Evogenix fine-tunes Absalus antibodies in strategic alliance

If you need to give your humanised monoclonal antibodies (MAbs) a gecko-like grip on their therapeutic targets, who do you call?

Late last year Californian biotech Absalus Inc made a trans-Pacific call to Sydney biotech EvoGenix. Absalus was impressed by Evogenix’s technology for fine-tuning proteins by shifting protein evolution from T-model Ford into fast-forward mode.

Today the two companies announced a strategic alliance that EvoGenix CEO Dr Merilyn Sleigh describes as being enormously important to the future of both companies, and prospective clients.

Evogenix and Absalus will offer clients a custom redesign and tuning service, that will humanise mouse MAbs and fine-tune them to optimise their affinity for their target antigens.

Several companies around the world, including Absalus and Protein Design Laboratories, provide a service for humanising murine antibodies, but Sleigh says that reshaping the scaffold structures that support the antibody molecule’s finger-like active domains often loosen its “fit” with its target antigen.

EvoGenix proprietary protein-evolving technology allows researchers to improve protein function by exploring variations on the original molecule’s theme, created by artificially induced “mutations”.

The CSIRO-developed technology exploits an error-prone RNA polymerase enzyme that makes random copying errors as it transcribes the gene’s original DNA code into messenger RNAs (mRNAs).

Each new “mutant” mRNA yields a different protein molecule. Potentially, billions of new variants can be created.

The EvoGenix technology takes the millions of different mRNAs and expresses them in a cell-free protein-synthesis system. The humanised antibodies, still linked to their mRNA recipes, are then exposed to a surface coated with the target antigen.

The antibodies that bind tightest to the antigen are recovered, with instructions attached. The genetic code for the best-fitting antigen can be subjected to several more iterations of the same process, to further improve its affinity for the antigen.

At the end of the selection process, the recipe for the best-fitting antigen is copied into DNA, and the resulting new gene is plugged into a cell culture system to synthesise the antibody in kilogram quantities.

Sleigh says that if conventional humanising process reduces the binding affinity of the original mouse antibody by a factor of 10, it means the therapeutic dose of the antibody must be increased tenfold – the EvoGenix technology can restore and even improve the binding affinity of the final, humanised antibody.

After the call from Absalus President Dr Steffen Nock late last year, Sleigh flew to California in January for further talks. “Since then it’s just been a matter of thinking about how we could work together, and putting the agreement together.