Targeted delivery of therapeutic agents to human adipocytes
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Publication Number
US-11690804-B2
Publication Date
2023-07-04
Expiration Date
Abstract
Compositions and methods relating to modulating thermogenic regulation are disclosed. The compositions and methods can be used to treat diseases or conditions such as obesity or cardiometabolic disorders such as type 2 diabetes mellitus, NAFLD and NASH. Compositions include an adipocyte-targeting composition that includes a therapeutic agent capable of modulating thermogenic regulation, a targeting element facilitating cellular uptake and delivery of the therapeutic agent to a targeted adipocyte, and liposomal particles comprising sphingomyelin, DMPC, and cholesterol, wherein the liposomal particles enhance intra-cellular penetration of the therapeutic agent and protect the therapeutic agent from degradation.
Core Innovation
The invention provides an adipocyte-targeting composition comprising a therapeutic agent capable of modulating lipid oxidation and/or thermogenic regulation, together with a targeting element facilitating cellular uptake and delivery of the therapeutic agent to a targeted adipocyte. The thermogenic regulation includes effects associated with lipid oxidation and thermogenic regulation, including UCP activity.
The composition also includes liposomal particles comprising sphingomyelin, DMPC, and cholesterol. The liposomal particles enhance intra-cellular penetration of the therapeutic agent and protect the therapeutic agent from degradation, while the lipid system is configured to improve delivery to targeted adipocytes while maintaining therapeutic-agent integrity.
Additional aspects describe therapeutic agents that modulate lipid oxidation and/or thermogenic regulation, including miRNA agents and small-molecule/biologic agents, together with targeting constructs and linkers. Targeting elements are configured to bind adipocyte-associated markers/transporters such as Fatty Acid Translocase (FAT/CD36/SCARB3), Aquaporin 7 (AQP7), Perilipin 1 (PLIN1), or Perilipin 2 (PLIN2), and related constructs include oligonucleotide-fatty acid conjugates (AdipomiRs) and Hexarelin–oligonucleotide conjugates (HexamiRs).
A further described therapeutic-agent form includes an oligonucleotide linked to Hexarelin via a disulfide bond. Related variants specify that the oligonucleotide is an antagomir of miR-22 or an agomir of miR-515, and that the oligonucleotide has a length range as described in the document.
Claims Coverage
The partial content identifies two independent claims. Together, they cover an adipocyte-targeting composition with a therapeutic agent, a targeting element, and specific sphingomyelin/DMPC/cholesterol liposomal particles, and an adipocyte-targeting therapeutic agent consisting of an oligonucleotide linked to Hexarelin via a disulfide bond.
Adipocyte-targeting composition with thermogenic/lipid-oxidation modulation
An adipocyte-targeting composition comprising a therapeutic agent capable of modulating lipid oxidation and/or thermogenic regulation; a targeting element facilitating cellular uptake and delivery of the therapeutic agent to a targeted adipocyte; and liposomal particles comprising sphingomyelin, DMPC, and cholesterol that enhance intra-cellular penetration of the therapeutic agent and protect the therapeutic agent from degradation.
Hexarelin-linked oligonucleotide therapeutic agent via disulfide bond
An adipocyte-targeting therapeutic agent comprising an oligonucleotide linked to Hexarelin via a disulfide bond.
Claim coverage in the partial content is anchored on adipocyte targeting of thermogenic/lipid-oxidation modulators using liposomal particles composed of sphingomyelin, DMPC, and cholesterol with enhanced intracellular penetration and protection from degradation, and on a specific Hexarelin–oligonucleotide linkage via a disulfide bond.
Stated Advantages
Enhances intra-cellular penetration of the therapeutic agent.
Protects the therapeutic agent from degradation.
Documented Applications
Treating obesity and cardiometabolic disorders by modulating thermogenic regulation, including lipid oxidation and UCP activity.
Addressing type 2 diabetes mellitus and NAFLD/NASH through adipocyte-targeting compositions that modulate thermogenic regulation.
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