What if it were possible to build, clone, and amplify candidate sequence constructs hands-free overnight?

Join us to learn how Telesis Bio’s automated BioXp synthetic biology solutions are designed to help you break free from traditional lead synthesis bottlenecks and significantly accelerate your antibody discovery pipeline.

Our automated benchtop BioXp system is designed to help scientists streamline biologics workflows by empowering:

• Accelerated discovery: On-demand overnight synthesis of a variety of DNA constructs utilized across antibody development workflows
• Improved productivity: Focus on strategic science by eliminating hands-on molecular biology benchwork with push-button automation
• Consolidated workflows: Build on your schedule while maintaining chain of custody of critical proprietary reagents

Speaker:

Jason Lehmann, PhD.
Senior Product Marketing Manager
Telesis Bio

 The methods provide direct observation of the electron density of biomolecules under a certain solution condition without any fixation process, crystallization, and freezing, thus liberating observation of the actual shape under formulated conditions. This works best for molecules sizing around monoclonal antibodies, till to Adeno-associated virus (AAV) but accepts much smaller molecules like mid-size pharma and the other side as well, larger viruses and virus-like particles (VLPs).

It gives versatile statements of conformational changes, thus enabling to monitor of higher order structure differences by altered solution conditions or by complex formations leading to direct epitope mapping of an antigen-antibody complex or monitoring of the products in culture media for quality control or even checking conformational aging that has been little controlled ever.

Talk attendees will learn about:

• In situ 3D observation of therapeutic antibody molecule in solution.
• Top-down characterization without prerequisite information: affinity to unexpected phenomena and novel modalities.
• Possible usage in discovery, design development, formulation, and even inline product monitoring based on a tertiary and quaternary structure itself and their basis.
• Comparisons among existing methods, X-ray crystallography, CryoEM imaging, SPMs: Pros and limitations.

Speaker:

Takashi Sato, Ph.D.
Deputy General Manager, Application Laboratories
Rigaku

Sutro’s proprietary, linear-scalable cell-free protein synthesis platform provides an attractive alternative to widely used cell-based methods for large molecule drug development and manufacturing given its speed, tunability, and flexibility. To enable the rapid transition of therapeutic antibody candidates from discovery through development, we have designed discovery platforms that integrate with our cell-free expression system. Taking advantage of ribosome display, a cell-free directed evolution method, we have selected and optimized antibody fragments from highly diverse libraries up to ~1012 in size. Antibody libraries have been designed to incorporate natural amino acid diversity in CDRs within stable frameworks that are codon optimized for downstream cell-free expression. Ribosome display of multi-chain Fabs in our antibody libraries is enabled by use of a common light-chain. However, the sensitivity of ribosome display to changes in buffers and temperature makes some techniques (e.g., use of high temperature) difficult and precludes direct cell-based selections. To overcome these limitations and extend our discovery capabilities, we have also designed phage displayed antibody libraries (scFv, common LC Fab, and scFab) optimized for cell-free expression. Antibody fragments selected from these discovery platforms can be rapidly reformatted to IgG and expressed in cell-free reactions for high-throughput characterization. Taken together, these approaches represent a robust antibody discovery pipeline streamlined to enable therapeutic development within Sutro’s cell-free expression system.

Speaker:

Garrett G. Gross
Senior Scientist
Sutro Biopharma

This webinar will provide an overview of the antibody discovery process highlighting the critical steps involved in developing effective antibody-based therapeutics. The goal is to guide the audience through the different stages of antibody drug discovery, shedding light on the latest advancements, methodologies, and challenges encountered along the way. In addition, the webinar will cover Benchling’s Antibody Solution Accelerator, a set of ready to use configurations necessary to capture the process of drug discovery.

The audience will come away with an understanding of the following critical elements and how Benchling’s Antibody Solution Accelerator can support them:

• Target Identification: The crucial step of identifying and validating specific molecular targets that play a role in disease pathogenesis.
• Screening: Methods to identify potential antibody candidates.
• Hit Generation: Strategies employed to generate antibody hits with desirable binding properties.
• Lead Selection: Criteria and assays used to assess factors such as binding affinity, specificity, stability, and pharmacokinetic properties to choose the most suitable leads for further development.
• Lead Optimization: Lead antibodies are modified to enhance their therapeutic potential. Explore techniques like antibody engineering, affinity maturation, and antibody humanization to improve properties such as stability, efficacy, and manufacturability.
• In Vivo Safety & Efficacy: Assessing the performance of the antibody in mice and other model organisms.

Speakers:

Sanjay Saraf
Product Manager
Benchling

Vega Shah, PhD
Senior Product Marketing Manager
Benchling

 Therapeutic monoclonal antibodies (mAbs) need to not only show high target-specificity but also demonstrate favorable developability. The term “developability” refers to a multi-parameter design element that measures the manufacturability of an antibody candidate via evaluating its biophysical characteristics, reflecting its potential to progress from discovery to clinical application. Computational developability parameter (DP) profiling now enables the assessment of antibody developability at high-throughput. While it has been suggested that natural antibody repertoires provide valuable guidance for therapeutic antibody selection, we lack comprehensive quantification of natural DP plasticity. (redundancy, predictability, and sensitivity) and how the DP landscapes of human-engineered and natural antibodies relate to one another. To address these knowledge gaps, we assembled a dataset comprising over two million natural and human-engineered antibodies (patent-submitted, therapeutic, and kymouse), predicted their structures and computed their DPs (40 sequence-based and 46 structure-based DPs). We show that the developability landscapes across species (mouse, human) and chain (heavy, light) harbor distinct signatures. We report greater redundancy and higher predictability among sequence DPs, as opposed to structure-based ones, suggesting a less restricted design space for structural developability considerations. We found minimal correlation between sequence and developability similarity, highlighting the considerable developability shifts introduced with minimal sequence alterations. Using molecular dynamics simulations, we discovered that current antibody structure prediction tools could be providing (developability) snapshots of the conformational ensemble. Finally, based on the DPs explored, we found that the developability spaces of human-engineered antibodies are mere subspaces of the natural ones. By charting the extent of the antibody developability space, we contribute to the long-standing goal of in silico and rational therapeutic antibody design.

Speaker:

Eva Smorodina
Research Assistant at the University of Oslo (Norway), Greiff Lab
Prospective SABS R3 DPhil student at the University of Oxford (UK)