Breaking Barriers in Alzheimer's Disease: the Role of Advanced Drug Delivery Systems.

Alzheimer's disease (AD), characterized by cognitive impairment, brain plaques, and tangles, is a global health concern affecting millions. It involves the build-up of amyloid-ß (Aß) and tau proteins, the formation of neuritic plaques and neurofibrillary tangles, cholinergic system dysfunction, genetic variations, and mitochondrial dysfunction. Various signaling pathways and metabolic processes are implicated in AD, along with numerous biomarkers used for diagnosis, risk assessment, and research. Despite these, there is no cure or effective treatment for AD. It is critically important to address this immediately to develop novel drug delivery systems (NDDS) capable of targeting the brain and delivering therapeutic agents to modulate the pathological processes of AD. This review summarizes AD, its pathogenesis, related signaling pathways, biomarkers, conventional treatments, the need for NDDS, and their application in AD treatment. It also covers preclinical, clinical, and ongoing trials, patents, and marketed AD formulations.

Bacterial extracellular biopolymers: Eco-diversification, biosynthesis, technological development and commercial applications.

Synthetic polymers have been widely thriving as mega industries at a commercial scale in various commercial sectors over the last few decades. The extensive use of synthetic polymers has caused several negative repercussions on the health of humans and the environment. Recently, biopolymers have gained more attention among scientists of different disciplines by their potential therapeutic and commercial applications. Biopolymers are chain-like repeating units of molecules isolated from green sources. They are self-degradable, biocompatible, and non-toxic in nature. Recently, eco-friendly biopolymers such as extracellular polymeric substances (EPSs) have received much attention for their wide applications in the fields of emulsification, flocculation, preservatives, wastewater treatment, nanomaterial functionalization, drug delivery, cosmetics, glycomics, medicinal chemistry, and purification technology. The dynamicity of applications has raised the industrial and consumer demands to cater to the needs of mankind. This review deals with current insights and highlights on database surveys, potential sources, classification, extremophilic EPSs, bioprospecting, patents, microenvironment stability, biosynthesis, and genetic advances for production of high valued ecofriendly polymers. The importance of high valued EPSs in commercial and industrial applications in the global market economy is also summarized. This review concludes with future perspectives and commercial applications for the well-being of humanity.

Ephrin receptor type-A2 (EphA2) targeting in cancer: a patent review (2018-present).

INTRODUCTION: EphA2 is a tyrosine kinase receptor and is considered a promising target in cancer. Different approaches are used to target EphA2 receptor, and a lot of preclinical data demonstrate the potential exploitation of this receptor in clinical oncology for diagnosis and cancer therapy, including immunotherapy. AREAS COVERED: In this review, we have summarized the recent patents involving the EphA2 targeting in cancer. For this aim, we used the patent database Patentscope covering the time period of 2018-present. Preclinical and clinical data of the inventions were considered when published on peer reviewed journals. Moreover, the clinicalTrial.gov identifiers (NCT numbers) were included when available. For an easier and more immediate reading, we classify the patents in different categories, considering the nature (aptamers, small molecules, antibodies, peptides, antigens and chimeric antigen receptors) of the inventions exploiting EphA2 in clinical oncology. EXPERT OPINION: Despite the availability of a plethora of chemically diverse agents, there are no approved anticancer drugs targeting EphA2 yet. However, these intellectual properties, some of which supported by strong preclinical evidence, keep the hope that, after more than 30 years from its discovery, we will finally see the first EphA2 targeting agent approved in clinical oncology.

Advanced Nanotechnological Approaches for Effective Delivery of Rutin: An Updated Review.

Polyphenols are a group of naturally occurring compounds that have intriguing biological activities. Among these compounds is rutin, a polyphenolic flavanol found in many plants, including passion flowers, buckwheat seed, fruits and fruit rinds, and citrus fruits (such as orange, grapefruit, lemon, and lime). Various studies have demonstrated rutin to possess antibacterial, antifungal, antiallergic, anti-inflammatory, anti-diabetic, anti-adipogenic, anti-carcinogenic, anti-apoptotic, anti-osteoporotic, radioprotective, gastroprotective, neuroprotective, and nephroprotective activities. Despite its benefits, rutin's therapeutic applicability is severely limited due to its low water solubility, sensitivity to oxidation, and dissolving rate. However, these problems can be overcome by employing an efficient delivery approach. An extensive number of nanocarriers can be developed for medicinal use if pre-clinical as well as human-clinical studies are completed. The current review presents an overview of effective rutin nano-formulations for targeted therapy in various health disorders. This review article discusses the clinical evidence, current status, as well as future opportunities of rutin nanocarriers for increasing rutin's bioactivity for possible medicinal uses.

The evolution of plant phenomics: global insights, trends, and collaborations (2000-2021).

Introduction: Phenomics, an interdisciplinary field that investigates the relationships between genomics and environmental factors, has significantly advanced plant breeding by offering comprehensive insights into plant traits from molecular to physiological levels. This study examines the global evolution, geographic distribution, collaborative efforts, and primary research hubs in plant phenomics from 2000 to 2021, using data derived from patents and scientific publications. Methods: The study utilized data from the EspaceNet and Lens databases for patents, and Web of Science (WoS) and Scopus for scientific publications. The final datasets included 651 relevant patents and 7173 peer-reviewed articles. Data were geocoded to assign country-level geographical coordinates and underwent multiple processing and cleaning steps using Python, Excel, R, and ArcGIS. Social network analysis (SNA) was conducted to assess collaboration patterns using Pajek and UCINET. Results: Research activities in plant phenomics have increased significantly, with China emerging as a major player, filing nearly 70% of patents from 2010 to 2021. The U.S. and EU remain significant contributors, accounting for over half of the research output. The study identified around 50 global research hubs, mainly in the U.S. (36%), Western Europe (34%), and China (16%). Collaboration networks have become more complex and interdisciplinary, reflecting a strategic approach to solving research challenges. Discussion: The findings underscore the importance of global collaboration and technological advancement in plant phenomics. China's rise in patent filings highlights its growing influence, while the ongoing contributions from the U.S. and EU demonstrate their continued leadership. The development of complex collaborative networks emphasizes the scientific community's adaptive strategies to address multifaceted research issues. These insights are crucial for researchers, policymakers, and industry stakeholders aiming to innovate in agricultural practices and improve crop varieties.

Patent data-driven analysis of literature associations with changing innovation trends.

Patents are essential for transferring scientific discoveries to meaningful products that benefit societies. While the academic community focuses on the number of citations to rank scholarly works according to their "scientific merit," the number of citations is unrelated to the relevance for patentable innovation. To explore associations between patents and scholarly works in publicly available patent data, we propose to utilize statistical methods that are commonly used in biology to determine gene-disease associations. We illustrate their usage on patents related to biotechnological trends of high relevance for food safety and ecology, namely the CRISPR-based gene editing technology (>60,000 patents) and cyanobacterial biotechnology (>33,000 patents). Innovation trends are found through their unexpected large changes of patent numbers in a time-series analysis. From the total set of scholarly works referenced by all investigated patents (~254,000 publications), we identified ~1,000 scholarly works that are statistical significantly over-represented in the references of patents from changing innovation trends that concern immunology, agricultural plant genomics, and biotechnological engineering methods. The detected associations are consistent with the technical requirements of the respective innovations. In summary, the presented data-driven analysis workflow can identify scholarly works that were required for changes in innovation trends, and, therefore, is of interest for researches that would like to evaluate the relevance of publications beyond the number of citations.

Enabling equitable and affordable access to novel therapeutics for pandemic preparedness and response via creative intellectual property agreements.

The COVID-19 pandemic demonstrated that the current purely market-driven approaches to drug discovery and development alone are insufficient to drive equitable access to new therapies either in preparation for, or in response to, pandemics. A new global framework driven by equity is under negotiation at the World Health Organization to support pandemic preparedness and response. Some believe that the global intellectual property (IP) system itself is part of the problem and propose a purely Open Science approach. In this article, we discuss how existing IP frameworks and contractual agreements may be used to create rights and obligations to generate a more effective global response in future, drawing on experience gained in the COVID Moonshot program, a purely Open Science collaboration, and the ASAP AViDD drug discovery consortium, which uses a hybrid, phased model of Open Science, patent filing and contractual agreements. We conclude that 'straight to generic' drug discovery is appropriate in some domains, and that targeted patent protection, coupled with open licensing, can offer a route to generating affordable and equitable access for therapy areas where market forces have failed. The Extended Data contains a copy of our model IP policy, which can be used as a template by other discovery efforts seeking to ensure their drug candidates can be developed for globally equitable and affordable access.

Drug discovery and development organizations usually recoup their investment in this risky and expensive process by filing patents on drug candidates which, if granted, give them a time-limited monopoly on the manufacture, sale or licensing of the drug. This means they can negotiate its price and terms of distribution, which creates distortions in access globally. In an alternative 'Open Science' approach, R&D organizations publish all the information about a prospective drug without applying for patents, meaning that anyone can use this knowledge to make and sell the drug, while the R&D organizations have no control over how it is priced or distributed. In a pandemic, fast-spreading viruses must be rapidly contained by delivering drugs to where they are most needed. This requires innovation and global access, but this is stifled in both models ­ in the first because of patent abuses, in the second because the lack of control may jeopardize the most efficient development. The authors share a model that prioritizes globally fair and affordable pricing by creating 'maximally permissive licenses' based on 'minimally defensive patents'. They explain the practical and bioethical background to their proposals and share an example of collective management of intellectual property and licensing agreement that is being used in the AI-driven Structure-enabled Antiviral Platform (ASAP) Center's Pandemic Preparedness work.

Trends in Viral Vector-Based Vaccines for Tuberculosis: A Patent Review (2010-2023).

Tuberculosis (TB) is an ancient global public health problem. Several strategies have been applied to develop new and more effective vaccines against TB, from attenuated or inactivated mycobacteria to recombinant subunit or genetic vaccines, including viral vectors. This review aimed to evaluate patents filed between 2010 and 2023 for TB vaccine candidates. It focuses on viral vector-based strategies. A search was carried out in Espacenet, using the descriptors "mycobacterium and tuberculosis" and the classification A61K39. Of the 411 patents preliminarily identified, the majority were related to subunit vaccines, with 10 patents based on viral vector platforms selected in this study. Most of the identified patents belong to the United States or China, with a concentration of patent filings between 2013 and 2023. Adenoviruses were the most explored viral vectors, and the most common immunodominant Mycobacterium tuberculosis (Mtb) antigens were present in all the selected patents. The majority of patents were tested in mouse models by intranasal or subcutaneous route of immunization. In the coming years, an increased use of this platform for prophylactic and/or therapeutic approaches for TB and other diseases is expected. Along with this, expanding knowledge about the safety of this technology is essential to advance its use.

Novel drug delivery systems in colorectal cancer: Advances and future prospects.

Colorectal cancer (CRC) is an abnormal proliferation of cells within the colon and rectum, leading to the formation of polyps and disruption of mucosal functions. The disease development is influenced by a combination of factors, including inflammation, exposure to environmental mutagens, genetic alterations, and impairment in signaling pathways. Traditional treatments such as surgery, radiation, and chemotherapy are often used but have limitations, including poor solubility and permeability, treatment resistance, side effects, and post-surgery issues. Novel Drug Delivery Systems (NDDS) have emerged as a superior alternative, offering enhanced drug solubility, precision in targeting cancer cells, and regulated drug release. Thereby addressing the shortcomings of conventional therapies and showing promise for more effective CRC management. The present review sheds light on the pathogenesis, signaling pathways, biomarkers, conventional treatments, need for NDDS, and application of NDDS against CRC. Additionally, clinical trials, ongoing clinical trials, marketed formulations, and patents on CRC are also covered in the present review.

Application of sphingolipid-based nanocarriers in drug delivery: an overview.

Sphingolipids (SL) are well recognized for their cell signaling through extracellular and intracellular pathways. Based on chemistry different types of SL are biosynthesized in mammalian cells and have specific function in cellular activity. SL has an ampiphilic structure with have hydrophobic body attached to the polar head enables their use as a drug delivery agent in the form of nanocarriers. SL-based liposomes can improve the solubility of lipophilic drugs through host and drug complexes and are more stable than conventional liposomal formulations. Preclinical studies of SL nanocarriers are reported on topical delivery, oral delivery, ocular delivery, chemotherapeutic delivery, cardiovascular delivery and Alzheimer's disease. The commercial challenges and patents related to SL nanoformulations are highlighted in this article.

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Machine learning to promote translational research: predicting patent and clinical trial inclusion in dementia research.

Projected to impact 1.6 million people in the UK by 2040 and costing £25 billion annually, dementia presents a growing challenge to society. This study, a pioneering effort to predict the translational potential of dementia research using machine learning, hopes to address the slow translation of fundamental discoveries into practical applications despite dementia's significant societal and economic impact. We used the Dimensions database to extract data from 43 091 UK dementia research publications between the years 1990 and 2023, specifically metadata (authors, publication year, etc.), concepts mentioned in the paper and the paper abstract. To prepare the data for machine learning, we applied methods such as one-hot encoding and word embeddings. We trained a CatBoost Classifier to predict whether a publication will be cited in a future patent or clinical trial. We trained several model variations. The model combining metadata, concept and abstract embeddings yielded the highest performance: for patent predictions, an area under the receiver operating characteristic curve of 0.84 and 77.17% accuracy; for clinical trial predictions, an area under the receiver operating characteristic curve of 0.81 and 75.11% accuracy. The results demonstrate that integrating machine learning within current research methodologies can uncover overlooked publications, expediting the identification of promising research and potentially transforming dementia research by predicting real-world impact and guiding translational strategies.

Microbial Bioherbicides Based on Cell-Free Phytotoxic Metabolites: Analysis and Perspectives on Their Application in Weed Control as an Innovative Sustainable Solution.

Weeds cause significant agricultural losses worldwide, and herbicides have traditionally been the main solution to this problem. However, the extensive use of herbicides has led to multiple cases of weed resistance, which could generate an increase in the application concentration and consequently a higher persistence in the environment, hindering natural degradation processes. Consequently, more environmentally friendly alternatives, such as microbial bioherbicides, have been sought. Although these bioherbicides are promising, their efficacy remains a challenge, as evidenced by their limited commercial and industrial production. This article reviews the current status of microbial-based bioherbicides and highlights the potential of cell-free metabolites to improve their efficacy and commercial attractiveness. Stirred tank bioreactors are identified as the most widely used for production-scale submerged fermentation. In addition, the use of alternative carbon and nitrogen sources, such as industrial waste, supports the circular economy. Furthermore, this article discusses the optimization of downstream processes using bioprospecting and in silico technologies to identify target metabolites, which leads to more precise and efficient production strategies. Bacterial bioherbicides, particularly those derived from Pseudomonas and Xanthomonas, and fungal bioherbicides from genera such as Alternaria, Colletotrichum, Trichoderma and Phoma, show significant potential. Nevertheless, limitations such as their restricted range of action, their persistence in the environment, and regulatory issues restrict their commercial availability. The utilization of cell-free microbial metabolites is proposed as a promising solution due to their simpler handling and application. In addition, modern technologies, including encapsulation and integrated management with chemical herbicides, are investigated to enhance the efficacy and sustainability of bioherbicides.

Cutting-edge Approach of Carbon Nanostructures: Targeted Drug Delivery to Central Nervous System.

Drug delivery through the blood-brain barrier (BBB) is one of the key challenges in the modern era of medicine due to the highly semipermeable characteristics of BBB that restrict the entry of various drugs into the central nervous system (CNS) for the management of brain disorders. Drugs can be easily incorporated into carbon nanocarriers that can cross the bloodbrain barrier. Numerous nanocarriers have been developed, including polymeric nanoparticles, carbon nanoparticles, lipid-based nanoparticles, etc. Among these, carbon nanostructures could be superior due to their easier BBB penetration and strong biocompatibility. Several CDs (Carbon dots) and CD-ligand conjugates have explored effectively penetrating the BBB, which enables significant progress in using CD-based drug delivery systems (DDS) to manage CNS diseases. Despite the drug delivery applications, they might also be used as a central nervous system (CNS) drug; few of the carbon nanostructures show profound neurodegenerative activity. Further, their impact on neuronal growth and anti- amyloid action is quite interesting. The present study covers diverse carbon nanostructures for brain-targeted drug delivery, exploring a variety of CNS activities. Moreover, it emphasizes recent patents on carbon nanostructures for CNS disorders.

Paclitaxel in colon cancer management: from conventional chemotherapy to advanced nanocarrier delivery systems.

Paclitaxel, a potent chemotherapeutic agent derived from the bark of the Pacific yew tree, has demonstrated significant efficacy in the treatment of various cancers, including colon cancer. This comprehensive review delves into the conventional treatments for colon cancer, emphasizing the crucial role of paclitaxel in contemporary management strategies. It explores the intricate process of sourcing and synthesizing paclitaxel, highlighting the importance of its structural properties in its anticancer activity. The review further elucidates the mechanism of action of paclitaxel, its pharmacological effects, and its integration into chemotherapy regimens for colon cancer. Additionally, novel drug delivery systems, such as nanocarriers, liposomes, nanoparticles, microspheres, micelles, microemulsions, and niosomes, are examined for their potential to enhance the therapeutic efficacy of paclitaxel. The discussion extends to recent clinical trials and patents, showcasing advancements in paclitaxel formulations aimed at improving treatment outcomes. The review concludes with prospects in the field underscoring the ongoing innovation and potential breakthroughs in colon cancer therapy.

Protein tyrosine phosphatase inhibitors: a patent review and update (2012-2023).

INTRODUCTION: Protein tyrosine phosphatases (PTPs), essential and evolutionarily highly conserved enzymes, govern cellular functions by modulating tyrosine phosphorylation, a pivotal post-translational modification for signal transduction. The recent strides in phosphatase drug discovery, leading to the identification of selective modulators for enzymes, restoring interest in the therapeutic targeting of protein phosphatases. AREAS COVERED: The compilation of patents up to the year 2023 focuses on the efficacy of various classes of Tyrosine phosphatases and their inhibitors, detailing their chemical structure and biochemical characteristics. These findings have broad implications, as they can be applied to treating diverse conditions like cancer, diabetes, autoimmune disorders, and neurological diseases. The search for scientific articles and patent literature was conducted using well known different platforms to gather information up to 2023. EXPERT OPINION: The latest improvements in protein tyrosine phosphatase (PTP) research include the discovery of new inhibitors targeting specific PTP enzymes, with a focus on developing allosteric site covalent inhibitors for enhanced efficacy and specificity. These advancements have not only opened up new possibilities for therapeutic interventions in various disease conditions but also hold the potential for innovative treatments. PTPs offer promising avenues for drug discovery efforts and innovative treatments across a spectrum of health conditions.

The potential impact of the Comprehensive and Progressive Agreement for Prans-Pacific Partnership on Thailand's hepatitis C treatment program.

BACKGROUND: Thailand has expressed interest in joining the Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP), a twelve-country plurilateral trade agreement whose original incarnation included the United States of America (USA). When the USA withdrew from this agreement, key intellectual property clauses relevant to pharmaceuticals were suspended. These could be reinstated should the CPTPP Parties decide to do so. METHODS: This study uses two scenarios to cost the impact the CPTPP would have had on Thailand's 2020 hepatitis C treatment regime if Thailand joined the CPTPP and suspended clauses were reinstated. RESULTS: Joining the CPTPP could have increased the cost more than tenfold if suspended CPTPP clauses were reinstated and Thailand was not willing or able to issue compulsory licenses. Based on the 2020 budget, the price for this possible scenario could have reduced hepatitis C treatment coverage by 90%. CONCLUSIONS: Acceding to trade agreements such as the CPTPP that require increasing intellectual property protection, could compromise Thailand's hepatitis C program and other national treatment programs reliant on affordable generic medicines. The CPTPP could also prevent Thailand from relying on its own pharmaceutical capabilities to manufacture medicines needed to sustain its treatment programs.

Multifaceted role of erlotinib in various cancer: nanotechnology intervention, patent landscape, and advancements in clinical trials.

Erlotinib (ELB) is a tyrosine kinase inhibitor that targets the activity of Epidermal Growth Factor Receptor (EGFR) protein found in both healthy and cancerous cells. It binds reversibly to the ATP-binding site of the EGFR tyrosine kinase. ELB was approved by the US Food and Drug Administration (FDA) in 2004 for advanced non-small cell lung cancer (NSCLC) treatment in patients who relapsed after at least one other therapy. It was authorized for use with gemcitabine in 2005 for the treatment of advanced pancreatic cancer. In addition to lung cancer, ELB has shown promising results in the treatment of other cancers, including breast, prostate, colon, pancreatic, cervical, ovarian, and head and neck cancers. However, its limited water solubility, as a BCS class II drug, presents biopharmaceutical problems. Nanoformulations have been developed to overcome these issues, including increased solubility, controlled release, enhanced stability, tumor accumulation, reduced toxicity, and overcoming drug resistance. In older patients, ELB management should involve individualized dosing based on age-related changes in drug metabolism and close monitoring for adverse effects. Regular assessments of renal and hepatic functions are essential. This review provides an overview of ELB's role of ELB in treating various cancers, its associated biopharmaceutical issues, and the latest developments in ELB-related nanotechnology interventions. It also covers ELB patents granted in previous years and the ongoing clinical trials.

Sorry you asked? Mayo, Myriad, and the battles over patent-eligibility.

Genetic testing for inherited cancer risk changed dramatically when the US Supreme Court handed down unanimous rulings in Mayo v. Prometheus (2012) and Myriad v. Association for Molecular Pathology (2013). Those decisions struck down claims to methods based on 'laws of nature' (Mayo) and DNA molecules corresponding to sequences found in nature (Myriad). Senators Thom Tillis (R-NC) and Christopher Coons (D-DE) introduced legislation that would abrogate those decisions and specify narrow statutory exclusions to patent-eligibility in §101 of the US Patent Act. What would be the consequences of doing so? The Supreme Court decisions coincided with changes in how genetic tests were performed, reimbursed and regulated. Multi-gene sequencing supplanted oligo-gene testing as the cost of sequencing dropped 10,000-fold. Payers dramatically changed reimbursement practices. Food and Drug Administration regulation was proposed and remains in prospect. Databases for clinical interpretation made data freely available, augmenting a knowledge commons. The spectacular implosion of Theranos tempered investment in molecular diagnostics. These factors all complicate explanations of why venture capital funding for molecular diagnostics dropped relative to other sectors. Restoring patent-eligibility would put renewed pressure on other patent doctrines, such as obviousness, enablement and written description, that were not raised in the Supreme Court cases.