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JP WO2008/066199 A1 2008.6.5 (57)【要約】 本発明は、アクチビンを
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3. 00 00 II 0000 zer G MI Endocrinol 2004 Nov 18 11 2765 761 0000000000000 00000 htt p ww wako chem si yaku nf gene arti cl e pdf Manual pdf x 5 C 0 00 00 1000000 LI II II I LI II II L II LI II II II II II II II L II L II L LI II 1000000 Od 0 Jonathan RT Lakey 0 7 Nucleofector Solution bufferH 000000 0 Nucl eof ector syste II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II U I e 1 000 000 L LI LI 00000000000 II II
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13. 1 IC P 22525 23 01 2008 05 02 2008 I SAZ dut ug 100 8915 4 3 03 3581 1101 AR 3448 15 210 2 2007 4 45 02008 066199 1 2008 6 5 PCT JP2007 073352 IFY NISHIMURA W et al A switch from to expression accompanies differentiation to pancreatic cells Dev Biol 2006 05 15 Vol 293 No 2 pages 526 to 539 Epub
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15. 10 20 30 40 50 11 02008 066199 1 2008 6 5 http ww st go p pr i nf o i nf 0320 i ndex htm II II II II II Evans et al 1981 Na ture 292 154 6 Martin GR et al 1981 Proc Natl Acad Sci 78 7634 8
16. 21 02008 066199 1 2008 6 5 1000000000000000000000000000000000000000 HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 1 11 1111 1000000000000000000000000000000000000000 sti nul ation index Bergert Knoch KP isterfeld Jager Ouwendijk J Kersting S Saeger HD Soli nena Effect of oxygenated perfluorocarbons on isolated rat pancreatic islets inculture Cell T ranspl ant 2005 14 7 441 8
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19. L LI II II II II II II II II II II Thorson et al Science 1 WCell Research Institu 998 282 1145 7 II II II LI II LI II II II II II II II II II II II II 0 te ht t p ww wi cel or g LI LI 12 WO2008 066199 1 2008 6 5 1000000000000000000000000000000000000000 LI LI II II LI LI II II II II II II II II II II II II 0 II II II II II II II II II II II II II II II II II II II II II I Zulewski Abraham Gerlach Daniel PB Moritz W Mlle B Vallejo Thomas Habener JF Multi potenti al nestin positi ve stemcells i sol ated from adult pancreatic islets differenti ate ex vivo i nto pancreatic end ocri ne exocrine and hepatic phenotypes Diabetes 2001 50 3 521 33
20. troglitazone C 17 02008 066199 1 2008 6 5 II II II 1 II I II II II II II II II II 1 Staudacher C Ricordi C Stella Socci Canmelli L Ferrari Dicarlo V Mnerva Chir 31 1665 1668 1985 Ricordi C Finke EH Lacy PE Diabetes 35 649 653 1986 Narushi na Okits T Y Soto Gutierrez Rivas Carrillo JD Navarro Al varez N Chen Y anaka Noguchi H Matsunoto 5 MLakey JR Kobayashi E Tanaka Kobay ashi N Maintenance of nouse rat and pig pancreatic islet functions by cocultu re wth human islet deri ved fibroblasts Cell Transpl ant 2006 15 4 325 34
21. 6 02008 066199 1 2008 6 5 II II II II II II II II II II II II II II II II II II 100000000000000000 I LI LI II II II II II II II I II II II II II II II II L II II II II II II L II L II II II II II II II II II II II II II II II II II II II 0 LI II LI II II II II II II II II 0000000060 porcine endogenous retrovirus II II II II II II II II II II II II II II II II II II Patience CI Nat Med 1997 3 3 282 286 II II II I LI II II II II II II II LI II II II II 0 LI LI II II II II II II Sc i ence
22. Oct 3 40 Sox2 c wc MI I4L LI LI LI LI LI II II II II II II II II II 0 L C5 Takahashi Tanabe Ohnuki Narita Ichisaka Yamanaka S 2007 131 5 861 72 20 30 40 50 02008 066199
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24. 588828 IntCl C12N5 06 A01K67 027 A61F2 02 61M35 12 61 1 36 M6103 10 C12N5 10 C12N15 09 OPER CHEST ENS HO ERE OE 1 54 1 7 0245 3 MEER LEAR BIOSIS MEDLINE WPIDS STN JMEDPlus JDrean2 JSTPlus JDream2 X 5 AMOUR a al Production of pancreatic hormone expressing endocrine cells Eon human embryonic stem cells Nat Biotechnol 2006 Nov Vol 24 No 11 pages 1392 to 1401 Epub 2006 10 19 C i A CIR BHDREX RE E H BIO HE 5 B L ERAT 5 ROR
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38. document of particular relevance the claimed invention cannot be date considered novel or cannot be considered to involve an inventive document which may throw doubts on priority claim s or which is step when the document is taken alone cited to establish the publication date of another citation or other document of particular relevance the claimed invention cannot be special reason as specified considered to involve an inventive step when the document is document referring to an oral disclosure use exhibition or other means combined with one or more other such documents such combination document published prior to the international filing date but later than the being obvious to a person skilled in the art priority date claimed document memiber of the same patent family Date of the actual completion of the international search Date of mailing of the international search report 23 January 2008 23 01 08 05 February 2008 05 02 08 Name and mailing address of the ISA Authorized officer Japanese Patent Office 1 0 second sheet April 2007 44 02008 066199 1 2008 6 5 PCT JP2007 073352 1 IntCL CI2N5 06 2006 01 i A01K67 027 2006 01 1 61 2 02 2006 01 i A61K35 12 2006 01 i 61 1 36 2006 01 A61P3 10 2006 0114 C12N5 10 2006 01 i C12N15 09 2006 01
39. JMEDPlus JDream2 JSTPlus JDream2 C DOCUMENTS CONSIDERED BE RELEVANT E DOCUMENTS CONSIDERED TO BE RELEVANT Category Citation of document with indication where appropriate of the relevant passages Relevant to claim No AMOUR et al Production of pancreatic 1 29 hormone expressing endocrine cells from human embryonic stem cells Nat Biotechnol 2006 Nov Vol 24 No 11 pages 1392 to 1401 Epub 2006 10 19 NISHIMURA W et al A switch from MafB to MafA expression accompanies differentiation to pancreatic B cells Dev Biol 2006 05 15 Vol 293 No 2 pages 526 to 539 Epub 2006 04 03 WO 2004 050827 A2 TECHNION RESEARCH amp DEVELOPMENT FOUNDATION LTD 17 June 2004 17 06 04 amp EP 1567639 A2 amp US 2006 0040385 Al Further documents are listed in the continuation of Box C Further documents are listed in the continuation of Box See patent family annex See patent Further documents are listed in the continuation of Box See patent family annex annex Special categories of cited documents T later document published after the international filing date or priority document defining the general state of the art which is not considered to date and not in conflict with the application but cited to understand of particular relevance the principle or theory underlying the invention earlier application or patent but published on or after the international filing x
40. gt DI ooo DI L1 L3 r3 C e noo per O LI sia i LI L3 L I L I LI L I DI um OO r3 z N L I I ag I 2 X C gt oY DI DI a SFO l oY DI DI DI 9 E I 28 02008 066199 1 2008 6 5 Jenny Barths Seymour PA Sander M Gradwohl Pancreatic islet progenitor cells in neurogeni n 3 yell ow fluorescent protein knock add on M Endocrinol 18 11 2765 76 20048 0 0000 0 0000000000 00200
41. 2001 May18 292 5520 1389 1394 0 Hori YO Proc Natl Acad Sci USA 2002 10 99 25 16105 16110 II II I agopal JQ D Science 2003 an17 299 5605 363 0 0 0 II Si pi one Diabetologia 2004 47 3 499 508 L 00 0 M yazaki S Di abetes 2004 53 4 p 1030 1037 000 Anour i 10 1038 nbt 1259 000 100000000 Sci ence 2001 May18 292 5520 1389 1394 Proc Natl Acad Sci USA 2002 10 99 25 16105 16110 100 Sci ence 2003 an17 299 5605 363 II II Di abetol ogi a 20 04 47 3 p 499 508 0 0000 Di abetes 2004 53 4 1030 1037 100 Di abetes 2004 53 10 2603 2609 II II II II II II II II II II II II Hansson M Diabetes 2004 53 10 2603 2609 1 Nat Biotech published online 19 October 2006 do Biotech published
42. Di ckinson and Conpan 100000000000 00 0000 Activin 0000000 gt 1 x MED 2 000 LI II II II II I II II II LI II II II II II II II II II II 02008 066199 1 2008 6 5 26 10 20 C 10 10 publ ished online 19 October 2006 doi Bi ot ech Nat LI LI 30 40 50 C I LI LI I LI LI 1000
43. II II II 00000000000 00000000 Dow 5 i m C 29 02008 066199 A1 2008 6 5 10000 s nB 10000000000000 u ud LI I II II II II II II II II II II U X 8 10000000000000000000000000 II II II C z aoe age C 0 ebs Ringer Bal anced Buffered M mih aen il n Srivastava S Goren nsulin constituti vel y secreted by beta cells is necessary for gl ucose sti mul ated insulin se
44. u 30 II 4 mg dl 02008 066199 1 2008 6 5 42 HO 8 4 9 9 2 L 00 4 007 I 7 E oz G 2 RE O Bx eV ORAM ER AAR EBEN o MERE GUAE o SET MERERI A AE LIT ERE PML KS LIER OUST O 009 LI II X b mg dl 2008066199000001 43 02008 066199 A1 2008 6 5 LL II II INTERNATIONAL SEARCH REPORT International application No PCT JP2007 073352 A CLASSIFICATION OF SUBJECT MATTER 12 5 06 2006 01 1 4201 67 027 2006 0131 A61F2 02 2006 01 i A61K35 12 2006 01 1 A61M1 36 2006 01 i 61 10 2006 01 1 12 5 10 2006 01 1 C12N15 09 2006 01 n According to International Patent Classification IPC or to both national classification and IPC B FIELDS SEARCHED Minimum documentation searched classification system followed by classification symbols C12N5 06 A01K67 027 A61F2 02 A61K35 12 A61M1 36 A61P3 10 C12N5 10 C12N15 09 Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched Electronic data base consulted during the international search name of data base and where practicable search terms used BIOSIS MEDLINE WPIDS STN
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48. 2008 066199 1 2008 6 5 ns Trial Diabetes Control and cations Trial Research Group N Eng 1993 329 977 986 20 30 40 II II II II II BHHHHHHHHHHH 1000000000000 Lunel sky Sci ence 2001 18 292 5520 1389 1394 L Assady 5 Di abetes 2001 50 1691 1697 LI LI II II II 1 II II II
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50. HEBHHHHHHHHHHHHCas Meneur Elg hazi L Czerni chow P Scharfmann dermal growth factor increases undifferen tiated pancreatic enbryonic cells in vitro a balance between proliferation and differentiation Diabetes 2001 Jul 50 7 1571 9 L LI LI LI II I II II II II II II II II II II II II 0 00000060
51. HHHHHHHHHHH 1 1 DIST 1141 po BS BOE II 10 2 10 S 8 1 PETTO 00000000000 0 000000000000000000000000000000000000 IHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH Jun mw nin 00x00 00000000000000x00s00000000000050 22 02008 066199 1 2008 6 5 LI II LI II II II II II II II II II II II 000000 000 II II II II II II II II II II II II II II I II LI II II II II II II II II II II II II II II 00 000000000 Al ej andr Soto Gutierrez Naoya Kobayashi Jorge David Ri vas Carrillo Navarro Al va rez Debai o Zhao Teru Ckitsu Hirofum Noguchi Hesham Basma Yashuhi ko Tabata Yong Chen Ki Tanaka chi ki Narushi Atsushi Tadayoshi Ueda Hee Sook Jun 1 Yoon Jane Lebkowski Noriaki Tanaka amp Ira Fox Reversal o f mouse hepatic failu
52. SC SD SE SG SK SL SM SV SY TJ TM TN TR TT TZ UA 0 US UZ VC ZA ZM ZW 74 74 72 100098464 100149630 100154449 REF 2033 15 9 54 fds EUS 5 0000 LI II II II LI II 0 II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II I II LI I II II II II II II II II II II II II II II II II II II II II II II II II II II II II IIII II II II II CL I II II II LI II II II II II II II II II II II II II II II II II II II II II II II II II II II LI II CI II LI II LI II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II LI LI II II II II LI II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II 000000000000 II 02008 066199 A1 2008 6 5 2 10 LI LI
53. creti on Di abetes 2003 52 8 2049 56 1000000000000000000 100000000 I LI LI VI II II LI II II II II II II II II I II UH LI II II II II II II II II II II I CHHHHHHHHHHHHHHH II II II Biotech published online 19 October 2006 doi 10 1038 L 1259 LI II II II LI II LI II II II II II II II II II II II II II II II II II II II II II II II II II II II II 0 II 1 1I 1 I II II II 30 02008 066199 A1 2008 6 5 Int Dev Biol 2006 50 1 17 26 LI LI LI II II II II II II II II II II II II II II II 000000 Developrent 2001 128 24 5109 177 IlHHHHHH HHHHHHHHH
54. online 19 October 2006 doi 10 1038 L1259 LI LI LI LI LI II LI II LI LI II II II II LI II II II II II II II II II II II II II 000000 Nat otech published online 19 October 2006 doi 10 1038 nbt 1259 00000 LI LI LI II II II II LI LI Int J De v Biol 2006 50 1 17 26 100000 0 0 0 Bhusha Devel opment 7 2001 128 24 5109 17 02008 066199 1 2008 6 5 10000000000000
55. re usi ng an i mpl anted li ver assi st devi ce contai ni ng ES ce 1 deri ved hepatocytes nature bi otechnol ogy Vol 24 No 111 pp1412 1419 Pub ished online 05 November 2006 10 1038 nbt 12571 100000000000000000000000000000000000 LI II II II II II II II II 0 100000000 0 Circe Biomedical Inc 10000000000000000000000000000000000 CC dars Sinai Medi cal Center 0 000000000 II II II II II II II II II II II II II II DenretriouJ II II LI LI LI LI II II II II II II II II II II II II II II II II II II II II Hepat Assi st 0 Hui Rozga J Denetriou Hepatobiliary Pancreat Surg 2001 8 1 15 000000000000000000000000000 Modul ar Extracorporeal Liver System 1 LI 0010 00000000
56. rtin Si dhoumJenny M Barths Seymour PA Sander M Gradwo hl Pancreatic islet progenitor cells in neurogenin 3 yellow fluorescent prote in knock add on mice Mol Endocrinol 18 11 2765 76 20040 21111 1 1 11 0 100000 H 40 x 2100000000000000 100000000 SE 1000000000 I LI II II II L II 100000000 100000 I II II II II II II II x L LI X LI II II II II II II II I LI II II II II II II II 10 I LI LI II II II II II II II II II II II II II II II 0 LI II II II II II II II II II II II II 0D00OO0000000000000000000000000000000000 50 02008 066199 1 2008 6 5 16 10 20 30 40 50 exendi 40
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