The European Patent Board of Appeal has made a significant ruling in case T 0816/22, revoking a patent for C1-esterase inhibitor (C1-INH) treatment in kidney transplant patients, citing insufficient evidence of therapeutic efficacy. The decision marks a crucial precedent in how post-published clinical trial data can affect patent validity.
Patent Background and Clinical Context
The patent EP 3071219 covered the use of C1-esterase inhibitor for treating antibody-mediated rejection (AMR) in kidney transplant patients. The treatment targeted patients sensitized to donor organs due to previous transplants, blood transfusions, or pregnancies. C1-INH was already established as a treatment for acute hereditary angioedema (HAE) attacks.
The patented treatment protocol specified administering Cinryze® (C1-INH formulation) at doses between 5,000-20,000 units, divided over 10-20 days. Initial Phase II data showed promising results in reducing chronic glomerulopathy, a recognized manifestation of AMR, compared to placebo.
Phase III Trial Results and Patent Challenge
The subsequent Phase III trial, which maintained the same dosing regimen but involved a larger patient cohort, produced contradictory results. At the 6-month mark, the data showed no therapeutic advantage over placebo:
- Placebo group: 47.5% patients with new or worsening transplant glomerulopathy
- Cinryze® group: 50% patients with new or worsening transplant glomerulopathy
The trial was terminated at 36 months after meeting pre-specified futility criteria, though the patent holder argued this was primarily a commercial decision.
Legal Implications and Board's Decision
The Board emphasized that while therapy doesn't require complete disease cure—improvement or symptom reduction would suffice—the Phase III data demonstrated a complete absence of therapeutic effect using the claimed dosage regimen. This finding directly contradicted the patent's core therapeutic claims.
The ruling establishes that post-published clinical trial data can be used to challenge patent sufficiency under Article 83 of the European Patent Convention (EPC). This decision could have far-reaching implications for second medical use patents, particularly when subsequent clinical trials fail to support initial therapeutic claims.
