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|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 . Antic , et al. , ELAV tumor antigen , Hel -N1 , increases translation of 21, 2008 , provisional application No . 61/ 036 , 049 , neurofilamentMmRNA and induces formation of neurites in human teratocarcinoma cells , Genes Development, 13 ( 4 ) :449 -461 (1999 ) . filed on Mar. 12 , 2008 , provisional application No . Ashiya , et al . , A neuron - specific splicing switch mediated by an 61 / 199 , 108 , filed on Nov. 12 , 2008 , provisional array of pre- mRNA repressor sites : evidence of a regulatory role for application No . 61 /036 ,058 , filed on Mar. 12 , 2008 . the polypyrimidine tract binding protein and a brain - specific PTB counterpart, RNA , 3 ( 9 ): 996 - 1015 ( 1997 ) . ( 51 ) Int. Cl. Brodersen , et al . , The social life of ribosomal proteins , FEBS CI2N 15 /62 ( 2006 .01 ) Journal , 272 ( 9 ) : 2098 -2108 (2005 ) . 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 ) . Ceman , et al. , Isolation of an FMRP - associated messenger Lee , et al. , Cocaine - induced dendritic spine formation in D1 and D2 ribonucleoprotein particle and identification of nucleolin and the dopamine receptor- containing medium spiny neurons in nucleus fragile X - related proteins as components of the complex , Molecular accumbens, Proceedings of the National Academy of Science, USA , Cell Biology , 19 ( 12 ) : 7925 - 7932 ( 1999 ) . 103 ( 9 ) : 3399 - 3404 (2006 ) . Chaible , et al . , Genetically -modified animals for use in research and Lerner and Steitz , Antibodies to small nuclear RNAs complexed biotechnology, Genetic Molecular Research , 9 ( 3 ) : 1469 - 1482 with proteins are produced by patients with systemic lupus erythe ( 2010 ) . matosus , Proceedings of the National Academy of Science USA , Chambers , et al. Translational regulation of hepatic HMG - COA 76 ( 11 ) : 5495 - 9 ( 1979 ) . reductase by dietary cholesterol, Biochem Biophys Res Commun , Liang , et al. , An estrogen -dependent polysomal protein binds to the 232( 2 ): 278 -281 ( 1997 ) . 5 ' untranslated region of the chicken vitellogenin mRNA , Nucleic Christopher, et al. Implications of N and C - terminal proximity for Acids Research , 19 ( 9 ) :2289 - 2294 ( 1991) . protein folding, Journal of Molecular Biology , 257 ( 1 ) : 175 -87 Lin , et al. , The primary structure of rat liver ribosomal protein L37 . ( 1996 ) . Homology with yeast and bacterial ribosomal proteins , Journal of Chu , et al. , Identification of a thymidylate synthase Biologic Chemistry, 258 ( 17 ) : 10664 - 10671 ( 1983 ) . ribonucleoprotein complex in human colon cancer cells , Molecular Misulovin , et al. , A rapid method for targeted modification and Cell Biology , 14 ( 1 ) :207 -213 ( 1994 ) . screening of recombinant bacterial artificial chromosome, Journal Chu , et al. , Identification of in vivo target RNA sequences bound by of Immunology Methods, 257 ( 1 - 2 ) :99 - 105 (2001 ) . thymidylate synthase , Nucleic Acids Research , 24 ( 16 ) :3222 -3228 Nevskaya et al. , Ribosomal protein LI recognizes the same specific ( 1996 ) . structural motif in its target sites on the autoregulatory mRNA and Copeland , et al . A novel RNA binding protein , SBP2, is required for 23S rRNA , Nucleic Acids Research , 33 ( 2 ) :478 -485 (2005 ) . the translation of mammalian selenoprotein mRNAs, EMBO Jour Noain et al. , Identification of brain neurons expressing the nal, 19 ( 2 ) : 306 - 314 ( 2000 ) . dopamine D4 receptor gene using BAC transgenic mice , European De Jonge et al. , Transcriptional profile of the human peripheral Journal of Neuroscience , 24 ( 9 ) : 2429 - 2438 ( 2006 ) . nervous system by serial analysis of gene expression , Genomics , Office Action for U . S . Appl. No . 10 /494 , 248 , (dated Dec . 23 , 2010 ) , 82 ( 2 ) : 97 - 108 (2003 ) . 14 pages . Doyle , et al . , Application of a translational profiling approach for Office Action for U . S . Appl. No . 10 / 494 , 248 , (dated Feb . 19 , 2010 ) , the comparative analysis of CNS cell types , Cell, ( 2008 ) . 21 pages. European Search Report and Opinion for EP Application No . Office Action for U . S . Appl. No . 10 /494 , 248, ( dated Jul . 29, 2008 ) , 09719684 . 4 ( dated Feb . 21 , 2012 ) . 27 pages . Fisher , et al. , Pulse labeling of small nuclear ribonucleoproteins in Office Action for U . S . Appl. No . 10 /494 ,248 , (dated Jun . 5 , 2009 ) , vivo reveals distinct patterns of antigen recognition by human 20 pages. autoimmune antibodies , The Proceedings of the National Academy Office Action for U . S . Appl. No. 10 /494 , 248 ( dated Sep . 25 , 2007 ) , of Science US A . , 81( 10 ) : 3185 - 3189 ( 1984 ) . 13 pages . Gerfen , et al. , D1 and D2 dopamine receptor -regulated gene expres Office Action for U . S . Appl. No . 12 /918 ,761 , 12 pages (dated Aug . sion of striatonigral and striatopallidal neurons, Science, 250 (4986 ) : 26 , 2014 ) , 10 pages. 1429 - 1432 ( 1990 ) . Office Action for U . S . Appl. No . 13/ 104, 316 (dated Jul. 26 , 2012 ) , Gimautdinova , et al. , The proteins of the messenger RNA binding 14 pages. site of Escherichia coli ribosomes, Nucleic Acids Research , Peng, et al. , RNA stabilization by the Au - rich element binding 9 ( 14 ) : 3465 - 3481 ( 1981) . protein , HuR , an ELAV protein , The EMBO Journal , 17 ( 12 ) :3461 Gong , et al. , A gene expression atlas of the central nervous system 3470 ( 1998 ) . based on bacterial artificial chromosomes . Nature, 425 (6961 ) :917 Remacha et al. , Proteins PI, P2 , and PO , components of the 925 (2003 ) . eukaryotic ribosome stalk . New structural and functional aspects , Gong , et al ., Targeting Cre recombinase to specific neuron popula Biochem Cell Biology , 73 ( 11 - 12 ) : 959 - 968 ( 1995 ) . tions with bacterial artificial chromosome constructs , Journal of Ristevski, S . , Making better transgenic models : conditional , tem Neuroscience , 27 ( 37 ) :9817 - 23 (2007 ) .
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    (19) TZZ _T (11) EP 2 475 988 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C12Q 1/6886 (2018.01) C12Q 1/6809 (2018.01) 14.11.2018 Bulletin 2018/46 C12Q 1/6806 (2018.01) (21) Application number: 10816090.4 (86) International application number: PCT/US2010/048293 (22) Date of filing: 09.09.2010 (87) International publication number: WO 2011/031877 (17.03.2011 Gazette 2011/11) (54) USE OF MICROVESICLES IN ANALYZING NUCLEIC ACID PROFILES VERWENDUNG VON MIKROVESIKELN BEI DER ANALYSE VON NUKLEINSÄUREPROFILEN UTILISATION DE MICROVÉSICULES DANS L’ANALYSE DE PROFILS D’ACIDE NUCLÉIQUE (84) Designated Contracting States: US-A1- 2005 003 426 US-A1- 2008 268 429 AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO • SKOG JOHAN ET AL: "Glioblastoma PL PT RO SE SI SK SM TR microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic (30) Priority: 09.09.2009 US 241014 P biomarkers", NATURE CELL BIOLOGY, MACMILLAN MAGAZINES LTD, vol. 10, no. 12, 1 (43) Date of publication of application: December 2008 (2008-12-01), pages 1470-1476, 18.07.2012 Bulletin 2012/29 XP002526160, ISSN: 1465-7392, DOI: 10.1038/NCB1800 [retrieved on 2008-11-16] (60) Divisional application: • TAYLOR D D ET AL: "MicroRNA signatures of 18199345.2 tumor-derived exosomes as diagnostic biomarkers of ovarian cancer", GYNECOLOGIC (73) Proprietor: The General Hospital Corporation ONCOLOGY, ACADEMIC PRESS, LONDON, GB, Boston, MA 02114 (US) vol.
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    WO 2016/164463 Al 13 October 2016 (13.10.2016) P O P C T

    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/164463 Al 13 October 2016 (13.10.2016) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07H 21/04 (2006.01) C12N 15/113 (2010.01) kind of national protection available): AE, AG, AL, AM, C07H 21/00 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (21) Number: International Application DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US20 16/0262 18 HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (22) International Filing Date: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, 6 April 2016 (06.04.2016) MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (25) Filing Language: English SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (26) Publication Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 62/144,219 7 April 2015 (07.04.2015) kind of regional protection available): ARIPO (BW, GH, 62/168,528 29 May 2015 (29.05.2015) GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 62/181,083 17 June 2015 (17.06.2015) TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicant: THE GENERAL HOSPITAL CORPORA¬ DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, TION [US/US]; 55 Fruit Street, Boston, Massachusetts LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, 021 14 (US).