![]() On another level, the immunogenicity of murine-derived antibodies was overcome by humanizing their encoding genes with specific sequences of human origin andtransgenic mice able to synthesize fully human antibodies were successfully created. Initially, the introduction of antibody fragments allowed a more uniform and deeper penetration of the targeted tissue and reduced unwanted activation of Fc-mediated immune reactions. Major scientific advancements including Recombinant DNA Technology, Hybridoma Technology, and Polymerase Chain Reaction have considerably impacted the use of monoclonal antibodies providing technical and effective solutions to overcome the shortcomings encountered with conventional antibodies. The use of monoclonal antibodies represents an important and efficient diagnostic and therapeutic tool in disease management and modern science but remains limited by several factors including the uneven distribution in diseased tissues as well as undesired activation of side immune reactions. This study represents the first comparative in silico model of snakebite envenomation and treatment. Comparisons to existing antivenoms and experimental rescue studies highlight the large dose reductions that could result from recombinant antivenom use. Variable venom dose tests were applied to visualise effective antivenom dose levels. As a case study, intramuscular envenomation by Naja sumatrana (equatorial spitting cobra) and its treatment using Fab, F (ab’)2, and IgG antivenoms was simulated. Elimination and biodistribution parameters were regressed against molecular weight to predict the dynamics of IgG, F (ab’)2, Fab, scFv, and nanobody antivenoms, spanning a size range of 15–150 kDa. A two-compartment mathematical model of envenomation and treatment was defined and the system was parameterised using existing data from rabbits. The purpose of this study was to establish a computational model of systemic snake envenomation and treatment, for the quantitative assessment and comparison of conventional and next-generation antivenoms. Computational simulations represent a powerful tool to explore the interplay between these varied antivenom scaffolds and venoms, to assess whether a pharmacokinetically optimal antivenom exists. These scaffolds similarly span a wide molecular weight range and subsequently display diverse pharmacokinetic behaviours. In recent years, a range of scaffolds have been applied to antivenom development. ![]() Snake venom toxins span a wide molecular weight range, influencing their absorption, distribution, and elimination within the body. Snakebite envenomation is responsible for over 100,000 deaths and 400,000 cases of disability annually, most of which are preventable through access to safe and effective antivenoms. ![]() We will also discuss current topics of interest surrounding the potential use of antibody fragments for intracellular targeting and blood–brain barrier (BBB) penetration. In this review, we will discuss the structure, production, and mechanism of action of EMA/FDA-approved fragments and of those in clinical and pre-clinical development. They offer several advantages over full-length monoclonal antibodies, particularly a lower cost of goods, and because of their small size they can penetrate tissues, access challenging epitopes, and have potentially reduced immunogenicity. ![]() Antibody fragments can be used on their own or linked to other molecules to generate numerous possibilities for bispecific, multi-specific, multimeric, or multifunctional molecules, and to achieve a variety of biological effects. The development of smaller, antigen binding antibody fragments, derived from conventional antibodies or produced recombinantly, has been growing at a fast pace. Since the licensing of the first monoclonal antibody therapy in 1986, monoclonal antibodies have become the largest class of biopharmaceuticals with over 80 antibodies currently approved for a variety of disease indications.
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