CHEMICALLY AND THERMODYNAMICALLY STABLE INSULIN ANALOGUES AND IMPROVED METHODS FOR THEIR PRODUCTION

摘要

The subject matter of this invention is directed towards chemically and thermodynamically stable single-chain insulin (SCI) analogues that are resistant to deamidation and fibrillation. The invention further discloses improved methods for the recombinant expression, purification and refolding of SCI.

主权项

1. A single chain insulin (SCI) compound of the formula:
Stable B chain-C′-Stable A chain  Formula (I)having the properties of high affinity for the insulin receptor and low affinity for the IGF-1 receptor with chemical and thermodynamic degradation profiles such that the SCI can be formulated and stored for extended periods of time without refrigeration;
wherein Stable B chain and Stable A chain are modified human insulin chains; and wherein C′ covalently links Stable B chain and Stable A chain, and is a peptide of about 5 to 9 amino acids comprising the following sequence: Y-P-G-D-X (SEQ ID NO: 1); wherein X is any amino acid.