The recent USPTO decision to preliminarily hold the U.S patent for Tenofovir Disoproxil Fumarate (TDF) invalid has now also been followed by Brazil.
On 8 April, Brazil's Instituto Nacional da Propriedade Industrial (INPI) published a notice initially refusing Gilead's Brazilian patent application no. PI 9801145-4 for TDF. Coinciding with INPI's notice, Brazil's Ministry of Health issued Ministerial Directive 681, declaring TDF to be in the public interest. According to one source we have spoken with in Brazil, the Ministry of Health's declaration was made without knowledge that INPI had initially refused the patent.
According to IP Watch's report on the story, the grounds for refusal of the TDF patent application under Brazil's Law No. 9279/96 were:
- Article 10 (VIII) - that therapeutic methods for use in humans are not inventions;
- Article 13 - the invention lacks inventive activity and/or is obvious;
- Articles 24 and 25 - insufficiency and that the claims must be based on the specification in a manner that clearly defines the subject matter to be protected.
We understand that the decision of INPI was assisted by observations filed by the local generic company Farmanguinhos, as permitted under Article 31 of the law. According to a translated version of the observations we have seen, Farmanguinhos submitted a number of prior patents claiming the fumarate salt for other medications approved by the FDA that initially had poor bioavailability. As a result Farmanguinhos claimed there was no inventive activity for selecting the fumarate salt for TDF, which was also argued in the opposition we prepared on behalf of Indian patient groups. Indeed, we also raised as a ground of opposition under s25(1)(h)/s8 of the Indian Patents Act the ongoing examination and observations against the TDF patent application in Brazil and Gilead's obligation to keep the Indian Patent Office informed. It remains to be seen how the Indian Patent Office interprets this ground in light of INPI's decision.
Gilead now has 90 days to respond to the refusal issued by INPI. In the event the decision to refuse the patent stands, Gilead can appeal under Article 212 within 60 days of the final refusal.
However, even if the patent is granted by INPI, according to procedure as we understand it, the final decision for the granting of pharmaceutical patents rests with the regulatory body Agencia Nacional de Vigilancia Sanitaria (ANVISA). The controversial role of ANVISA in deciding on pharmaceutical patents was incoporated into Law No. 9279/96 under Article 229 - C and it is understood that the body has hired thirty or more personnel to specifically analyse patent applications. So even if Gilead succeeds in overcoming INPI's objections, it may face a tougher task overcoming ANVISA, given its role in public health matters and the declaration that TDF be in the public interest.
It is also worth noting that unlike in India, Gilead does not appear to have filed a patent for Tenofovir Disoproxil, the intermediate compound. If the patent application for TDF is refused in Brazil, Gilead may rue that decision or oversight.
Relevant to all this is the question who will supply TDF to Brazil if the patent is refused? One source we have spoken with says that Brazilian companies are gearing up to manufacture the drug. The difficult part will be the ability of such companies to manufacture API, something Brazil had fallen behind in recently, but now seems to have been working to improve on.
Notably, the eleven Indian companies that took a licence from Gilead to manufacture API and sell TDF are all locked out from exporting to Brazil under the agreement - the reason being Gilead saw Brazil as a profitable market and chose not to categorise it as a low-income developing country. Cipla on the other hand, the only company in India opposing the Tenofovir patents and who did not take a licence, could emerge from this handsomely if India also refuses the TDF patents and Brazil requires assitance manufacturing API or the end formulation. It will be interesting to see how the Indian licensees of TDF will react to such a scenario.
The fallout from all this is that should the patent not be granted, the Brazilian Government will pay a price that is in parity with other developing countries, which would be around $200 pppy as opposed to the current $1,387. As a result, Brazil's free ARV program will be able to re-allocate savings to other much needed ARVs and drugs.