Opdivo biosimilars one step closer to market entry as EPO revokes BMS patent

Bristol-Myers Squibb (BMS) is fighting hard to defend several patents covering its blockbuster drug Opdivo. The drug, which contains the monoclonal antibody nivolumab as its active ingredient, treats head and neck cancer as well as melanoma. The US pharmaceutical company recently lost two important patents in EPO opposition proceedings.

Nivolumab, marketed by BMS under the brand name Opdivo, is one of the leading immunotherapy antibodies used in oncology. Alongside MSD’s pembrolizumab (Keytruda), it targets the PD-1/PD-L1 pathway.

Under attack

The EPO’s most recent decisions centre on EP 3 322 731 and EP 3 288 980. After the Opposition Division revoked EP 731 in late 2023, BMS lodged an appeal but withdrew it early this year. More recently the Boards of Appeal revoked EP 980, which covers a treatment for PD-L1-positive melanoma using an anti-PD-1 antibody.

In its decision published in the EPO register today, the Boards of Appeal found that the claimed subject-matter, in particular the combination of a flat-dose regimen with nivolumab monotherapy, extended beyond the content of the application as filed (case ID: T 0715/24).

The active ingredient in Opdivo, the monoclonal antibody nivolumab, is covered by EP 2 161 336. The Opposition Division upheld the basic patent in amended form in 2017. SPCs exist in several countries, for example in France. SPCs and data exclusivity protect the EP 336 until end of 2030.

The latest rulings form part of a large-scale challenge — mostly by straw men — to several patents relating to Opdivo. Related patents include EP 3 464 373, EP 3 858 859 and EP 3 377 534, which are also subject to oppositions. EP 4 679 094 has just been filed and is currently subject to examination.

Among the pharma companies currently known to be working on biosimilars for Opdivo are Amgen and Sandoz. According to information on Amgen’s website, trials for its own nivolumab product, ABP 206, are currently in phase 3. The Sandoz biosimilar pipeline states that its product is “in clinical development”. Intas and its generics and biosimilars subsidiary, Accord, are also developing a biosimilar of Opdivo in collaboration with Xbrane.

Patent holder Bristol-Myers Squibb relied on a Munich-based team from the UK patent attorney firm Mewburn Ellis. Munich-based partner Thomas Wolter and Edward Couchman from the Cambridge office represented the US pharmaceutical company before the Boards of Appeal.

Wolter has a long-standing client relationship with BMS, stemming from his time at Munich-based IP firm Reitstötter Kinzebach. When he joined Mewburn & Ellis in 2020, he took the client with him. The firm regularly undertakes filing and prosection work for BMS at the EPO, as well as opposition proceedings.

In the case of EP 980, five opponents challenged the patent. The Munich-based firm df-mp represented three of the five opponents. Partners Hans Ulrich Dörries, Elisabeth Greiner and Sandra Pohlman acted as straw men. Partner Simon Geiger and associate Tom Schwarzer were also involved in the opposition proceedings.

df-mp regularly acts for Amgen, one of the generic drug companies working on a biosimilar of Opdivo. The team represented Amgen against Sanofi in the epic battle over the cholesterol-lowering drug Rapatha/Praluent, until the parties reached a settlement this spring.

Multiple firms as straw men

Patent attorney Marco Fachini of Kraus & Lederer represented another anonymous opponent. The firm is well known for its regular litigation work for Sandoz, which has a nivolumab biosimilar in the pipeline. For example, the firm acted for Sandoz’s German subsidiary Hexal in a dispute with BMS concerning Eliquis and with Biogen concerning Tecfidera. However, df-mp also acts for Hexal, for example against Astellas and The Regents of the University of California regarding the patent and SPC for the prostate cancer drug Xtandi.

Patent attorney and partner Andreas Obermeier of Bird & Bird acted for another anonymous opponent through the firm’s own entity for straw man oppositions, Pajaro. Patent attorney Anne Halbach assisted, while lawyers Boris Kreye and Elsa Tzschoppe advised on legal matters.

All these firms were also involved in the opposition concerning EP 731, with additional opponents including ISA Pharmaceuticals, represented by Kirkpatrick; Regeneron, represented by J.A. Kemp; BioNTech, represented by ZSP. MSD and other straw men were represented by Patent Boutique, Maiwald, and Appleyard Lees.