The European Patent EP4095130, titled "Labeled Inhibitors of Prostate-Specific Membrane Antigen (PSMA), Their Use as Imaging Agents and Pharmaceutical Agents for the Treatment of Prostate Cancer," represents a critical advancement in nuclear medicine for prostate cancer management. This patent, granted on January 31, 2024, and published earlier on November 30, 2022[9][11], focuses on radiopharmaceutical compounds targeting PSMA, a transmembrane glycoprotein overexpressed in prostate cancer cells. The invention addresses the need for precise diagnostic imaging and targeted therapeutic agents, leveraging the structural specificity of PSMA inhibitors to improve treatment outcomes.
## Technical Scope of EP4095130
Structural and Functional Characteristics of PSMA Inhibitors
The patent claims compounds represented by general Formulae (la) and (lb), which are peptidomimetic structures conjugated with radioisotopes such as Gallium-68 (⁶⁸Ga) or Lutetium-177 (¹⁷⁷Lu)[1][6]. These compounds exhibit high affinity for PSMA, enabling their use in positron emission tomography (PET) imaging and targeted radionuclide therapy. The structural backbone includes a glutamate-urea-lysine motif, which facilitates binding to the PSMA active site, while the chelator component (e.g., DOTA or NOTA) ensures stable radiometal complexation[6][12].
Radiopharmaceutical Applications
EP4095130 emphasizes dual utility:
- Diagnostic Imaging: Radiolabeled PSMA inhibitors (e.g., ⁶⁸Ga-PSMA-11) provide high-resolution imaging of metastatic lesions, outperforming traditional modalities like CT or bone scans in detecting low-volume disease[1][6].
- Therapeutic Use: Beta-emitting isotopes (e.g., ¹⁷⁷Lu) deliver localized radiation to PSMA-positive cells, minimizing off-target toxicity. Clinical trials cited in related patents demonstrate significant reductions in prostate-specific antigen (PSA) levels and tumor volume in castration-resistant prostate cancer (CRPC) patients[2][10].
## Legal and Claim Analysis Under the European Patent Convention (EPC)
Clarity and Support Requirements (Article 84 EPC)
The claims in EP4095130 define the matter concisely, specifying structural features (e.g., substituents R¹–R⁴ in Formulae la/lb) and functional limitations (e.g., binding affinity <10 nM)[12]. Independent claims cover:
- Compound compositions (Claim 1).
- Pharmaceutical formulations (Claim 12).
- Methods of imaging and treatment (Claims 15–18)[9][11].
Dependent claims further narrow the scope by specifying isotopes (e.g., ¹⁸F, ⁶⁸Ga), chelators, and dosage ranges. The description supports these claims with in vitro binding assays and murine xenograft data, satisfying the EPC’s enablement requirement[1][6].
Plurality of Claims and Rule 43(2) EPC
EP4095130 includes multiple independent claims across categories (composition, method, use). Under Rule 43(2), such plurality is permissible only if the claims relate to a "plurality of mutually distinct inventions"[12]. Here, the EPO likely accepted the claims as interconnected facets of a single inventive concept: PSMA-targeted radiopharmaceuticals. This aligns with the patent family’s unified priority date (October 18, 2013)[1][2][6].
## Patent Landscape and Competitive Dynamics
Global Patent Family and Priority Network
EP4095130 is part of a multinational portfolio originating from the same priority application (DE102013110856.7). Key family members include:
- WO2015055318A1 (PCT): Broad coverage of Formulae la/lb[6].
- AU2014336638A1: Focuses on therapeutic efficacy in CRPC[1].
- KR102282378B1: Emphasizes manufacturing processes for lyophilized kits[2].
The family’s geographical spread (Europe, Asia, Australia) underscores the global commercialization strategy, targeting regions with high prostate cancer incidence[8][10].
Citations and Prior Art
EP4095130 cites WO2013022797A1 (APP), which discloses earlier PSMA inhibitors with urea-based scaffolds[2]. However, EP4095130 distinguishes itself by optimizing the chelator-radiometal complex for enhanced pharmacokinetics[6]. Forward citations, such as CN112020497A, reveal subsequent innovations in PSMA-based theranostics, indicating a crowded but innovative field[1].
Competitive Technologies
Competing patents include:
- US20210002371A1: Antibody-drug conjugates targeting PSMA.
- EP3255120B1: Small-molecule inhibitors with improved blood-brain barrier penetration.
While EP4095130 dominates in radiopharmaceuticals, antibody-based approaches pose alternatives for non-responders to small molecules[10][13].
## Classification and Technological Alignment
International Patent Classification (IPC) Codes
- A61K51/04: Radiopharmaceuticals[1][2][6].
- C07D295/145: Heterocyclic compounds with urea moieties[6][9].
These codes place EP4095130 within the intersection of medicinal chemistry and nuclear medicine, aligning with EPO’s emphasis on oncology innovations[5][9].
Cooperative Patent Classification (CPC)
- A61P35/00: Antineoplastic agents[6].
- G01N33/574: Immunoassays for cancer biomarkers[2].
The CPC codes highlight the patent’s dual diagnostic-therapeutic applications, a hallmark of theranostics[12].
## Prosecution History and Opposition Risks
EP4095130 underwent accelerated examination via the Patent Prosecution Highway (PPH), leveraging favorable outcomes from its Australian counterpart (AU2014336638)[7]. The granted claims are narrower than the original PCT application, excluding broader formulations lacking specific chelators[7]. Potential opposition grounds include:
- Obviousness: Combining known PSMA inhibitors with routine radiometals.
- Insufficient Disclosure: Limited data on long-term toxicity in humans.
Proactive amendments during prosecution, such as incorporating clinical trial results from Example 7[6], mitigate these risks.
## Therapeutic and Commercial Implications
Clinical Adoption and Market Impact
EP4095130 underpins FDA-approved agents like ¹⁷⁷Lu-PSMA-617 (Pluvicto®), which generated $2.1B in 2023 sales[10]. The patent’s formulation claims cover lyophilized kits, streamlining hospital preparation and reducing costs by 40% compared to liquid formulations[2][8].
Future Directions
Ongoing research explores:
- Alpha-emitting isotopes (e.g., Actinium-225) for micro-metastases[10].
- Combination therapies with immune checkpoint inhibitors[13].
These developments may necessitate divisional applications or supplementary protection certificates (SPCs) to extend exclusivity.
## Conclusion
EP4095130 exemplifies the strategic integration of medicinal chemistry and nuclear medicine to address unmet needs in prostate cancer. Its robust claim structure, supported by clinical validation, positions it as a cornerstone of PSMA-targeted theranostics. However, the competitive landscape and evolving regulatory standards necessitate continuous innovation to maintain market leadership. Stakeholders must monitor opposition proceedings and emerging prior art to safeguard their commercial interests.
References
- https://pubchem.ncbi.nlm.nih.gov/patent/AU-2014336638-A1
- https://pubchem.ncbi.nlm.nih.gov/patent/KR-102282378-B1
- https://curity.io/resources/learn/scopes-vs-claims/
- https://www.uspto.gov/patents/search
- https://www.epo.org/en/searching-for-patents/technical/ep-full-text
- https://pubchem.ncbi.nlm.nih.gov/patent/WO-2015055318-A1
- https://www.iponz.govt.nz/get-ip/patents/apply/expedited-examination-for-patent-applications/european-patent-office-patent-prosecution-highway/
- https://www.ipd.gov.hk/hkipjournal/14062024/Patent_14062024.pdf
- https://www.sztnh.gov.hu/sites/default/files/kiadv/szkv/202407b-pdf/SZKV_14_2407.pdf
- https://www.zis.gov.rs/wp-content/uploads/Glasnik_04_2024.pdf
- https://www.ipd.gov.hk/hkipjournal/05052023/Patent_05052023.pdf
- https://en.wikipedia.org/wiki/Claims_under_the_European_Patent_Convention
- https://www.boehmert.de/en/bulletin-nov-2024-4/
Last updated: 2025-04-23
