US010653712B2 United States Patent ( 10 ) Patent No.: US 10,653,712 B2 Hoge et al. (45 ) Date of Patent : May 19 , 2020 (54 ) HIGH PURITY RNA COMPOSITIONS AND 6,528,262 B1 3/2003 Gilad et al. METHODS FOR PREPARATION THEREOF 8,383,340 B2 2/2013 Ketterer et al. 8,710,200 B2 4/2014 Schrum et al . 8,754,062 B2 6/2014 De Fougerolles et al. (71 ) Applicant: Moderna TX , Inc., Cambridge, MA 8,822,663 B2 9/2014 Schrum et al. (US ) 8,999,380 B2 4/2015 Bancel et al. 9,221,891 B2 12/2015 Bancel et al . (72 ) Inventors : Stephen Hoge , Brookline , MA (US ) ; 9,303,079 B2 4/2016 Bancel et al. 9,464,124 B2 10/2016 Bancel et al. William Issa , Dedham , MA (US ) ; 9,512,456 B2 12/2016 Wang et al. Edward J. Miracco , Arlington , MA 9,597,380 B2 3/2017 Chakraborty et al . (US ) ; Jennifer Nelson , Brookline, MA 9,868,691 B2 1/2018 Benenato et al. (US ) ; Amy E. Rabideau , Waltham , MA 9,872,900 B2 1/2018 Ciaramella et al. 10,064,934 B2 9/2018 Ciaramella et al . 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( 2006.01 ) U.S. Appl . No. 15 /674,585 , filed Aug. 11, 2017, Ciaramella et al . A61P 35/00 ( 2006.01 ) U.S. Appl. No. 15/ 674,591 , filed Aug. 11 , 2017, Ciaramella et al . C12N 15/10 ( 2006.01 ) U.S. Appl . No. 15 / 266,791 , filed Sep. 15 , 2016 , Bancel et al . GOIN 33/68 (2006.01 ) U.S. Appl. No. 15 / 905,576 , filed Feb. 26 , 2018 , Bancel et al. ( 52 ) U.S. Cl. U.S. Appl. No. 15 /674,872 , filed Aug. 11 , 2017 , Besin et al. ??? A61K 31/7105 ( 2013.01 ) ; A61P 31/04 (Continued ) (2018.01 ) ; A61P 31/12 ( 2018.01) ; A61P 33/00 ( 2018.01) ; A61P 35/00 (2018.01 ) ; CO7K Primary Examiner Jennifer Pitrak McDonald 14/505 ( 2013.01 ) ; C12N 15/10 ( 2013.01 ) ; ( 74 ) Attorney , Agent, or Firm Wolf , Greenfield & C12P 19/34 ( 2013.01 ) ; GOIN 3376851 Sacks, P.C. (2013.01 ) (57 ) ABSTRACT The invention relates to improved RNA compositions for ( 58 ) Field of Classification Search use in therapeutic applications . 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