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Larry Gold, Craig Tuerk

Important screening process used in biochemistry to find unique oligonucleotides capable of binding to specific proteins that cause disease

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Preiskategorie
Außereuropäische Staaten
Technisches Gebiet
Biotechnologie
Firma
NeXstar Pharmaceuticals
The inventors discovered that nucleic acids can bind to a protein to potentially intercept proteins that cause disease.

European Inventors of the Year 2006 in the category "Non-European countries"

Larry Gold and Craig Tuerk (NeXstar Pharmaceuticals, Boulder, USA) with their SELEX technology invented an important screening process used in biochemistry to find unique oligonucleotides capable of binding to specific proteins that cause disease. This pioneering invention led to an aptamer or drug called Macugen which has eye treatment applications and is due to be approved in Europe in the coming weeks. It is hoped that SELEX technology will also result in drugs for cancer therapy and prove useful in the fight against AIDS.

Getting a Grip

For sufferers of age-related macular degeneration – the leading cause of blindness in people over fifty – the discovery American scientists Larry Gold and Craig Tuerk made in a Colorado University laboratory in 1989 may be life altering.

Gold and Tuerk developed a process which they would name Systematic Evolution of Ligands by Exponential Enrichment. SELEX (Patent EP0533838, date of publication and mention of the grant of the patent December 3, 1997) was the discovery that nucleic acids could bind to any protein, and therefore potentially bind to and intercept proteins that cause disease.

Sixteen years later, Macugen (pegaptanib sodium injection) was launched in the US, and as of February 2006 it is legally deliverable as an approved drug in Europe. The drug – which uses Gold and Tuerk’s discovery – slows or sometimes even halts “wet” age-related macular degeneration by blocking an essential signal that causes abnormal blood vessels in the eye to grow and leak. It is these leaking, or “wet,” blood vessels around the centre of the retina that cause blind spots and blurred vision in AMD sufferers.

“It’s a very significant step forward because it treats a patient group for which there is no currently recommended treatment,” said Adnan Tufail, a consultant ophthalmologist at Moorfields in the United Kingdom, the largest specialist eye hospital in the world. He noted that the closest existing treatment, Verteporfrin, works for only one quarter of the sufferers whereas Macugen could potentially treat everyone.

While there is much interest in the drug from eye doctors, it was initially hoped – back in that Colorado laboratory, and in the companies which Larry Gold subsequently formed – that SELEX would lead to drugs to treat cancer and AIDS. However, scientists working at Gold’s NeXagen company (which later became NeXstar Pharmaceuticals) found it difficult to create an aptamer (a molecule that can bind to another molecule) that was both cost-effective and would behave as they wanted.

Meanwhile, venture capitalists Warbug Pincus pressured Gold to develop applications which could potentially yield greater returns, and that meant high- profile diseases such as cancer. It wasn’t until Gilead acquired NeXstar in 1999 and teamed up with (OSI) EyeTech that the push to use the breakthrough as the basis for an AMD treatment really began. During its first ten weeks on the American market (OSI) EyeTech was showing a gross product revenue for Macugen of $25.4 million.

“In just ten weeks, we believe that Macugen has changed the treatment paradigm for neovascular age-related macular degeneration,” claimed Eyetech CEO David Guyer in the company’s 2005 (first quarter) financial report.

The Bull Market Biotech Investor, which publishes long-term investing advice, is slower to jump on the bandwagon, stating: “Some analysts have projected that Macugen sales may reach $1 billion per year, which appears to be an aggressive estimate for a drug that only addresses the wet form of AMD.”
With Macugen trials across Europe now complete and its EMEA approval secured, it is now down to local agencies in each European country to decide whether the costs and benefits of the drug make it feasible for their particular territory.

“Various (European) countries at various points over the next year will gain access to Macugen,” said Elisa Artime, a Macugen representative in the UK.
And with the first patients in Britain already receiving treatment, it looks as though Europeans will soon know whether Macugen really is the revolution in AMD treatment that many hope it will be.

Meanwhile, the two inventors have taken very different career paths since their discovery: Tuerk left NeXagen in 1994, many years before his invention would ultimately lead to Macugen. He currently teaches biochemistry and genetics at Kentucky’s Morehead State University.
His colleague, Gold, is the founder of SomaLogic, where he continues his work on aptamers. Dr. Gold was made a member of the American Academy of Arts and Sciences in 1993, and the National Academy of Sciences in 1995.

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