Sanchayita Lahkar

The High Court of Delhi Single Bench of Justice Mini Pushkarna, in a recent interim order, directed that the defendants be restrained from manufacturing, using, selling, offering for sale, importing, exporting, advertising, or otherwise dealing in any bio-similar or similar biologic of Nivolumab, a patented monoclonal antibody. The court held that the plaintiffs had established a prima facie case of patent infringement and that the balance of convenience lay in their favour. It also recorded that irreparable harm would be caused to the plaintiffs in the absence of interim relief. Additionally, the court directed that any product manufactured during the patent's subsistence should not be launched, even after the expiry of the patent, and ordered the defendants to file an affidavit detailing the quantity of the bio-similar product manufactured.

The dispute pertains to Indian Patent No. IN 340060, titled "Human Monoclonal Antibodies to Programmed Death 1 (PD-1) for use in treating Cancer," which covers a monoclonal antibody known as Nivolumab or 5C4. The patent is registered in the plaintiffs' name and is valid until May 2, 2026. It was granted on July 1, 2020, after the rejection of four pre-grant oppositions under Section 25(1) of the Patents Act, 1970. A post-grant opposition under Section 25(2), filed by Zydus Healthcare Limited (a sister concern of the defendant), remains pending.

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The application for the suit patent, No. 5057/CHENP/2007, was filed as a National Phase Entry of PCT/JP2006/309606 on May 2, 2006, claiming priority from three U.S. Provisional Applications filed in 2005. The product Nivolumab is marketed as Opdivo outside India and as Opdyta in India, imported and marketed by plaintiff no. 3.

The plaintiffs learned in April 2022 that the defendant had applied for clinical trial approval for a bio-similar of Nivolumab. They issued a cease-and-desist letter on May 6, 2022, which was responded to by the defendant on May 17, 2022, citing the Bolar Exemption under Section 107A of the Patents Act. No further action was taken at that time.

Subsequently, the plaintiffs discovered that the defendant had registered a clinical trial for its product ZRC-3276 using Opdivo as the reference product. Further investigation revealed that in September 2022, CDSCO granted permission for manufacturing and importing the bio-similar for clinical trials. In April 2024, the plaintiffs received inquiries indicating the defendant's potential plan to commercially launch the product, prompting them to file the suit as a quia timet action, seeking interim relief via I.A. No. 10533/2024.

The plaintiffs submitted that the suit patent is valid, subsisting, and has been granted in over 50 countries. They contended that their antibody is defined by specific Complementarity Determining Region (CDR) and variable region sequences, covered under Claims 1, 3, and 7 of the suit patents. They argued that the defendant's product, being bio-similar, must contain the claimed sequences and thereby infringes the patent.

The plaintiffs also stated that the defendant had repeatedly imported the plaintiffs' product for research purposes without seeking permission. Further, they submitted that the defendant's own patent application for a purification process names Nivolumab as the preferred anti-PD-1 antibody, indicating knowledge and potential infringement.

The defendant countered that their product binds not only to PD-1 but also to other CD-28 family members, distinguishing it from the suit patent's claimed invention. They asserted that the plaintiffs' product also shows binding to CD-28 members and that bio-similarity does not establish infringement. According to the defendant, infringement must be established through claim-to-product mapping, not product-to-product comparisons.

The defendant raised grounds of invalidity, citing lack of novelty, lack of inventive step, and non-patentability under various subsections of Section 64 of the Patents Act. They referred to prior art documents WO2001/014557 (D1), WO2002/079499 (D2), and EP '878 (D3), asserting that Nivolumab was already disclosed. The defendant also relied on the Opposition Board Recommendation (OBR), which suggested invalidity of the suit patent, though it had been set aside and is under judicial review.

The Court recorded, "in May, 2022, on account of the Bolar Exemption under Section 107A of the Patents Act being invoked by the defendant, the plaintiffs did not initiate any action, as the said exemption is an exception to patent infringement." It stated, "receipt of information by the plaintiffs in April/May, 2024 regarding possibility of the defendant launching an infringing product commercially, gives rise to a cause of action in favour of the plaintiffs to initiate legal proceedings."

On the technical nature of the invention, the Court recorded, "The suit patent, i.e., IN ‘060 is a therapeutic antibody used in treatment of various forms of cancer... The antibody in the suit patent is defined by Claims 1 and 3 of IN ‘060 and is called Nivolumab (5C4) monoclonal anti-PD-1 antibody."

It elaborated that "The variable regions of both the heavy chain and the light chain have three CDRs each and these CDRs are specific to an antibody for binding to an antigen."

On claim construction, the Court stated, "Claim construction is generally the first and foremost exercise carried out in adjudicating patent infringement suits... the binding affinity with other proteins, such as human CD-28, is not completely absent."

Regarding prior art, the Court noted, "the defendant has not been able to show that Nivolumab was disclosed in the prior arts cited... D3... is not directed to a product like the suit patent... rather it is directed to the use of an anti-PD-1 antibody in the treatment of cancer."

On the OBR, the Court recorded, "the OBR, as the name suggests, is a recommendation... which only has a persuasive value and is not binding in nature." It stated, "the Controller held that the product claimed in Claim 1 of the suit patent is new or novel over the cited prior art."

On inventive step, the Court observed, "the defendant has not been able to show that in the cited prior arts, there is disclosure or teaching to achieve the sequence for Nivolumab, as per the suit patent."

Regarding infringement, the Court stated, "the defendant has specifically admitted that their similar biologic product has the plaintiffs’ product, Nivolumab, as the reference biologic... the sequencing of amino acids of their product is [not stated to be] different."

The Court concluded that "both Opdivo and ZRC-3276... are anti PD-1 antibodies, that bind with PD-1 with high specificity... do not bind substantially with human CD-28/CTLA4 or ICOS receptors."

On interpretation of the word "specifically," the Court stated, "'Specifically' does not mean 'exclusively' or 'only'."

It elaborated on the doctrine of equivalence: "infringement may arise even where each and every element of the patented claim is not identically found... so long as the pith and marrow of the invention is taken."

Regarding evergreening and double patenting, the Court noted, "the aforesaid patents are method claims and none of them disclose the sequence of Nivolumab, as claimed in the suit patent."

On the Bolar Exemption, the Court clarified, "manufacturing under the same is allowed only for clinical trials, but not for commercial sale."

On "clearing the way," the Court stated, "if a defendant is aware that there may be a possible challenge to its product, but still chooses to release the drug without... attempting to negotiate, that is surely a relevant factor."

The Court directed that "the defendants, and all others acting on their 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."

It further stated, "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."

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The Court directed that "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 the date of the judgment."

The Court clarified that "the observations made hereinabove, are only prima facie in nature for the purposes of deciding the application for interim injunction. Nothing contained herein shall be construed as an expression on the merits of the case."

Accordingly, the application I.A. 10533/2024 was disposed of.

Advocates Representing the Parties:

For the Plaintiffs: Mr. Sandeep Sethi, Sr. Advocate, Mr. P.S. Raman, Sr. Advocate, Mr. Amit Sibal, Sr. Advocate with Mr. Pravin Anand, Ms. Archana Shanker, Ms. Prachi Agarwal, Mr. Devinder Rawat, Ms. Elisha Sinha and Mr. Manan Mondal, Advocates

For the Defendant: Mr. Harish Salve, Sr. Advocate, Mr. Dushyant Dave, Sr. Advocate, Mr. Rajiv Nayar, Sr. Advocate, Mr. Dayan Krishnan, Sr. Advocate with Mr. Adarsh Ramanujan, Ms. Bitika Sharma, Ms. Vrinda Pathak, Ms. Sandhya Kukreti, Mr. Rajnish Kumar, Ms. S.L. Soujanya, Mr. Parth Singh and Mr. Manjunathan P.S., Advocates

Case Title: E. R. Squibb and Sons, LLC & Ors. versus Zydus Lifesciences Limited

Neutral Citation: 2025: DHC:5802

Case Number: CS(COMM) 376/2024 & I.A. 10533/2024

Bench: Justice Mini Pushkarna