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Botulinum neurotoxins (BoNTs) comprise seven agreed-on serotypes, A through G. In 2014, a novel chimeric neurotoxin produced by clostridial strain IBCA10-7060 was reported as BoNT/H, with subsequent names of BoNT/FA or BoNT/HA based on sequence homology of the N-terminus to BoNT/F, the C-terminus to BoNT/A and neutralization studies. The purpose of this study was to define the immunologic identity of the novel BoNT. monoclonal antibodies (mAbs) to the novel BoNT/H N-terminus were generated by antibody repertoire cloning and yeast display after immunization with BoNT/H LC-HN or BoNT/F LC-HN. 21 unique BoNT/H LC-HN mAbs were obtained; 15 from the BoNT/H LC-HN immunized library (KD 0.78 nM to 182 nM) and six from the BoNT/F-immunized libraries (KD 20.5 nM to 1490 nM). A total of 15 of 21 mAbs also bound catalytically inactive BoNT/H holotoxin. The mAbs bound nine non-overlapping epitopes on the BoNT/H LC-HN. None of the mAbs showed binding to BoNT serotypes A-G, nor any of the seven subtypes of BoNT/F, except for one mAb that weakly bound BoNT/F5. The results, combined with the chimeric structure and neutralization by anti-A, but not anti-F antitoxin indicate that immunologically the novel BoNT is BoNT/HA. This determination has significant implications for existing countermeasures and potential vulnerabilities.

Background: Canada's Patented Medicine Prices Review Board (PMPRB) uses external and internal reference pricing (IRP) to regulate patented drug list prices. PMPRB has changed external reference countries from 7 to 11 to include countries with prices closer to the OECD median. We examined the impact on the list prices for patented medicines had the amendment been implemented from 2013., Methods: Using IQVIA MIDAS® quarterly sales data, we selected branded products that were launched in Canada in 2013-2018. The list price for each product in each country was calculated as its average annual price during the 3rd year post Canadian launch. The median international price (MIP) was the median of the list prices of PMPRB7 (MIP7) and PMPRB11 (MIP11). We assumed the same IRP would be (scenario 1) or would not be used (scenario 2)., Results: Among the selected 400 products, 80.3 % (321) had MIP7 and MIP11 (launched in at least one reference country); 18.3 % did not have MIP11. The total current expenditures were $7,134.4 M. In scenario 1, MIP11 would not be binding for most products and expenditures would decline only by 0.7 %. If IRP were abolished, expenditures might decline by 14.1 % if the launching sequence would not change., Conclusions: MIP11 might not be binding for most medicines. The impact depends on whether to retain the IRP and approaches taken for medicines without MIP11., Competing Interests: Declaration of competing interest Wei Zhang is leading a project funded through a grant-in-aid received by the University of British Columbia (fund recipient) from Pfizer Canada. Wei Zhang is not the fund recipient and this project is not related to the topic of the paper. All other authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Large language models (LLMs) are a type of machine learning model that learn statistical patterns over text, such as predicting the next words in a sequence of text. Both general purpose and task-specific LLMs have demonstrated potential across diverse applications. Science and medicine have many data types that are highly suitable for LLMs, such as scientific texts (publications, patents and textbooks), electronic medical records, large databases of DNA and protein sequences and chemical compounds. Carefully validated systems that can understand and reason across all these modalities may maximize benefits. Despite the inevitable limitations and caveats of any new technology and some uncertainties specific to LLMs, LLMs have the potential to be transformative in science and medicine., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Periodontal disease is a multifactorial pathogenic condition involving microbial infection, inflammation, and various systemic complications. Here, a systematic and comprehensive review discussing key-points such as the pros and cons of conventional methods, new advancements, challenges, patents and products, and future prospects is presented. A systematic review process was adopted here by using the following keywords: periodontal diseases, pathogenesis, models, patents, challenges, recent developments, and 3-D printing scaffolds. Search engines used were "google scholar", "web of science", "scopus", and "pubmed", along with textbooks published over the last few decades. A thorough study of the published data rendered an accurate and deep understanding of periodontal diseases, the gap of research so far, and future opportunities. Formulation scientists and doctors need to be interconnected for a better understanding of the disease to prescribe a quality product. Moreover, prime challenges (such as a lack of a vital testing model, scarcity of clinical and preclinical data, products allowing for high drug access to deeper tissue regions for prolonged residence, lack of an international monitoring body, lack of 4D or time controlled scaffolds, and lack of successful AI based tools) exist that must be addressed for designing new quality products. Generally, several products have been commercialized to treat periodontal diseases with certain limitations. Various strategic approaches have been attempted to target certain delivery regions, maximize residence time, improve efficacy, and reduce toxicity. Conclusively, the current review summarizes valuable information for researchers and healthcare professional to treat a wide range of periodontal diseases., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

In the pharmaceutical industry, the patent protection of drugs and medicines is accorded importance because of the high costs involved in the development of novel drugs. Over the years, researchers have analyzed patent documents to identify freedom-to-operate spaces for novel drug candidates. To assist this, several well-established public patent document data repositories have enabled automated methodologies for extracting information on therapeutic agents. In this study, we delve into one such publicly available patent database, SureChEMBL, which catalogues patent documents related to life sciences. Our exploration begins by identifying patent compounds across public chemical data resources, followed by pinpointing sections in patent documents where the chemical annotations were found. Next, we exhibit the potential of compounds to serve as drug candidates by evaluating their conformity to drug-likeness criteria. Lastly, we examine the drug development stage reported for these compounds to understand their clinical success. In summary, our investigation aims at providing a comprehensive overview of the patent compounds catalogued in SureChEMBL, assessing their relevance to pharmaceutical drug discovery., (© 2024. The Author(s).)

On the occasion of the 20th anniversary of the discovery of acrylamide in food, an analysis of patents related to the mitigation of this compound in food products obtained through immersion frying was carried out. For this purpose, a comprehensive search, compilation, and information analysis were conducted using free online databases such as Google Patents, Patenscope, and Lens. The search yielded a total of 79 patents within the considered time period (2002-2022). The countries with the highest number of granted patents were the United States, the European Union, and South Korea. The patents were classified into four main approaches: raw material modification (49%), application of pre-treatments (27%), process modification (16%), and measurement techniques (8%). Among the results, Frito-Lay, an American company, stands out as the food industry company with the highest number of granted patents, totaling 15. Based on this review, it is concluded that while a significant number of patents have been granted in recent years, there is still a lag in developing countries. Furthermore, more studies are needed to determine acrylamide in starchy food matrices subjected to immersion frying different from potatoes., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Díaz-Ávila WY et al.)

Introduction: Hematopoietic progenitor kinase 1 (HPK1), a 97-kDa serine/threonine Ste20-related protein kinase, functions as an intracellular negative regulator, primarily in hematopoietic lineage cells, where it regulates T cells, B cells, dendritic cells, and other immune cells. Loss of HPK1 kinase activity results in exacerbated cytokine secretion, enhanced T cell signaling, improved viral clearance, and thus increased restraint of tumor growth. These findings highlight HPK1 as a promising target for immuno-oncology treatments, culminating in the advancement of candidate compounds targeting HPK1 to clinical trials by several biotech enterprises., Areas Covered: Through searching PubMed, Espacenet-patent search, and clinicaltrials.gov, this review provides a comprehensive analysis of HPK1, encompassing its structure and roles in various downstream signaling pathways, the consequences of constitutive activation of HPK1, and potential therapeutic strategies to treat HPK1-driven malignancies. Moreover, the review outlines the patents issued for small molecule inhibitors and clinical investigations of HPK1., Expert Opinion: To enhance the success of tumor immunotherapy in clinical trials, it is important to develop protein degraders, allosteric inhibitors, and antibody-drug conjugates based on the crystal structure of HPK1, and to explore combination therapy approaches. Although several challenges remain, the development of HPK1 inhibitors display promising in preclinical and clinical studies.

ImportanceWomen in ophthalmology are growing in number and have made strides in traditional metrics of professional achievement. Professional ties to industry represent another potential means of career advancement, recognition, and income.ObjectiveTo report the representation of women among ophthalmologists receiving industry remuneration for research, consulting, honoraria, grants, royalties, and faculty/speaker roles.Design, setting, and participantsIn this observational, retrospective study, the Centers for Medicare and Medicaid Services Open Payments database for payments to ophthalmologists by biomedical companies was reviewed for representation, median payments, and mean payments by women and men for industry relationships in 2013 and 2014. The analysis was performed from July 2015 to November 2015.Main outcomes and measuresThe primary outcome measures were percentage representation of women vs men overall and in industry research, consulting, speaking roles, royalties and licenses, grants, services other than consulting, and honoraria. Secondary outcome measures included mean and median payments from industry to female vs male ophthalmologists.ResultsIn 2013, 4164 of 21 380 (19.5%) ophthalmologists were women, and of 1204 ophthalmologists analyzed for industry payments, 176 (4.2%) women had industry ties compared with 1028 (6%) men (P

The opinion of the United States Court of Appeals for the Federal Circuit, In re Roslin Institute, rejecting patent claims to mammals cloned from somatic cells, was rendered about a month before the United States Supreme Court's decision in Alice Corp. v. CLS Bank International. The Alice opinion explicitly sets out the standard for determining whether an invention falls within statutory patentable subject matter. Thus one is thus left to wonder what the Roslin opinion might have looked like had it been decided only a few weeks later, after the Alice decision was published, with the benefit of the Supreme Court's further direction on patentable subject matter. In this essay I explore whether in hindsight the Alice standard might have dictated a different outcome in Roslin, suggesting how the two-part test articulated by the Supreme Court in Alice might apply to a 'products of nature' analysis for cloned mammals. Drawing on that analysis, I then use the Roslin case as a vehicle to highlight certain issues with the Supreme Court's current subject matter jurisprudence as applied to biotechnology. By juxtaposing Dolly with Alice, it becomes clear that the Supreme Court has revivified a number of dormant biotechnology patent problems in the guise of subject matter analysis.

BindingDB, www.bindingdb.org, is a publicly accessible database of experimental protein-small molecule interaction data. Its collection of over a million data entries derives primarily from scientific articles and, increasingly, US patents. BindingDB provides many ways to browse and search for data of interest, including an advanced search tool, which can cross searches of multiple query types, including text, chemical structure, protein sequence and numerical affinities. The PDB and PubMed provide links to data in BindingDB, and vice versa; and BindingDB provides links to pathway information, the ZINC catalog of available compounds, and other resources. The BindingDB website offers specialized tools that take advantage of its large data collection, including ones to generate hypotheses for the protein targets bound by a bioactive compound, and for the compounds bound by a new protein of known sequence; and virtual compound screening by maximal chemical similarity, binary kernel discrimination, and support vector machine methods. Specialized data sets are also available, such as binding data for hundreds of congeneric series of ligands, drawn from BindingDB and organized for use in validating drug design methods. BindingDB offers several forms of programmatic access, and comes with extensive background material and documentation. Here, we provide the first update of BindingDB since 2007, focusing on new and unique features and highlighting directions of importance to the field as a whole.

A great deal has been said in recent years about patent disclosure. But to say that there is a disclosure function in the patent system implies that there is non-disclosure functioning in the patent system as well. For some information to be disclosed in a patent, other information must go undisclosed; for some things to be included, other things must be excluded. In this article I review the surprising number of doctrines that allow and encourage patent applicants to remain silent about aspects of their inventions. I find that some silences in patents are inadvertent, while some are deliberate; some are necessary, while some are strategic. I conclude that a combination of such explicit and tacit silences allows patents to function as boundary objects, that is, as artifacts that have sufficiently definite meaning to be useful in disparate social worlds, but which simultaneously are sufficiently ambiguous to become objects of collaboration between disparate social worlds. Because innovation is known to occur when localized knowledge is transferred across social boundaries, this function of the patent document is critical to its stated purpose, and occurs largely because of its open rhetorical spaces. Thus, rather than fixating on enhanced disclosure, I argue that much of the critical work of the patent system can and should occur in the open rhetorical spaces where patents are silent.

The opinion of the United States Court of Appeals for the Federal Circuit, In re Roslin Institute, rejecting patent claims to mammals cloned from somatic cells, was rendered about a month before the United States Supreme Court's decision in Alice Corp. v. CLS Bank International. The Alice opinion explicitly sets out the standard for determining whether an invention falls within statutory patentable subject matter. Thus one is thus left to wonder what the Roslin opinion might have looked like had it been decided only a few weeks later, after the Alice decision was published, with the benefit of the Supreme Court's further direction on patentable subject matter. In this essay I explore whether in hindsight the Alice standard might have dictated a different outcome in Roslin, suggesting how the two-part test articulated by the Supreme Court in Alice might apply to a 'products of nature' analysis for cloned mammals. Drawing on that analysis, I then use the Roslin case as a vehicle to highlight certain issues with the Supreme Court's current subject matter jurisprudence as applied to biotechnology. By juxtaposing Dolly with Alice, it becomes clear that the Supreme Court has revivified a number of dormant biotechnology patent problems in the guise of subject matter analysis.

Introduction: Recent years have witnessed great achievements in drug design and development targeting the phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT) signaling pathway, a pathway central to cell growth and proliferation. The nearest neighbor protein-protein interaction networks for PI3K and AKT show the interplays between these target proteins which can be harnessed for drug discovery. In this review, we discuss the drug design and clinical development of inhibitors of PI3K/AKT in the past three years. We review in detail the structures, selectivity, efficacy, and combination therapy of 35 inhibitors targeting these proteins, classified based on the target proteins. Approaches to overcoming drug resistance and to minimizing toxicities are discussed. Future research directions for developing combinational therapy and PROTACs of PI3K and AKT inhibitors are also discussed., Area Covered: This review covers clinical trial reports and patent literature on inhibitors of PI3K and AKT published between 2020 and 2023., Expert Opinion: To address drug resistance and drug toxicity of inhibitors of PI3K and AKT, it is highly desirable to design and develop subtype-selective PI3K inhibitors or subtype-selective AKT1 inhibitors to minimize toxicity or to develop allosteric drugs that can form covalent bonds. The development of PROTACs of PI3Kα or AKT helps to reduce off-target toxicities.

Introduction: The multi-subunit SWI/SNF chromatin remodeling complex is a key epigenetic regulator for many cellular processes, and several subunits are found to be mutated in human cancers. The inactivating mutations of SMARCA4, the ATPase subunit of the complex, result in cellular dependency on the paralog SMARCA2 for survival. This observed synthetic lethal relationship posits targeting SMARCA2 in SMARCA4-deficient settings as an attractive therapeutic target in oncology., Areas Covered: This review covers patent literature disclosed during the 2019-30 June 2023 period which claim ATPase inhibitors and PROTAC degraders that bind to the ATPase domain of SMARCA2 and/or SMARCA4. A total of 16 documents from 6 applicants are presented., Expert Opinion: The demonstration of cellular dependence on SMARCA2 ATPase activity in SMARCA4-deficient settings has prompted substantial research toward SMARCA2-targeting therapies. Although selectively targeting the ATPase domain of SMARCA2 is viewed as challenging, several ATPase inhibitor scaffolds have been disclosed within the last five years. Most early compounds are weakly selective, but these efforts have culminated in the first dual SMARCA2/SMARCA4 ATPase inhibitor to enter clinical trials. Data from the ongoing clinical trials, as well as continued advancement of SMARCA2-selective ATPase inhibitors, are anticipated to significantly impact the field of therapies, targeting SMARCA4-deficient tumors.

Introduction: Ferulic acid (FA) is a phenolic phytochemical that has garnered the attention of the research community due to its abundant availability in nature. It is a compound that has been explored for its multifaceted therapeutic potential and benefits in modern and contemporary healthcare., Areas Covered: This review furnishes a compilation of the molecular mechanisms underlying the anti-diabetic, anticancer, antioxidant, and anti-inflammatory effects of FA. We also aim to excavate an in-depth analysis of the role of nanoformulations to achieve release control, reduce toxicity, and deliver FA at specified target sites. To corroborate the safety and efficacy of FA, a multitude of pre-clinical studies have also been conducted by researchers and have been discussed comprehensively in this review. The various patented innovations and newer paradigms pertaining to FA have also been presented., Expert Opinion: Enormous research has been conducted and should still be continued to find the best possible novel drug delivery system for FA delivery. The utilization of nanocarriers and nanoformulations has intrigued the scientists for delivery of FA, but before that, it is necessary to shed light upon toxicity, safety, and regulatory concerns of FA.

Introduction: Nucleic acid-based therapeutics offer groundbreaking potential for treating genetic diseases and advancing next-generation vaccines. Despite their promise, challenges in efficient delivery persist due to the properties of nucleic acids. Nanoparticles (NPs) serve as vital carriers, facilitating effective delivery to target cells, and addressing these challenges. Understanding the global landscape of patents in this field is essential for fostering innovation and guiding decision-making for researchers, the pharmaceutical industry, and regulatory agencies., Areas Covered: This review provides a comprehensive overview of patent compositions, applications, and manufacturing aspects concerning NPs as nucleic acid delivery systems. It delves into temporal trends, protection locations, market dynamics, and the most influential technological domains. In this work, we provide valuable insights into the advancements and potential of NP-based nucleic acid delivery systems, with a special focus on their pivotal role in advancing cutting-edge therapeutic solutions., Expert Opinion: Investment in NPs for nucleic acid delivery has significantly surged in recent years. However, translating these therapies into clinical practice faces obstacles, including the need for robust clinical evidence, regulatory compliance, and streamlined manufacturing processes. To address these challenges, our review article summarizes recent advances. We aim to engage researchers worldwide in the development of these promising technologies.

Introduction: HMGB1 is a non-histone chromatin protein released or secreted in response to tissue damage or infection. Extracellular HMGB1, as a crucial immunomodulatory factor, binds with several different receptors to innate inflammatory responses that aggravate acute and chronic liver diseases. The increased levels of HMGB1 have been reported in various liver diseases, highlighting that it represents a potential biomarker and druggable target for therapeutic development., Areas Covered: This review summarizes the current knowledge on the structure, function, and interacting receptors of HMGB1 and its significance in multiple liver diseases. The latest patented and preclinical studies of HMGB1 inhibitors (antibodies, peptides, and small molecules) for liver diseases are summarized by using the keywords 'HMGB1,' 'HMGB1 antagonist, HMGB1-inhibitor,' 'liver disease' in Web of Science, Google Scholar, Google Patents, and PubMed databases in the year from 2017 to 2023., Expert Opinions: In recent years, extensive research on HMGB1-dependent inflammatory signaling has discovered potent inhibitors of HMGB1 to reduce the severity of liver injury. Despite significant progress in the development of HMGB1 antagonists, few of them are approved for clinical treatment of liver-related diseases. Developing safe and effective specific inhibitors for different HMGB1 isoforms and their interaction with receptors is the focus of future research.

Introduction: The TGF-β signaling pathway is a complex network that plays a crucial role in regulating essential biological functions and is implicated in the onset and progression of multiple diseases. This review highlights the recent advancements in developing inhibitors targeting the TGF-β signaling pathway and their potential therapeutic applications in various diseases., Area Covered: The review discusses patents on active molecules related to the TGF-β signaling pathway, focusing on three strategies: TGF-β activity inhibition, blocking TGF-β receptor binding, and disruption of the signaling pathway using small molecule inhibitors. Combination therapies and the development of fusion proteins targeting multiple pathways are also explored. The literature search was conducted using the Cortellis Drug Discovery Intelligence database, covering patents from 2021 onwards., Expert Opinion: The development of drugs targeting the TGF-β signaling pathway has made significant progress in recent years. However, addressing challenges such as specificity, systemic toxicity, and patient selection is crucial for their successful clinical application. Targeting the TGF-β signaling pathway holds promise as a promising approach for the treatment of various diseases.

Antibodies are key proteins of the adaptive immune system, and there exists a large body of academic literature and patents dedicated to their study and concomitant conversion into therapeutics, diagnostics, or reagents. These documents often contain extensive functional characterisations of the sets of antibodies they describe. However, leveraging these heterogeneous reports, for example to offer insights into the properties of query antibodies of interest, is currently challenging as there is no central repository through which this wide corpus can be mined by sequence or structure. Here, we present PLAbDab (the Patent and Literature Antibody Database), a self-updating repository containing over 150,000 paired antibody sequences and 3D structural models, of which over 65 000 are unique. We describe the methods used to extract, filter, pair, and model the antibodies in PLAbDab, and showcase how PLAbDab can be searched by sequence, structure, or keyword. PLAbDab uses include annotating query antibodies with potential antigen information from similar entries, analysing structural models of existing antibodies to identify modifications that could improve their properties, and facilitating the compilation of bespoke datasets of antibody sequences/structures that bind to a specific antigen. PLAbDab is freely available via Github (https://github.com/oxpig/PLAbDab) and as a searchable webserver (https://opig.stats.ox.ac.uk/webapps/plabdab/)., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Since the COVID-19 outbreak in early 2020, researchers and studies are continuing to find drugs and/or vaccines against the disease. As shown before, medicinal plants can be very good sources against viruses because of their secondary compounds which may cure diseases and help in survival of patients. There is a growing trend in the filed patents in this field., Aims: In the present study, we test and suggest the inhibitory potential of five herbal based extracts including 7α-acetoxyroyleanone, Curzerene, Incensole, Harmaline, and Cannabidiol with antivirus activity on the models of the significant antiviral targets for COVID-19 like spike glycoprotein, Papain-like protease (PLpro), non-structural protein 15 (NSP15), RNA-dependent RNA polymerase and core protease by molecular docking study., Methods: The Salvia rythida root was extracted, dried, and pulverized by a milling machine. The aqueous phase and the dichloromethane phase of the root extractive were separated by two-phase extraction using a separatory funnel. The separation was performed using the column chromatography method. The model of the important antivirus drug target of COVID-19 was obtained from the Protein Data Bank (PDB) and modified. TO study the binding difference between the studied molecules, the docking study was performed., Results: These herbal compounds are extracted from Salvia rhytidea, Curcuma zeodaria, Frankincense, Peganum harmala , and Cannabis herbs , respectively. The binding energies of all compounds on COVID-19 main targets are located in the limited area of 2.22-5.30 kcal/mol. This range of binding energies can support our hypothesis for the presence of the inhibitory effects of the secondary metabolites of mentioned structures on COVID-19. Generally, among the investigated herbal structures, Cannabidiol and 7α- acetoxyroyleanone compounds with the highest binding energy have the most inhibitory potential. The least inhibitory effects are related to the Curzerene and Incensole structures by the lowest binding affinity., Conclusion: The general arrangement of the basis of the potential barrier of binding energies is in the order below: Cannabidiol > 7α-acetoxyroyleanone > Harmaline> Incensole > Curzerene. Finally, the range of docking scores for investigated herbal compounds on the mentioned targets indicates that the probably inhibitory effects on these targets obey the following order: main protease> RNA-dependent RNA polymerase> PLpro> NSP15> spike glycoprotein., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Actinomycetes are present in various terrestrial and aquatic habitats, predominantly in the soil rhizosphere, encompassing marine and freshwater ecosystems. These microorganisms exhibit characteristics that resemble both bacteria and fungi. Numerous actinomycetes exhibit a mycelial existence and undergo significant morphological transformations. These bacteria are widely recognized as biotechnologically significant microorganisms utilized for the production of secondary metabolites. In all, over 45% of all bioactive microbial metabolites are produced by actinomycetes, which are responsible for producing around 10,000 of them. The majority of actinomycetes exhibit substantial saprophytic characteristics in their natural environment, enabling them to effectively decompose a diverse range of plant and animal waste materials during the process of decomposition. Additionally, these organisms possess a sophisticated secondary metabolic system, which enables them to synthesize almost two-thirds of all naturally occurring antibiotics. Moreover, they can create a diverse array of chemical compounds with medical or agricultural applications, including anticancer, antiparasitic, and antibacterial agents. This review aims to provide an overview of the prominent biotechnological domains in which actinobacteria and their metabolites demonstrate noteworthy applicability. The graphical abstract provides a preview of the primary sections covered in this review. This paper presents a comprehensive examination of the biotechnological applications and metabolites of actinobacteria, highlighting their potential for patent innovations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Cancer is a leading cause of death and a significant public health issue worldwide. Standard treatment methods such as chemotherapy, radiotherapy, and surgery are only sometimes effective. Therefore, new therapeutic approaches are needed for cancer treatment. Sea anemone actinoporins are pore-forming toxins (PFTs) with membranolytic activities. RTX-A is a type of PFT that interacts with membrane phospholipids, resulting in pore formation. The synthesis of recombinant proteins in a secretory form has several advantages, including protein solubility and easy purification. In this study, we aimed to discover suitable signal peptides for producing RTX-A in Bacillus subtilis in a secretory form., Methods: Signal peptides were selected from the Signal Peptide Web Server. The probability and secretion pathways of the selected signal peptides were evaluated using the SignalP server. ProtParam and Protein-sol were used to predict the physico-chemical properties and solubility. AlgPred was used to predict the allergenicity of RTX-A linked to suitable signal peptides. Non-allergenic, stable, and soluble signal peptides fused to proteins were chosen, and their secondary and tertiary structures were predicted using GOR IV and I-TASSER, respectively. The PROCHECK server performed the validation of 3D structures., Results: According to bioinformatics analysis, the fusion forms of OSMY_ECOLI and MALE_ECOLI linked to RTX-A were identified as suitable signal peptides. The final proteins with signal peptides were stable, soluble, and non-allergenic for the human body. Moreover, they had appropriate secondary and tertiary structures., Conclusion: The signal above peptides appears ideal for rationalizing secretory and soluble RTX-A. Therefore, the signal peptides found in this study should be further investigated through experimental researches and patents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Major depressive disorder is considered one of the most common and prevalent diseases worldwide, affecting children, adults, and the elderly. Currently, several antidepressant drugs are available on the market, but the low adherence of patients due to the slow therapeutic response is a problem to be solved. In this way, cyclodextrins become an alternative to circumvent the limitations and improve the physicochemical and pharmacological properties of this class of drugs. Thus, the objective of this work is to carry out a current review of patents associating antidepressant drugs and cyclodextrins. The patent search was performed in two patent databases, the World Intellectual Property Organization and the European Patent Office using terms in the title and abstract fields and the international patent classification code for antidepressant drugs. In the end, 27 patent documents were selected and divided into three classifications, physical-chemical characterization study, pre-clinical in vivo trials, and clinical trials. The scientific evidence found in the patents considers the use of cyclodextrins as an important alternative to improve the therapeutic and physicochemical properties of antidepressant drugs, among the main improved properties are, solubility, stability, masking taste and odor, bioavailability.

Background: There are patents available related to fermented food and beverages which enhance to human health. Citrus limetta (Mosambi) has a high content of flavonoids and exhibits antioxidant activity, which could stimulate the digestive system and be useful for gastroprotective activity. It supports digestion by neutralizing the acidic digestive juices and reducing gastric acidity., Objective: This study explored the potential of using waste peel extract from Citrus limetta to prevent ulcers. The study specifically sought to assess the anti-ulcer properties of fermented and non-fermented extracts and compare them. Further, the study looked at the potential benefits of treating or preventing ulcers with Citrus limetta waste peels and whether fermentation affected the efficacy of the treatment., Methods: Thirty female Wistar albino rats were equally distributed into five different groups. Group 1 received distilled water (20 ml/kg/b.w); Group 2 received indomethacin (mg/kg/b.w); Group 3 received omeprazole (20 mg/kg/b.w); Group 4 received aqueous extract of Mosambi peel (400 mg/kg/b.w) and Group 5 received fermented product of extract of Mosambi peel (400 mg/kg/b.w)., Results: Findings explored that, compared to non-fermented citrus fruit juice, biofermented exhibited less gastric volume (1.58 ± 0.10 ml vs. 1.8 ± 0.14 ml), reduced MDA levels (355.23 ± 100.70 μmol/mg protein vs. 454.49 ± 155.88 μmol/mg protein), and low ulcer index (0.49 ± 0.07 vs. 0.72 ± 0.14)., Conclusion: The results suggest that the bio-fermented product of Citrus limetta peel has better anti-ulcer potential against peptic ulcer induced by indomethacin in Wistar albino rats compared to non-fermented., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The current Intellectual Property Rights (IPR) framework supports the commercialization of seed improvement, monoculture, and the patent protection of novel plant varieties, microorganisms, and genetically modified animals. As a consequence, our rich biogenetic diversity is irreversibly dissipating. However, we need to figure out how to create a methodology for elective choices that will achieve harmony between the official Intellectual Property (IP) structure and maintainable biodiversity components. The majority of the biotechnology sector's programmes in India are managed by the Department of Biotechnology. It is under the Ministry of Science and Technology. Its goals are to provide services in the fields of study, infrastructure, human resource development, biotechnology popularisation, industry promotion, and establishment of centres of excellence. Implementation of practise biosafety regulations for genetically modified organisms, recombinant DNA products, and programmes is based on biotechnology for the good of society. This creates an information network for India's bioinformatics mission in the local, national, and worldwide scientific community., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder determined by immune-mediated platelet demolition and reduction of platelet production. Romiplostim is a new thrombopoiesis motivating peptibody that binds and stimulates the human thrombopoietin receptor the patent of which was registered in 2008. It is used to treat thrombocytopenia in patients with chronic immune thrombocytopenic purpura. Romiplostim is a 60 kDa peptibody designed to inhibit cross-reacting immune responses. It consists of four high-affinity TPO-receptor binding domains for the Mpl receptor and one human IgG1 Fc domain. Escherichia coli is a good host for the fabrication of recombinant proteins such as romiplostim. The expression of a gene intended in E. coli is dependent on many factors such as a protein's inherent ability to fold, mRNA's secondary structure, its solubility, its toxicity preferential codon use, and its need for post-translational modification (PTM). This review focuses on the structure, function, mechanism of action, and expressive approach to romiplostim in E. coli ., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The pituitary glands normally produce and stores gonadotropic hormones (GnH) that are responsible for ovulation and spermiation in animals. However, whether fish pituitary extracts can elicit same effects in treated animals need elucidation as a prelude to their practical usage in animals., Objectives: The aim of this study was to investigate the oestrus-inducing potential of the pituitary gland extract of the Africa Catfish ( Clarias gariepinus ) in immature Wistar rats., Methods: The experiment involved the use of 18 immature female Wistar rats and 10 male catfish brood stocks with the use of six Wistar rats per groups as follows: Group A had human chorionic gonadotropin (hCG) treatment. Group B had only normal saline treatment as the control whereas Group C had the C. gariepinus pituitary extract administration to induce oestrus with treatments occurring twice six hours apart in each group., Results: There was an obvious expression of visible signs of heat and the presence of uterine horn oedema with significant ( p < 0.05) increase in reproductive tract weight and uterine width and length. However, only progesterone levels increased significantly ( p < 0.05) in the hCG and the C. gariepinus pituitary extract treated groups compared to other assayed hormones., Conclusion: These results showed that C. gariepinus pituitary extract has the capacity to induce oestrus in Wistar rats because of its gonadotropic effects, which needs further investigations at higher doses and for longer exposure periods for possible oestrus induction and synchronization in higher mammals. Further favourable results could herald the possible patent of the catfish pituitary extract for either experimental or commercial use in mammals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Circular RNAs (circRNAs) are important biological molecules associated with the pathogenesis of multiple cancers., Objective: This work aimed to investigate the function and molecular mechanism of circ&#95;0070203 in high-grade serous ovarian cystadenocarcinoma (HGSOC)., Methods: circRNA microarray was conducted to detect the circ&#95;0070203 expression in HGSOC tissues. Bioinformatics analysis was used to find the binding sites between circ&#95;0070203, miR- 370-3p and TGFβR2. Real-time quantitative reverse transcription PCR (RT-qPCR) was executed to detect the expressions of circ&#95;0070203, miR-370-3p and TGFβR2 in HGSOC tissues and SKOV3 cells. Dual-luciferase reporter gene assay was used to validate the relationships between miR-370-3p and circ&#95;0070203 or TGFβR2. Besides, transwell assays were conducted to assess the migrative, invasive abilities of ovarian cancer (OC) cells. Western blotting was adopted to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins. The related patents were also studied during the research., Results: Circ&#95;0070203 and TGFβR2 were upregulated, while miR-370-3p was downregulated in FIGO stage III-IV HGSOC tissues and SKOV-3 cell lines. circ&#95;0070203 overexpression changed the expression of other EMT-related proteins and enhanced the migrative, invasive abilities of OC cells, while silencing circ&#95;0070203 worked oppositely. Mechanistically, circ&#95;0070203 could upregulate TGFβR2 expression in OC cells via sponging miR-370-3p., Conclusion: Circ&#95;0070203 could promote the epithelial-mesenchymal transition, invasion, and metastasis of HGSOC via regulating the miR-370-3p/TGFβR2 axis. Our findings provided a potential biomarker for HGSOC therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Tuberculosis (TB) is considered a significant health problem caused by Mycobacterium tuberculosis . It is one of the second-deadly infectious diseases right after AIDS. Several factors such as poor patient compliance, high dose intake, low drug bioavailability and prolonged treatment of disease are responsible for the prevalence of multi-drug resistance tuberculosis and extensively drug-resistant tuberculosis cases. Therefore, developing such drug-resistant bacterial strains has created a robust and efficient system that can improve the therapeutic effectiveness of anti-tubercular drugs. This review manuscript highlights the therapeutic outcomes of a nanotechnology-based drug delivery system in treating TB. Various novel nanoformulations for anti-mycobacterial drugs have been explored. Such novel approaches would have shown several advantages such as sustained/controlled drug release, reduced dose frequency, and resolved poor patient compliance over many free anti-tubercular drugs. This framework will provide valuable information on various nanoparticle-based technology employed in treating TB infectious disease. Patent data were searched in google patent and nanoformulations outcomes for TB management improves health of patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Chlorogenic acid (CA, United States Patent No. 10772340), a natural biologically active food ingredient, displays potent antitumor activity against a variety of cancer cells. However, the mechanism underlying its anticancer effect is not well elucidated., Objective: In the present study, we hope to dissect the mechanism underlying the anticancer effects of CA in pancreatic cancer cells., Methods: The cytotoxicity of CA in pancreatic cancer cells was determined by MTT assay. Flow cytometry was performed to evaluate the cells apoptosis, while a clonogenic assay was carried out to check the colony formation of cancer cells. Transwell assay was performed to assess the cells migration and invasion. The protein expression of AKT/GSK-3β/β-catenin signaling pathway was detected by Western Blot., Results: Our data indicated that CA inhibited the proliferation of PANC-28 and PANC-1 cells in a dose and time-dependent manner. CA was able to inhibit colony formation, migration, and invasion ability and trigger apoptosis in PANC-28 and PANC-1 cells. Further study showed that CA down-regulated the expression of AKT, p-AKT(Thr308), p-GSK-3β(Ser9), β-catenin, N-cadherin, and vimentin while enhancing the expression of cleaved-caspase 3 and cleaved-caspase 7 in PANC-28 and PANC-1 cells., Conclusion: Our study provides significant evidence that CA is able to inhibit the growth of pancreatic cancer via the AKT/GSK-3β/β-catenin signaling pathway., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

DNA is a remarkably precise medium for copying and storing biological information. It serves as a design for cellular machinery that permits cells, organs, and even whole organisms to work. The fidelity of DNA replication results from the action of hundreds of genes involved in proofreading and damage repair. All human cells can acquire genetic changes in their DNA all over life. Genetic mutations are changes to the DNA sequence that happen during cell division when the cells make copies of themselves. Mutations in the DNA can cause genetic illnesses such as cancer, or they could help humans better adapt to their environment over time. The endogenous reactive metabolites, therapeutic medicines, and an excess of environmental mutagens, such as UV rays all continuously damage DNA, compromising its integrity. One or more chromosomal alterations and point mutations at a single site (monogenic mutation) including deletions, duplications, and inversions illustrate such DNA mutations. Genetic conditions can occur when an altered gene is inherited from parents, which increases the risk of developing that particular condition, or some gene alterations can happen randomly. Moreover, symptoms of genetic conditions depend on which gene has a mutation. There are many different diseases and conditions caused by mutations. Some of the most common genetic conditions are Alzheimer's disease, some cancers, cystic fibrosis, Down syndrome, and sickle cell disease. Interestingly, scientists find that DNA mutations are more common than formerly thought. This review outlines the main DNA mutations that occur along the human genome and their influence on human health. The subject of patents pertaining to DNA mutations and genetic disorders has been brought up., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Around 1.5 billion people in the world are affected by complex neurological disorders, and the figure is increasing alarmingly due to unsatisfactory clinical outcomes. To date, no conventional formulation can show a promising effect on the control or prevention of neurodegeneration. However, Nano delivery tools have shown better penetration and profound action on the targeted area of the brain., Methods: Although existing Nano therapeutic approaches are abundant but would not reach the clinic due to their improper bioavailability, BBB restricts its entry and causes improper biodistribution, so it is a challenge to use certain bioactive as a potential therapy in neurodegenerative disorders. Hybrid nanocarriers are nano-vesicular transported systems which could be utilized as carriers for the delivery of both hydrophilic and hydrophobic compounds. Available patents on nanodelivery for therapeutic approaches will also include in this review., Results: Hybrid Nano delivery system may provide good stability to polar and nonpolar compounds and improve their stability., Conclusion: This manuscript updates the available findings on the Nano vesicular system to deliver drugs for neurodegenerative disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

One of the major disturbing pathways within cancer is "The Kirsten rat sarcoma viral oncogene homolog (KRAS) pathway", and it has recently been demonstrated to be the most crucial in therapies and diagnostics. KRAS pathway includes numerous genes. This multi-component signaling system promotes cell growth, division, survival, and death by transferring signals from outside the cell to its interior. KRAS regulates the activation of a variety of signaling molecules. The KRAS oncogene is a key player in advancing a wide range of malignancies, and the mutation rank of this gene is a key feature of several tumors. For some malignancies, the mutation type of the gene may offer information about prognostic, clinical, and predictive. KRAS belongs to the RAS oncogene family, which consists of a compilation of minor GTP-binding proteins that assimilate environmental inputs and trigger internal signaling pathways that control survival, cell differentiation, and proliferation. This review aims to examine the recent and fascinating breakthroughs in the identification of new therapies that target KRAS, including the ever-expanding experimental approaches for reducing KRAS activity and signaling as well as direct targeting of KRAS. A literature survey was performed. All the relevant articles and patents related to the KRAS pathway, the mutation in the KRAS gene, cancer treatment, and diagnostics were found on PubMed and Google Patents. One of the most prevalent causes of cancer in humans is a mutation in the K-RAS protein. It is extremely difficult to decipher KRAS-mediated signaling. It allows transducing signals to go from the cell's outer surface to its nucleus, having an influence on a variety of crucial cellular functions including cell chemotaxis, division, dissemination, and cell death. Other involved signaling pathways are RAF, and the phosphatidylinositol 3 kinase also known as AKT. The EGFR pathway is incomplete without KRAS. The activation of PI3K significantly contributes to acquiring resistance to a mixture of MEK inhibitors and anti-EGFR in colorectal cancer cell lines which are mutated by KRAS. A series of recent patent studies towards cancer diagnostics and therapeutics reveals the paramount importance of mutated protein KRAS as an extensive driver in human tumors. For the prognosis, diagnosis, and treatment of colorectal cancer, KRAS plays a critical role. This review concludes the latest and vowing developments in the discovery of novel techniques for diagnosis and drugs that target KRAS, the advancements in experimental techniques for signaling and inhibiting KRAS function, and the direct targeting of KRAS for cancer therapeutics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The search for novel compounds targeting Peroxisome Proliferator-Activated Receptors (PPARs) is currently ongoing, starting from the previous successfully identification of selective, dual or pan agonists. In last years, researchers' efforts are mainly paid to the discovery of PPARγ and δ modulators, both agonists and antagonists, selective or with a dual-multitarget profile. Some of these compounds are currently under clinical trials for the treatment of primary biliary cirrhosis, nonalcoholic fatty liver disease, hepatic, and renal diseases., Areas Covered: A critical analysis of patents deposited in the range 2020-2023 was carried out. The novel compounds discovered were classified as selective PPAR modulators, dual and multitarget PPAR agonists. The use of PPAR ligands in combination with other drugs was also discussed, together with novel therapeutic indications proposed for them., Expert Opinion: From the analysis of the patent literature, the current emerging landscape sees the necessity to obtain PPAR multitarget compounds, with a balanced potency on three subtypes and the ability to modulate different targets. This multitarget action holds great promise as a novel approach to complex disorders, as metabolic, inflammatory diseases, and cancer. The utility of PPAR ligands in the immunotherapy field also opens an innovative scenario, that could deserve further applications.

Background: The forthcoming problems will be of food, and soil due to environmental alteration, growing populations, pollution, and exhaustion of natural resources among other factors. Hydroponic farming has the capacity to alleviate the intimidation of these con-cerned issues in the agricultural system. Hydroponics is recommended as an alternative way to enhance product yield compared to conventional agriculture., Objective: The present study aimed to determine the different growth parameters and constituents of soil-grown and hydroponically grown Trachyspermum ammi and Foeniculum vulgare for the first time, which could be a patentable in future., Methods: In this study, extraction was carried out by maceration method using methanol as a solvent whereas, growth parameters were performed by the leaves number, plant height, and leaf area. Chlorophyll content was also performed in both sources. Further, a comparison of chemical constituents from different sources was analyzed by GC-MS., Results: The bioactive components in hydroponically grown T. ammi were found more as compared to soil-grown T. ammi . The GC-MS analysis revealed the presence of various compounds in the methanolic extract of plant materials., Conclusion: Hence, hydroponics could be an alternative in agriculture and this system is now accepted globally. This method provides diverse perspectives for farmers to harvest high-yield, better quality, and enhanced bioactive compounds., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Psoriasis is an inflammatory and proliferative autoimmune dermatological disorder. It is a skin ailment that is defined by particular, drab-red or peach-pink stiff areas with silvery scales patches. Other typical characteristics include the proliferation of epidermal layer, aberrant keratinization, hyperkeratosis, increased micro capillary vascularization, and infiltration of inflammatory mediator loaded cells. Conventional pharmacotherapies currently available can only provide minor advantages. Nanomedicines based on nanotechnology can potentially improve the efficacy and safety of psoriasis medications. Apoptosis plays an important pathogenetic role in many chronic inflammatory diseases, including those of dermatological interest, in particular, regarding psoriasis. In this regard, treatments with antioxidant properties could be appropriate therapeutic options. We reviewed the available studies on the efficacy of antiapoptotic therapies in psoriasis. We'll look at phytochemicals in this review, which are natural components found in plants with antiapoptotic activity that are frequently used to treat psoriasis. For improved topical treatment, we also take into consideration the advantages of loading phytoconstituents as medicines into lipid based nanocarriers. The utilization of herbal nanomedicines in psoriasis, as well as nano delivery carrier system for phytoconstituents with improved therapeutic profiles and decreased toxicity, are the subjects of this review. The study's purpose is to find more effective herbal nanomedicines for treating psoriasis. In the treatment of psoriasis, phytoconstituents that have shown antipsoriatic potential in recent years, as well as phytoconstituents loaded based nanomedicines, have a lot of promising roles to be explored. Furthermore, very few patents have been found in the field of nanotechnology utilizing lipid-based nanocarrier system for the treatment of psoriasis. Therefore, this review greatly compels the researcher to validate the process development of lipid-based drug delivery system for the patentability of the product. This should be in a view of shifting in the applicability of the drug delivery system for general public health as a potential treatment option in psoriasis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Neurological disorders (ND) have affected a major part of our society and have been a challenge for medical and biosciences for decades. However, many of these disorders haven't responded well to currently established treatment approaches. The fact that many active pharmaceutical ingredients can't get to their specified action site inside the body is one of the main reasons for this failure. Extracellular and intracellular central nervous system (CNS) barriers prevent the transfer of drugs from the blood circulation to the intended location of the action. Utilizing nanosized drug delivery technologies is one possible way to overcome these obstacles. These nano-drug carriers outperform conventional dosage forms in many areas, including good drug encapsulation capacity, targeted drug delivery, less toxicity, and enhanced therapeutic impact. As a result, nano-neuroscience is growing to be an intriguing area of research and a bright alternative approach for delivering medicines to their intended action site for treating different neurological and psychiatric problems. In this review, we have included a short overview of the pathophysiology of neurological diseases, a detailed discussion about the significance of nanocarriers in NDs, and a focus on its recent advances. Finally, we highlighted the patented technologies and market trends, including the predictive analysis for the years 2021-2028., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: SARS-CoV-2, a highly dynamic beta-coronavirus, can afflict all age groups. Notably, over 16100 mortalities have been recorded among children as yet. In this regard, many vaccine projects are operational to assess immuno-potency among young cohorts. A bulk of reports have evidenced the efficacy of these immunization technologies in the elderly population, though the impact is yet to be determined among children., Objectives: This review is envisioned to outline the current efficacy of contributing vaccine technologies and examine the dose-dependent impact of immunization regimens in lowering the risks of SARS-CoV-2 infections among children and adolescents. Furthermore, the current review exclusively estimated the vaccine impact at current doses., Methods: A total of 52 research papers extracted from PubMed, Pubmed Central, Science Direct, Research Gate, Google Scholar and Semantic Scholar were screened along with an emphasis on patents. Inclusion criteria involved all published reports directly or indirectly linked to the contributing vaccine candidates that are operational among the young cohort. Unrelated research papers were excluded from the study. Key search terminologies included information on vaccine identifiers, such as name, type and clinical trial ID, and successively restricted to children and adolscents age groups., Results: Several vaccine designs, such as mRNA-based vaccinations, viral vector vaccines, DNA vaccines, inactivated vaccines, recombinant vaccines, and protein-based immunizations, are being examined at various stages of clinical trials to gauge the effects on children and adolescents. With reference to the published reports, the mRNA 1273 (1610 GMT; 6-10 yrs, 1401 GMT; 12-15 yrs), BNT162b2 (1407 GMT; 6 months- <2 yrs, 1535 GMT; 2-4 yrs, 4583 GMT; 5-11 yrs, 1239.5 GMT; 12-15 yrs) and Ad5 nCoV (1037.5 GMT; 6-17 yrs) offered relatively high neutralization titers with sharp seroconversion rates compared to MVC-COV1901 (648.5 GMT; 12-17 yrs) and ZyCoV-D (133.49 GMT; 12-17 yrs), which produced modest immune responses., Conclusion: Currently, the WHO is analyzing emerging evidence to issue an emergency use list of vaccines for vaccinating children and adolescents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)