Patent SG-11201901305Y-A (SG)
Title: Mice comprising mutations resulting in expression of c-truncated fibrillin-1
Inventor: HUNT CHARLEEN
IPC: A01K67/027
Filed: 2017-07-28
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property C.--.` 41111111111HDEIREEMODIEENEEDEIIIIMMEMIE Organization International Bureau (10) International Publication Number (43) International Publication Date .../- WO 2018/023014 Al 01 February 2018 (01.02.2018) WIP0 I PCT (51) International Patent Classification: MADA, Jesper; c/o Regeneron Pharmaceuticals, Inc., 777 A01K 67/027 (2006.01) Old Saw Mill River Road, Tarrytown, NY 10591 (US). (21) ECONOMIDES, Aris, N.; c/o Regeneron Pharmaceuti- International Application Number: PCT/US2017/044409 cals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591 (US). (22) International Filing Date: (74) Agent: SCHILLING, Stephen, H. et al.; Alston & Bird 28 July 2017 (28.07.2017) LLP, Bank of America Plaza, 101 South Tryon Street, Suite (25) Filing Language: English 4000, Charlotte, NC 28280-4000 (US). (26) Publication Language: English (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (30) Priority Data: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, 62/368,924 29 July 2016 (29.07.2016) US CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, (71) Applicant: REGENERON PHARMACEUTICALS, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, INC. [US/US]; 777 Old Saw Mill River Road, Tarrytown, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, NY 10591-6707 (US). KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (72) Inventors: HUNT, Charleen; c/o Regeneron Pharmaceu-OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, ticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 10591 (US). MASTAITIS, Jason; c/o Regeneron Pharma-TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. — ceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591 (US). GONG, Guochun; c/o Regeneron Phar- (84) Designated States (unless otherwise indicated, for every maceuticals, Inc., 777 Old Saw Mill River Road, Tarry- kind of regional protection available): ARIPO (BW, GH, = town, NY 10591 (US). LAI, Ka-Man Venus; 127 West GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, Main Street, Unit 201, Tarrytown, NY 10591 (US). GRO- UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, = = (54) Title: MICE COMPRISING MUTATIONS RESULTING IN EXPRESSION OF C-TRUNCATED FIBRILLIN-1 = = Sequence SEQ = = FibrillIn-1 Alleles (Nucleotide ID Amino Acid) NO Human WT ...GAGTGTAAGATCAATGGCTACCCCAAACGGGGCAGGAAACGGAGAAGCACAAACGAAACT,.. ...ECK I N G Y P K R G R K RR S T N E T... 9 10 = — = Human Variant • ...GAGTGTGATCAATGGCTACCCCAAACGGGGCAGGAAACGGAGAAGCAC.AAACGAAACTGA... 11 = ...ECDQWLPQ T G Q E T E K HK RN* 12 13 14 Mouse WT ...CAGTCTAAGATCAACGCCTACCCAAMCGAGGCCGGAPACGGAGAAGCACGAACGAAACG... — — — — -, G = = ...ECK I N YPK , P/G/RKRR/S T j j NE 7 ... Engineered Mouse Vanant GAGTGTGATCAATGGCTACCCCGGGGCAGGAAACGGAGAAGCACAAACGAAACTGA_ .,. CAAA 15 = _ = MAID 8502 TT HRN* 16 I _ = — MAID 8520 PPASSEMDDN SLS PEACYEC I KINGYPKAAQ SHLPATRPET EKHERNGCLR HPGRV 1 I i 17 Expected , I 1 i MAID 8502 PPASSEMDDN SLSPEACYEC:DQWLPQTGQE TEKHKRN ] 18 — 1-1 FIG. 3 iv 1-1 0 en (57) : Provided are non-human animals comprising a mutation in the Fbnl gene to model neonatal progeroid syndrome with el c:::: , congenital lipodystrophy (NPSCL). Also provided are methods of making such non-human animal models. The non-human animal -- --- GC models can be used for screening compounds for activity in inhibiting or reducing NPSCL or ameliorating NPSCL- like symptoms , 1 or screening compounds for activity potentially harmful in promoting or exacerbating NPSCL as well as to provide insights in to the 0 mechanism of NPSCL and potentially new therapeutic and diagnostic targets. N O [Continued on next page] WO 2018/023014 Al MIDEDIMOMOIDEIREIO I 0 101101 0111111MMHEMOVOIS TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, 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, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: — as to the identity of the inventor (Rule 4.170) — as to the applicant's entitlement to claim the priority of he earlier application (Rule 4.17(iii)) Published: — with international search report (Art. 21(3)) — with sequence listing part of description (Rule 5.2(a))