In this work, an overview of the biosimilars market, pipeline and industry targets is discussed. Biosimilars typically have a shorter timeline for approval (8 years) compared to 12 years for innovator drugs and the development cost can be 10–20% of the innovator drug. The biosimilar pipeline is reviewed as well as the quality management system (QMS) that is needed to generate traceable, trackable data sets. One difference between developing a biosimilar compared to an originator is that a broader analytical foundation is required for biosimilars and advances made in developing analytical similarity to characterize these products are discussed. An example is presented on the decisions and considerations explored in the development of a biosimilar and includes identification of the best process parameters and methods based on cost, time, and titer. Finally factors to consider in the manufacture of a biosimilar and approaches used to achieve the target-directed development of a biosimilar are discussed.
Hydrothermal vents are considered as one of the most extremely harsh environments on the Earth. In this study, the complete mitogenomes of hydrothermal vent squat lobsters, Munidopsis lauensis and M. verrilli, were determined through Illumina sequencing and compared with other available mitogenomes of anomurans. The mitogenomes of M. lauensis (17,483 bp) and M. verrilli (17,636 bp) are the largest among all Anomura mitogenomes, while the A+T contents of M. lauensis (62.40%) and M. verrilli (63.99%) are the lowest. The mitogenomes of M. lauensis and M. verrilli display novel gene arrangements, which might be the result of three tandem duplication–random loss (tdrl) events from the ancestral pancrustacean pattern. The mitochondrial gene orders of M. lauensis and M. verrilli shared the most similarities with S. crosnieri. The phylogenetic analyses based on both gene order data and nucleotide sequences (PCGs and rRNAs) revealed that the two species were closely related to Shinkaia crosnieri. Positive selection analysis revealed that eighteen residues in seven genes (atp8, Cytb, nad3, nad4, nad4l, nad5, and nad6) of the hydrothermal vent anomurans were positively selected sites. 相似文献
Myelosuppression is one of the major side-effects of most anticancer drugs. To achieve myeloprotection, one bicistronic vector encoding anti-apoptotic protein human WEE l (WEElHu) and proliferation-stimulating stem cell factor (SCF) was generated. In this study, we selected human umbilical cord blood CD34^+ cells as the in vitro model in an attempt to investigate whether WEEIHu, rather than conventional drug-resistant genes, can be introduced to rescue cells from the damage by chemotherapeutic agents such as cisplatin, adriamycin, mitomycin-c and 5-fluorouracil. Cell viability and cytotoxicity assay, colony-forming units in culture assay and externalization of phospholipid phosphatidylserine analysis showed that the expression of WEElHu and SCF in CD34^+ cells provided the cells with some protection. These findings suggest that the expression of WEElHu and SCF might rescue CD34^+ cells from chemotherapyinduced myelosuppression. 相似文献
A weak ion exchange monolithic column prepared by modifying the GMA-MAA-EDMA (glycidyl methacrylate-methacrylic acid-ethylene glycol dimethacrylate) monoliths with ethylenediamine was applied to remove matrix compounds in biological fluid. Using this monolithic column, on-line clean-up and screening of oxacillin and cloxacillin in human urine and plasma samples had been investigated. Chromatography was performed by reversed-phase HPLC on a C(18) column with ultraviolet detection at 225 nm. Results showed that the ion exchange monolithic column could be used for deproteinization and retaining oxacillin and cloxacillin in human urine and plasma, which provided a simple and fast method for assaying drugs in human urine and plasma. 相似文献
Cell membrane proteome analysis is limited by inherent membrane hydrophobicity. Conventional membrane protein extraction techniques use detergents, chaotropes and organic acids that require sample clean-up or pH adjustment, and are associated with significant sample loss. We extracted membrane proteins from red blood cells (RBCs) using methanol (MeOH), trifluoroethanol (TFE) and urea, and identified membrane proteins using 2-D LC coupled with MALDI-TOF/TOF-MS. We show that organic solvents MeOH- and TFE-based methods have membrane protein analysis efficiencies comparable to urea, and are complementary for the recovery of both hydrophilic and hydrophobic peptides. The mean grand average of hydropathicity (GRAVY) value of identified peptides from the TFE-based method (-0.107) was significantly higher than that of the MeOH-based method (-0.465) (p<0.001). Sequential and adjunctive use of the organic solvents MeOH and TFE increases the number of proteins identified, and the confidence of their identification. We show that this strategy is effective for shotgun membrane proteome analysis. 相似文献
Biomedical application of nanotechnology is a rapidly developing area that raises new prospect in the improvement of diagnosis and treatment of human diseases. The ability to incorporate drugs or genes into a functionalized nanoparticle demonstrates a new era in pharmacotherapy for delivering drugs or genes selectively to tissues or cells. It is envisioned that the transfer of nanoengineering capability into disease therapy will provide constant and concentrated drug delivery to targeted tissues, minimizing systemic side effects and toxicity. We have in this article highlighted the recent state of the art in nanomedicine, focusing particularly on the achievement of nanotechnology in nanoscale drug and gene delivery in vitro and in vivo. In addition, a specific emphasis has been placed on the use of nanotechnology to improve controlled drug release and sustainable drug delivery in solid tumors and on new drug therapies for age-related neurodegenerative disorders. 相似文献