Antibody Design & Protein Engineering

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Antibody design & protein engineering solutions that accelerate biologics development.

We can help optimize and de-risk your programs lead candidate. Abzena’s antibody design and protein engineering experts look to de-risk your program to give you the best chance of success by combining protein engineering expertise with state-of-the-art analytics. This allows us to design drug candidates with minimal liabilities and maximum functionality.

For over 20 years Abzena has been providing antibody design and protein engineering solutions to accelerate biopharmaceutical development, and overcome a wide range of drug design challenges.

From antibody discovery through to cell line development we can engineer, express, purify and characterize your molecules. Utilizing experience from successfully delivering many hundreds of projects, our experts work relentlessly to meet your needs, enhance efficiency, and mitigate risk.

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Protein Engineering

Protein engineering has become a serious tool in the development of antibodies and other protein therapeutics. Considerations such as immunogenicity, half-life, post translational modifications, and format have all become critical to the development of therapeutic proteins.

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.

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Antibody Humanization & Protein Deimmunization

Immunogenicity is always a potential concern for any new drug. Non-human developed derived antibodies (e.g. from mouse, rabbits or llamas), or proteins in general, can often lead to loss of therapeutic efficacy and unwanted negative responses by the patient through the development of anti-drug antibodies (ADA’s). Abzena has developed a unique approach to the deimmunization of proteins and the humanization of antibodies through our proprietary Composite Human Antibody™ technology (CHAb™).

Abzena’s CHAb™ approach 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.

We build work packages based around your specific requirements ranging from our ‘Design Only’ offering through to our full ‘Design, Expression and Characterization’ package, giving you the flexibility based around your requirements.

Our ‘Design Only’ service for either CHAb™ or Germline humanization CDR grafting, gives you the flexibility to carry out investigations on your own timescale.

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.

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Improving Antibody Manufacturability

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.

We can design, express and test the function of all liability removed constructs, de-risking your antibody as it moves through clinical development.

Affinity Maturation

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.

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Bispecific Engineering

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.

Bispecific & Multispecific Antibodies

Isotype Switching & Fc Engineering

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.

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Abzena has significant experience in Fc engineering to modulate the function of an antibody through, e.g. either reducing or increasing effector function, or through modulating the half-life of a therapeutic, all aimed at ensuring that we tailor the properties of the antibody to your precise specification.

Bioconjugation

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.

Bioconjugation Services

Antibody & Protein Production

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.

Protein & Antibody Expression