Antigen Binding Proteins to Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9)

摘要

Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an 5 antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described. WO 2009/026558 PCT/US2008/074097 1-----------------------------------------------50 PCSK9parent (1) OZUNUGOYEiMIIAj '5EdGLAAP$1k5G5A~'iFRIKdPWESPG3YVV PCSK9mutants (1) R _1iRRRR RR FiliRdl lPWfi PdlYVV 51--- pro domain ------------------------------ 100 PCSK9parent (51) VNIIiIT LN NiTKII~if9FINGLLPGFLVf§fd PCSK9mutants (51) V-'Lj lKS! S TgF LKlIAil E-li TKIIAlFiGLLPGFLMEliF L 101-------------------=======50 PCSK9parent (101) ILELAILf LMNiUdYIEEDSSVFISIFINIlEItIPPRYRAf0EidPidGGI4V PCSK9mutants (101) EIL L YEI 1 IlPPRYR lIPIGGV 151================================ -------=== 200 PCSK9parent (151) E EAS CDSI-GTHL PCSK9mutants (151) EVYLLD'II|RRRH|EEEIDGRVRRRERRRERRRRRRERRR CDRqGTHL 201===---=============---=----------= = -====250 PCSK9parent (201) AGVVSG fAGVAINgfMRSI NVLNdGNGtVSGTLIGLEINI!NZ5~QvdB~9 PCSK9mutants (201) AGVVSGFPAGVA lidNlMRSlVLNClG1GlVSGTLIGLElR S P 251================= catalytic domain =========300 PCSK9parent (251) 7PLVVLLPLAGYSIVLtACQ RLIN GVVLVTAAGNF1 DDAC YSPA2A PCSK9mutants (251) 'PLVVLLPLAdlYSEVL lAdARLAEGVVLVTAAGNEEDDACRYSPARA 301============================================------350 PCSK9parent (301) PEVITVGATNQDQP TIGTI4GTNFGRCVDLFAPGEdIIGAS8CSC5' PCSK9mut ants (301) PEVI TVGA TNIRNRP(PMiiliGPGTNFGRCVDLFAPGl 9I I GAS$1 CSI Cli 351-= = = = = = = = = = == = = = = = = = = = = 400 PCSK9parent (351) 5 GSAAVGAIMjA5ILiAIL~ SK9IEEF PCSK9mutants (351) |PSGTAHAI I 401===------------------------------------------450 PCSK9parent (401) INININTPI LVA LPP5TN SG LFCRTVWSS WSRIbAl CAB PCSK9mutants (401) '__RRTALVALPPRRRRRRLFCRTWIS RRRECB 451--------------------------------------------500 PCSK9parent (451) EELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGP2GVYAIARCCLLP PCSK9mutants (451) EELLSCSSFSRSGKRRGERMERQGGKLVCRAHNR9GRCGVYAIARCCLLP 501-------------- v domain ------------------------ 550 PCSK9parent (501) QANCSVHdAPPZEAIN GTI-iViSfdQHQ GHVLTGCSSHVEfldG'IKPPIMLR PCSK9mutants (501) QACSViiAPPA lIiGII Cl liGHVLTGCSSHailIlGi KPFliLR 551---------------------------------------------------600 PCSK9parent (551) PINGdNQCVGHREASIHASCCHAPGLECkVKEIIPAVQEidVTPfCIZGW PCSK9mutants (551) PFIPlQCVGHREASIHASCCHAPGLEC(RRR IPAi ElVT/lCfGW 601--------------------------------------------650 PCSK9parent (601) TLTGCSALPGTSHVLGAYAIMDNTCVVR$NDVSTTGSTSEIEAVTAVAICCN PCSK9mutants (601) TLTGCSALPGTSHVLGAYAliDNTCVVRD ER _ V A 651 --------- 680 PCSK9parent (651) SPHLAQASQELQGSSDYKDDDKHHHHHHHH (SEQ ID NO:303) PCSK9mutants (651) S&HLAQASQELQGSSDYKDDDKHHHHHHHH (SEQ ID NO:304)