Indian Supreme Court Decision in Novartis (Glivec) case

John Richards
Ladas & Parry LLP

Introduction

The Indian Supreme Court has upheld oppositions to Novartis’s patent application for the beta crystalline form of the mesylate salt of Imatinib and held claims to this product unpatentable.

The beta crystalline form claimed in the application is sold as Glivec (aka Gleevec), a widely acclaimed anti-cancer drug, acting by selective destruction of cancer cells.   It was accepted during the Indian proceedings that Imatinib itself was not suitable for oral administration because it has very little solubility so that “if given in solid dosage form, Imatinib free base would sit in the stomach like a brick and would pass out with no therapeutic effect”. The beta crystalline salt of the mesylate salt on the other hand was highly bioavailable.

The application was opposed before grant on the basis of lack of inventive step over disclosure of Imatnib itself and failure to comply with the requirements of Section 3(d) of the Indian Patent Act which inter alia provides that patents shall not be granted for something that is “a mere discovery of a new form of a known substance which does not result in enhancement of the known efficacy of the substance”.  The attack succeeded in opposition proceedings.  On appeal to the Intellectual Property Appeal Board, the claim was found to possess inventive step but not to comply with Section 3(d).  The Supreme Court held the claims to be unpatentable on both grounds.

Extraordinary Direct Appeal from Intellectual property appeal board to Supreme Court

Novartis appealed the decision of the Intellectual Property Appeal Board directly to the Supreme Court rather than taking the normal route of an appeal to the High Court. The Supreme Court extraordinarily accepted the case on the basis of the importance of the issues involved such that an appeal to the Supreme Court would inevitably have taken place  and the fact that had an intermediate appeal been undertaken, any patent that might be  granted would have expired before any Supreme Court decision following an intermediate appeal.

Is Section 3(d) and Amplification of the Requirement for Inventive Step or Does it Impose  Separate requirements?

The first part of the Supreme Court’s decision dealt with the question of whether Section 3(d) was simply an attempt to define inventive step more precisely or constituted a distinct ground for rejection.

In addressing this, the Court discussed the circumstances under which Section 3(d) had been amended by Parliament in 2005 into its present form.  In doing this, the Court noted that the present version of Section 3(d) had been adopted as part of a revision of Indian patent law to bring it into conformity with India’s obligations under TRIPs which had also included repeal of India’s prior bar on the grant of patents for “substances intended for use, or capable of being used, as food or as medicine or drug”.  The Court noted that this bar had been incorporated into the law for the first time in 1970 and had been credited with promoting major developments in the Indian pharmaceutical industry.  It was also noted that passage of the 2005 amendment by Parliament was dependent on opposition support and that in the debate leading up to its enactment, reference had been made to communications from inter alia the HIV/AIDS Director of the World Health Organization pointing out that the 2001 Doha Declaration showed that “the [TRIPS] Agreement can and should be interpreted and implemented in a manner supportive of WTO Members’ right to protect public health and, in particular, promote access to medicines for all.”

The Court noted that as a result of the points made during the Parliamentary debate, and in particular to address concerns raised about possible “evergreening” of pharmaceutical patents, in order to secure passage of the bill, the government had added amended Section 3(d) to provide that a patent could not be granted for

 the mere discovery of a new form of a known substance which does not result in enhancement of the known efficacy of that substance

and added an “explanation” of Section 3(d) to the bill.  This reads as follows:

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.

The Court then considered arguments as to whether these amendments were made simply to reinforce the requirement for an inventive step was required for patentability and concluded:

The amended portion of Section 3(d) clearly 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.

Application of Section 3(d) to the present case

The application of Section 3(d) presented two issues to be decided: 1) what was meant by a “known substance” and 2) what was meant by “efficacy”.

Meaning of “known”

Novartis argued that the known compound against which both questions of inventive step and the improved efficacy required under Section 3(d) was the free base form of Imatinib which, as noted above, is not suitable for oral administration.  The Supreme Court disagreed holding that the appropriate reference point was the mesylate salt.   Novartis’s first patent application (referred to as “the Zimmermann patent”) covering Imatinib itself had contained conventional language about converting free bases into corresponding salts and specifically mentioned salts with “inorganic acids such as hydrochloric acid, sulfuric acid or a phosphoric acid or with suitable organic carboxylic acids or sulfonic acids …”.  There was no specific mention of the mesylate, although this is the salt of a sulfonic acid.  No equivalent application had been filed in India because the invention had been made at a time when there was no product patent protection available for pharmaceutical product in India.

It was noted by the Indian Supreme Court that prior to the priority date of the application in suit, Novartis had filed an Investigational New Drug Application with the United States Food and Drug Administration requesting permission to carry out clinical trials in the United States of the mesylate salt of Imatinib and it was stated that this was “covered” by the U.S. Zimmerman patent.  Subsequently, Novartis had requested patent term extension in the United States for that patent based on FDA approval of the mesylate salt.  It was also noted that several publications before the priority date of the present application had referred to tests using the mesylate salt of “CGP 57148″, although from the reports it does not appear that CGP 57148 was identified publicly as Imatinib before the priority date of the present application.

Against this background, the Indian Supreme Court stated, “we are completely unable to see how Imatinib Mesylate can be said to be a new product … Imatinib Mesylate is all there in the Zimmerman patent.”  The Court rejected arguments that just because something fell within the scope of the claims of a patent, this did not mean that there had been disclosure of that specific thing, saying:

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 the coverage in a patent might go much beyond the disclosure thus seem to negate the fundamental rule underlying the grant of patents.

The Court returned to this theme later saying:

before … proceeding further, we would like to say that in this country the law of patent, after the introduction of product patent for all kinds 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 the coverage and the disclosure under the patent; where the scope of the patent is determined not on the intrinsic worth of the invention but by the artful drafting of its claims by skillful 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.

In light of the discussions made above, we firmly reject the appellant’s case that Imatinib Mesylate is a new product and the outcome of an invention beyond the Zimmermann patent. We hold and find that Imatinib Mesylate is a known substance from the Zimmermann patent itself.

Efficacy

Once the Court had established to its own satisfaction that the mesylate was known, it was clear that the beta crystalline form was a “form” of that substance to which Section 3(d) applied and so the question was whether it had enhanced efficacy over non-crystalline forms of the salt.  Comparisons with the properties of the free base became irrelevant.

As to what was meant by efficacy, the Court said the following:

Efficacy means “the ability to produce a desired or intended result”. … [T]he test of efficacy would depend upon the function, utility or the purpose of the product under consideration. Therefore, in the case of a medicine that claims to cure a disease, the test of efficacy can only be “therapeutic efficacy”. The question then arises, what would be the parameter of therapeutic efficacy and what are the advantages and benefits that may be taken into account for determining the enhancement of therapeutic efficacy? With regard to the genesis of Section 3(d), and more particularly the circumstances in which Section 3(d) was amended to make it even more constrictive than before, we have no doubt that the “therapeutic efficacy” of a medicine must be judged strictly and narrowly. … [S]trict interpretation is based not only on external factors but there are sufficient internal evidence that leads to the same view. … [T]he explanation requires the derivative to “differ significantly in properties with regard to efficacy”. What is evident, therefore, is that not all advantageous or beneficial properties are relevant, but only such properties that directly relate to efficacy, which in case of medicine, as seen above, is its therapeutic efficacy.

Consequently, “mere change of form with properties inherent in that form would not qualify as ‘enhancement of efficacy’”.  This being the case,

the physico-chemical properties of beta crystalline form of Imatinib Mesylate:  namely (i) more beneficial flow properties, (ii) better thermodynamic stability, and (iii) lower hygroscopicity, may be otherwise beneficial but these properties cannot even be taken into account for the purpose of the test of Section 3( d) of the Act, since these properties have nothing to do with therapeutic efficacy.

This then left the question of improved bioavailability.  Despite argument to the contrary, the Court accepted that in appropriate cases, this could be regarded as demonstrating enhanced therapeutic efficacy, but this would need to be “specifically claimed and established by research data”.  There were no such data in the present case.

Conclusion

The Court concluded its discussion of whether the claimed invention was barred under Section 3(d) as follows:

We have held that the subject product, the beta crystalline form of Imatinib Mesylate, does not qualify the test of Section 3(d) of the Act but that is not to say that Section 3( d) bars patent protection for all incremental inventions of chemical and pharmaceutical substances. It will be a grave mistake to read this judgment to mean that Section 3(d) was amended with the intent to undo the fundamental change brought in the patent regime by deletion of [the prohibition on the grant of patents on pharmaceutical products] from the Patent Act.

As noted above, the Court also found the claims to lack an inventive step.  However, there is no full discussion of the reasons for this, the Court apparently viewing this as an inevitable concomitant of its decision on Section 3(d).

Comments

It is probably not surprising, although disappointing,  that the Court held that only therapeutic efficacy and not properties relating, for example, to storage stability, cannot be considered in determining whether Section 3(d) has been complied with. Of perhaps more concern is the holding that a broad teaching renders “known” everything falling within its scope.  This may have implications for “genus/species” or “selection” inventions beyond pharmaceutical industry.

Within the pharmaceutical field the decision presents a further complication to the “patent early or patent late” debate created by the different approaches in Europe where decisions such as those of the U.K. Supreme Court in Human Genome Sciences v. Eli Lilly [2011] UKSC 51 and the European Patent Office in Factor-9/Johns Hopkins T1329/04 encourage early patent filing once a plausible utility has been identified and East Asia where data are required, thereby delaying filing.  The present decision in India seems to indicate that protection for the effective drug could only have been obtained had there been no prior disclosure of Imatinib salt.  That is, the applicant should not disclose anything until it has a commercially viable product.  This hardly seems a way to promote science and the useful arts, but of course there is no such requirement in the Indian Constitution.