Nature reviews. By Bhaven N. Sampat and Kenneth C. Shadlen. Patent protection for drugs in India has been a contentious issue in recent years, with several high-profile denials of patents — for example, for Novartis’ anticancer drug imatinib mesylate (Glivec; also known as Gleevec).
Much of the debate around pharmaceutical patenting in India has focused on a particular provision — Section 3(d) — of the Indian Patent Act, which was introduced in 2005 as part of India’s implementation of the World Trade Organization’s Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS). It has been argued that Section 3(d) makes it difficult to obtain patents for new drugs in India (Health Affairs 33, 1567–1575; 2014; and see the 2015 Special 301 Report in Further information), which has led to numerous calls to overturn or rethink this provision. Here, however, we argue that the attention paid to Section 3(d) may be misleading and that another element of India’s TRIPS implementation may be more relevant to the current pharmaceutical patenting landscape in India.
TRIPS, which entered into effect in 1995, requires countries to grant pharmaceutical product patents. Prior to this time, few developing countries did so. In complying with TRIPS, India took steps that aimed to ameliorate the feared effects of pharmaceutical patenting on access to medicines. One of these steps was the inclusion of Section 3(d), which aims to curb the granting of patents to new forms, compositions and uses of existing substances — so-called ‘secondary patents’. Secondary patents are legally more vulnerable, not only in India but globally. For example, in the United States, most secondary patents are overturned when litigated to completion (Science 339, 1386–1387; 2013). Indeed, in the case of Glivec, the secondary patent was the subject of a US patent challenge (Science 337, 414–415; 2012). This challenge resulted in a settlement that allowed generics to enter the market nearly immediately upon expiration of the compound patent, suggesting that Novartis had less than full confidence in the secondary patent in the United States (FiercePharma, 15 May 2014).
While Section 3(d) has attracted considerable attention, another aspect of India’s TRIPS implementation was to disallow any patents with a priority year (that is, the year of first global filing) before 1995. During the TRIPS negotiations, pharmaceutical companies lobbied to make patent protection on pre-1995 molecules mandatory, arguing that not doing so would substantially delay the commercial benefits from TRIPS (The Pharma Marketletter, 22 May 1995). These attempts failed.
How important is the 1995 cut-off date? Assuming that the earliest patent for a drug is its compound patent, the majority of the 430 drugs with patents approved by the US Food and Drug Administration (FDA) between 1995 and 2013 had their first patents filed before 1995 (Fig. 1a). Even among the drugs that have been approved since 2010, nearly a quarter (24%) had their first patents filed before 1995 (Fig. 1b). A total of 23 of these 430 drugs ranked among the top 50 drugs by 2012 US sales, and 20 of those 23 compounds had pre-1995 priority dates (see Supplementary information S1 (table)). Pre-1995 compound patents are not eligible for protection in India, regardless of Section 3(d) or any other features of the post-2005 Indian pharmaceutical patent system.
Drugs with pre-1995 primary patents must rely on ‘weaker’ secondary patents as their only form of protection in India, as illustrated by the Glivec case. Novartis’ compound patent had a priority date of 1992 (Fig. 1), so was not eligible for protection in India. The company’s application for a secondary patent, covering a crystalline form of the 1992 compound, was rejected in India on the basis of Section 3(d) and other grounds. As a result, Novartis was left with no patent protection at all in India for Glivec.
The outcome in the Glivec case has been interpreted as evidence that Section 3(d) makes patenting in India too hard; if even a drug like Glivec is unable to obtain patent protection in India, something must be wrong with Section 3(d). However, the case also illustrates the interaction of Section 3(d) with the initial policy choice to make pre-1995 molecules ineligible for patents. As 1995 recedes further into the past, drugs with post-1995 compound patents will become typical. As Section 3(d) mainly affects secondary patents, we expect these drugs to obtain patent protection in India. There are exceptions: drugs without compound patents anywhere, and drugs with compound patents that can be construed as derivative and that are therefore vulnerable to Section 3(d). However, most new molecular entities have compound patents (J. Health Econ. 31, 327–339; 2012), and showing that a compound patent is derivative is difficult. Of note, this seems to be the basis of the Indian Patent Office’s recent rejection — currently under appeal — of the patent application on sofosbuvir (Sovaldi), Gilead’s new hepatitis C treatment.
The various aspects of TRIPS implementation are interdependent in ways that matter for the future of drug patenting in India. For drugs with pre-1995 compound patents that are not eligible in India, Section 3(d) and other restrictions on secondary patenting may determine whether a drug gets any patent protection at all. For drugs with post-1995 compound patents that are likely to be patented in India, the main effects of Section 3(d) and other restrictions on secondary patents will be on the duration of protection.
The difference between an explanation for rates of pharmaceutical patenting based on Section 3(d) versus one based on decisions not to allow patents on pre-1995 molecules is that the effects of the latter are temporary. We anticipate that if Section 3(d) is implemented as intended — to limit secondary patents — then as 1995 fades further into the past, most new molecular entities will get one patent in India, but only one. Whether this is enough protection to balance innovation and access, we cannot say. However, Section 3(d) will not necessarily make India a patent-free zone.
Nature Reviews Drug Discovery 14, 519–520 (2015) doi:10.1038/nrd4681 Published online 17 July 2015