Antibody Design & Protein Engineering

Abzena has a long and successful history of providing protein engineering solutions to accelerate biopharmaceutical development and overcome a wide range of challenges. Abzena’s portfolio of antibody and protein engineering services offers a range of standard and custom solutions, which include protein deimmunization and antibody humanization, broader developability of lead sequences and the removal of sequence liabilities, affinity maturation, bispecific design and formation as well as isotype reformatting.

Therapeutic antibody candidates can often contain liabilities within the sequences. 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.

By combining in silico tools together with sophisticated analytics we are able to identify and rank liabilities by level of risk. This combined analysis coupled together with Abzena’s developability solutions, identifies concerns, and suggests substitutions for their removal based on our vast experience in the field.

Some antibodies require improvements to their overall binding potential. At Abzena we have a well-established affinity maturation process using scFv-based phage display to improve the binding affinity or other desired properties of an antibody for its target antigen by random or directed mutation, without impacting specificity.

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.

The Fc part of an antibody is more than just a scaffold for the variable domains. The Fc plays a critical role in the overall function of the antibody and is responsible for mediating immune effector functions and in vivo IgG stability. Consequently, for most therapeutic indications, having the right antibody class and format is as important as having the right antigen specificity.

We can take your parental antibody and perform class or isotype switching to investigate the effect of different Fc moieties on the activity of the antibody.

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.

We deliver stage-appropriate antibody production packages tailored to your development needs, based around our CHO mammalian expression systems. All our proteins and antibodies undergo rigorous quality control which includes the assessment of purity and integrity. Extended analytics are also available to further evaluate the standard and novel characteristics of your biologic.

For specific projects, small-scale, research-grade bacterial expression is also available.