Scientists create antibodies stable enough to produce in large quantities

Scientists in Australia have created antibodies that are stable enough to produce in large quantities, thus overcoming one of the most pressing problems facing the pharmaceutical industry.

Creating antibodies that are stable enough to meet stringent requirements necessary for production in large quantities, injection into patients and long-term storage has been one of the most pressing problems facing the pharmaceutical industry.

Now, Dr Daniel Christ and PhD students Kip Dudgeon and Romain Rouet from the Antibody Engineering Laboratory at Sydney’s Garvan Institute have developed specific mutations that universally increase the stability of antibody molecules. The findings have been published in the Proceedings of the Academy of Science (PNAS).

Dr Christ said: "When we talk to collaborators in industry, we find that 30-50 per cent of the antibody-based drugs they develop have to be put on hold because they don’t meet quality tests that the companies or regulatory agencies such as the US Food and Drug Administration, require before marketing or approving these molecules.

"Until now, the issue of antibody instability has been tackled on a case-by-case basis, which is only tinkering with the problem. When you’re dealing with such a diverse population of molecules, you have to make sure that the method you develop is generally applicable – and that’s what we’ve done."

There are up to 100 million antibodies of different kinds circulating the human body at any one time. They have constant and variable regions, but can also often be unstable because there is an infinite variability of antibody structures.

The mutations created by the Garvan team fix the stability problem without compromising the antigen binding properties of an antibody. They achieved this by working with both the heavy and the light chain, which makes the mutations less sticky and much less entangled. They also make the antibodies more robust against common storage methods such as freeze drying.