Genedata Biologics

Applications

Bispecific Antibody Engineering

Recent advances in antibody engineering have been driven by new antibody generation technologies and increasingly sophisticated antibody and antibody-based formats, such as bispecifics and multi-specific antibodies. Able to simultaneously co-engage with different antigen targets, these new antibody formats are currently being broadly adopted by the biopharmaceutical industry, primarily for developing the next-generation of oncology and immune system therapies.

Each of these engineered candidate molecules needs to be expressed and evaluated, which poses serious data management and analysis challenges. Genedata BiologicsTM systematically designs, clones, and tests large numbers of novel next-generation antibody formats, such as bi- and multi-specifics, knobs-into-holes (KinH), Fab-scFv, IgG-scFv, DVD-Ig, tandem-scFv-Fc and their parametric variants (e.g., linkers, V-domain order, Fc). The system also automates downstream expression, purification, and characterization processes, which substantially increases throughput.

Genedata Biologics resolves major bottlenecks in high-throughput molecular biology and cloning processes. These processes are required to systematically generate and validate DNA constructs to express the desired next-generation molecules. The platform supports multi-specific engineering strategies by identifying the most successful combination of antigen binders and formats and scales up cloning and production by directly integrating with laboratory automation equipment. By automatically aggregating all assay and analytics results, Genedata Biologics also facilitates decision-making to choose the best candidate to move forward.

Developability & Manufacturability Assessment

Choosing a biologics candidate to move forward into development is a very cost- and time-critical step in biopharmaceutical R&D. Therefore, an early and comprehensive assessment of a candidates’ developability profile and critical quality attributes (CQA) is crucial. However, performing developability assessments early in discovery, means dealing with more molecular entities and more heterogeneous data, which poses a significant challenge.

Genedata Biologics enables a systematic assessment of a candidate’s developability risk profile at any point in the process. The system evaluates intrinsic molecular properties that may influence the technical development of the drug candidate, such as challenges during drug product formulation. Genedata Biologics enables the identification of predictive developability parameters based on molecule, sample, and analytics data collected during a candidate’s life cycle. Common problems identified by Genedata Biologics include aggregation, formulation instability, and reduced pharmacological activity. In addition, the system assesses the manufacturing risk to determine a drug’s “manufacturability” with regards to problems including potential issues with expression and purification. Finally, Genedata Biologics evaluates a candidate’s properties that affect molecule robustness on a biophysical and biochemical level. Typical tests include stability (e.g., pH, freeze–thaw, high- and low-temperature stability tests), degradation (e.g., resulting from extreme pH values, light, oxidation), viscosity, thermal stability, solubility, glycosylation characterization, and immunogenicity.

In this way, Genedata Biologics performs an in-depth developability assessment to provide the necessary basis for an informed decision on which candidate molecules to transition from research to development.

ADC Design, Engineering & Testing

Antibody Drug Conjugates (ADCs), or immunoconjugates, play an increasingly important role as a new class of oncology medicines that use the selectivity of monoclonal antibodies to achieve targeted delivery of cytotoxic drugs. However, the underlying ADC discovery and development process is complex and poses significant challenges in that systematic ADC design uses a combination of optimal conjugation strategies (e.g., lysines, cysteines, Fc glycans, non-natural amino acids), linkers (e.g., cleavable, non-cleavable), and small-molecule toxophores such as MMAE, DM1, or Calicheamicin.

Genedata Biologics supports the full ADC discovery process from antibody screening and engineering, to antibody expression, purification, drug conjugation, and reporting of ADC-specific analytics (e.g., DAR, drug distribution, homogeneity). The platform enables the registration and tracking of large panels of ADC candidates and incorporates results from analytics and functional assays in one integrated system, thereby substantially increasing throughput and efficiency during the ADC discovery process.

Inventory Management

Genedata Biologics provides comprehensive and fully integrated inventory management functionalities for warehousing biological samples. The inventory database represents the central repository for inventory information, such as sample type and content, amount, concentration, physical location, labware, storage conditions, distribution status, and other relevant information. Aliquot groups can be created for cell line batches, protein expression batches, protein purification batches, cell line batches and other biological entities. The freezer, location within the freezer, and type of freezer are recorded for each aliquot group. Both barcoded, as well as non-barcoded, containers can be managed. The system tracks all aliquot distribution information (e.g., shipped volume, recipient, date) for all sample transactions and automatically updates remaining aliquot numbers and sample volumes in real-time. Samples can be reserved for special purposes (e.g., reference sample), set aside for future distribution and use, or disposed of in case they are permanently removed from the inventory. All metadata on the nature of a particular sample is provided by the direct integration with Genedata Biologics, which provides one-button access to all information on the sample, such as for a purified antibody sample and its full history including used plasmids and cell lines for expression, purification protocol, and all analytics and sample QC information (e.g., purity, endotoxin, N/C terminus checks). Query tools provide a simple way to find relevant inventory information and the physical location of a particular sample, such as by sample identifier or by metadata information.

Patent Submission

Biologics patent applications typically contain large numbers of sequences and various combinations of sequence segments. The process of compiling and annotating these sequence lists can be time consuming at best, and in the worst case, errors may go unnoticed until after the patent application has been published. In fact, a substantial number of published patent applications contain serious errors. Typical errors include cases in which the CDR or variable domain combinations are not unique and unintentionally claimed redundantly within a patent application or a CDR or variable domain definition are not consistent between the patent application text and the sequence listing. Other typical errors are having individual sequences concatenated instead of listed as separate sequences or listing incorrect sequence variants.

Genedata Biologics helps to prevent such serious errors by automatically tracking, annotating, processing, and properly formatting all relevant sequences for patent applications. The system increases quality and eliminates costly mistakes in patent applications by systematically tracking, organizing, annotating, and reporting all relevant sequences. Genedata Biologics provides the necessary flexibility to extend sequence listings during the patent extension period until the final sequence listing submission, and once submitted, lock all the data to the document to 'freeze' the final submission. Finally, the platform facilitates the final submission by patent lawyers as it easily generates sequence list reports ready for patent submission via direct integration with standard submission tools such as the PatentIn software.

Genedata Biologics is equally useful for scientists, inventors, and patent counsels and lawyers who jointly work on patent submissions. The platform provides a clear and accurate common vocabulary for referencing molecules that are relevant for each patent submission.

Lead Discovery from B-Cells

B-cell-based antibody discovery is an increasingly used strategy to identify highly specific, affinity-matured monoclonal antibodies. Genedata BiologicsTM removes major bottlenecks from this process, significantly increasing the throughput and the quality of B-cell-derived therapeutic antibody candidates. One major challenge is the screening and V-region gene recovery of thousands of clones. The process involves cDNA generation from sorted B-cells, PCR amplification and sequencing of V-regions, various molecular cloning procedures, as well as the recovery and co-transfection of cognate light and heavy chains into host cells for functional screening of the monoclonal antibodies.

Genedata Biologics streamlines every stage of the highly complex B-cell-based discovery process. By registering all molecules, samples, and assay data created along the discovery workflow, the complete history of the antibody clones - which undergo multiple format changes from B-cells to PCR products, plasmids, and transfected cells - is tracked and monitored. Moreover, quality control and functional assays data such as ELISA, FACS, and SPR experiments is managed by the system. In combination with V-region sequencing results, this allows unique integration of molecule sequence and functional information and enables informed decision making when choosing lead candidates to move forward.