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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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1.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     3  JP VC2008  066199   1 2008  6  5  0                  
2.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     10    20    30    40    50     14        02008  066199   1 2008  6  5                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
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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5.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    L II LI                                                                                                  100000   I LI II II II II   L II L II               100000       U   U                      100000  Definitive Endodernt  60 00 0 000 0 0000 0 0 0 U 0 Visceral En   doder m               Mes endoderm  htt p      ww          ri ken                                        p j p  04 news arti cl es  pdf   051201 ni shi          mesendoder    pdf                     LI II II   II II    II II II II                                         0                                        ventral pancreatic bud           10000000   dorsal pancreatic bud                       http      ww             usei     p  09              5 pdf   2005  10  21  pdf                                                                                             
6.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          6 LI LI II II  Hunan Brain    crovascul ar  Endothelial          50                  0 Human Choroi d PI exus  Endothelial Cells                   Human Intestinal Mcrova  scul ar Endothelial Cells  Human Cardi ac                      lar Endothelial Cell 50 10  Human Aortic Endothel i al  Cells                                         Retinal Endothelia  Cel    s            0 Human Unbilical Vein  Endothelial Cells    0 0 Human Umbilical Arte  ry Endothelial Cells  20  x  D D Mit s  x                100000000   LI LI 0  00   C 0 00 1000000 100 0000 30      LI LI I  L LI                                                                                    enhanced yellowfluore  scence                              HHHHHHHHHHHHHH                                                 H                                                    1000000000                r G Ma
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8.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          8        02008  066199   1 2008  6  5  10000000000000000000  100000000000000  LI LI II LI LI II II II II II II II II II II II     II II II  L LI I II LV     LI II II II LI II II II II II II II II    LI II II       1 II II II II U       LI II II   II II II II    LI II II       11 II II II II II 0000 II    LI II    1 II II II II U       LI II II    II           II II II II II II II II    U II  I LI LI LI LI II II II II II II II II    II LI II II II II  LI LI II LI LI II II II II II II 0000000    LI II 11 II II II II II II I I II 0000  L LI II LI LI II II II II II II II II 0000000  LI LI II LI II II II II II II II II II II II II II II II I     LI II II II II II II II     LI LI II LI LI II II II II II II II II 0000000    LI II II       11 II 1 I I II II II UU    LI II 1 1 1 II II U       LI II II       1 II II II II U     I LI LI LI LI II II II II  I II II 1 II UU    LI II II       1 II II II II II II II II    II II      
9.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           30    40    50     19        02008  066199   1 2008  6  5                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          LI II 1 II II II II II I I II II lu                                                                                                                                                                                  L L    LI LI II II   Mtsunoto S    4  5                                      2002  74  1414   5                                               flat I LI II II II II II II II II II II II 0
10.                                                                                                                                                                                                                                                                                                                                                                                                   38  nbt 1259                                                                                                                                                           02008  066199   1 2008  6  5     27                                                                                                                                                     10    20  30    40                                                                                                                                                                                                                                        50                                                                                                                                                                                                                                                                                                                                                                                                                                                  5      oscene      _                          DI      DI                     
11.                                                                                                                                                                                                                                                                                                                                                   L LI II II II II LI                 L LI II II        L LI II         1000000000000000000000000     LI II 1    II II      II II II    II II II II II II II U II                L LI LI LI II II LI II II II II II 0000000000000   L LI L LI II II II II I LI LI LI LI II II  II  I II II II II II II II II II 01010111 10                                                                                                    Nagata H  Ito    Shirota     Edge A  MCowan TC  Fox 1   Route of hepatocyte delivery affects hepatocyte engraftment in the spleen  Tra                                                                                                                                                                                                                                                                                                                                                                                                                                        nspl ant ati on  76 4   732 4  2003                                                                                                                1000000000000000       HHHHHHHHHHHH IHHHHHHH
12.                                                                                                                                                                                                                                                              10    20    30    40    50     18        02008  066199   1 2008  6  5                        LI II      LI II 1 1 1 II II    II II                         I LI LI II II L LI II II II II II II II II II II II II II 0                                1                ded II II II II II II I II II II 00 0  Mat ri gel 000000000                                                                                                                         1000                    0                                                                                                                                                                                                                                                                                                                                                                   1000000000000000  1000000000000  1000000000000  1000000000000      hepatocyte nuclear factor 3                 mning region Y   LI II II II II II II II II II U     100 100000 000000                                                             00000000000    LI  LI  LI  LI  LI  LI                                                                                                                                                 
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 
14.                                                                                                                                                                                                                            02008  066199   1 2008  6  5      24              1                  LI LI             I LI LI                      1000       I I 1 II                                       I I 1 II          I LI LI                      1000                100000                                             100000                I LI LI                I LI LI                I LI LI               LI LI                   10                                                                                                                               20                                        LI LI                        100000                1000  I LI LI      LI LI                I LI LI       I LI LI                                             0000000          htt p      ww  i nterq              ox         se  se39  563961006                                                      0000                            30                           40                                                                 00000                                                                                                                                                                                           50                   I LI LI               LI LI                        LI LI    1000     
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                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
17.                                                                                                                                                         oana O          Ea                                                               10    20    30    40    50          02008  066199   1 2008  6  5     23                      10    20                                                                 I LI LI                I LI LI                                                                                                                 LI LI    I LI LI LI  I LI LI                I LI LI                                                I LI LI                I LI LI                                                                                                          I LI LI                                                               1000  I LI LI                                                                                                      30                40                                                               I LI LI                                                                                        I LI LI                                                                                                                                                                        C                   50                                                                                                                                                                   
18.                                                                                                                         10    20          02008  066199 A1 2008  6  5     37     0000                                                 a              2 6 89 2      60   00  7 001      9 FOF 09 76  9601 911               018 2 98  098 Les       6 Lee 698            8 028 681 SEL         6 16 96    8 08          4 98 81 6L 88 78 62              08 LL 08 81 98 61  9 6 98 78 81 89  9 z ou        18 68 28 06 18 98 88 76 68 18 08 88    8 TOU 48          1                              ra  506 Pell 816 81 56        68 129 69 LTL 198 6101  56           8 8         8601 9501        4611 Ezi 98  FEIT 261 POT 2401        86 6     461 ICI   cl lat        IVI        921 621      V 621 GLE        E  001 86 86 VII        681 bel 611 011 86 LIT        696 ou       801 011        II vel        181 LIT SII  6 101 tel ELE g ou Big  901 201 86   01 801 811 VI   01 881 76 86        F6E                     101 SOT 011 801 201        801 611 901 96 681 886            __ ez                     WATO AHAAA  838095         Oe  IT    00  829 5091 666 899  9 16 799  lt 08 1612 9881 6097 962          SE    0966 L668 5666 9109 8666 8766  2066 8688 BOLE 9170 05662 VEST FELE           819 1867        007 SOF 96  282 202 797 181 888  09  406  168 986 626 188 666  68 986 768 196 682     5 881        VoU       68    266 68  968 685 886 LLE 98  895        196 LI 115 g ou  8        60   gt 07 886 816 ZLE 1  612 vol 696  
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                                   
23.                                                    E       E                   EA     nature protocols vol 1  no 2     49        1000000000000000  BASS MN  ala 3             a E     poc TS                                                                                                                                                                                                                                                 10    20          02008  066199   1 2008  6  5      32          LI III II                                        1          2 8                               SERERE 8   O NINC        27                        NINO  sexe  80                    NANO  Ha Be   HRL CAU LIN          A n       69 H  A                        H      NINO          08768          i i B        INdING         86                      EYL Seat         INING  8888   rn Zl  SE OEC         3824 Co 3UXESK QUA EE FEK    wdooz   wdost   door  2070 6070 01740 6070 9070                   40 26  000 600 MURE    URINA nm            25  610  9 0 1870 0 1870             8                  6070 1870 6870 8870 6270                                  070 220 9270 100 6170        Seat 8 eo NINO           37  80               NZ A 4231   100 cro               8070        A ALL      UT  0070 6070           AE ALARA GOH       620               8071 6 71               ZO NAN  9170 8970 1170 1970 2170 PA HY                          90  0 9270 O   020 9070             O NUNC                4  37 73U           
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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35.      fragnented                                                                                                  LI II II II                II 1 II I II I II II II II    II     os              L II II 1 II II II II II II II 00 00000 II 000000000    II    II                II               II              II II II II 0         I                                                           II    0        II                                                                               I I II II II                        II                 II     0               100000000000000000000000000                  100000000000000000000000000    LI II    II    II II II II II II 0  L LI II          II II II II    II              000                         Net  Biotech     publ i shed online  19 October 2006  doi  10  1038  nbt 1259  000  1000000000000    II II    II         II           0       II      I I II I II II II II II II II II II II II II II II II II II I I II II II 0 II II II II II II II 0                                                                                         31           02008  066199   1 2008  6  5                                                                                                                                                                                                                                                                                                                                                                                     
36.     20          02008  066199 A1 2008  6  5      39     0000                                                   IV a 8879 6 74 6v c 889 6021        69 162 Tp 2621 066       6706 0728 0  88       8 8768 0718 0791 8718 8798 0768 1 8 8708 0781        76 16 96 68 08 vL EZ 98 81 6L 88 78 EL    ou       08 LL 08 84 98 64  9 62 98 78 84  9 79            16 26 88 26 78 06 26 46 86 98 88 76 88         4  2  Tp Sur                        2399       6011   911 OF OL 008 720 8 6178   976 886 8901 8891             56          0501 9101 FOOT 8 6 00071 FOOT 9001 2001 8801      9661 8801 83816           16 78 18 v8   6 t6 06 96 96 081        991 78  S ou 0  76   6 88 18 96 16 96 16 001 611        181 846 y ou 48    801 011        201 901 96 001 86 SIT 011 181 481 996    ou  406         VII 811 901      SIT VII IIT    51 181 OLI  91 268        408  III 101 SOT 011 801 801        001 011 LEI 6v1 LLI 845 Tou              8    BEAU AA eg        MTV kuy ES                 HT    09  ISPI 8691 0081 E92 8601 6701 6661 2011 88 8901 9091        8 m abu  9609 POOP 8666 9766 8766 97886 0886 986 0712 9800 8612 OPIZ 85 6               8       POF 00  GOP 96        5   02  05 112 896        208  168 986 6       186 66  866 986 76  LEZ 612 Tec 812 885 you 0408  917 ZIE 807 POF 866 886 886 066 615 112 918 185 LLE    ou              68  LLE PLE 282 896 ZLE 296 661 861 102 681 798 COU  AM  166 66 G6E 166 168 76  68  116 805 PIG LIZ 122 LLE T OU      a        8                       Yt quit B      Y ns   L7 MERE
37.     LI  LI  LI  LI    1000000000                                                            spheri cal                                                                                                    bor der                                                                                                      rregular  LI LI II II II II II II LI II II II II II II II II II II II II II II II II II                L L I LI LI I LI LI II II II II II II II II II II II II II O     well rounded    LI                                           L LI II II II II I LI LI LI LI II II II  I  I II II II II II II II 000000                integrity                          LI  LI  LI  LI  LI  LI  LI  LI  LI    fragnent ed                                                                                                                            0 II LI LI 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                                                                                                                                                                                                                                                                                                                                                L3 L3 F                                                                                                  D L3 L3 L3                   L1       ao A         E                                                                            n        
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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46. 000000   I LI II II II II II II II II II II II II II II II II II II II II II 0    L U   U    L II II II II II II L II    0000                           x 51        L         211 1 11   11  11 e  ERI  LI LI II II II II II II II II II II II II II II I I II II CI II II 0  B                                   x RESUME               ES  L LI LI II II II II II II II II II II II II II II II II II II II II 00000000000         HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH  I LI LI II II II II II II II II II II II II II II II II II II 0000000000000    LI II II II II II II II II II II II II II II 0 10000000   LI II II II II II  L L L                                         http   www sci encel   onli         com product s  endot hel                                                                            10    20    30    40                       15           02008  066199 A1 2008  6  5                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
47. 2006  04  03           WO 2004 050827 A2  TECHNION RESEARCH  amp  DEVELOPMENT FOUNDATION  LTD       2004  06  17   amp       1567639   2  amp  US 2006 0040385   1    BRPCT LSA 210      2                          2007448       46        02008  066199   1 2008  6  5                                                                                                                                                                                               72         000 10101111     HHHHHHHHHHHHHH 00000000000000000   72       11111                    1            IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII             48024                                            45065 AA91X 825 BB15 8819         40081 AB35                                                                                                                                                                                                        
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                                                                                                   
49. 2176    CUEBEZIT           FO NWN  88   6871         CUORI 8 SINGING                       LIN                     fogne      SESS    LO IWdING              58 07                                                 NINC          CEST Ago OEY Cibi eat           W3HIWG  EASES   ARMONIA                 EH OTEK a See 5  Wd00z   dos    NWd001    2070 6070 2170 6070 9070 IIM                 LRAT K    009 200                         AOE              8170 190 150 970  80                          60 0 1870 620 6670 620        SES         NINO    600      0 950  50 670             2 NANO       895      37 830  BRE A  oc           LAG         PI O 10 190 8870 9270      I URS DEA           10 0 70 0      A AIRE ES              9 70 105 8878 9676 8975                 NANO     990 1811 10  621 160 MIIV       1                               1870   20 1870 070                  NINO    KESA i UE   87 80  XA FORI                   Flat      5 2 I    ON MM  ooo  LI   1                  0000                           36        02008  066199         1 2008  6 5                                                                                                                                                                                                                                                 severe conbi ned i munodefi ci ency                   U 0   U Hog  EE I III    II VI             se 9                                                                                                          
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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