[The post is co-authored with Vikram Raj Nanda. A big thanks to Swaraj and Praharsh for their inputs.]
In a detailed 262-page order (pdf) dated 12th September, 2025, Dr Usha Rao, the Deputy Controller of Patents and Designs, annulled Novartis’ patent over its cardiac drug ‘Vymada’ (marketed internationally as ‘Entresto’). The Controller had cumulatively dealt with several post-grant oppositions that had been filed by the Indian Pharmaceutical Alliance, along with two firms: IPCA (Indian Pharmaceutical Combine Association) Laboratories and MicroLabs.
Entresto has been one of Novartis’ best-selling drugs over the years and has had a long history of litigation as well (see earlier posts by Yogesh and Praharsh here). The opposition proceedings in this Entresto dispute have received their fair share of attention as well. First, consequent to the pre-grant opposition, we saw the Single and Division Bench rulings, clarifying the difference between examination and opposition processes in the Indian patent regime (discussed by Yogesh and Praharsh above.) Then, more recently, Anushka offered a detailed analysis of the High Court’s refusal to entertain what might otherwise have been a legitimate request for cross-examination, citing Novartis’s delay and prior conduct during the post-grant opposition process. Finally, after extensive examination and opposition process, multiple writ petitions were filed during different stages of the examination, and we now have this revocation order by the Controller. This post seeks to provide an overview of the Controller’s revocation order and discuss its implications for the Indian pharmaceutical and intellectual property interface.
General Overview and The Market Importance of Entresto
Entresto is a drug consisting of a fixed-dose combination of sacubitril and valsartan that is prescribed for hypertension and heart failure. It has been one of Novartis’ most successful drugs globally, with its revenue indicating a consistent growth trajectory, rising from USD 4.644 billion in 2022 to USD 6.035 billion in 2023 and further to USD 7.8 billion in 2024.
In India, there have been several patent disputes relating to the drug over the years. As per media reports, several pharma companies had attempted to launch generics of the said drug in the past (Natco, Torrent, MSN, and Eris) but had been injuncted by Novartis during the subsistence of its patent (see here).
Stemming from a PCT application dated January 16, 2003, and claiming priority from US Provisional 60/349660, Novartis filed a national phase application 1538/CHENP/2004 for pharmaceutical compositions comprising Valsartan and NEP inhibitors. This application was eventually granted a patent (IN 229051) in 2009 and has now expired (in 2023). While the ‘051 patent was being examined, Novartis filed a National Phase Application No.4412/DELNP/2007 (pdf) (stemming from PCT/US2006/043710 (pdf)) for the crystalline “supramolecular complex” of sacubitril and valsartan (pdf) with a priority date of November 8, 2006. In 2016, Micro Labs Limited, IPCA Laboratories, and Indian Pharmaceuticals Alliance filed a pre-grant opposition under Section 25(1) of the Patents Act, challenging the 4412/DELNP/2007 patent application (pdf). It argued, inter alia, that the claimed invention offered no substantial therapeutic advantage over existing formulations (i.e the now expired IN229051) (para 6.2) and therefore failed to satisfy the requirements of patentability. However, a patent was granted dated 14/12/2022 to Novartis AG, Switzerland, bearing Patent No. 414518 with the Controller finding no evergreening of the expired patent. The grant was challenged again by three post-grant oppositions, which were filed by three different opponents (IPCA Laboratories, Indian Pharmaceutical Alliance and Micro Labs Limited) under Rule 57 of the Patent Rules 2003.
Broadly, the following grounds of opposition were filed which were then accepted by the controller: Section 25(2)(b) (the invention had already been published before its priority date [I], Section 25(2)(c) (it was already claimed in an earlier Indian patent application) [II], Section 25(2)(e) (the claimed subject matter was obvious and lacked inventive step) [III], Section 25(2)(f) (not patentable under the Act) [IV], Section 25(2)(g) (the specification was insufficiently detailed to enable its performance) [V], Section 25(2)(h) (failure to properly disclose information regarding corresponding foreign filings as required under Section 8). While each of these grounds resulted in the revocation, this post shall attempt to zero in on the core thread of the Controller’s order.
The ‘Heart’ of the Matter: Why Did the Controller Decide Against Novartis?
Having outlined the case broadly, we shall seek to discuss what really is at the core of the Controller’s reasoning in this long 262-page order. Firstly, we believe one of the foremost factors that sealed Entresto’s fate was Novartis’ own submissions in a prior case wherein it sought an injunction and successfully obtained an injunction against Natco Pharma Ltd. (see here). The dispute in that case involved a similar supramolecular version of Entresto, and in that case, Novartis had expressly asserted that its earlier patent, IN 229051, covered not only the valsartan-sacubitril combination but also any supramolecular complex thereof (p.28). Consequently, it was noted by the Controller that Novartis cannot make such inconsistent submissions before different fora. This is largely estoppel-based reasoning adopted by the Controller, noting that a party cannot blow hot and cold at the same time and make such inconsistent statements across cases.
The second, and more important, factor that led the Controller to their decision was Section 3(d) of the Patents Act.
This provision has been subject to several academic debates over the years (see here and here). To put it simply, it bars the patentability of a new form of a ‘known substance’, unless it results in an increase in its ‘therapeutic efficacy’ [see Novartis vs UOI (2013)]. For our purposes, there is essentially a two-step inquiry here – first, to identify the ‘known substance’ that is to be used as a comparator with the ‘new substance’, and second, there must be a demonstrable increase in the ‘therapeutic efficacy’ or the new substance from the earlier known substance (prior art).
Now, this is exactly where Novartis failed. Novartis had cited several studies and expert affidavits in support of its submissions, but none actually ended up either comparing the supramolecular complex (new substance) with the original patent IN’051 (prior art) or demonstrating any increase in therapeutic efficacy. For instance, the studies cited by Novartis largely compared the supramolecular complex with [I] valsartan monotherapy (inappropriate as the prior art was a combination of valasartan and sacubitril) or [II] with sacubtril calcium + valasartan free acid (inappropriate comparator as the relevant comparator here was a combination of valsartan disodium and sacubitril monosodium). Furthermore, the expert affidavits provided comparisons with enalapril (a compound unrelated to the original patent) [See Dr. Gauri Billa’s affidavit]. Additional studies cited such as the ‘Ruilope et. al’ compared the ability of lowering blood pressure of the supramolecular complex with Valsartan, which once again, did not prove to be the right comparator. One testimony by Dr Michael Motto did indicate some improved physicochemical properties (solubility, crystallinity, etc.), but nothing that convinced the Controller that the therapeutic efficacy standard had been met.
Accordingly, the Controller concluded that Novartis’ evidence demonstrated no real efficacy improvement from its earlier patent IN’051 and hence, the bar under Section 3(d) was attracted. While there is no specific discussion on evergreening by the Controller, this case does largely serve as another in the long saga of cases that reiterates the standard laid down by the SC in Novartis (2013), reaffirming that if a new form or molecular enhancement is to pass the rigours of Section 3(d), it must demonstrate an enhancement in efficacy with clear accompanying data. Furthermore, this decision perhaps may also underscore in future disputes that even where efficacy data is provided, the comparator must be the correct one, i.e., that enhanced efficacy must be from the prior art and not through isolated or selectively chosen studies.
Some Concluding Thoughts
In sum, this Controller has played an instrumental role in denying Novartis’ attempt to continue its patent over the valsartan-sacubitril combo. As mentioned, in the past several companies had attempted to launch generic versions (Natco, Torrent, MSN, and Eris). This move by the Controller may pave the way for more affordable generics to be launched in the market. Outside India, Novartis’ drug has already seen some intense competition from generics launched in the US market (see Reuters’ report here). Of course, as a caveat, it must be kept in mind that this is all subject to Novartis’ right to appeal the Controller’s decision.
However, given the detailed order here and the patent would have expired within a year, it remains uncertain whether Novartis would even try to file an appeal. Additionally, it cannot be gainsaid that Novartis’ conduct in this matter has also attracted the ire of the courts (see here and here). Previously, two aspects of Novartis’s conduct are worth mentioning: (1) its failure to intimate the Patent Office about writ petitions pending before the Delhi High Court relating to certain opponent filings, heard just a day before the post-grant opposition hearing; and (2) its categorical refusal to participate in the hearings unless cross-examination of the opponent’s expert was first allowed, even at the cost of facing ex parte proceedings that ultimately led to revocation. Taken together, this decision may just deliver the final blow to Novartis’s prolonged attempt to extend its exclusivity over the valsartan-sacubitril combination, bringing an end to its Entresto chapter in India.