Lead Selection & Optimization

Lead Selection & Optimization

Lead Molecule Selection and Optimization

Lead selection and optimization is a critical process in the identification, selection and optimization of molecules that meet predefined requirements and that can then 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 further helps improve these properties.

Octet systems are improving the speed and efficiency of the selection and optimization workflows, with high throughput and easy to develop 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.


Titer Determination on the Octet 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 the potency of the drug molecule.  Octet titer and protein concentration determination are more robust to cell culture and media, making them desirable as replacement for ELISA and HPLC in both 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 system excels at these large-scale studies due to assay speed, throughput, and exceptional reproducibility.

  • Sample plate format allows for the use of crude and non-purified samples
  • Automation capable Octet HTX and Red 384 allow for walk away high through-put analysis

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Off-Rate Screening on Octet Systems

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. With the Octet system, clones with high affinities and low off-rates can be rapidly identified and selected for further characterization. Many biotechnology companies utilize the Octet system 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 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 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 Pioneer FE 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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Customized Quantitation of Recombinant Therapeutic Proteins

Using High Precision Streptavidin Biosensors (SAX)

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Kinetic Analysis of AB Binding to Membrane Protein on Captured...

Membrane proteins govern the majority of input and output signals of cells and represent the largest class of pharmaceutical drug targets, making...

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A Rapid Method to Quantitatively Screen Bispecific Antibody Using Protein A and His1K Biosensors cover

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...

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

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Application Note cover

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

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

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Automating Octet Assays for Ligand Screening

Drug development and production is challenging. Avitide, based in Lebanon, New Hampshire, provides on-demand development and supply of...

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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...

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OneStep Lead Characterization of High Affinity Biologic...

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

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Enhancing Efficiency and Economics in Process Development and Manufacturing of Biotherapeutics cover

Enhancing Efficiency and Economics in Process Development and...

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

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Reducing Variability in Small Molecule Screening and Kinetics...

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...

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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Accelerating Antibody Discovery by Monitoring Titer and...

Significantly reduce time to develop antibodies by combining titer and glycan screening

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Pioneer FE SPR System

Pioneer FE SPR System

Make Decisions Earlier in Fragment Screens with the Pioneer FE

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Pioneer SPR System

Complete solution for biomolecular interaction analysis with next generation SPR injections

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Octet HTX

96-Channel Ultra High Throughput Octet System: Octet HTX

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

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Octet RED384

16-Channel High Throughput Octet System: Octet RED384

The Octet RED384 16-channel instrument provides analytical performance similar to the 8- channel Octet RED96 system, but with higher levels of...

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Octet RED96e

8-Channel Octet System: Octet RED96e

The 8-channel Octet systems perform quantitation of 96 samples in 32 minutes and kinetic screening of 64 samples in 1.5 hours.

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Octet QKe

8-Channel Octet System: Octet QKe

Unmatched versatility for discovery, development, and quality control

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