The End Of The Evergreens

 Joshua Teoh examines the Indian Supreme Court decision in the Novartis Case

 

INTRODUCTION

On 1 April 2013, the Supreme Court of India in Novartis AG v Union of India & Others [2013] 3 Madras Law Journal 421 rejected the appeal of Novartis AG (“Novartis”) against the Indian patent office’s refusal to patent the beta crystalline form of a chemical compound called Imatinib Mesylate, a therapeutic drug for chronic myeloid leukaemia and certain kinds of tumours, marketed under the trade names “Glivec” or “Gleevec”.

In this landmark decision, the Supreme Court has imposed strict requirements on the practice of “evergreening” pharmaceutical products in India. "Evergreening" is a common practice in the pharmaceutical industry. It describes a practice whereby a patentee seeks to extend the patent life of his current invention by making modifications or changes to that invention and thereafter applying to patent his modified invention, thereby extending the duration of protection of the original invention.

 

THE ZIMMERMANN PATENT

Several derivatives of a compound known as N-phenyl-2-pyrimidine-amine, including a free base called Imatinib, were patented in the United States in 1996 under US Patent No. 5,521,184 (“Zimmermann Patent”) and in Europe in 2000 under European Patent No. EP-A-0564409 (“European Zimmermann Patent”). These derivatives were invented by Jürg Zimmermann of CIBA Geigy which later merged with Sandoz to form Novartis.

The N-phenyl-2-pyrimidine-amine derivatives, including Imatinib, are capable of inhibiting certain protein kinases, especially protein kinase C and PDGF (platelet-derived growth factor)-receptor kinase and thus have valuable anti-tumour properties and can be used in the preparation of pharmaceutical compositions for anti-tumoral drugs and drugs against atherosclerosis.

 

NOVARTIS’ PURPORTED INVENTION

A key feature of the Novartis case is Imatinib Mesylate, a salt derived by adding methanesulfonic acid to Imatinib, one of derivatives under the Zimmermann Patent. Novartis claimed that they are the first to achieve the beta crystalline form of Imatinib Mesylate (“the subject product”) through a two-stage invention, which begins with producing the salt, Imatinib Mesylate, and later developing the beta crystalline form of the salt.

On 17 July 1998, Novartis filed an application for the grant of a patent for the subject product at the Chennai Patent Office. In the application, Novartis claimed that the subject product has, among others, the following properties: (i) more beneficial flow properties; (ii) better thermodynamic stability; and (iii) lower hygroscopicity than the alpha crystal form of Imatinib Mesylate.

Novartis further claimed that the above mentioned properties make the subject product “new” as it “stores better and is easier to process”, has “better processability” and has a “further advantage for processing and storing”.



HISTORY OF NOVARTIS’ PATENT APPLICATION

Although the Novartis’ Indian patent application was only made on 17 July 1998, it claimed for a priority date of 18 July 1997, which is the date on which Novartis first applied for grant of patent for the subject product in Switzerland.

At the time when Novartis filed its patent application in India, the law in that country with regard to product patent was in a transitional stage where pharmaceutical products were not patentable. This caused the Novartis’ patent application to lay dormant under an arrangement called “the mailbox procedure” until the relevant law had been amended to allow its patentability.

The Novartis application for patent was taken out of the “mailbox” for consideration only after the amendments made to the Indian Patents Act 1970 (“the Act”) had taken effect from 1 January 2005. However, before it was taken up for consideration, the patent application had attracted five pre-grant oppositions from five different parties.

The Assistant Controller of Patents and Designs heard all five oppositions on 15 December 2005 and rejected Novartis’ patent application for the subject product through five separate, though similar, orders handed down on 25 January 2006. The Assistant Controller held, among others, that:

(1) the subject product was anticipated by prior publication, such as the Zimmermann Patent;
(2) the subject product was obvious to a person skilled in the art in view of the disclosure provided in the Zimmermann Patent specifications; and
(3) the subject product's patentability was disallowed by section 3(d) of the Act.

Subsequently, Novartis filed writ petitions to challenge the decision of the Assistant Controller at the Madras High Court, but the matters were transferred to the Intellectual Property Appellate Board (“IPAB”) upon its formation and dealt with by way of appeals. Upon hearing the appeals, the IPAB reversed the findings of the Assistant Controller on the issues of anticipation and obviousness.

However, the IPAB held that the patentability of the subject product was hit by section 3(d) of the Act which requires a higher standard of inventive step, and that the subject product was also barred by section 3(b) of the Act which prohibits the grant of patent by reason that it could create havoc in the lives of poor people due to the high pricing of the subject product. Nevertheless, the IPAB held that the process for preparing the subject product could be patented.

Dissatisfied with the IPAB’s decision to reject granting a patent for the subject product itself, Novartis filed a direct appeal to the Supreme Court of India. The Supreme Court also decided to concurrently hear the appeal of two other parties, NATCO Pharma Ltd and Cancer Patients Aid Association, against the IPAB’s decision to grant a patent to Novartis for the process for the preparation of the subject product.

 

AMENDMENTS TO THE INDIAN PATENTS ACT 1970

Prior to 1 January 2005, section 5 of the Act in essence barred the grant of patent to substances intended for use, or capable of being used, as food or medicine or drugs, or prepared or produced by chemical processes. As such, Novartis’ patent application was considered only after the Act had been amended by the Government of India to comply with the terms of the Agreement on Trade-Related Aspects of Intellectual Property Rights.

Among the amendments which came into effect from 1 January 2005, the most significant one was the deletion of section 5 of the Act. This amendment opened the doors to the patenting of food, medicine and drug products. Other crucial amendments made to the Act include replacing sections 2(1)(j) and 2(1)(ja) and adding words and an explanation paragraph to section 3(d).

Section 2(1)(j) inter alia provides that an “invention” is a product or process that involves an inventive step and is capable of industrial application, that is, it is capable of being made or used in an industry.

According to Section 2(1)(ja), an “inventive step” is a feature of an invention that involves technical advancement from existing knowledge, or has economic significance, or both, and that makes the invention not obvious to a person skilled in the art.

Section 3 sets out various matters that are not regarded as inventions within the meaning of this Act, of which paragraph (d) provides 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.”

The explanation paragraph that was added to Section 3(d) of the Act states that for the purposes of this clause, salts, esters, ethers, polymorphs, metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combinations and other derivatives of known substance shall be considered to be the same substance, unless they differ significantly in properties with regard to efficacy.

 

ISSUES BEFORE THE INDIAN SUPREME COURT

The issues before the Supreme Court included, among others, the following questions:

(1) How section 3(d) interplays with sections 2(1)(j) and 2(1)(ja) of the Act;
(2) Whether the subject product qualifies as an “invention” within the meaning of sections 2(1)(j) and 2(1)(ja); and
(3) If the subject product qualifies as an “invention” under sections 2(1)(j) and 2(1)(ja), whether its patentability could still be denied on the ground that section 3(d) pulls it out of the category of “invention”.

The issue as to the applicability or otherwise of the controversial section 3(b) which precludes the grant of a patent on grounds of hardship that may be caused to end-users who are not financially well-off, was not pursued in the Supreme Court.

 

THE INDIAN SUPREME COURT’S FINDINGS

The Supreme Court (“the Court”) had no doubt that the amendment to section 3(d) of the Act was meant to deal with chemical substances, and more particularly, pharmaceutical products. The Court was of the view that the amended section 3(d) sets up a second tier of qualifying standards for chemical substances and pharmaceutical products for the purpose of leaving the door open for true and genuine inventions but also at the same time, to check any attempt at repetitive patenting or extension of the patent term on spurious grounds. Nevertheless, the Court viewed section 3(d) as representing the “patentability” concept which is separate and distinct from the “invention” concept.

In determining whether the subject product was truly an invention of its own, the Court found that the active ingredient of the subject product, namely Imatinib Mesylate, had its genesis from the Zimmermann Patent. It was discovered that the subject product was launched by Novartis in the United States market under the name Gleevec on the basis of the Zimmermann Patent itself. For the purposes of obtaining approval to market Gleevec to consumers, Novartis had stated in its application to the relevant U.S. food and drug safety authorities that Imatinib Mesylate was covered under the Zimmermann Patent. The Court noted that Novartis had used its European Zimmermann Patent to stop another drug company, NATCO Pharma Ltd, from selling in the United Kingdom a generic drug called VEENAT 100 capsules, which like Gleevec, has Imatinib Mesylate as its active ingredient. The Court also found that several scientific publications in 1996 had made reference to Imatinib Mesylate and its anti-tumoral properties.

In view of the matters described above, the Court found Imatinib Mesylate to be a known substance. The Court was unable to see how Imatinib Mesylate could be said to be novel or not obvious to a person skilled in the art, having observed that the compound came into being through the invention in the Zimmermann Patent. Consequently, the Court held that the active ingredient of the subject product, Imatinib Mesylate, did not pass the test of “invention” laid down in sections 2(1)(j) and 2(1)(ja) of the Act.

The Court then proceeded to consider whether the subject product could be accepted to be new. The Court found the subject product to be a new form of a known substance found in the Zimmermann Patent. Consequent upon such finding, the Court proceeded to consider whether the subject product would satisfy the test in section 3(d) of the Act which requires a new form to differ significantly in efficacy as compared to other known forms. In relation to medicines, the Court adopted a restrictive interpretation of “efficacy” in section 3(d) and held that not all advantageous or beneficial properties are relevant but only those that have therapeutic efficacy.

The Court took the view that properties which are inherent to a particular form would not qualify as enhancing the efficacy of a known substance. The Court acknowledged that the properties claimed of the subject product, namely more beneficial flow properties, better thermodynamic stability and lower hygroscopicity, may be important but had nothing to do with enhanced therapeutic efficacy. Accordingly, the Court ruled that such properties were inherent to the form.

Similarly, the Court refused to accept that a 30% increase in bioavailability, which is the degree or rate at which drug is made available in the human body, may necessarily lead to an enhancement of therapeutic efficacy. Furthermore, there was no evidence offered to indicate that the subject product would produce an enhanced or superior efficacy (therapeutic) on a molecular basis over what could have been achieved with Imatinib free base. Accordingly, the Court found that the pharmacological effects of the subject product are equally possessed by Imatinib in free base form. Thus, the subject product failed to pass the test in section 3(d) of the Act.

The Court observed that in cases of new chemical products, especially pharmaceuticals, it may not necessarily mean that the product must be something new altogether or not existing before. Such product may be something “different from a recent previous” or “be regarded as better than what went before” or “in addition to another or others of the same kind”. In cases where the product claimed for is a new form of a known substance with known efficacy, then the relevant product must, in addition to sections 2(1)(j) and 2(1)(ja), pass the test of enhanced therapeutic efficacy under section 3(d) read with the explanation paragraph thereto.

In closing, the Court was also critical of the fact that Novartis was in fact marketing Imatinib Mesylate that was not in the beta crystalline form which they sought to patent and as such, appeared to be attempting to patent a product that it was not actually selling.

 

CONCLUSION

The amendments to the Act have opened the doors in India to allow patenting of food and medicine products, which are in essence chemicals, whilst at the same time, providing sufficient safeguards to prevent any abuse of such allowance.

The decision by the Supreme Court has effectively applied the provisions in the amended Act, especially section 3(d), to prevent the attempted “evergreening” practice by Novartis to patent a known compound, Imatinib Mesylate, in a different form which has no new or different therapeutic properties as compared to the earlier form of the same compound.

The standard set by the Supreme Court in relation to the test of enhanced efficacy under section 3(d) of the Act shows that not any kind of improvement to a known chemical substance would render it patentable, despite the improved form being novel. To pass the test of enhanced efficacy, the new form of a known substance must show new useful properties which are not inherent to its earlier form. Further, in the case of a pharmaceutical drug, the new useful properties that it possesses must be therapeutic in effect.

This decision of the Supreme Court does not sound the death knell for the practice of “evergreening” of pharmaceutical products in India but sets significantly higher thresholds that have to be satisfied before a patent will be granted for the modified product.

Writer’s e-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

 
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