Peptech celebrates as US anti-TNF patents secured

Sydney biotech company and antibody specialist Peptech has secured a prize patent for its anti-TNF antibody technology in the United States, the world's most lucrative market.

The US Patent and Trademark Office this week advised Peptech that it will issue Patent No 6,451,983, titled "Tumor Necrosis Factor Antibodies" to the company on September 17.

The announcement represents the full fruition of a far-sighted decision by the company in the late 1980s, when it decided to cease in-house research on tumor necrosis factor.

TNF is a potent intracellular signalling molecule that originally came to light because of its key role in an immune-system surveillance system that detects and destroys potentially cancerous cells and tissues.

It the time, the technology did not exist to produce human monoclonal antibodies; repeated use of "alien" mouse anti-TNF antibodies could have provoked potentially lethal anaphylactic shock in cancer patients.

In shelving the anti-TNF antibody project, the company decided to apply for a patent all antibodies, including custom-designed antibody fragments, capable of neutralising the activity of TNF.

In the 1990s, TNF was recognised as a major player in multiple, common auto-immune disorders, including rheumatoid arthritis, the skin disorder psoriasis, inflammatory bowel disease, or Crohn's disease. Peptech found itself in possession of what was, in effect, a master patent covering the therapeutic applications of antibodies for a growing list of auto-immune disorders involving TNF.

Peptech already receives a royalty stream from sales of anti-TNF monoclonal Remicade, developed by Johnson and Johnson subsidiary Centocor. Remicade is sold in Australia, Canada, France, Germany, Italy and Switzerland and the UK, and is the world's biggest-selling antibody-based therapy for rheumatoid arthritis and other auto-immune disorders.

Germany's Knoll AD, now owned by Abbott Laboratories, expects to receive approval to market its rival anti-TNF therapeutic D2E7 next year.

The US patent will generate a huge increase in Peptech's revenues, initially from Remicade, and next year, from D2E7. MD Stephen Kwik says global sales of Remicade alone are predicted to be $US1.3 billion in 2003, and the US market is likely to account for $US1.2 billion of that figure.

"This s a very significant development for the company," said Kwik. He says the revenues are likely to take Peptech into profit next year, after the company announced a half-year loss last March of $4.6 million, although it will not affect the anticipated loss for the current financial year, ending September 30.

Kwik says Peptech is keen to begin developing second-generation anti-TNF therapeutics based on new, single-domain antibodies developed in collaboration with UK-based antibody-engineering company Domantis.

Domantis - originally launched last year as Diversys - was founded by Cambridge University research Dr Greg Winter, the inventor of "humanised" mouse antibodies, and so-called phage antibody technology, which uses a process akin to Darwinian evolution to rapidly custom-design antibodies for virtually any therapeutic target, or to neutralise toxins.

Peptech invested in the launch of Domantis last year, and will increase its shareholding to a third next April. Under its agreement with Domantis, Peptech has acquired the right to use Winter's third-generation technology for producing single-domain antibodies, and to nominate four of its own therapeutic targets.

Single-domain antibodies are tiny, cut-down molecules that consist solely of the "sharp" end of conventional antibodies - the grasping, finger-like projections that mould themselves to the shape of the target molecule, or antigen.

Being much smaller than MABS, single-domain antibodies can penetrate cavities and crevices in large molecules that are normally inaccessible to the immune system, and to conventional antibody-based therapeutics.

Peptech has already nominated one of its four therapeutic targets, and Domantis is has made significant progress in its development - Kwik says this first single-domain therapeutic will again be directed at a TNF-related disorder.