GLUCAGON ANALOGS EXHIBITING ENHANCED SOLUBILITY IN PHYSIOLOGICAL pH BUFFERS
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Abstract
Modified glucagon peptides are disclosed having improved solubility while retaining glucagon agonist activity. The glycogen peptides have been modified by substitution of native amino acids with, and/or addition of, charged amino acids to the carboxy terminus of the peptide. The modified glucagon agonists can be further modified by pegylation, or the addition of a carboxy terminal peptide selected from the group consisting of SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 23, or both to further enhance the solubility of the glucagon agonist analogs.
115 Citations
55 Claims
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1-37. -37. (canceled)
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38. A glucagon peptide with improved solubility that is an analog of SEQ ID NO:
- 1 comprising one, two, or three charged amino acid(s) C-terminal to the amino acid at position 27 of the glucagon peptide and optionally comprising up to 7 additional amino acid modifications relative to SEQ ID NO;
1 which further increase solubility or stability or glucagon activity of the glucagon peptide. - View Dependent Claims (39, 40, 41, 42, 43, 45, 49, 50, 51, 52, 53, 54, 55)
- 1 comprising one, two, or three charged amino acid(s) C-terminal to the amino acid at position 27 of the glucagon peptide and optionally comprising up to 7 additional amino acid modifications relative to SEQ ID NO;
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44. A glucagon peptide with improved solubility comprising the sequence of SEQ ID NO:
- 33 or an analog of SEQ ID NO;
33, wherein said analog differs from SEQ ID NO;
33 by one to three amino acid substitutions, said amino acid substitutions located at one or more positions selected from positions 1, 2, 5, 7, 10, 11, 12, 13, 14, 16, 17, 18, 19, 20, 21 and 24 of the analog, with the proviso that said glucagon peptide comprises a charged amino acid at position 28 or 29, or an additional acidic amino acid added to the carboxy terminus of the peptide. - View Dependent Claims (46, 47, 48)
- 33 or an analog of SEQ ID NO;
Specification