Download or read book Aggregation of Therapeutic Proteins from Dilute Towards Concentrated Conditions written by Lucrèce Hélène Nicoud and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Aggregation of Therapeutic Proteins written by Wei Wang and published by John Wiley & Sons. This book was released on 2010-12-28 with total page 400 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book gives pharmaceutical scientists an up-to-date resource on protein aggregation and its consequences, and available methods to control or slow down the aggregation process. While significant progress has been made in the past decade, the current understanding of protein aggregation and its consequences is still immature. Prevention or even moderate inhibition of protein aggregation has been mostly experimental. The knowledge in this book can greatly help pharmaceutical scientists in the development of therapeutic proteins, and also instigate further scientific investigations in this area. This book fills such a need by providing an overview on the causes, consequences, characterization, and control of the aggregation of therapeutic proteins.
Download or read book Aggregation in Concentrated Protein Solutions written by Maria Castellanos Mantilla and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Aggregation of therapeutic proteins is currently one of the major challenges in the bio-pharmaceutical industry, because aggregates could induce immunogenic responses and compromise the quality of the product. Current scientific efforts, both in industry and academia, are focused on developing rational approaches to screen different drug candidates and predict their stability under different conditions. Moreover, aggregation is promoted in highly concentrated protein solutions, which are typically required for subcutaneous injection. In order to gain further understanding about the mechanisms that lead to aggregation, an approach that combined rheology, neutron scattering, and molecular simulations was undertaken. Two model systems were studied in this work: Bovine Serum Albumin in surfactant-free Phosphate Buffered Saline at pH = 7.4 at concentrations from 11 mg/mL up to ~519 mg/mL, and a monoclonal antibody in 20 mM Histidine/Histidine Hydrochloride at pH = 6.0 with 60 mg/mL trehalose and 0.2 mg/mL polysorbate-80 at concentrations from 53 mg/mL up to ~220 mg/mL. The antibody used here has three mutations in the CH2 domain, which result in lower stability upon incubation at 40 C with respect to the wild-type protein, based on size-exclusion chromatography assays. This temperature is below 49 C, where unfolding of the least stable, CH2 domain occurs. This dissertation focuses on identifying the role of aggregation on the viscosity of protein solutions. The protein solutions of this work show an increase in the low shear viscosity in the absence of surfactants, because proteins adsorb at the air/water interface forming a viscoelastic film that affects the measured rheology. Stable surfactant-laden protein solutions behave as simple Newtonian fluids. However, the surfactant-laden antibody solution also shows an increase in the low shear viscosity from bulk aggregation, after prolonged incubation at 40 C.Small-angle neutron scattering experiments were used to characterize the antibody aggregates responsible for this non-Newtonian response. From the neutron scattering data, a weak barrier leading to reversible aggregation is identified. Therefore, proteins aggregate weakly after colliding hydrodynamically, unless they find a favorable contact with high binding energy. Two types of antibody aggregates were identified: oligomers with average radius of gyration of ~10 nm, and fractal aggregates larger than ~ 0.1 [mu]m formed by a reaction-limited aggregation process. A characteristic upturn in the scattered intensity at low wavevector and a low shear viscosity increase are observed in aggregated protein solutions. These features are removed by filtering with a 0.2 [mu]m filter, which also eliminates the submicron fractal aggregates. Biophysical characterization supports the conclusions from the rheology and neutron scattering experiments. Finally, molecular dynamics simulations were used to understand the effects of disulfide bonds on the conformational stability of serum albumin. Changes in disulfide bonds in the native structure could lead to partial unfolding, and the formation of aggregates through inter-molecular disulfide bonds. Therefore, it is important to understand the role of each disulfide bond on the structure and dynamics of the protein. After removing disulfide bonds, changes occur in the dynamic correlations between different residues, the secondary and tertiary structure of albumin. However, not all disulfide bonds affect the conformation of the protein. Removal of all disulfide bonds using molecular dynamics is proposed as a practical prescreening tool to identify disulfide bonds that are important for the conformational stability. As a result, some disulfide bonds can be mutated without affecting the conformation of the protein.
Download or read book Therapeutic Proteins written by C. Mark Smales and published by Springer Science & Business Media. This book was released on 2008-02-04 with total page 481 pages. Available in PDF, EPUB and Kindle. Book excerpt: With the recent completion of the sequencing of the human genome, it is widely anticipated that the number of potential new protein drugs and targets will escalate at an even greater rate than that observed in recent years. However, identification of a potential target is only part of the process in developing these new next generation protein-based “drugs” that are increasingly being used to treat human disease. Once a potential protein drug has been identified, the next rate-limiting step on the road to development is the production of sufficient authentic material for testing, charact- ization, clinical trials, and so on. If a protein drug does actually make it through this lengthy and costly process, methodology that allows the production of the protein on a scale large enough to meet demand must be implemented. Furthermore, large-scale production must not compromise the authenticity of the final product. It is also nec- sary to have robust methods for the purification, characterization, viral inactivation and continued testing of the authenticity of the final protein product and to be able to formulate it in a manner that retains both its biological activity and lends itself to easy administration. Therapeutic Proteins: Methods and Protocols covers all aspects of protein drug production downstream of the discovery stage. This volume contains contributions from leaders in the field of therapeutic protein expression, purification, characterization, f- mulation, and viral inactivation.
Download or read book Analysis of Aggregates and Particles in Protein Pharmaceuticals written by Hanns-Christian Mahler and published by John Wiley & Sons. This book was released on 2012-01-24 with total page 480 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book describes how to address the analysis of aggregates and particles in protein pharmaceuticals, provides a comprehensive overview of current methods and integrated approaches used to quantify and characterize aggregates and particles, and discusses regulatory requirements. Analytical methods covered in the book include separation, light scattering, microscopy, and spectroscopy.
Download or read book Biofunctional Surface Engineering written by Martin Scholz and published by CRC Press. This book was released on 2014-02-21 with total page 339 pages. Available in PDF, EPUB and Kindle. Book excerpt: Successful biofunctional surface engineering will determine the future of medical devices such as orthopedic implants, stents, catheters, vaccine scaffolds, wound dressings, and extracorporeal circulation devices. Moreover, the biosensor and diagnostic chip technology will evolve rapidly due to the growing medical need for personalized medicine. A
Download or read book Stress induced Aggregation of Therapeutic Proteins written by Lu Liu and published by . This book was released on 2013 with total page 137 pages. Available in PDF, EPUB and Kindle. Book excerpt: Therapeutic proteins are inherently unstable. Stresses such as freeze-thawing and agitation can induce protein aggregation, and consequently reduce drug efficacy or cause adverse immunogenicity. The aims of this thesis were to better understand stress-induced protein aggregation through novel findings in other disciplines such as biophysics and interfacial sciences. We studied the effects of pH and additives on freezing-induced perturbations of tertiary structure of a monoclonal antibody (mAb) by intrinsic tryptophan (Trp) fluorescence spectroscopy. We found freezing-induced protein aggregation may or may not first involve the perturbation of its native structure, followed by the assembly processes to form aggregates. Depending on the solution conditions, either step can be rate-limiting. This study demonstrates the potential of fluorescence spectroscopy as a valuable tool for screening therapeutic protein formulations subjected to freeze-thaw stress. We investigated the effects of excipients on protein aggregation during agitation as well as the effects of same compounds on interfacial shear rheology of the protein at air-liquid interface. Heparin, sucrose, and Polysorbate 80 (PS80) alone could not effectively inhibit a model protein keratinocyte growth factor 2 (KGF2, FGF10) aggregation during non-agitated and agitated incubation. The combination of PS 80 and heparin or sucrose substantially inhibited aggregation during both protocols. Interfacial shear rheology provides insight regarding the rate of gel formation and the role of non-ionic surfactants at the interface. There is a correspondence between formulations that exhibited interfacial gelation and formulations that exhibited agitation-induced aggregation. We also found filters used to remove particles from protein solutions actually shed particles, which stimulated protein aggregation during stresses such as agitation. Particles shedding from syringe filters varied greatly among the filters types from the manufacturers. Furthermore, particles shed from the filters may change the rate of protein aggregation during agitation. Last but not least, we found bevacizumab repackaged in plastic syringes could contain protein aggregates and was contaminated by silicone oil microdroplets. Freeze-thawing or other mishandling can further increase levels of particle contaminants. This study may help to reduce mishandling of repackaged bevacizumab caused adverse effects in patients with eye diseases.
Download or read book Protein Refolding written by George Georgiou and published by . This book was released on 1991 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: the refolding process is often the critical bottleneck in the production of high-value proteins, and recently acquired insights have yet to be translated into technological advantages. These proceedings bridge the gap between fundamental and applied studies, addressing such issues as in vivo protein folding, protein aggregation and inclusion body formation, elucidation of the folding pathway, characterization of folding intermediates, and practical considerations in protein renaturation. The symposium was part of the 199th ACS National Meeting, Boston, April 1990. Annotation copyrighted by Book News, Inc., Portland, OR
Download or read book Colloidal Dispersions written by William Bailey Russel and published by Cambridge University Press. This book was released on 1991 with total page 548 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers the physical side of colloidal science from the individual forces acting between particles smaller than a micrometer that are suspended in a liquid, through the resulting equilibrium and dynamic properties. A variety of internal forces both attractive and repulsive act in conjunction with Brownian motion and the balance between them all decides the phase behaviour. On top of this various external fields, such as gravity or electromagnetic fields, diffusion and non-Newtonian rheology produce complex effects, each of which is of important scientific and technological interest. The authors aim to impart a sound, quantitative understanding based on fundamental theory and experiments with well-characterised model systems. This broad grasp of the fundamentals lends insight and helps to develop the intuitive sense needed to isolate essential features of the technological problems and design critical experiments. The main prerequisites for understanding the book are basic fluid mechanics, statistical mechanics and electromagnetism, though self contained reviews of each subject are provided at appropriate points. Some facility with differential equations is also necessary. Exercises are included at the end of each chapter, making the work suitable as a textbook for graduate courses in chemical engineering or applied mathematics. It will also be useful as a reference for individuals in academia or industry undertaking research in colloid science.
Download or read book Protein Self Assembly written by Jennifer J. McManus and published by Humana. This book was released on 2020-08-08 with total page 266 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume explores experimental and computational approaches to measuring the most widely studied protein assemblies, including condensed liquid phases, aggregates, and crystals. The chapters in this book are organized into three parts: Part One looks at the techniques used to measure protein-protein interactions and equilibrium protein phases in dilute and concentrated protein solutions; Part Two describes methods to measure kinetics of aggregation and to characterize the assembled state; and Part Three details several different computational approaches that are currently used to help researchers understand protein self-assembly. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Thorough and cutting-edge, Protein Self-Assembly: Methods and Protocols is a valuable resource for researchers who are interested in learning more about this developing field.
Download or read book Rational Design of Stable Protein Formulations written by John F. Carpenter and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 218 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recombinant proteins and polypeptides continue to be the most important class of biotechnology-derived agents in today's pharmaceutical industry. Over the past few years, our fundamental understanding of how proteins degrade and how stabilizing agents work has made it possible to approach formulation of protein pharmaceuticals from a much more rational point of view. This book describes the current level of understanding of protein instability and the strategies for stabilizing proteins under a variety of stressful conditions.
Download or read book Continuous Biopharmaceutical Processes written by David Pfister and published by Cambridge University Press. This book was released on 2018-10-11 with total page 349 pages. Available in PDF, EPUB and Kindle. Book excerpt: This innovative reference provides a coherent and critical view on the potential benefits of a transition from batch to continuous processes in the biopharmaceutical industry, with the main focus on chromatography. It also covers the key topics of protein stability and protein conjugation, addressing the chemical reaction and purification aspects together with their integration. This book offers a fine balance between theoretical modelling and illustrative case studies, between fundamental concepts and applied examples from the academic and industrial literature. Scientists interested in the design of biopharmaceutical processes will find useful practical methodologies, in particular for single-column and multi-column chromatographic processes.
Download or read book Therapeutic Proteins written by Vladimir Voynov and published by Humana Press. This book was released on 2016-05-01 with total page 516 pages. Available in PDF, EPUB and Kindle. Book excerpt: Emphasizing the newest developments in the field, this volume presents detailed methodswith added emphasison therapeutic protein discovery. It features key tips and valuable implementation advice to ensure successful results."
Download or read book Specific Ion Effects written by Werner Kunz and published by World Scientific. This book was released on 2010 with total page 347 pages. Available in PDF, EPUB and Kindle. Book excerpt: Specific ion effects are important in numerous fields of science and technology. This book summarizes the main ideas that came up over the years. It presents the efforts of theoreticians and supports it by the experimental results stemming from various techniques.
Download or read book Basic Principles of Analytical Ultracentrifugation written by Peter Schuck and published by CRC Press. This book was released on 2016-01-05 with total page 318 pages. Available in PDF, EPUB and Kindle. Book excerpt: Analytical ultracentrifugation (AUC) can supply rich information on the mass, shape, size distribution, solvation, and composition of macromolecules and nanoscopic particles. It also provides a detailed view of their reversible single- or multi-component interactions over a wide range of affinities. Yet this powerful technique has been hard to mast
Download or read book Handbook of Biological Therapeutic Proteins written by Sarfaraz Niazi and published by CRC Press. This book was released on 2024-04-15 with total page 413 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since 1972, which marks the invention of recombinant engineering, more than 500 therapeutic proteins have been approved for clinical use. Today, biological drugs constitute almost 70% of all new drugs and have a biological origin. The first edition of this book dealt with biosimilars, and this edition (i.e., the second edition) focuses on new drugs, yet limits to therapeutic proteins. Newer technologies for drug development represent the updated topics in the book and include repur-posing, AI- driven identification of newer designs, novel expression systems, manufacturing using these systems, rapidly changing regulatory pathways, and legal hurdles. This edition discusses how to identify, develop, manufacture, and take multibillion dollar products to market within the shortest possible time. Features: Complete and thorough coverage of the regulatory and technological challenges of developing generic therapeutic proteins Comprehensive, discovery to market, newer technologies, regulatory planning and IP hurdles are included that are not found elsewhere Expanded volume that must be in the hands of every company interested in biological drugs, including the mRNA-based biopharmaceutical companies fast appearing on the market Discusses how to identify, develop, manufacture, and take multibillion dollar products to market in the shortest possible time Renowned author and entrepreneur in the field of drug discovery and production
Download or read book Pharmaceutical Excipients written by Otilia M. Y. Koo and published by John Wiley & Sons. This book was released on 2016-10-03 with total page 369 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides an overview of excipients, their functionalities in pharmaceutical dosage forms, regulation, and selection for pharmaceutical products formulation. It includes development, characterization methodology, applications, and up-to-date advances through the perspectives of excipients developers, users, and regulatory experts. Covers the sources, characterization, and harmonization of excipients: essential information for optimal excipients selection in pharmaceutical development Describes the physico-chemical properties and biological effects of excipients Discusses chemical classes, safety and toxicity, and formulation Addresses recent efforts in the standardization and harmonization of excipients
