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Recognizing reality, Uwe Schoenbeck, PhD, senior vice president and chief scientific officer for Emerging Science & Innovation (ES&I) at Pfizer, has synthesized and made functional core lessons from two of the past decade's best business books: According to Schoenbeck, ESLs are highly experienced in the relevant disease area and embedded within the respective therapeutic areas, resulting in high strategic alignment of the opportunity being sourced and avoiding opportunities that are not a strategic fit (1). The ES&I team, in conjunction with colleagues working in Business Development, has stood out for bringing genuinely creative partnership ideas and innovations into an already creative and crowded environment. [...]a collaboration with Codex DNA will potentially streamline the mRNA production process by facilitating synthetic DNA assembly, another notable fruit of the team's labour to bring forth a competitive pipeline in gene therapy.
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From the perspective of the IRB, the requirements for data safety monitoring as appropriate for assent by minors, for permission from parents, is already there to apply to COVID-19 research. If you had a research protocol seeking to enroll minors, and it required them to give up standard of care therapy in order to participate and they had asthma, that would be cause for concern by the IRB. Russell-Einhorn: We've drawn lines to review this research for adults vs. pediatrics for numerous years. Since we do make a distinction between a minor and an adult, and a 17-yearold is considered a minor.
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Background & Aim: Gene therapies has become recognized for its remarkable clinical benefits in a variety of medical applications, in particular recent approval of an Ad vector-based COVID-19 vaccines have attracted recent global attention. Here, we present key considerations for GMP compliant process development for Coxsackie virus type B3 (CVB3), an oncolytic virus designed for clinical trial in triple-negative breast cancer. Methods, Results & Conclusion(s): CVB3 is a non-enveloped, linear single-strand RNA virus with a size of approximately 27-33 um in diameter. From the initial type using the zonal rotor centrifuge to the advanced type using the tangential flow filtration system and ion chromatograph, we considered the points of the design concept in constructing the manufacturing process. The final design system is constructed as a closed and single-use manufacturing system in which all processes from upstream large-scale cell culture to downstream target purification and concentration steps. In brief, HEK293 cell suspension extended in 3L serum-free medium infected with CVB3, up to 3.6 times 10 to 7 of TCID50 /mL before going to downstream steps, made total 150 mL of final products as 8.43 times 10 to 7 of TCID50/mL concentration. Although further quality control challenges remain that is removal of product-related impurities such as human cellular proteins and residual DNA/RNA to increase virus purity, this concept is effectively applicable even for other types of viruses as GMP manufacturing processes, and would be also important for technology transfer to future commercial production.Copyright © 2023 International Society for Cell & Gene Therapy
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[...]the committee recommended granting a conditional marketing authorization for Retsevmo (selpercatinib) for the treatment of cancers displaying a rearranged during transfection (RET) gene fusion, including RET-fusion positive non-small cell lung cancer, RET-fusion positive thyroid cancer, and RET-mutant medullary-thyroid cancer (1). The committee also recommended granting a marketing authorization under exceptional circumstances for Lumoxiti (moxetumomab pasudotox) for the treatment of relapsed or refractory hairy cell leukaemia (1). In January, the European Commission (EC) granted conditional marketing authorization to Moderna's COVID-19 vaccine (8), following a positive recommendation by EMA, based on positive Phase III clinical trial data that showed over 90% efficacy in participants at risk of severe COVID-19 and a 94% reduction in the number of symptomatic COVID-19 cases (9).
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[...]it can be difficult to provide and ensure the same degree of quality, consistency, and compliance in a point-of-use facility compared to a centralized manufacturer. While you have possibly solved the issue of patient access and therapy transport, you have introduced logistical issues with maintaining supply chain and support (engineering, maintenance, calibration, etc.) logistics. The facility is intended to serve a local patient population instead of a global population. [...]the scale of production for a point-of-use facility is going to be smaller by design. The design team would need to account for the site location requirements, and, if the point-of-use facility is intended to be mobile and relocatable, the span of site requirements it may encounter.
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Elizabeth Rickenbacher, PhD, Director of Strategy for 4G Clinical, has over 15 years of experience in the field of life sciences, and is an eClinical RTSM solutions subject matter expert. Given what we see now, we can expect advancements in RTSMs to handle future iterations of decentralized trial designs, cell and gene therapy trials, digital supply chains as well as much more complexity in terms of adaptive designs, particularly in oncology trials. From a technical and process point of view, there is a trend toward more self-service components to ease the administrative burden of adapting study parameters such as managing cohorts;enhanced flexibility to the patient level as patient advocacy for their own care continues to increase;as well as functionality to support the protocol designs of tomorrow's trials.
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Late-Breaking and COVID-19 Oral Communication SessionLB/CO01.1 A Novel Adeno Associated Virus (AAV) Gene Therapy (FLT180a) Achieves Normal FIX Activity Levels in Severe Hemophilia B (HB) Patients (B-AMAZE Study): P. Chowdary1,2, S. Shapiro3, M. Makris4, G. Evans5, S. Boyce6, K. Talks7, G. Dolan8, U. Reiss9, M. Phillips1, A. Riddell1, M.R. Peralta1, M. Quaye2, E. Tuddenham1, J. Krop10, G. Short11, S. Kar11, A. Smith11, A. Nathwani1,2 1Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital NHS Foundation Trust, London, United Kingdom2University College London, London, United Kingdom3Oxford Haemophilia & Thrombosis Centre and Oxford NIHR BRC, Oxford, United Kingdom4University of Sheffield, Sheffield, United Kingdom5Kent & Canterbury Hospital, Canterbury, United Kingdom6University Hospital Southampton, Southampton, United Kingdom7Newcastle Haemophilia Comprehensive Care Centre, Newcastle, United Kingdom8Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom9St Jude Children's Research Hospital, Memphis, United States10Freeline, Boston, United States11Freeline, Stevenage, United Kingdom...Copyright © 2020 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.
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Background & Aim: The new UCOE models we have recently developed, tested on many cell groups (including mouse ES and human iPS cells) and human mAb recombinant production studies as well, shows a powerful resistance to DNA methylation- mediated silencing and provides a higher and stable transfection profile. By the urgent need of vaccine development for COVID-19 during the pandemic, in this study we aimed to produce a potential recombinant vaccine by using the new generation UCOEs models of our own design. Methods, Results & Conclusion(s): Existing new-generation UCOE models and standard plasmid vectors to be used as control group were provided. Then, the sequences related to the PCR method were amplified for sufficient stock generation and cloning experiments. Verification in the plasmid vector was carried out in gel electrophoresis. Transfection of 293T cells was performed with clone plasmids carrying antigen genes and plasmids carrying genetic information of lentivirus units for the production of lentiviral vectors. Afterwards, 293T cells produced lentiviral vectors carrying antigen genes. Harvesting of these vectors was carried out during 48th and 72nd hours. Afterwards, CHO cells were transduced with appropriate quantity of lentiviral vectors. Isolation and purification of targeted proteins from the relevant medium were performed by HPLC and Q-TOF methods. A part of the spike and nucleocapsid gene sequences of COVID-19 were firstly cloned into our UCOE models. These UCOEs plasmids were then transferred into 293T cells along with plasmids carrying the genes that will form the lentivirus vectors (LVs). After harvesting and calculation of LV vector titers, the cloned vectors were then transfected into the CHO cells which the targeted recombinant production of the antigen proteins will be carried out. Antigenic structures were then isolated from the culture medium of CHO cells in following days for confirmation. Using HPLC and qTOF mass spectrometer methods, these structures in the medium were confirmed to be the units of spike and nucleocapsid proteins of the COVID-19 virus. In order to produce large amount of the recombinant antigens, the culture was then carried out with bioreactors in liters. At the final stage, these recombinantly produced antigen proteins were tested on rats to measure their immunogenic responses, and the study recently been completed successfully as a potential recombinant vaccine against COVID-19.Copyright © 2023 International Society for Cell & Gene Therapy
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[...]ustekinumab concentrated solution and ustekinumab injection are the first IL-12/IL-23 inhibitors to be studied by EDQM for monograph development via the P4 process (13). First "horizontal standard" for biotherapeutic monographs Today, there are several TNF-alpha inhibitor products available, and manufacturers have used a wide variety of methods to assess the potency of these mAbs. Two other horizontal standards are currently being elaborated by EDQM: "Capillary Isoelectric Focusing for Recombinant Therapeutic ~ Monoclonal antibodies (2.5.44)" and "Size Exclusion Chromatography for Recombinant Therapeutic Monoclonal Antibodies (2.5.43)" (19). The final change to CGT standards is to general chapter "Raw Materials of Biological Origin for the Production of Cell-based Therapy Medicinal Products (5.2.12)."
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This review highlights ten important advances in the neuromuscular disease field that were first reported in 2020. The overarching topics include (i) advances in understanding of fundamental neuromuscular biology; (ii) new / emerging diseases; (iii) advances in understanding of disease etiology and pathogenesis; (iv) diagnostic advances; and (v) therapeutic advances. Within this broad framework, the individual disease entities that are discussed in more detail include neuromuscular complications of COVID-19, supervillin-deficient myopathy, 19p13.3-linked distal myopathy, vasculitic neuropathy due to eosinophilic granulomatosis with polyangiitis, spinal muscular atrophy, idiopathic inflammatory myopathies, and transthyretin neuropathy/myopathy. In addition, the review highlights several other advances (such as the revised view of the myofibrillar architecture, new insights into molecular and cellular mechanisms of muscle regeneration, and development of new electron microscopy tools) that will likely have a significant impact on the overall neuromuscular disease field going forward.
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Lipid nanoparticles as delivery system for mRNA have recently attracted attention to a broader audience as COVID-19 mRNA vaccines. Their low immunogenicity and capability to deliver a variety of nucleic acids renders them an interesting and complementary alternative to gene therapy vectors like AAVs. An important quality attribute of LNPs is the copy number of the encapsulated cargo molecule. This work describes how density and molecular weight distributions obtained by density contrast sedimentation velocity can be used to calculate the mRNA copy number of a degradable lipid nanoparticle formulation. The determined average copy number of 5 mRNA molecules per LNP is consistent with the previous studies using other biophysical techniques, such as single particle imaging microscopy and multi-laser cylindrical illumination confocal spectroscopy (CICS).
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The development of stem cell transplantation technology has opened up the possibility of curing many diseases that were difficult to treat in the past. There are ethical issues in the field of widespread clinical use of human embryonic stem cells, and tissue rejection may also occurs after transplantation. One way to solve these problems is to generate specific pluripotent stem cells directly from patient cells to study specific treatments. Induced stem cells refer to a type of cell produced by the reprogramming of human somatic cells into exogenous transcription factors, which are very similar to embryonic stem cells. Both types of cells express human pluripotent factors and embryonic stem cell surface markers, and have the potential to differentiate into 3 germ layers.The induced pluripotent stem cells can be induced to differentiate into different cells under different conditions. At present, stem cell therapy has entered the clinical trial stage in many fields, and this paper discusses the stem cell regenerative medicine in the field of cardiovascular disease, eye disease, and COVID-19. This paper is a review of the current status of stem cell treatment and the challenges it is facing. © 2023 SPIE.
Subject(s)
Betacoronavirus/metabolism , Coronavirus Infections/prevention & control , Drug Industry , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Vaccines, DNA , Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus/genetics , Betacoronavirus/immunology , COVID-19 , Coronavirus Infections/therapy , Government Regulation , Lymphocytes/cytology , Lymphocytes/metabolism , Pneumonia, Viral/therapy , RNA Interference , RNA, Messenger/immunology , RNA, Messenger/metabolism , RNA, Small Interfering/therapeutic use , SARS-CoV-2 , Vaccines, DNA/immunology , Vaccines, DNA/metabolism , gamma-Globulins/immunology , gamma-Globulins/therapeutic useABSTRACT
Nanomedicine, nanotechnology, and nanodelivery systems are techniques that are of great interest to various researchers. The high surface area and other distinct physical properties of nanoparticles makes them suitable as nanomedicine for targeted drug delivery systems, MRI imaging, diagnosing kits, biomarkers, gene therapy, and many more applications. This chapter will highlight the special features of nanomedicines, their synthesis methods, and their clinical uses for targeted drug delivery. None of us is unaware of or untouched by the virus COVID-19. Outbreaks of viral diseases can potentially occur at any time and it is very challenging to deal with viruses owing to their mutation capability. It has been seen from the literature that nanomedicine has proved helpful for targeted drug delivery at the infected site without any harm to any other part of body, especially in cancer treatment. Nanomedicine has come out as lifesaving strategy: nanomedicine or nanoparticles-based strategies have strong potential to fight against viruses not only for human beings but also for animals. Nanoparticles have the special ability to bind with the virus epitope resulting in inactivation of the virus. There are several nanocarriers with the potential to replace conventional drug delivery systems with targeted drug deliveries. The nanocarriers or nanomedicine can work with small dosages, minimal toxicity, and desired flow of release of drug at the infected site. This chapter will thoroughly cover the advances in the nanomedicine field along with the challenges involved and future scope in improving the lives of livestock. © 2023 Elsevier Inc. All rights reserved.