PCT Portraits

More than 1.2 million international patent applications covering new technology of every description have been filed since the Patent Cooperation Treaty (PCT) began operating in 1978. Continuing our series of snapshots, WIPO Magazine dips into the database of PCT applications and seeks out the people behind the patents. In this edition we find three very different inventions with medical applications.

Nobel Prize for the Silence of the Genes

At 4:40 am on October 2, 2006, Craig Mello in Massachusetts was going back to bed after checking his diabetic daughter’s blood sugar level when the phone rang. At a similar hour in California, Andrew Fire was woken by what he assumed was a wrong number call. The phone calls – from Sweden – informed the two scientists that they had been jointly awarded the 2006 Nobel Prize for Medicine.

In 1998 Dr. Craig Mello and Dr. Andrew Fire discovered a fundamental mechanism for controlling the flow of genetic information in living cells, solving a puzzle that had baffled scientists in different disciplines for years. They found a way to silence - or switch off - specific genes by disabling the gene's "messenger" RNA molecules. RNA (ribonucleic acid) is similar to DNA, but more active and performs many of the cell’s more difficult tasks, such as instructing a gene to produce a protein. It is by making proteins that an individual gene produces its effect. By silencing this effect, it is possible to identify the function of specific genes.

In the few years since they published their findings, RNA interference has become an essential research tool with multiple applications. In his interview for Nobelprize.org, Dr. Fire cited a study in Holland, "where they used RNA interference to characterize a given tumor type. Once they figured it out they said, ‘You could treat this with aspirin!’" Biomedics are also now using RNA interference to try to switch off disease-causing genes, with the aim of developing a new class of pharmaceuticals with the potential to treat diseases from diabetes and flu to AIDS and cancer.

Andrew Fire, who was working at the time for the Washington-based Carnegie Institution, and Craig Mello, at the University of Massachusetts Medical School, did their groundbreaking experiment in a tiny worm, the C. elegans. They found they could block the effect of a specific gene by injecting worms with a double-stranded RNA. A friend and colleague of Andrew Fire’s, geneticist David Schwartz, recalls the hours of unglamorous labor that went into the research: "I'd be working in the middle of the night and Andy would be hunched over his microscope next door, feeding his worms. He had to push food their way with a tiny brush."

Both scientists stress that they provided just one key piece of a jigsaw to which numerous researcher had contributed throughout the world. "Science is a group effort," Andrew Fire told reporters.

Andrew Fire, Craig Mello and their research colleagues filed PCT applications in 1998 and 2000 for "genetic inhibition by double stranded RNA" and for "RNA interference pathway genes as tools for genetic interference."

More information: http://nobelprize.org/ 

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A peptide derived from the venom of the king cobra may produce a pain-killer several times more potent than morphine.  (Courtesy of Peter Mirtschin, Venom Supplies Pty Ltd.)

Pills from Poisons

Take one part venom from the rough-scaled snake; mix with scientific brains from the National University of Singapore (NUS); pass through a well-oiled technology transfer office; and sprinkle liberally with entrepreneurial flair. The result? Pro-Therapeutics, a Singaporean start-up company, set up to develop novel therapeutic drug products based on peptides derived from animal toxins.

Among the products in the pipeline are a pain-killer peptide derived from king cobra venom, which has analgesic properties said to be several thousand times more potent than morphine; an anti-coagulant peptide, derived from the venom of the Australian rough-scaled snake, which prevents the formation of blood clots; and an anti-angiogenic peptide which inhibits the spread of blood vessel cells, for treatment of cancers and eye diseases.

Professor R. Manjunatha Kini, a protein chemist at the NUS Department of Biological Sciences, is the company’s chief scientific officer and a co-founder. Well attuned to the value of intellectual property, he has had seven PCT applications published in the last eight years.

Professor Kini’s fascination with poisonous snakes stemmed from a childhood spent in India. This was to inspire his life’s work, devoted over 27 years to studying venom from some of the world’s most lethal reptiles in a quest for new ways to fight human afflictions. "Snake venoms are unique cocktails of pharmacologically active proteins and peptides," Professor Kini explains. "Some of these toxins help us in deciphering the molecular mechanisms of normal physiological processes. Some can also help in developing therapeutic agents for the treatment or prevention of human diseases."

But the nature of these proteins is such that, to date, they have been limited to use in treatments delivered by injection. Now, using patented technologies licensed from the NUS, the Pro-Therapeutics team is working to re-engineer the proteins in order to produce small novel peptides that can be administered as pills. The breakthrough, when it comes, will open up a growing market for peptide therapeutics estimated in 2003 at US$9 billion.

More information: www.protherapeutics.com

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"You won’t feel a thing.." (Courtesy of Terumo Corporation)

Metal Magician Meets Engineering Wizard

A hypodermic needle so fine that it makes injections pain-free. This was the challenge proposed by the Tokyo-based medical equipment manufacturer, Terumo Corporation, with the goal of alleviating the daily discomfort of insulin injections for diabetic children. It was met by bringing together Terumo’s engineer, Tetsuya Oyauchi, who has a string of patents to his name for medical syringes, and Masayuki Okano, the 73-year old head of a small metal pressing factory.

The usual method of manufacturing needles is to hollow out a tiny cylinder of metal. But the thinner the cylinder, the more difficult this procedure becomes. Terumo Corporation’s quest for an ultra-thin needle had been turned down as impracticable by a string of large metalwork firms, before they turned to Mr. Okano, whose skilled craftsmanship, Web Japan reports, had earned him a reputation as a metalwork magician.

"I thought if no one else can do it, I will," said Mr. Okano. He tried a different approach, defying experts who had advised him that it was not possible. Taking a super thin sheet of stainless steel, he rolled it into a tiny tapered cylinder, then sealed it by welding the seam.

Refined and developed with the medical engineering expertise of Tetsuya Oyauchi, Terumo’s PCT application for a tapered "injection needle and liquid-introducing implement" was published in 2004. The resulting product, the Nanopass 33 syringe, went on the market in July 2005. Terumo claims that the tip, which measures just 0.2 millimeters across - no wider than two strands of hair - is 20 percent thinner than conventional needles, and that it reduces discomfort to no more than a mosquito bite.

The Nanopass 33 needle was awarded the 2005 Grand Prize for Good Design by the Japan Industrial Design Promotion Organization, winning the award by a wide margin of votes. "It is fun to make something that doesn’t exist in the world," commented Mr. Okano.

More information: web-japan.org/trends/science/sci051220.html

By Elizabeth March, WIPO Magazine Editorial Staff, Communications and Public Outreach Division