The nanoparticle, which targets tumour cells while evading the body's immune system, promises to deliver larger and more effective doses of drugs to cancers, while simultaneously sparing patients many of the distressing side-effects of chemotherapy.

Animal studies have indicated that the treatment can shrink tumours "essentially to zero", while being better tolerated than conventional cancer treatments. Final toxicology studies are about to begin.

A trial involving about 25 cancer patients is scheduled to start within a year. If successful,it could lead to a licensed drug within five years.

Although the therapy was originally designed for prostate cancer, it is expected to be effective against other solid tumours, such as forms of breast, lung and brain cancer. Patients with some of these cancers, as well as prostate cancer, may be included in the first trial.

The technology, developed by BIND Biosciences, a company based in Cambridge, Massachusetts, should also be suitable for delivering drugs for treating other conditions, as well as for the chemotherapy agents that it has been set up to carry.

"This should be the first targeted nanoparticle delivering a chemotherapeutic to enter clinical trials," Jeff Hrkach, the company's vice-president of pharmaceutical sciences, said. "We're then looking to develop this as a broad platform that could also be used to treat cardiovascular disease, inflammation, even infectious disease."

The nanoparticle, known as BIND 014, is designed to solve three of the major challenges in drug delivery: how to ensure therapeutic molecules get to the right place in the body, how to release them slowly over several days, and how to keep the body's immune system from recognising them as foreign and destroying them.

It does this by packing drugs inside a "special delivery parcel" developed by Robert Langer, of the Massachusetts Institute of Technology, and Omid Farokhzad, of Harvard University, who founded BIND Biosciences.

This nanoparticle's diameter is 1,000 times smaller than that of a human hair, measuring about 100 nanometres - or one ten-millionth of a metre - across. It has four elements, the first of which is its payload, a common chemotherapy drug called docetaxel or Taxotere.

The docetaxel molecules are enclosed in a matrix made of a biodegradable polymer known as polylactic acid, which breaks down slowly over several days so that the drug is released gradually. This means that a single injection of nanoparticles can have a long-lasting effect.

This drug-filled "warhead" is then covered with a "stealth coating" of polyethylene glycol, which helps the particle to hide so that it is not attacked by elements of the body's immune system such as antibodies and macrophage cells. Normally, nanoparticles for drug delivery risk being recognised by the immune system and destroyed.

"Regular nanoparticles struggle to get through to tumours," Professor Langer said. "They get eaten by macrophages. By containing the drug within this molecule, we can avoid the macrophages."

The final element of the particle is its smart targeting system, in the form of special enzymes attached to the outer coating known as targeting ligands. These are designed to bind to a molecule found on prostate cancer cells called prostate-specific membrane antigen (PSMA), so that the particles accumulate at the site of tumours before releasing their drugs.

"It's an anchor, rather than a homing beacon," Dr Hrkach said. "If we do things right and get it to the tumour, when the particles get there they stay there.

"What's different about this delivery system is that we believe we can very explicitly target the disease site, while also protecting the nanoparticle from the body's immune system. You can get a high concentration at the site of the tumour and a lower concentration everywhere else.

"By virtue of doing that you're not exposing the body to the side-effects of chemotherapy so much, while at the same time getting larger doses of drug to the tumour."

Professor Langer said: "We've created a nanoparticle decorated with two molecules, one of which helps it to dodge the immune system, while the other helps it to target cancer cells."

The drug has been successfully tested against human prostate tumours grown under the skin of mice, in studies that have shown both that the drug accumulates around tumours and reduces them in size. "It's shrunk tumours in animals essentially to zero," Professor Langer said.

As the PMSA molecule targeted by the nanoparticle is also found in the blood vessels grown by many other solid tumours, it should be suitable for treating other cancers.

"We think that going after that same targets with that same drug, we can not only go after prostate cancer but a considerably long list of other solid tumours," Dr Hrkach said. "The plan is to start clinical trials in the third quarter of next year. We're now transferring our efforts to manufacturing enough material for a clinical study."

Battle against a common killer

• Prostate cancer is the most common cancer among men in Britain; it was diagnosed in 35,000 men in 2006

• About 10,200 men die of the disease each year

• Seventy per cent of men with newly diagnosed prostate cancer survive for at least five years

• About 60 per cent of cases occur in men over the age of 70

• It is usually diagnosed by digital rectal examination and/or a test for prostate-specific antigen, a protein, followed by a biopsy

• Treatments include surgery, chemotherapy, radiotherapy and hormone therapy

• Scientists have identified about two dozen genes that affect the risk of prostate cancer

• Sufferers have included Francois Mitterrand, the former President of France; Rudy Giuliani, the former Mayor of New York; Dennis Hopper, the actor; Frank Zappa, the singer; John Kerry, the former US presidential candidate; Linus Pauling, the scientist; and Nelson Mandela

An article, by Matthew J. Higgins of the Georgia Institute of Technology and Stuart J.H. Graham of the University of California, Berkeley Law School suggests that the current Hatch-Waxman regime having a 5-year data exclusivity term and provisions for generic drug companies to challenge innovator drug patents is responsible for the dramatic drop-off in new small molecule drugs (from an average of 35 in 1996-2001 to 20 in 2002-07), and that the solution is to increase (indeed, double) the data exclusivity term for conventional drugs to 10 years, consistent with trends in Europe, Canada, and Japan

The authors start by reviewing the economic incentives for generic drug challenges to innovator drug patents. The biggest factor is the 180-day exclusivity period awarded to the generic challenger that is the first to file an Abbreviated New Drug Application (ANDA). The authors estimate that the average revenue garnered by a generic during this period is $60 million, which is 12 times the average cost of ANDA litigation ($5 million). This differential exists because during that 6-month period the first successful generic challenger can price the generic substitute just below the brand-name drug price (representing a "savings" to consumers). This potential windfall has motivated generic companies to engage in "prospecting" by filing numerous ANDAs with Paragraph IV certifications (that the patent protecting the innovator's drug is invalid). This conclusion is supported by a review of the number of ANDA lawsuits filed over the past ten years:

A total of 749 lawsuits have been filed challenging innovator drug patents during this period, involving 243 brand-name drugs. The authors note that the FTC has shown that "72% of Paragraph IV challenges filed between 1992 and 2000 resulted in litigation, with the generic drug challenger winning 42% of the time," citing Generic Entry Prior to Patent Expiration: An FTC Study (FTC, Washington, DC, 2002). Moreover, the drugs challenged in recent years have revenues of less than $100 million, showing that "blockbuster" drugs are no longer the only targets of Paragraph IV challenges.

The economic effect on innovator drug companies is large, averaging about a 12% loss in revenue. This loss "exceeded companies' gains from the patent extensions awarded to them," according to the authors, an outcome that is ironic considering the policy "balance" of the Hatch-Waxman regime between reducing the time needed for a generic drug to reach the market after innovator patent expiry and restoration of patent term lost to the period of regulatory review. Using Merck's Fosamax as an example, the authors state that Teva's successful Paragraph IV challenge permitted generic competition 4 years before Merck's patents were to expire, costing the company about $1.5 billion. (Teva is reported to have 160 pending ANDA filings and to be involved in 92 Paragraph IV challenges, "putting at risk over $100 billion in sales," citing Teva's Securities and Exchange Commission Form 20-F filing in 2007.) This lost revenue represents the cost of bringing two new drugs to market in the U.S.
As a result, innovator pharmaceutical companies are motivated to produce new branded drug offerings that bolster their existing franchises subject to generic challenge. However, these are not "new" drugs, but rather are predominantly reformulations representing only "marginal improvements" over existing forms of these drugs. The rate and number of successful Paragraph IV challenges is also reducing the average effective patent life for innovator drugs, particularly "blockbuster" drugs which remain the most attractive targets for Paragraph IV challenge (and the correspondingly higher value of the 180-day generic exclusivity term).
The authors suggest as a solution changing the data exclusivity term under the Hatch-Waxman act from 5 years to 10 years, using a comparison with other "Western" countries as justification:

Citing Professor Grabowski's research, as well as a report from the National Academies of Science and Engineering and the Institutes of Medicine (Rising Above the Gathering Storm: Energizing and Employing America for a Brighter Economic Future (National Academies Press, Washington, DC, 2007), the authors assert that extending the period of data exclusivity is necessary to overcome the "market failure" in the pharmaceutical industry caused by the Hatch-Waxman Paragraph IV challenges of patents on innovator drugs. While they also suggest other regulatory incentives for drug development in particular areas (such as Alzheimer's disease and osteoarthritis), "[a]t a minimum, we should all note that Paragraph IV challenges are contributing to this failure when discussing the future of health care and long-term access to new treatment."
The irony of this report will not be lost on anyone following the data exclusivity period debate over follow-on biologics, and the authors' conclusions provide a direct challenge to those advocating a shortened term for biologic drugs based on the "successes" of the Hatch-Waxman regime for small molecule drugs.