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.

A patent review of SHP2 allosteric inhibitors (2018-present).

INTRODUCTION: SHP2 (Src homology region 2-containing protein tyrosine phosphatase 2) is a target of interest for cancer therapy due to its key role in the regulation of the RAS/MAPK signal transduction pathway downstream of Receptor Tyrosine Kinases (RTKs). Moreover, SHP2 can inhibit T cells via the PD-1/PD-L1 pathway. SHP2 plays a critical role in numerous physiological and pathological cellular processes, such as cell proliferation, survival, and migration. AREAS COVERED: This review examines SHP2 allosteric inhibitors reported in patents published in Espacenet and Scifinder databases from 2018 to present. An overview of claimed structures is conducted, focusing attention on structural modifications compared to SHP099, the first described allosteric inhibitor of SHP2. EXPERT OPINION: Multiple potent allosteric SHP2 inhibitors have been discovered, disclosed, and tested in a variety of preclinical cancer models with strong evidence of efficacy. Fifteen compounds are currently in clinical development, but none of them have been approved for marketing. Until now, long-term benefit of SHP2 inhibitors as monotherapy agents have not been demonstrated due to acquired mechanisms of resistance and/or lack of efficacy. However, combination therapies with a variety of agents, such as MEK, BRAF, EGFR, RAS-G12C and PDL-1 inhibitors, have high potential and are currently an extensive area of investigation.

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.

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.

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.

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.

Enhancing cancer immunotherapy: Exploring strategies to target the PD-1/PD-L1 axis and analyzing the associated patent, regulatory, and clinical trial landscape.

Cancer treatment modalities and their progression is guided by the specifics of cancer, including its type and site of localization. Surgery, radiation, and chemotherapy are the most often used conventional treatments. Conversely, emerging treatment techniques include immunotherapy, hormone therapy, anti-angiogenic therapy, dendritic cell-based immunotherapy, and stem cell therapy. Immune checkpoint inhibitors' anticancer properties have drawn considerable attention in recent studies in the cancer research domain. Programmed Cell Death Protein-1 (PD-1) and its ligand (PD-L1) checkpoint pathway are key regulators of the interactions between activated T-cells and cancer cells, protecting the latter from immune destruction. When the ligand PD-L1 attaches to the receptor PD-1, T-cells are prevented from destroying cells that contain PD-L1, including cancer cells. The PD-1/PD-L1 checkpoint inhibitors block them, boosting the immune response and strengthening the body's defenses against tumors. Recent years have seen incredible progress and tremendous advancement in developing anticancer therapies using PD-1/PD-L1 targeting antibodies. While immune-related adverse effects and low response rates significantly limit these therapies, there is a need for research on methods that raise their efficacy and lower their toxicity. This review discusses various recent innovative nanomedicine strategies such as PLGA nanoparticles, carbon nanotubes and drug loaded liposomes to treat cancer targeting PD-1/PD-L1 axis. The biological implications of PD-1/PD-L1 in cancer treatment and the fundamentals of nanotechnology, focusing on the novel strategies used in nanomedicine, are widely discussed along with the corresponding guidelines, clinical trial status, and the patent landscape of such formulations.

Fisetin from Dietary Supplement to a Drug Candidate: An Assessment of Potential

Fisetin is a bioactive compound found in numerous fruits and vegetables, including strawberries, apples, grapes, persimmon, cucumber, onion, etc. The compound is also wellknown for its neurotrophic, anti-inflammatory, anti-carcinogenic, anti-diabetic, and other healthpromoting properties. Although there is increasing agreement that it has therapeutic properties, but its poor water solubility, high lipophilicity, and lower oral bioavailability make it difficult to use clinically. Extensive research has attempted to overcome these restrictions by developing novel and superior delivery systems. Considering the diverse potential, this review is the first to summarise the available data on Fisetin to collate the information related to analytical methods, pharmacological action, their mechanisms, regulatory aspects, and toxicity profile. It also covers the marketed products, related clinical trials, and patent updates of the moiety. In addition, an endeavor has been attempted to discuss and assess the various drug delivery systems employed to increase the biological attributes of Fisetin. The presented manuscript is the first to present a compendium of up-to-date literature on all of the domains considered necessary for this type of natural molecule to carve down its path from being a mere dietary supplement to a promising therapeutic drug candidate. The manuscript is expected to benefit the researchers working on natural and bioactive compounds, industrial scientists, and the general population interested in Fesitin.

The interactive effect of the career horizon and power of CEO on invention patents.

Invention patents are of great importance to firms, and thus understanding how invention patents are achieved is becoming increasingly important in the literature. Although previous research has shown that both CEO career horizon and CEO power are important for invention patents, little attention has been paid to their potential interactive effect. Investigating their interactive effect would be both theoretically meaningful and practically valuable. Using a sample of firms listed on the A-share market of the Shanghai and Shenzhen stock exchanges from 2010 to 2022, it is found that there is an interactive effect between CEO career horizon and CEO power, and that their interaction has a negative impact on invention patents. Furthermore, the interactive effect varies across different kinds of firms. This paper contributes to the literature on upper echelons theory by highlighting the interactive effects of multiple CEO characteristics on firm innovation.

The impact of patentees assessment based on the heterogeneous patent innovation network.

As a vital factor in technological innovation, patentee plays a significant role in the process of scientific and technological innovation, researching patentee has attracted the attention of experts and scholars. Previously, scholars have mainly quantified patent indicators or constructed homogeneous information networks to analyze patentees, but these methods cannot objectively measure the impact of patentees. Therefore, this study proposes a novel approach to assessing patentee impact based on a heterogeneous information network. The proposed method distinguishes the weight of different types of nodes using a weighted mechanism and extracts three types of fine-grained characteristics of network nodes. This approach results in the construction of a heterogeneous patent innovation network and the development of a new patentee impact assessment algorithm called CWAPN. Using Chinese green patents in the field of energy conservation and environmental protection as an example, experimental results show that the CWAPN algorithm can effectively assess the impact of patentees. Thereby identifying patentees who have made outstanding contributions to sustainable development in China.

Analysis of current technology status for the industrialization of cultured meat.

Cultured meat is expected to become an important material for future food production; however, contrary to initial expectations, the full-scale industrialization of cultured meat is slow and the actual level and opened technology amount is very limited. This study reviews the publicly available technologies of cultured meat and suggests future developmental directions and research agenda. As a result of analyzing papers, patents, and press releases published over the past 10 years, it was found that cultured meat production technology is still at the prototype production level. This is because most papers published are about culture medium and scaffold development, culture conditions, and there is almost no research on finished cultured meat products. Worldwide, most of the filed patents are for producing cultured meat principles; most of them do not use food-grade materials and are not economically feasible for industrialization. Therefore, future research on the industrialization of cultured meat should focus on effective acquisition technologies for satellite cells; cell lineage and undifferentiated state maintenance technologies; the development of serum-free media and culture devices; the prevention of genetic modification, safety verification, and mass production. Furthermore, basic research on mechanisms and influencing factors related to cultured meat production is warranted.

Advancements in lipid-based delivery systems for functional foods: a comprehensive review of literature and patent trends.

Lipid-based delivery systems (LDS) have emerged as cornerstone techniques for bolstering the bioavailability of lipophilic bioactive compounds, addressing challenges related to solubility, stability, and absorption. This critical review examined a substantial dataset of 6,907 scientific articles and 3,021 patents from 2001-2023, elucidating the multifaceted evolution of LDS, with a particular focus on its industrial and patent-driven perspective. Notably, there were pronounced surges in functional food patent applications in 2004, 2011, and 2019. The trajectory revealed a shift from foundational nanoemulsions to more complex structures, such as double/multiple emulsions, solid lipid nanoparticles, Pickering emulsions, and bigels. The review further identified the top 10 leading institutions shaping this domain. Technologies like spray-drying, microfluidics, and phase gelation had revolutionized the landscape, resulting in refined sensory experiences, innovative reduced-fat formulations, enriched beverages, tailor-made infant nutrition, and nuanced release mechanisms for flavors. The review also spotlighted current research frontiers, notably Pickering emulsions, bigels, and multiple emulsions. These emerging technologies not only exemplified the ongoing innovation in the field but also underscored their potential in reshaping the future landscape of value-added functional foods.

Exploring regulatory flexibility to create novel incentives to optimize drug discovery.

Efforts by governments, firms, and patients to deliver pioneering drugs for critical health needs face a challenge of diminishing efficiency in developing those medicines. While multi-sectoral collaborations involving firms, researchers, patients, and policymakers are widely recognized as crucial for countering this decline, existing incentives to engage in drug development predominantly target drug manufacturers and thereby do little to stimulate collaborative innovation. In this mini review, we consider the unexplored potential within pharmaceutical regulations to create novel incentives to encourage a diverse set of actors from the public and private spheres to engage in the kind of collaborative knowledge exchange requisite for fostering enhanced innovation in early drug development.

Exosomes: A New Hope for Angiogenesis-Mediated Bone Regeneration.

Bone is a metabolically dynamic structure that is generally remodeled throughout the lifetime of an individual but often causes problems with increasing age. A key player for bone development and homeostasis, but also under pathological conditions, is the bone vasculature. This complex system of arteries, veins, and capillaries forms distinct structures where each subset of endothelial cells has important functions. Starting with the basic process of angiogenesis and bone-specific blood vessel formation, coupled with initial bone formation, the importance of different vascular structures is highlighted with respect to how these structures are maintained or changed during homeostasis, aging, and pathological conditions. After exemplifying the current knowledge on bone vasculature, this review will move on to exosomes, a novel hotspot of scientific research. Exosomes will be introduced starting from their discovery via current isolation procedures and state-of-the-art characterization to their role in bone vascular development, homeostasis, and bone regeneration and repair while summarizing the underlying signal transduction pathways. With respect to their role in these processes, especially mesenchymal stem cell-derived extracellular vesicles are of interest, which leads to a discussion on patented applications and an update on ongoing clinical trials. Taken together, this review provides an overview of bone vasculature and bone regeneration, with a major focus on how exosomes influence this intricate system, as they might be useful for therapeutic purposes in the near future.

Insights into Intra Periodontal Pocket Pathogenesis, Treatment, In Vitro-In Vivo Models, Products and Patents, Challenges and Opportunity.

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.

The dawning era of oral thin films for nutraceutical delivery: From laboratory to clinic.

Oral thin films (OTFs) are innovative dosage forms that have gained tremendous attention for the delivery of nutraceuticals. They are ultra-thin, flexible sheets that can be easily placed on the tongue, sublingual or buccal mucosa (inner lining of the cheek). These thin films possess several advantages for nutraceutical delivery including ease of administration, rapid disintegration, fast absorption, rapid onset of action, bypass first-pass hepatic metabolism, accurate dosing, enhanced stability, portability, discreetness, dose flexibility and most importantly consumer acceptance. This review highlights the utilization OTFs for nutraceutical delivery, their composition, criteria for excipient selection, methods of development and quality-based design (QbD) approach to achieve quality product. We have also provided recent case studies representing OTFs as promising platform in delivery of nutraceuticals (plant extracts, bioactive molecules, vitamins, minerals and protein/peptides) and probiotics. Finally, we provided advancement in technologies, recent patents, market analysis, challenges and future perspectives associated with this unique dosage form.

PCSK9 inhibitors: a patent review 2018-2023.

INTRODUCTION: Proprotein convertase subtilisin/kexin 9 (PCSK9) plays a crucial role in breaking down the hepatic low-density lipoprotein receptor (LDLR), thereby influencing the levels of circulating low-density lipoprotein cholesterol (LDL-C). Consequently, inhibiting PCSK9 through suitable ligands has been established as a validated therapeutic strategy for combating hypercholesterolemia and cardiovascular diseases. AREA COVERED: Patent literature claiming novel compounds inhibiting PCSK9 disclosed from 2018 to June 2023 available in the espacenet database, which contains more than 150 million patent documents from over 100 patent-granting authorities worldwide. EXPERT OPINION: The undisputable beneficial influence of PCSK9 as a pharmacological target has prompted numerous private and public institutions to patent chemical frameworks as inhibitors of PCSK9. While several compounds have advanced to clinical trials for treating hypercholesterolemia, they have not completed these trials yet. These compounds must contend in a complex market where new, costly, and advanced drugs, such as monoclonal antibodies and siRNA, are prescribed instead of inexpensive and less potent statins.

Unravelling the in vivo dynamics of liposomes: Insights into biodistribution and cellular membrane interactions.

Liposomes, as a colloidal drug delivery system dating back to the 1960s, remain a focal point of extensive research and stand as a highly efficient drug delivery method. The amalgamation of technological and biological advancements has propelled their evolution, elevating them to their current status. The key attributes of biodegradability and biocompatibility have been instrumental in driving substantial progress in liposome development. Demonstrating a remarkable ability to surmount barriers in drug absorption, enhance stability, and achieve targeted distribution within the body, liposomes have become pivotal in pharmaceutical research. In this comprehensive review, we delve into the intricate details of liposomal drug delivery systems, focusing specifically on their pharmacokinetics and cell membrane interactions via fusion, lipid exchange, endocytosis etc. Emphasizing the nuanced impact of various liposomal characteristics, we explore factors such as lipid composition, particle size, surface modifications, charge, dosage, and administration routes. By dissecting the multifaceted interactions between liposomes and biological barriers, including the reticuloendothelial system (RES), opsonization, enhanced permeability and retention (EPR) effect, ATP-binding cassette (ABC) phenomenon, and Complement Activation-Related Pseudoallergy (CARPA) effect, we provide a deeper understanding of liposomal behaviour in vivo. Furthermore, this review addresses the intricate challenges associated with translating liposomal technology into practical applications, offering insights into overcoming these hurdles. Additionally, we provide a comprehensive analysis of the clinical adoption and patent landscape of liposomes across diverse biomedical domains, shedding light on their potential implications for future research and therapeutic developments.