Branched PEG remodeling and glycosylation of glucagon-like peptide-1 [GLP-1]
First Claim
1. A mutant glucagon-like peptide-1 (GLP-1)-glucagon-like peptide-2 (GLP-2) fusion peptide of formula
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Abstract
The present invention provides polypeptides that include an O-linked glycoconjugate in which a species such as a water-soluble polymer, a therapeutic agent of a biomolecule is covalently linked through an intact O-linked glycosyl residue to the polypeptide. The polypeptides of the invention include wild-type peptides and mutant peptides that include an O-linked glycosylation site that is not present in the wild-type peptide. Also provided are methods of making the peptides of the invention and methods, pharmaceutical compositions containing the peptides and methods of treating, ameliorating or preventing diseased in mammals by administering an amount of a peptide of the invention sufficient to achieve the desired response.
358 Citations
17 Claims
- 1. A mutant glucagon-like peptide-1 (GLP-1)-glucagon-like peptide-2 (GLP-2) fusion peptide of formula
- 7. An isolated nucleic acid comprising a polynucleotide sequence encoding a mutant glucagon-like peptide-1 (GLP-1)-glucagon-like peptide-2 (GLP-2) fusion peptide, wherein the mutant GLP-1-GLP-2 fusion peptide comprises an O-linked glycosylation site that does not exist in the corresponding wild-type GLP-1 or GLP-2 peptide, and wherein the mutant GLP-1-GLP-2 fusion peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
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11. A method for making a glycoconjugate of a mutant glucagon-like peptide-1 (GLP-1)-glucagon-like peptide-2 (GLP-2) fusion peptide, which comprises an O-linked glycosylation that does not exist in the corresponding wild-type GLP-1 or GLP-2 peptide, comprising the steps of:
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(a) recombinantly producing the mutant GLP-1-GLP-2 fusion peptide, and (b) enzymatically glycosylating the mutant GLP-1-GLP-2 fusion peptide with a modified sugar at the O-linked glycosylation site, wherein the mutant GLP-1-GLP-2 fusion peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs;
54-73.
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12. A pharmaceutical composition of a mutant glucagon-like peptide-1 (GLP-1)-glucagon-like peptide-2 (GLP-2) fusion peptide comprising an effective amount of a mutant GLP-1-GLP-2 fusion peptide, which comprises an O-linked glycosylation site that does not exist in the corresponding wild-type GLP-1 or GLP-2 peptide, wherein the mutant GLP-1-GLP-2 fusion peptide is glycoconjugated with a modified sugar, and wherein the mutant GLP-1-GLP-2 fusion peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 54-73.
- View Dependent Claims (13)
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14. A method of providing glucagon-like peptide-1 (GLP-1) therapy to a subject in need of GLP-1 therapy, the method comprising, administering to the subject an amount of an O-linked glyco-PEG-ylated mutant glucagon-like peptide-1 (GLP-1)-glucagon-like peptide-2 (GLP-2) fusion peptide sufficient to provide a therapeutic effect, wherein the mutant GLP-1-GLP-2 fusion peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 54-73, thereby providing GLP-1 therapy.
- View Dependent Claims (15)
Specification