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| Hai Lala at Matalamitaka Huoleht I |HAI LALA AT MATALAMITAKAUS009816096B2 HUOLEHT I (12 ) United States Patent (10 ) Patent No. : US 9 ,816 , 096 B2 Heintz et al. (45 ) Date of Patent: Nov . 14 , 2017 ( 54 ) METHODS AND COMPOSITIONS FOR 6 , 143 , 566 A 11/ 2000 Heintz et al. TRANSLATIONAL PROFILING AND 6 , 156 , 574 A 12 / 2000 Heintz et al. 6 , 252 , 130 B1 6 / 2001 Federoff MOLECULAR PHENOTYPING 6 , 270, 969 B1 8 / 2001 Hartley et al. 6 , 403 ,374 B1 6 / 2002 Tsien et al. (71 ) Applicant: THE ROCKEFELLER 6 , 410 , 317 B1 6 /2002 Farmer UNIVERSITY , New York , NY (US ) 6 , 441 , 269 B1 8 / 2002 Serafini et al . 6 , 485 , 912 B1 11/ 2002 Heintz et al. @ 6 , 495 , 318 B2 12 / 2002 Harney ( 72 ) Inventors: Nathaniel Heintz , Pelham Manor, NY 6 ,635 ,422 B2 10 / 2003 Keene et al. (US ) ; Paul Greengard , New York , NY 6 , 821, 759 B1 11/ 2004 Heintz et al . (US ) ; Myriam Heiman , New York , NY 7 , 098, 031 B2B2 8 /2006 Choulika et al . (US ) ; Anne Schaefer , New York , NY 7 ,297 ,482 B2 11 /2007 Anderson et al . (US ) ; Joseph P . Doyle , New York , NY 7 , 393 , 632 B2 7 / 2008 Cheo et al. 2003 /0119104 A1 6 /2003 Perkins et al . (US ) ; Joseph D . Dougherty , St. Louis , 2004 / 0023256 A1 2 / 2004 Puglisi et al . MO (US ) 2005 / 0009028 Al 1 /2005 Heintz et al. 2006 /0183147 AL 8 /2006 Meyer - Franke (73 ) Assignee : THE ROCKEFELLER 2011/ 0314565 Al 12 /2011 Heintz et al . UNIVERSITY , New York , NY (US ) FOREIGN PATENT DOCUMENTS ( * ) Notice : Subject to any disclaimer , the term of this patent is extended or adjusted under 35 EP 1132479 A1 9 / 2001 WO WO -01 / 48480 A1 7 /2001 U . S . C . 154 (b ) by 0 days . WO WO - 01 / 58954 A2 8 / 2001 WO WO -01 / 58954 A3 3 / 2002 ( 21 ) Appl. No. : 14 / 553, 937 WO WO -02 /064749 A2 8 / 2002 WO WO - 2002 / 064749 A3 3 / 2003 ( 22 ) Filed : Nov . 25 , 2014 WO WO -03 / 064604 A2 8 / 2003 WO WO -03 /064604 A3 11/ 2003 (65 ) Prior Publication Data US 2015 /0082470 A1 Mar. 19 , 2015 OTHER PUBLICATIONS Agafonov , et al. , Proteins on ribosome surface : measurements of Related U . S . Application Data protein exposure by hot tritium bombardment technique, Proceed (63 ) Continuation of application No. 12 / 918 ,761 , filed as ings of the National Academy of Science U S A , 94 ( 24 ): 12892 application No . PCT/ US2009 /001614 on Mar . 12 , 12897 ( 1997 ). 2009 , now abandoned . Anthony , et al ., Creating somatic cell genetic mosaics in the mouse , Cell , 121 ( 3 ) : 322 - 323 (2005 ) . (60 ) Provisional application No . 61 / 070 ,327 , filed on Mar . 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C12N 15 / 11 ( 2006 .01 ) Broude , et al. , Proteins of the 30 - S subunit of Escherichia coli GOIN 33 /50 ( 2006 . 01 ) ribosomes which interact directly with natural mRNA , European A01K 67 /027 ( 2006 .01 ) Journal of Biochemistry , 132 ( 1 ) : 139 - 45 ( 1983 ) . ( 52 ) U . S . CI. Buskila , et al ., Serum monoclonal antibodies derived from patients CPC . .. .. .. C12N 15 /62 ( 2013 . 01 ) ; A01K 67 / 0278 with multiple myeloma react with mycobacterial phosphoinositides ( 2013 .01 ) ; C12N 15 / 111 (2013 .01 ) ; GOIN and nuclear antigens, Clin Exp Immunol, 76 ( 3 ) :378 -83 ( 1989 ). 33 /5023 (2013 . 01) ; GOIN 33 / 5058 ( 2013 .01 ) ; A01K 2217 / 206 ( 2013 .01 ) ; A01K 2227 / 105 (Continued ) (2013 .01 ) ; A01K 2267 /01 (2013 .01 ) ; C12N Primary Examiner — Channing S Mahatan 2320 / 12 ( 2013 .01 ) ; GOIN 2800 /285 ( 2013 .01 ) (74 ) Attorney, Agent, or Firm — Choate , Hall & Stewart (58 ) Field of Classification Search None LLP ; Rober N . Sahr ; David E . Shore See application file for complete search history. (57 ) ABSTRACT (56 ) References Cited Methods and compositions are provided for translational profiling and molecular phenotyping of specific tissues, cells U . S . PATENT DOCUMENTS and cell subtypes of interest . The methods provided herein 5 ,075 ,227 A 12 / 1991 Hagen facilitate the analysis of gene expression in the selected 5 , 795 , 723 A 8 / 1998 Tapscott et al. subset present within a heterogeneous sample . 6 , 110 , 711 A 8 / 2000 Serafini et al . 6 , 130 , 090 A 10 / 2000 Heintz et al . 18 Claims, 54 Drawing Sheets US 9 ,816 ,096 B2 Page 2 References Cited Kubota , et al. Nuclear and nucleolar targeting of human ribosomal ( 56 ) protein S25 : ; common features shared with HIV - 1 regulatory pro teins , Oncogene , 18 ( 7 ) : 1503 - 1514 ( 1999 ) . OTHER PUBLICATIONS Lalanne , et al . Complete sequence of mouse S6 ribosomal protein , Nucleic Acids Research , 15 ( 12 ) :4990 ( 1987 ) . 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