Hearing Update: Novartis argues that section 3(d) not applicable to its patent application 12 September 2012, New Delhi. Continuing arguments on behalf of Novartis, Mr Gopal Subramaniam, senior counsel, took the Bench through the Complete Specification of Novartis’ patent application for the beta-crystalline form of imatinib mesylate that was filed before the Patent Controller in India. He said that it has to be ascertained whether the application has to be tested with reference to section 2(1)(j) or with reference to section 3(d). While explaining the background of this patent application, he said that the application relates to a particular form of acid addition salt of methanesulphonic acid of imatinib free base. He said that imatinib free base is disclosed in Zimmerman patent granted in 1993. Responding to Justice Alam’s request to elaborate about the Zimmerman patent, Mr Subramaniam said that there was, at the relevant time, continuing research in relating to medicines including compounds which could work against cancer. He said that medicines that could work against tumour were also examined to see if they would work against cancer because, at that time when research on tumour-inhibiting compounds was progressing, it was considered that cancer was a certain kind of tumour. Mr Subramaniam submitted that the 1993 Zimmerman patent, which had been granted a patent in the United States, disclosed a Markush formula that covered a wide range of compounds having anti-tumour properties. Justice Alam inquired if the Zimmerman patent had been used as prior art against Novartis’ present application in respect of novelty and inventive-step/obviousness. Answering in the affirmative, Mr Subramaniam said that the Zimmerman patent, which was also Novartis’ own patent, was being held against Novartis as prior art. He said that the Respondents (opponents) have, in fact, argued that the disclosures in the Zimmerman patent were adequate for a skilled person to arrive not only at imatinib mesylate but also at the beta-crystalline form of imatinib mesylate. Pointing out that the Intellectual Property Appellate Board (IPAB) has held in Novartis’ favour on this count, Mr Subramaniam said that the IPAB held that the Zimmerman patent disclosed a large varieties of compounds and wide varieties of acids and salts but did not mention particular combinations to produce particular compounds. In furtherance of this argument, Mr Subramaniam took the Bench through the Zimmerman patent. Pointing to the Markush structure disclosed in the Zimmerman patent, he explained that a large number of possible compounds could be substituted to the formula and that the resultant compounds could be used in therapy of tumoural diseases. He said that the Zimmerman patent itself listed several examples, of which the compound exemplified at number 21 was imatinib free base. Mr Subramaniam urged that though the Zimmerman patent also mentioned methanesulphonic acid, it did not mention the combination of imatinib and methanesulphonic acid. Replying to a question from Justice Alam, Mr Subramaniam said that a person skilled in the art would not have been able to arrive at the claimed invention as there are any number of acids and any number of salts. He said that the combination of methanesulphonic acid with imatinib and the process to arrive at this combination are most relevant. He submitted that the choice of the particular acid and the process and conditions under which imatinib free base and methanesulphonic acid are to be combined is not disclosed in the Zimmerman patent. Mr Subramaniam, therefore, argued that the Zimmerman patent does not contain an enabling disclosure, which would make it possible for a skilled person to arrive at the beta-crystalline form of imatinib mesylate. He said that imatinib free base cannot be administered to the human body as it is; therefore, the manner in which imatinib could be taken and administered as a pill into the human body required research. He reiterated that it was Novartis’ research which had led to the conclusion that imatinib and methanesulphonic acid could be successfully combined to make imatinib mesylate, which involved an inventive step. He said that the beta-crystalline form of imatinib mesylate, too, was the result of Novartis’ research. Referring the judges back to Novartis’ patent specification, Mr Subramaniam said that Novartis’ invention comprises of two steps— (i) starting from imatinib free base and finding the particular acid, i.e. methanesulphonic acid, to make the particular salt and (ii) finding the manner and conditions in which imatinib free base and methanesuplhonic acid are combined to make a crystalline form which could be administered into the body. He urged that the beta-crystalline form of imatinib mesylate was arrived at because it has properties such as less hygroscopicity, ability to withstand humidity and ability to have a flow of properties. Explaining the meaning of flow properties to the court, Mr. Subramaniam said that it is the ability of the drug to flow from the machine such that the entire imatinib flows without being stuck in the machine. On being questioned by Justice Alam about Zimmerman’s rights over imatinib and whether the beta-crystalline form of imatinib mesylate would infringe the Zimmerman patent, Mr Subramaniam said that Zimmerman was an employee of Novartis as the patent belonged to Ciba-Geigy, a predecessor of Novartis, and clarified that the patent was only named after the individual who came up with that particular Markush formula. Justice Alam inquired if the Zimmerman patent had been filed without performing the examples described in it and also without testing the efficacy of imatinib free base. Mr Subramaniam replied that efficacy was measured through empirical standards and that the Zimmerman patent disclosed only the potentiality of the use of the compounds mentioned therein. Pointing out that the Zimmerman patent stated that the compounds disclosed by it could be used for treatment of tumours, Justice Alam asked whether it therefore meant that the compound exemplified in example 21 was a known substance of known efficacy. Responding to this, Mr Subramaniam said that though the Zimmerman patent could be regarded as prior art with respect to novelty and inventive step, it could not be regarded as prior art/known substance for the purposes of section 3(d). He added that the efficacy of imatinib was not known and that the use mentioned in the Zimmerman patent was a pharmacological description. He submitted that efficacy could be determined only after human clinical trials and not at the time of filing a patent application. Justice Alam asked if this interpretation (efficacy established through clinical trials on human beings) could be advanced as human clinical trials comes at a later stage as compared to the stage of granting patents. Mr Subramaniam replied that section 3(d) is an exception to section 2(1)(j) (definition of invention) and that the section has a very limited application. He said that the section was introduced only to prohibit evergreening of patents. Explaining his interpretation of section 3(d), Mr Subramaniam stated that imatinib was not in existence at the time the Zimmerman patent was sought. He added that the efficacy of imatinib and imatinib mesylate had not been measured as it had not been administered to humans and that, therefore, neither imatinib nor imatinib mesylate could be known substances for the purpose of section 3(d). He said that any patent seeking an addition over Gleevec/beta-crystalline form of imatinib mesylate would attract section 3(d). To support his proposition, Mr Subramanian relied on an English judgment involving a patent for a derivative of a known compound. He said that, in the case, Beecham held patents for ampicillin, which was a known antibiotic. Bristol, another company, sold hetacillin, a derivative of ampicillin made by adding acetone. Mr Subramaniam said that, in that case which covered what section 3(d) intended to cover, hetacillin was described as “ampicillin with a hat on”. Justice Alam asked if the beta-crystalline form of imatinib mesylate claimed by Novartis was imatinib with “a three piece suit”. Justice Ranjana Desai sought a clarification on the interpretation being advanced. Mr Subramaniam replied that, although imatinib was known in prior art, it was not the known substance for the purposes of section 3(d), as its efficacy had not been shown or established by clinical trials. He said that, in the present case, clinical trials were conducted only on the beta-crystalline form of imatinib mesylate and therefore there was no other “known substance” prior to Novartis’ invention. He submitted that, therefore, section 3(d) would not be applicable to this case and that Novartis did not have to demonstrate enhanced efficacy for the beta-crystalline form of imatinib mesylate. Mr Subramaniam also advanced an alternate argument that, assuming that section 3(d) would be applicable, the beta-crystalline form of imatinib mesylate, in fact, has enhanced efficacy. Responding to Justice Alam’s query whether it was his contention that section 2(1)(j), section 2(1)(ja) and section 3(d) were mutually exclusive, Mr Andhyarujina, senior counsel appearing for Novartis, said that the section 3(d) would not be applicable to this case as the IPAB had upheld Novartis’ beta-crystalline form of imatinib mesylate as an “invention”. Noting that efficacy was the controlling word of section 3(d) and its explanation, Mr Subramaniam reiterated that, for section 3(d) to apply, the known substance and its efficacy must be known and established. He submitted that section 3(d) could not act as an antidote to invention and that sections 2(1)(j) and 2(1)(ja) could not be subservient to section 3(d). He further urged that the inventive step lies in arriving at the particular beta-crystalline form of imatinib mesylate as well as in the increased efficacy of that form. Noting the similarity in the structure of imatinib and in the claims set out by Novartis, Justice Alam inquired about the actual chemical structure of imatinib mesylate. Mr Subramaniam replied that the complete specification does not disclose the exact structure of imatinib mesylate because the methanesulphonic acid was charged and the base is not, so it could attach itself at any of the nitrogen bonds in the imatinib molecule and that, therefore, chemists could not predict where it would be attached and a diagram depicting the exact position of the charged methanesulphonic acid addition salt on imatinib could not be shown. On being questioned by Justice Alam regarding the issue of maintainability of the petition, Mr Subramaniam listed three primary reasons. First, there were only 4–5 years left for the term of patent were a patent to be granted and any delay would further reduce this time. Second, another Bench of the Supreme Court had earlier already commenced hearing arguments in the matter on merits before one of the judges recused himself. Third, there was a question of public purpose involved in this case which needed to be resolved as the interpretation of section 3(d) would be a recurring question and should, therefore, be settled as soon as possible. He pointed out that the test laid down by the Madras High Court was one of therapeutic efficacy and that the IPAB had held that bioavailability of a drug does not enhance its therapeutic efficacy. He, therefore, submitted that the Supreme Court had to clarify on the meaning of efficacy, therapeutic efficacy and whether bioavailability qualified as therapeutic efficacy. On the issue of maintainability, Mr Grover, senior counsel appearing for CPAA, and Mr Salve, senior counsel appearing for Cipla, informed the Court that though they had raised objections as to the maintainability of Novartis’ petition before the Supreme Court on the ground that Novartis had not approached the Madras High Court first, they would prefer for the Supreme Court to decide on this matter. Rajeshwari Hariharan, counsel appearing for Natco, informed the Court that Natco still maintained its objections on this issue. On being asked by Justice Alam as to why the Zimmerman patent could not be taken as showing ‘known efficacy’ of imatinib, Mr. Subramaniam replied that efficacy must be tested in the optimum form, which is possible only through clinical trials, and that therefore imatinib’s efficacy was not known. He further mentioned that the known substance should be tangible and must possess efficacy. For efficacy to of a compound to be known in the sense of section 3(d), he argued that the compound should have been able to be administered to human beings. He said that section 3(d) was not attracted as neither imatinib nor imatinib mesylate had been administered to human beings. Arguing for a strict interpretation of section 3(d), Mr Subramaniam maintained that clinical trials in human beings would be required to prove the efficacy of imatinib and that, at the time of the Zimmerman patent, imatinib was dormant. Mr Subramaniam argued that if known efficacy was not interpreted as proven efficacy, then anyone would be able to obtain a patent by showing that their subsequent form was more efficacious. He urged that section 3(d) required demonstrability, which is empirical efficacy. As Mr Subramaniam relied on documents to explain how Gleevec functioned, Justice Alam sought a clarification regarding the active molecule in Gleevec and asked if the imatinib was the active molecule and the mesylate salt was merely the carrier of the active molecule. Mr Subramaniam replied that though the active molecule was indeed imatinib, the carrier was equally important because, without the carrier, the active molecule was not capable of being administered. Mr Subramaniam then moved on to the legislative history of section 3(d). Alluding to the TRIPS Agreement, Mr Subramaniam said that the Patents Act, 1970 was amended to comply with this Agreement. Referring the judges to article 27 of the TRIPS Agreement, he submitted that the provision indicated a requirement of granting patents to both processes and products. Adverting to the amendments in 2005, which introduced product patents for pharmaceuticals in India and section 3(d) in its present form, Mr Subramaniam read out excerpts from the speech of the then Minister of Commerce and Industry during the Parliamentary debates leading to the passage of the Patent Amendment Bill, 2005, in which the public interest of preventing evergreening was referred to as an issue that had to be addressed. Thereafter, Mr Subramaniam cited the Report of the Mashelkar Committee and read out its terms of reference and said that this Report suggested how section 3(d) ought to be interpreted in the context of the TRIPS Agreement. In response to a query from Justice Alam about the reason the Committee was constituted, Mr Subramaniam replied that the expert committee had been constituted to deliberate on whether it would be TRIPS-compliant to restrict patenting of microorganisms and to restrict patenting of pharmaceutical substances to only a new chemical entity or new medical entity. He pointed out that, with reference to the question on pharmaceuticals, the Committee had suggested that it would not be TRIPS-compliant to restrict patenting to new chemical entities alone and that incremental innovations should be granted patents in India. After obtaining a clarification that the law in India had not been changed since the submission of the Report, Justice Alam inquired about the relevance of the Report. Mr Subramanian replied that the Mashelkar Committee Report was being cited as it underlined the concern regarding evergreening and mentioned that invention did not always mean a new product. Mr Subramaniam urged that there were two ways of interpreting section 3(d). First, to interpret it as a carving out of article 27 of the TRIPS Agreement as suggested by Mr Salve, senior counsel appearing for Cipla. Second, to interpret section 3(d) harmoniously with article 27 of the TRIPS Agreement such that it served a public purpose. Mr Subramaniam also submitted that article 27(2) of the TRIPS Agreement (which lays down a list of exclusions) made it clear that section 3(d) was not meant to be a carve-out. Responding to a question from Justice Alam about the relevance of interpreting section 3(d) in light of article 27(2) of the TRIPS Agreement, Mr Subramaniam replied that his submission was that section 3(d) should be interpreted harmoniously with India’s international obligations under article 27(1) of the TRIPS Agreement so that it did not destroy patent protection. Mr Subramaniam furnished to the Court copies of Novartis’ undertaking supported by an affidavit regarding the continuance of the patient assistance program for Gleevec. However, Mr Grover, senior counsel for CPAA, objected to the attempt to introduce new facts about Novartis’ Patient Assistance Programme through the form of an undertaking. Mr Salve, senior counsel for Cipla, said that he welcomed the undertaking as it would provide an opportunity to explain pricing strategies of multinational pharmaceutical companies. The Court rose for the day. Mr Subramaniam will continue his arguments on 13 September 2012.