Grover appeared for TB survivors Nandita Venkatesan and Phumeza Tisile before the Assistant Controller of Patents and Designs, and also argued a public interest litigation filed at the Bombay High Court by TB survivors Mira Yadav and Brinelle D’Souza, for the issue of compulsory licences on TB medication Bedaquiline and Delamanid.
ON March 23, which happened to be World Tuberculosis (TB) Day, the Indian Patent Office rejected the American pharmaceutical corporation Johnson and Johnson’s (J&J) application for patent on the vital anti-TB drug Bedaquiline fumarate. If granted, it would have extended J&J’s patent monopoly on Bedaquiline beyond its expiry in July 2023 till 2027. To date, J&J has had a monopoly on manufacturing the Bedaquiline compound, used for the treatment of multidrug resistant (MDR) TB patients for whom the first line of drug treatment has failed.
The application for the patent was challenged by the Maharashtra Network of Positive People, a civil society organisation, in one opposition, and TB survivors Nandita Venkatesan and Phumeza Tisile (the former an Indian national and the latter a South African) in another opposition, both of which were heard by the patent office. J&J had filed multiple applications for patents on Bedaquiline fumarate in many other countries.
In her order, Latika Dawara, Assistant Controller of Patents and Designs, noted that J&J’s application failed to meet the requirements of Sections 2(1)(ja) (definition of ‘inventive step’), 3(d) and 3(e) (what are not inventions) of the Patents Act, 1970. Its application under Section 15 (power of Controller to refuse or require amended applications, etc., in certain cases) of the Patents Act was also rejected.
In 2014, globally, an estimated 20 percent of previously treated cases with MDR-TB were reported. With approximately 147,000 people suffering from MDR-TB, India is among the countries with one of the highest DR-TB burden.
Senior advocate Anand Grover had appeared for Venkatesan and Tisile before the Assistant Controller of Patents and Designs. In addition, in March 2021, Grover had argued a public interest litigation filed at the Bombay High Court by TB survivors Mira Yadav and Brinelle D’Souza— the latter being the co-convener of the Jan Swasthya Abhiyan, a network of health activists combatting inequities in health— for the issue of compulsory licences on Bedaquiline and Delamanid under Sections 92 (special provision for compulsory licences on notifications by the Central government) and 100 (power of Central government to use inventions for purposes of government) of the Patents Act. These drugs are patented— Bedaquiline by Belgium-based pharma company Janssen Pharmaceuticals, Inc., a subsidiary of J&J, and Delamanid by Japan-based pharma company Otsuka Pharmaceutical.
Grover spoke with The Leaflet on anti-TB drug access in India, the process of grant of patent rights, the strategy of ‘evergreening’ adopted by pharmaceutical corporations, and compulsory licences.
Q: What is the extent of the need for access to anti-TB drugs Bedaquiline and Delamanid in India?
A: Firstly, the TB epidemic is a major health problem all over the world, but more particularly in India. In 2017, India had 27 per cent of the global TB cases. In 2019, the private and public sectors notified 2,404,815 TB cases across India.
In the last decade, there has been a considerable increase in drug-resistant TB (DR-TB), which is an active tuberculosis disease caused by resistance to one or more anti-TB drugs. The National Strategic Plan for TB: 2017–25 – Elimination by 2025 recognises that India has the highest burden of multidrug-resistant TB (MDR-TB) in the world.
In 2014, globally, an estimated 20 percent of previously treated cases with MDR-TB were reported. With approximately 147,000 people suffering from MDR-TB, India is among the countries with one of the highest DR-TB burden. Cases of extremely drug-resistant TB (XDR-TB) and totally drug-resistant TB (TDR-TB) have also been reported to be on the rise in India.
Secondly, before the discovery of antibiotics for treatment, TB was fatal. Now TB has become treatable over a period of time with a combination of drugs. For treating MDR-TB and XDR-TB, the new drugs Bedaquiline and Delamanid were introduced. These drugs are oral, have a more effective role in treatment, and have to be taken for a shorter duration. This makes the need for their availability desperate and immediate.
On the other hand, traditional treatment of MDR-TB and XDR-TB requires the use of second-line anti-TB drugs that entail a high-pill burden, injectables, long treatment duration, and adverse side effects, including hearing loss and kidney failure.
Q: What are the main factors for granting patent rights in India in terms of international law?
A: The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS agreement) was signed by all members of the World Trade Organisation, and came into force on January 1, 1995. Every signatory country was required to comply with the TRIPS Agreement and make laws in accordance with it by various dates. So, while most developed countries were to comply within one year, for the least developed countries, that period has now been extended to 2033. India was required to comply with the TRIPS Agreement within ten years, that is, by January 1, 2005.
In the case of Bedaquiline, the initial patent term is till July 2023. But if the fumarate salt would have been patented, the patent on the fumarate form would have been till 2027, thus extending it by four years. By grant of a patent in new forms, the patent term is extended, which is termed ‘evergreening’. Section 3(d) tries to address ‘evergreening ‘.
Unlike other international agreements, such as human rights conventions, the TRIPS agreement has teeth. Non-compliance can lead to sanctions, as India found out when we did not introduce legislation in the interregnum between 1995 till 2005. We were to introduce the interim legislation providing for Exclusive Marketing Rights (EMR), which we did not.
Consequently, the United States dragged India to the TRIPS Dispute Settlement Tribunal set up under the TRIPS Agreement. The tribunal ruled against us. We filed an appeal at the appellate tribunal but we lost there too. Ultimately, we had to introduce the EMR legislation in 1999. Had we not, India would have had sanctions imposed upon it.
Under the TRIPS agreement, all signatory countries have to provide protection for products as well as processes. A patent is a grant given by a governmental authority; in India, that authority is the patent controller. As it is a grant by the government, the government can also withdraw it.
Universally, the most important criteria for patents are two-fold. Firstly, the invention needs to be new or ‘novel’, that is, it must not have been published in any written form or not have been practised anywhere in the world. If it has been either published or practised, the claimed invention is not ‘novel’. It should be noted that the exact claimed invention must have been either written about or practised.
The second important criterion is to check whether the product is ‘inventive’, which is the opposite of the notion of obviousness. If it is inventive, it cannot be obvious to a ‘person skilled in the art’ (POSITA). For instance, a POSITA will see what is the nature of the landscape of a product of a particular field, on the basis of which the POSITA can determine whether the claimed invention is a jump or an ‘inventive step’ on the prior art.
It is a complex process when the invention is claimed to be of a particular date. The claim may be argued years later from the date of the invention, requiring the POSITA to place herself at the time of invention. For instance, in our case, it needs to be enquired what the landscape of Bedaquiline is at the time of the claimed invention, which is called ‘the priority date’ and whether the fumarate salt is an inventive step over the prior art.
Thus, the questions are: a) at the time of the priority date, what is the landscape in the field of the claimed invention?, and b) in that context, is the claimed invention obvious or not?
Q: What about India; do we have different patent laws?Can you explain how the strategy of ‘evergreening’ or serial patenting is adopted by pharmaceutical corporations?
A: Patent laws are similar all over the world, but there are important differences. Thus, apart from these two parameters prevailing internationally, in India, we have another parameter, that is, Section 3(d) of the Patents Act.
When, in around 2005, India was required to have a TRIPS-compliant patent law, it was noticed that nearly 76 percent of the pharmaceutical inventions patented in the United States and Europe were simply new forms of old, known substances without much therapeutic benefit to patients. The civil society, the opposition and even the Indian government were looking for ways to address this.
Most of the drugs invented initially are in the base form. New forms can be made easily. Thus, the form of salt makes them more soluble and more bioavailable. The crystalline form is pure. Additionally, new forms can be obtained by making them into solid tablets, liquids, gaseous and so on. In these new forms, the active ingredient is the same substance. It is that ingredient which acts therapeutically in the body. But with the new form, there is usually no increase in efficacy.
Like in Novartis, Janssen did not show any data to prove any increase in efficacy, much less a significant increase. Hence, the claimed invention was hit by Section 3(d).
Through the introduction of Section 3(d) of the Patents Act, the idea was said to be that if a new form of a known substance is sought to be claimed as an invention, it will not be patented unless there is a “significant increase in efficacy”.
By patenting new forms of the same substances, the length of the patent term is extended. Thus, in the case of Bedaquiline, the initial term is till July 2023. But if the fumarate salt would have been patented, the patent on the fumarate form would have been till 2027, thus extending it by four years. By grant of a patent in new forms, the patent term is extended, which is termed ‘evergreening’. Section 3(d) tries to address this ‘evergreening ‘.
Q: How did all this play out in the patent claim by Janssen over the Bedaquiline fumarate?
A: When I appeared for Venkatesan and Tisile, we responded to Janssen’s amended claims and argued that the fumarate salt was already disclosed in ‘prior art’ (any writing prior to the priority date is prior art), and it was, therefore, not ‘novel’. The patent controller rejected our argument on novelty. However, on the ground of obviousness, the patent controller agreed with us. ‘Prior art’ disclosed the fumarate salt form and it was also straightforward to make it. She held that there is no ‘inventive step’.
As far as Section 3(d) was concerned, in the Supreme Court’s judgement of Novartis AG versus Union of India & Ors. (2013), the Swiss multinational pharma company Novartis AG claimed that the drug Imatinib Mesylate is more bioavailable. (Bioavailability is the amount of drug available to the target organ). Bioavailability can go up if, for instance, from the base, you make a salt form which is more soluble than the base form.
However, the Supreme Court had held that bioavailability does not necessarily translate into efficacy. To prove therapeutic efficacy, the data on the function of each drug should be shown, which the party claiming the patent failed to do.
In the case of Bedaquiline, Jannsen claimed that because the fumarate salt of Bedaquiline was more bioavailable, it was more efficacious than Bedaquiline itself. However, like in Novartis, they did not show any data to show any increase in efficacy, much less a significant increase. Hence, the claimed invention was hit by Section 3(d).
We also argued that the Bedaquiline formulate is not standalone, but is a mixture consisting of other components. Section 3(e) of the Patents Act says that pure mixtures will not be granted patent unless it is shown to have a ‘synergistic effect’.
‘Synergistic effect’ means that the total efficacy of the mixture is more than the sum of the two components. For instance, suppose component A gives you an efficacy of five and component B gives you an efficacy of ten, and the total efficacy is 15 without mixing. If on mixing, the effect is more than 15, it has a ‘synergistic effect’. Janssen failed to show that by data in this respect. Therefore, it failed in proving its claim under Section 3(e).
Q: What does the rejection of J&J’s application to extend their patent rights over Bedaquiline signify?
A: Janssen won’t have patent rights over Bedaquiline after July 2023, which means that generic companies can now produce the drugs without being arraigned in an infringement proceeding on the patent of Bedaquiline. If the patent had been granted, then since Janssen was using Bedaquiline and the fumarates, other generic companies would not have been able to make the fumarate salt at all.
When generic companies enter the market, and ideally five should be able to in this case, with the competition, the price is reduced to nearly 10 percent.
With the absence of a monopoly, generic companies will be able to come in, and instead of a cost of US $400, that is, the rate at which Bedaquiline is sold to the government, the price will be revised to a mere US $40 for the whole course. Thus, when generic companies enter the market, and ideally five should come in, with the competition, the price is reduced to nearly 10 percent.
Q: In the Bombay High Court, you have argued for granting compulsory licences for the anti-TB drugs Bedaquiline and Delamani. Can you explain the concepts of compulsory licences versus voluntary licences?
A: If someone from the United States wants to sell a product in India, they will licence a distributor on certain terms and conditions to sell and distribute that product in India. The two parties would have voluntarily agreed to have a licence, amounting to a ‘voluntary licence’. As opposed to that, a compulsory licence is issued by the patent controller without the consent of the owner of the patent. The TRIPS agreement and all patent laws provide for a ‘compulsory licence’.
A compulsory licence is a compulsion by the law and by the government, which is provided under Section 84 (compulsory licences) of the Patents Act. Section 84 states such a licence can be issued on the fulfilment of any of three conditions, namely, if reasonable requirements of the public are not satisfied, or if the price is not affordable, or if the patent has not worked in India.
Under this provision, a private entity has to attempt negotiations to get a voluntary licence from the patent owner. If that move fails, the applicant has to move the patent controller against the patent owner and apply for a compulsory licence, and satisfy the conditions under Section 84, after which there is a procedural hearing, followed by an order. This happened in Bayer Corporation versus Natco Pharma Limited (2013)before the Indian Intellectual Property Appellate Board.
Under Section 92 of the Patents Act, the government can issue compulsory licensing orders in circumstances involving a national emergency, extreme urgency or for public non-commercial use. Under Section 100 of the Patents Act, the government can use the patented product or process for its own use. Thus, in the procedure under Section 92, a compulsory licence will be issued and given to a private entity, and under Section 100, the government will now make it for its own use, or get somebody else to make the same for it. We argued under both Sections 92 and 100 for compulsory licences of Bedaquiline and Delamanid.