Has the developed world been TRIPSed up?

Gary-Moss

The decision of the Indian Supreme Court in the Glivec case raises interesting questions about patent protection in developing countries. Gary Moss teases out the issues.

On April 1, 2013 the Indian Supreme Court pronounced its decision denying Novartis’ patent relating to its anti-cancer drug Glivec/Gleevec[1]. The reaction to the decision has been one of celebration on the part of patient groups and the Indian pharmaceutical industry – who have viewed the decision as ensuring that lifesaving medicines remain available in developing countries at affordable prices, and as preventing the alleged practice of pharmaceutical companies to “evergreen” their monopolies – and one of dismay on the part of major pharmaceutical companies who have muttered dark threats about the future of research-based activities in India and other developing countries.

This article will not take sides in this ongoing debate. But the decision in itself is interesting because it highlights a number of differences in approach to issues of patent protection between the courts of the so called “Developed World”, which have wrestled with concepts of patent law for well over 100 years, and the courts of those countries which are only now having to come to grips with these topics. It also highlights that how courts approach such issues will inevitably depend on their starting points and that those starting parts in turn are very dependent on their historical perspective. Further, given that the case in question was decided under laws which were implemented by India following its accession to the TRIPS accord, one might also question whether the industrialized countries of the “west”, which made TRIPS an essential part of the Uruguay round of GATT negotiations, has actually received everything they bargained for.

The decision itself is lengthy, nearly 100 pages and comprising 196 paragraphs. Of necessity, this article will only be able to provide a brief review.

The underlying facts

The patent in suit related to a crystalline form of a product known as imatinib, a compound with anti-tumor properties. Imatinib in its free base form was invented by Jurg Zimmerman at Novartis[2] and was the subject of patent applications in the US and Europe claiming priority from a Swiss application filed in 1992. The US Application resulted in a granted patent dated May 1996 – referred to as the “Zimmerman patent.”

Imatinib in its free base form was toxic and therefore could not be administered to patients. In July 1998 Novartis filed with the Indian patent office an application for a further form of imatinib, namely the mesylate salt in a specific crystallized form designated as the beta form. Novartis claimed that this new form involved a two-stage invention over the form disclosed in the Zimmerman application, namely the production of imatinib mesylate and then the development of the beta crystal form of the salt. The advantages of this beta crystal form were claimed to be (i) more beneficial flow properties (ii) better thermodynamic stability and (iii) lower hygroscopicity. The net result was said to be that the product “stores better and is easier to process.”

Novartis’ application had attracted opposition by four Indian pharmaceutical companies, along with Cancer Patients Aid Association. In December 2005, following a hearing, the application was rejected by the Assistant Controller of Patents and Designs on the grounds, inter alia, that the claimed invention was anticipated by the Zimmerman patent, was obvious in the light of the Zimmerman disclosure and further that patentability of the invention was disallowed by section 3(d) of the Indian Patents Act. The latter provision is discussed in more detail below.

In June 2009 the Intellectual Property Appellate Board heard the Novartis appeal from that decision. It reversed the Assistant Controller’s decisions on novelty and obviousness, but upheld his decision on section 3(d). Novartis then appealed to the Supreme Court and it was that appeal which resulted in the decision of April 1, 2013[3].

What did the Zimmermann Patent disclose?

An issue which loomed large in the case was the exact scope of disclosure of the Zimmermann Patent. Novartis claimed that imatinib mesylate was not part of the disclosure and thus, as stated above, its initial production constituted the first part of the inventive concept. It was produced by subjecting the product of Example 21 of the Zimmermann Patent (there were 37 examples in all) to treatment with methanesulfonic acid to produce the mesylate.

However, salts in general were disclosed in the Zimmermann patent. It was expressly stated that the compounds of the relevant formula included their respective salts. For example:

“Owing to the close relationship between the novel compounds in free form and in the form of their salts, including those salts which can be used as intermediates, for example, in the purification of the novel compounds or for the identification thereof… any reference to the free compounds should be understood as including the corresponding salts, where appropriate and expedient.”

There were many similar statements. And Claim 23 was to a compound of Claim 1 “or a pharmaceutically acceptable salt thereof.”

In 1998 and again in 2001 Novartis submitted New Drug Applications (NDAs) to the US Food and Drug Administration (FDA) for imatinib mesylate for the treatment of chronic myeloid leukemia. The drug was referred to under the name “Gleevec[4]”. In the patent information furnished as part of the NDAs, the product was declared to be covered by the Zimmermann Patent. That patent was also said to cover the composition, formulation and/or method of use of imatinib mesylate.

After approval was obtained in 2001 Novartis sought patent term extension for the Zimmermann Patent based on the time taken for regulatory review. The application referred to claims which it said covered imatinib mesylate. It said

“Each of claims 1-5,10-13, and 23 claim a compound or compounds which include the approved product, imatinib mesylate. Claim 21 claims a composition containing a compound or compounds which including the approved product. Claim 22 claims a method of treating tumors in warm-blooded animals with a compound or compounds which include the approved product…”

In addition Novartis has threatened one of the Indian opponents, NATCO, with an action under its equivalent European patent, alleging that the patent claimed, among other things, the compound imatinib and acid addition salts of that compound such as the mesylate salt.

Thus, the Court asked, how could it be said that imatinib mesylate was “new” at the time of the application for the patent in suit?

Novartis’ answer to this was to highlight the distinction between that which is covered by a patent and that which is disclosed. They relied in particular on the English Court of Appeal’s decision in A C Edwards v Acme Signs & Displays Limited [1992] RPC 131 and the decision of the US Court of Customs and Patent Appeals in In Re Hogan 559 F.2d 595. Detailed consideration of those decisions is beyond the scope of this article, but suffice it to say that the Indian Supreme Court was having none of it. In two particularly telling passages it stated as follows

“The dichotomy that is sought to be drawn between coverage or claim on the one hand and disclosure or enablement or teaching in a patent on the other hand, seems to strike at the very root of the rationale of the law of patent. Under the scheme of patent, a monopoly is granted to a private individual in exchange of the invention being made public, so that, at the end of the patent term, the invention may belong to the people at large who may be benefited by it. To say that coverage in a patent might go much beyond the disclosure seems to negate the fundamental rule underlying the grant of patents. [Emphasis in original]

And

“….we would like to say that in this country the law of patent, after the introduction of product patent for all kind of substances in the patent regime, is in its infancy. We certainly do not wish the law of patent in this country to develop on lines where there may be a vast gap between coverage and disclosure under the patent; where the scope of the patent is determined not by the intrinsic worth of the invention but by the artful drafting of its claims by skilful lawyers, and where patents are traded as a commodity not for production and marketing of the patented products but to search for someone who may be sued for infringement of the patent” [Emphasis in original]

The Court was firmly of the view that imatinib mesylate was disclosed in the Zimmermann Patent. Thus the alpha crystal form was not “new”.

Section 3(d) Patents Act 1970

Section 3(d) of the Indian Patents Act 1970 provides as follows:

“Section 3. What are not inventions.- The following are not inventions within the meaning of this Act, ……

(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 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.

Explanation. – 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 in their properties with regard to efficacy.”

In order to understand the potential ambit of this provision (which is not found in either European or US law) it is necessary to trace the history of patent law within India. As the Court said:-

“The best way to understand a law is to know the reasons for it.”

In the 78 paragraphs and 42 pages which follow the Court traced the origins of this section. What follows is necessarily a very brief synopsis.

The Patents Act 1970 provided in section 5 that substances intended for the use, or capable of being used as a food or medicine, were not in themselves patentable; instead only claims for the methods of process or manufacture were patentable. This followed the report of a Parliamentary Committee which had been set up in 1957 to look into the issue and which came to the conclusion that such products should not be the subject of protection. The Court also reviewed data on the effect which this provision has had on the Indian domestic pharmaceutical industry, pointing out that whereas in 1970 Indian-based companies held only 32% of the market for pharmaceutical products, by 2004 that proportion had risen to 77%.

However, on January 1, 1995 the Uruguay round of GATT came into force along with the TRIPS Agreement. TRIPS obliged the members of the WTO to provide in their laws that “patents shall be available for any inventions, whether products or processes, in all fields of technology provided that they are new, involve an inventive step and are capable of industrial application.” This was generally regarded as “outlawing” provisions which excluded medicinal products from patentability.

Certain other provisions of TRIPS enabled members to delay the implementation of this particular provision until January 1, 2005. The Indian Government passed an Ordinance on December 31, 2004 which provided for the necessary amendments but that was due to lapse on March 31, 2005. Suffice to say that there was considerable opposition in India (including within Parliament) as to the implementation of this change in the law, having regard to the potential consequences for public health and also its potentially detrimental impact on the Indian pharmaceutical industry. The Court’s judgment makes detailed reference to that opposition and the extensive debate which took place in Parliament. Some of that opposition also related to the perceived misuse of the patent system by the pharmaceutical industry and the so-called practice of “evergreening” featured large among the abuses. But the relevant law was passed. At the end of the debate on the new bill the minister who had sponsored the bill stated as follows:

In regard to evergreening, I just want to read out section 3(d) which says that a mere discovery of a new property or new use for a known substance or the mere use of known process in a new product – these are exceptions, these will not be granted any patent – and substance obtained by the mere admixture resulting only in aggregation of properties of components thereof, or processes of producing such substances will not be given patents.”

Novartis argued that in substance section 3(d) did not add anything to the requirements already in the Act that an invention must be new and involve an inventive step. It submitted that section 3(d) was included in the legislation out of an abundance of caution but bearing in mind TRIPS, a product which met the criteria of novelty, inventiveness and industrial applicability could not be rejected under section 3(d). That submission was firmly rejected by the Court. It concluded that having regard to the legislative history section 3(d) provided an additional patentability hurdle which had to be met in order for medicinal substances to receive protection:

“On reading clause (j) [novelty] and (ja) [inventive step] of section 2(1) with section 3(d) it would appear that the Act set different standards for qualifying as inventions things belonging to different classes, and for medicines and drugs and other chemical substances, the Act sets the invention threshold further higher, by virtue of the amendments made in section 3(d) in the year 2005”.

Was Glivec caught by section 3(d)?

The first question to be determined was: what was the precursor product against which Glivec had to be compared? As indicated previously, the Court had reached the conclusion that the alpha crystal form of imatinib mesylate was a known substance based on the disclosure of the Zimmermann Patent. Accordingly the Court concluded that the comparison had to be between the alpha and beta crystal forms and not between the imatinib in its free base form and the beta crystal form as Novartis had argued.

However, this left Novartis with a problem. The Zimmermann Patent did disclose the pharmacological properties (in other words anti-tumoural effects) of the free base form, which properties were also present in the beta crystal mesylate. Novartis submitted studies which purported to show that the beta crystal form exhibited approximately 30% improvement in bioavailability over the free base form. But having regard to the Court’s previous conclusion that the mesylate itself was known from the Zimmermann Patent (albeit not the beta crystal form), the free base form was not considered to be the appropriate comparator.

That left Novartis having to argue that the beta crystal form exhibited enhanced efficacy over alpha crystal form. Novartis relied on the aspects detailed above, namely more beneficial flow properties, better thermodynamic stability and lower hydrgropicity. But in the Court’s view none of these were indicators of enhanced efficacy, which is the word used in section 3(d).

The Court did go on to consider Novartis’ argument that the increased bioavailability of the beta crystal form over the free base form meant that the former met the efficacy test. The Court came to the conclusion that increased bioavailability on its own may not necessarily lead to an enhancement of therapeutic effect and that in order to satisfy the test laid down by section 3(d) such an effect must be specifically claimed and established by research data. And in this case there was nothing from Novartis to show this.

Discussion

It has been suggested to the author that the decision of the Indian Supreme Court was little more than a “standard” rejection on the grounds of non-obviousness. It is hoped that sufficient has been said already to indicate that this was far from the case. Admittedly it would have been open to the Court to have reached the conclusion that the patent in suit was simply an obvious development of the Zimmermann Patent and have left matters at that. But, as can be seen, the Court went considerably further.

First, in determining that the Zimmermann Patent disclosed imatinib mesylate, the Court firmly rejected the notion that there can be a substantial difference between coverage and disclosure. Furthermore, in reaching its conclusion as to what the Zimmermann Patent disclosed the Court relied on statements made by Novartis, even though the construction of a patent is supposed to be an….. to continue reading this story please click here

Résumé

Gary Moss, UK Solicitor and Head of EIP Legal

Gary’s career as a leading IP lawyer spans more than 30 years and he has acted in large scale UK IP disputes and cross-border IP disputes both in Europe and the United States. He led the case of Kirin-Amgen v Hoechst Marion Roussel, and Research in Motion v Visto Corporation. Gary handles all aspects of IP litigation, licensing, technology transfer and commercial agreements. He has particular expertise in pharmaceuticals, biotechnology, IT, and technology transfers.


 

[1] The product in question is marked as “Gleevec” in the US and “Glivec” in Europe, Australia and Latin America. For ease of reference only the name “Glivec” will be used in this article.

[2] In actuality the invention was made at Ciba Geigy which was subsequently acquired by Novartis but nothing turns on this.

[3] During the period under consideration the Indian system for determining issues relating to patent applications was undergoing reform which resulted in this case raising a number of procedural issues which are not relevant to the subject under discussion and which have therefore been omitted.

[4] See note 2 above.