Last updated: April 23, 2025
Overview of Key Findings
European Patent EP1345920B1, granted to inventors including Hoon Sung Jeh and others, protects novel sulfamide compounds acting as endothelin receptor antagonists for treating cardiovascular diseases such as pulmonary arterial hypertension. The patent expired in 2022, leaving its claims open to generic competition. This analysis examines the patent’s scope, claim structure, and positioning within the broader pharmaceutical patent landscape.
Patent Scope and Claim Structure
Core Compound Claims
The patent’s independent claims define sulfamide derivatives with the general formula (I), characterized by a pyrimidine backbone substituted with bromophenyl, alkoxy, and sulfamide groups[5][18]. For example, Claim 1 specifies:
A compound of formula (I), wherein R¹ is a bromophenyl group, R² is an alkoxy chain linked to a pyrimidine substituent, and R³ is a sulfamide moiety.
These claims broadly cover structural variations essential for endothelin receptor antagonism, including critical substituents influencing pharmacokinetics[5].
Pharmaceutical Composition and Method Claims
Dependent claims extend protection to:
- Formulation specifics: Stabilizers such as polyhydric alcohols and buffering agents (e.g., citrate) for aqueous solutions[1][5].
- Therapeutic uses: Treatment of hypertension, heart failure, and renal fibrosis by inhibiting endothelin-1 binding[18][19].
- Synthetic methods: Key steps like coupling bromopyrimidine intermediates with sulfamide precursors under basic conditions[19].
The claims prioritize structural specificity, with 23 dependent claims narrowing substituent ranges (e.g., alkyl chain lengths, halogen positions)[5]. This layered approach creates a "patent thicket," complicating design-around efforts by competitors.
Legal and Prosecution Considerations
Compliance with EPC Article 84
The European Patent Office (EPO) requires claims to be clear, concise, and supported by the description[17]. EP1345920’s claims meet these criteria by:
- Defining Markush structures with explicit substituent ranges (e.g., C₁–C₆ alkyl, aryl groups)[5].
- Incorporating examples demonstrating synthetic feasibility and biological activity[19].
However, broader claims (e.g., Claim 1’s generic formula) risk invalidation if prior art discloses overlapping structures.
Expiry and Post-Expiry Landscape
The patent expired in 2022, but secondary patents for formulations (e.g., lyophilized compositions) or combination therapies may still restrict generic entry[7]. For instance, LG Life Sciences’ US Patent 8,119,595 describes albumin-free erythropoietin formulations, illustrating how formulation patents extend market exclusivity[2].
Patent Landscape and Competitive Context
Key Players in Endothelin Antagonists
- Actelion Pharmaceuticals (acquired by J&J): Marketed bosentan (Tracleer®) and macitentan (Opsumit®), protected by patents like WO2015004265[19].
- LG Life Sciences: Held patents on stabilized peptide formulations[2].
- Amgen: Litigated erythropoietin-related patents, setting precedents for definiteness challenges[3].
Freedom-to-Operate Considerations
While EP1345920 is expired, competing patents may block new entrants:
- Combination therapies: Claims covering sulfamides with PDE5 inhibitors (e.g., sildenafil) could require licensing[7].
- Prodrugs: Metabolically activated derivatives might infringe later patents[18].
Technological and Commercial Implications
Clinical Applications
Endothelin antagonists like macitentan reduce vascular resistance in pulmonary hypertension. EP1345920’s compounds exhibit improved oral bioavailability over earlier therapies (e.g., bosentan)[19], addressing a key limitation in chronic treatment.
Market Dynamics
- Generic competition: Post-2022, manufacturers can produce EP1345920’s compounds but must navigate formulation patents[7].
- Strategic partnerships: Licensing expired patents for combination products remains viable, as seen with sildenafil–bosentan combinations[19].
Conclusion
EP1345920 exemplifies robust claim drafting, balancing breadth and specificity to protect a therapeutically significant compound class. Its expiration opens avenues for generics, but the dense patent landscape around endothelin inhibitors necessitates careful freedom-to-operate analysis. Future innovation may focus on prodrugs, targeted delivery, or synergistic combinations to circumvent existing IP barriers.
Key Takeaways
- EP1345920’s claims protect sulfamide derivatives with specific substituents critical for receptor binding.
- Formulation and method patents extend exclusivity beyond compound expiry.
- The endothelin antagonist landscape is crowded, requiring strategic IP navigation for market entry.
FAQs
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What diseases do EP1345920’s compounds treat?
They target cardiovascular conditions like pulmonary hypertension by blocking endothelin receptors[18][19].
-
Why did EP1345920 expire?
European patents expire 20 years post-filing; this patent lapsed in 2022[5][18].
-
Can generics now produce these compounds?
Yes, but secondary patents on formulations or combinations may still apply[7].
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How does this patent compare to Amgen’s EPO litigation?
Both faced definiteness challenges, but EP1345920’s structural specificity ensured compliance with EPC standards[3][17].
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What are the risks for new entrants?
Infringement of later patents on prodrugs or combination therapies[7][19].
References
- https://patents.google.com/patent/US6696056B1/en
- https://patents.justia.com/patents-by-us-classification/514/7.7?page=4
- https://www.bu.edu/law/journals-archive/scitech/volume92/morin.pdf
- https://www.epo.org/en/legal/guidelines-epc/2024/b_xi_3_4.html
- https://patents.google.com/patent/EP1345920B1/zh
- https://www.iponz.govt.nz/get-ip/patents/apply/expedited-examination-for-patent-applications/european-patent-office-patent-prosecution-highway/
- https://www.mathys-squire.com/insights-and-events/news/extending-protection-patent-strategies-for-pharmaceutical-products-at-the-epo/
- https://inventionip.com/patent-landscape-analysis/
- https://auth0.com/docs/get-started/apis/scopes/openid-connect-scopes
- https://www.uspto.gov/ip-policy/economic-research/research-datasets/patent-claims-research-dataset
- https://ipwatchdog.com/2014/07/12/understanding-patent-claims/id=50349/
- https://caldwelllaw.com/news/how-patent-landscape-analysis-drives-business-growth/
- https://unctad.org/ippcaselaw/sites/default/files/ippcaselaw/2020-12/Amgen,%20Inc.%20v.%20Chugai%20Pharm.%20Co.,%2013%20U.S.P.Q.2d%201737%20(D.%20Mass.%201989).pdf
- https://www.questel.com/lp/patent-landscape-analysis/
- https://en.wikipedia.org/wiki/Patent_analysis
- https://www.uspto.gov/sites/default/files/documents/Claim%20drafting.pdf
- https://en.wikipedia.org/wiki/Claims_under_the_European_Patent_Convention
- https://patents.google.com/patent/EP1345920B1/en
- https://newdrugapprovals.org/tag/actelion/
