Indian Supreme Court places clarity on the concept of "evergreening" of drug patents

The Indian Supreme Court on April 1, 2013 denied a patent for the Novartis breakthrough drug Glivec (Imatinib mesylate). Although the case primarily focused on the concept of evergreening in Indian patent law, in the background lies the controversial issue of striking a balance between providing incentives for continued research and development and adequate access to drugs.

The active ingredient of Glivec is a specific chemical form of Imatinib, namely, the beta crystalline form of Imatinib mesylate, which exhibits greater stability and bioavailability than the alpha crystalline form and the free base form. The drug is regarded a breakthrough in cancer treatment, specifically leukemia.

A patent for the free base form of Imatinib was first granted in 1996 in several countries. However, a patent for this free base form was not obtained in India, as patents to drugs per se were not then provided for in Indian patent law. Novartis later filed and obtained separate patents for the specific beta crystalline form of Imatinib mesylate used as the active ingredient of Glivec, in several countries, including South Africa. An application for a patent in India for this beta crystalline form serves as the basis for the current dispute. The concept of patenting modified forms of a drug after the original substance patent has expired is called “evergreening”, which is prohibited under Indian patent law. This prohibition, which is incorporated as Section 3 (d) of the Indian Patents Act, is the central issue in this case. Section 3 (d) states that new forms (including salts, isomers and crystal polymorphs) of known substances are not eligible for patent protection unless they “differ significantly in properties with regard to efficacy”, as compared with the parent compound. In other words Section 3(d) prohibits patenting of new forms of known substances unless the new forms differ significantly in terms of efficacy from the known substances.

Novartis argued that in order to rely on Section 3(d), the efficacy of the new form has to be compared with the known efficacy of the known substance. Novartis contended that neither Imatinib nor Imatinib Mesylate had any known efficacy at the time that the original patent for the free base form was filed and therefore there was no question of producing data evidencing enhancement of efficacy under Section 3(d). The Supreme Court however reached the conclusion that Imatinib Mesylate was not only a known substance but the efficacy of Imatinib and Imatinib mesylate was equally well known on the basis of the original patent. The beta crystalline form of Imatinib Mesylate was therefore a new form of a known substance Imatinib Mesylate whose efficacy is established. It was held that Section 3(d) therefore applies and the provisions of enhancement of efficacy have to be clearly established to overcome the provision.

Novartis was not able to overcome the prohibition by way of data evidencing enhancement of therapeutic efficacy. The benefits that Novartis relied on were physical attributes such as better flow properties, better thermodynamic stability and lower hygroscopicity. Novartis also mentioned that there was an improvement in bioavailability.

However, based on these properties alone, it was held that the beta form did not satisfy the definition of enhanced efficacy under Section 3(d) of the Indian Patents Act.

It appears that the Section 3(d) of the Indian Patents Act must be read very strictly. The courts will only look for greater efficacy and any other advantages of a drug do not play a role in determining whether “evergreening” applies.

So, what does this decision mean for South Africa? It is significant to note that a similar provision or equivalent of Section 3(d) does not exist in the South African Patents Act. Further, the Novartis patent for Glivec (i.e. the beta crystalline form of Imatinib mesylate) has also been filed in South Africa and is set to expire in 2018. If this patent were challenged in South Africa, then the courts would apply existing legal tests to determine if the patent lacked novelty and inventiveness, these two factors being the primary criteria for patentability in South Africa.

As the beta crystalline form of Imatinib mesylate is in essence a selection over the teaching of the original patent, the major factor that the South African courts would look to in this case is that of inventiveness. In other words is the beta crystalline form of Imatinib mesylate inventive over that of the original free base form of Imatinib? The test for inventiveness, which has been adopted by our Courts, is as follows:

  1. What is the inventive step said to be involved in the patent in suit?
  2. What was, at the priority date, the state of the art relevant to that step?
  3. In what respect does the step go beyond, or differ from, the state of the art?
  4. Having regard to such development or difference, would the taking of the step be obvious to the skilled person?

In its defence in India , Novartis argued that the beta crystalline form of Imatinib mesylate has (i) more beneficial flow properties, (ii) better thermodynamic stability and (iii) lower hygroscopicity; and thus is easier to process and store. According to South African law on selection patents, provided that the selected members all have some substantial, special, peculiar advantage over the other, unselected members, which advantage was not obvious having regard to what was common knowledge at the effective date, then the selection would be regarded as inventive. Therefore, the advantages as argued by Novartis will surely play a role in the test above.

In South Africa, determining inventiveness would not be limited to improved efficacy, but could also include improved physical properties, such as those argued by Novartis and mentioned above. Thus, it is likely possible that a South African court would come to a different conclusion that the Indian court on the validity of the Glivec patent. In the aftermath of the Glivec decision, concerns will surely be raised as to how multinational pharmaceutical companies will consider future patent filings for different forms of the same molecule, not just in India but throughout the world.

Compiled by: Tertia Beharie

This article was published in the Business Day Law and Tax Review on 13 May 2013.

Date published: 2013/06/13
Author: Tertia Beharie

Tags: patent news india supreme court drug patents norvatis