SCHELLENBERGER VOLKER,SILVERMAN JOSHUA,STEMMER WILLEM P.,WANG CHIA-WEI,GEETHING NATHAN,SPINK BENJAMIN
申请号：
NZ62217412
公开号：
NZ622174A
申请日:
2012.09.12
申请国别(地区):
NZ
年份:
2015
代理人:
摘要：
Disclosed is a composition for use in achieving an intestinotrophic effect in a subject comprising a recombinant fusion protein comprising (i) a glucagon-like protein-2 (GLP-2) sequence selected from the group consisting of the sequences of SEQ ID NOS: 1 and 3-23, and (ii) an extended recombinant polypeptide (XTEN), wherein the XTEN is a sequence exhibiting at least 90% sequence identity to a sequence selected from the group consisting of the sequences in Table 4, and wherein the XTEN is further characterized in that: (a) the XTEN comprises at least 36 amino acid residues (b) the sum of glycine (G), alanine (A), serine (S), threonine (T), glutamate (E) and proline (P) residues constitutes more than 80% of the total amino acid residues of the XTEN (c) the XTEN is substantially non-repetitive such that (i) the XTEN contains no three contiguous amino acids that are identical unless the amino acids are serine (ii) at least 80% of the XTEN sequence consists of non-overlapping sequence motifs, each of the sequence motifs comprising 9 to 14 amino acid residues consisting of four to six amino acids selected from glycine (G), alanine (A), serine (S), threonine (T), glutamate (E) and proline (P), wherein any two contiguous amino acid residues do not occur more than twice in each of the non-overlapping sequence motifs or (iii) the XTEN sequence has a subsequence score of less than 10 (d) the XTEN has greater than 90% random coil formation as determined by GOR algorithm (e) the XTEN has less than 2% alpha helices and 2% beta-sheets as determined by Chou-Fasman algorithm and (f) the XTEN lacks a predicted T-cell epitope when analysed by TEPITOPE algorithm, wherein the TEPITOPE threshold score for the prediction by the algorithm has a threshold of &ndash9, wherein the fusion protein exhibits an apparent molecular weight factor of at least 4 and is capable of achieving an intestinotrophic effect in a subject using a dosage of 2.5 nmol/kg to 6250 nmol/kg, or 25 nmol/kg to 3750 nmol
