Humanized Monoclonal Antibody Technology
Tumbler is a multi-factor optimization platform used for antibody humanization. As the antibody is tumbled through our proprietary technology, it is made “more human,” and is optimized for affinity, removal of liabilities, thermostability, species cross-reactivity, and selective activation.
In addition, clients using Tumbler can introduce a second target binding modality on the same paratope, also known as bi-epitopic antibodies. Similarly, Tumbler is used to retrofit antibodies to cross to a new version of the original target. Repurposing drugs and lead candidates is a cost effective route of drug discovery.
Tumbler humanized antibody technology offers the following lead characteristic profiles:
Antibody humanization with Tumbler far exceeds chimeric CDR grafting. As the graph below indicates, our lead candidates are more human than a graft, reaching 90% or more identity to known humanized monoclonal antibody structures while retaining or even improving antibody affinity.
The Tumbler platform is the only system that has the capability to produce identical replicas of human antibodies.
Antibody discovery is complex and challenging. Potentially, after many years into your project, you may find your one lead candidate meets all expected parameters, but doesn’t bind as strong to the target as it needs to. This platform is an optimal affinity maturation tool reaching as much as two log increased KD for lead candidates; in other words, that’s 130 times the improvement. Even better, you won’t get just a single improved version, rather an entire panel of humanized antibodies with varying paratopes so you can analyze and select for the best antibody affinity version.
The below kinetics graph shows a panel of leads and illustrates rapid antibody optimization with 10 times improvement in binding activity.
Tumbler - Rapid Optimization
Clinical Profile Enhancement
The clinical profile of your humanized monoclonal antibody is what makes it perform well during pre-clinical and clinical trials. Tumbler phage libraries are heated up to 68°C, so only antibodies that survive this heat challenge will make it into the panning. We also have full control over the library build removing all liabilities and can typically increase the expression level compared to starting clones.
All Tumbler-derived lead candidates will be thermostable and well-equipped for progressing to trials. Our antibody humanization scientists will work closely with you to select the right subset of candidates from a Tumbler run.
It is essential to protect lead candidate assets through patents. We provide you with not only one optimized antibody, but an entire set of leads. In addition, you will receive bioinformatics sequence characterizations and sequence space descriptions, such as PWMs. This will equip you for successful and broad IP protection.
Target Modulation or Paratope Modulation
Tumbler is a library-based approach. Therefore we can perform various forms of modulations to the antibody and the generated paratope sequence space is explored in a Tumbler antibody humanization campaign. It’s common for our starting clones to have designated affinity and antibody specificity to the human variant of the target. Engineering cross-reactivity to cynomolgus monkey and even mouse versions of the target is one of our most common requests for paratope modulation.
Paratope surface area real estate can be utilized to engineer true bi-epitopics, also known as antibodies, that bind to two different targets with the same paratope. Paratopes use around 60 amino acids, but only about 15 amino acids are necessary to exert specific binding to a given target. This leaves enough room to offer binding to a second target during your antibody humanization campaign.
Distance of paratopes from start to finish can be significant. Our antibody humanization projects have resulted in paratopes with up to 20 amino acids varied from starting antibody to final lead candidate. In this regard, we were able to span ten years of viral evolution by modifying anti-SARS antibodies to bind and neutralize SARS-CoV-2.
This demonstrates the power of the Tumbler antibody humanization software and the SuperHuman antibody library to provide significant reach for target and paratope modulation.
Working With Us: Discover the Benefits of Our No-Risk, Rapid & Free Prequalification
We can rapidly perform a prequalification step, pre-scope of work (SOW) sequence analysis for your project at no charge. This step de-risks the antibody humanization project right away, so your resources are not wasted. After the assessment, and the project is underway, there are go/no go decision points in which the team and the client decide to continue or not, offering additional setpoints to save time and money.
Tumbler Antibody Optimization Process and Timelines
In addition to the lead molecule, a Tumbler campaign will yield these deliverables:
- Risk assessment, sequence, and structural characterization of your starting antibody
- Primary screening profile and sequences for up to eight plates of antibody variants (usually kinetics)
- 50 clones reformatted into full IgG or whatever you need
- Full characterization profile of these 50 clones (kinetics, FACS, ELISA)
- SAR - Sequence activity relationship - report
- Humanization report (if applicable)
End-To-End Platform for Therapeutic Antibody Discovery and Development
Our Tumbler antibody humanization technology, along with our scFv library and VHH library, creates a unique end-to-end antibody discovery and development platform for comprehensive, scientifically proven therapeutic antibody projects. Learn more about the integrated target to clinic portfolio:
- In vivo pharmacology
- In vitro biology
- Safety pharmacology
- Biologics testing solutions
- Antibody production
Frequently Asked Questions (FAQs) About Antibody Humanization Using Tumbler
Can any antibody be optimized?
Yes, the Tumbler antibody humanization platform is very flexible, and in addition, we perform an evaluation on your sequence before any agreement or contract is signed.
Does Tumbler antibody humanization technology work with any target?
Yes, we have successfully optimized antibodies for:
- Small molecules
- Ion Channels
- Difficult viral targets
- CAR-T constructs
How long does an antibody humanization campaign take?
We treat every project individually. Our experts work with your team to develop a custom antibody humanization work plan to obtain the antibody you need. We’re happy to have a short evaluation consult and provide timelines and deliverables for your antibody optimization project.
How many improved variants of my clone will I receive?
Charles River will reformat up to 50 clone variants, but Tumbler output far exceeds that number. Our experts will work with you to select the best possible candidates out of the panel of leads. Since you own the starting antibody, the full data package and all of the clone variants will be transferred to you as part of the project deliverables.