Making new drugs the hard way.

A new drug can have its origin in either pharma, biotech or academia. In general, discovery scientists working in pharma and biotech are advantaged over their academic counterparts and the relative advantages and disadvantages associated are discussed in depth. Against all odds, an increasing number of important drugs have had their origins in academia. This article reports three case studies from the Liotta Research Group (LRG), which explores the special circumstances that allowed these drug development campaigns to be successful. The first involves the antiretroviral agent, emtricitabine. In this case efficient synthetic methodology, developed in the LRG, coupled with some key university and commercial sector partnerships, enabled a group of academic collaborators to discover and develop a highly effective HIV reverse transcriptase inhibitor. The second case study involves the discovery and development of the breakthrough hepatitis C drug, sofosbuvir. Based on key input from Professors Schinazi and Liotta at Emory University, scientists at the Emory startup, Pharmasset, identified the nucleoside core of the drug that would become sofosbuvir. Subsequent analysis of its phosphorylation profile by Pharmasset scientists suggested that converting it to its corresponding monophosphate prodrug would circumvent a kinase block and enable it to be an effective hepatitis C polymerase inhibitor. The third case study describes the formation of DRIVE (Drug Innovation Ventures at Emory)/EIDD (Emory Institute for Drug Development), which were created to circumvent unintended impediments for carrying out academic drug discovery and development. Although DRIVE/EIDD is a wholly-owned, not-for-profit subsidiary of Emory University, it contains many attributes that enables it to operate much more nimbly than a typical academic laboratory. With an experienced drug development team and no shareholders to distract them, DRIVE/EIDD was able to focus its attention of the development of drugs to address viral diseases of global concern. In particular, their strategy to identify and develop an antiviral agent active against multiple single-stranded RNA viruses led to molnupiravir, a broadly active, oral drug that received Emergency Use Authorization for the treatment of SARS-CoV-2 infections (i.e., COVID-19).

Introducing biosimilar competition for cell and gene therapy products.

This article provides an early analysis of the potential for creating future biosimilar competition for cell and gene therapies (CGTs) to lower prices and improve patient access, building on a unique set of interviews with relevant experts. Our discussion addressed regulatory, manufacturing, intellectual property, and market size challenges. Due to CGTs' complexity, meeting the regulatory requirement of 'high similarity with no clinically meaningful differences' will be difficult. Gene therapies are likely better candidates for biosimilar development than cell therapies. Biosimilarity should be met when gene therapy biosimilars contain the same genetic sequence as a reference product, and the variability in the vector meets the high similarity standard. Manufacturing challenges, including the lack of standardized platforms, high production costs, and complexity, pose significant obstacles. It may also be important to demonstrate biosimilarity within the manufacturing process. Intellectual property barriers, specifically patenting, trade secrecy, and regulatory exclusivity, could hinder biosimilars' ability to gain market share, although recent Supreme Court decisions limiting the breadth of patent claims could ease barriers to future CGT competition, including from biosimilars. Finally, inadequate market sizes might create hurdles, especially for curative treatments, as patient pools shrink following treatment by the reference CGT.

The impact of intellectual property demonstration policies on carbon emission efficiency.

Confronted with the concurrent challenges of economic advancement and environmental management, this study explores whether implementing Intellectual Property Demonstration Policies (IPDP) can be a covert force in enhancing carbon emission efficiency. Utilizing panel data from 280 prefecture-level cities in China over the period 2007-2019, we employ a quasi-natural experimental design, incorporating multiple-period difference-in-differences models, mediation effect models, and spatial Durbin difference-in-differences models to assess the impacts of IPDP on carbon emission efficiency, its mechanisms of action, and its spatial spillover effects. The regression results of the multi-period difference-in-differences model reveal a statistically significant enhancement in carbon emission efficiency due to IPDP, with an impact coefficient of 0.044. Through heterogeneity tests, it is observed that the influence of IPDP on carbon emission efficiency varies based on regional characteristics, carbon emission levels, and the extent of marketization. The mediation effect model demonstrates that IPDP enhances carbon emission efficiency by fostering green technological innovation and facilitating the transformation of industrial structures. Furthermore, the spatial Durbin difference-in-differences model illustrates that IPDP positively influences the carbon emission efficiency of neighboring regions, indicating favorable spatial spillover effects. Notably, the indirect effect coefficients in the geographical distance matrix, economic distance matrix, and economic-geographical nested matrix are calculated as 0.673, 0.250, and 0.386, respectively. These findings offer compelling theoretical and empirical support for strengthening the intellectual property framework to optimize its environmental impact.

Intellectual property licensing of therapeutics during the COVID-19 crisis: lessons learnt for pandemic preparedness and response.

During the COVID-19 pandemic, intellectual property licensing through bilateral agreements and the Medicines Patent Pool were used to facilitate access to new COVID-19 therapeutics in low- and middle-income countries (LMICs). The lessons learnt from the application of the model to COVID-19 could be relevant for preparedness and response to future pandemics and other health emergencies.The speed at which affordable versions of a new product are available in LMICs is key to the realization of the potential global impact of the product. When initiated early in the research and development life cycle, licensing could facilitate rapid development of generic versions of innovative products in LMICs during a pandemic. The pre-selection of qualified manufacturers, for instance building on the existing network of generic manufacturers engaged during the COVID-19 pandemic, the sharing of know-how and the quick provision of critical inputs such as reference listed drugs (RLDs) could also result in significant time saved. It is important to find a good balance between speed and quality. Necessary quality assurance terms need to be included in licensing agreements, and the potentials of the new World Health Organization Listed Authority mechanism could be explored to promote expedited regulatory reviews and timely access to safe and quality-assured products.The number, capacity, and geographical distribution of licensed companies and the transparency of licensing agreements have implications for the sufficiency of supply, affordability, and supply security. To foster competition and support supply security, licenses should be non-exclusive. There is also a need to put modalities in place to de-risk the development of critical pandemic therapeutics, particularly where generic product development is initiated before the innovator product is proven to be effective and approved. IP licensing and technology transfer can be effective tools to improve the diversification of manufacturing and need to be explored for regional manufacturing for accelerated access at scale in in LMICs and supply security in future pandemics.

Ethical Considerations and Fundamental Principles of Large Language Models in Medical Education: Viewpoint.

This viewpoint article first explores the ethical challenges associated with the future application of large language models (LLMs) in the context of medical education. These challenges include not only ethical concerns related to the development of LLMs, such as artificial intelligence (AI) hallucinations, information bias, privacy and data risks, and deficiencies in terms of transparency and interpretability but also issues concerning the application of LLMs, including deficiencies in emotional intelligence, educational inequities, problems with academic integrity, and questions of responsibility and copyright ownership. This paper then analyzes existing AI-related legal and ethical frameworks and highlights their limitations with regard to the application of LLMs in the context of medical education. To ensure that LLMs are integrated in a responsible and safe manner, the authors recommend the development of a unified ethical framework that is specifically tailored for LLMs in this field. This framework should be based on 8 fundamental principles: quality control and supervision mechanisms; privacy and data protection; transparency and interpretability; fairness and equal treatment; academic integrity and moral norms; accountability and traceability; protection and respect for intellectual property; and the promotion of educational research and innovation. The authors further discuss specific measures that can be taken to implement these principles, thereby laying a solid foundation for the development of a comprehensive and actionable ethical framework. Such a unified ethical framework based on these 8 fundamental principles can provide clear guidance and support for the application of LLMs in the context of medical education. This approach can help establish a balance between technological advancement and ethical safeguards, thereby ensuring that medical education can progress without compromising the principles of fairness, justice, or patient safety and establishing a more equitable, safer, and more efficient environment for medical education.

Rise of the (3D printing) machines in healthcare.

Three-dimensional printing (3D printing) or "additive manufacturing" first came to prominence in the field of engineering, in particular in the transport sector where the value of its fast and accurate prototyping and manufacture of spare parts was quickly recognised. However, over the last ten years, this revolutionary technology has disrupted established manufacture in an increasingly diverse range of technical areas. Perhaps the most unexpected of these is pharmaceuticals - not merely the manufacture of products such as surgically inserted implants, but also of dosage formulations themselves - now available in all manner of printed delivery forms and vehicles and showing promising control of release properties though 3D printing process choices. This review will provide an overview of how 3D printing technology has developed and expanded across technological boundaries during the past decade, with a closer look at the current opportunities and barriers to its widespread adoption, particularly in the medical and pharmaceutical sectors. Special attention has been paid to patents as a boost and barrier to the expansion of 3D printing in the medical and pharmaceutical sector, with a focus on the patent literature.

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.

Propiedad intelectual y derecho de la competencia en el sector farmacéutico durante la pandemia de COVID-19

La pandemia de COVID-19 demostró que las políticas públicas relacionadas con la propiedad intelectual y el derecho de la competencia no fueron adecuadas o suficientemente articuladas para permitir el acceso oportuno de la población a las vacunas de manera equitativa, debido a distorsiones en su fabricación, distribución y venta cuando éstas estuvieron disponibles durante la pandemia. Esta investigación tiene como objetivo analizar, desde una perspectiva jurídica, si los problemas observados se originan en una inadecuada aplicación de la legislación que regula la propiedad intelectual y su relación con otras políticas públicas vinculadas a la competencia, o, eventualmente, en el ejercicio abusivo de tales derechos, y que, como consecuencia, distorsionaría el proceso de competencia en los mercados nacionales y regionales.

The COVID 19 pandemic demonstrated that public policies related to intellectual property and competition law were not adequate or sufficiently articulated to allow timely access to vaccines in an equitable manner, due to distortions in the manufacture, distribution, and sale of COVID-19 vaccines when they were available during the pandemic. This research aims to analyze, from a legal perspective, whether the observed problems originate in an inadequate application of intellectual property legislation and its relationship with other public policies related to competition, or, eventually, in the abusive exercise of such rights, which, as a consequence, would distort the process of competition in national and regional markets.

A pandemia de COVID 19 demostrou que as políticas públicas relacionadas com a propriedade intelectual e o direito de competência não foram adequados ou suficientemente articulados para permitir o acesso oportuno da população às vacinas de maneira equitativa, devido a distorções na fabricação, distribuição e venda de vacinas COVID-19, quando estavam disponíveis durante a pandemia. Esta investigação tem como objetivo analizar, desde uma perspectiva jurídica, se os problemas observados se originam em uma inadequada aplicação da legislação que regula a propriedade intelectual e sua relação com outras políticas públicas vinculadas à competência ou, eventualmente, no exercício abusivo de tais direitos, e que, como consequência, distorceria o processo de competência nos mercados nacionais e regionais.

Regulatory considerations and intellectual property rights of repurposed drugs.

Drug repurposing has emerged as a promising approach in the drug discovery and development process as it offers safe and effective therapeutic options in a time effective manner. Though the issues related to pre-clinical and clinical aspects of drug development process are greatly addressed during drug repurposing yet regulatory perspectives gain even more However, like traditional drug development the repurposed drugs face multiple challenges. Such challenges range from the patenting rights, novelty of repurposing, data and market exclusivity to affordability and equitable access to the patient population. In order to optimize the market access of repurposed drugs, regulatory organizations throughout the world have developed accelerated approval procedures. The regulatory bodies have recognized the importance of repurposing approaches and repurposed drugs. Regulatory bodies can encourage the development of repurposed drugs by providing incentives to pharmaceutical companies and more accessible and affordable repurposed agents for the general population. This chapter summarizes the regulatory and ethical considerations pertaining to the repurposed drugs and highlights a few cases of intellectual property rights for repurposed drugs that have helped improve patient's access to safe, efficacious and cost-effective therapeutic options.

Biobank donation in search of public benefits and the potential impact of intellectual property rights over access to health-technologies developed: A focus on the bioethical implications.

The availability of biomaterials is a key component of health research and the development of new health-technologies (including, diagnostics, medicines, and vaccines). People are often encouraged by biobanks to donate samples altruistically to such biobanks. While empirical evidence suggests many donors are motivated by the desire to contribute towards developing new health-technologies for society. However, a tension can arise as health-technologies whose development is contributed to by donors' biomaterials will often be protected by intellectual property rights (IPRs), including patents. Patents give rightsholders control over how patented technologies are used and can be used in a way that impedes public access to technologies developed. Yet, there are no binding European legal obligations mandating disclosure to donors of how IPRs can operate over downstream health-technologies and how they could impact access to health-technologies developed, nor are there legally binding obligations to ensure public accessibility of technologies developed. Focusing on the bioethical implications posed, this article argues that the current situation can impact donors' autonomy and dignity interests. A more holistic approach is needed for biobank donation, which embeds a consideration of donors' expectations/interests from the point of donation through to how such samples are used and how health-technologies developed are accessed. We put forward avenues that seek to address such issues.

Regulatory insights into nanomedicine and gene vaccine innovation: Safety assessment, challenges, and regulatory perspectives.

This analysis explores the principal regulatory concerns linked to nanomedicines and gene vaccines, including the complexities involved and the perspectives on how to navigate them. In the realm of nanomedicines, ensuring the safety of nanomaterials is paramount due to their unique characteristics and potential interactions with biological systems. Regulatory bodies are actively formulating guidelines and standards to assess the safety and risks associated with nanomedicine products, emphasizing the need for standardized characterization techniques to accurately gauge their safety and effectiveness. Regarding gene vaccines, regulatory frameworks must be tailored to address the distinct challenges posed by genetic interventions, necessitating special considerations in safety and efficacy evaluations, particularly concerning vector design, target specificity, and long-term patient monitoring. Ethical concerns such as patient autonomy, informed consent, and privacy also demand careful attention, alongside the intricate matter of intellectual property rights, which must be balanced against the imperative of ensuring widespread access to these life-saving treatments. Collaborative efforts among regulatory bodies, researchers, patent offices, and the private sector are essential to tackle these challenges effectively, with international cooperation being especially crucial given the global scope of nanomedicine and genetic vaccine development. Striking the right balance between safeguarding intellectual properties and promoting public health is vital for fostering innovation and ensuring equitable access to these ground-breaking technologies, underscoring the significance of addressing these regulatory hurdles to fully harness the potential benefits of nanomedicine and gene vaccines for enhancing healthcare outcomes on a global scale. STATEMENT OF SIGNIFICANCE: Several biomaterials are being proposed for the development of nanovaccines, from polymeric micelles, PLGA-/PEI-/PLL-nanoparticles, solid lipid nananoparticles, cationic lipoplexes, liposomes, hybrid materials, dendrimers, carbon nanotubes, hydrogels, to quantum dots. Lipid nanoparticles (LNPs) have gained tremendous attention since the US Food and Drug Administration (FDA) approval of Pfizer and Moderna's COVID-19 vaccines, raising public awareness to the regulatory challenges associated with nanomedicines and genetic vaccines. This review provides insights into the current perspectives and potential strategies for addressing these issues, including clinical trials. By navigating these regulatory landscapes effectively, we can unlock the full potential of nanomedicine and genetic vaccines using a range of promising biomaterials towards improving healthcare outcomes worldwide.

Cambodia's Imminent Graduation from Least Developed Country Status: What Will be the Impact of the TRIPS Agreement on Access to HIV and Hepatitis C Medicines in Cambodia?

Cambodia has experienced exponential economic growth in recent years and is expected to graduate from least developed country (LDC) status within the next decade. Membership of the World Trade Organization (WTO) will require Cambodia to grant product and process patents for pharmaceuticals upon LDC graduation. This study aims to measure the impact of the WTO Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) on the price of HIV and hepatitis C medicine in Cambodia once it graduates from LDC status and is obliged to make patents available for pharmaceutical products and processes. Using scenarios based on likely outcomes of accession to the TRIPS Agreement, it measures the impact on the price of the HIV treatment program and compares that impact with the hepatitis C treatment program. Graduation from LDC status would be expected to result in a modest increase in the cost of the antiretroviral (ARV) treatment program and very large increases in the cost of the direct acting antivirals (DAA) treatment program. If annual treatment budgets remain constant, patent protection could see 1,515 fewer people living with HIV able to access ARV treatment and 2,577 fewer people able to access DAA treatment (a drop in treatment coverage of 93%).

Innovative Solutions for Patients Who Undergo Craniectomy: Protocol for a Scoping Review.

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

Considerations for Clinician-Educators Developing Online Educational Content: A Narrative Review.

In modern medical education, clinician-educators are increasingly called upon to develop online education to complement or replace in-person instruction. Despite a growing need for online curricula, many medical professionals lack training and experience in digital content development, deployment, assessment, and maintenance. Previous studies offer guidance on some aspects of online education development but often overlook key components, such as accessibility, legal considerations, financial implications, and sustainability challenges. This review offers medical professionals a broad overview of these important issues. We discuss various pedagogical considerations, including aligning educational goals and objectives with the digital content, choosing the appropriate online interface, and employing strategies to mitigate cognitive load while maximizing accessibility to create an inclusive online learning environment. We offer practical tips for creating effective, high-quality, and enduring audio-visual content and reflect on initial content deployment, testing, assessment, and revision. We discuss the intricacies of obtaining continuing medical education credits when the target audience includes faculty members. We address several legal issues online educators must consider, such as copyright laws, intellectual property rights, and medical liability. The review concludes with a discussion of sustainability mechanisms and financial considerations to ensure the long-term success of the educational program. Our recommendations aim to equip medical professionals embarking on a digital education journey with practical tools to produce effective, inclusive, and sustainable online content while considering legal implications.

SecureNet: Proactive intellectual property protection and model security defense for DNNs based on backdoor learning.

With the widespread application of deep neural networks (DNNs), the risk of privacy breaches against DNN models is constantly on the rise, resulting in an increasing need for intellectual property (IP) protection for such models. Although neural network watermarking techniques are widely used to safeguard the IP of DNNs, they can only achieve passive protection and cannot actively prevent unauthorized users from illicit use or embezzlement of the trained DNN models. Therefore, the development of proactive protection techniques to prevent IP infringement is imperative. To this end, we propose SecureNet, a key-based access license framework for DNN models. The proposed approach involves injecting license keys into the model through backdoor learning, enabling correct model functionality only when the appropriate license key is included in the input. To ensure the reusability of DNN models, we also propose a license key replacement algorithm. In addition, based on SecureNet, we designed defense mechanisms against adversarial attacks and backdoor attacks, respectively. Furthermore, we introduce a fine-grained authorization method that enables flexible granting of model permissions to different users. We have designed four license-key schemes with different privileges, tailored to various scenarios. We evaluated SecureNet on five benchmark datasets including MNIST, Cifar10, Cifar100, FaceScrub, and CelebA, and assessed its performance on six classic DNN models: LeNet-5, VGG16, ResNet18, ResNet101, NFNet-F5, and MobileNetV3. The results demonstrate that our approach outperforms the state-of-the-art model parameter encryption methods by at least 95% in terms of computational efficiency. Additionally, it provides effective defense against adversarial attacks and backdoor attacks without compromising the model's overall performance.

The impact of intellectual property rights protection on green innovation: A quasi-natural experiment based on the pilot policy of the Chinese intellectual property court.

In the context of high-quality economic development in China, it is important to promote green innovation development by protecting intellectual property rights (IPR). Taking the pilot policy of the intellectual property courts in Beijing, Shanghai, and Guangzhou for example in a quasi-natural experiment, this article examines the effect of IPR protection on the development of corporate green innovation and its mechanisms by using a difference-in-differences model and a mediating effect model based on Chinese enterprise data from 2011 to 2019. The study found that first, IPR protection promotes enterprise green technological innovation; second, IPR protection affects green innovation through enterprise financing constraints and R&D investment; that is, increasing enterprise R&D investment and alleviating enterprise financing constraints are two important channels through which IPR protection promotes enterprise green technological innovation.

Recent Technological and Intellectual Property Trends in Antibody-Drug Conjugate Research.

Antibody-drug conjugate (ADC) therapy, an advanced therapeutic technology comprising antibodies, chemical linkers, and cytotoxic payloads, addresses the limitations of traditional chemotherapy. This study explores key elements of ADC therapy, focusing on antibody development, linker design, and cytotoxic payload delivery. The global rise in cancer incidence has driven increased investment in anticancer agents, resulting in significant growth in the ADC therapy market. Over the past two decades, notable progress has been made, with approvals for 14 ADC treatments targeting various cancers by 2022. Diverse ADC therapies for hematologic malignancies and solid tumors have emerged, with numerous candidates currently undergoing clinical trials. Recent years have seen a noteworthy increase in ADC therapy clinical trials, marked by the initiation of numerous new therapies in 2022. Research and development, coupled with patent applications, have intensified, notably from major companies like Pfizer Inc. (New York, NY, USA), AbbVie Pharmaceuticals Inc. (USA), Regeneron Pharmaceuticals Inc. (Tarrytown, NY, USA), and Seagen Inc. (Bothell, WA, USA). While ADC therapy holds great promise in anticancer treatment, challenges persist, including premature payload release and immune-related side effects. Ongoing research and innovation are crucial for advancing ADC therapy. Future developments may include novel conjugation methods, stable linker designs, efficient payload delivery technologies, and integration with nanotechnology, driving the evolution of ADC therapy in anticancer treatment.

Exploring how IP marketing (media marketing) influences consumer shopping psychology through quantitative and empirical analysis.

As the concepts of intellectual property and media marketing have gained popularity, media marketing has gradually become an integral part of intellectual property marketing, and its use has become more widespread. However, the field of intellectual property marketing (media marketing) has become confused and faces challenges such as loss of uniqueness and weak consumer connections. Existing research efforts have focused on marketing strategies for branded intellectual property, but have neglected the important perspective of consumer psychology and behaviour. In this study, we use the AISAS model to segment digital marketing and delve into consumer psychology and behavioural factors that influence intellectual property marketing (media marketing). This exploration covers intellectual property content at the attention stage, intellectual property value at the interest stage, emotional trust at the search stage, mental consumption at the purchase stage and fan interaction at the sharing stage. We conducted a comprehensive analysis of the data using SPSS and AMOS, and integrated a consumer attitude questionnaire. The final findings confirm that intellectual property content, value, emotional trust, spiritual consumption and fan interaction all positively influence consumer psychology and behaviour. In addition, we make consumer-centric recommendations to extend the life cycle of intellectual property and promote sustainable brand development.