Tenofovir Disoproxil Fumarate (TDF) is a drug highly recommended by the World Health Organisation (WHO) for the treatment of HIV/AIDS. Till date, the medicine has been mostly marketed by Indian pharmaceutical companies through a voluntary licence scheme negotiated with the California-based Gilead Sciences few years back. Before the product patent regime had been introduced in India in 2005, the country allowed local generic manufacturers to sell cheap versions of Aids drug cocktails, known as antiretrovirals. According to an article penned by Randeep Ramesh in The Guardian (available here), exports by Indian companies had helped to cut the price of antiretroviral treatment from $15,000 per patient per year in the 1990s to as low as $200, thereby resulting into Indian companies providing almost 2/3 of the world’s cheap Aids therapies. Already having a global patent on Tenofovir till 2018, Gilead had sought to obtain a patent in India sometime back. This move (discussions on which can be found in this blog here, and on anti-competitive practices involved here) had been immediately met with large-scale opposition and ire from activist groups and associations such as The Indian Network for People Living with HIV and the Delhi Network of Positive People, who were quick to file pre-grant oppositions against said application (RTI Applications had been filed in this context, regarding which one can know the details from here). According to campaigners, since AIDS patients develop a resistance to “first-line” drugs, there will be no scope for a reduction in prices of second-generation medicines like Gilead’s Viread, which are several times more expensive than older treatments, without the Indian generic drugs. Officials from Gilead had been known to have issued a veiled threat (see here) that unless the patent is granted, the aforementioned licensing scheme with the Indian companies might cease to continue. Apropos, in last April, India’s health minister Anbumani Ramadoss, had issued a statement in reference to a dispute with Novartis, that New Delhi could be forced to overrule patents and issue licenses for firms to produce vital drugs if deemed in the public interest. In developed countries, Tenofovir costs $5,718 per patient per year, while Cipla has been marketing a generic version called Tenvir, at a cost of $700 per person per year in India and expects to make it available in Africa eventually at an even lower price.
A pre-grant opposition essentially allows one to oppose patent applications filed by an applicant and a decision on the patent is given after the Patent Controller’s office hears arguments from different stakeholders. The Patent Office in Chennai had earlier rejected Novartis’ patent on cancer drug Glivec after opposition from cancer-patient organisations, among others. The major legal ground of opposition to the patent application in this case was the argument that TDF is created by the addition of a salt (fumaric acid) to an existing compound (tenofovir disoproxil) and should not therefore be granted a patent.
In this context, publications pre-dating Gilead’s application for TDF had been cited by the opposition, which teach that fumaric acid is a suitable pharmaceutically acceptable salt to use for phosphonate nucleotide analogues and their esters, like TD, in order to achieve better bioavailability and stability. Several science journals have also been indicated to direct how to go about salt selection for basic drugs for optimisation purposes and which specifically mention fumaric acid.
Furthermore, it was also argued that provisions such as Section 3(d) of the Patents Act, 1970, which states that patents should not be granted for known substances (including the salts of the known substance) that do not show improved efficacy, should block Gilead’s application. As it had been simply claiming the salt of TD and the specification filed fails to show any therapeutic efficacy, the application failed to overcome this hurdle. In the light of the Glivec decision in particular, increased/better bioavailability should not equate to efficacy. In addition to the aforesaid arguments, the Alternative Law Forum, which had been representing the Opposition, also brought attention to several procedural flaws in Gilead’s application and misrepresentations in the patent specification regarding the claimed advantages of the invention, in particular as to why the fumaric acid salt performs better than other salts. According to the counsel of the Opposition, the fact that Gilead only demonstrates a comparison against only one other salt, citrate (which would obviously have been known not to work alongside a soluble drug like TD) showed a manipulation of evidence to obtain a patent.
The Patent Office has tended to agree to the aforesaid arguments, when it refused the grant of patent to Gilead in the beginning of this month. However, since Gilead had made several patent applications on the same medicine (for different claims), the generic companies will have to wait for the patent office’s decisions on other pleas before they can launch the product. According to industry sources, Gilead is likely to appeal against the patent office decision.
On an interesting note, this has perhaps been the first time that a foreign advocacy group has been seen working together with Indian NGOs to oppose a medicine patent application in the country. Brazilian AIDS advocacy group Brazilian Interdisciplinary AIDS Association (ABIA) and a local NGO, Centre for Residential Care and Rehabilitation (SAHARA), while filing pre-grant oppositions, had said that a patent in India would have a direct impact on the ability of Brazil to produce and access affordable generic versions of the drug. In 2008, the Brazilian government had declared Tenofovir to be of ‘public interest’ in treating people living with HIV (See here).
On June 30, 2009 the Brazilian Patent Office (INPI) had also issued a final refusal of Gilead’s patent application no. PI 9801145-4 for TDF, although Gilead had already filed divisional application no. PI9816239-0 on March 31, 2009, which is still pending. Brazil’s interest in this matter thus seems to be pretty obvious, since the country will not be able to procure generic versions from India if Tenofovir gets a patent in India. On the other hand, if the patent is rejected, Indian generic companies would be able to supply Tenofovir to Brazil and other middle-income countries. This would also mean Brazil could purchase affordable generic versions of Tenofovir from multiple producers competing against each other.
let me take this opportunity to re-iterate some of my earlier observations regarding the efficacy data, specifications provided by the patent applicants. i wont jump to conclusion and would refrain from commenting on the gilead’s td case, as i am not privy to gilead’s version of the whole affair. but from my personal experience in handling such matters, i can say that (1)on the one hand, interpretation and implementation of section 3(d) requires impartiality/objectivity and even section 3(d) itself needs to be tweaked (may b, somewhat like what shamnad has proposed) to bring about that impartiality, (2)but on the other hand, the pharma mncs, too, need to realise two things, (i)evergreening shall no longer be permitted and (ii)one can no more take the indian patent system for granted (esp. as far as disclosure of data on efficacy and wordings of specifications and claims are cponcerned). regarding the sub-point no.(ii), i have observed from my practical experience that many a times the pharma biggies have taken things lightly and not provided sufficient data on efficacy (despite having them in their possession). mncs need to be careful, esp. in the light of the stricter (or slightly over-zealous/skewed?) interpretation/implementation of section 3(d). the indian patent regime may b right in attempting to prevent evergreening/incremental improvements thru section 3(d), but the limited interpretation of efficacy (“therapeutic efficay”, per novartis judgment) is unfortunate. so, beware pharma mncs, as u ve to bear the brunt of the maturing (e.g. section 3(d)) new indian patent regime, which has some inevitable side-effects (e.g. “therapeutic efficacy”), too.
The author has mentioned above that Gilead has global patent for Tenofovir till 2018. AFAIK there is nothing known as “global patent” or “international patent”. Can somebody clarify me what the author means by ‘global patent’ in above context?