Patenting in India: Novartis Loses Glivec Patent Battle

The patent in question relates to the betacrystalline form of Imatinib Mesylate. Imatinib is a specific protein kinase inhibitor which can be used in the preparation of pharmaceutical compositions for use as anti-tumour and atherosclerosis drugs. The US patent covering Imatinib was granted in 1996 (the ‘Zimmermann Patent’) and disclosed various derivatives of a compound, of which Imatinib was a single example, in addition to corresponding salts.

Novartis was granted US Food and Drug Administration (FDA) approval for Gleevec (marketed as Glivec in Europe) in 2001. The active component listed for Gleevec was Imatinib Mesylate, which Novartis claimed was covered by the Zimmermann Patent. Indian patent law is traditionally viewed as hostile to pharmaceuticals and Section 5 of the 1970 Patents Act, which was in force at the time of the Zimmermann Patent application, expressly excluded the patentability of substances intended for use as a medicine or drug. This exclusion prevented Novartis prosecuting the original Zimmermann Patent application in India. During the late 1990s, however, India was twice taken to the World Trade Organisation panel for contravening the ‘Trade Related Aspects of Intellectual Property Rights’ (TRIPS) agreement due to a lack of provision for the protection of pharmaceutical and agricultural chemical products. These actions compelled the Indian Government to amend the definition of an ‘invention’ in Indian patent law such that pharmaceutical products were no longer excluded. In order to placate domestic angst regarding how this amendment would impact India’s generics pharmaceuticals industry and its reputation as ‘the pharmacy of the world’, the government concurrently amended Section 3(d) of the Patent Act to introduce a second tier of qualifying standards for pharmaceutical products. The principle requirement of this amendment was that a new form of a known pharmaceutical substance must have enhanced efficacy over the known substance. It is within this framework of Indian patent law that the substantive issues of the present case were heard by the Supreme Court.

Novartis submitted that the teachings of the Zimmermann Patent did not extend beyond Imatinib itself and that arriving at the beta crystalline form of Imatinib Mesylate required two inventions from the Zimmermann Patent. To produce Imatinib Mesylate one would be required to select Imatinib from the extensive list of possible compounds and subsequently choose methanesulfonic acid to produce the salt. An additional invention would then be necessary to arrive at the beta crystal form.

The Supreme Court, however, rejected Novartis’ submission that Imatinib Mesylate was novel over the Zimmermann Patent, citing the following reasons:

1. The Zimmermann Patent teaches how to use Imatinib, or a pharmaceutically acceptable salt thereof, in a pharmaceutical composition for treating tumours;
2. Novartis had relied on the Zimmermann Patent to gain FDA approval for Gleevac, the active component of which is Imatinib Mesylate. Novartis had also received an extended patent term on the Zimmermann Patent in the US due to the time taken to gain regulatory approval for Gleevac;
3. Novartis had prevented a third party from marketing Imatinib Mesylate in the UK on the basis that it infringed the Zimmermann Patent.

The Supreme Court accepted that the beta crystalline form of Imatinib Mesylate was not known from the Zimmermann Patent and proceeded to test it for inventiveness under Section 3(d) of the Act. The central issue for assessing inventiveness under Section 3(d) was determined as the requirement for improved efficacy over the known substance. In the case of a medicine, the Court defined that efficacy related to ‘therapeutic efficacy’ and therefore, contrary to the approach followed in many other regions, non-therapeutic advantages such as improved safety or stability could not be considered to confer inventiveness.

Novartis submitted that the beta-crystalline form provided beneficial flow properties, improved thermodynamic stability, lower hygroscopicity and improved bioavailability compared to Imatinib Mesylate itself. However, due to the Supreme Court’s narrow interpretation of the term efficacy, flow properties, thermodynamic stability and hygroscopicity were considered to be physical properties which had no impact on therapeutic efficacy. Critically, when considering bioavailability the Court determined that “increased bioavailability alone may not necessarily lead to an enhancement of therapeutic efficacy”.

The Supreme Court therefore ruled that the beta crystalline form of Imatinib Mesylate fails both the tests of invention and patentability as set out in Indian patent law and dismissed the appeal.

This decision has clearly caught the imagination of the wider public due to the emotive backdrop in which it has been set by numerous editorials and blogs. On further reflection, however, it appears that the decision is a matter of patentability in a jurisdiction which is notoriously hesitant to grant patents for pharmaceutical products. In its summary, the Supreme Court is careful to note that the decision does not bar protection for all incremental inventions of pharmaceutical substances. Nonetheless, it seems that the threshold for patentability of pharmaceutical products will remain a challenge in India and that data demonstrating an improved therapeutic effect will be essential for protecting incremental pharmaceutical inventions in this jurisdiction.