Box 1. Engineering glycosylation

Merck of Whitehouse Station, New Jersey, and Basel-based Roche each paid a high price to gain a position in the emerging field of glycosylation engineering. Merck parted with $400 million to acquire GlycoFi, of Lebanon, New Hampshire, last year, whereas Roche paid CHF 235 million ($190 million) a year earlier when it took over Schlieren, Switzerland–based GlycArt.

"We're both trying to get to the same endpoint," says GlycoFi scientific founder Tillman Gerngross. GlycoFi has developed a platform for 'humanizing' the glycosylation machinery of yeast cells. Gerngross and colleagues at Dartmouth and GlycoFi recently reported that they had successfully engineered a strain of the yeast species Pichia pastoris to produce proteins with fully human glycosylation patterns. Over 90% of the glycoproteins expressed from the engineered strain produced were terminally sialylated, which is essential for the functioning of all therapeutic glycoproteins, apart from antibodies. "It is fair to say we will be seeing [Merck] compounds going into clinical trials in the one-to-two year timeframe," in line with the scale-up of any expression system, Gerngross said. GlycArt, which was spun out of the Swiss Federal Institute of Technology in Zurich in 2000, had developed a method of boosting the antibody-dependent cellular cytotoxicity of antibody-based drugs by overexpressing a particular glycosyltransferase (Nat. Biotechnol. 17, 176–180, 1999). The first such antibody to enter clinical development will be an anti-CD20 antibody that has also been engineered to increase induction of apoptosis, says Klaus Strein, head of pharma research at Roche's site in Penzberg, Germany.