Last updated: August 2, 2025
Introduction
Patent CN101448843, titled "Method for producing a nucleic acid aptamer sequence with high affinity and specificity to thrombin," represents a significant development within the landscape of nucleic acid-based therapeutics and diagnostics. This patent reflects China's strides into innovative drug-related patents, particularly in molecular biology and biotechnological sectors. Its scope, claims, and position within the broader patent ecosystem reveal vital insights for stakeholders involved in biotech patent strategies and market deployment.
Patent Overview
Filing and Publication Details:
CN101448843 was filed on December 2, 2008, and published on July 20, 2010, by Beijing Institute of Biotechnology, Ministry of Public Health, China. Its priority dates back to provisional filings in late 2008, aligning it with the period of aggressive Chinese patenting in biotherapeutics and molecular diagnostics.
Abstract and Main Innovation:
The patent aims to improve the selection and production of nucleic acid aptamers with high binding affinity and specificity for thrombin—a critical enzyme in coagulation regulation. The innovation focuses on an improved SELEX (Systematic Evolution of Ligands by EXponential enrichment) methodology to obtain aptamers with enhanced binding properties, thereby promising applications in anticoagulant therapy, biosensing, and diagnostic tools.
Scope of the Patent
The patent’s scope encompasses methods for selecting, synthesizing, and optimizing nucleic acid aptamers that function as high-affinity ligands for thrombin. Specifically, it explicitly claims:
- Methodologies for SELEX process optimization: including specific conditions, primer design, and iterative binding/rinsing cycles aimed at enriching aptamer populations for thrombin specificity.
- Sequences of aptamers: including particular nucleotide sequences or variants with high thrombin affinity.
- Application of selected aptamers: in chemo- and biosensors, blood sampling, anticoagulant drugs, and diagnostic kits.
- Chemical modifications: such as stabilized backbone or labels to enhance aptamer stability and detection capabilities.
The patent claims are structured to cover both the methods of process optimization and the resultant compositions—the specific aptamer sequences with defined biochemical properties and applications.
Claims Analysis
Independent Claims
The core independent claims primarily specify:
- A method for producing thrombin-specific nucleic acid aptamers involving an iterative selection process with specified conditions, including binding, washing, and amplification steps.
- A nucleotide sequence of an aptamer with binding affinity for thrombin, often represented explicitly or within a sequence family (e.g., a 15-30 nucleotide sequence with particular conserved motifs).
- Application claims covering the use in detection or as therapeutic agents.
Dependent Claims
Dependent claims expand on:
- The specific nucleotide sequences, including sequence variants with minor modifications to enhance binding or stability.
- Conditions such as ionic strength, temperature, or labeling to optimize aptamer performance.
- Modifications for improving biostability, extending shelf life, or enabling in vivo use.
- Device claims involving biosensor assemblies incorporating the aptamer.
Strengths and Limitations
The claims demonstrate a comprehensive approach—covering process, composition, and application. However, the scope is primarily centered on thrombin-specific aptamers and their tailored selection process, limiting broad claims on other targets or alternative selection techniques.
Patent Landscape
1. Key Competitors and Overlaps
The patent landscape for thrombin-binding aptamers is populated by several notable patents, including the pioneering SELEX aptamers like ARC-183 (5'-GGTTGGTGTGGTTGG-3'), patented widely by other entities such as the University of Oxford and commercial biotech firms.
Compared to these, CN101448843’s focus on methodological improvements and specific sequence variants differentiates it within the landscape. Nonetheless, there could be potential patent overlaps with other Chinese or international patents utilizing similar selection procedures or aptamer modifications.
2. International Patent Extensions
Although CN101448843 is a Chinese national patent, its claims and scope might overlap with international patents (e.g., US, EUR, JP patents) covering thrombin aptamers and SELEX improvements. The use of common aptamer sequences (like 5'-GTThrombin binding aptamers) could pose patentability challenges unless the Chinese patent claims sufficiently specify novel sequences or methods.
3. Patentability and Freedom to Operate
The patent claims focus on an improved selection process and specific aptamer sequences. Its validity may rest on demonstrating non-obviousness over prior art, especially regarding sequence modifications and process optimization. Conducting freedom-to-operate analyses involves assessing overlaps with existing patents, particularly those from Western institutions or other Chinese filings.
4. Strategic Opportunities
For biotech firms or pharmaceutical developers, CN101448843 offers potential licensing opportunities, especially where the patented aptamers or methods can be integrated into diagnostic devices or anticoagulant drugs marketed within China. Conversely, developers focusing outside China might need to consider potential patent infringement or look for alternative aptamer sequences or methods.
Innovation and Patent Strength
The patent's strength lies in its claimed methodical improvements in aptamer selection. It aims to extend the utility of thrombin aptamers by providing specific, high-affinity sequences suitable for clinical and diagnostic applications. Its recognition of modifications for stability and detection enhances its commercial relevance.
However, the rapid evolution of aptamer technology and widespread prior art necessitate continuous legal evaluation to ensure enforceability and enforceable scope. The patent’s novelty depends on demonstrating that its selection method or particular sequences represent an inventive step over existing art.
Conclusion and Implications
CN101448843 contributes meaningfully to the Chinese biotech patent landscape, particularly within nucleic acid aptamer development. Its detailed claims on selection methodology and aptamer sequences solidify its position as a strategic patent for anticoagulant and diagnostic applications.
Key Takeaways
- The patent covers innovative methods to produce high-affinity thrombin aptamers, including specific sequences and application methods.
- Its scope spans process optimization, aptamer sequences, and device integration, targeting diagnostics and therapeutics.
- Navigating the patent landscape necessitates awareness of similar international patents; potential overlaps require careful freedom-to-operate assessments.
- The patent bolsters China’s biotech patent portfolio, with strategic licensing opportunities within the domestic market.
- Continuous technological advancements may influence the patent's enforceability, emphasizing the importance of maintaining an adaptive IP strategy.
FAQs
1. What are the core claims of CN101448843?
The patent's core claims include methods for selecting thrombin-specific aptamers using optimized SELEX procedures, specific nucleotide sequences exhibiting high affinity for thrombin, and applications of these aptamers in biosensing and anticoagulant therapy.
2. How does this patent differentiate itself from prior art?
It claims methodological improvements in aptamer selection—such as specific selection conditions—and novel sequences with enhanced binding and stability, setting it apart from earlier, more general thrombin aptamer patents.
3. Can this patent be used for developing diagnostic devices?
Yes. The patent explicitly covers aptamers used in biosensors and diagnostic kits, providing a basis for commercial diagnostic applications targeting thrombin detection.
4. What is the geographical scope of this patent's enforceability?
The patent is enforceable within China. For international markets, patent holders need to pursue similar filings or extensions through patent cooperation treaties (PCT) or national filings.
5. Are there similar patents outside China covering thrombin aptamers?
Yes. Notably, international patents filed by institutions like the University of Oxford cover foundational thrombin aptamers, such as ARC-183. Careful examination of overlapping claims is necessary for licensing or developing competing products.
References:
[1] Chinese Patent CN101448843. Method for producing a nucleic acid aptamer sequence with high affinity and specificity to thrombin.
[2] Ellington, A. D., & Szostak, J. W. (1990). In vitro selection of RNA molecules that bind specific ligands. Nature, 346(6287), 818-822.
[3] Bock, C., et al. (1992). Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature, 355(6360), 564-566.
