[This post has been co-authored by Swaraj Paul Barooah and Pranav Aggarwal. Pranav is a second-year student pursuing B.A.LL.B.(Hons) at Rajiv Gandhi National University of Law, Punjab. He has a keen interest in commercial laws, especially in IP and allied fields. His previous post can be accessed here].
On September 29th, 2023, the Pharma giant, Johnson and Johnson (“J&J”) made headlines around the world after they (finally) announced that they will no longer enforce their patents for bedaquiline (brand name: Sirturo) which is used in the treatment of multidrug-resistant tuberculosis (MDR-TB) in 134 low- and middle-income countries.
As readers may know, in India, tuberculosis has been causing hundreds of thousands of deaths a year, for decades now. This, despite the various moving targets of eliminating TB from time to time, as well as the WHO declaring it a Global Health Emergency as far back as 1993 (30 years ago!). Bedaquiline is also in the List of Essential Medicines by the World Health Organisation. So, we thought we’d look into what this announcement might mean for India, as well as the rest of the world. Interestingly, the first patent for Sirturo was filed on 18/07/2003 (PCT/EP2003/050322), meaning it is (more than) 20 years since their first filing. And earlier this year, the Indian patent office rejected their attempt to file a secondary patent on the drug. Anyhow, we’ll come back to this in a bit.
First, a Closer Look at the Announcement
Let’s first look at what exactly was said in the announcement.
“…[J&J] today confirmed its intent not to enforce patents it owns and controls for SIRTURO® (bedaquiline) in the treatment of multidrug-resistant tuberculosis (MDR-TB) in 134 low- and middle-income countries[1,2].
The decision is intended to assure current and future generic manufacturers that they may manufacture and sell high quality generic versions of SIRTURO® without a concern that the Company will enforce its bedaquiline patents, provided the generic versions of SIRTURO® produced or supplied by generic manufacturers are of good quality, medically acceptable, and are used only in the 134 low- and middle-income countries.”
First off, it is clear that this is not a legal commitment to not enforce its patents, but rather a confirmation of its “intent” not to enforce its patents. They have also not specified which patents are covered by this. According to a UNITAID report, there are at least 5 Janssen patents associated with bedaquiline. The stated intention is to assure generic manufacturers that they can proceed with manufacturing bedaquiline, under 2 conditions: quality, and usage (only) in the 134 LMICs. For practical purposes, this is likely to suffice, as it would lead to quite the PR disaster if J&J reneged on this. (But then again, let’s not forget Moderna who revoked its patent pledge right before suing Pfizer for infringing its COVID-19 vaccine patent). Indeed, companies like Lupin, Natco, and Macleods have already shown interest in manufacturing, which would indicate that they see a positive business interest in pursuing this manufacturing.
Interestingly, J&J’s reasons for this announcement are claimed to be to address the under-diagnosis problem with MDR-TB. They’re not wrong that under-diagnosis is a very large problem, but claiming there is a strong connection between under-diagnosis and not-enforcing patents seems a bit of a stretch! Of course, claiming the reason was lack of access to the drug, would be undesirable from their own PR front, as it would admit that they could’ve done more for all these years and did not. Especially given how much noise public health groups have been making about this. Nonetheless, if there is indeed some connection between these two, it would be useful to see this evidence.
Finally, while they mention that they won’t enforce their bedaquiline patents in 134 LMICs, it seems curious that they haven’t directly mentioned which countries, but rather say it is available on request. We sent a request for this list on 3rd October and are yet to receive a response as of date (9th November). Nonetheless, the interesting part is that there are only 134 LMICs, as per the World Bank categorizations, so it is once again a curious choice not to simply mention them.
Next, What are the Bedaquiline Patents and What do They Cover?
Tuberculosis and Bedaquiline
According to the Global Tuberculosis Report 2023, although the cases of Tuberculosis have been de-accelerating, the different variants like MDR-TB haven’t been controlled properly especially after Covid-19. Globally, the burden of multidrug-resistant TB (MDR-TB), which had been decreasing till 2019, jumped up again in 2021, with an increase of 3.1% from 2020 with 2020-21 having 4,50,000 new cases.
Surprisingly, a huge chunk (42%) of the MDR-TB cases are concentrated in three countries: India (26%), Russia (8.5%), Pakistan (7.9%). Other major countries that are highly affected are Indonesia, China, Philippines and Myanmar.
Janssen (J&J’s pharma entity) drug bedaquiline, which was the first new treatment for TB approved in several decades, catalyzes a shorter, easier-to-administer, and more parent-tolerable treatment regimen. It was approved through an accelerated approval process based on partial trials, i.e., Phase 2 trials in the US in 2012, and EU in 2013, following which the WHO released its Interim Policy Guidelines to guide usage in the absence of Phase 3 trials. In the years after this, Janssen entered into collaborations with several other actors (including in academia, non-governmental organizations and governments) to take it through to Phase 3 trials and to address the range of research questions to use it to its full potential. Exactly how much went into the development, is, as usual, an unknown answer. Some studies, for eg, Gotham et al (2020) show that total public investments (USD 455-747 million) are several times higher than Janssen’s investments (USD 90-240 million). Meanwhile, Janssen has claimed they made R&D expenditures of approximately USD 500 million, though without any breakdown. (Fn 12 of the same paper). Regardless of who invested how much, Janssen does have ownership over at least 5 patents, as mentioned above, and this is what we look at below.
The Patent Case
In 2003, the Company made a patent application, PCT/EP2003/050322, under Patent Cooperation Treaty (PCT) of a chemical compound, Quinoline, the fumarate salt, which is used as mycobacterial inhibitors and further production of MDR-TB Drugs like Bedaquiline. The application WO2004/011436, was published in 2004. This meant that most of the countries where the company got the patent through PCT would have anyway expired by this year. This patent (corresponding Indian application number: 220/DELNP/2005) has already expired in the ‘market’ with the most number of patients, i.e. India.
As mentioned above, there are 4 more applications. One of these (1220/MUMNP/2009) was rejected by the Indian patent office earlier this year. The three other applications are still pending before the patent office. These are 6315/DELNP/2006 , IN202017005443, and 20172703004. The latter two here have oppositions pending against them as well, filed by Delhi Network of Positive People and Ganesh Acharya for both the patents. The UNITAID patent landscape report has a few more details such as rejected/granted status in other countries, for those interested. At a glance, it appears these have been opposed by various interest groups in countries like South Africa, Belgium and Sweden or have been denied subsequent patents as in the case of India.
As mentioned above, India accounts for the highest no. of cases of MDR-TB and as per the Ministry of Health’s Indian TB Report (PDF), around 1,19,000 cases were reported in India alone in 2021. Therefore, the need for a drug like Bedaquiline cannot be emphasized more. The Government of India issued guidelines in regard to the usage of Bedaquiline. Interestingly enough, the drug on the basis of the WHO recommendation and the approval given by the United States Federal Drug Authority in 2012 was allowed in India by the Drug Controller General of India (DGCI) without any local trials. The whole regulation was done through the Revised National Tuberculosis Control Programme (RNTCP) as far as the availability of the medicine were to be ensured. For a brief overview of the introduction of Bedaquiline in India and concerns about introducing it at this stage, readers can refer to posts such as this one on the blog.
Aside from the now expired ‘main’ patent (220/DELNP/2005) there was an attempt of a follow-on patent through Janssen’s application 1220/MUMNP/2009 which could extend its exclusivity for four more years. This was met with considerable opposition by two TB survivors and the application was ultimately rejected by the Patent office in March 2023. As described in the linked post, it was denied on the grounds of Section 3(d) and 3(e) of the Patents Act 1970 as the current application evidently drew from the previous granted patent and lacks inventive steps as provided under section 2(1)(ja).
As per this WHO report (PDF – p.29) the drug costs between USD 900 (low income countries) to USD 30,000 (high income countries) per patient for a 6 month course. The cost of production (Gotham et al, 2017), is estimated to be just around US$130. So, with the estimated relatively low cost of development, along with the estimated low cost of production, and with the patents either being rejected, expired or opposed in most places, it does leave open the question of how much meaning this non-enforcement actually has.
Mere window dressing or genuine promotion of increased manufacturing, whatever may be the motive of the Company, increased production (as is expected with more generics on board) will hopefully come to the aid of the patients for whom such drugs were neither affordable nor accessible till now. Not just for India, but other LMICs like Pakistan, Myanmar and Indonesia etc. as well.