Formulated and/or co-formulated liposome compositions containing PD-1 antagonist prodrugs useful in the treatment of cancer and methods thereof
Inventors
Stover, David • Bharali, Dhruba • Hay, Bruce A • Safaie, Tahmineh
Assignees
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Publication Number
US-12059470-B2
Publication Date
2024-08-13
Expiration Date
Abstract
Formulated and/or co-formulated nanocarriers (e.g., LNPs and/or SLNPs) comprising PD-1 Prodrugs and methods of making the nanocarriers are disclosed herein. The PD-1 Prodrug compositions comprise a drug moiety, a lipid moiety, and linkage unit that inhibit PD-1-L1/L2. The PD-1 Prodrugs can be formulated and/or co-formulated into a nanocarrier to provide a method of treating cancer, immunological disorders, and other disease by utilizing a targeted drug delivery vehicle.
Core Innovation
The invention relates to lipid-based nanocarriers and a PD-1 prodrug for use in treating a subject suffering or diagnosed with cancer. The nanocarrier comprises a PD-1 Prodrug having a specified chemical structure and a pharmaceutically acceptable salt, and the PD-1 prodrug concept is described as a drug moiety together with a lipid moiety and a cleavable linkage unit.
The disclosure provides exemplar PD-1 prodrug chemical structures, including Formula I and Formula II, and specific PD-1 prodrug drug moieties identified as PD3 through PD7. It further describes lipid and liposome formulation options, including cholesterol-containing lipid conjugates, DPPG, DMPG, helper lipids, and linkage unit concepts with ester and biodegradable linkages cleavable by esterases.
The disclosed nanocarrier platform includes liposome, lipid nanoparticle, and solid-lipid nanoparticle architectures, with examples of PD-1 prodrug/lipid combinations and co-formulation concepts. The compositions are described for PD-1 pathway blockade and cancer treatment, including combinations with toll-receptor agonists, A2a receptor antagonists, immune modulating agents, and doxorubicin.
Claims Coverage
The claim set contains one independent claim covering treating a subject suffering or diagnosed with cancer by administering an effective amount of a nanocarrier comprising a PD-1 Prodrug having a specified chemical structure and a pharmaceutically acceptable salt. The dependent claims refine the nanocarrier type, add co-formulated immune modulators or therapeutics, and narrow subject, cancer, and particle characteristic ranges.
Nanocarrier comprising a PD-1 prodrug with specified chemical structure
Administering to a subject in need an effective amount of a nanocarrier that comprises a PD-1 Prodrug having the following chemical structure.
Pharmaceutically acceptable salt
Using a pharmaceutically acceptable salt of the PD-1 prodrug within the method of treating the subject.
Treating a subject suffering or diagnosed with cancer
Treating a subject suffering or diagnosed with cancer by administering the effective amount of the nanocarrier comprising the PD-1 Prodrug.
Solid-lipid nanoparticle nanocarrier
The nanocarrier comprises a solid-lipid nanoparticle (SLNP).
Co-formulated toll-receptor agonist
The method is formulated with a toll-receptor agonist, wherein the SLNP is SLNP-PD3-TR5.
SLNP and liposome with defined Zav size and PDI
The SLNP has a Zav size between 70 nm and 120 nm and the liposome has a PDI between 0.001 and 0.250.
Co-formulated A2a receptor antagonist and doxorubicin
The method is co-formulated with an A2a receptor antagonist and with doxorubicin to produce an SLNP designated SLNP-PD3-AR5-DOX.
Treatment of melanoma
The method is applied to cancer that is melanoma.
The claims center on administering a nanocarrier that includes a PD-1 Prodrug having a specified chemical structure and a pharmaceutically acceptable salt for cancer treatment, with dependent claims specifying SLNP-based formulations, liposome-related particle characteristics, co-formulated agents, and melanoma.
Stated Advantages
Controlled and/or targeted delivery is stated for lipid-based nanocarriers.
Documented Applications
Treating a subject suffering or diagnosed with cancer by administering a nanocarrier comprising a PD-1 Prodrug.
Treating melanoma as a specific cancer application.
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