Geneva, 12 May (Sangeeta Shashikant) -- Legal and political opposition in India to the patent application for a key AIDS drug has highlighted a looming problem that patients may increasingly find new medicines unaffordable, not only in India but in many developing countries that rely on Indian-manufactured generic drugs.

On 9 May, an opposition to the patent application on the AIDS drug tenofovir disoproxil fumarate (TDF) was filed at the Delhi Patent Office by The Indian Network for People Living with HIV/AIDS (INP+) and the Delhi Network of Positive People.

They are challenging an application filed by the US-based company Gilead. It plans to file patents in 97 countries by the end of this year.

According to Medicins Sans Frontieres (MSF), Gilead's price for the drug is $5,718 per patient per year and it has not made an offer to make it available at a more affordable rate to middle-income countries such as Brazil, India, Thailand and China.

The Indian generic drug company Cipla makes available a generic version of TDF at one-seventh the international price of the branded product. The company has also registered an opposition to Gilead's patent application.

If, however, the patent is eventually granted, companies like Cipla would not be able to continue generic production, unless it then applies for and is granted a voluntary license by the patent holder or a compulsory license by the government, and royalty is paid.

This is the second patent application on an AIDS drug that is opposed by Indian NGOs. The first opposition was filed on 30 March 2006 by the INP, the Manipur Network of Positive People (MNP), and the Lawyers' Collective HIV/AIDS Unit to a patent application filed in the Kolkata patent office by Glaxo Group Limited for Combivir, a fixed-dose combination of two AIDS drugs (zidovudine/lamivudine, or AZT/3TC).

These groups argued that Glaxo's Combivir (AZT/3TC) is not a new invention but simply a combination of two existing drugs.

In both cases besides the claim that these products are not "novel" or "inventive", crucial criteria that have to be fulfilled prior to enjoying the grant of patent monopoly, the opponents also are concerned that a patent will hamper access to life-saving medicines.

Tenovofir is an important option for patients starting AIDS treatment for the first time, and for those who have been on antiretroviral treatment therapy (ART) for some time and require access to newer drugs due to occurrence of toxic effects or as they develop resistance to first-line drug regimens.

It is argued on behalf of INP that forming a salt (fumaric acid) out of an existing compound (tenofovir disoproxil), is a common practice within the pharmaceutical industry, and thus should not be considered a new invention, and thus the patent application should be rejected.

Medecins Sans Frontieres (MSF), in supporting the Indian NGOs' opposition to the TDF patent application, says it needs to access the drug for its HIV/ AIDS treatment projects around the world.

In its project in Khayelitsha, South Africa, due to difficulty in accessing TDF, only 40 of nearly 4,000 patients, receive the drug. "We need tenofovir for more and more of our patients, but the supply from Gilead has simply been too unreliable, so we can't put more patients on it," said Dr. Eric Goemaere of MSF in South Africa.

"We have all been waiting impatiently to get tenofovir as a generic from India. Our project is a microcosm for what is to come elsewhere, and it is clear [that] the world desperately needs more sources of this essential drug," he added.

Tenovofir is also recommended by the latest World Health Organization (WHO) antiretroviral treatment guidelines in developing countries for use in first and second-line drug regimens in resource poor settings.

It is usually prescribed because of fewer known side effects associated with the use of this drug in adults. Although widely available in the US and Europe, it is mostly unaffordable to the developing world.

According to Loon Gangte, of the Delhi Network of Positive People: "For many of us living with HIV/AIDS, newer drugs like tenofovir offer new hope of continuing treatment. With patents interfering with our lives, we have no choice but to oppose them."

If the patent is granted, it will set a dangerous precedent for global access to newer essential drugs, said Anand Grover, Director of the Lawyers Collective HIV/AIDS Unit.

On 25 January 2006, the Indian patent office rejected Novartis' patent application (related to a particular crystal form of the salt of imatinib mesylate) for its anti-cancer drug imatinib mesylate (Gleevec), on the grounds that the application claims a 'new form of a known substance'.

This was a victory for the Cancer Patient Aid Association of India and some Indian generic companies, which had filed a pre-grant opposition.

Global concerns over access to medicines heightened when in 2005 India, a major supplier of generic medicines for many countries, had to amend its patent law to allow the patenting of pharmaceutical products, due to its obligations under the TRIPS Agreement.

Between 1970 and 2005, the Indian patent law only allowed for the patenting of process but not for pharmaceutical products, an important factor that led to a thriving generic industry in India, with exports to many parts of the world.

The generic medicines were sold at a fraction of the price of the branded versions. With the change in the Indian law, many are worried that access to generic versions especially of newer drugs will be hampered.

Local and international health groups lobbied for some flexibilities within the Indian patent law system and for stricter patentability standards. One outcome is that the patent law allows for opposition to patent applications at the pre-grant stage.

The amended patent law also disallows the patenting of "me too" products (i.e. the patenting of a drug that is structurally very similar to known patented drugs, with only minor differences). This should reduce patents on pharmaceutical products that do not fulfill the standards of novelty and inventive step, both prerequisites for obtaining a patent.

The amended Indian patent law provides several grounds for rejecting a patent. For example, the mere discovery of a new form of a known substance, which does not result in the enhancement of the known efficacy of that substance, is not patentable.

An explanation to the clause states that salts, esters, ethers, polymorphs, metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combinations and other derivatives of known substance shall be considered to be the same substance, unless they differ significantly in properties with regard to efficacy.

Although the law was passed at the beginning of 2005, India had provided a mailbox system (an obligation under the TRIPS Agreement) wherein companies could file their patent application for pharmaceuticals in India from as early as 1995. However, the examination of these applications only started after the revision of the patent law i. e. in 2005.

The patent applications for tenofovir and Combivir are two of the thousands of applications (many pertaining to pharmaceuticals) that are being processed.

On 3 March, the first drug patent following the law amendment was granted to Roche for peginterferon alfa-2a (Pegasys), a new generation hepatitis C therapy.

No company will be able to produce generic version of that drug until 2017, when the patent term expires. Thus the only available drug on the market will be the Roche product which is available at about $5,000 per six month treatment course, which is too costly for most patients in developing countries.

If TDF is patented in India, generic production would be at risk and availability to patients in developing countries would be hampered.

It would then be also difficult or impossible to develop fixed-dose combinations (FDCs, which combine two or three drugs in a single pill), such as TDF/3TC and efavirenz (EFV).

The use of FDC simplifies treatment, and as a result adherence to the treatment increases. However, even if one drug in the combination is patented, it becomes impossible for a generic company to produce the FDC.

For example, even if ARVs such as lamivudine (3TC) and efavirenz (EFV) are not patented, a patent on TDF would prevent Indian generic companies from developing the much-needed FDC, a crucial requirement for combating the problem of HIV/AIDS. +