Calcitonin Mimetics for Treating Diseases and Disorders

Abstract

Calcitonin mimetic peptides having an amino acid sequence in accordance with SEQ ID NO:8 or SEQ ID NO:53, each of which may be carboxylated at its N-terminal or otherwise modified to reduce the positive charge of the first amino acid and independently of that may be amidated at its C-terminal, and in each of which the 1 and 7 position cysteine residues may together be replaced by α-aminosuberic acid (Asu) are useful for methods of treating diabetes (Type I and/or Type II), obesity, excessive food consumption, metabolic syndrome, rheumatoid arthritis, non-alcoholic fatty liver disease, osteoporosis, or osteoarthritis, poorly regulated blood glucose levels, poorly regulated response to glucose tolerance tests, or poorly regulated food intake.

What is claimed is: 
     
         1 . A peptide comprising an amino acid sequence in accordance with SEQ ID NO: 8 or SEQ ID NO: 53. 
     
     
         2 . The peptide as claimed in  claim 1 , comprising an amino acid sequence of any of SEQ ID NOS: 5-8, or 54-59, each of which may be carboxylated at its N-terminal or otherwise modified to reduce the positive charge of the first amino acid and independently of that may be amidated at its C-terminal, and in each of which the 1 and 7 position cysteine residues may together be replaced by α-aminosuberic acid (Asu). 
     
     
         3 . The peptide as claimed in  claim 1 , comprising an amino acid sequence of any of SEQ ID NOS: 28-42, or 60-77 each of which may be carboxylated at its N-terminal or otherwise modified to reduce the positive charge of the first amino acid and independently of that may be amidated at its C-terminal, and in each of which the 1 and 7 position cysteine residues may together be replaced by α-aminosuberic acid (Asu). 
     
     
         4 . The peptide as claimed in  claim 1 , comprising an amino acid sequence of any of SEQ ID NOS: 45-52, or 20-27; each of which may be carboxylated at its N-terminal or otherwise modified to reduce the positive charge of the first amino acid and independently of that may be amidated at its C-terminal, and in each of which the 1 and 7 position cysteine residues may together be replaced by α-aminosuberic acid (Asu). 
     
     
         5 . The peptide as claimed in  claim 1 , having an amino acid sequence of any of SEQ ID NOS: 9, 78, 79, 10, 11, 80, or 12. 
     
     
         6 . The peptide as claimed in  claim 1 , wherein the peptide is carboxylated at its N-terminal. 
     
     
         7 . The peptide as claimed in  claim 1 , wherein the peptide is modified at its N-terminal to reduce the positive charge of the first amino acid. 
     
     
         8 . The peptide as claimed in  claim 1 , wherein the peptide is amidated at its C-terminal. 
     
     
         9 . The peptide as claimed in  claim 1 , wherein the 1 and 7 position cysteine residues of the peptide are substituted by α-aminosuberic acid (Asu). 
     
     
         10 . The peptide as claimed in  claim 1 , formulated for enteral administration. 
     
     
         11 . The peptide as claimed in  claim 1 , formulated for parenteral administration. 
     
     
         12 . The peptide as claimed in  claim 11 , formulated for injection. 
     
     
         13 . The peptide as claimed in  claim 1 , formulated with a carrier for oral administration. 
     
     
         14 . The peptide as claimed in  claim 13 , wherein the carrier comprises N-(5-chlorosalicyloyl)-8-aminocaprylic acid (5-CNAC), sodium salt of 10-(2-Hydroxybenzamido)decanoic acid (SNAD), or sodium salt of N-(8-[2-hydroxybenzoyl]amino)caprylic acid (SNAC). 
     
     
         15 . A pharmaceutical composition comprising the peptide of  claim 1  coated with citric acid particles wherein the coated citric acid particles increase the oral bioavailability of the peptide 
     
     
         16 . A method for treating Type II diabetes, obesity, excessive food consumption, metabolic syndrome, rheumatoid arthritis, non-alcoholic fatty liver disease, osteoporosis, osteoarthritis, improving glycemic control, or poorly regulated food intake comprising administering the peptide as claimed in  claim 1 . 
     
     
         17 . A method for treating Type II diabetes, obesity, excessive food consumption, metabolic syndrome, rheumatoid arthritis, non-alcoholic fatty liver disease, osteoporosis, osteoarthritis, improving glycemic control, or poorly regulated food intake comprising administering the peptide as claimed in  claim 1  in conjunction with metformin or another insulin sensitizer.