Extended recombinant polypeptides and compositions comprising same

• Main Authors: GEETHING NATHAN, CLELAND JEFFREY L, TO WAYNE, WANG CHIA-WEI, STEMMER WILLEM P, SILVERMAN JOSHUA, SPINK BENJAMIN, SCHELLENBERGER VOLKER
• Format: Patent
• Language: English
• Published: 31.10.2014
• Subjects: CHEMISTRY; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES

Disclosed is an isolated nucleic acid comprising a polynucleotide sequence which encodes a fusion protein comprising a biologically active protein and a first extended recombinant polypeptide (XTEN) wherein the XTEN comprises at least 36 amino acid residues and wherein the XTEN is characterized in that: (a) at least about 90% of the XTEN sequence consists of non-overlapping sequence motifs, wherein the sequence motifs are selected from the group consisting of SEQ IND NOS:182-203 and 1715-1722; (b) the sum of glycine (G), alanine (A), serine (S), threonine (T), glutamate (E) and proline (P) residues constitutes more than about 90% of the total amino acid sequence of the XTEN; (c) the XTEN sequence is substantially non-repetitive such that (i) the XTEN sequence contains no three contiguous amino acids that are identical unless the amino acids are serine residues, or (ii) within each of the sequence motifs, any two contiguous amino acid residues does not occur more than twice in each of the sequence motifs; (d) the XTEN sequence lacks a predicted T-cell epitope when analyzed by TEPITOPE algorithm, wherein the TEPITOPE algorithm prediction for epitopes within the XTEN sequence is based on a score of -9 or greater; (e) the XTEN sequence has greater than 90% random coil formation as determined by GOR algorithm; and (f) the XTEN sequence has less than 2% alpha helices and 2% beta-sheets as determined by Chou-Fasman algorithm.