USOO9714433B2 (12) United States Patent (10) Patent No.: US 9,714.433 B2 Sakurada et al. (45) Date of Patent: *Jul. 25, 2017 (54) HUMAN PLURIPOTENT STEM CELLS 4.937,190 A 6/1990 Palmenberg et al. INDUCED FROM UNDIFFERENTATED 5,225.348 A 7/1993 Nagata et al. 5,266.491 A 11/1993 Nagata et al. STEM CELLS DERVED FROM A HUMAN 5,268,290 A 12/1993 Hasegawa et al. POSTNATAL TISSUE 5,288,514 A 2f1994 Ellman 5,324,645 A 6/1994 Takahara et al. (71) Applicant: Kyoto University, Kyoto (JP) 5.449,614 A 9, 1995 Danos et al. 5,519,134 A 5/1996 Acevedo et al. 5,525,735 A 6/1996 Gallop et al. (72) Inventors: Kazuhiro Sakurada, Kanagawa (JP); 5,549,974 A 8, 1996 Holmes Tetsuya Ishikawa, Tokyo (JP); Hideki 5,591,624 A 1/1997 Barber et al. Masaki, Tokyo (JP); Shunichi 5,637,456 A 6/1997 Roth et al. Takahashi, Hyogo (JP) 5,652,122 A 7/1997 Frankel et al. 5,674,980 A 10, 1997 Frankel (73) Assignee: KYOTO UNIVERSITY, Kyoto (JP) 5,707,618 A 1/1998 Armentano et al. 5,716,832 A 2f1998 Barber et al. 5,744,320 A 4/1998 Sherf et al. (*) Notice: Subject to any disclaimer, the term of this 5,817.491 A 10, 1998 Yee et al. patent is extended or adjusted under 35 5,817492 A 10, 1998 Saito et al. U.S.C. 154(b) by 217 days. 5,830,725 A 11/1998 Nolan et al. 5,834,256 A 11/1998 Finer et al. This patent is Subject to a terminal dis 5,858,740 A 1/1999 Finer et al. claimer. 5,910,434 A 6/1999 Rigg et al. 5,955,331 A 9, 1999 Danos et al. (21) Appl. No.: 14/195,698 (Continued) (22) Filed: Mar. 3, 2014 FOREIGN PATENT DOCUMENTS (65) Prior Publication Data AU 200820 1280 A1 4/2008 CN 1012.505O2 A 8, 2008 US 2014/0206083 A1 Jul. 24, 2014 (Continued) Related U.S. Application Data OTHER PUBLICATIONS (62) Division of application No. 12/663,840, filed as Perkins et al. Anemia and perinatal death result from loss of the application No. PCT/EP2007/010019 on Nov. 20, murine ecotropic retrovirus receptor mCAT-1.Genes & Develop 2007, now abandoned. ment, 1997, vol. 11, pp. 914-925.* A reprogramming rush. Editorial. Nature. Mar. 27, 2008. 452:388. (30) Foreign Application Priority Data Published online Mar. 26, 2008. Adachi et al. Role of SOX2 in maintaining pluripotency of human embryonic stem cells. Genes Cells. May 2010; 15(5):455-70. Jun. 15, 2007 (JP) ................................. 2007-1593.82 Adewumi et al., Characterization of Human Embryonic Stem Cell Lines by the International Stem Cell Initiative, Nat. Biotechnol. (51) Int. Cl. 25(7):803-16, 2007. CI2N 5/074 (2010.01) Adhikary et al. Transcriptional regulation and transformation by CI2N 15/85 (2006.01) Myc proteins. Nat Rev Mol Cell Biol. Aug. 2005;6(8):635-45. (52) U.S. Cl. Akimov et al., Bypass of Senescence, Immortalization, and Trans CPC ........... CI2N 15/85 (2013.01); C12N5/0696 formation of Human Hematopoietic Progenitor Cells, Stem Cells (2013.01); C12N 2501/602 (2013.01); C12N 23: 1423-33, 2005. 2501/603 (2013.01); C12N 2501/604 (Continued) (2013.01); C12N 2501/606 (2013.01); C12N Primary Examiner — Thaian N Ton 25.10/00 (2013.01); C12N 2799/027 (2013.01) (74) Attorney, Agent, or Firm — Knobbe, Martens, (58) Field of Classification Search Olson & Bear LLP CPC ............ C12N 5/0696; C12N 2501/602; C12N 2501/603; C12N 2501/604; C12N (57) ABSTRACT 2501/606; C12N 2510/00; C12N 15/85; C12N 2501/605; C12N 2501/608; C12N Establishment of human pluripotent stem cells having prop 15/63; C12N 2799/027; C12N 2501/60; erties close to human ES cells with the genome of the patient C12N 15/86; C12N 2506/45; C12N per se that can circumvent immunological rejection of 2501/727; C12N 2506/1307; C12N transplanted cells from cells derived from a postnatal human 5/0657; C12N 5/0678; C12N 5/0606; tissue are described. Human pluripotent stem cells can be A61K 35/545 induced by introducing three genes of Oct3/4, Sox2 and Klf See application file for complete search history. 4, or three genes of Oct3/4, Sox2 and Klf 4 plus the c-Myc gene or a histone deacetylase (HDAC) inhibitor of undif (56) References Cited ferentiated stem cells present in various human postnatal U.S. PATENT DOCUMENTS tissues in which each gene of Tert, Nanog, Oct3/4 and Sox2 has not undergone epigenetic inactivation. 4,650,764 A 3, 1987 Temin et al. 4,861,719 A 8, 1989 Miller 2 Claims, 22 Drawing Sheets US 9,714.433 B2 Page 2 (56) References Cited 2008/O132803 A1 6/2008 Friedlander 2008.0171358 A1 7, 2008 Perrault U.S. PATENT DOCUMENTS 2008.0171385 A1 7/2008 Bergendahl et al. 2008/0206865 A1 8/2008 Zhang et al. 6,013,517 A 1/2000 Respess et al. 2008, 0233610 A1 9, 2008 Thomson et al. 6,017,735 A 1/2000 Ohare 2008/027.4914 A1 11/2008 Yamanaka et al. 6,017,761 A 1/2000 Rigg et al. 2008/0280362 A1 11/2008 Jaenisch et al. 6,025, 192 A 2/2000 Beach et al. 2008/0293143 A1 11/2008 Lin et al. 6,140, 111 A 10, 2000 Riviere et al. 2008/0299.548 A1 12/2008 Yamanaka 6,146,874. A 11/2000 Zolotukhin et al. 2009/0047263 A1 2/2009 Yamanaka et al. 6,153,432 A 1 1/2000 Halvorsen et al. 2009.0068742 A1 3/2009 Yamanaka 6,153,745 A 11/2000 Williams et al. 2009,019 1159 A1 7/2009 Sakurada et al. 2009,019 1171 A1 T/2009 Ma 3.36 E. 2.38 SE. A. 2009/0227032 A1 9, 2009 Yamanaka et al. 6.255,071 B1 7/2001 Beach et al. 2009/0246875 A1 10, 2009 Yamanaka et al. 6,312.948 B1 11/2001 Cohen-haguenauer 2009, 0299763 A1 12/2009 Sakurada 6,312,949 B1 1 1/2001 Sakurada et al. 2009/0304646 A1 12/2009 Sakurada et al. 6,333,195 B1 12/2001 Respess et al. 2009/0324559 A1 12/2009 Sakurada 6,395,5466,365,352 B1 4/20025, 2002 ZobelYerramilli et al. et al. 28:889, A. 388 MilkSaCSO 2010.0062533 A1 3/2010 Yamanaka 8.8% R 383 SMS et al. 2010/0062534 A1 3/2010 Hochedlinger 6,521,453 B1 2/2003 Crameri et al. 2010.0075421 A1 3/2010 Yamanaka 6,521,455 B2 2/2003 O’Hare et al. 2.99. A. ;388 S. d 6,605,275 B1 8, 2003 Bowse et al. Ca 6,660,514 B1 12/2003 Zioninet al. 2010/01 20069 A1 5/2010 Sakurada 6,773,920 B1 8/2004 Dalby et al. 2010, O144031 A1 6/2010 Jaenisch 6,833,269 B2 12/2004 Carpenter 2010, O184051 A1 7/2010 Hochedlinger 6,835,567 B1 12/2004 Sah et al. 2010, O184227 A1 7/2010 Thomson 6,841,535 B2 1/2005 Divita et al. 2010/02100 14 A1 8/2010 Yamanaka 6,872,528 B2 3/2005 Klatzmann et al. 2010/0216236 Al 8, 2010 Yamanaka 6,875,578 B2 4/2005 Giuliano et al. 2010, 0221827 A1 9/2010 Jaenisch 6,881,825 B1 4/2005 Robbins et al. 2010. 0233804 A1 9, 2010 Zhou 35E, SS KEY 388 A .239 Swata 703953 B2 4/2006 E. et al. 2010/0279.404 A1 11/2010 Yamanaka 7030,292 B2 4.2006 Yanet al. 2011/0014164 A1 1/2011 Huangfu et al. 7,070,994 B2 7/2006 Barber et al. 2011 0039332 A1 2/2011 Sakurada et al. 7,250,255 B2 7/2007 Yamanaka 2013,0059386 A1 3/2013 Yamanaka et al. 7,439,064 B2 10/2008 Thomson et al. 2013,0065311 A1 3/2013 Yamanaka et al. 8,048,999 B2 11/2011 Yamanaka et al. 2014/OO57355 A1 2/2014 Thomson et al. 8,058,065 B2 11/2011 Yamanaka et al. 2015.OO72417 A1 3/2015 Yamanaka et al. 8,129, 187 B2 3/2012 Yamanaka et al. 8,211,697 B2 7/2012 Sakurada et al. FOREIGN PATENT DOCUMENTS 8,278,104 B2 10/2012 Yamanaka et al. 8.298,825 B1 10/2012 Hochedlinger et al. CN 1O1550428 A 10/2009 2002/O123146 A1 9/2002 Klatzmann et al. EP 1970446 A1 9, 2008 2003/OOO3574 A1 1/2003 Toma et al. JP 2-227O75 9, 1990 2003/0044976 A1 3/2003 Dominko et al. JP 2002-065261 3, 2002 2004/004.8297 A1 3, 2004 Scherf JP 2003-009854 1, 2003 2004/O137460 A1 7/2004 Yamanaka et al. JP 2004-161682 A 6, 2004 2005, 0026133 A1 2/2005 Nakatsuji et al. JP 2005-359537 12/2005 2005, 0162419 A1 7/2005 Kim et al. JP 2008-283972 11/2008 2006, OO30041 A1 2/2006 Furcht et al. WO WO95/10619 A2 4f1995 2006, OO88599 A1 4/2006 Prasad et al. WO WO 97.05265 A1 2, 1997 2006/0095319 A1 5, 2006 Cardwell WO WO 98.02529 A1 1, 1998 2006/0246064 A1 1 1/2006 Boyle WO WOOO, 18885 A1 4/2000 2007.0053884 A1 3, 2007 Suda et al. WO WOOO, 23567 A3 T 2000 2007/O155O13 A1 7/2007 Akaike et al. WO WOOOf73423 A1 12/2000 2007/0202592 A1 8/2007 Kitagawa et al.