How much of a win is a patent rejection for domestic generics production? In this post, I discuss the specific points of IPO’s refusal as a continuation of Indian patent jurisprudence on Section 3(d), and why, irrespective of the essentiality of patent law to the discourse on generics, contrary to news reports, a single patent refusal alone is not sufficient in improving access to cancer therapies.
The Making of a Blockbuster Drug
Venetoclax is a blockbuster cancer drug jointly developed by AbbVie and Roche, marketed under the brand name ‘Venclexta’. It is the first orally administrable medicine used in the treatment of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) and acute myeloid leukemia (AML). B-cell lymphoma 2, or Bcl-2, is a family of evolutionary proteins that regulate cell death (apoptosis) by controlling mitochondrial membrane permeability. Since Bcl-2 inhibits apoptosis, the active pharmaceutical ingredient (API) in venetoclax works by blocking Bcl-2 and allowing cancer cells to undergo naturally programmed cell death. This also helps counteract drug resistance in cancer patients. Additionally, venetoclax has proven useful in giving geriatric patients access to an anti-cancer medicine when they cannot sustain chemotherapy.
All of this makes venetoclax an important medicine as a first-line treatment (when used by itself, first-line therapy is the one accepted as the best treatment). The pharmacological mechanism of venetoclax is unique from other direct and indirect competing drugs, and other investigational Bcl-2 inhibitors are currently not as established. For a drug to be considered ‘blockbuster’, one metric is that the annual revenue should be above 1 Billion USD. In 2025, the annual global product profit for AbbVie from Venclexta was 2.79 Billion USD. In stark contrast, for its consumers the cost of medicine is notably expensive, often necessitating financial aid – the Australian Pharmaceutical Benefit Scheme included Venclexta in its list of subsidised medicines in 2021.
The Making of an IPO Refusal Report
On 17th October, 2011 AbbVie Inc. filed patent application no. 8004/DELNP/2011 titled “Apoptosis-Inducing Agents for the Treatment of Cancer and Immune and Autoimmune Diseases”. The FER was given in November, 2017. Seven pre-grant oppositions were filed in the course of seven years from 2018 to 2025. On 31st December, 2025 a deputy controller of patents and designs rejected this application on technical grounds of lack of inventive step under Sections 2(1)(j)(a) and 25(1)(e), non-patentability under Sections 3(d), 3(e) and 25 (1)(f) and insufficiency of disclosure under Section 25(1)(g) of the Patents Act, 1970.
The subject matter of claims 1-11 was found lacking inventive step. The deputy controller found that ‘the basic chemical structure… which includes Venetoclax’ has already been disclosed in prior art and has the same functionality. Further, ‘the data given in the present application are merely Bcl-2 inhibition data and that too for only a few compounds out of the thousands of compounds claimed in the Markush.’ This Markush claim was also the reason for partial refusal of the same patent application in China in November, 2022 when the CNIPA had invalidated it on finding a lack of novelty (see here).
Additionally, the IPO has held that ‘in absence, of any biological data for all the claimed compounds in the present specification, it cannot be decided whether the claims actually have the claimed anti-cancer activity or not.’ As per the refusal, the patent application did not contain any data evidencing increased therapeutic efficacy ‘for all the millions of claimed compounds.’ The basic chemical structure according to formula (II) which included Venetoclax in the present application had already been disclosed in patents ‘US 2007/0015787A1’(apoptosis promoters) & ‘WO 2005049593A2’ (N-acylsulfonamide apoptosis promoters) and have the same functionality in disclosing compounds and sulfonamide derivatives useful in the treatment of cancer. Therefore, the claimed genus and the substituents of the present application were found disclosed in prior art. This created a bar on patentability under Section 3(d). Data on in vitro receptor binding capacity was found insufficient for not being indicative of how it would specifically aid clinical outcomes due to cancer’s unpredictability and inter-individual tumour variability.
The controller’s logic mirrors the previous rejections of derivative compounds. This understanding aligns with Novartis (see Yogesh’s critique of Novartis). The jurisprudence on Section 3(d) continues to evolve, though not always in the most linear trajectory (see posts by Yukta, Priyam and Roshan, Prashant Reddy, Shivam, Bharathwaj, Ayush and Srishti). In another recent decision in Taiho Pharmaceutical the Delhi High Court has, inter alia, again summarised the baseline, ‘Section 3(d) bars the patentability of a ‘new form’ of a ‘known substance’ unless it demonstrates enhanced therapeutic efficacy.’
The deputy controller found the claim specifications insufficient and unclear in their disclosure for enabling a person skilled in the art (POSITA) to make the invention. The claims contained a very broad disclosure of the genus that did not ‘reasonably lead’ a POSITA to any particular species that could be used to make the apoptosis-inducing agents for ‘all types of listed cancers’, or be ‘resulting in tangible clinical result’ without ‘undue experimentation.’ Reliance has been made to Novozymes for lack of synergy (Srishti’s post discusses why Section 3(e) needs more analysis).
Praharsh notes how the strict demand for enhanced efficacy has increased reliance on clinical trial data. This requirement can be fulfilled through a post-priority filing. In the aftermath of Novartis, the data proving enhanced efficiency needs to go beyond in vitro datasets and results. The Venetoclax application could not overcome this barrier. This again tied back to the Markush claims. In vitro data was found insufficient for reasons of “1. unpredictability of receptor binding studies which is further compounded by, 2. existence of large number of factors affecting specific receptor targeting in vivo 3. existence of huge number of inter-individual variables in a particular cancer and within a particular tumour.” Clinical trial data was not supplied. The post-filing affidavit detailing superior selectivity of the compound was found reaching beyond the scope of initial disclosures.
The Making of Generics
This rejection of AbbVie’s patent application permits the production of venetoclax generics five years earlier than if the patent had been granted. The most sustainable option for patients in India would be domestic production. A list of active API suppliers of venetoclax includes Dr. Reddy’s and Natco, established generics producers that seem well-suited to engage in product manufacture. Though none of them has publicly expressed interest thus far, given the scope and scale of venetoclax in the market, this should change soon. I return now to my opening question: news articles on this topic (see here and here ) hail the IPO refusal as an absolute opportunity for low-cost access to cancer treatment. Undoubtedly, the lack of a patent opens the door for generics and biosimilars; however, there are more closely associated systemic issues in law and policy – namely, access and efficacy – that need to be considered.
Drug Cost & Quality
A recent research from China claims to be the first detailed analysis of the cost-effectiveness of venetoclax from the perspective of healthcare access in developing countries. It finds in favour of affordability of venetoclax-based first-line treatment in adults with CLL in Asia-specific economies. However, in India a 2024 medical research study that conducted an opinion poll of Indian oncologists found significant cost limitations in access to this medicine, often leading to prescriptions of other drugs because of lack of coverage in state health insurance schemes and unaffordability by patients. I could find one generic variant called Ventoxen being made in and imported from Everest Pharma, Bangladesh. The price difference between this generic and the branded medicine box in the Indian market is insignificant. However, the cost may decrease owing to the removal of basic customs duty in the new budget.
Interestingly, prescription habits were also found influenced by an innovator versus generics perspectives, ‘Given the… unreliability over generic venetoclax, 40% of physicians chose to try another BTKi over venetoclax-based therapies’. Contrastingly, in a different 2024 study, a team at AIIMS Rishikesh found a ‘generic preparation’ of venetoclax to be effective and safe when administered in a single-centre setup (I have reached out to the authors about where they sourced the generic from and will update when I receive a reply). As the division within the medical community, the government’s quality control and safety testing mechanism for generics also continues to divide opinions. Indian medico-legal policies continue to push for generics prescriptions. But this American study claims that generics manufactured in India showed higher side effects than their equivalents manufactured in the USA. An Indian study has also raised questions on the quality of generics and testing process. Bulk supply of Indian generics has, however, been approved by the Chinese health ministry.
Drug combinations in prescriptions
Another issue of access is that venetoclax is often prescribed in combination with other cancer drugs. The Chinese study found venetoclax + obinutuzumab combination to be the best prescription, but Indian oncologists do not prescribe this combination because at current prices one dose of obinutuzumab costs as much as six doses of an alternate drug. Another cancer drug that is used in combination with venetoclax is ibrutinib. Generic ibrutinib was found safe, effective and cost efficient but had become the subject of a Delhi HC injunction. Tejaswini has argued on how the court failed to anaylse the fourth-factor test to assess the public interest ground for pharmaceuticals. There was eventually an out of court settlement. The ibrutinib patent expires this year. Thus, even if one drug becomes accessible for reasons of patent rejection, lapse, etc. it does not solve the general issue of medicine affordability and access, especially when prescriptions include drug combinations where the remaining medicine is unaffordable.
Pending Litigation
Finally, in this particular case, delayed patent prosecution consequently delays when access becomes available. Pre-grant oppositions were filed for over seven years. The Delhi High Court was requested to intervene because the patent office took an unreasonably long time in issuing notices of pre-grant oppositions and also in reserving these orders after the hearings. The point is simple – if patent prosecution happened in a time-abiding manner, then access to generic medicine would have been arranged much sooner. Despite a win for the generics industry, the overall story of venetoclax at the IPO shows that a single patent rejection is not a panacea for the ills of cost, access and efficacy.
