The Supreme Court of India has recently issued their decision in the Novartis/Glivec case, providing guidance on the patentability of incremental modifications to chemical or pharmaceutical inventions.
Glivec (“Gleevec” in the US, also known as “Imatinib”) is a tyrosine-kinase inhibitor developed by Novartis and used to treat a number of cancers, including chronic myelogenous leukemia (CML). It was lauded as one of the first “magic bullet” anti-cancer drugs – the tyrosine-kinase target of Imatinib is present only in cancerous cells, allowing the drug to specifically target those cancerous cells with little damage to healthy cells.
Patents encompassing Imatinib in free base form had been granted in the US and Europe but no application was filed in India as, at the time of development, product patents to pharmaceuticals were not permitted in India.
Following India’s accession to TRIPS, patent legislation was amended to allow product patents to pharmaceuticals. By this stage Imatinib (in free base form) was known; however, Novartis filed an application relating to previously undisclosed form of Imatinib: the beta crystalline structure of Imatinib Mesylate, a salt of Imatinib.
Novartis’ patent application relating to this second form of Imatinib was initially refused, both during examination and at the first instance of appeal, as it was deemed contrary to Section 3(d) of the Patents (Amendment) Act.
Section 3 of the Patents (Amendment) Act defines what are considered not to be inventions under the Act and Section 3(d) was introduced in response to concerns about the potential negative impact on public health resulting from the newly available pharmaceutical product patents. According to Section 3(d), the following is not an invention:
“3(d): 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…”
It was the interpretation of this clause, together with the requirements an incremental pharmaceutical invention must meet to overcome it, that the Supreme Court undertook in assessing, and ultimately dismissing, the Novartis appeal.
What is “efficacy”?
Novartis had demonstrated that the beta crystalline form of Imatinib had improved physicochemical properties, for example, better thermodynamic stability, lower hygroscopicity and better flow properties, when compared to the non-crystallised form. However, the pharmacological properties of the two forms as tyrosine-kinase inhibitors were found to be the same. Nevertheless, Novartis contended that the improved physical properties meant the beta crystalline form was not excluded under Section 3(d) as it possessed the required “enhancement of the known efficacy”.
The Supreme Court disagreed. The Court considered the term “efficacy” to mean “the ability to produce a desired or intended result”. In relation to a drug or medicine that claims to treat a disease, this must mean “the test of efficacy can only be “therapeutic efficacy””. The question was therefore what amounted to improved “therapeutic efficacy”.
As Section 3(d) was introduced in an attempt to reduce the risk of negative effects on public health arising from pharmaceutical product patents, the Court concluded that “therapeutic efficacy”, as an exception from the exclusion of Section 3(d), must be construed strictly and narrowly. Physical properties such as those demonstrated by Novartis (improved stability, flow properties etc.), whilst beneficial for storage and manufacture, were found not to amount to improved “therapeutic efficacy”.
The Novartis appeal was therefore dismissed and the application rejected.
Despite concerns in India and elsewhere in the world that allowing patents to inventions involving minor modifications to pharmaceutical products would have a huge negative impact on public health in India and abroad, the Supreme Court made it clear that Section 3(d) does not bar patent protection for all incremental inventions of chemical and pharmaceutical substances. Rather, it merely introduces a higher bar for patentability which such inventions must meet. As stated in the decision:
“Section 3(d) sets up a second tier of qualifying standards for chemical substances/pharmaceutical products in order to leave the door open for true and genuine inventions but, at the same time, to check any attempt at repetitive patenting or extension of the patent term on spurious grounds”.
In order to meet this second tier, incremental chemical or pharmaceutical inventions will have to demonstrate an improvement in “efficacy”. Following the Novartis decision, it appears this improvement will have to be in the specific, narrow purpose of the already-known product. For medicines, this will have to be the “therapeutic efficacy”, although exactly what amounts to “therapeutic efficacy” remains to be determined. However, it is clear that improved physicochemical properties are unlikely to be sufficient and pharmacological data is likely to be required.
It should also be noted that, although the relevant “efficacy” for medicinal products has been defined, no such guidance has been provided for chemical products intended for other purposes. However, the Supreme Court has indicated that “the test of efficacy would depend upon the function, utility or the purpose of the product”. A direct consideration of this function or purpose and provision of data demonstrating how it has been improved are now all the more important if patent protection in India is desired.
Despite concerns, the Novartis decision does not preclude incremental pharmaceutical or chemical patents. However, applicants should be aware that a higher threshold is likely to be imposed on such inventions.