Process for preparing insulin compounds
AssigneeNovo Nordisk A/S
InventorsAre Bogsnes, Ingun Christensen, Per Balschmidt
Life of this patent
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Abstract
A preferred way of converting insulin precursors into insulin compounds is to perform an enzymatic peptide cleavage in an aqueous medium and, thereafter, without removal of the intermediate product formed, to add an amino acid ester or a peptide ester and an organic solvent so that the desired coupling takes place.
Claims45
A process for preparing an insulin compound, said process comprising two steps, a first cleavage step and a second coupling step, wherein said cleavage step comprises:
- reacting an insulin precursor with an enzyme in a reaction mixture containing at least about 55% water (weight/weight) to produce an intermediate cleavage product;
- and said coupling step comprises:
- adding a nucleophile compound to the intermediate cleavage product of said coupling step in a reaction mixture having a content of water from about 10% to about 50% water (weight/weight), and reacting said intermediate cleavage product with said nucleophile compound to produce said insulin compound, wherein said nucleophile compound is selected from the group consisting of:
- an amino acid ester and an amino acid amide.
A process for preparing an insulin compound, said process comprising two steps, a first cleavage step and a second coupling step, wherein said cleavage step comprises:
- reacting an insulin precursor with an enzyme in a reaction mixture containing at least about 55% water (weight/weight) to produce an intermediate cleavage product;
- and said coupling step comprises:
- adding a nucleophile compound to the intermediate cleavage product of said coupling step in a reaction mixture having a content of water from about 10% to about 50% water (weight/weight), and reacting said intermediate cleavage product with said nucleophile compound to produce said insulin compound, wherein said nucleophile compound is selected from the group consisting of:
- an amino acid ester and an amino acid amide and wherein the intermediate cleavage product produced in said first cleavage step is not isolated prior to said second coupling step.
Dependencies are inferred from the claim text.