Why use in vitro antibody libraries?

There are many ways of generating human antibodies for therapeutics, basically split between immunization and in vitro naïve antibody library approaches. Whichever method is used, industry has been wrestling with three critical challenges: diversity, affinity and developability.

Antibodies must have biological activity, so the greater the diversity of available antibodies, the greater the chance an antibody with appropriate biological activity can be found. Once an antibody with biological activity has been found, high affinity is usually required.

However, antibodies with excellent activity and affinity, may not be useful as therapeutics if they are not developable.

The main advantage of In vitro selection from naïve libraries is the ability to directly select for specific properties. This contrasts with immunization, where researchers screen what the immune system provides. Notwithstanding the advantages of selection over screening, immunization has been generally preferred, as antibodies from historical naïve libraries tended to have lower diversities, lower affinities and more developability problems.

With its Generation 3 Platform, Specifica has overcome the challenges of diversity, affinity and developability, making antibody libraries so effective that the advantages of in vitro selection can now be fully realized, and complex selections can be carried out.

Developability is a concept coined to describe a favorable set of in vitro biophysical characteristics such as reduced aggregation propensity and polyreactivity, which tend to be associated with improved in vivo properties and reflect the ease with which an antibody can be developed into a drug.
A typical Specifica campaign involves selecting antibodies binding to receptor A, but not closely related receptor B, cross-reacting with the cynomolgus version of A, and inhibiting binding of the ligand for A. This can be easily done with the Generation 3 Platform but is much more challenging when screening  immune responses.

Over 100 naive libraries built.

Thought Leaders in Antibody Libraries

At Specifica we live Antibody Libraries. Forever innovating, we have generated over 100 naive individual Libraries using different scaffolds, formats, variable gene sources and diversity sets. We learn from failure – a better teacher than success. We understand the complexities of Antibody Library construction. By using cutting edge next generation sequencing (NGS) for quality control at all steps of construction and validation we are able to count, rather than estimate, the number of different antibodies in each Specifica library, so ensuring our high diversity standards.

Whether a Generation 2 or a Generation 3 Library, high guaranteed diversities mean more antibodies, recognizing more epitopes, with higher affinities, against more targets. Libraries are usually provided in phage display formats, and, except for Fab, can also be supplied in the yeast display format.

Antibody Formats

We presently build Generation 2 libraries in two main formats: scFv and Fab, while Generation 3 libraries are available as scFv, Fab and VHH.

The scFv and Fab formats can also be built as fixed light chain libraries, suitable for generating antibody pairs for use in bispecifics.

VHH libraries are based on well behaved therapeutic VHH molecules into which replicated natural diversity from rearranged human VH3 genes are inserted into CDR1-2, and amplified HCDR3s from unique donors inserted into CDR3.

Exclusively yours

Donors providing lymphocytes to create Specifica naive libraries are only used to build libraries for you, ensuring each library is unique and exclusive to you. Specifica’s Generation 2 Libraries are natural antibody libraries created from the rearranged antibody genes found in natural B lymphocytes, while Generation 3 Libraries are based on well-behaved therapeutic scaffolds with quality built in by design, rather than by testing.

In addition to in-house designs, we also collaborate closely with you to create custom libraries in which essential elements are optimized according to your needs.

 When you adopt the Specifica Platform we provide you with phage stocks of your own exclusive Generation 3 Antibody library to get you started; enough bacterial stocks to keep you going for decades; vectors; comprehensive manuals including phage and yeast display selection, straightforward affinity maturation, and scFv to IgG reformatting. Full training at Specifica will empower you to generate the best therapeutic antibodies in your labs.

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