By Tatum Anderson for Intellectual Property Watch
Indian generic manufacturers may be allowed to export a cheaper HIV/AIDS treatment to middle-income countries if US pharmaceutical company Gilead fails to win a patent for the drug in India. And a turnaround by the United States on the same patent may influence the outcome.

Currently, the largest Indian generic companies are prohibited from supplying a drug called tenofovir or its constituent materials to middle-income countries like Brazil, Thailand and China.

That is because in 2003, Gilead launched a special programme which seeks to provide tenofovir at cost to the poorest countries in the world. It later struck several special deals with Indian generic manufacturers, called voluntary licences, allowing them to copy its drug and sell tenofovir at reduced prices to patients in these countries.

But crucially, the voluntary licences contained provisions that prevent exports to countries not classed as the poorest states in the world. Despite that, many manufacturers, including Ranbaxy, opted for Gilead’s voluntary licenses in 2006. As a result, only one major Indian generic manufacturer, Cipla, is currently legally able to export to Brazil because it refused to sign up for a voluntary licence.

The voluntary licences are particularly controversial, because there are no actual patents for tenofovir in India.

This month, however, the Indian patent office is expected to begin reviewing Gilead’s application for patents on tenofovir. If it rejects the applications, there might be profound effects across the world, however. Gilead has told Intellectual Property Watch that the provisions preventing export to middle-income countries might no longer apply if it failed to win a patent.

A Gilead spokesperson said: “If Gilead does not gain patents in India we would not enforce our agreements with the Indian generic companies.”

The company adds, however, that patents on tenofovir in middle-income countries like Brazil would prevent them from importing generics anyway.

Not surprising then, that public health groups in both India and Brazil want Gilead’s patent applications in both countries to be rejected. Gilead also has applied for a patent in Brazil.

Several groups in India have already used legal tools to oppose Gilead’s patent applications in the last two years, for instance. The Indian Network for People Living with HIV/AIDS (INP+), the Delhi Network of Positive People (DNP+), Indian NGO Sahara, which provides residential care for AIDS sufferers and Indian pharmaceutical company Cipla have all filed so-called pre-grant oppositions to the Indian patent office.

These formal documents, which detail why a patent should not be granted, argue that the drug is not novel enough to warrant a patent under Indian patent law – the same grounds used by the Indian patent office to reject Swiss pharmaceutical Novartis’s controversial patent application for cancer drug Glivec last year and German company Boehringer Ingelheim’s AIDS treatment nevirapine last month.

Health Groups Take Steps

More recently, health groups have been taking drastic steps.

Last week, a Brazilian AIDS advocacy group even filed a legal opposition to Gilead’s patent application in India. The Brazilian Interdisciplinary Aids Association (ABIA) asked the Indian regulator not to grant a patent to the US pharmaceutical company in an attempt to enable Brazil to make the drug available to those who cannot afford it.

Brazilian activists say an Indian tenofovir patent would prevent Brazil from importing tenofovir or its constituent components from Indian generic companies, either because of the voluntary licences or because the patent would prevent manufacture of cheaper, generic copies or intermediates.

Tenofovir is so expensive, that despite its classification as a middle-income country, Brazil cannot afford to provide universal AIDS treatments, activists say. As reported previously in Intellectual Property Watch, the annual cost of this antiretroviral in Brazil is U$1,387 per patient per year. In contrast, India produces generic tenofovir for US$158 per patient per year.

Activists are supported by charities like Médecins Sans Frontières, which say the drug sometimes can be priced at an unreasonably high level and there can be significant variation in the cost. For instance, Brazil, South Africa (and Thailand) have similar gross domestic products but tenofovir costs six times more in Brazil than South Africa.

For its part, the originator pharmaceutical industry says patents are essential tools to ensure it can invest in developing new treatments. It has been aggressive in lobbying to prevent middle-income countries from benefiting from low-price drug schemes aimed at the poorest countries.

Gilead says tenofovir, which is seen as important treatment that is recommended by both the US and World Health Organization (WHO), should be patented. A spokesperson said, “We believe Viread [tenofovir’s brand-name] represents an important scientific and medical innovation.”

Decisions by India and Brazil to grant Gilead patents depends on their own assessments of novelty but also a crucial decision being taken currently in the United States.

Gilead has filed applications for three patents related to tenofovir in India; one for the drug whose full name is actually tenofovir disoproxil fumarate (TDF), another for the intermediate compound used to make TDF, named, tenofovir disoproxil (the compound tenofovir disoproxil is chemically altered to create what is called a salt). The last patent is for a chemical method that is not being contested.

Opponents claim that neither the intermediate nor final product, TDF, is inventive enough to be patentable. Indeed, under section 3(d) of the Indian Patent Act, which states that salts and esters of known substances are not patentable unless they can show an enhancement of efficacy.

Tahir Amin, a lawyer at I-Mak, a non-profit group which drafted the pre-grant opposition document for INP+ and DNP+ in 2006 said, “Claiming whether salt is something inventive strikes at the heart of section 3(d) in India.”

He said Gilead has overstated the therapeutic improvement gained by creating tenofovir disoproxil or converting it to TDF, for instance. These improvements are not sufficient to warrant a patent, he said.

US Decisions Affecting Global Outcome

However, events in the United States threaten to affect India’s decision.

At the end of January 2008, the US Patent and Trademark Office (USPTO) revoked four patents related to tenofovir and held by Gilead in US. The decision came after a US public interest group, Public Patent Foundation (PUBPAT) claimed prior art exists that should have prevented those patents begin granted in the first place.

However, Gilead has appealed the decision and by June this year USPTO had re-examined two of the four patents and changed its position, saying they were in fact patentable. It has yet to finish re-examining the final two patents.

The outcome of the final two patents is of immense importance to Gilead, India and Brazil. That is because they correspond to patents Gilead is trying to win in India and Brazil.

If the USPTO re-examines the final two patents and decides to uphold them, its decision could have profound implications.

“If the patents are all granted in the US, we understand Gilead will use these decisions to lean heavily on the Indian and Brazil patent offices,” said Amin. “Indeed, I think this is already happening in Brazil.”

Tatum Anderson may be reached at info@ip-watch.ch.