EFFICACY IN PHARMACEUTICAL PRODUCTS: NOVARTIS AG v. UNION OF INDIA

This article has been authored by Anamika Tiwari, a law student at O P Jindal Global University.

Introduction:

India has been at the forefront of creating an alternative patent law model that has since been emulated by many developing countries. The Patent System in India is governed by the Indian Patent Act, 1970 which has seen several amendments and the latest amendment was in 2005. Grant of a patent provides exclusive rights to the patent holder to make, practice, sell, license the patented invention for a period of 20 years. On 1st April, 2013, the Supreme Court passed a landmark judgement in Novartis AG v Union of India, where Novartis challenged the rejection of its patent application Beta Crystalline form of “Imatinib mesylate”. The Supreme Court rejected the challenge as the drug did not produce any enhanced or superior therapeutic efficacy and on the grounds the there was no innovative step involved. The other major reason for the rejected of the challenge made by Novartis was to prevent the evergreening of already patented drugs.

Efficacy and section 3(d) of the Indian Patent Act.

Section 3(d) of the Indian Patent Act states that “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.” Section 3(d) of the Indian Patent Act, gives important to the term ‘efficacy’, however, does not elaborate it much. According to the Oxford English Dictionary, ‘efficacy’ can be defined as the potential of a drug to produce desired therapeutic effect. The Madras High Court observed that ‘efficacy’ with respect to pharmaceutical product defined it as effectiveness of a newly discovered drug in relieving from the disease and producing the desired effect on the patient body. The court observed that applicant seeking patent for the novel drug had to bring out difference between the present drug and the patented drug about its therapeutic efficacy.

Novartis AG v Union of India:

Brief Facts:

Novartis International AG, one of the largest international pharmaceutical companies in 1998, according to TRIPS filed an application before the Chennai Patent Office for the grant of the patent for anti-cancer drug ‘Gilvec’ used to treat Chronic Myeloid Leukemia (CML) and Gastrointestinal Stromal Tumors (GIST), invented from the Beta crystalline form of “Imatinib mesylate”. This drug is famous for the treatment of cancer and has been patented in more than 35 countries. When the application was filed, the grant was restricted to methods or processes and not for products of India. Imatinib free base was granted patent in 1993 in the US but not in India because India did not provide for pharma patents prior to 1995. After the Patent (Amendment) Act, 2005, section 5 of the Patent Act was repealed and the patent was granted for not only methods and processes but also for products in India.

In 2005, the patent application of Novartis for ‘Gilvec’ was taken into consideration. However, in 2006, the Madras Patent Office refused the patent application for Glivec stating that the said drug did not exhibit any major changes in therapeutic effectiveness over its pre-existing form, which was already patented. The said decision was based on Section 3(d) of the Indian Patents (Amendment) Act, 2005 which provides a known substance can only be patented if its new forms exhibit “enhanced efficacy”.

After that, Novartis filed two writ petitions before the Madras High Court under Article 226 of the constitution. The case was then transferred to Intellectual Property Appellant Tribunal (IPAB) in 2007. IPAB head and dismissed the application stating that even though the invention satisfies the tests of novelty and non-obviousness, however, it fails to pass the test laid down in section 3(d) of the Patents Act.

Novartis after this, filed a Special Leave Petition before the Supreme Court of India in 2009 against the order passed by IPAB under Article 136 of the constitution.

The main issues raised in this case were:

(i) Whether the invention was inconsistent with respect to section 3(d) of the Act?

(ii) What is the interpretation of section 3(d) of the Indian Patent Act?

(iii) Whether the invention qualifies for the test of novelty and inventive step for the alleged product?

Judicial Interpretation:

The court accepted the IPAB’s decision that the original patent claims to imatinib did not encompass the claims to the beta crystalline form of imatinib mesylate. The court observed that even though beta crystalline could be considered a ‘novel’ invention, it did not pass the test of enhanced efficacy as laid down in section 3(d) of the Indian Patents Act. This formed the ground of rejection of the patent application of Novartis. Section 3(d) clearly specifies that a new form of a known substance in not patentable under Indian law unless it enhances its known “known efficacy”.

The term ‘efficacy’ in section 3(d) was interpreted by the court referring to ‘therapeutic efficacy’. The court said that Novartis should have shown enhanced therapeutic efficacy beta crystalline over imatinib mesylate. Novartis argued that the physico- chemical properties of the polymorph form of the imatinib molecule, i.e., better flow properties, better thermodynamic stability and better and lower hygroscopocity, resulted in improved efficacy and hence is patentable under Indian Law. These all were considered as meaningless with respect to efficacy as they did not provide any therapeutic efficacy to the drug.

Another important question before the court was whether increased bioavailability of beta crystalline constituted to enhanced therapeutic efficacy. With respect to this question, the court said that merely increase in bioavailability does not always mean increase in therapeutic efficacy. It was held by the court that the patent application needed to show, through the submission of clinical trials data that increase in bioavailability does result an increase in therapeutic efficacy. In this case, no such evidence stating that the increase in bioavailability actually led to enhanced therapeutic affect of the substance on human body was produced by Novartis. Therefore, the patent application of Novartis was hit by section 3(d) of the Indian Patent Act, and the decision of IPAB was upheld by the court.

Through this judgement, the Supreme Court affirmed that with respect to pharmaceutical products, India has adopted an approach that is stricter than US or the EU. In India, the patent application that the new form of the known compound is different from the old form, but also that this modification will result in the improvement of the patient.

Impact of Novartis Case:

The landmark judgement given by the Supreme Court in Novartis AG v Union of India dealt with scope, application and interpretation of section 3(d) of the Indian Patent Act. No doubt that this judgement broader implications on both multinational and domestic pharmaceutical companies. After this judgement there remains no ambiguity regarding patentability criteria under section 3(d) and its enhanced efficacy to mean the enhanced therapeutic efficacy in cases of drugs and medicines.

This judgement would lead to invention of more genuine pharmaceutical product, thus creating an environment of genuine research and developmental activities. Apart from this, it will an atmosphere of competition and promote genuine incremental invention.

Conclusion:

The Supreme Court through this judgment has interpreted enhanced efficacy to mean therapeutic efficacy. The court has made it clear that section 2(d) in no way bars incremental invention. Especially, with respect to bioavailability of a product, the court never said that increased bioavailability could not provide enhanced efficacy to the product. However, to prove that a scientific evidence or a clinical data had to be produced before the court. The court left open the question whether enhanced efficacy refers narrowly to curative effect, or more broadly to improved safety profile and reduced toxicity.

This judgement has surely paved way for creating of real incremental invention by both international and domestic pharmaceutical companies. There is no doubt that this verdict will have a positive effect motivating research and development of genuine drugs which could be used for betterment of the public at large. Creating a competitive environment between international and national pharmaceutical companies it will help in reducing the costs of life saving drugs.