Patent AU-2011211408-A1 (AU)
Title: Compositions and methods comprising an EGFL7 antagonist for modulating vascular development
Inventor: ELLEN FILVAROFF
IPC: A61K31/7088
Filed: 2011-08-12
Abstract: The present invention provides methods of using EGFL7 antagonist to modulate vascular development. Also provided herein are methods of screening for modulators of EGFL7 activity. 5 Furthermore, methods of treatment using EGFL7 antagonists are provided. 2760259_1 (GHMauers) P62282.AU. I 29/07/11 a -I VT fLMW LYt'A-V" T-EHAYR R~RVC.AVRAHG- -- DPVSES 43 human I MQTMWGSGELLVAWFL'VLAADGT EHVYR SRR 9VTVGISG-- -GSISET 47 mouse i -MWKVSCLVTGYLLILAVTSAAA -HLYR GRlCSADGHPG-TVSVTQS 47 xenopus* 1 ---MYTALLLSSSLFLLHVTC-T QTHSH RRV6.VGDVWSRRVSYSTES1 46 zebraflsh 44 VOYQiFLT:TqIDGi tATYRTI yRT AY RRSPGLAPARPR'A-CCP.,WI92 human 48 V YQPiYLjTCDGH STYRT;I RTAV RSPGVTPARPR:A-CCP W9B mouse 48 V PHs IMTLEGH TYR T KVSY QVS-RKTSFPL S-CCP 95 xenopus . 47 FLQPVHKPYtMQNHMTYKTTRA NL PE .. zebrafish 93 6; R -S'. DC:S442 human 97 K TSGLPGA. G I PP S IRPGH' P D.T 146 mouse frB1GAQTHS ~ ~fG T4!Q SNK'p NALRT ~R'T-HVD-'lEK14zerfh 98 R: IGAQTHS* RLQ C. T SNKE PA _ I II )0E.S 145 xenopus* 97 R MH -S HN N, CEQS S VRPNH L R F 144 Zebrafish 143 ARRGGP IT IAY0CEHSL SA.GTL VP GPPRVAPNPT- - 191 human 147 TGEAS P: R IVGY G QSPSA GTR LS GPSPVAPNPTA 196 mouse 148 DGTHQ6S S' :FS ECL VVYRLMAUGKT RK APTVPPASPTSV 195 xenopus* 145 EQ-S L.F CE FSLDEK TS ASSRNTGGG- - - 192 zebraflsh 192 - - -@VDSAMK NVQRCQSRVD Ll@EKQLVL:A!L HSL9A SQA L ERG. --- L 233 human 197 - Q-VDSMARE'EVYRLIQARVDV-LiQXLQLVL AblHSLA SRS T EHG- --- L 238 mouse 196 E S I P H 8 V K EMAERKIDVL KLHLLLTPFQGL'T T F S P DD - A 240 xenopus* 193 - -LqLVE NV TEVQ I.{iKNRVE L L EQKiEMVIA PFT TtLL P L OGAGDT NS F L 238 zebraish 234 PD PGS LL V H $.F&QLGh ID L8b 4I 1 6F.LtQ L G S 92MSK K D S 273 human (SEQ ID NO:1) 239 QDPGSL AH.FQQLDRDYLS EQVSF.LE'HLGSCS~CiKK D L 278 mouse (SEQ IDNO:2) 241 ADPIAL!TR L QL.DIWllD S egl 1 FiEER L E TVSCK T E L 280 xenopus* (SEQIDNO:3) 239 SE R TNF L S. H,SL QQ DR'fE.LEVGFEER IGAGCQE N -27 zebraflsh (SEQIDNOA) b CGCGACA GTWAOCGM TGGCCGGG CTCOGCAAGG C&CACGTBA TAITAXTG C AGOASCTG ATTAACASCT -80 T&CAAG CAAACAACA CA&CCTCADT CTCTCTTTCT CTGTCAS&C &CACCTOASA A&CASACAGA CTGACAGAGA 1 AS_ 4 antisense oligo tr intron V TTAC&CAGC ATTCTBCTC TCCITCT T6TTTCTCCT OC&TTGACC TOB&CACCTG AGACTC&CAG ?C&TC&CBGG 81 YVTA L IL S !SSL rLL I K1V1 C TPO HS xHXG Forward PCR primer &GGASAS!G'I sTG TGTCTG CG&IGIG CTT&CASC&C CAMCIT CTTAGGCTG ThC&CAAAC 161 REI R lB V9RT9yS 1 EiV SB IP L QPIVx NP CTACATCACC AWU'GCCAA ACCACGGA GTGCASCACG TACA' RTM AACAGCACA GAAAA.C&T ACAAAA CC 241 T I T CQ Eti xRd c S? 7 ytxatop (Targeted intron) A halantisense oligo TACCATOCAC CATCAAC7CA CGTAWYG9C TGTTTTCAG GACCATCTAC AAB''CTT ASAM G CCACA 321 T I x T 8 y! 101V IRA 8CCTAATC TC&ATTTA CCABAATGC TOTCC T BGAAGOC&T GCATTC&CAC ACISCAACC &AGGG&TG 401 &PI f1 PIc c CPBaW R d R 51 HHSHNciCKO A VG Reverse PCR primer TBACAGTGT TGTBCA ACG GACTCG TGT AACGC MATCACTOTO CCTSTCTSG ASGAXGGCA BOCGATTCT 481 ES GANc VG G G S i c rIHC A C L RG Gi BRIG GCCMTAGA TGTBGACSAG TULAGGT CTCAGCACTG GTCTCA S TTTGMTA CGCTG6AS TTTTCAATGT 561 Q0I V ! DECRI zA QHxC SQ C V N LBS F0cC GTGGTGAS M-OATChe 2lIGG&CGM GATMWCA CAXGTTCAA AAACCYOC TCCTCACGG &CACTGG 641 VCE c BIa B L DE DIII SI xBP A SS3R N T OG ASG'PTIGGG TThGGGA AAGTTCTGA ABOTC&D &VCCYA AC GACCGG GCTCCTGOG C'SAACG 721 BIBL LIE I WVTS9 E 7C I Ll EV R E L LS3 CLIS A&TG0tG AAcCCTTC ACCaCCiCC TACCTC'WG TGOGGAGG CGACMG& 8CTTCTSTC TGAGCGAACC 801 t VL A PP 7TIL L P L B GAG DIE S IL S ERT AA.TCCTGT CCCACTCTCT G GCAGCTG GCCGCLYCG AMCGCICAG CGAACAGTC SCTTCCTGG A G 881 It TL S H 8L QCQL D RI E 9LS 10 L E QT rLI I I CGACGCCTT GOCTTChGG AAACTAGC GATCAACGCC ATCAC1 PGC ACAGGCTGAC CCA'CAAACA TTCTCAA&. 961 G A C G C Q E I Stop AACACGAGG AAATCTT GAAACTCTTT ATTTGGCACA GABCCGGTB ATOATTG TTCATGTC8T GTCATTAAC 1041 &TTGGAT GTTGASTCA GGAGAAATGT AAMTTAT T ATTTATAATT CCATGTTCTC TCATGASTT ATGCTTTTTB 1121 OAXAAGTTOC A7TCCTTTTT TACG!CTCAT TTTTGTAAT AAAACTGCTT AAATCTTAAA AAAAAAAAA AAAAAAAA 1201 AmA (SEQ ID NO:5)