Lead Selection & Optimization

Lead Selection & Optimization

Lead Molecule Selection and Optimization

Lead selection and optimization is a critical process in the identification of molecules that meet predefined requirements and can be progressed to the next step of development. While biologics lead selection mainly involves the screening of lead biological molecules to select those with desired functional and biophysical characteristics, optimization helps improve these properties. 

Octet® BLI systems are improving the speed and efficiency of selection and optimization workflows with high throughput and easily developed assays for applications like affinity ranking, epitope binning of large antibody matrices, Fc-receptor binding, glycosylation screening, antibody-antigen specificity, binding characterization and titer analysis.

Featured Applications

Titer Determination on the Octet® BLI Platform 

Titer and protein concentration determination is a critical process in the development of biologics drug molecules. The active protein concentration can be used to determine potency of the drug molecule. Titer and protein concentration determination are more robust to cell culture and media, making them desirable as replacement for enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC) in upstream and downstream processes. 

  • Analyze a full 96-well plate of samples for IgG titer in as little as two minutes 
  • Use crude and unpurified samples 
  • Automate for walkaway high throughput analysis

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Epitope Binning and Cross-Competition Assays

In early drug development, cross-competition studies are necessary to characterize hundreds of antibody clones. Since monoclonal antibodies in different bins bind to distinct antigen epitopes and display diverse functional characteristics, epitope binning studies can increase the likelihood of choosing a lead antibody with the desired biological activity. 

Epitope binning studies rely on the sequential binding of two antibodies to an antigen, and are performed using dozens of antibody pairs in cross-competition matrices. The Octet® BLI platform excels at these large-scale studies due to assay speed, throughput and exceptional reproducibility. 

  • Sample plate format allows for use of crude and non-purified samples
  • Automation capable Octet® RH96 and RH16 allow for walk away high throughput analysis

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Off-Rate Screening Utilizing Octet® BLI technology

When screening crude samples with unknown concentrations, off-rate screening is a powerful tool for predicting sample properties. Library screening by ELISA does not enable ranking of antibodies based upon their affinities for an antigen. Using Octet® BLI systems, clones with high affinities and low off-rates can be rapidly identified and selected for further characterization. Many biotechnology companies utilize the technology in automated affinity screening and off-rate screening of positive clones obtained from ELISA-based primary screens.

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Kinetic Characterization and Clone Selection 

Monitoring the binding of candidate molecules to targets is a critical process in lead molecule selection and can aid in the selection of desirable clones. Octet® BLI systems generate highly-precise data on molecular binding affinities, specificities and association/dissociation rate constants and in a high throughput manner. 

  • Accurately determine ka, kd, and KD
  • Screen up to 96 clones simultaneously in 96 or 384-well plates
  • Perform analysis directly in crude samples - no need for sample purification

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Fragment Screening

Fragment-based drug design (FBDD) has become an increasingly popular platform for the identification of lead candidates in drug discovery programs. The detection and characterization of fragment binding events is facilitated by sensitive biophysical technologies capable of detecting low affinity interactions of low molecular weight compounds. The Octet® SF3 system has the necessary sensitivity and throughput to provide complete fragment screens on libraries of several thousand compounds in just a few weeks per target.

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Resources

Integrating Octet® BLI into Early Antibody Discovery Workflows

Improve the overall drug discovery process to increase the success rate of preclinical candidates

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Customized Quantitation of Recombinant Therapeutic Proteins

Using Octet® SAX Biosensors

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A Rapid Method to Quantitatively Screen Bispecific Antibodies Using Protein A and Octet® His1K Biosensors

Screen Bispecific Antibody Using Protein A and His1K Biosensors

Rapid quantitative screening of bispecific antibodies using Protein A and HIS1K biosensors

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Cover: Characterizing Membrane Protein Interactions by Bio-Layer Interferometry

Characterizing Membrane Protein Interactions by Bio-Layer Interferomet...

Example studies on how the Octet® system can be used to analyze membrane protein interactions, even allowing the use of unpurified crude matrices and...

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Application Note cover

Label-Free Technologies for Accurate Determination of Affinity and Kin...

From target molecule identification to lead selection and optimization, equilibrium affinity and kinetics rate constants are critical parameters in th...

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Streamlining Affinity Analysis for Accelerated Lead Screening

Antibody and other protein therapeutics are a major focus in drug discovery pipelines today. The overall process for developing protein therapeutics e...

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OneStep Lead Characterization of High Affinity Biologic Interactions w...

Biopharmaceutical drug discovery and development have celebrated the approval of breakthrough treatments in diseases of inflammation, cancer and infec...

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Enhancing Efficiency and Economics in Process Development and Manufact...

Analytical techniques that measure protein quantity and quality are used in nearly all stages of research, process development and manufacturing of bi...

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Reducing Variability in Small Molecule Screening and Kinetics Applicat...

Minimizing the variability of background signals is a key parameter to the success of demanding applications such as small molecule analysis

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Fragment Based Drug Discovery on Pioneer Systems Using Next Generation...

Fragment-based drug design (FBDD) has become an increasingly popular platform for the identification of lead candidates in drug discovery programs.

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Cell Line Development: Accelerating Antibody Discovery by Monitoring Titer and Glycosylation With the Octet® Platform

Application Guide: Cell Line Development

Accelerating Antibody Discovery by Monitoring Titer and Glycosylation With the Octet® Platform

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Octet® SF3 SPR

Octet® SF3 SPR 

Generate high-quality kinetics and affinity data in a fraction of the time compared to standard multi-cycle kinetics using the Octet® SF3.

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Octet® BLI rapidly determines recombinant protein concentration as a control parameter in cell line development.

96-Channel Ultra High Throughput Octet System: Octet® RH96

Monitors up to 96 biosensors simultaneously, enabling label-free detection for protein quantitation and kinetic characterization at unmatched speed

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16-Channel High Throughput Octet System: Octet® RH16

Ideal for high-throughput applications that demand high sensitivity and low sample volume requirements

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8-Channel System: Octet® R8

Unmatched Flexibility and Versatility in Protein Analysis

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