Global drug manufacturers represented by the Organisation of Pharmaceutical Producers of India (OPPI) have sought 'legislative review' of the section 3(d) of the Indian Patents Act and a redefining of the 'efficacy criteria'.
Section 3(d) of the Indian Patent Act restricts grant of patent for "incremental innovations" in many drugs unless it provides significant therapeutic advantages to existing molecules.
Recently there have been questions on existence of section 3(d) and the defining of term efficacy in that section, how is enhanced efficacy defined in the section. The dispute relates to India's IPR regime, which prevents patenting of known drugs, and linking the marketing approval of drugs with their patent status, among other issues.
OPPI proposal forwarded by the PMO is the need to link the patent office and the drug regulatory authorities. OPPI has sought the alignment of the applicable statutes, so that rights granted under one statute are not taken away under the other.
This article is created to give a full view and meaning of section 3 (d), how the section is having good standing. How it is being taken and understood wrongly and the explanation that there is not complete rejection under section 3(d), and if there is genuine innovation and improvement, then a patent can be granted for different forms of existing components.
Section 3(d) says 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, is not patentable.
ITS INTERPRETATION IS SOMETHING LIKE THIS:
Mere discovery of a new form of a known substance which does not result in the enhancement of the known efficacy of that substance is not patentable. Which means different forms of a known substance must differ significantly in the properties with regard to efficacy.
The examiner makes comparison with regard to properties or enhancement of efficacy between the known substance and the new form of known substance. In case the new form is further converted into another new form, the comparison is made between the already existing form and another new form but not between the base compound and another new form.
The efficacy need not be quantified in terms of numerical value to determine whether the product is efficacious because it is not possible to have a standard numerical value for efficacy for all products including pharmaceutical products.
In regard to 'efficacy' in pharmaceutical products, the Madras High Court observed: "going by the meaning for the word "efficacy" and "therapeutic" ... ..., what the patent applicant is expected to show is, how effective the new discovery made would be in healing a disease/ having a good effect on the body? In other words, the patent applicant is definitely aware as to what is the "therapeutic effect" of the drug for which he had already got a patent and what is the difference between the therapeutic effect of the patented drug and the drug in respect of which patent is asked for."
"Due to the advanced technology in all fields of science, it is possible to show by giving necessary comparative details based on such science that the discovery of a new form of a known substance had resulted in the enhancement of the known efficacy of the original substance and the derivatives so derived will not be the same substance, since the properties of the derivatives differ significantly with regard to efficacy." (Novartis AG v. Union of India W.P. 24760/06)
Mere discovery of new property of a known substance
A mere discovery of a new property of known substance is not considered patentable. For instance, the paracetamol has antipyretic property. Further discovery of new property of paracetamol as analgesic can not be patented. Similarly, ethyl alcohol is used as solvent but further discovery of its new property as anti knocking, thereby making it usable as fuel, can not be considered patentable.
MERE DISCOVERY OF ANY NEW USE OF KNOWN SUBSTANCE
A mere discovery of new property of known substance is not considered patentable. For instance, new use of Aspirin for treatment of the cardiovascular disease, which was earlier used for analgesic purpose, is not patentable.
HOWEVER, A NEW AND ALTERNATIVE PROCESS FOR PREPARING ASPIRIN IS PATENTABLE.
Similarly, the new use of methyl alcohol as antifreeze in automobiles. The use of methanol as a solvent is known in the prior art. A new use has been claimed in this claim as antifreeze which is not allowable. Further, a new use of Chloroquine for Sarcoidosis (a fungal disease) and for Infectious mononucleosis (a viral disease) and for Diabetic neuritis (inflammation of nerves) is not patentable.
Mere use of a known process is not patentable unless such known process results in a new product or employs at least one new reactant. Similarly mere use of known apparatus or machine for another purpose is also not considered patentable.
In a patent application No. 782/Cal/1981, dated 13th July, 1981, an invention related to pharmaceutical composition exhibiting anti-phlogistic, antipyretic and analgesic activity and high gastroenteric tolerance in unit doses form which contained imidazol salicylate as the active ingredient in the amount of 100-600 mg and an inert carrier was claimed which was later amended to a process for the preparation of novel composition containing imidazole salicylate having formula 1, as the active principle. It was held by the Controller that the active compound such as imidazole salicylate was known in the art and applicant could not develop any special property or even improve upon the property of the compound to be mixed up with the usual carrier to form the composition. Furthermore, the description contained no indication of using any special type of solvent for its purification by re-crystallization and, therefore, the invention was not patentable under section 3(d) of the Act. (Decisions on Patent and Designs vol. (4) published by Patent Office Technical Society).
A suit filed by Swiss drug maker Novartis AG in the Madras high court after the company's patent application for a beta crystalline form of a known cancer drug, imatinib mesylate, was rejected by the Chennai patent office in 2005. The Supreme Court's decision on Novartis' appeal is awaited.
A case filed by German drug maker Bayer AG and its local associates is questioning the Drug Controller General of India's right to approve a generic version of liver cancer drug Nexavir by Cipla Ltd. This case is also pending with the Supreme Court after the Delhi high court rejected Bayer's petition.
The term 'significant' cannot be used while interpreting the section because it is vague (the term varies with regard to the application) Therefore, in order for a new drug (in respect of which a patent is asked for) to have greater efficacy when compared to a known drug, the new drug must not be bio-equivalent to the patented drug i.e. the new drug must lie outside the defined range of bio-equivalency when compared to the existing drug.
The reason why Big Pharma dislikes Section 3(d) is that it makes it difficult to get patent rights for new (physical) forms or admixtures of previously known New Chemical Entities (NCEs) unless these seemingly trivial changes bring 'significant improvement in the efficacy' of the product in question. If vigorously implemented, Section 3(d) can thwart stockpiling of separate 20-year patents for multiple attributes of a single product. It is not that the Indian patent offices haven't granted patents for deserving incremental inventions that are of real therapeutic value to the patient-consumer. In a review petition filed by Ind Swift Industries under Section 77 of the Patents Act, the petition called for review of the Deputy Controller's decision in an unsuccessful pre-grant opposition to Cadila's application by Ind Swift Industries. Cadila's application (now a Patent) concerned Crystalline form Clopidogrel Besylate, which is used to prevent clotting of blood and in treatment of cardiac ailments.
Ind Swift cited a couple of documents on studies which compared the efficacy of crystalline clopidogrel besylate with clopidogrel bisulphate and clopidogrel hydrogen sulphate and concluded that there was no "overall significant difference" in the antiplatelet effect of the crystalline form.
The Deputy Controller however affirmed the decision given in the pre-grant proceedings based on the material submitted by Cadila during the examination and opposition proceedings. He endorsed the view taken in the pre-grant order, wherein it was held that crystalline clopidogrel besylate "has superior beneficial properties, which greatly enhance its commercial value".
The value needs to be equated well to get the beneficial effect of final results. Comparing clopidogrel bisulphate and crystalline clopidogrel besylate, he observed that the concentration of the inactive metabolite increased over a period in the former thereby reducing the therapeutic efficacy of the drug. On the contrary, no inactive metabolite was detected in crystalline clopidogrel besylate claimed by Cadila, which increased the shelf life of the drug.
On the issue of stability, Deputy Controller observed that the pure crystalline form remained stable and free-flowing after 2 months even when compared to solvated forms of crystalline clopidogrel besylate. Also, the pure crystalline form was found to be less cardiotoxic than the solvated form.
In view of the above, the Deputy Controller held that Cadila's application did not attract Section 3(d). In this decision, the Deputy Controller avoided, or probably desisted from discussing numerical limits to be set in understanding what constitutes "enhanced efficacy". Deputy Controller seems to take an approach, where a host of characteristics which contribute to enhanced efficacy of the drug, would be relevant for the purposes of evaluating it on the anvil of Section 3(d). Importantly, such factors could include enhanced shelf-life of the drug as opposed to pure therapeutic efficacy of a certain dosage.
If the Section 3(d) is reviewed and amended then a lot of non-patentable products will squeeze into the Indian market with a monopoly. Till Section 3(d) is there, global Pharma companies cannot market drugs which are not novel. Simple physical modifications will not be patentable in presence of Section 3(d) the pharmaceutical industries reluctant towards further improvement of a known drug or discovery of new therapeutic use of a known substance. It is clear from the above paragraphs and discussions, that pharmaceutical research does not halt on patenting of one pharmaceutical activity mainly due to ongoing research the same drug may be found to have other beneficial properties which was previously unrecognized. Therefore, from the viewpoint of a pharma industry the exemption of swiss-type claim format in India is unwelcoming and would rather harm to the Industry.
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