- Monoclonal and Polyclonal Antibodies Research
- Protein purification and stability
- Biosimilars and Bioanalytical Methods
- Antimicrobial Resistance in Staphylococcus
- Glycosylation and Glycoproteins Research
- Advanced Biosensing Techniques and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Biochemical and Structural Characterization
- Toxin Mechanisms and Immunotoxins
- Bacterial biofilms and quorum sensing
- Streptococcal Infections and Treatments
- Transgenic Plants and Applications
- Birth, Development, and Health
- Biosensors and Analytical Detection
- Material Properties and Applications
- Bacterial Identification and Susceptibility Testing
- Cell Adhesion Molecules Research
- Microfluidic and Bio-sensing Technologies
- Bacterial Genetics and Biotechnology
- Radiopharmaceutical Chemistry and Applications
- Per- and polyfluoroalkyl substances research
- Immunodeficiency and Autoimmune Disorders
- 3D Printing in Biomedical Research
John Wiley & Sons (United States)
2020
Triangle
2020
Indianapolis Zoo
2020
Kentucky Science Center
2020
Pfizer (United States)
2012-2019
Bioanalytica (Switzerland)
2007
Thomas Jefferson University
1991
University of Cambridge
1987-1989
University of Zurich
1988
Implementation of in vitro assays that correlate with vivo human pharmacokinetics (PK) would provide desirable preclinical tools for the early selection therapeutic monoclonal antibody (mAb) candidates minimal non-target-related PK risk. Use these minimizes likelihood mAbs unfavorable be advanced into costly and clinical development. In total, 42 varying isotype soluble versus membrane targets were tested studies. MAb physicochemical properties assessed by measuring non-specific interactions...
Therapeutic antibodies continue to develop as an emerging drug class, with a need for preclinical tools better predict in vivo characteristics. Transgenic mice expressing human neonatal Fc receptor (hFcRn) have potential pharmacokinetic (PK) model project PK of monoclonal (mAbs). Using panel 27 mAbs broad range, we sought characterize and establish utility this animal provide guidance its application development mAbs. This set was administered both hemizygous homozygous hFcRn transgenic...
A large body of data exists demonstrating that neonatal Fc receptor (FcRn) binding an IgG via its CH2-CH3 interface trends with the pharmacokinetics (PK) IgG. We have observed PK molecules vary widely, even when they share identical domains. This led us to hypothesize domains distal from could contribute FcRn and affect PK. In this study, we explored role these in altering affinity between FcRn. Using a surface plasmon resonance-based assay developed examine steady-state (KD) FcRn, dissected...
A 6.2-kilobase chromosomal DNA fragment from a methicillin-resistant Staphylococcus epidermidis strain was cloned into carnosus by using staphylococcal plasmid pCA44 as the vector. The recombinant obtained, pBBB21, conferred methicillin resistance on its host and responsible for synthesis of low-affinity penicillin-binding protein (PBP), PBP 2'. 2' determined S. expressed membrane-bound in reacted with monoclonal antibodies directed against aureus origin, hybridized to (mec)-specific aureus....
System-wide quantitative characterization of human neonatal Fc receptor (FcRn) properties is critical for understanding and predicting PK (pharmacokinetics) as well the distribution mAbs Fc-fusion proteins using PBPK (physiologically-based pharmacokinetic) modeling. To this end, tissue-specific FcRn expression half-life are important model inputs. Herein, tissue was measured by peptide immunoaffinity chromatography coupled with high-resolution mass spectrometry. concentrations across 14...
The neonatal Fc receptor (FcRn) is a homeostatic responsible for prolonging immunoglobulin G (IgG) half-life by protecting it from lysosomal degradation and recycling to systemic circulation. Tissue-specific FcRn expression critical parameter in physiologically-based pharmacokinetic (PBPK) modeling translational pharmacokinetics of Fc-containing biotherapeutics. Using online peptide immuno-affinity chromatography coupled with high resolution mass spectrometry, we established quantitative...
Background: Method developers of plate-based ligand-binding assays (LBAs) often face challenges establishing selectivity, specificity and range quantitation to meet the needs a particular study. Case studies are presented compare different immunoassay platforms (plate-based vs microfluidic system) in method development support pharmacokinetic pharmacodynamic studies. Results: Studies highlight LBAs establish as result nonspecific background signal, matrix interference, lack linearity drug...
Background and Purpose A monoclonal antibody (PF‐00547659) against mucosal addressin cell adhesion molecule (MAdCAM), expressed as both soluble (sMAdCAM) trans‐membrane (mMAdCAM) target forms, showed over 30‐fold difference in antibody‐target K D between vitro (Biacore) clinically derived (K D, in‐vivo ) values. Back‐scattering interferometry (BSI) was applied to acquire physiologically relevant values which were used establish vivo correlation (IVIVC). Experimental Approach BSI obtain...
Polyclonal antibodies were raised against the membrane-bound penicillin-binding protein (PBP 2') present in methicillin-resistant strains of Staphylococcusaureus (MRSA) and used to detect its presence membranes from grown under varying conditions for expression resistance. The antibody preparation reacted with another membrane methicillin-sensitive S. aureus (MSSA) which migrated same position as PBP 2' on SDS gel electrophoresis. Pretreatment antisera sensitive removed recognising high-M r,...
Tools for mapping and quantifying monoclonal antibody (mAb) peptide biotherapeutics distribumtion were evaluated by comparing data from three independent methods conducted at the whole body, organ or tissue, cellular levels.[3H]-mAb1 [3H]-peptide A administered intravenously to rats followed quantitative whole-body autoradiography, kidney macro-autoradiography micro-autoradiography.[3H]-mAb1 concentrations measured in anatomical regions ranging body sub-organ level, such as glomerulus, with...
The additional penicillin-binding protein (PBP 2′) that is important in determining intrinsic resistance methicillin-resistant strains of Staphylococcus aureus (MRSA) has been detected immunologically from a variety world-wide locations. This also definitively identified both and as PBP S. epidermidis (MRSE). assay described rapid, specific sensitive used to detect 2′ haemolyticus but not β-lactam resistant Streptococci.
Abstract Antibody‐like biopharmaceuticals cross the placenta by utilizing existing transport pathways (e.g., FcRn receptor). There are limited data evaluating this transfer during organogenesis in any species. Understanding placental of antibody‐like can help to predict risk developmental toxicity across species, including humans. To complement previously published rat with humanized IgGΔ2 (hIgG2), timing and magnitude cynomolgus monkey embryo/fetal biodistribution maternally administered...
The additional penicillin-binding protein (PBP) 2′ that is important in determining intrinsic resistance methicillin-resistant strains of Staphylococcus aureus (MRSA) has been purified by affinity chromatography using monoclonal antibodies. Monoclonal antibody 1/423.10.351 reacted ELISA with detergent extracts membranes from resistant organisms, but not immunoblots PBP separated SDS-PAGE. Immunoprecipitation experiments showed extracts. latter antibody, covalently coupled to A-Sepharose...