ENGINEERED POYPEPTIDES HAVING ENHANCED DURATION OF ACTION AND REDUCED IMMUNOGENICITY

摘要

Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including once weekly administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including lipodystrophy, dyslipidemia, hyperlipidemia, overweight, obesity, hypothalamic amenorrhea, Alzheimer's disease, leptin deficiency, fatty liver disease or diabetes (including type I and type II). Additional diseases and disorders which can be treated by the compounds and methods described herein include nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), metabolic syndrome X and Huntington's Disease.

主权项

1. An engineered polypeptide comprising:
an albumin binding domain polypeptide (ABD) and a first peptide hormone domain (HD1) comprising a leptin, a leptin analog or an active fragment thereof, wherein said ABD comprises
at least 95% identity to SEQ ID NO:300, with the proviso that X7 is not L, E or D; or alternatively, with the proviso that the amino acid sequence is not SEQ ID NO:679.