Formulated and/or co-formulated liposome compositions containing toll-like receptor (“TLR”) agonist 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-11896646-B2
Publication Date
2024-02-13
Expiration Date
Abstract
Formulated and/or co-formulated liposomes comprising TLR prodrugs and/or TLR Lipid Moieties and methods of making the liposomes are disclosed herein. The TLR prodrug compositions comprise a drug moiety, a lipid moiety, and linkage unit that inhibit Toll-Like Receptor (e.g., TLR1/2, TLR4, and/or TLR7). The TLR prodrugs can be formulated and/or co-formulated into a liposome 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 Toll-like receptor (TLR) prodrug concepts in which a drug moiety and a lipid moiety are joined by a biologically cleavable linkage unit (LU). The LU connects the drug moiety with the lipid moiety, producing a defined TLR prodrug chemical structure. The drug moiety comprises a TLR agonist, and the overall prodrug is positioned as a TLR prodrug composition.
Representative TLR prodrug chemical structures are described as Formula I and Formula II. The document enumerates example TLR inhibitor agents including TR3, TR5, TR5(A), TR6, TR6(A) and variants such as TR5(B) and TR6(A). Representative lipid components are also described, including CHEMS (cholesterol hemisuccinate), stearic acid, and other named lipids, along with LU examples such as a hydromethylcarbamate linker.
The document situates the resulting TLR prodrugs for use in drug delivery by encapsulation in nanocarriers, including liposomes. The described context includes treatment areas such as human cancer and immunological disease treatment. The document also provides extensive context regarding TLR targets, including TLR1/2, TLR4, and TLR7/8.
Claims Coverage
The independent claim coverage centers on two primary categories: a Toll-like receptor (TLR) prodrug composition defined by a drug moiety, a lipid moiety, and a linkage unit (LU), and a nanocarrier that includes the TLR prodrug and releases an active TLR inhibitor after cleavage of the LU.
TLR prodrug composition with LU-conjugated drug and lipid moieties
A Toll-like receptor (TLR) prodrug composition comprising a drug moiety, a lipid moiety, and a linkage unit (LU), wherein the drug moiety comprises a TLR agonist and wherein the LU conjugates the drug moiety with the lipid moiety, and wherein the TLR prodrug has the chemical structure as disclosed.
Nanocarrier releasing an active TLR inhibitor after LU cleavage
A nanocarrier comprising a TLR prodrug whereby the nanocarrier releases an active TLR inhibitor after cleavage of the LU.
Overall, the claims focus on a defined TLR prodrug architecture where a TLR agonist drug moiety is conjugated to a lipid moiety via a linkage unit, and on nanocarriers that contain the LU-conjugated prodrug such that cleavage of the LU yields an active TLR inhibitor.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Human cancer treatment.
Immunological disease treatment.
Drug delivery by encapsulation in nanocarriers, including liposomes.
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