The MAB Discovery platform relies on the broad natural immune response and antibody maturation of wild type rabbits combined with B cell cloning. By doing so, we generate a plethora of therapeutic monoclonal antibody candidates which cover various target epitopes, show diverse functional properties and have high affinities requiring no further optimization. It is this diversity generation that we are striving for. And this is enabled by our proprietary, high-performance technology platform.
MAB Discovery GmbH based in Munich, was founded in 2010 and started operations in 2011 with experienced pharma scientists with a proven track record in drug development. MAB Discovery complies with the highest industrial standards of big pharma, but operates with the flexibility, speed and innovative spirit of a young biotech. The company’s outstanding technology platform offers its collaboration partners access to a large variety of fully functional drug candidates, and a unique route to CMC-compliant humanized mAb’s in 10-12 months.
Dr. Fischer spent 26 years in R&D at Boehringer-Mannheim/Roche Pharma Research where he focused on the discovery and development of biological based therapeutics.Stephan was a member of the team that developed erythropoietin (NeoRecormon®) and was the scientific and global project leader of the team that developed the thrombolytic reteplase (Retavase®, Rapilysin®) from discovery to launch. Stephan was a member of the global regulatory strategy committee for Biologics and the global task force for biosimilars. As Senior Vice President, Stephan led the Biologics research organization and developed the global strategy for Roche Biologicals with a focus on innovation and new technologies. Stephan received his PhD in Microbiology and conducted his post-doc at the European Molecular Biology Labs.
For over 26 years at Boehringer Mannheim / Roche, Dr. Krell was responsible for the development of high through put assays and screening of new diagnostic and biotechnological enzymes, natural compounds and low molecular weight compounds. More recently, Hans has focused on the discovery and characterization of novel therapeutic antibodies, employing innovative biochemical and cellular based screens. In addition, Hans has been actively involved in global project management. Hans (co-) authored more than 40 patent applications and 60 publications. Hans holds a PhD from Freiburg University in biochemistry.
Rabbit antibodies are known for their excellent affinities and specificities; even generating antibodies to unique epitopes. The explanation for these attributes and the broad diversity of antibodies are the mechanisms employed by the rabbit immune system [read more].
In order to yield the most diverse repertoire of target specific rabbit antibodies, and to allow for a fast identification of the monoclonal antibody with the best functional profile, as many of the IgG expressing B-cell clones as possible are selected and screened in an automated process. 15,000 to 60,000 B-cell clones are isolated and cultured individually per campaign. The secreted monoclonal antibodies can be functionally tested in high throughput assays.
After sequencing thousands of target-specific antibody genes, it is remarkable that we have never isolated the same sequence from different rabbits immunized with the same immunogen. This supports the assumption that gene conversion produces individual rabbits with a unique gene repertoire for antibodies. Also, the sequence redundancy rate in one individual animal is very low. This is the result of the empirically optimized immunization and sampling protocol. We can guarantee novel sequences from each campaign, a solid basis for IP [read more].
Function, efficacy and safety profile of therapeutic antibodies can be highly dependent on the antibody isotypes and Fc modifications. Therefore, we introduced special features to allow for flexibility in targeted modification of the antibody’s Fc part [read more].
- Wild-type rabbits create very potent antibodies with pM affinities already in an early phase of the immune response.
- Affinity maturation is not required to isolate potent molecules.
- Activity screens are possible in B-cell supernatants, including screening for Fc function and cell binding assays.
- Each rabbit is unique and will create novel antibodies.
- Very low sequence redundancy within one animal (< 10%).
- The large number of obtainable leads enables direct humanization and selection for CMC related quality criteria which results in a minimal modality risk for development.
- In silico analysis of manufacturability as an intrinsic part of lead selection after humanization.
- Transient recombinant expression selects for well producible molecules.
- Selected fully humanized MABD antibodies have good drug-like characteristics.
MAB Discovery delivers high quality, functional monoclonal antibodies via sophisticated, high-throughput selection of B cells generated by immunization. The immunogen can be a full-length recombinant or partially purified protein preparation, as well as whole cells, DNA or peptide conjugates. The MAB Discovery approach always delivers a vast number of high quality candidates with regard to potency and epitope coverage.
MAB Discovery employs a proprietary immunization schedule, enabling a focused and highly successful strategy for each and every individual antigen target. This schedule allows early prediction of project success.
The use of wild type rabbits for the immunization and functional B-cell cloning strategy of MAB Discovery suits not only classical target proteins and receptors, but also to a wide variety of more challenging immunogens, e.g. GPCRs, ion channels, carbohydrates, and small sized epitopes.
- Many immunogens possible (Protein, cells, DNA,…)
- Proprietary immunization schedule
- Immunogen dependent immunization schedule
- Different bleeds can be analyzed
- Prediction of success at an early time point possible
B Cell Cloning
According to the targeted immunization and sampling schedule, peripheral blood lymphocytes are prepared. B-cells are cloned by fluorescence activated cell sorting (FACS) and deposited as single cells into proprietary growth medium. The cloning is fully automated and thousands of B cell clones can be sorted, which leads to a much higher hit rate compared to conventional hybridoma technology, other B-cell cloning methods or phage-library generation from immunized animals. This guarantees that most, if not all of the possible target epitopes can be assessed. During cultivation, these monoclonal B-cells secrete the monoclonal antibody into the supernatant. As natural diversity of light and heavy chain combination is not influenced by the MAB Discovery process, resulting monoclonal antibodies already exhibit high stability and affinity from the start. Therefore, costly, cumbersome and time-consuming affinity maturation steps are not required.
- Isolation of thousands of B cells ensures superior hit rate
- Proprietary sampling, cloning and B-cell cultivation process ensures best in class and unique epitope coverage
- Natural selection of light and heavy chain combination is retained; resulting in high specificity, stability and affinity
- Automated, reliable and fast process
Cultivated B-cell clone supernatants contain sufficient quantities of monoclonal antibody to enable several screening assays to be run in parallel at an early stage. Whenever possible, cell-based functional assays are included. As monoclonal selection by binding alone is generally not sufficient to predict function as well as therapeutic efficiency, the inclusion of cell-based activity assays at this stage is key to the identification of therapeutic antibody candidates. B-cell clones with interesting activity are then picked and processed.
Where screening assays are not already in place, or not yet described in the literature MAB Discovery develops, wherever possible, customized assays and candidate selection strategies to ensure the most efficient and successful project delivery. If required, Fc mediated functions can also be tested.
- Integration of functional assays at screening stage is the key to success
- Ability to perform multiple assays from B cell clone supernatant greatly increases effectiveness of screening strategy
- Screening for Fc mediated function possible due to 100% interaction with human Fc mediated receptor assays
- Ability to set up assays from scratch or adapt established assays to our high-throughput platform
- High throughput screening platforms ensures we discover the "rare event" so no blockbuster clones are ever left behind!
- Integration of functional assays at screening stage is the key to success
Sequence Analysis and Humanization
B-cells and supernatants are separated after B cell cultivation. B-cell clones with interesting activity in the supernatant are processed, and the sequences of light and heavy chain variable regions are determined. This is followed by direct humanization of all antibodies or creation of a chimeric rabbit-human sequence. The codon-optimized sequence for mammalian expression as well as expression plasmids are synthesized accordingly.
Superior humanization protocols
To further leverage the MAB Discovery platform, we have partnered with a global leader in antibody humanization technologies, Fusion Antibodies, Belfast, UK, (www.fusionantibodies.com/).
This partnership enables clients to not only generate best in class, functional antibodies, but fully humanize them from the outset, saving months in project development.
- Antibody humanization is seamlessly built in to the platform shaving months of a project timeline
- Sequencing of all the antibody hits light and heavy chain variable regions is possible ensuring complete security for downstream assessment
- Sequence analysis including diversity assessment and screening for potential CMC liabilities helps inform lead candidate selection strategy
- Different humanization workflows – classical and fast track- tailored to optimize the workflow.
Recombinant expression of humanized or chimeric antibodies is part of the general discovery work-flow. During this process different formats of the constant domain can be selected depending on the intended application, including the selection of different natural or engineered Fc variants. The automated process is applied to up to several hundred recombinant humanized hits. HEK293 cells are transfected in an automated way; therefore, several hundred antibodies could be expressed at the same time. Following cultivation, the recombinant antibodies are purified from the cell supernatants. After purification, concentrations of the antibody containing eluates are determined and normalized to facilitate confirmation testing. Assay data of the primary screen are confirmed with the recombinantly produced antibodies. The confirmation yield from B-cell supernatant to recombinant hits is very high (80 to 90%). In addition, if required, larger amounts of selected candidate antibodies can be produced.
- Humanized or chimeric antibodies can be generated
- Different isotypes and engineered Fc variants of immunoglobulins from different species available
- Sufficient levels of protein readily available via scaled up expression ensuring there is no limit to downstream testing/screening
- Identification of naturally high affinity antibodies means no affinity maturation is required saving significant time and cost
- Recombinantly expressed monoclonals with an array of affinities and range of epitopes provides options for lead selection depending on predefined target product profiles
Professional project management by a team of highly experienced pharma and biotechnology experts is a cornerstone of the MAB Discovery collaboration offering. Indeed, MAB Discovery sees itself as an extension of a client’s internal drug discovery and R&D group; not as an independent contractor. Prior to project initiation, a project manager is assigned who coordinates all communication with the partner, including critical pre-project discussions around the establishment of the integrated functional screening assays.
- Highly experienced project managers, including large pharma industry project experts
- Customized project workflow and timing
- Regular updates on deliverables and milestones
- Reliable on-time communication
MAB Discovery employs a highly efficient, fully automated, high throughput platform from immunization to recombinantly expressed leads. All steps are embedded into a barcode guided data system, enabling retracing of all recombinantly produced antibodies back to its original B-cell clone. The high level of automation and full traceability allows the processing of hundreds of hits with high speed and efficiency. All data are stored in the MAB Discovery LIMS system. This proprietary data base ensures tracking and documentation, and is also integral part of the company's risk management system.
- Cost efficient, automated platform for antibody generation enables levels of novel antibody discovery unsurpassed by manual methods
- Full barcode tracking of the discovery and selection process ensuring full traceability and risk management
- Data protection and documentation which comply with the most stringent pharma QA & RA requirements
- LIMS controlled automation drives cost efficiency and speed
Working with us
MAB Discovery enables its collaboration partners to discover, isolate and characterize monoclonals of unprecedented quality in terms of potency, functionality and epitope coverage. Based on individual client consulting, customized study design, target selection, and immunization strategy, the robust MAB Discovery process recognizes all relevant aspects for fast and successful delivery of sets of fully functional monoclonal antibodies, even for very challenging antigens.
MAB Discovery provides a superior route from immunization to delivery of well-characterized candidate expressing cell lines. The technology has been successfully employed for big pharma customers, and allows for discovery of antagonists, agonists as well as development of novel anti-infective approaches and strategies.
MAB Discovery successfully shares its outstanding experience and leading technology position with its partners, and follows a flexible cooperation business model including a technology access fee, research funding, milestone payments, royalty components as well as flexible working packages based on FTE rate.
Collaboration project agreement between MAB Discovery GmbH and BioNTech AG
Neuried, Germany - November 6, 2017:
MAB Discovery GmbH today announced that it has entered into the second collaboration project agreement with BioNTech AG, Mainz. The unique MAB Discovery technology platform for the generation of novel antibody therapeutics will be applied for proprietary targets provided by BioNTech. Financial terms of the agreement were not disclosed.
“We are excited to be selected again as a partner for BioNTech. This underscores the high performance of our rabbit-based antibody discovery platform,” said Dr. Stephan Fischer, CEO of MAB Discovery.
Sean Marett, COO of BioNTech added, “Our collaboration with MAB Discovery in 2013 was highly productive and we are delighted to expand our relationship to generate unique antibodies against a set of therapeutically relevant targets.”
MAB Discovery delivers high quality, functional monoclonal antibodies via sophisticated, high-throughput selection of B cells generated by immunization, and delivers a vast number of high quality candidates with regard to potency and epitope coverage. The use of wild type rabbits for immunization and the functional B-cell cloning strategy of MAB Discovery suits not only classical target proteins and receptors, but also to a wide variety of more challenging immunogens, e.g. GPCRs, ion channels, carbohydrates, and small sized epitopes.
MAB Discovery, based in Munich, was founded and established in 2010 by experienced pharma scientists with proven track record in drug development. MAB Discovery complies with the highest industrial standards of big pharma, but operates with the flexibility, speed and innovative spirit of young biotech’s. The company’s outstanding technology platform generally offers its collaboration partners access to a large variety of functional drug candidates to choose from, and a unique route to CMC-compliant humanized mAb’s in 10-12 months.
From A9 Nuernberg
Take the highway No. 68 to A 92 “Neufahrn” towards Stuttgart/Augsburg/München West and continue on highway A 99 direction Lindau/Stuttgart. Stay on A 99 towards Lindau take exit No. 4 onto A 96 towards Lindau. Keep right and take the first exit (No. 34) Germering/Krailling. Turn left onto Germeringer Strasse. You are going through Planegg and continue on Münchener Strasse towards Neuried. MAB Discovery is in the center of Neuried just after a crossroad where you keep straight on. On the right side you will see the MAB Discovery sign and the entrance to the parking lot. MAB Discovery is in No. 10, ground floor.
From A8 Stuttgart and A96 Lindau
Take the highway exit No. 81 to A99, “München-West” towards Garmisch-P./Lindau and continue for about 7 km. Keep right and take the exit No. 4 to A 96 “München-Süd-West” towards Lindau. Take the first exit (No. 34), turn left onto Germeringer Strasse. You are passing Planegg and continue on Münchener Strasse. . MAB Discovery is in the center of Neuried just after a crossroad where you keep straight on. On the right side you will see the MAB Discovery sign and the entrance to the parking lot. MAB Discovery is in No. 10, ground floor.
From Munich Airport
Take main exit towards west/all directions, turn onto A 92 towards Munich for about 21 km. Then continue on A99 for about 17 km. Take exit No. 4 onto A 96 towards Lindau, keep right and take the first exit (No. 34) Germering/Krailling. Turn left onto Germeringer Strasse. You are going through Planegg and continue on Münchener Strasse towards Neuried. MAB Discovery is in the center of Neuried just after a crossroad where you keep straight on. On the right side you will see the MAB Discovery sign and the entrance to the parking lot. MAB Discovery is in No. 10, ground floor
Take the S-Bahn S1 or S8 from Munich Franz Joseph Strauss Airport to Marienplatz. Get off and change to the U-Bahn U3 to Fürstenried West. Get off at the terminal station and take the bus Nr 260, 267, or 936. Get off at Neuried Rathaus. Cross the street, turn left and go back 200m. On the right side you will see the MAB Discovery sign and the entrance to the parking lot. MAB Discovery is in No. 10, ground floor.
By public transport
From Munich main station, take the U1 to direction Manfallplatz, or U2 to direction Messestadt Ost change at Sendlinger Tor to U3 to Fürstenried West. Get off at the terminal station and take the bus Nr 260, 267, or 936. Get off at Neuried Rathaus. Cross the street, turn left and go back 200m. On the right side you will see the MAB Discovery sign and the entrance to the parking lot. MAB Discovery is in No. 10, ground floor.