The banning of diabetes drug pioglitazone (now looking set to be revoked) has put Merck’s patented drug sitagliptin or Januvia back into the limelight in India. Critics of the ban have highlighted the added expense of moving patients from pio to sitagliptin, a possible alternative. This is a good time to take another look at a patent infringement lawsuit currently pending between Merck and Mumbai’s Glenmark which launched a generic of sitagliptin in India some months ago.
Merck (MSD Pharmaceuticals in India) claims that Glenmark has violated its sitagliptin patent on the grounds that Glenmark’s versions (Zita and Zita Met) contain the same phosphate salts as the patented medicines.
In April, Justice Rajiv Sahai Endlaw dismissed Merck’s interim application requesting that Glenmark stop manufacturing and selling versions of Merck’s diabetes medicines, Januvia and Janumet (a combination of sitagliptin with off-patent drug metformin).
Insignificant price difference
This case is particularly interesting because it differs from other recent patent infringement cases. While previous cases have focused on the issues of access and pricing, this case is likely to center on the technicalities of Indian intellectual property (IP) rights law.
Although courts have cited affordability as grounds for rejecting patent infringement appeals in previous cases, the price differential between the products of Merck and Glenmark is not significant nor the issue in this case. Notably, Merck emphasized this point in order to allay the influence of the Indian Supreme Court’s decision regarding the Novartis drug Glivec.
Given this, there is some consensus that the key arguments will be on the technicalities of IP law. Specifically, those related to multiple patenting of single inventions and injunctions against infringement by generic producers. The clarity, or ambiguity, provided by this decision will have important implications for the IP rights ecosystem in India.
A rose by another name?
A review of Merck’s patents reveals that Januvia is protected by two patents in India, specifically IN209816 and IN219148. Sitagliptin itself is covered by product patent IN209816, while IN219148 is a process patent covering intermediates used in the manufacture of Sitagliptin. In the context of the infringement claims, Glenmark’s use of the phosphate salt is key.
Merck’s allegation seems to be bolstered by the details specified in patent IN209816, where salt forms are defined as, “When the compound of the present invention is basic, salts may be prepared from pharmaceutical acceptable non-toxic acids, including inorganic and organic acids. Such acids include acetic, benzenesulfonic, benzoic, camphorsuifonic, citric, clhanesulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, isclhionic, lactic, maleic, malic, mandclic, methanesulfonic, mucic, nitric, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric, p-toluenesulfonic acid, and the like. Particularly preferred are citric, hydrobromic, hydrochloric, maleic, phosphoric, sulfuric, fumaric, and tartaric acids.” (Complete specification of the patent is available here).
Accordingly, it seems reasonable to conclude that the production of sitagliptin phosphate, which cannot be done without producing sitagliptin, constitutes patent infringement. This conclusion seems to be further strengthened by the fact that phosphoric acid in not just mentioned in the patent, but is listed as one that is “particularly preferred” by patent IN209816.
Conflicting rulings
Specifically, two elements stand out as particularly important. First, the Januvia case points to the complexity of India’s intellectual property laws and the apparent conflicts across recent patent rulings. In particular, this case and the ruling against Novartis’ Glivec. In this case, Glenmark’s arguments rely heavily on the differentiation of its generic due to the salt form used.
In contrast, in the Novartis case, the claim was overturned on the grounds that the new salt form utilized was unpatentable since it was merely a new form of a known substance. Secondly, the Januvia case has renewed calls for patent linkage regulations. In essence, the regulatory and marketing approval of a drug product would be linked to its patent status (more details may be found here).
Merck questioned the marketing approval of Glenmark’s product and endeavored to prevent the sale of Glenmark’s generics on the grounds that such sales constituted infringement since Merck has a valid patent on sitagliptin. Advocates argue that generic marketing approval affects patent rights and therefore such a linkage is necessary.
Opportunity for clarity
The Januvia case presents another opportunity to bring additional clarity and lucidity to the Indian intellectual property rights ecosystem. The future of innovation depends on predictability and transparency and this case may either strengthen the incentives for innovation or undermine the system with additional ambiguity. The rulings will help shape the Indian market and have significant implications for Indian patients.
Currently, India is the country with the largest diabetic population and Januvia is the preferred therapy. There are approximately 65 million Type 2 diabetes patients in India, and the number is expected to reach close to 70 million by 2025. This case will cast a long shadow over their treatment options and continued innovation on diabetes and other diseases.
Dr Kristina Lybecker is Associate Professor of Economics at Colorado College in Colorado Springs. Kristina is an economist with a PhD from the University of California at Berkeley. She specialises in innovation and intellectual property rights and has been writing on these issues for 12 years. She is currently employed full-time at Colorado College. In the interests of transparency, the writer states that she has been commissioned to work for the pharmaceutical industry on issues of innovation, corruption, counterfeiting and intellectual property rights. However, she has not been compensated or otherwise rewarded for this piece which stems from her intellectual interest in the topic and closely relates to her academic research.
Pic sourced from http://www.coloradocollege.edu
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