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RAPID-ACTING INSULIN ANALOGUES OF ENHANCED STABILITY
专利权人:
CASE WESTERN RESERVE UNIVERSITY
发明人:
Michael A. WEISS
申请号:
US16462440
公开号:
US20190322719A1
申请日:
2017.11.21
申请国别(地区):
US
年份:
2019
代理人:
摘要:
A two-chain insulin analogue contains a modified A-chain polypeptide and a modified B-chain polypeptide. The A-chain polypeptide comprises one or more of: a His or Glu substitution at position A8, a Glu substitution at position A14; and a Gln or Arg substitution at positon A17. The B-chain polypeptide comprises one or more of: a deletion of the amino acids at position B1, B1-B2, B1-B3, B30 or a combination thereof; an Ala or Glu substitution at position B2; a Glu substitution at position B3. The analogue exhibits thermodynamic stability in a zinc-free solution, decreased self-association, maintains biological potency, and no increased mitogenicity. The analogue exhibits resistance to chemical degradation and physical degradation. A method of treating a patient with diabetes mellitus or obesity comprises administering a physiologically effective amount of the insulin analogue or a physiologically acceptable salt thereof to a patient.
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