Patent ID: 9062126
Filing Date: 2015-06-23
Classification: A61K,A61P,C07K

Abstract:
1. An isolated polypeptide comprising an amino acid sequence variant of the mature alpha-2-macroglobulin/low density lipoprotein receptor-related protein-associated protein 1 (RAP) set out in SEQ ID NO: 121, wherein said RAP variant binds selectively to a pair of complement-type repeats within a protein selected from the group consisting of very low density lipoprotein receptor (VLDLR), matriptase and CD320, with an affinity that is at least 3-fold greater than the affinity of wild-type RAP for the same pair of complement-type repeats, wherein the RAP variant consists of (a) a polypeptide having an amino acid sequence at least 90% identical to SEQ ID NO: 121 and comprises mutations at at least two of the following positions: 251, 256, 257, 266 and 270, and optionally comprises a mutation at one or more of positions 175, 205, 213, 217, 226, 230, 232, 239, 246, 249, 251, 256, 257, 261, 266, 267, 268, 270, 273, 287, 290, 294, 296, 297, 298, 305, 312 or 313 of mature RAP; or (b) a polypeptide having an amino acid sequence at least 90% identical to amino acids 200-323 of SEQ ID NO: 121 and comprises mutations at at least two of the following positions: 251, 256, 257, 266 and 270, and optionally comprises a mutation at one or more of positions 205, 213, 217, 226, 230, 232, 239, 246, 249, 251, 256, 257, 261, 266, 267, 268, 270, 273, 287, 290, 294, 296, 297, 298, 305, 312, or 313 of mature RAP.