Articles tagged ”FabRICATOR”

FabRICATOR® in a DAR Analysis of Antibody-Oligonucleotide Conjugates

September 16, 2021 | Applications, References |

In this paper, scientists at Spectroswiss and Orion Pharma present a novel strategy for DAR analysis of structurally complex antibody-oligonucleotide conjugates using SmartEnzymes™ and a proteoform integration approach combined with native SEC-Orbitrap FTMS.
 
Read more »

FabRICATOR in a Comprehensive Characterization of a Bispecific Antibody

September 9, 2021 | Applications, References |

Scientists at University of Geneva and Centre d’Immunologie Pierre-Fabre here describes a comprehensive intact and middle-level characterization of a commercial bispecific antibody by using a variety of orthogonal chromatographic methods coupled to MS.
 
Read more »

Purification of Antibody Fragments via Hydrophobic Interactions


The importance of monoclonal antibodies (mAbs) as therapeutic agents is steadily increasing, and each year nearly 300 novel mAbs are being evaluated for their therapeutic effectivity. Interest has also been expressed in the use of antibody fragments as therapeutic agents. The physiochemical properties of the fragments differ significantly from that of intact antibodies, and the fragments can more easily be coupled to dyes, toxins and vesicles for diagnostic purposes, cancer therapy and improved drug delivery, respectively.
Read more »

Analytical Methods to Monitor Site-Specific ADC Generation with GlyCLICK®


Scientists at the University of Strasbourg and University of Geneva use innovative native MS and IM methodologies for analytical characterization of a site-specific ADC generated with the GlyCLICK technology.

 

Antibody-drug conjugates (ADCs) combine the benefits of tumor-targeting monoclonal antibodies with the cytotoxic effect of drug payloads covalently linked to the antibody. The ADC generation process has evolved from non-selective and uncontrolled conjugation in early generation products, to site-specific conjugation resulting in homogenous and well-defined ADCs. Conjugation at the antibody Fc glycan sites using the GlyCLICK technology has proven to be an attractive option for the generation of site-specific ADCs.
Read more »

Middle-up Analysis of Monoclonal Antibodies using FabRICATOR®


With their molecular specificity for biological targets, monoclonal antibodies (mAbs) have revolutionized the field of research and medicine. Due to numerous post-translational modifications causing heterogeneity in the structure of mAbs, a comprehensive characterization of the physiochemical properties is necessary to ensure the quality, efficacy and safety of mAb-based therapeutic drugs.
Read more »

IgG Proteases for Gene Therapy Applications

June 16, 2021 | Applications |

The development and successful commercialization of gene therapy technologies as new treatments have spurred great interest and investments in this field of research. Many challenges remain to be solved to establish gene therapy as a mainstream line of treatment, but there are currently many promising and life-changing gene therapy programs in preclinical and clinical development. Preexisting antibodies against the capsid of adeno-associated virus (AAV) vectors is a major challenge for many gene therapies that could block uptake and limit the transduction of the new genetic material. The anti-AAV antibodies are prevalent both in humans and preclinical disease models. In patient populations, up to 50% of the patients could be excluded from treatment due to high titers of anti-AAV antibodies. Several strategies are explored to reduce the antibody response, once such is enzymatic pretreatment using IgG-specific proteases.
Read more »

New Application Note on Antibody Oxidation Analysis


A Rapid LC-MS Assay for Monitoring of mAb Oxidation at the Subunit Level
 
Methionine oxidation is considered a critical quality attribute of therapeutic antibodies and may impact the clinical safety and efficacy. Therefore, monitoring of methionine oxidations is required during the discovery, development, and production of therapeutic antibodies. Traditional methods to characterize oxidation rely on tryptic peptide mapping and LC-MS, a labor intensive and time- consuming process that generates large data sets and requires trained and skilled manual interpretations.
Read more »

FabRICATOR in an Evaluation of Mobile-phase Additives for LC-MS Characterization of mAbs


Biopharmaceuticals, including monoclonal antibodies (mAbs), have become an important class of therapeutics. The manufacturing procedure of mAbs is complex, and many possible variants of a particular mAb can be generated as a result of enzymatical and chemical modifications. Some of these modifications are critical for the efficacy and safety of the therapeutic mAb and are known as critical quality attributes (CQAs). CQAs need to be thoroughly monitored to ensure the quality and safety of the therapeutic agent.

Read more »

Automated Biotransformation Analysis of ADCs using FabRICATOR

The development of antibody-drug conjugates (ADCs) has evolved from first generation formats prepared by random conjugation technologies to next generation ADCs generated by site-specific conjugation. While significant improvements in overall efficacy and safety is displayed by site-specific formats, bioanalysis remains challenging due to complex in vivo biotransformation events including deconjugation, linker-payload cleavage and payload metabolism.

 

In this work, scientists at Bristol-Myers Squibb describe the development of an automated and fast affinity capture method using a cartridge-based platform combined with LC-HRMS analysis for biotransformation assessment of site-specific ADCs.

Read more »

FabRICATOR used to Locate Modification Sites of IgG Caused by Reducing Agents

A charge heterogeneity is an unfavorable phenomenon observed for mAbs and is considered as a critical quality attribute since it can alter the efficacy and pharmacokinetics of biopharmaceuticals. Acidic and basic species of an IgG are due to various chemical modifications on the molecule. The origin of acidic species has previously been reported to be formed by deamidation, oxidation of side-chains, cysteinylation, glycosylation, glycation, sialylation and fragmentation while the basic species comes from C-terminal lysine clipping, pyro-glu cyclization, succinimide formation and aggregation. Scientists at Boehringer Ingelheim together with scientists at NMI at University of Tübingen recently published a study characterizing the root cause of charged species of an IgG1 mAb.

Read more »