Patent SG-11201811202W-A (SG)
Title: Human liver chimeric non-human animal with deficient p450 oxidoreductase and methods of using same
Inventor: BISSIG KARL-DIMITER
IPC: A01K67/027
Filed: 2017-06-27
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property 111111101111 0 1110101011111 011101 0 01111111100111111H1101111111011110111111 Organization International Bureau (10) International Publication Number (43) International Publication Date ......0\"\" WO 2018/005471 Al 04 January 2018 (04.01.2018) W I PO I PCT (51) International Patent Classification: HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, AO1K 67/027 (2006.01) A01K 67/02 (2006.01) KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (21) International Application Number: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, PCT/US2017/039474 OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (22) International Filing Date: TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 27 June 2017 (27.06.2017) (84) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of regional protection available): ARIPO (BW, GH, (26) Publication Language: English GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (30) Priority Data: TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 62/355,102 27 June 2016 (27.06.2016) US EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, 62/509,942 23 May 2017 (23.05.2017) US MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, (71) Applicant: BAYLOR COLLEGE OF MEDICINE KM, ML, MR, NE, SN, TD, TG). [US/US]; 1 Baylor Plaza, Houston, Texas 77030 (US). (72) Inventor: BISSIG, Karl-Dimiter; c/o Baylor College of Published: Medicine, 1 Baylor Plaza, Houston, Texas 77030 (US). — with international search report (Art. 21(3)) — with sequence listing part of description (Rule 5.2(a)) (74) Agent: PAVAO, Matthew et al.; Cooley LLP, 1299 Penn- _ sylvania Avenue, NW, Suite 700, Washington, District of Columbia 20004 (US). — = Designated States (unless otherwise indicated, for every (81) kind of national protection available): AE, AG, AL, AM, = _ AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, _ = CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, Title: HUMAN LIVER CHIMERIC NON-HUMAN ANIMAL WITH DEFICIENT P450 OXIDOREDUCTASE AND (54) METHODS OF USING SAME (57) : The present disclosure provides a chimeric non-human animal com- prising human hepatocytes, methods for preparing the chimeric non-human animal = Figure 1A comprising human hepatocytes and methods of utilizing the chimeric non-human an- = = PIRF mouse strain imal comprising human hepatocytes to screening and identifying metabolites for any Por gene . LoxP Low type of drugs, typically small molecule drugs, which might affect human liver func- = _ Wild-type E5 E6 all-tions and any other bodily function. Lo re Conditional E7 = = deletion = 112-rg gene s 2300bp = Wild-type GI Mill-13- 131-31 IM = Deletion -E -131-11:1- Rag2 gene5 850bp li Wild -type El .4 \/ PSI Deletion == I E1 I IN 71' in 1700bp Fah gene5 Wild type - - M - EI - 1:11/ IM - 2I IF © © ,-.... Deletion - 01 - 131 - 21 . MM 1211 -- 1-1 0 N 'Embryonic stem cell targeting (See, Figure 4) A .,,,, § Zygote injection with Cas9 and gRNA (See, Figure 5)