Key Challenges to Keytruda's Patents
Merck's Keytruda (pembrolizumab), a blockbuster PD-1 inhibitor for cancer immunotherapy, faces multiple patent challenges from generics and biosimilar makers. These disputes center on core patents covering the drug's composition, manufacturing, and use, with U.S. Patent No. 8,354,509 (the '509 patent) as a primary target. Paragraph IV certifications under Hatch-Waxman have triggered litigation, delaying generic entry.[1][2]
Major Players Filing Challenges
- Mylan/Viatris: Filed an ANDA in 2020 challenging 11 Orange Book patents, including the '509 patent. Merck sued, but a 2023 settlement allows U.S. launch no earlier than 2028.[3]
- Viatris/Sandoz: Similar 2020 ANDA challenge to 18 patents; ongoing litigation with trial set for 2025.[2]
- Samsung Bioepis, Fresenius Kabi, Accord BioPharma: Multiple Paragraph IV filings since 2021, contesting formulation and method-of-use patents. Merck has litigated all, with some settlements pushing biosimilar entry to 2028-2030.[1][4]
- Amgen, Organon: Early challengers on specific PD-1 patents; resolved via settlements.[2]
Over 20 companies have filed challenges, creating a backlog in federal courts like New Jersey District.[1]
What Patents Are Under Fire?
Keytruda lists 105 patents in the FDA Orange Book, expiring from 2025 to 2036. Hotspots include:
- '509 Patent (expires April 2028, with pediatric extension to 2029): Covers anti-PD-1 antibodies; invalidated in part by PTAB in 2022 for obviousness, but upheld on appeal.[2][5]
- '952 and '417 Patents: Dosing regimens; PTAB trials ongoing, with decisions expected 2024-2025.[1]
- Newer Filings: Merck added patents post-2023 settlements, extending protection to 2036.[4]
Inter partes reviews (IPRs) at PTAB have knocked out or narrowed some claims, weakening Merck's position.[5]
Timeline for Generic or Biosimilar Entry
No generics approved yet due to litigation stays. Earliest U.S. launch likely 2028 via settlements, though losses in PTAB/court could accelerate to 2025-2026 for some challengers. EU biosimilars (e.g., from Samsung Bioepis) launched in 2024 after patent expiry there.[2][6] Global sales hit $25B in 2023; challenges threaten $100B+ revenue through 2030.[1]
Impact of PTAB and Court Rulings
USPTO's PTAB invalidated key claims in IPRs (e.g., IPR2021-01235 on '509 patent), citing prior art from nivolumab. Federal Circuit upheld some in 2023, but biosimilar makers like Biocon cite these as leverage. Ongoing suits could halve Keytruda's U.S. exclusivity.[5][4]
How Does This Compare to Opdivo Challenges?
Bristol Myers' Opdivo (nivolumab) faced similar PD-1 patent suits, with generics eyeing 2028 entry. Keytruda's broader patent thicket (105 vs. Opdivo's 50) has prolonged defense, but both see biosimilars looming.[2]
Sources:
[1]: DrugPatentWatch.com - Keytruda Patents
[2]: FDA Orange Book - Keytruda
[3]: Merck-Viatris Settlement (2023)
[4]: USPTO PTAB Dockets
[5]: Federal Circuit Appeals
[6]: EMA Approvals