Antibody Libraries for Antibody Development
Don’t waste time in translation or dealing with poor attributes. The right therapeutic-ready monoclonal antibody library rapidly delivers human antibody hits right out of the gate, and they are unparalleled in their developability, enabling the fastest route to the clinic.
Rapidly discover unique antibodies against any target of interest with this antibody library screening phage display technology. The graph below shows how timelines are shortened by eliminating immunization, hybridoma, humanization and optimization phases. It also illustrates how the Distributed Bio technology delivers greater number of hits.
Charles River and Distributed Bio offer two antibody libraries: Cosmic and SuperHuman.
The Cosmic Antibody Library™ is comprised of 100 billion unique full-human antibodies, with the diversity to deliver therapeutic leads against the hardest targets, including GPCRs, ion channels, pMHC complexes, anti-HIV bnAbs, allosteric modulators, mouse/human cross-reactive epitopes, anti-idiotypics, and bi-epitopics. Leads are perfect for IgGs, CAR-Ts, bi-specifics, ADCs, and nanobody applications. Eliminate risk of first-to-file as 50 molecules are delivered exclusively to you.
The SuperHuman antibody library is Distributed Bio's first library guided by machine learning and computational optimization, consisting of antibodies carefully selected from humanity’s natural immune repertoire and engineered to perform optimally as therapeutics.
This platform is ideally suited for CAR-T discovery. The antibody scFv format provides a plug and play environment, reducing time in the workflow.
Use this custom antibody library and antibody discovery platform to:
Identify hits with unprecedented speed
With hits against even the most challenging targets, the platform dramatically reduces therapeutic hit discovery time to as little as 4 weeks.
Watch this video to see how a client reduced discovery time by using the SuperHuman library. The client first panned yeast display, then phage display, and finally mice models with no promising results. The client eventually found success with the SuperHuman library.
Ensure more hits through diversity
The SuperHuman library is over 100x more diverse than any previous human antibody library. This unprecedented diversity has resulted in a unique engineering opportunity: a library that generates over 300 unique hits against every one of the antigens in the pipeline. Given the number of hits, this library can be panned under normally impossible aggressive conditions, recovering hundreds of picomolar binders, saturating coverage of hits against every epitope, and isolating multispecies cross-reactive members against target homologs without additional engineering.
Pre-optimize hits now to save time and reduce costs later
While the CDR-H3 and V-gene frameworks define much of a clone’s interaction with the target, variations in the other CDRs can impact affinity and breadth of reactivity. The human antibody library was designed with about 5 billion CDR-H3s but 76 billion total antibodies. Due to the combinatorial design, each hit from the antibody library screening will appear with multiple variants. The result is key engineering guidance and optimization of every hit right out of the naive library.
Compile, Analyze, and Optimize Antibodies
Artificial intelligence-based Tumbler technology provides a method for rapidly generating 500+ million versions of an input antibody in order to affinity mature, thermostabilize, deimmunize, species-cross react, biochemical liability remove, humanize, pH sensitize, and otherwise engineer an input antibody.
AbGenesis is a user-friendly, cloud-based computational platform that compiles and analyzes sequence data quickly so researchers can rapidly complete antibody and immune repertoire analyses. From analyzing individual cells to millions of B-cell and T-cell receptors, as well as linking sequence and phenotype (affinity, expression efficiency, stability) data, AbGenesis allows researchers to derive meaningful insights and make informed decisions on all facets of antibody discovery.
End-to-end Platform for Therapeutic Antibody Discovery and Development
This antibody discovery platform technology with antibody library screening from Distributed Bio together with the extensive capabilities of Charles River creates a unique end-to-end platform for therapeutic antibody discovery programs. Learn more about the integrated target to clinic portfolio:
- In vivo pharmacology
- In vitro biology
- Safety pharmacology
- Biologics testing solutions
- Antibody production
In 1986, the US FDA approved the first mAb to limit organ transplant rejection. Follow the journey, where next generation antibody discovery technologies contribute to therapeutic or diagnostic mAbs now approved. Read the article
Antibody Library Screening Frequently Asked Questions (FAQs):
What is the Cosmic Antibody Library™?
The Cosmic Antibody Library™ is an antibody discovery library consisting of 100 billion human antibodies – as many as there are stars in the galaxy. The new tool rapidly and reliably delivers hits against even the most difficult biologic targets. Cosmic’s vast collection of human antibodies has been engineered for the highest diversity, thermostability, and non-immunogenicity, empowering drug hunters with unique, exclusive, druggable hits. Cosmic delivers therapeutic leads against the hardest targets, including GPCRs, ion channels, pMHC complexes, anti-HIV bnAbs, allosteric modulators, mouse/human cross-reactive epitopes, anti-idiotypics, and bi-epitopics. Leads are perfect for IgGs, CAR-Ts, bi-specifics, ADCs, and nanobody applications.
Does this antibody library have success with challenging target classes such as GPCRs?
Clients often partner with Charles River on challenging targets. For antibody hit discovery programs against difficult targets such as G-protein-coupled receptors GPCRs, anti-idiotype antibodies, pMHC-complex targeting antibodies, and challenging epitopes on targets like PD1, Charles River can help. This antibody discovery platform successfully generated hits against the class A GPCR CXCR5 and has optimized hits against another (undisclosed) GPCR. There is no longer a need to go to non-human antibodies to target GPCRs. Beyond target discovery, Charles River can help with pharmacology studies, regulatory safety support and all the way through to IND.
Why is specificity important in antibody discovery?
Specificity, or dangerous and problematic off-target effects against a different gene product than the intended target, is particularly problematic for CAR-T and pMHC-targeting antibodies. The SuperHuman antibody library screening technology addresses specificity in three ways. It:
- Incorporates an immense library with up-front deselection against other off-targets
- Builds the library from fully human complementarity-determining regions (CDRs) that have already been pre-filtered by the human body
- Uses high-throughput sequencing of hundreds of millions of antibody reads from multiple panning programs, ensuring antibodies against a given target have not enriched against any other target
To learn more about specificity, read Identifying specificity groups in the T cell receptor repertoire, published in Nature 21 June 2017.
How does SuperHuman antibody library screening avoid immunogenicity liabilities?
Immunogenicity doesn’t manifest itself until human trials. Liabilities can surface at this late stage and the therapeutic can be rendered inactive and even cause negative health outcomes in recipients. The SuperHuman antibody library addresses immunogenicity up front by using antibodies that look entirely human by design. It includes antibodies with no mutations in the frameworks. This phage display antibody library includes only frameworks with dominant alleles found in all human populations in addition to CDR diversity that contains only the variations that the human body is able to produce.
What is the SuperHuman antibody library?
The SuperHuman antibody screening library, delivered by Distributed Bio and made commercially available by Charles River, is a custom antibody screening library that was computationally optimized for both sequence diversity and engineering fitness. Through the analysis of human antibody repertoires and known monoclonal therapeutics in human phase trials, it delivers thousands of unique hits with superior affinity, cross-species coverage, and improved drug-like characteristics in as little as four weeks. Interested in learning more? Consult a Charles River antibody discovery specialist.