LONDON - UK start-up company Evolutec Ltd. expects to succeed in patenting a broad range of novel immune-modifying proteins derived from the saliva of ticks, after receiving its first notice of acceptance.

The notice, from the New Zealand patent office, covers all vasoactive amine-binding proteins obtained from the saliva of all blood-feeding ectoparasites, and from the saliva or venom of snakes, scorpions and spiders.

The molecules have wide therapeutic potential, influencing inflammation, hemostasis - including blood clotting and dilation of blood vessels - and immune response. To date Evolutec has identified 100 molecules and progressed six into development.

CEO Clive Bennett told BioWorld International that unlike smash-and-grab parasites such as mosquitoes or horseflies, which feed and flee, ticks spend a leisurely two weeks taking a meal of blood. "Ticks are long feeding and need to control immune responses for a long time. For example, they need to prevent coagulation. Ticks have the means to hide from the host's immune system, a stealth approach that requires them to secrete a very sophisticated armory of immune-modifying proteins."

Bennett views the notice of allowance as the first external validation of the originality of the company's discovery research. It has filed similar patent applications in 26 countries, with no significant objections to date. Although most of Evolutec's work is on tick saliva, it has filed for rights in other organisms it believes secrete similar proteins.

Evolutec, which operates as a virtual company, expects to start clinical trials of its two lead compounds before the end of 2000. They both are from a new class of compounds, discovered by Evolutec, called histocalins. These bind free histamine. The first trial will be in allergic conjunctivitis, the second in asthma.

The company, based in Oxford, was set up in 1998 with venture funding of #1.8 million (US$2.7 million). Bennett, who joined at the start of 2000 from Hoechst Marion Roussel (now Aventis), is now raising the next round of financing. "The aim is to get enough to last one and a half to two years. In that time we should further the science and get into some partnerships."

Evolutec's platform technology enables it to isolate biologically active compounds and identify the genes that code for these molecules. The technology derives from research by Pat Nuttall, a professor at Oxford University and head of the Centre for Ecology and Hydrology. The government-funded center, formerly called the Institute of Virology and Environmental Microbiology, has an equity stake in Evolutec.

Nuttall's original focus was on the transmission of viruses carried by ticks, leading her to study the privileged environment viruses find at the tick-host interface. "This led to investigation of how the tick generates this immuno-privileged site. It turns out that the tick is able to modify a whole variety of immune reactions," Bennett said. Tick salivary glands are of equivalent size to lungs in humans.

Apart from histocalins, the molecules isolated include tryptases and serocalins. "We are in the opposite position to most biotech companies in that we have more leads than, as a small company, we can exploit," Bennett said. He expects to find very early stage partners for some of these.

Evolutec has an investigator in the U.S. with a well established clinical trials protocol for allergic conjunctivitis. "We expect this to go through more quickly than usual because of the well established protocol," Bennett said. "In asthma, the company will work with a number of centers in the UK and overseas. The animal work is extremely interesting, although, of course, until it is in man you don't know what will happen. We believe our compound may be able to deal with all types of asthma because it works across the cascade of events."

The company also intends to develop DNA vaccines against a variety of human diseases, including Lyme disease, that are carried by ticks. The work also will be applied in animal health.