Delhi HC Bars Zydus From Launching Cancer Drug Nivolumab Biosimilar Till 2026
New Delhi: In a major setback to Zydus Lifesciences, the Delhi High Court has restrained the company from launching its proposed biosimilar of the cancer immunotherapy drug Nivolumab until May 2, 2026, the date on which the suit patent expires. The court's order came as part of an interim injunction in favour of global pharmaceutical major Bristol Myers Squibb (BMS) and its affiliates, who claimed that Zydus's biosimilar infringed their valid and subsisting Indian Patent No. IN 340060.
The plaintiffs in the case, E.R. Squibb and Sons LLC, Ono Pharmaceutical Co. Ltd., and BMS India, filed suit seeking a permanent injunction against Zydus for alleged patent infringement. Their suit focused on IN 340060, titled “Human Monoclonal Antibodies to Programmed Death 1 (PD-1) for use in treating Cancer”, which covers the biologic cancer drug Nivolumab. Known globally as Opdivo® and marketed in India as Opdyta®, the drug is a therapeutic monoclonal antibody used in the treatment of multiple cancers, including lung, kidney, head and neck cancers, and melanoma.
According to the court, “The suit patent covers and claims a monoclonal antibody, also known as ‘Nivolumab’ or ‘5C4’, in the complete specification of IN ‘060. Nivolumab is a therapeutic antibody used in the treatment of various forms of cancer.” The patent, granted on July 1, 2020, has a term of 20 years from May 2, 2006, and is set to expire on May 2, 2026.
The plaintiffs argued that they first became aware in April 2022 that Zydus had applied to the Central Drugs Standard Control Organisation (CDSCO) for clinical trial approval of a Nivolumab biosimilar. A cease-and-desist letter was issued to Zydus on May 6, 2022, to which the company responded by invoking the “Bolar exemption” under Section 107A of the Patents Act, asserting that its activities were limited to clinical research and thus non-infringing.
However, the plaintiffs later learned that Zydus had registered a clinical trial for its proposed biosimilar—coded ZRC-3276—identifying Nivolumab (Opdivo®) as the reference product. In April 2024, the plaintiffs received further evidence suggesting Zydus was preparing for a commercial launch during the patent term. They then approached the court seeking immediate injunctive relief, arguing that there was a credible threat of infringement. “There existed a real, credible and reasonable apprehension that the defendant intended to manufacture, launch and otherwise deal in Nivolumab during the term of the suit patent without the plaintiffs’ authorisation,” the court noted while summarising the plaintiffs’ submission.
The plaintiffs further alleged that Zydus had not obtained the patented drug from them, nor had they granted any licence. Imports of Nivolumab by Zydus were reportedly done without consent, and the biosimilar was being developed using the plaintiffs’ patented sequences. The suit relied on the patent’s claims, which explicitly cover the six Complementarity Determining Regions (CDRs) and the variable region sequences found in Nivolumab. The plaintiffs stated that “Nivolumab is covered and claimed by the suit patent through Claims 1 and 3 of the suit patent… therefore, any reference to Nivolumab by the defendant would constitute infringement.”
On the other hand, Zydus mounted a two-pronged defence. First, they denied that their biosimilar infringed the patent, arguing that their molecule did not bind exclusively to PD-1 but also to other members of the CD-28 protein family, and hence fell outside the scope of the claims. They claimed, “The inventive feature in the suit patent is claimed to have specific binding affinity to PD-1, while the defendant’s product also binds to other members of the CD-28 family.”
Second, Zydus challenged the validity of the suit patent. They cited several prior art documents—particularly WO 2004/004771, also known as D3—claiming that the plaintiffs themselves had previously disclosed the invention in an earlier patent application. “The suit patent is invalid on the grounds, that, Nivolumab was already claimed in the patent WO 2004/004771,” Zydus argued, asserting that the present patent lacked novelty and inventive step.
Zydus also pointed to an Opposition Board Recommendation (OBR) issued in post-grant opposition proceedings, which had found the patent to be invalid. However, the plaintiffs noted that the OBR was set aside by a single judge of the Madras High Court in March 2024, and while the matter was remanded after appeal, the recommendation remained non-binding. The Delhi High Court agreed with this position, stating, “The OBR... is a recommendation given by the Opposition Board to the Controller which only has a persuasive value and is not binding in nature.”
The court also dismissed Zydus’s claim of delay, noting that the plaintiffs’ cause of action arose only in April/May 2024, when they received credible information of the potential commercial launch. “Cause of action for initiating legal proceedings against the defendant arose only in the year 2024, when the knowledge with regards to the commercial launch... was received,” the judgment stated.
On the issue of patent validity, the court carefully examined the cited prior arts and concluded that none disclosed the specific amino acid sequences claimed in the suit patent. It held;
“The defendant has not been able to show that Nivolumab was disclosed in the prior arts cited by the defendant… The defendant has failed to show that any feature of the plaintiffs’ claimed invention is present in any of the cited references."
Subsequently, the court ruled that the plaintiffs had made out a strong prima facie case of infringement, would suffer irreparable harm if an injunction were not granted, and that the balance of convenience tilted in their favour. It noted;
"Considering the detailed discussion hereinabove, the plaintiffs have established a prima facie case in their favour. The balance of convenience also lies in favour of the plaintiffs. The plaintiffs shall suffer irreparable loss, in case interim relief as prayed for, is not granted. Accordingly, the defendants, and all others acting on its behalf, are restrained from manufacturing, using, selling, offering for sale, importing, exporting, advertising or dealing in any bio-similar/similar biologic of Nivolumab, the suit patent, during the pendency of the present suit."
"Further, the defendant is also restrained from launching any manufactured product, if any, manufactured during the pendency of the patent of the plaintiffs, even upon expiry of the patent. The defendant is accordingly directed to file an affidavit disclosing the quantity of its manufactured bio-similar product of Nivolumab, within a period of four weeks, from today."
Accordingly, the Delhi High Court confirmed its earlier interim order dated May 8, 2024, which restrained Zydus from launching or marketing its biosimilar ZRC-3276 without the court’s permission. That order will remain in force until the suit patent expires on May 2, 2026.
To view the original judgement, click on the link below:
