Bioconjugation

Antibody Drug Conjugates

Antibody drug conjugates (ADCs) are designed to precisely deliver drugs to the sites of disease and have found clinical success in oncology by  killing cancer cells selectively with cytotoxic drugs.  ADCs are made up of three main components: an antibody which targets the site of the disease, a drug, and a chemical linker to conjugate the drug to the antibody. The antibody carrying the drug is designed to bind to antigens on the surface of cells and then be internalized. Once inside the cell the drug is released from the ADC and, in the case of treatment for cancer, kills the cell. Targeting disease in this way with ADCs can minimise the side effects that patients experience by limiting damage to healthy cells.

Abzena can support companies developing ADCs from the discovery of the antibody to selection of the best candidate ADC, followed by manufacture of the linker reagent and antibody according to GMP standards for use in clinical studies.  Very few providers offer such a wide a range of services, technologies and manufacturing capabilities as Abzena for taking ADCs from concept to development.

Abzena can produce a range of ADC candidates from the same antibody and different types of linkers and payloads so that you can find the optimal solution for your target.

Antibody development services

Abzena can discover, affinity mature, humanize, develop manufacturing cell lines and manufacture antibodies, antibody fragments and other protein targeting moieties.

Conjugation technologies

Abzena provides a variety of methods for conjugating drugs to antibodies, including a proprietary linker technology, ThioBridge™, which attaches the drugs at accessible disulfide bonds. This technology has been shown to generate more homogeneous products with better stability than other conjugation techniques.  Abzena also has experience of conjugation to cysteines and lysines using traditional linkers.

Drug payload

Abzena has a toolbox of payloads available or can custom synthesize payloads with a variety of mechanisms of actions for your ADC, including microtubulin inhibitors and DNA intercalators for the treatment of cancer.

Analysis and characterisation

Abzena’s labs are equipped with an array of state-of-the-art analytical and preparative HPLC equipment and mass and NMR spectrometers to enable extensive analysis and characterisation of ADCs.

Manufacture

Abzena can manufacture the antibody or other targeting protein for an ADC to GMP standards at its facilities in San Diego (US).  The starting point can either be a manufacturing cell line developed by us or one provided by you. We can design and optimise the manufacturing process and then scale it up to provide material for use in Phase I and II clinical studies.

The payload and linker-payload (conjugation) reagent can be produced to GMP standards at our facility in Bristol, just outside Philadelphia (US). Non-GMP batches of ADC for GLP toxicology studies can also be produced at the site. Abzena will shortly have the capability to provide full GMP production of ADCs.

PEGylation

Abzena provides a range of site-specific conjugation technologies to optimise the pharmacokinetics (PK) and pharmacodynamics (PD) of therapeutic peptides and proteins, including antibody fragments and other protein scaffolds, by extending their half-life to reduce the frequency of dosing. This improves patient compliance and can reduce the cost of treatment.

Our proprietary PEGylation technologies enable polyethylene glycol (PEG) or other polymers to be attached to specified sites depending on the nature of the protein. TheraPEG™ conjugates PEG at disulfide bonds, HiPEG™ conjugates PEG to histidine-tags and CyPEG™ conjugates PEG to single cysteines. These technologies are used to conjugate both linear and branched PEG to therapeutic proteins as well as for protein labelling.

The conjugation processes are extremely efficient, helping keep the cost of manufacture down, and the conjugated products are more stable and homogeneous than can be achieved with other well-established conjugation technologies.

We can PEGylate your protein or peptide in our laboratories or provide you with our conjugation reagents so you can undertake the work yourself. Our reagents are available in a range of PEG molecular weights and formats, including linear and branched PEGs.

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