Compositions and methods for treating diabetes, hypertension and hypercholesterolemia
Inventors
THAI, NGOC • POLLETT, JONATHAN
Assignees
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Publication Number
US-10751384-B2
Publication Date
2020-08-25
Expiration Date
Abstract
The present invention provides a pharmaceutical formulation comprising a therapeutically effective amount of a polypeptide corresponding to one or more of SEQ ID No(s) 1, 2, 3 or 4. The therapeutically effective amount of polypeptide may be formulated for administration to a subject in need of treatment as an oral formulation, a parenteral formulation, a topical formulation, an aqueous formulation, a solid formulation, a lyophilized formulation, or a trans-dermal formulation. Also disclosed are methods for treating at least one of diabetes, hyperglycemia, hypercholesterolemia, and hypertension in a subject, comprising administering to the subject a therapeutically effective amount of a polypeptide according to SEQ ID Nos. 1-4.
Core Innovation
The patent discloses RPS2-derived therapeutics for treating diabetes, hyperglycemia, hypercholesterolemia, and hypertension by administering pharmaceutical formulations that comprise a purified or synthetic 40S ribosomal protein S2 (RPS2) polypeptide. The therapeutics include polypeptides corresponding to SEQ ID NOs 1-4, including fragments and analogs, and include embodiments with at least 95% identity to SEQ ID NO:1 in the claimed methods.
The disclosed methods are grounded in reported therapeutic effects in animal models using IMG-1 polypeptides based on SEQ ID NO:1. Reported outcomes include normalized fasting blood glucose to less than 200 mg/dL, reduced systolic and diastolic blood pressure to below 140/90 mmHg, decreased HbA1c, and reduced cholesterol.
The patent also describes mechanistic and structure-activity findings relating to specific regions of SEQ ID NO:1-derived polypeptides. Active regions are identified such that a C-terminal fragment (IMG-1L) retains activity, while an N-terminal fragment (IMG-1S) lacks activity, and additional reported observations include lowering glucagon without changing insulin levels, improving insulin resistance, and suppressing hepatic glucose production in diet-induced obese (DIO) mice.
Claims Coverage
The patent includes two independent claims. Both independent claims center on administering a therapeutically effective amount of a polypeptide with at least 95% identity to SEQ ID NO:1, with explicit physiological outcome thresholds for blood glucose, cholesterol, and/or blood pressure, when administered to a diabetic subject.
Treating metabolic conditions by administering a SEQ ID NO:1 polypeptide with identity and outcome thresholds
Administering to the subject a pharmaceutical formulation comprising a therapeutically effective amount of a polypeptide having at least 95% identity to SEQ ID NO:1 and able to reduce blood glucose levels to less than 200 mg/dl, reduce cholesterol levels to less than 200 mg/dl, and/or lower blood pressure to less than 140/90 mmHg when administered to a diabetic subject.
Causing reduction in multiple metabolic parameters using a SEQ ID NO:1 polypeptide with identity and outcome thresholds
Administering to the subject a pharmaceutical formulation comprising a therapeutically effective amount of a polypeptide having at least 95% identity to SEQ ID NO:1 and able to reduce blood glucose levels to less than 200 mg/dl, reduce cholesterol levels to less than 200 mg/dl, and/or lower blood pressure to less than 140/90 mmHg when administered to a diabetic subject, in order to cause reduction in one or more of blood glucose levels, hepatic glucose production, cholesterol levels, glucagon levels, and blood pressure.
Across both independent claims, coverage is provided for methods of treating diabetes- and metabolic-related conditions by administering a pharmaceutical formulation containing a SEQ ID NO:1 polypeptide with at least 95% identity, where the administered polypeptide is able to achieve numeric reductions in blood glucose (<200 mg/dL), cholesterol (<200 mg/dL), and/or blood pressure (<140/90 mmHg) in a diabetic subject.
Stated Advantages
Normalized fasting blood glucose to less than 200 mg/dL in animal models.
Reduced systolic and diastolic blood pressure to below 140/90 mmHg.
Decreased HbA1c.
Lowered cholesterol levels (including levels below 200 mg/dL as reported).
Lowered glucagon without changing insulin levels.
Improved insulin resistance and suppressed hepatic glucose production.
Retained therapeutic activity in a C-terminal fragment (IMG-1L) while an N-terminal fragment (IMG-1S) lacked activity.
Documented Applications
Treating diabetes, hyperglycemia, hypercholesterolemia, and hypertension in a subject via pharmaceutical formulations comprising SEQ ID NO:1-based polypeptides.
Reducing one or more of blood glucose levels, hepatic glucose production, cholesterol levels, glucagon levels, and blood pressure in a subject by administering the SEQ ID NO:1 polypeptide formulation to a diabetic subject.
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