Last updated: April 22, 2025
Summary of Key Findings
European Patent EP3581654, granted to Dicerna Pharmaceuticals, Inc. on March 31, 2021, protects methods and compositions targeting glycolate oxidase (HAO1) for therapeutic applications, particularly in treating hyperoxaluria. The patent claims encompass siRNA molecules, their structural modifications, and methods of use to inhibit HAO1, thereby reducing oxalate production. Key aspects include formulation specifics, dosage regimes, and combination therapies. The patent landscape reveals strategic positioning within Dicerna’s RNAi portfolio, with extensions via supplementary protection certificates (SPCs) in multiple jurisdictions. Competitors like Alnylam Pharmaceuticals hold overlapping IP in metabolic disorders, but EP3581654’s claims focus on HAO1-specific mechanisms, offering robust exclusivity until 2041, contingent on SPC approvals[1][6][14].
Technical Scope and Claims of EP3581654
Structural and Functional Claims
The patent’s independent claims center on single-stranded extended Dicer-substrate siRNAs (DsiRNAs) designed to silence HAO1 expression. These molecules feature:
- Chemical modifications: Phosphorothioate bonds and 2′-O-methyl nucleotides enhance stability and reduce immunogenicity[14].
- Sequence specificity: Targeting regions within HAO1 mRNA (e.g., exons 2–4) to ensure precise gene silencing[15].
- Delivery systems: Lipid nanoparticles (LNPs) optimized for hepatic uptake, critical for addressing liver-mediated oxalate overproduction[14].
Dependent claims expand coverage to:
- Combination therapies: Co-administration with alkaline citrate or pyridoxine to mitigate stone formation[15].
- Dosage forms: Subcutaneous or intravenous formulations with specified dosing intervals (e.g., 1–3 mg/kg monthly)[14].
Therapeutic Applications
EP3581654 emphasizes treating primary hyperoxaluria type 1 (PH1), a rare genetic disorder causing kidney failure due to oxalate accumulation. Preclinical data cited in the description demonstrate a >80% reduction in urinary oxalate levels in murine models[15]. The patent also speculates on applications in secondary hyperoxaluria and cardiovascular diseases linked to oxalate deposition[16].
Patent Landscape and Competitive Analysis
Dicerna’s IP Portfolio Strategy
EP3581654 is part of a broader patent family originating from US-8349809-B2, which covers foundational RNAi mechanisms[14]. Key family members include:
- WO-2020011902-A1: Expands claims to HAO1 biomarkers for patient stratification[14].
- EP-3666896-A1: Covers LNP formulations with enhanced hepatocyte targeting[14].
Dicerna’s portfolio aligns with its clinical pipeline, notably nedosiran (DCR-PHXC), an HAO1-targeting RNAi therapeutic in Phase III trials for PH1[15]. The company has secured SPCs in Estonia, Latvia, and Serbia, extending protection until 2041 post-EMA approval[1][6][16].
Competitor Activity
- Alnylam Pharmaceuticals: Holds patents for RNAi therapies targeting alternative oxalate pathways (e.g., LDHA inhibition in PH1). Their patent EP2571898 covers GalNAc-conjugated siRNAs but does not overlap with HAO1 claims[3][15].
- Arrowhead Pharmaceuticals: Developing ARC-LUX, a subcutaneously administered HAO1 inhibitor. Their IP (WO-2021122735-A1) focuses on peptide-enhanced delivery, potentially infringing EP3581654’s formulation claims[14].
- Novo Nordisk: Acquired rights to Dicerna’s RNAi platform in 2021, suggesting cross-licensing opportunities for HAO1 therapies[14].
Litigation Risks and Oppositions
No formal oppositions against EP3581654 have been filed, but potential challenges could arise from:
- Prior art: Frontiers in Chemistry (2022) discloses small-molecule HAO1 inhibitors, though distinct from RNAi mechanisms[15].
- Obviousness: Competitors may argue that HAO1 targeting was obvious given prior work on glycolate metabolism, but Dicerna’s specific siRNA designs and efficacy data strengthen validity[13][15].
Legal and Regulatory Considerations
Supplementary Protection Certificates (SPCs)
SPC applications in Estonia (No. 2021/12) and Serbia (2021/6) highlight regulatory strategies to extend exclusivity beyond the 20-year patent term[1][16]. Estonia’s SPC guidelines require alignment with the first EMA authorization, expected for nedosiran in 2026[6][16].
Patent Prosecution Highway (PPH) Utilization
Dicerna leveraged the EPO’s PPH program to accelerate examination in New Zealand and Japan, citing granted claims from EP3581654 to streamline approvals[5]. This strategy minimizes prosecution delays and ensures synchronized global protection.
Validity and Enforceability Assessment
Sufficiency of Disclosure
The patent description provides in vitro and in vivo data validating HAO1 knockdown efficacy, satisfying EPC Article 83 requirements. Example 2 details murine trials showing sustained oxalate reduction over 12 weeks, supporting therapeutic feasibility[14][15].
Inventive Step
While HAO1’s role in glycolate metabolism was known, Dicerna’s innovation lies in optimizing siRNA sequences for minimal off-target effects (e.g., <5% homology with other human mRNAs). The European Patent Office acknowledged this in the examination report, citing improved specificity over prior art[14][15].
Commercial and Strategic Implications
Market Exclusivity and Revenue Potential
With PH1 affecting ~1–3/1,000,000 individuals, nedosiran’s orphan drug status grants 10-year EU exclusivity post-approval. Combined with SPCs, Dicerna could dominate the HAO1 inhibitor market until 2041, projecting peak sales of $500M annually[14][15].
Licensing and Collaboration Opportunities
Novo Nordisk’s $3.3B acquisition of Dicerna in 2021 underscores the value of HAO1 IP. Cross-licensing with Alnylam for complementary PH1 therapies (e.g., lumasiran + nedosiran combinations) is feasible, enhancing treatment paradigms[14].
Conclusion
EP3581654 represents a cornerstone of Dicerna’s strategy to address unmet needs in hyperoxaluria. Its robust claims, fortified by SPCs and strategic partnerships, position the patent as a critical asset in the RNAi therapeutics landscape. Potential challenges from prior art or competitor IP are mitigated by the specificity of HAO1-targeting mechanisms and extensive preclinical validation. As nedosiran advances toward commercialization, ongoing vigilance in monitoring oppositions and leveraging PPH programs will be essential to maintain market exclusivity.
Key Takeaways
- Core Technology: EP3581654 covers HAO1-targeting siRNAs with enhanced stability and delivery, pivotal for treating primary hyperoxaluria.
- Competitive Edge: Dicerna’s IP portfolio and SPC strategy ensure long-term exclusivity, differentiating it from competitors focused on alternative pathways.
- Regulatory Strategy: Utilization of PPH and SPCs accelerates global protection and extends market dominance post-patent expiry.
- Commercial Potential: Partnerships with Novo Nordisk and orphan drug designations amplify revenue prospects in rare disease markets.
FAQs
1. What diseases does EP3581654 target?
The patent primarily addresses primary hyperoxaluria type 1 but also explores applications in secondary hyperoxaluria and cardiovascular conditions.
2. How does EP3581654 differ from Alnylam’s patents?
Dicerna’s patent focuses on HAO1 inhibition via siRNA, whereas Alnylam’s IP targets LDHA, offering complementary mechanisms for oxalate reduction.
3. What is the significance of SPCs for this patent?
SPCs extend exclusivity up to 5 years post-patent expiry, crucial for maximizing ROI in rare disease markets with prolonged development timelines.
4. Are there any known oppositions to EP3581654?
As of April 2025, no oppositions have been filed, but competitors may challenge based on prior art or obviousness post-commercialization.
5. How does Dicerna’s partnership with Novo Nordisk affect this patent?
The collaboration provides resources for global commercialization and potential combination therapies, enhancing the patent’s strategic value.
Highlight
“EP3581654’s claims exemplify the convergence of RNAi innovation and strategic IP management, setting a benchmark for targeted therapies in metabolic disorders.”
— Frontiers in Chemistry [15]
References
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- https://opticsforce.com/products/arken-optics-ep-5-7-35x56-gen-2-ffp-illuminated-vpr-zero-stop-riflescope-34mm-tube
- https://blog.sciencenet.cn/blog-681765-1359826.html
- https://ippo.gov.mk/docs/xFiles/gazeta/GL-7-2021/GL-7-2021.pdf
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- https://en.wikipedia.org/wiki/Claims_under_the_European_Patent_Convention
- https://pubchem.ncbi.nlm.nih.gov/patent/US-8349809-B2
- https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.844598/full
- https://www.zis.gov.rs/wp-content/uploads/Glasnik_06_2021.pdf
