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Publication Number
US-12286625-B2
Publication Date
2025-04-29
Expiration Date
Abstract
Increase of energy expenditure as an effective treatment of obesity and related disorders is a target for drug research and development. A 15% increase of energy expenditure is believed to be sufficient to achieve significant weight and fat mass reduction while providing meaningful improvement of metabolic parameters. Disclosed herein is a method for pharmacological inhibition of miR-22-3p, which represents a new therapeutic approach for treating human obesity, diabetes, and hypercholesterolemia.
Core Innovation
The invention relates to a mir-22 miRNA antagonist defined by a formula referenced as SEQ ID NO: 4. The disclosed antagonist is directed to miR-22, including mature miR-22-3p as a specified target form.
The invention further describes administration of a mir-22 inhibitor to cells, including adipocytes and related cells, and therapeutic nucleic-acid agents targeting thermogenic regulators in obesity and metabolic disorders. The linked metabolic mechanism includes increased thermogenesis via KDM3A/KDM6B demethylase activity, with upregulation of PPARA and UCP1, and downstream mitochondrial proton leak/thermogenesis.
The disclosed work further describes delivery and construct embodiments including conjugation to a polypeptide, C10-35 chain fatty acids, liposomes comprising phospholipids/cholesterol and optional targeting peptides, and nanoparticles/exosomes with adipocyte targeting. Example content also reports nuclease-stable aptamers and modified-nucleic-acid constructs using modified nucleotides and post-SELEX optimization, together with in vivo DIO mouse studies showing reduced weight and fat mass and improved metabolic parameters.
Claims Coverage
The independent claim is directed to a mir-22 miRNA antagonist of a specified formula identified as SEQ ID NO: 4. The claim set refines this antagonist with mature miR-22-3p targeting and delivery or conjugation limitations, yielding six inventive features.
Mir-22 miRNA antagonist of SEQ ID NO: 4
A mir-22 miRNA antagonist defined by the formula referenced as SEQ ID NO: 4.
Mature miR-22-3p targeting
The mir-22 miRNA antagonist targets the mature miR-22-3p (miR-22-3p).
Polypeptide conjugation
The mir-22 miRNA antagonist is conjugated to a polypeptide.
Polypeptide with GVITRIR sequence
The conjugated polypeptide comprises the sequence GVITRIR (SEQ ID NO: 1).
C10-35 fatty acid conjugate
The conjugated fatty acid is a C10-35 chain fatty acid.
Minimum delivery to adipocytes
At least 50% of the mir-22 miRNA antagonist is delivered to adipocytes of the subject.
Overall, the claims coverage centers on a SEQ ID NO: 4 mir-22 miRNA antagonist, refined to target mature miR-22-3p and further limited by polypeptide conjugation, a GVITRIR-containing polypeptide, C10-35 fatty acid conjugation, and a minimum adipocyte delivery threshold.
Stated Advantages
Increased thermogenesis via KDM3A/KDM6B demethylase activity, including mitochondrial proton leak/thermogenesis.
Weight loss and fat mass reduction.
Improved glucose/insulin/cholesterol.
Adipokine modulation, including leptin and adiponectin modulation.
Documented Applications
Pharmacological inhibition of miR-22-3p described in the context of obesity, diabetes, and hypercholesterolemia.
Therapeutic use involving administration of a mir-22 inhibitor to cells including adipocytes and related cells, with adipocyte targeting.
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