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(12) United States Patent (10) Patent No.: US 9,605.243 B2 D'amour Et Al

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(12) United States Patent (10) Patent No.: US 9,605.243 B2 D'amour Et Al USOO9605243B2 (12) United States Patent (10) Patent No.: US 9,605.243 B2 D'Amour et al. (45) Date of Patent: Mar. 28, 2017 (54) MARKERS OF DEFINITIVE ENDODERM 6,117,986 A 9, 2000 Nardone et al. 6,165,993 A 12/2000 Herrmann et al. (71) Applicant: ViaCyte,7 Inc., San Diego, CA (US) 6,251,6716,200,806 B1 3/20016/2001 ThomsonHogan et al. (72) Inventors: Kevin Allen D'Amour, San Diego, CA 3. R 1658 R.S.A. (US); Alan D. Agulnick, San Diego, 6,506,574 B1 1/2003 Rambhatla et al. CA (US); Emmanuel Edward Baetge, 6,872,389 B1 3/2005 Faris Encinitas, CA (US) 6,921,811 B2 7/2005 Zamora et al. s 7,033,831 B2 4/2006 Fisk et al. 7,153,684 B1 12/2006 Hogan (73) Assignee: ViaCyte, Inc., San Diego, CA (US) 7.256,042 B2 8/2007 Rambhatla et al. - 7,326,572 B2 2/2008 Fisk et al. (*) Notice: Subject to any disclaimer, the term of this 7,510,876 B2 3/2009 D'Amour et al. patent is extended or adjusted under 35 23: R: 258 Nation et al U.S.C. 154(b) by 0 days. 8,586,357- I k B2 11/2013 D'Amour'Amour et al. 2002/00721 17 A1 6/2002 Xu et al. (21) Appl. No.: 14/066,441 2002/0090723 A1 7/2002 Carpenter et al. 2003. O138948 A1 7/2003 Fisk et al. (22) Filed: Oct. 29, 2013 2003. O138949 A1 7/2003 Bhushan et al. 2003/0175956 A1 9, 2003 Bodnar et al. (65) Prior Publication Data 2003. O190748 A1 10, 2003 Thomson 2003/0224411 A1 12/2003 Stanton et al. US 2014/0134726 A1 May 15, 2014 2004/O1274.06 A1 7/2004 Presnell et al. 2004/0229350 A1 11/2004 Strelchenko et al. O O 2005, 0079159 A1 4/2005 Shastri et al. Related U.S. Application Data 2005. O158853 A1 7, 2005 D'Amour et al. 2006, OOO3446 A1 1/2006 Keller et al. (63) Continuation of application No. 12/093,590, filed as 2006, OO19387 A1 1, 2006 r a application No. PCT/US2006/043932 on Nov. 13, 2006/0040385 A1 2/2006. Itskovitz-Eldor et al. 2006, now Pat. No. 8,586,357, and a 2006,0040387 A1 2/2006 Fisk et al. continuation-in-part of application No. 11/021,618, 388858 A. $39. (St. al filed on Dec. 23, 2004, now Pat. No. 7,510,876. 2006/0276420 A1 12/2006 Kellerelly etet al.al. (60) Provisional application No. 60/736,598, filed on Nov. (Continued) 14, 2005, provisional application No. 60/532,004, filed on Dec. 23, 2003, provisional application No. FOREIGN PATENT DOCUMENTS 60,586,566, filed on Jul. 9, 2004, provisional EP O 543 942 6, 1993 application No. 60/587,942, filed on Jul. 14, 2004. EP 1298 201 A 4/2003 (51) Int. Cl (Continued) CI2N 5/00 (2006.01) CI2N 5/071 (2010.01) OTHER PUBLICATIONS CI2N 5/073 (2010.01) Hoshi et al. (2007, Endocrinology, vol. 148(9), pp. 4251-4258).* (52) U.S. Cl. Armelin HA. (1973, PNAS, vol. 70(9), pp. 2702-2706).* CPC ......... CI2N 5/0617 (2013.01); CI2N 5/0603 Smolich et al., (1993, Mol. Biol. Cell, vol. 4, pp. 1267-1275).* (2013.01); C12N 2501/16 (2013.01) Fayet et al. (2002, Thyroid, vol. 12(7), pp. 539-546).* (58) Field of Classification Search 2008, Ireland KA., Visualizing Human Biology, 3rd Ed., Wiley and CPC .................................................... C12N 5/06.17 Sons Inc.,, 35 pagespag total. Reubinoff et al. (2000, Nature Biotechnology, vol. 18, pp. 399 St. licati- - - - - -file? - - - - - - - - - - - - - ice achi" 404).* ee a1Ca1Opp TO CO.p SeaCl 1SOW.ry (Continued) (56) References Cited Primary Examiner — Thaian N Ton U.S. PATENT DOCUMENTS Assistant Examiner — David A Montanari 4,683, 195 A 7, 1987 Mullis (74) Attorney, Agent, or Firm — Klarquist Sparkman, 4,683.202 A 7, 1987 Mullis LLP 4,816,567 A 3/1989 Cabilly et al. 5.453,357 A 9/1995 Hogan 5,670,372 A 9/1997 Hogan (57) ABSTRACT 5,690,926 A 11/1997 Hogan 5,817,637. A 10, 1998 Weiner et al. Disclosed herein are reagent-cell complexes comprising one EC A 3. 3. Y. et al. or more definitive endoderm cells. Also described herein are 5.866.366 A 2, 1999 R compositions for detecting definitive endoderm. Method of 5,869,620 A 2f1999 Whitlow et al. enriching, isolating and/or purifying definitive endoderm 6,015,671 A 1, 2000 Field cells are also disclosed. 6,090,592 A 7/2000 Adams et al. 6,090,622 A 7/2000 Gearhart et al. 6,117,635 A 9, 2000 Nazarenko et al. 2 Claims, 38 Drawing Sheets US 9,605.243 B2 Page 2 (56) References Cited Barringer et al., “Blunt-end and single-strand ligations by Escherichia coli ligase: influence on an in vitro amplification U.S. PATENT DOCUMENTS schemem.” Gene, (1990) 89(1): 117-22. Barry et al. “Production of monoclonal antibodies by genetic 2007. O154984 A1 7/2007 D'Amour et al. immunization.” Biotechniques 16 : 616-620. (1994). 2007/0281355 A1 12/2007 Dalton et al. Battle et al., “The transcription factor Snail is a repressor of 2009,02532O2 A1 10/2009 D'Amour et al. 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