Overview of CN104619857 and Its Technical Scope
CN104619857, titled "Euglobulin-based method for determining the biological activity of defibrotide," protects a diagnostic assay for measuring the pharmacological efficacy of defibrotide, a drug used to treat severe hepatic veno-occlusive disease. The patent claims a method involving:
- Contacting a plasmin-specific substrate with mammalian euglobulin and defibrotide.
- Continuously measuring the reaction product to quantify defibrotide’s biological activity, defined as 25–35 IU/mg[9][19].
The scope is defined by independent claims covering the method’s procedural steps, reagent specificity (euglobulin fraction), and the quantifiable activity range. Dependent claims further restrict the substrate type (e.g., chromogenic plasmin substrates) and measurement techniques (spectrophotometry)[9].
Claim Structure and Legal Boundaries
Key Claim Features
- Method Claims: Focus on enzymatic interaction between defibrotide and plasmin via euglobulin, ensuring reproducibility in activity measurement[9][19].
- Product-by-Process Claims: The defined biological activity (25–35 IU/mg) ties the method to defibrotide’s therapeutic efficacy, indirectly extending protection to compliant drug batches[14][19].
- Dependent Claims: Narrow the substrate, measurement parameters, and euglobulin preparation methods[9].
Examination Challenges in China
Under China’s patentability criteria for medical methods:
- Claims must reflect technical solutions anchored in product structure or manufacturing processes[5][18].
- Pure diagnostic methods are excluded, but CN104619857 circumvents this by framing the assay as a quality control tool for drug manufacturing[18][19].
- The specification’s emphasis on reagent composition (e.g., euglobulin fraction purity) satisfies the requirement for structural anchoring[5][18].
Patent Landscape Analysis
Competitive Filings and Family Members
CN104619857 belongs to a global family of 40+ patents, including US, EP, and JP grants, indicating strategic protection for defibrotide’s therapeutic and diagnostic applications[9]. Key competitors in related spaces include:
- Arbutus Biopharma: Dominates mRNA delivery patents, but defibrotide’s niche application limits direct overlap[4].
- Dr. Reddy’s: Active in challenging secondary patents via litigation, as seen in Warner-Lambert/Pregabalin cases[13].
Trends in Chinese Pharmaceutical Patenting
- Secondary Patent Dominance: Post-TRIPS, China grants secondary patents for formulations, dosages, and diagnostic methods, provided they demonstrate technical innovation[7][16].
- Utility Model vs. Invention Patents: CN104619857 is an invention patent, subject to stricter novelty/non-obviousness checks. Utility models (shape/structure improvements) are less common in pharma[5][16].
- Litigation Risks: Generic manufacturers often file Type 4.2 declarations (non-infringement) against method patents, as seen in dapagliflozin cases[19].
Validity and Enforcement Considerations
Invalidity Risks
- Prior Art: Older plasmin activity assays (e.g., KR20040090959) could challenge novelty if they disclose similar substrate-euglobulin interactions[9].
- Inventive Step: The combination of known reagents (plasmin substrate + euglobulin) may face obviousness objections unless synergistic efficacy is proven[6][18].
Enforcement Strategies
- Orange Book Listings: While China’s Orange Book system is unofficial, listing CN104619857 could deter generics by triggering patent linkage delays[19].
- Litigation Precedents: Courts often side with innovators if claims are narrowly drafted and validated by clinical data, as in Chugai v. Haihe Pharma[19].
Strategic Recommendations for Patent Holders
- Fortify Dependent Claims: Emphasize novel reagent preparation techniques (e.g., euglobulin isolation methods) to withstand invalidation[5][18].
- Monitor Generics: Track Type 4.2 declarations and preemptively file infringement suits under Article 76 of China’s Patent Law[19].
- Leverage Data Exclusivity: Pair patent protection with data exclusivity for defibrotide’s clinical trial data, extending market exclusivity post-patent expiry[14][16].
Conclusion
CN104619857 exemplifies China’s evolving approach to secondary pharmaceutical patents, balancing innovation incentives with generic access. Its enforceability hinges on precise claim drafting that aligns with technical solution requirements and proactive litigation strategies. As China’s patent linkage system matures, such method patents will play a pivotal role in safeguarding biopharmaceutical innovations.
References
- https://papers.ssrn.com/sol3/papers.cfm?abstract_id=2844964
- https://www.rimonlaw.com/the-importance-of-getting-the-claim-scope-right-in-a-us-patent-application-i/
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- https://arxiv.org/abs/2303.00288
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- https://papers.ssrn.com/sol3/papers.cfm?abstract_id=739964
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- https://pubchem.ncbi.nlm.nih.gov/patent/KR-20190016148-A
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- https://www.uspto.gov/web/offices/pac/mpep/s2751.html
- https://patseer.com/a-quick-guide-to-pharmaceutical-patents-and-their-types/
- https://english.cnipa.gov.cn/module/download/downfile.jsp?classid=0&showname=13-Patent+Landscape_+China+and+Belt+and+Road+Partner+Countries+%282013-2023%29.pdf&filename=fbd6219df7de4ef8a817581c038eb211.pdf
- https://www.knowmade.com/patent-landscape/
- https://www.juve-patent.com/sponsored/ccpit-patent-and-trademark-law-office/patenting-medical-use-inventions-in-china/
- https://ipo.org/wp-content/uploads/2022/06/UNOFFICIAL-CN-Orange-Book-user-guide-Nov2022.pdf
- https://awapoint.com/clarifying-the-patentability-of-medical-use-inventions-in-china/
Last updated: 2025-04-23
