SpicyIP Tidbit: Patent Office Rejects Dolutegravir Application, Paving Way for Affordable HIV Drugs
SpicyIP
[This post is authored by Yukta Chordia. Yukta is a 4th year BA LLB (Hons.) student at Maharashtra National Law University, Nagpur and is passionate about Intellectual Property Law and Media and Entertainment Law, with a strong interest in ADR. Her previous post can be accessed here.]
A big thanks to Swaraj sir and Praharsh sir for their inputs on the post.
The Controller of Patents, Kolkata, on 3rd October, 2024, rejected the patent application for an HIV drug- Dolutegravir by VIIV Healthcare and Shionogi & Co. Ltd. This decision, coming after nearly a decade of legal battles and multiple pre-grant oppositions from different advocacy groups and Natco, paves the way for affordable generic versions to enter the market.
The different pre-grant oppositions contended that the claims failed the test of Section 3(d) of the Patents Act and ought to be rejected on this ground alone. The Controller found the claims to be not patentable under Section 3(d) as the applicants (VIIV Healthcare and Shionogi and Co. Ltd.) failed to prove “therapeutic activity.”
Background of the Case
The patent application in question (Application No. 3865/KOLNP/2007) was filed on October 10, 2007, by VIIV Healthcare for an invention titled “Polycyclic Carbamoylpyridone Derivative Having HIV Integrase Inhibitory Activity.” This application sought to protect Dolutegravir’s (DTG) main compound, a key HIV integrase inhibitor (which is a class of antiretroviral drugs used for treating HIV) and other related antiretrovirals (ARVs), including ViiV’s new ARV, Cabotegravir, being developed in both tablet and long-acting injectable forms. The application was filed under a ‘Markush claim,’ where several (even millions!) of possible interrelated compounds, which can be used interchangeably, are included in a single patent application/ claim.
Dolutegravir is a critical drug in the treatment of HIV, known for its high barrier to drug resistance, and is especially beneficial for patients who have failed treatment with other antiretrovirals (ARVs). Its effectiveness is why the World Health Organization (WHO) has recommended it as an alternative first-line treatment for HIV, and it is now a preferred drug for all lines of treatment of HIV infection according to India’s National Guidelines for HIV Care and Treatment.
The Opponents and Oppositions
Between 2013 and 2019, the application faced six pre-grant oppositions, which seem to have significantly contributed to the Controller’s reasoning in rejecting the application. The oppositions were filed by-
- Delhi Network of HIV+ People Living with HIV/ AIDS (DNP+) (Opponent 1)
- Bengal Network of HIV+ People Living with HIV/AIDS (BNP+) and Mr. Firoz Khan (Opponent 2)
- Mr. Sanjeev Sharma (Opponent 3)
- Dr. Mira Shiva (Opponent 4)
- Natco Pharma Limited (Opponent 5)
- Sankalp Rehabilitation Trust (Opponent 6)
Although the patent application faced multiple opposition grounds, only some were found valid by the Controller. Opponents 1 and 3 raised the ground of lack of novelty under Section 2(1)(j), but this was dismissed as they failed to provide any substantial evidence, while the applicant effectively distinguished their compounds from prior art. However, the Controller found valid the objection of obviousness under Section 2(1)(ja), raised by Opponents 1 through 6, as the applicant’s claim that specific substituents in Dolutegravir (DTG) and Cabotegravir (CTG) enhanced HIV integrase activity was unsubstantiated; in fact, prior art cited by opponents showed similar or even better activity without these substituents, leading to the conclusion that the invention lacked an inventive step.
Another ground found valid by the Controller was the ground of non-patentability under Section 3(d), raised by Opponents 1, 2, 3, 4, and 6, since the applicant failed to prove “therapeutic activity” of the compounds in terms of any integrase inhibitory activity against HIV. Under Section 10(4), Opponents 1, 2, 4, 5, and 6 contended that the applicant’s disclosure was insufficient. The Controller found the ground partially valid, finding that Claims 1-2 lacked critical details on the synthesis and activity of Dolutegravir, while Claims 3-4 provided enough data and the process for Cabotegravir. (see below for the screenshot of these claims) Lastly, all opponents raised the issue of non-disclosure of information required under Section 8, but this ground was ultimately dismissed as it was neither argued during the oral hearing nor supported by written submissions.
[Side Note: The Controller’s decision overlooked the industrial applicability requirement under Section 2(1)(j), raised by Opponents 1, 3, and 4 — an essential ingredient in assessing whether the claims meet the definition of “invention.” While the patent was ultimately rejected on other grounds, addressing all objections is crucial to building the jurisprudence of ‘invention’ to prevent the grant of patents on ‘inventions’ that do not merit them (as discussed here).]
Section 3(d) as a Barrier to Evergreening: Lessons from the Novartis and Dolutegravir Case
Section 3(d) of the Patents Act, aims to prevent “evergreening”—where pharmaceutical companies try to extend patent life with minor changes to drugs. One of the safeguards under the provision states that “mere discovery of a new form of a known substance which does not result in the enhancement of the known efficacy of that substance”, is not an invention. The rejection of the patent application for Dolutegravir and Cabotegravir under Section 3(d) of the Indian Patents Act is well-reasoned and draws heavily from the principles established in Novartis v. Union of India.
The Supreme Court, in that case emphasized that “efficacy” means therapeutic efficacy in the case of pharmaceutical products and held that the therapeutic efficacy of compounds claimed must be established with evidence of appropriate research and clinical data which must be found in the specification. Additionally, therapeutic efficacy must be established by comparing it with the closest possible known compound. The burden of proof is on the patent applicant to show the enhanced efficacy to satisfy the requirement of Section 3(d).
In the present case, the Controller of Patents found that the applicant failed to provide sufficient evidence to prove that the claimed invention showed any enhanced therapeutic efficacy compared to known compounds like those disclosed in prior art. The opponents successfully argued that the compounds claimed in the patent were merely derivatives of known substances, without any data demonstrating significant improvements in their therapeutic activity. Further, such information has to be provided in the complete specification itself. The absence of such data in this instance significantly weakened the applicants’ case, ultimately leading to the rejection of their claims under Section 3(d).
Although, the present decision refuses to grant a patent for one of the derivatives of Dolutegravir and Cabotegravir, a number of secondary or related patent applications have been filed in India (as reported here and here), including an application on a method of producing a derivative of Dolutegravir or a derivative of Cabotegravir, filed as 886/CHENP/2013 (Granted Application, Patent Number: 319709). Presently, VIIV and Shionogi have a patent on the Dolutegravir/Cabotegravir intermediates production processes and intermediates, filed as 1971/KOLNP/2011 (Patent Number: 295128) until December 2029. They also have a patent on Cabotegravir prodrugs, filed as 196/KOLNP/2011 (Patent Number: 291942) until July 2029. [Side Note: Jannsen adopted a similar strategy by filing a secondary patent application for treatment of multi-drug resistant tuberculosis drug treatment, however, this secondary patent application was rejected by the patent office (as discussed here).]
Socio-Economic Impact
Apart from the legal discussion, the rejection of ViiV’s patent application has critical socio-economic implications, especially in India, where access to affordable healthcare has been under constant pressure from patent exclusivities. Granting the patent would have restricted competition, driving up prices and making the drug inaccessible for many who rely on affordable medications. The rejection can also have a positive ripple effect in other developing countries, which rely on affordable generic drugs from India for their HIV/AIDS treatment programs.
As drug resistance continues to grow, the need for new medications like Dolutegravir has become increasingly urgent. As nearly 16 million people in developing nations benefit from generic HIV drugs made in India, maintaining this pipeline is vital for sustaining their treatment programs. Patients living with HIV, who have already developed resistance to current treatments, are in urgent need of this drug. Without this, they face life-threatening gaps in treatment (reported here).