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41.
Daniel M. Strauss Scott Lute Zinaida Tebaykina Douglas D. Frey Cintia Ho Gregory S. Blank Kurt Brorson Qi Chen Bin Yang 《Biotechnology and bioengineering》2009,104(2):371-380
During production of therapeutic monoclonal antibodies (mAbs) in mammalian cell culture, it is important to ensure that viral impurities and potential viral contaminants will be removed during downstream purification. Anion exchange chromatography provides a high degree of virus removal from mAb feedstocks, but the mechanism by which this is achieved has not been characterized. In this work, we have investigated the binding of three viruses to Q sepharose fast flow (QSFF) resin to determine the degree to which electrostatic interactions are responsible for viral clearance by this process. We first used a chromatofocusing technique to determine the isoelectric points of the viruses and established that they are negatively charged under standard QSFF conditions. We then determined that virus removal by this chromatography resin is strongly disrupted by the presence of high salt concentrations or by the absence of the positively charged Q ligand, indicating that binding of the virus to the resin is primarily due to electrostatic forces, and that any non‐electrostatic interactions which may be present are not sufficient to provide virus removal. Finally, we determined the binding profile of a virus in a QSFF column after a viral clearance process. These data indicate that virus particles generally behave similarly to proteins, but they also illustrate the high degree of performance necessary to achieve several logs of virus reduction. Overall, this mechanistic understanding of an important viral clearance process provides the foundation for the development of science‐based process validation strategies to ensure viral safety of biotechnology products. Biotechnol. Bioeng. 2009; 104: 371–380 © 2009 Wiley Periodicals, Inc. 相似文献
42.
Sture Lindegren Luciana N. S. Andrade Tom B?ck Camila Maria L. Machado Bruno Brasil Horta Carlos Buchpiguel Ana Maria Moro Oswaldo Keith Okamoto Lars Jacobsson Elin Cederkrantz Kohshin Washiyama Emma Aneheim Stig Palm Holger Jensen Maria Carolina B. Tuma Roger Chammas Ragnar Hultborn Per Albertsson 《PloS one》2015,10(5)
The aim of this preclinical study was to evaluate the characteristics of the monoclonal antibody Rebmab200, which is a humanized version of the ovarian-specific murine antibody MX35. This investigation contributes to the foundation for future clinical α-radioimmunotherapy of minimal residual ovarian cancer with 211At-Rebmab200. Here, the biodistribution of 211At-Rebmab200 was evaluated, as was the utility of 99mTc-Rebmab200 for bioimaging. Rebmab200 was directly compared with its murine counterpart MX35 in terms of its in-vitro capacity for binding the immobilized NaPi2B epitope and live cells; we also assessed its biodistribution in nude mice carrying subcutaneous OVCAR-3 tumors. Tumor antigen and cell binding were similar between Rebmab200 and murine MX35, as was biodistribution, including normal tissue uptake and in-vivo tumor binding. We also demonstrated that 99mTc-Rebmab200 can be used for single-photon emission computed tomography of subcutaneous ovarian carcinomas in tumor-bearing mice. Taken together, our data support the further development of Rebmab200 for radioimmunotherapy and diagnostics. 相似文献
43.
Gunilla Journath Niklas Hammar Stig Elofsson Anette Linnersj? Max Vikstr?m G?ran Walldius Ingvar Krakau Peter Lindgren Ulf de Faire Mai-Lis Hellénius 《PloS one》2015,10(11)
Background
In 1988, a cardiovascular prevention program which combined an individual and a population-based strategy was launched within primary health-care in Sollentuna, a municipality in Stockholm County. The aim of this study was to investigate time trends in the incidence of and mortality from acute myocardial infarction and all-cause mortality in Sollentuna compared with the rest of Stockholm County during a period of two decades following the implementation of a cardiovascular prevention program.Materials and Methods
The average population in Sollentuna was 56,589 (49% men) and in Stockholm County (Sollentuna included) 1,795,504 (49% men) during the study period of 1987–2010. Cases of hospitalized acute myocardial infarction and death were obtained for the population of Sollentuna and the rest of Stockholm County using national registries of hospital discharges and deaths. Acute myocardial infarction incidence and mortality were estimated using the average population of Sollentuna and Stockholm in 1987–2010.Results
During the observation period, the incidence of acute myocardial infarction decreased more in Sollentuna compared with the rest of Stockholm County in women (-22% vs. -7%; for difference in slope <0.05). There was a trend towards a greater decline in Sollentuna compared to the rest of Stockholm County in the incidence of acute myocardial infarction (in men), acute myocardial mortality, and all-cause mortality but the differences were not significant.Conclusion
During a period of steep decline in acute myocardial infarction incidence and mortality in Stockholm County the municipality of Sollentuna showed a stronger trend in women possibly compatible with favorable influence of a cardiovascular prevention program.Trial Registration
ClinicalTrials.gov NCT02212145 相似文献44.
Development of a modular virus clearance package for anion exchange chromatography operated in weak partitioning mode
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Timothy Iskra Ashley Sacramo Chris Gallo Ranga Godavarti Shuang Chen Scott Lute Kurt Brorson 《Biotechnology progress》2015,31(3):750-757
Anion exchange chromatography (AEX) operated under weak partitioning mode has been proven to be a powerful polishing step as well as a robust viral clearance step in Pfizer's monoclonal antibody (mAb) platform purification process. A multivariate design of experiment (DoE) study was conducted to understand the impact of operating parameters and feedstream impurity levels on viral clearance by weak partitioning mode AEX. Bacteriophage was used initially as a surrogate for neutral and acidic isoelectric point mammalian viruses (e.g., retrovirus and parvovirus). Five different mAbs were used in the evaluation of process parameters such as load challenge (both product and impurities), load pH, load conductivity, and contact time (bed height and flow‐rate). The operating ranges obtained from phage clearance studies and Pfizer's historical data were used to define an appropriate operating range for a subsequent clearance study with model retrovirus and parvovirus. Both phage and virus clearance evaluations included feedstreams containing different levels of impurities such as high molecular mass species (HMMS), host cell proteins (HCPs), and host cell DNA. For all the conditions tested, over 5 log10 of clearance for both retrovirus and parvovirus was achieved. The results demonstrated that weak partitioning mode AEX chromatography is a robust step for viral clearance and has the potential to be included as part of the modular viral clearance approach. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:750–757, 2015 相似文献
45.
Min Zhang George R. Miesegaes Michael Lee Daniel Coleman Bin Yang Melody Trexler‐Schmidt Lenore Norling Philip Lester Kurt A. Brorson Qi Chen 《Biotechnology and bioengineering》2014,111(1):95-103
Protein A chromatography is widely used as a capture step in monoclonal antibody (mAb) purification processes. Antibodies and Fc fusion proteins can be efficiently purified from the majority of other complex components in harvested cell culture fluid (HCCF). Protein A chromatography is also capable of removing modest levels of viruses and is often validated for viral clearance. Historical data mining of Genentech and FDA/CDER databases systematically evaluated the removal of model viruses by Protein A chromatography. First, we found that for each model virus, removal by Protein A chromatography varies significantly across mAbs, while remains consistent within a specific mAb product, even across the acceptable ranges of the process parameters. In addition, our analysis revealed a correlation between retrovirus and parvovirus removal, with retrovirus data generally possessing a greater clearance factor. Finally, we describe a multivariate approach used to evaluate process parameter impacts on viral clearance, based on the levels of retrovirus‐like particles (RVLP) present among process characterization study samples. It was shown that RVLP removal by Protein A is robust, that is, parameter effects were not observed across the ranges tested. Robustness of RVLP removal by Protein A also correlates with that for other model viruses such as X‐MuLV, MMV, and SV40. The data supports that evaluating RVLP removal using process characterization study samples can establish multivariate acceptable ranges for virus removal by the protein A step for QbD. By measuring RVLP instead of a model retrovirus, it may alleviate some of the technical and economic challenges associated with performing large, design‐of‐experiment (DoE)—type virus spiking studies. This approach could also serve to provide useful insight when designing strategies to ensure viral safety in the manufacturing of a biopharmaceutical product. Biotechnol. Bioeng. 2014;111: 95–103. © 2013 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. 相似文献
46.
47.
Laura Farrant Stig Irving Olsen Arne Wangel 《The International Journal of Life Cycle Assessment》2010,15(7):726-736
Background, aim, and scope
Clothes are often discarded when much of their potential lifetime is left. Many charitable organizations therefore collect used clothing and resell it as second-hand clothes for example in Eastern Europe or Africa. In this connection, the question arises whether reusing clothes actually results in a decrease of the environmental burden of the life cycle of clothing. The environmental burden of clothing has been studied in several studies. However, most of these studies focus solely on the energy consumption aspects and pay little attention to the potential benefits of diverting used clothing from the waste stream. The aim of the study was to assess the net environmental benefits brought by the disposal of used clothing through charities who return them for second-hand sales assuming that second-hand clothes to some extent replace the purchase of new clothes. 相似文献48.
Emiliano Buffo Andrea Battisti Michael Stastny Stig Larsson 《Agricultural and Forest Entomology》2007,9(1):65-72
1 The pine processionary moth Thaumetopoea pityocampa is expanding its geographical range in Europe, as a consequence of enhanced winter survival under a warmer climate. A combination of daytime nest temperatures and night air temperatures determines the number of hours larvae are able to feed (hours above realized feeding threshold, RFT). 2 We tested the RFT‐based model for survival across multiple areas of the insect’s range in the Italian Alps over a 2‐year period. In a series of translocation experiments using natural temperature gradients as spatial analogues for global warming, we transferred colonies of T. pityocampa larvae to sites within zones of historical distribution, recent distribution, and outside the present range. The sites included traditional (Pinus nigra, Pinus sylvestris) as well as novel (Pinus mugo, Pinus uncinata, Pinus cembra) hosts. 3 Survival during precold (August to November), cold (December to February) and postcold (March to May) periods were analysed against climatic variables (temperature and rainfall) and predictors developed by the model. 4 Host species did not significantly affect final survival, with the exception of slower larval development, and resulting lower cold tolerance, on P. cembra than on P. mugo at the same site. 5 Across all the sites and hosts, final survival of colonies depended on the number of feeding hours during the cold period (RFT), which explained 82% of the variance in a regression model. We recommend using RFT, or its surrogate daily mean minimum temperature when nest temperature is not available, in predictive models of range expansion of T. pityocampa under climate change scenarios. 相似文献
49.
The annual routines and seasonal ecology of herbivorous zooplankton species are relatively well known due to their tight coupling with their pulsed food source, the primary production. For higher trophic levels of plankton, these seasonal interactions are less well understood. Here, we study the mid-winter feeding of chaetognaths in high-Arctic fjord ecosystems. Chaetognaths are planktivorous predators which comprise high biomass in high-latitude seas. We investigated the common species Parasagitta elegans around the Svalbard archipelago (78–81°N) during the winters of 2012 and 2013. Our samples consisted of individuals (body lengths 9–55 mm) from three fjords, which were examined for gut contents (n = 903), stable isotopes, fatty acid composition, and maturity status (n = 352). About a quarter of the individuals contained gut contents, mainly lipid droplets and chitinous debris, whilst only 4 % contained identifiable prey, chiefly the copepods Calanus spp. and Metridia longa. The δ15N content of P. elegans, and its average trophic level of 2.9, confirmed its carnivorous position and its fatty acid profile [in particular its high levels of 20:1(n-9) and 22:1(n-11)] confirmed carnivory on Calanus. Observations of undeveloped gonads in many of the larger P. elegans, and the absence of small individuals <10 mm, suggested that reproduction had not started this early in the year. Its average feeding rate across fjords and years was 0.12 prey ind.?1 day?1, which is low compared to estimates of spring and summer feeding in high-latitude environments. Our findings suggest reduced feeding activity during winter and that predation by P. elegans had little impact on the mortality of copepods. 相似文献
50.
Christian Skov Kim Aarestrup Finn Sivebæk Stig Pedersen Trude Vrålstad Søren Berg 《Biological invasions》2011,13(6):1269-1274
North American signal crayfish (Pacifastacus leniusculus) are invasive in Europe and pose a serious threat to indigenous European crayfish such as the noble crayfish (Astacus astacus). This is mainly because signal crayfish is the carrier of crayfish plague agent, Aphanomyces astaci, which freshwater crayfish from all other continents are highly susceptible to. Until recently, the distribution of signal crayfish in Danish streams has been considered local and restricted to a small geographical area. Here we present data demonstrating that signal crayfish are now widespread in Denmark, including the largest Danish river, River Gudenå. For one of the rivers where co-existing signal crayfish and indigenous noble crayfish were documented, sensitive molecular tests could not detect the crayfish plague agent Aphanomyces astaci in either species. Hence, it seems that not all signal crayfish are chronic carriers of the disease. For the remaining freshwater systems with the introduced signal crayfish, the infection status is presently unknown. Large areas of the freshwater systems in Denmark also remain unexplored with respect to presence/absence of signal crayfish and noble crayfish. Nevertheless, our preliminary data that covers about 14% of the Danish rivers, strongly suggests that signal crayfish should be considered as a common invader that poses an increased threat to the biota in Danish streams, in particular for the indigenous noble crayfish. 相似文献