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US 2015/0159148 A1Published application
Pegylated aspartyl-trna synthetase polypeptides
AssigneeaTyr Pharma, Inc.
InventorsYing Ji Buechler, Chi-Fang Wu, Jeffrey Greve, John D. Mendlein
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Abstract
The present invention provides PEGylated aspartyl-tRNA synthetase (DRS) polypeptides, compositions comprising the same, and methods of using such polypeptides and compositions for treating or diagnosing a variety of conditions. The PEGylated DRS polypeptides of the invention have improved controlled release properties, stability, half-life, and other pharmacokinetic properties compared to non-PEGylated DRS polypeptides.
Claims26
1-60. (canceled)
A PEGylated aspartyl-tRNA synthetase (DRS) polypeptide selected from,
- (a) a DRS polypeptide comprising the sequence set forth in SEQ ID NO:3 DRS(1-154), which is modified by C76S substitution, where a maleimide monomethoxy polyethylene glycol (mPEG) derivative of about 40,000 Daltons is covalently attached via a thio ether linkage to C130;
- (b) a DRS polypeptide consisting essentially of the sequence set forth in SEQ ID NO:3 DRS(1-154), which is modified by C76S substitution, where a maleimide monomethoxy polyethylene glycol (mPEG derivative of about 40,000 Daltons is covalently attached via a thio ether linkage to C130;
- (c) a DRS polypeptide consisting of the sequence set forth in SEQ ID NO:3 DRS(1-154), which is modified by C76S substitution, where a maleimide monomethoxy polyethylene glycol (mPEG) derivative of about 40,000 Daltons is covalently attached via a thio ether linkage to C130;
- (d) a DRS polypeptide of about 150 to 200 amino acids in length comprising the sequence set forth in SEQ ID NO:3 DRS(1-154), which is modified by C76S substitution, where a maleimide monomethoxy polyethylene glycol (mPEG) derivative of about 40,000 Daltons is covalently attached via a thio ether linkage to C130;
- (e) a DRS polypeptide of about 100 to 200 amino acids in length comprising the sequence set forth in SEQ ID NO:11 DRS(23-154), which is modified by C76S substitution, where a maleimide monomethoxy polyethylene glycol (mPEG) derivative of about 40,000 Daltons is covalently attached via a thio ether linkage to C130;
- (f) a DRS polypeptide of about 150 to 200 amino acids in length comprising the sequence set forth in SEQ ID NO:3 DRS(1-184), which is modified by C76S substitution, where a maleimide monomethoxy polyethylene glycol (mPEG) derivative of about 40,000 Daltons is covalently attached via a thio ether linkage to C130;
- (g) a DRS polypeptide of about 135 to 150 amino acids in length comprising the sequence set forth in SEQ ID NO:105 DRS(13-146), which is modified by C76S, substitution, where a maleimide monomethoxy polyethylene glycol (mPEG) derivative of about 40,000 Daltons is covalently attached via a thio ether linkage to C130;
- and
- (h) a PEGylated full length aspartyl-tRNA synthetase (DRS) polypeptide, comprising the sequence set forth in SEQ ID NO:1, which is modified by at least one cysteine modification selected from the group consisting of C76, C203, C259, C334, and C349, where a maleimide monomethoxy polyethylene glycol (mPEG) derivative of about 40,000 Daltons is covalently attached to a solvent exposed cysteine residue.
6 more elements
62-68. (canceled)
89-90. (canceled)
Dependencies are inferred from the claim text.