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Tommunom U Dit Arti Mitte TOMMUNOMUS009822353B2 U DITARTI MITTE (12 ) United States Patent (10 ) Patent No. : US 9 ,822 , 353 B2 Buechler et al . ( 45 ) Date of Patent: Nov . 21 , 2017 ( 54 ) PEGYLATED ASPARTYL - TRNA 5 ,753 , 480 A 5 / 1998 Lawlor SYNTHETASE POLYPEPTIDES 5 , 756 , 327 A 5 / 1998 Sassanfar et al . 5 ,759 ,833 A 6 / 1998 Shiba et al. 5 , 776 ,749 A 7 / 1998 Hodgson et al. (71 ) Applicant : a Tyr Pharma, Inc ., San Diego , CA 5 , 795 ,757 A 8 / 1998 Hodgson et al . (US ) 5 , 798 , 240 A 8 / 1998 Martinis et al . 5 , 801, 013 A 9 / 1998 Tao et al . (72 ) Inventors : Ying Ji Buechler, Carlsbad , CA (US ); 5 , 866 , 390 A 2 / 1999 Lawlor 5 , 885 , 815 A 3 / 1999 Sassanfar et al . Chi - Fang Wu , San Diego , CA (US ) ; 5 , 928 , 920 A 7 / 1999 Hodgson et al. Jeffrey Greve , Berkeley , CA (US ); 5 , 939 , 298 A 8 / 1999 Brown et al. John D . Mendlein , Encinitas , CA (US ) 6 , 225, 060 B1 5 / 2001 Clark et al. 6 , 255, 090 B1 7 / 2001 Famodu et al. ( 73 ) Assignee : aTyr Pharma, Inc ., San Diego , CA 6 , 265 ,188 B1 7 / 2001 Brown et al. (US ) 6 , 428 , 960 B1 8 / 2002 Clark et al. 6 , 548 , 060 B1 4 / 2003 Kim 6 , 696, 619 B1 2 / 2004 Famodu et al. ( * ) Notice: Subject to any disclaimer, the term of this 6 ,852 , 512 B2 2 / 2005 Choi et al. patent is extended or adjusted under 35 6 , 903 , 189 B2 6 /2005 Schimmel et al. U . S . C . 154 ( b ) by 257 days . 7 , 037 , 505 B2 5 / 2006 Kim et al . 7 , 067 , 126 B2 6 / 2006 Schimmel et al. 7 , 144 , 984 B2 12/ 2006 Schimmel et al. ( 21 ) Appl. No .: 14 / 360 , 573 7 ,196 , 068 B2 3 / 2007 Kim et al. 7 , 273 , 844 B2 9 / 2007 Schimmel et al . ( 22 ) PCT Filed : Dec . 6 , 2012 7 , 282 , 208 B2 | 10 / 2007 Kim 7 , 413 , 885 B2 8 / 2008 Schimmel et al. ( 86 ) PCT No. : PCT/ US2012 / 068296 7 ,459 , 529 B2 12 / 2008 Kim 7 ,476 , 651 B2 1 / 2009 Schimmel et al. $ 371 ( c ) ( 1 ) , 7 , 521 , 215 B2 4 /2009 Schimmel et al . ( 2 ) Date : May 23 , 2014 7 ,528 , 106 B2 5 /2009 Friedlander et al . (87 ) PCT Pub. No. : W02013 /086228 (Continued ) PCT Pub . Date : Jun . 13, 2013 FOREIGN PATENT DOCUMENTS CA 2531146 3 / 2005 (65 ) Prior Publication Data CN 1341725 3 / 2002 US 2015 /0159148 A1 Jun . 11, 2015 (Continued ) Related U . S . Application Data OTHER PUBLICATIONS ( 60 ) Provisional application No. 61/ 567, 602, filed on Dec . International Preliminary Report on Patentability for International 6 , 2011 . Application No. PCT/ US2009 / 048915 , dated Jan . 5 , 2011 . International Search Report and Written Opinion for International (51 ) Int. Ci. Application No. PCT/ US2009 / 048915 , dated Nov . 2 , 2009 . C12N 9 / 96 ( 2006 .01 ) Office Action for U . S . Appl. No . 12 /482 , 151 , dated Oct . 11 , 2011 , A61K 38 / 43 ( 2006 .01 ) 43 pages . ( 2006 .01 ) Office Action for U . S . Appl. No. 12 /482 , 151, dated Mar. 18 , 2011 , C12N 9 / 00 11 pages. A61K 47 / 48 ( 2006 .01 ) International Preliminary Report on Patentability for International A61K 38 /00 ( 2006 .01 ) Application No. PCT/ US2009 /046910 , dated Dec. 13 , 2010 . A61K 38 /53 ( 2006 .01 ) (52 ) U . S . CI. (Continued ) CPC . .. .. .. .. C12N 9 / 93 ( 2013 .01 ) ; A61K 47/ 48215 ( 2013 .01 ) ; C12N 9 / 96 (2013 . 01 ) ; C12Y Primary Examiner — Kagnew H Gebreyesus 601/ 01023 (2013 .01 ) ; A61K 38 / 00 (2013 .01 ) ; A61K 38 /53 (2013 .01 ) ; C12Y 601/ 01012 (74 ) Attorney , Agent, or Firm — Cooley LLP ( 2013 .01 ) (58 ) Field of Classification Search (57 ) ABSTRACT CPC .. C12N 9 / 96 ; A61K 38 /43 ; CO7K 2319 /30 ; C12Y 601 / 01012 ; C12Y 601 / 01023 The present invention provides PEGylated aspartyl- tRNA See application file for complete search history . synthetase ( DRS ) polypeptides , compositions comprising the same, and methods of using such polypeptides and (56 ) References Cited compositions for treating or diagnosing a variety of condi tions. The PEGylated DRS polypeptides of the invention U . S . PATENT DOCUMENTS have improved controlled release properties , stability , half 5 ,370 , 995 A 12 / 1994 Hennecke et al. life , and other pharmacokinetic properties compared to 5 , 484 , 703 A 1 / 1996 Raben et al . non -PEGylated DRS polypeptides . 5 ,663 , 066 A 9 / 1997 Raben et al. 5 , 747 , 315 A 5 / 1998 Lawlor 5 , 750 , 387 A 5 / 1998 Hodgson et al. 9 Claims, 12 Drawing Sheets US 9 ,822 , 353 B2 Page 2 References Cited 2009 /0226966 AL 9 / 2009 Yokoyama et al . ( 56 ) 2009 / 0227002 A1 9 / 2009 Schultz et al. U . S . 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