Glucagon/GLP-1 receptor co-agonists
First Claim
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1. An isolated peptide comprising:
- (a) the amino acid sequence of SEQ ID NO;
37;
(b) or a variant peptide thereof, wherein the variant peptide comprises;
(i) an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO;
37 wherein the variant peptide exhibits enhanced activity at the GLP-1 receptor, as compared to native glucagon, and exhibits at least 100-fold selectivity for the human GLP-1 receptor versus the GIP receptor, or(ii) an amino acid sequence based on SEQ ID NO;
37, but differs in one or more of the following ways;
a. the variant peptide comprises an acylated amino acid or an alkylated amino acid;
b. an acylated amino acid or an alkylated amino acid is replaced with the corresponding amino acid of native glucagon (SEQ ID NO;
1) at that position or a conservative substitution of the native amino acid, and optionally a new acylated or alkylated amino acid is introduced at a different position;
c. the variant peptide comprises an amino acid covalently attached to a hydrophilic moiety;
d. an amino acid covalently attached to a hydrophilic moiety is replaced with the corresponding amino acid of native glucagon (SEQ ID NO;
1) at that position, and optionally a new amino acid covalently attached to a hydrophilic moiety is introduced at a different position;
e. the C-terminal amino acid of the variant peptide comprises a C-terminal amide in place of a C-terminal alpha carboxylate;
f. an amino acid at any of positions 1 through 29 is replaced with the corresponding amino acid of native glucagon (SEQ ID NO;
1) at that position;
org. or any combinations thereof;
or a pharmaceutically acceptable salt of the peptide or variant peptide.
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Abstract
Provided herein are peptides and variant peptides that exhibit enhanced activity at the GLP-1 receptor, as compared to native glucagon.
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Citations
23 Claims
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1. An isolated peptide comprising:
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(a) the amino acid sequence of SEQ ID NO;
37;(b) or a variant peptide thereof, wherein the variant peptide comprises; (i) an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO;
37 wherein the variant peptide exhibits enhanced activity at the GLP-1 receptor, as compared to native glucagon, and exhibits at least 100-fold selectivity for the human GLP-1 receptor versus the GIP receptor, or(ii) an amino acid sequence based on SEQ ID NO;
37, but differs in one or more of the following ways;a. the variant peptide comprises an acylated amino acid or an alkylated amino acid; b. an acylated amino acid or an alkylated amino acid is replaced with the corresponding amino acid of native glucagon (SEQ ID NO;
1) at that position or a conservative substitution of the native amino acid, and optionally a new acylated or alkylated amino acid is introduced at a different position;c. the variant peptide comprises an amino acid covalently attached to a hydrophilic moiety; d. an amino acid covalently attached to a hydrophilic moiety is replaced with the corresponding amino acid of native glucagon (SEQ ID NO;
1) at that position, and optionally a new amino acid covalently attached to a hydrophilic moiety is introduced at a different position;e. the C-terminal amino acid of the variant peptide comprises a C-terminal amide in place of a C-terminal alpha carboxylate; f. an amino acid at any of positions 1 through 29 is replaced with the corresponding amino acid of native glucagon (SEQ ID NO;
1) at that position;
org. or any combinations thereof; or a pharmaceutically acceptable salt of the peptide or variant peptide. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)
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- 19. An isolated peptide comprising the amino acid sequence of SEQ ID NO:
Specification