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(12) United States Patent (10) Patent No.: US 9,714.433 B2 Sakurada Et Al

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(12) United States Patent (10) Patent No.: US 9,714.433 B2 Sakurada Et Al 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. 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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. 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