Posted 15 January 2015
By Michael Mezher
Gilead Sciences has been denied a patent for its blockbuster drug Sovaldi (sofosbuvir) in India. India’s patent office rejected the application for the drug due to a lack of evidence that “minor changes in the molecule” substantially improved the drug.
Gilead has not said if it will appeal the decision to reject its patent; however, the door is now open to generic companies in India to produce the drug without licensing.
Sovaldi made headlines in 2014 for both its significant improvement over previous treatments for hepatitis C (HCV) as well as its price tag. At its launch, Sovaldi was priced at $84,000 in the US, a figure that drew the attention of US lawmakers and payer groups. Prices for Sovaldi vary by market; in Germany and the UK the drug launched at the equivalent of $66,000 and $57,000, respectively.
While the price tag for Sovaldi is low compared to many cancer drugs and treatments for rare diseases, which can run upward of $300,000 for a course, the sheer number of patients affected by the HCV has caused payers around the globe to question how they will pay for the drug. The World Health Organization (WHO) estimates there are more than 170 million people with HCV worldwide.
Despite the drug's high costs in western countries, Gilead was poised to make the drug available for far less in India. Gilead announced in September 2014 that it signed voluntary licensing arrangements with seven Indian generic drug manufacturers to produce the drug for sale in India and 90 other developing and middle-income countries. While Gilead planned to sell its branded version of Sovaldi in India for $900, generic manufacturers expected to sell the drug for less. Even at that steep discount, critics questioned whether the drug would be affordable for people in India, where the GDP per capita is only $1499.
Intellectual Property in India
India's patent system has long been a source of controversy.
The United States Trade Representative has included India in its “Priority Watch List” for countries that “present the most significant concerns regarding insufficient [intellectual property rights] protection or enforcement.” The pharmaceutical industry has also been vocal with its concerns regarding intellectual property in India.
India’s current patent system has been in place since 2005. Before then, India’s 1970 Patents Act only allowed for “process patents” for pharmaceuticals whereby a company could recreate another’s product by making changes to the production process. Under the process patent system, India’s pharmaceuticals industry flourished, growing to one of the largest in the world.
Since the Patents Act was amended in 2005, companies have been able to patent the composition of their products. However, a provision of the act designed to prevent the practice of “evergreening,” where a company makes minor changes to a product to refresh its patent protection, has allowed India’s patent office to be strict in awarding patents for drugs. Section 3(d) reads:
"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 or the mere discovery of any new property or new use for a known substance or of the mere use of a known process, machine or apparatus unless such known process results in a new product or employs at least one new reactant [are not inventions within the meaning of this act].”
An explanation is included in the act for this section which reads:
“For the purposes of this clause, 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,”
Section 3(d) has been used to deny drug patents where minor improvements are made and is cited in both the patent office’s decision and the opposition filed against Gilead’s patent application.
Supreme Court Precedent
Gilead's Sovaldi, the patent for which was rejected by India's Patent Office on 13 January 2015, is not the first high-profile drug to be denied a patent in India under Section 3(d). After Novartis was denied a patent for its cancer drug Glivec (imatinib) it appealed the decision by the Indian Patent office in a fight that went to the Indian Supreme Court.
In 2013, the court upheld the decision to reject Novartis’ patent on the grounds that the drug was a newer version of a “known substance.” Furthermore, the court stated Novartis’ claim that the beta crystalline form of imatinib mesylate had 30% greater bioavailability compared to imatinib in free base form did not demonstrate an improvement in efficacy that would make Section 3(d) inapplicable.
In the court decision (par. 180–192), the court established that the efficacy requirement in Section 3(d) means proving that a substance has enhanced therapeutic efficacy.
In its decision to reject Gilead’s patent application (6087/DELNP/2005), India’s patent office refers to the therapeutic efficacy requirement established in the Novartis case. The decision observes that though the changes described in the application make Sovaldi “novel and Inventive,” the application filed by Gilead does not prove its enhanced “therapeutic efficacy” compared to its “closest prior art,” compound D1 (patent WO2001/92282).
The decision goes on, “In other words we can say that a molecule with minor changes in addition to the novelty must show significantly enhanced therapeutic efficacy as compared to the nearest prior art molecule which is structurally and functionally close.” Additionally, the decision states that there was not sufficient data in the application to “prove the improvement in therapeutic efficacy.”
Opposition and Impact
So far the Indian Patent Office's decision has been greeted favorably by some non-governmental organizations.
Dr. Manica Balasegaram, executive director for Médecins Sans Frontières' (MSF) Access Campaign called the patent rejection a “good opportunity … to treat the 185 million people infected with hepatitis C worldwide.”
MSF has been critical of Gilead, and has argued that its licensing program for Sovaldi requires “providers in developing countries to comply with a web of onerous and potentially harmful procedures that aim to preserve Gilead’s ability to charge exorbitant prices in developed countries.”
Other critics took procedural actions against Gilead’s attempt to patent its product in India.
The Initiative for Medicines, Access & Knowledge (I-MAK), which had filed oppositions to key patent applications for Sovaldi, also praised the decision. Tahir Amin, a lawyer and director for I-MAK, said about the rejection: “The bottom line here is that India’s patent law doesn’t give monopolies for old science.”
The opposition filed by I-MAK argued that the claims in Gilead’s application “lack inventive step and do not amount to a technical advance over prior published matter/existing knowledge in the field as they would have been obvious to a person skilled in the art.”
Government of India