Antibody Design & Protein Engineering

Immunogenicity is always a potential concern for any new drug. Humanization and deimmunization is an essential part of the process for the development of therapeutic antibodies and proteins derived from non-human sources. Abzena’s proprietary platforms facilitate the design process by eliminating human T cell epitopes, significantly reducing potential immunogenicity and improving the safety profile of therapeutic candidates.

Antibody Humanization

Abzena’s Composite Human Antibody™ (CHAb™) solution focuses specifically on the reduction of predicted immunogenicity hotspots across the sequence using iTope-AI, Abzena exclusive proprietary in-silico immunogenicity prediction tool, to identify MHC class II binding peptide sequences. Abzena’s humanization approach focuses on introducing substitutions from multiple human germlines to specifically reduce this predicted immunogenicity. Our Composite Human Antibody™ platform combines the best attributes of deimmunization and humanization techniques to minimize the immunogenic potential, whilst retaining the original function of the mAb.

Protein Deimmunization

Our Composite Proteins™ deimmunization technology builds on the success of antibody humanization to design safer therapeutic proteins, devoid of human T cell epitopes, to minimize potential immunogenicity in patients without compromising activity.

Protein engineering is not limited to ‘surgical’ sequence manipulation – the development of novel therapeutic antibody modalities, such as bispecific or multispecific antibodies can require engineering at the domain level to bring together different specificities. By using our experience in reformatting sequences, we can help you design, express and test bispecific candidates to get you to the right format quickly.

Engineering of any kind will, by its nature, change the physico-chemical properties of the molecule compared to the starting sequence. Sequence liabilities can include: isomerization, deamidation and glycosylation sites, as well as free cysteines and other motifs. These, in turn can affect the function of the antibody over time, be a potential safety risk, or lead to manufacturing problems. Additionally, overall surface chemistry, such as hydrophobic patches can lead to poly-reactivity while charge distribution can affect pharmacokinetics (PK). By being aware and engineering out potential risks, you will smooth your developmental journey to the clinic.

Improving Antibody Manufacturability

By applying a range of stage-appropriate analyses we are able to rapidly select candidates that have the optimal properties for development and manufacturing.

Site-specific approaches towards conjugation are increasingly gaining traction due to the ability to generate homogeneous constructs with precise drug loading and predetermined sites of attachment. Of these site-specific approaches, several require engineering of a site-specific handle or tag into the sequence for efficient conjugation. At Abzena, we have significant experience of both engineering different site-specific motifs as well as of the conjugation itself, thereby allowing the exploration of a wide range of different conjugation approaches.