Methods for glucagon suppression using modified exendins
First Claim
1. A method of lowering plasma glucagon in a subject in need thereof, comprising:
- identifying a subject in need of therapeutic lowering of plasma glucagon levels; and
administering to said subject a composition comprising a therapeutically effective glucagon lowering amount of a modified exendin, a modified exendin analog or any combination thereof;
wherein said modified exendin and modified exendin analog each have an amino acid sequence that is mom than 30 amino acid residues in length;
wherein said modified exendin and modified exendin analog each have a half-life that is at least about 10% greater than the half-life of an unmodified exendin and unmodified exendin analog, respectively; and
wherein said modification comprises one or mom molecules linked to an exendin or exendin analog, wherein said molecule is selected from the group consisting of polyethylene glycol, gelatin and albumin, and said modification increases the molecular weight of said exendin or exendin analog by at least 10% as compared to the exendin or exendin analog without said one or more molecules.
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Abstract
We claim a method of lowering plasma glucagon in a subject in need thereof comprising administering to the subject a composition comprising a modified exendin or modified exendin analog, wherein said modification comprises one or more molecule linked to an exendin or the exendin analog wherein said molecule is selected from the group consisiting of polyethylene glycol, gelatin and/or albumin. The modified exendin or the modified exendin analog has activity of suppressing glucagon secretion and/or lowering glucagon levels in the subject and possesses increased biological half-life compared to unmodified exendin or unmodified exendin analog. The method is useful in treating hyperglucagonemia and other disorders that would be benefited by lowering plasma glucagon or suppressing glucagon secretion.
105 Citations
35 Claims
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1. A method of lowering plasma glucagon in a subject in need thereof, comprising:
- identifying a subject in need of therapeutic lowering of plasma glucagon levels; and
administering to said subject a composition comprising a therapeutically effective glucagon lowering amount of a modified exendin, a modified exendin analog or any combination thereof;
wherein said modified exendin and modified exendin analog each have an amino acid sequence that is mom than 30 amino acid residues in length;
wherein said modified exendin and modified exendin analog each have a half-life that is at least about 10% greater than the half-life of an unmodified exendin and unmodified exendin analog, respectively; and
wherein said modification comprises one or mom molecules linked to an exendin or exendin analog, wherein said molecule is selected from the group consisting of polyethylene glycol, gelatin and albumin, and said modification increases the molecular weight of said exendin or exendin analog by at least 10% as compared to the exendin or exendin analog without said one or more molecules. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 33, 34)
- identifying a subject in need of therapeutic lowering of plasma glucagon levels; and
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29. A method of lowering plasma glucagon in a subject in need thereof, comprising:
- identifying a subject in need of therapeutic lowering of plasma glucagon levels; and
administering to said subject a composition comprising between about 0.01 mg/day and about 5 mg/day of modified exendin analog or any combination thereof wherein said modified exendin and modified exendin analog each have an amino acid sequence that is more than 30 amino acid residues in length;
wherein said modified exendin and modified exendin analog each have a half-life that is at leas-t about 10% greater than the half-life of an unmodified exendin and unmodified exendin analog; and
wherein said modification comprises one or more polyethylene glycol polymers having a molecular weight of from About 500 to about 20,000 linked to an exendin or exendin analog. - View Dependent Claims (30, 31, 32, 35)
- identifying a subject in need of therapeutic lowering of plasma glucagon levels; and
Specification