent Office (EPO), the United States Patent and Trademark Office (USPTO), the World Intellectual Property Organization (WIPO), and the National Institute of Industrial Property Databases (INPI) were examined.
RESULTS: A total of 45 patents were categorized by country of origin, type of applicant, extraction method, and therapeutic indications. China had the highest number of patent filings (43.48%), and private companies were the primary technology patent holders (38.64%). Noteworthy extraction methods included ultrasound-assisted extraction, decoction, infusion, and maceration. The most utilized plant parts were leaves (44.44%), followed by fruits (35.56%), root bark (15.56%), and stems (4.44%). The main therapeutic indications identified were the treatment of hyperglycemia and dyslipidemia (43.33%), along with digestive problems, cosmetics, nutrition, and cleaning applications.
CONCLUSIONS: The study of patents covers discoveries and advancements often absent in scientific articles, making a review focused on this advanced information crucial for expanding existing scientific knowledge. Even if some therapies have been explored previously, patents can reveal innovative approaches and fresh perspectives that contribute to sustained scientific progress.

Repurposing is considered an attractive approach for developing new drug products. However, it consists of challenges relating to intellectual property (IP) protection, and regulatory approvals. This study aimed to analyze the recent trends in repurposed drugs approved by USFDA from 2010 to 2020 and to assess the challenges connected with bridging study requirements, patent protection, and exclusivities. Out of 1001 NDAs, 570 were approved via 505(b)(2) pathway. Of 570 NDAs, the highest number of approvals are allied to type 5-new formulations (42.4%), followed by type 3-new dosage forms (26.4%) and type 4-new combinations (13.1%). Of 570 NDAs, 470 are considered to examine the patent and exclusivity protection of which 341 have patent and/or exclusivity. A total of 97 type-3 and type-5 and 14 type-4 drugs have been approved based on human bioavailability/bioequivalence (BA/BE) data. For 131 type-3 and type-5 and 34 type-4 drugs, the applicants conducted new clinical (efficacy and/or safety) studies along with BA/BE (100 drugs) or without BA/BE (65 drugs) studies. In this review, mechanistic reasons for conducting new clinical investigations, IP and regulatory considerations along with broader perspective on new pharmaceutical approaches employed in 505(b)(2) drugs are illustrated that provide guidance for development of reformulations and combinations.

It is widely accepted that intellectual property legal requirements such as patents and data exclusivity can affect access to medicines, but to date there has not been a comprehensive review of the empirical evidence on this topic. The World Trade Organization\'s Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) requires Member States to implement minimum standards of intellectual property protection including patents for pharmaceutical products, but also contains \'flexibilities\' designed to address barriers to access to medicines. National intellectual property laws can also include TRIPS-plus rules that go beyond what is required by TRIPS. We aimed to systematically review literature that measures the impact of intellectual property rules on access to medicines, whether implemented as a result of TRIPS, TRIPS-plus provisions in other trade agreements, or unilateral policy decisions.
We searched Proquest, SCOPUS, Web of Science, PubMed, JSTOR, Westlaw and Lexis Nexis. Peer reviewed articles, government reports and other grey literature were included. Articles were eligible for inclusion if they were quantitative, in English, included a measure of cost, price, availability of or access to medicines, were about intellectual property or data exclusivity rules and published between January 1995 and October 2020. Ninety-one studies met our inclusion criteria. We systematically reviewed the studies\' findings and evaluated their quality using a modified quality assessment template.
Five broad overarching themes and 11 subthemes were identified based on the articles\' foci. They were: trade agreements (divided into EU FTAs and those that include the USA); use of TRIPS flexibilities (divided into compulsory licencing and parallel importation); patent expiry/generic entry/generic pathway (divided into comparative studies and single country studies); patent policies (also divided into comparative studies and single country studies) and TRIPS-plus rules (divided into data exclusivity, patent term extensions and secondary patenting). Most studies focused not on specific trade agreements, but on TRIPS-plus provisions, which can also be found within some trade agreements. The main finding of this review is that the stronger pharmaceutical monopolies created by TRIPs-plus intellectual property rules are generally associated with increased drug prices, delayed availability and increased costs to consumers and governments. There is evidence that TRIPS flexibilities can facilitate access to medicines although their use is limited to date. There were few studies that included resource poor settings, signalling a need for greater research in such settings where the impact on access to medicines is likely to be more damaging.

Generating functional protein variants with novel or improved characteristics has been a goal of the biotechnology industry and life sciences, for decades. Rational design and directed evolution are two major pathways to achieve the desired ends. While rational protein design approach has made substantial progress, the idea of using a method based on cycles of mutagenesis and natural selection to develop novel binding proteins, enzymes and structures has attracted great attention. Laboratory evolution of proteins/enzymes requires new tools and analytical approaches to create genetic diversity and identifying variants with desired traits. In this pursuit, construction of sufficiently large libraries of target molecules to search for improved variants and the need for new protocols to alter the properties of target molecules has been a continuing challenge in the directed evolution experiments. This review will discuss the in vivo and in vitro gene diversification tools, library screening or selection approaches, and artificial intelligence/machine-learning-based strategies to mutagenesis developed in the last 40 years to accelerate the natural process of evolution in creating new functional protein variants, optimization of microbial strains, and transformation of enzymes into industrial machines. Analyzing patent position over these techniques and mechanisms also constitutes an integral and distinctive part of this review. The aim is to provide an up-to-date resource/technology toolbox for research-based and pharmaceutical companies to discover the boundaries of competitor\'s intellectual property (IP) portfolio, their freedom-to-operate in the relevant IP landscape, and the need for patent due diligence analysis to rule out whether use of a particular patented mutagenesis method, library screening/selection technique falls outside the safe harbor of experimental use exemption. While so doing, we have referred to some recent cases that emphasize the significance of selecting a suitable gene diversification strategy in directed evolution experiments.

International trade has become more complicated and is now related to more aspects of health and the health system. As Thailand is active in international trade and health, understanding what knowledge exists and determining the knowledge gap is essential for generating the necessary evidence in order to promote better understanding and allow evidence-based policy decisions to be made. This study reviewed the existence of knowledge on international trade and health issues in a scoping review, focusing on Thailand during the period 1991-2020. In total, 156 studies from seven databases and manual searching were included. Of these, 46% were related to trade in health services and 39% were linked to intellectual property, particularly access to medicines. This review found only a very small amount of research on other issues and did not identify any study on trade policies or products related to health and international trade and the environment. We therefore recommend that further studies should be carried out to provide more critical evidence-in particular, more research focusing on the impacts of trade on health-related goods and the analysis of the positive and negative impacts of international trade on industry is needed. Furthermore, better knowledge management through the publication of research findings and making them searchable on international databases will increase the visibility of international trade, increase our knowledge of health issues, and provide supporting evidence.

Areas of open science (OS) policy and practice are already relatively well-advanced in several countries and sectors through the initiatives of some governments, funders, philanthropy, researchers and the community. Nevertheless, the current research and innovation system, including in the focus of this report, the life sciences, remains weighted against OS. In October 2017, thought-leaders from across the world gathered at an Open Science Leadership Forum in the Washington DC office of the Bill and Melinda Gates Foundation to share their views on what successful OS looks like. We focused on OS partnerships as this is an emerging model that aims to accelerate science and innovation. These outcomes are captured in a first meeting report: Defining Success in Open Science. On several occasions, these conversations turned to the challenges that must be addressed and new policies required to effectively and sustainably advance OS practice. Thereupon, in this report, we describe the concerns raised and what is needed to address them supplemented by our review of the literature, and suggest the stakeholder groups that may be best placed to begin to take action. It emerges that to be successful, OS will require the active engagement of all stakeholders: while the research community must develop research questions, identify partners and networks, policy communities need to create an environment that is supportive of experimentation by removing barriers. This report aims to contribute to ongoing discussions about OS and its implementation. It is also part of a step-wise process to develop and mobilize a toolkit of quantitative and qualitative indicators to assist global stakeholders in implementing high value OS collaborations. Currently in co-development through an open and international process, this set of measures will allow the generation of needed evidence on the influence of OS partnerships on research, innovation, and critical social and economic goals.

Mounting evidence indicates that worldwide, innovation systems are increasing unsustainable. Equally, concerns about inequities in the science and innovation process, and in access to its benefits, continue. Against a backdrop of growing health, economic and scientific challenges global stakeholders are urgently seeking to spur innovation and maximize the just distribution of benefits for all. Open Science collaboration (OS) - comprising a variety of approaches to increase open, public, and rapid mobilization of scientific knowledge - is seen to be one of the most promising ways forward. Yet, many decision-makers hesitate to construct policy to support the adoption and implementation of OS without access to substantive, clear and reliable evidence. In October 2017, international thought-leaders gathered at an Open Science Leadership Forum in the Washington DC offices of the Bill and Melinda Gates Foundation to share their views on what successful Open Science looks like. Delegates from developed and developing nations, national governments, science agencies and funding bodies, philanthropy, researchers, patient organizations and the biotechnology, pharma and artificial intelligence (AI) industries discussed the outcomes that would rally them to invest in OS, as well as wider issues of policy and implementation. This first of two reports, summarizes delegates\' views on what they believe OS will deliver in terms of research, innovation and social impact in the life sciences. Through open and collaborative process over the next months, we will translate these success outcomes into a toolkit of quantitative and qualitative indicators to assess when, where and how open science collaborations best advance research, innovation and social benefit. Ultimately, this work aims to develop and openly share tools to allow stakeholders to evaluate and re-invent their innovation ecosystems, to maximize value for the global public and patients, and address long-standing questions about the mechanics of innovation.