In an interim relief action in an infringement suit relating to biosimilars of Pertuzumab, a monoclonal antibody biologic, the Delhi High Court in CS(COMM) 159/2024 [F- Hoffmann -La Roche & Anr. (‘plaintiffs’) vs Zydus Lifesciences Ltd. (‘defendant’)], have directed the contesting parties to present before the court the material relevant for understanding not only the intricacies of patent law but also scientific principles that are foundational for the biologic and its biosimilar (similar biologic) contender. While adjudicating the plaintiff’s application for interim relief, the issue before the Court was the precise determination of whether the defendant’s biosimilar development encroaches upon the plaintiff’s patent rights or innovator reference biologic. In its order dated 23rd February 2024, the Court outlined a procedural framework that included the submission of claim mappings by parties, process disclosure by the defendant along with setting up of a confidentiality club, the assistance from parties’ experts along with possible use of ‘hot-tubbing’, and the prospect of appointing an independent scientific advisor.
Background
Plaintiffs filed a suit for infringement of two patents (‘suit patents’), both pertaining to a monoclonal antibody biologic (‘Pertuzumab’) used to inhibit tumour growth. One suit patent (IN 464646) relates to the process for making a composition comprising Pertuzumab and one or more variants. The other suit patent (IN 268632) relates to an aqueous pharmaceutical formulation comprising Pertuzumab and certain excipients. In February 2024, the plaintiffs became aware that the defendant had sought regulatory permission to manufacture a ‘New Drug Formulation’ for the sale or distribution of Pertuzumab. It was also revealed that the defendant had applied for permission to conduct clinical trials for their product as a similar biologic to that of the plaintiffs’ Pertuzumab, and the said application categorically mentioned the plaintiffs’ product, which is covered by suit patents as the reference biologic.
Arguments
The plaintiffs argued that a biosimilar is nearly identical to its reference biologic, and a biosimilar product is similar in terms of quality, safety, and efficacy to an already approved reference biologic product based on comparability. By claiming their product to be biosimilar to that of the plaintiffs’ product, the defendant admits that both products are identical in all important parameters. The defendant’s biosimilar closely mirrors the plaintiffs’ patented product and thereby infringes the formulation suit patent. Since no methodology for the production of the biosimilar has been disclosed, the plaintiffs also apprehended that the defendant’s process employed is identical to their process, thereby infringing on the process suit patent. Moreover, the plaintiffs produced the defendant’s patent application (No. 2021079337) relating to formulations of Pertuzumab. In such circumstances, plaintiffs brought a quia timet action as they strongly apprehended the imminent threat of the launch of the infringing biosimilar product. It was also submitted that the defendant had filed an unsuccessful pre-grant opposition to the process suit patent and was already aware of the plaintiffs’ rights.
Per contra, the defendant argued that no urgency was disclosed in the plaint to warrant the grant of an ex-parte ad interim injunction. The defendant further emphasised that the plaint did not disclose any claim mapping to demonstrate that the defendant’s product would be infringing upon the suit patents. Rather, the plaintiffs’ case rests on an untenable proposition that a similar biologic is identical to its reference biologic product and therefore amounts to infringement.
Court’s Analysis
At the outset, the Court discussed the regulatory pathway for biosimilars. Referring to ‘Guidelines on Similar Biologics’, the Court noticed that an abbreviated review process underscores the fundamental principle that a biosimilar, by leveraging the exhaustive data of its reference biologic (innovator’s product), can offer similar therapeutic benefits (quality, safety, and efficacy) without repeating the extensive clinical trials conducted for the innovator reference product. Biosimilars are designed to be highly similar to the reference product but not identical. However, the Court further observed that the regulatory guidelines focus on the approval process and do not directly address patent issues. Therefore, the Court held that the determination of infringement must begin with understanding the scope of the patent(s) held by the reference biologic. If the biosimilar utilises or embodies any aspect (including formulation and manufacturing process) that is patented by the reference biologic, only then could there be a case for patent infringement.
As the innovator reference biologic is protected under the suit patent (IN’632) and the similar biologic is encapsulated by claim 1 in the defendant’s patent application No. 2021079337, the Court is required to discern whether the formulation disclosed in the defendant’s patent application is a variant of Pertuzumab, different from the plaintiffs’ formulation patent, which is also “pharmaceutical formulation comprising Pertuzumab”. Therefore, as the first procedural step, the Court directed the plaintiffs to carry out the said claim mapping for infringement analysis. The defendant was also permitted to do the claim mapping.
The Court acknowledged the dual aspect of biologic’s intellectual property – its molecular structure and the sophisticated processes required for its reliable, safe, and consistent large-scale manufacturing within living systems. The regulatory guidelines for biosimilars stress the importance of process validation as well as the demonstration of a manufacturing procedure that is both highly consistent and robust. In scenarios where the host cell line utilised in the production of the reference biologic is publicly disclosed, there is a strong preference for employing the same host cell line in the manufacturing of similar biologics.
As the plaintiffs have a process patent (IN’646) and are also in the dark about the specific processes used by the defendant in making their biologic product, the Court intended to invoke Section 104A of the Patents Act. Under this provision, when a patent covers a process for obtaining a product, the burden of proof shifts to the defendant to demonstrate that its method for creating an identical product diverges from the patented process, subject to certain prerequisites. Therefore, the Court directed the defendant to reveal its process for developing the biosimilar for which drug approval/ licensing has been sought. However, the aforesaid information will be submitted in a sealed envelope to preserve sensitive information. The Court will also subsequently assess the need to establish a confidentiality club to manage the disclosed information and ensure that access to such information is appropriately controlled and limited to authorised individuals.
Decision
The Court issued several directions to crystalise the legal and technical facets of the case. Parties were required to provide all pertinent case laws and jurisprudence related to medical and patent matters concerning biologics, extending to both domestic and international precedents. To facilitate an organised examination of expert opinions, each party was directed to disclose the names and credentials of their respective experts in the field of biologics and related IP issues. The Court may employ ‘hot-tubbing’ for simultaneous questioning of experts from both sides in an open-court format, allowing for a direct comparison of their insights. The Court will also consider appointing an independent scientific advisor to provide neutral expert analysis on the nuances of biologics production and patent protection.
Conclusion
The outcome of this case will for sure lay down the rules and principles for dealing with infringement action in cases where the court is called upon to adjudicate the infringement action against Biosimilars that are designed to be highly similar to the reference product (infringing) but not identical. The direction of the court in this case would encourage the participation of experts and Hot tub discussions. In particular, the hot-tubbing protocol (concurrent evidence) will save considerable court time and crystallise areas of agreement and disagreement more effectively than traditional cross-examination (sequential evidence). The court would also devolve into regulatory guidelines that permit innovation/ development within the framework of existing biologics by adhering to stringent standards. In the case of an IP dispute, the Court would decide whether such biosimilar development infringes upon the originator’s patent rights. The quia timet action allows the innovator of the reference biologic to take preemptive measures against potential infringement. The procedural steps suggested by the Court in this case will offer a comprehensive adjudication of the interim application.
Authors: Manisha Singh and Neha Ruhela
First Published by Lexology: here