Patent ID: 9079971
Filing Date: 2015-07-14
Classification: A61K,A61P,C07K,C12N,Y02A

Abstract:
1. A modified FGF-21 polypeptide comprising a non-naturally encoded amino acid, wherein: (a) the polypeptide comprises a sequence at least 90% identical to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7; (b) the non-naturally encoded amino acid has the structure: wherein the R group is any substituent other than the side chain found in alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, pyrrolysine, or selenocysteine; (c) the polypeptide contains a substitution of an amino acid with the non-naturally encoded amino acid at a position corresponding to residue 72, 77, 86, 108, 110, 131, or 146 of SEQ ID NO: 1 or the corresponding amino acid position in SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7; (d) the polypeptide maintains the biological activity of human FGF-21 polypeptides; (e) the non-naturally encoded amino acid is linked to a linker, polymer, or biologically active molecule; and (f) the polypeptide has an in vivo half-life at least two-fold greater than the human FGF-21 polypeptide in SEQ ID NO: 1.