Patent threat to anti-HIV compounds is lifted

A landmark announcement made in London this week paves the way for researchers to combine different compounds for better protection against infection by HIV — without the fear of conflict over intellectual property rights.

The researchers involved are developing new microbicides. These are gels or creams designed to block the transmission of HIV during sexual intercourse, and are being increasingly seen as one of the most promising ways of combating the global AIDS epidemic.

The International Partnership for Microbicides, a private-public partnership, has now announced that it has acquired a royalty-free licence from the pharmaceutical company Tibotec (a subsidiary of the pharmaceutical giant Johnson and Johnson), to develop, manufacture and distribute an anti-HIV compound called TMC120 as a microbicide.

The move coincides with evidence that TMC120 and other compounds appear to be more effective microbicides when combined rather than used individually, at least in laboratory and animal studies.

If the best microbicide product were to require combining compounds owned by different companies, this could potentially lead to conflict over marketing them as a single formulation. Such is the case, for example, with the antiretroviral drugs used to treat people infected with HIV.

The new move means that this situation has been avoided, at least for microbicide treatment using TMC120. It was welcomed by Peter Piot, executive director of the Joint United Nations Programme on HIV/AIDS in Geneva, who described it in a press statement as “a major milestone in global efforts to develop a microbicide for all around the world, and … a model of the innovative collaboration that is crucial to reversing the AIDS epidemic”.

TMC120 and other ‘second-‘ and ‘third-generation’ microbicides act differently from the ‘first generation’ candidates that are currently entering clinical trials in Africa and Asia. The latter form physical or chemical ‘barriers’ against HIV crossing the wall of the vagina or cervix in women (and also possibly the rectum in men and women).

The new compounds are designed to act with greater precision than the ‘barrier’ microbicides by sticking either to HIV directly (and immobilising it) or to the receptors that the virus normally exploits on cells (thereby blocking infection). Another new class of microbicide is aimed at preventing the virus from reproducing inside cells.

It now seems, however, that the cost of this greater precision is that only one of several entry routes that HIV uses will be blocked with any one agent, and that the most effective treatment will involve using a combination of two or more compounds that work in slightly different ways.

According to Mark Wainberg of McGill University, Montreal, the microbicide researcher who is credited for helping to galvanise the recent growth of the field, TMC120 combines well, for example, with the drug Tenofovir to block HIV infection of cells that have been grown in the laboratory.

Meanwhile, Qinxue Hu and colleagues at St George’s Hospital in London have found that different combinations of antibodies are needed to prevent HIV from latching on to the different cell types that are found in the lining of the cervix. It appears that HIV exploits multiple entry points simultaneously, and each requires a slightly different form of protection.

A further boost to the idea that combining different substances may be the best way forward came from preliminary data presented to the London meeting by John Moore from the Aaron Diamond AIDS Research Center in New York. Moore’s experiments with macaque monkeys suggest that this combined approach provides greater protection against HIV infection.

Wainberg is optimistic that, as a result of the agreement with Tibotec, intellectual property issues will not hinder future work in this direction.

“The International Partnership for Microbicides, having licensed-in TMC120, has done a very nice thing which has the potential to make us go forward, which would be great,” he says. He adds that he is “100 per cent in favour of access” for people everywhere, regardless of patents.