A5019296875- Monoclonal and Polyclonal Antibodies Research
- Protein purification and stability
- Protein Structure and Dynamics
- Glycosylation and Glycoproteins Research
- Viral Infectious Diseases and Gene Expression in Insects
- Biosimilars and Bioanalytical Methods
- Advanced Chemical Physics Studies
- DNA and Nucleic Acid Chemistry
- Enzyme Structure and Function
- Cell Adhesion Molecules Research
- Computational Drug Discovery Methods
- Spectroscopy and Quantum Chemical Studies
- SARS-CoV-2 and COVID-19 Research
- Viral gastroenteritis research and epidemiology
- Escherichia coli research studies
- Platelet Disorders and Treatments
- Mass Spectrometry Techniques and Applications
- COVID-19 Clinical Research Studies
- Chemical Synthesis and Analysis
- Transgenic Plants and Applications
- Advanced Biosensing Techniques and Applications
- Molecular Junctions and Nanostructures
- thermodynamics and calorimetric analyses
- Biochemical and Structural Characterization
- Machine Learning in Bioinformatics
Boston Consulting Group (United States)
2024
Adimab (United States)
2013-2023
Galaxy Biotech (United States)
2016
Palo Alto Institute
2013-2015
PDL BioPharma (United States)
1993-2007
Cornell University
1987-1995
Florida State University
1994
The University of Texas Health Science Center at Houston
1989
Antibodies are a highly successful class of biological drugs, with over 50 such molecules approved for therapeutic use and hundreds more currently in clinical development. Improvements technology the discovery optimization high-potency antibodies have greatly increased chances finding binding desired properties; however, achieving drug-like properties at same time is an additional requirement that receiving attention. In this work, we attempt to quantify historical limits acceptability...
Abstract Several hydration models for peptides and proteins based on solvent accessible surface area have been proposed previously. We evaluated some of these as well four new ones in the context near‐native conformations a protein. In addition, we propose an empirical site–site distance‐dependent correction that can be used conjuction with any models. The set structures consisted 39 bovine pancreatic trypsin inhibitor (BPTI) each which was local minimum energy function (ECEPP) absence...
Shiga-like toxin-producing Escherichia coli have been associated with hemorrhagic colitis and the hemolytic uremic syndrome (HUS). Because Argentina has highest reported frequency of HUS in world, Argentine children were prospectively studied during seasons for evidence toxin-related diseases. On basis serology, fecal cytotoxin neutralization, stool cultures, DNA hybridization colony lysates, most had infection organisms. Children spring-summer diarrhea also commonly (32%, confidence...
Low expression, poor solubility, and polyspecificity are significant obstacles that have impeded the development of antibodies discovered from in vitro display libraries. Current biophysical characterization tools identify these ‘developability’ problems typically only applied after discovery process, thus limited to perhaps a few hundred candidates. We report flow cytometric assay using reagent (PSR) allows for identification counter selection polyspecific both during process. The reported...
The discovery of monoclonal antibodies (mAbs) that bind to a particular molecular target is now regarded routine exercise. However, the successful development mAbs (1) express well, (2) elicit desirable biological effect upon binding, and (3) remain soluble display low viscosity at high concentrations often far more challenging. Therefore, throughput screening assays assess self-association aggregation early in selection process are likely yield with superior biophysical properties. Here, we...
Contemporary in vivo and vitro discovery platform technologies greatly increase the odds of identifying high-affinity monoclonal antibodies (mAbs) towards essentially any desired biologically relevant epitope. Lagging throughput is ability to select for highly developable mAbs with drug-like properties early process. Upstream consideration developability metrics should reduce frequency failures later development stages. As field moves incorporating biophysical screening assays parallel...
Multiple studies of vaccinated and convalescent cohorts have demonstrated that serum neutralizing antibody (nAb) titers correlate with protection against coronavirus disease 2019 (COVID-19). However, the induction multiple layers immunity after severe acute respiratory syndrome 2 (SARS-CoV-2) exposure has complicated establishment nAbs as a mechanistic (CoP) hindered definition protective nAb threshold. Here, we show half-life–extended monoclonal (adintrevimab) provides about 50% symptomatic...
Although improvements in technology for the isolation of potential therapeutic antibodies have made process increasingly predictable, development biologically active monoclonal (mAbs) into drugs can often be impeded by developability issues such as poor expression, solubility, and promiscuous cross-reactivity. Establishing early stage screening assays capable predicting late behavior is therefore high value to minimize risks. Toward this goal, we selected a panel 16 representing different...
We present here a new iterative technique for reliable estimation of multidimensional free energy and potential mean force (PMF) values by computer simulation. This method is an extension the weighted histogram analysis [S. Kumar et al., J. Comput. Chem., 13, 1011, (1992)]. have tested generating free-energy-based Ramachandran plots computing PMF end-to-end distances several polypeptides using ECEPP/2 AMBER fields. © 1996 John Wiley & Sons, Inc.
A multidisciplinary method combining transcriptional data, specificity profiling, and biological characterization of an enzyme may be used to predict novel substrates. By integrating protease substrate profiling with microarray gene coexpression data from nearly 2,000 human normal cancerous tissue samples, three fundamental components a protease-activated signaling pathway were identified. We find that MT-SP1 mediates extracellular by regulating the local activation prometastatic growth...
The effectiveness of therapeutic monoclonal antibodies (mAbs) is governed not only by their bioactivity, but also biophysical properties. Assays for rapidly evaluating the properties mAbs are valuable identifying those most likely to exhibit superior such as high solubility, low viscosity and slow serum clearance. Analytical hydrophobic interaction chromatography (HIC), which performed at salt concentrations enhance interactions, an attractive assay with hydrophobicity. However, this...
Abstract Motivation The hydrophobicity of a monoclonal antibody is an important biophysical property relevant for its developability into therapeutic. In addition to characterizing heterogeneity, Hydrophobic Interaction Chromatography (HIC) assay that often used quantify the assess downstream risks. Earlier studies have shown retention times in this can be correlated amino-acid or atomic propensities weighted by surface areas obtained from protein 3-dimensional structures. goal study develop...
Abstract Low-energy conformations of a set tetrapeptides derived from the small protein bovine pancreatic trypsin inhibitor (BPTI) were generated by build-up procedure low-energy single amino acid residues. At each stage, various-size fragments built up all combinations smaller ones, total energies then minimized, and retained for next stage. The re-ordered including effects hydration. No information other than sequence was used to obtain hydrated tetrapeptides. latter supplemented with...
Abstract Methodology for calculation of side‐chain conformations in proteins is evaluated. The role and impact corrections to idealized rotameric structures are considered, by incorporating methods torsional optimization into rotamer‐packing algorithms. Off‐rotamer given continuum improve, over simpler procedures, the accuracy with which side chains buried amino acids can be predicted. analogy between protein calculations spin systems explored adapting simulation packing Implementations...
Here we describe an industry-wide collaboration aimed at assessing the binding properties of a comprehensive panel monoclonal antibodies (mAbs) against programmed cell death protein 1 (PD-1), important checkpoint in cancer immunotherapy and validated therapeutic target, with well over thirty unique mAbs either clinical development or market-approved United States, European Union China. The kinetics PD-1/mAb interactions were measured by surface plasmon resonance (SPR) using Carterra LSA...
Seven neutralizing murine monoclonal antibodies specific for the glycoprotein H of human cytomegalovirus were produced and used to construct a topological map two nonoverlapping antigenic sites that are bridged by third site. Neutralization assays with 15 laboratory or clinical strains indicated recognize three antigenically variable conserved epitopes within sites. The variable-domain genes encoding representing each cloned sequenced, molecular models their binding generated. Conformational...
Abstract An implementation of the variable-target-function procedure, first introduced by Braun and Gō [W. N. Gō, J. Mol. Biol. 186, 611–626 (1985)], has been used to generate conformations small protein bovine pancreatic trypsin inhibitor (BPTI), given a limited set simulated data that could be obtained nuclear magnetic resonance (NMR) techniques. A hybrid strategy was also calculate BPTI, same information. In strategy, low-energy structures medium-size fragments (decapeptides) BPTI were...
Abstract A method is developed to extract the entropy of polypeptides and proteins from samples conformations. It based on techniques suggested previously by Meirovitch, has advantage that it can be applied not only states in which molecule undergoes harmonic or quasiharmonic conformational fluctuations, but also random coil, as well mixtures these extreme states. In order confine search a region space corresponding stable state, transition probabilities are determined “looking future,”...
Successful discovery of therapeutic antibodies hinges on the identification appropriate affinity binders targeting a diversity molecular epitopes presented by antigen. Antibody campaigns that yield such broad "epitope coverage" increase likelihood identifying candidates with desired biological functions. Accordingly, epitope binning assays are employed in early stages to partition into families or "bins" and prioritize leads for further characterization optimization. The collaborative...
Therapeutic antibodies represent the most significant modality in biologics, with around 150 approved drugs on market. In addition to specific target binding mediated by variable fragments (Fvs) of heavy and light chains, possess effector functions through constant region (Fc) Fcγ receptors (FcγR), which allow immune cells attack kill using a variety mechanisms. However, for some applications, including T-cell-engaging bispecifics, this function is typically undesired. Mutations within lower...