Rational optimization of a monoclonal antibody improves the aggregation propensity and enhances the CMC properties along the entire pharmaceutical process chain
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Rational optimization of a monoclonal antibody improves the aggregation propensity and enhances the CMC properties along the entire pharmaceutical process chain
The discovery of therapeutic monoclonal antibodies (mAbs) mainly focuses on the biological activity they support the selection of highly potent drug candidates. these candidates, however, may have the physical attributes or chemical that causes a chemical that is not profitable, manufacturing, and controls (CMC) properties, such as titer inferior products, conformation and colloidal instability or poor solubility, which can inhibit or even prevent the development and manufacturing , Therefore, there is an urgent need to consider developability mAb candidates for lead identification and optimization.
This work provides a comprehensive proof of concept studies to significantly improve the developability of mAb variants that are optimized with the help of advanced in silico tool relative to the co-parenting a difficult-to-develop. Interestingly, a single amino acid substitutions in the variable domain of the light chain resulted in a three fold increase in titer of products after stable expression in Chinese hamster ovary cells. Microscopic investigation revealed that the wild type mAb-producing cells show potential inclusion antibody, whereas the cells in silico-producing optimized variants showed phenotype rescued.
Notably, the drug substance of variants in silico optimized contained substantially reduced levels of aggregate and fragment after the purification process downstream. Finally, the study formulations biodegrade significantly enhanced colloidal stability in silico optimized variants while folding and potential stability is maintained. This study emphasizes that the implementation of the initial bioinformatics lead generation and optimization of biotherapeutics reduce failures for further development activities and to support the reduction schedule and project resources.
Rational optimization of a monoclonal antibody improves the aggregation propensity and enhances the CMC properties along the entire pharmaceutical process chain
The quality and cost assessment of recombinant antibody fragments produced from mammalian, yeast and prokaryotic host cells: A case study before the development of pharmaceuticals.
monoclonal antibody fragment (Fab) are a promising class of therapeutic agents. Beatles aglycosylated protein expression and so many platforms have been developed including prokaryotic, yeast and mammalian cells. However, these platforms are not equal in terms of development of cell lines and culture time, product quality and the possibility of production costs greatly affect the success of the development of pharmaceutical drug candidates. This study is a humanized Fab fragment ACT017 ratings generated from two organisms (Escherichia coli and Pichia pastoris) and a host mammalian cell (CHO).
Following low production scale and Protein L-affinity purification in a generic condition, physico-chemical and functional quality of the assessment carried out prior to the economic analysis of industrial scale production using special software (Biosolve, Biopharm Services, UK).
The results showed a high titer production when using E. coli but related to the high heterogeneity of the protein content in the supernatant recovered. We also observed from Fab glycoforms produced from P. pastoris, while Fab secreted from CHO is the most homogeneous culture despite a longer time and a slightly higher estimate of the cost of goods. This study may help inform future pharmaceutical development of this class of therapeutic proteins.
Advanced Glycosylation End Product Specific Receptor (AGER) Antibody
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Rat Advanced Glycosylation End Product Specific Receptor (AGER) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
Rat Advanced Glycosylation End Product Specific Receptor (AGER) ELISA Kit
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Rat Advanced Glycosylation End Product Specific Receptor (AGER) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
Rat Advanced Glycosylation End Product Specific Receptor (AGER) ELISA Kit
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Rat Advanced Glycosylation End Product Specific Receptor (AGER) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
Rat Advanced Glycosylation End Product Specific Receptor (AGER) ELISA Kit
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Rat Advanced Glycosylation End Product Specific Receptor (AGER) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
Rat Advanced Glycosylation End Product Specific Receptor (AGER) ELISA Kit
Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Rat Advanced Glycosylation End Product Specific Receptor (AGER) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids with no significant corss-reactivity with analogues from other species.
Mouse Advanced Glycosylation End Product Specific Receptor (AGER)CLIA Kit
Description: This is Double-antibody Sandwich Chemiluminescent immunoassay for detection of Mouse Advanced Glycosylation End Product Specific Receptor (AGER) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
Mouse Advanced Glycosylation End Product Specific Receptor (AGER)CLIA Kit
Description: This is Double-antibody Sandwich Chemiluminescent immunoassay for detection of Mouse Advanced Glycosylation End Product Specific Receptor (AGER) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
Mouse Advanced Glycosylation End Product Specific Receptor (AGER)CLIA Kit
Description: This is Double-antibody Sandwich Chemiluminescent immunoassay for detection of Mouse Advanced Glycosylation End Product Specific Receptor (AGER) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
Mouse Advanced Glycosylation End Product Specific Receptor (AGER)CLIA Kit
Description: This is Double-antibody Sandwich Chemiluminescent immunoassay for detection of Mouse Advanced Glycosylation End Product Specific Receptor (AGER) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
Mouse Advanced Glycosylation End Product Specific Receptor (AGER) CLIA Kit
Description: Double-antibody Sandwich chemiluminescent immunoassay for detection of Mouse Advanced Glycosylation End Product Specific Receptor (AGER)Serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids
AGER (Advanced Glycosylation End Product Specific Receptor, MGC22357, RAGE, AGER) (Biotin)
Description: A sandwich quantitative ELISA assay kit for detection of Human Advanced Glycosylation End Product Specific Receptor (AGER) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Human Advanced Glycosylation End Product Specific Receptor (AGER) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Human Advanced Glycosylation End Product Specific Receptor (AGER) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Mouse Advanced Glycosylation End Product Specific Receptor (AGER) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Mouse Advanced Glycosylation End Product Specific Receptor (AGER) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Mouse Advanced Glycosylation End Product Specific Receptor (AGER) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Mouse Advanced Glycosylation End Product Specific Receptor (AGER) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Human Advanced Glycosylation End Product Specific Receptor (AGER) ELISA Kit
Names and indications of therapeutic monoclonal antibodies must comply with applicable regulations, which do not prevent the development of commercial strategies across the tradename. Some of these practices are based on legal considerations or the region while others are motivated by a real medical concerns. Finally, some have a significant financial impact on society.
