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.
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 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
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: 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.
Rat Advanced Glycosylation End Product Specific Receptor (AGER) ELISA Kit
Description: The test principle applied in this kit is Sandwich enzyme immunoassay. The microtiter plate provided in this kit has been pre-coated with an antibody specific to Rat AGER. Standards or samples are added to the appropriate microtiter plate wells then with a biotin-conjugated antibody specific to Rat AGER. Next, Avidin conjugated to Horseradish Peroxidase (HRP) is added to each microplate well and incubated. After TMB substrate solution is added, only those wells that contain Rat AGER, biotin-conjugated antibody and enzyme-conjugated Avidin will exhibit a change in color. The enzyme-substrate reaction is terminated by the addition of sulphuric acid solution and the color change is measured spectrophotometrically at a wavelength of 450nm ± 10nm. The concentration of Rat AGER in the samples is then determined by comparing the OD of the samples to the standard curve.
Rat AGER(Advanced Glycosylation End Product Specific Receptor) ELISA Kit
Description: The test principle applied in this kit is Sandwich enzyme immunoassay. The microtiter plate provided in this kit has been pre-coated with an antibody specific to Rat AGER. Standards or samples are added to the appropriate microtiter plate wells then with a biotin-conjugated antibody specific to Rat AGER. Next, Avidin conjugated to Horseradish Peroxidase (HRP) is added to each microplate well and incubated. After TMB substrate solution is added, only those wells that contain Rat AGER, biotin-conjugated antibody and enzyme-conjugated Avidin will exhibit a change in color. The enzyme-substrate reaction is terminated by the addition of sulphuric acid solution and the color change is measured spectrophotometrically at a wavelength of 450nm ± 10nm. The concentration of Rat AGER in the samples is then determined by comparing the OD of the samples to the standard curve.
Rat AGER(Advanced Glycosylation End Product Specific Receptor) 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.
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
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Advanced Glycosylation End Product Specific Receptor (AGER) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
Human Advanced Glycosylation End Product Specific Receptor (AGER) ELISA Kit
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Advanced Glycosylation End Product Specific Receptor (AGER) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
Human Advanced Glycosylation End Product Specific Receptor (AGER) ELISA Kit
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Advanced Glycosylation End Product Specific Receptor (AGER) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
Human Advanced Glycosylation End Product Specific Receptor (AGER) ELISA Kit
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Advanced Glycosylation End Product Specific Receptor (AGER) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
Human Advanced Glycosylation End Product Specific Receptor (AGER) ELISA Kit
Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human 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) ELISA Kit
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay 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) ELISA Kit
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay 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) ELISA Kit
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay 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) ELISA Kit
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay 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) ELISA Kit
Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Mouse 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.
Human Advanced Glycosylation End Product Specific Receptor (AGER) ELISA Kit
Description: The test principle applied in this kit is Sandwich enzyme immunoassay. The microtiter plate provided in this kit has been pre-coated with an antibody specific to Mouse AGER. Standards or samples are added to the appropriate microtiter plate wells then with a biotin-conjugated antibody specific to Mouse AGER. Next, Avidin conjugated to Horseradish Peroxidase (HRP) is added to each microplate well and incubated. After TMB substrate solution is added, only those wells that contain Mouse AGER, biotin-conjugated antibody and enzyme-conjugated Avidin will exhibit a change in color. The enzyme-substrate reaction is terminated by the addition of sulphuric acid solution and the color change is measured spectrophotometrically at a wavelength of 450nm ± 10nm. The concentration of Mouse AGER in the samples is then determined by comparing the OD of the samples to the standard curve.
Mouse AGER(Advanced Glycosylation End Product Specific Receptor) ELISA Kit
Description: The test principle applied in this kit is Sandwich enzyme immunoassay. The microtiter plate provided in this kit has been pre-coated with an antibody specific to Mouse AGER. Standards or samples are added to the appropriate microtiter plate wells then with a biotin-conjugated antibody specific to Mouse AGER. Next, Avidin conjugated to Horseradish Peroxidase (HRP) is added to each microplate well and incubated. After TMB substrate solution is added, only those wells that contain Mouse AGER, biotin-conjugated antibody and enzyme-conjugated Avidin will exhibit a change in color. The enzyme-substrate reaction is terminated by the addition of sulphuric acid solution and the color change is measured spectrophotometrically at a wavelength of 450nm ± 10nm. The concentration of Mouse AGER in the samples is then determined by comparing the OD of the samples to the standard curve.
Mouse AGER(Advanced Glycosylation End Product Specific Receptor) ELISA Kit
Description: The test principle applied in this kit is Sandwich enzyme immunoassay. The microtiter plate provided in this kit has been pre-coated with an antibody specific to Human AGER. Standards or samples are added to the appropriate microtiter plate wells then with a biotin-conjugated antibody specific to Human AGER. Next, Avidin conjugated to Horseradish Peroxidase (HRP) is added to each microplate well and incubated. After TMB substrate solution is added, only those wells that contain Human AGER, biotin-conjugated antibody and enzyme-conjugated Avidin will exhibit a change in color. The enzyme-substrate reaction is terminated by the addition of sulphuric acid solution and the color change is measured spectrophotometrically at a wavelength of 450nm ± 10nm. The concentration of Human AGER in the samples is then determined by comparing the OD of the samples to the standard curve.
Human AGER(Advanced Glycosylation End Product Specific Receptor) ELISA Kit
Description: The test principle applied in this kit is Sandwich enzyme immunoassay. The microtiter plate provided in this kit has been pre-coated with an antibody specific to Human AGER. Standards or samples are added to the appropriate microtiter plate wells then with a biotin-conjugated antibody specific to Human AGER. Next, Avidin conjugated to Horseradish Peroxidase (HRP) is added to each microplate well and incubated. After TMB substrate solution is added, only those wells that contain Human AGER, biotin-conjugated antibody and enzyme-conjugated Avidin will exhibit a change in color. The enzyme-substrate reaction is terminated by the addition of sulphuric acid solution and the color change is measured spectrophotometrically at a wavelength of 450nm ± 10nm. The concentration of Human AGER in the samples is then determined by comparing the OD of the samples to the standard curve.
Human AGER (Advanced Glycosylation End Product Specific Receptor) ELISA Kit
Description: A Rabbit polyclonal antibody against Mouse, Rat Advanced Glycosylation End Product Specific Receptor (AGER). This antibody is labeled with PE.
ELISA kit for Rat AGER (Advanced Glycosylation End Product Specific Receptor)
Description: A sandwich ELISA kit for detection of Advanced Glycosylation End Product Specific Receptor from Rat in samples from blood, serum, plasma, cell culture fluid and other biological fluids.
Rat Advanced Glycosylation End Product Specific Receptor / RAGE (AGER) CLIA Kit
Description: A Rabbit polyclonal antibody against Rat Advanced Glycosylation End Product Specific Receptor (AGER). This antibody is labeled with Biotin.
Advanced Glycosylation End Product Specific Receptor (AGER) Polyclonal Antibody (Human, Mouse), APC
Description: A Rabbit polyclonal antibody against Human, Mouse Advanced Glycosylation End Product Specific Receptor (AGER). This antibody is labeled with APC.
Advanced Glycosylation End Product Specific Receptor (AGER) Polyclonal Antibody (Human, Mouse), Cy3
Description: A Rabbit polyclonal antibody against Human, Mouse Advanced Glycosylation End Product Specific Receptor (AGER). This antibody is labeled with Cy3.
Advanced Glycosylation End Product Specific Receptor (AGER) Polyclonal Antibody (Human, Mouse), FITC
Description: A Rabbit polyclonal antibody against Human, Mouse Advanced Glycosylation End Product Specific Receptor (AGER). This antibody is labeled with FITC.
Advanced Glycosylation End Product Specific Receptor (AGER) Polyclonal Antibody (Human, Mouse), HRP
Description: A Rabbit polyclonal antibody against Human, Mouse Advanced Glycosylation End Product Specific Receptor (AGER). This antibody is labeled with HRP.
Advanced Glycosylation End Product Specific Receptor (AGER) Polyclonal Antibody (Human, Mouse), PE
Description: A Rabbit polyclonal antibody against Human, Mouse Advanced Glycosylation End Product Specific Receptor (AGER). This antibody is labeled with PE.
Advanced Glycosylation End Product Specific Receptor (AGER) Polyclonal Antibody (Mouse, Rat), APC
Description: A Rabbit polyclonal antibody against Mouse, Rat Advanced Glycosylation End Product Specific Receptor (AGER). This antibody is labeled with APC.
Advanced Glycosylation End Product Specific Receptor (AGER) Polyclonal Antibody (Mouse, Rat), Cy3
Description: A Rabbit polyclonal antibody against Mouse, Rat Advanced Glycosylation End Product Specific Receptor (AGER). This antibody is labeled with Cy3.
Advanced Glycosylation End Product Specific Receptor (AGER) Polyclonal Antibody (Mouse, Rat), FITC
Description: A Rabbit polyclonal antibody against Mouse, Rat Advanced Glycosylation End Product Specific Receptor (AGER). This antibody is labeled with FITC.
Advanced Glycosylation End Product Specific Receptor (AGER) Polyclonal Antibody (Mouse, Rat), HRP
Description: A Rabbit polyclonal antibody against Mouse, Rat Advanced Glycosylation End Product Specific Receptor (AGER). This antibody is labeled with HRP.
Advanced Glycosylation End Product Specific Receptor (AGER) Polyclonal Antibody (Rat), APC-Cy7
Description: A Rabbit polyclonal antibody against Rat Advanced Glycosylation End Product Specific Receptor (AGER). This antibody is labeled with APC-Cy7.
ELISA kit for Mouse AGER (Advanced Glycosylation End Product Specific Receptor)
Description: A sandwich ELISA kit for detection of Advanced Glycosylation End Product Specific Receptor from Mouse in samples from blood, serum, plasma, cell culture fluid and other biological fluids.
ELISA kit for Human AGER (Advanced Glycosylation End Product Specific Receptor)
Description: A sandwich ELISA kit for detection of Advanced Glycosylation End Product Specific Receptor from Human in samples from blood, serum, plasma, cell culture fluid and other biological fluids.
Human Advanced Glycosylation End Product Specific Receptor / RAGE (AGER) CLIA 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.