18 1 1 2 2 7 1970 3 DNA 4 5 A REMICADE TM 6 6-506120 New York University, Centocor, Inc. 1 1 TNF a A2 TNF b TNF
HERCEPTIN TM HUMIRA TM Genentech G HERCEPTIN trastuzumab 1998 FDA HER2 HER2 7 HERCEPTIN HERCEPTIN A 2 8 HERCEPTIN Chiron C HER2 US6, 054, 561 561 C G 9 561 1984 10 C 2 11 561 CAFC 561 561 1984 561 C 561 I-2 U 80/02 HERCEPTIN Abbott Laboratories HUMIRA TM Adalimumab 3861118 Abbott Laboratories 2006.10.6 HUMIRA 12 HUMIRA 3861118 1 F ab2 1 2 SEQ ID No: 1
LCVR SEQ ID No:2 HCVR 1 Fab Fd 1 HERCEPTIN HUMIRA 1ISIS Pharmaceuticals, Inc. 13 Vitravene DNA mrna mrna 2 Vitravene CMV d P- thio GCGTTTGCTCTTCTTCTTGCGdeoxyribonucleic acid eicosasodium salt CMV IE2 3 Vitravene Vitravene 1 Vitravene FDA, Orange book 4 US5, 264, 423, US5, 276, 019, US5, 442, 049, US5, 595, 978 14 2 Vitravene 2708960 3 8 14 2 8 16 PCT/US91/05815 1 IE1 IE2 DNA RNA DNA 9GGA CCG GGA CCA CCG TCG TC CGC AAG AAG AAG AGC AAA CGC 15 DNA RNA RNA 13CTG TCA AGT GGC ACC ATA CG GCG TTT GCT CTT CTT CTT GCG ACT CGG GCT GCC ACT TGA CAG DNA mrna RNA 3 CMVs IE1 IE2 DNA
CMVs CMVs CMV 1 DNA mrna AUG 608 697 1109 1159 CMV 13GGA CCG GGA CCA CCG TCG TC CGC AAG AAG AAG AGC AAA CGC DNA RNA mrna 17CTG TCA AGT GGC ACC ATA CG GCG TTT GCT CTT CTT CTT GCG ACT CGG GCT GCC ACT TGA CAG DNA mrna RNA 4 1 12 13 13 17 DNA CMV 1 5 11 2708960 2708960 1GGA CCG GGA CCA CCG TCG TC CGC AAG AAG AAG AGC AAA CGC 16 12 5 CTG TCA AGT GGC ACC ATA CG GCG TTT GCT CTT CTT CTT GCG ACT CGG GCT GCC ACT TGA CAG 17 11 ID 22 GCG TTT GCT CTT CTT CTT GCG 5 1 21 22 24 1 1 5 27
EP0544713B1 18 1 1 5 36 6 1 19 2006 RNA RNA interferencernai Andrew Z. Fire Craig C. Mello RNAi 8 DNA PCR RNAi mrna DNA RNAi RNAi RNAi RNAi RNAi RNAi mrna RNA dsrna mrna 1:1 dsrna RNase Dicer sirna small interfering RNA 21 23mer dsrna sirna RISC RNA-induced silencing complex mrna Fire 1998 C. elegans RNAi RNA Fire RNAi RNAi Fire
dsrna 2001 Max Plank Tuschl 21mer dsrna RNAi sirna RNAi 21 23mer dsrna sirna Tuschl sirna Fire RNAi sirna RNAi Fire RNAi 17 http:// www.jpo.go.jp/shiryou/index.htm RNAi PCT 1998 2003 1,280 56 2 8.6 3 6.6 2000 RNAi 18 4 14 5 3 22 Fire RNA US60/068, 562 US09/215, 257 1998 12 21 PCT/US98/27233 US6506559B1 2000 2003 1 10 2006 4 11 Fire 2000-525538 Fire 1 RNA RNA 10 50 1 22a b RNA RNA c RNA 37 1 21 29 1 29 1 US6506559B1 1 in vitro 10 RNA 50 1 RNA 50 25 RNA
Tuschl 2 1 2001 3 30 PCT PCT/US01/10188 2002 2001-573036 Tuschl PCT PCT 3 US06/193, 594, US06/265, 232, EP00126325.0US09/821, 832 1 2001 11 29 PCT PCT/EP2001/0139682003 2004 8 12 2006 5 23 2002-546670Tuschl Tuschl 1 RNA RNA 19 25 RNA RNA 13 1 12 1 RNA a 19 25 2 RNA RNA RNA b RNA RNA RNA 27 1 12 1 1 RNA 29 2 36 4 6 1 2 24 25 RNA RNA RNA 21 22 1 2 4 3 RNA RNA 26 28 RNA 19 23 26 28 Tuschl PCT RNA 13 2006 7 18 Tuschl Fire RNA 50 25 Tuschl 21 23 19 23 Fire Tuschl Fire RNA Tuschl Fire 29 1 in vitro RNAi RNAi
RNAi RNAi RNA RNAi in vitro 20 RNA NCBI 21 MeSH RNA sirna pegaptanib 22 SELEX 23 SELEX WO91/19813 24 USP5270163 2763958EP0786469B1 SELEX L.GOLD 25 SELEX USP5475096, 5670637 26 27 SELEX SELEX SELEX 2011 SELEX 28 PEG PEG ENZON 29 PEG USP5959455 30 PEG Macugen Eyetech OSI AMD 31 2005 1 Eyetech Macugen 2008 VEGF RNA 32 USP6426335
PEG 33 6 Eyetech 34 Eyetech 35 SELEX 36 SELEX Archemics 2001 exclusive lisence 37 Archemics 38 SELEX 39 40 16 2004 50 2000 1980 41 42 43 EMEA 2006 44 2006 4 Omnitrope 45 46 FDA FDA FDA FDA 2006 5 47 Federal Food, Drug and Cosmetic Act, FDCAPublic Health Service Act, PHSA 48 FDCA 49 PHSA FDCA FDA PHSA 50
FDA 51 52 53 54 DNA EPOGEN Amgen Amgen granulocyte-colony stimulating factor; G-CSF G-CSF 174 18kDa 180 20kDa 2 G-CSF Amgen Filgrastim Neupogen E.coli 175 r-methug-csf 18.8 kd E.coli N E.coli G-CSF 55 1991 2 20 FDA FDA BLA103353 4810643 Production of pluripotent G-CSF 5104651 Stabilized hydrophobic protein formulations of G-CSF 1856517 DNA1729335 2527365 2888969 56 Amgen 1 11 peg-filgrastim Neulasta 2002 1 31 FDA BLA125031 57 5824778 Chemically-modified G-CSF 06-517294 2003-3337612005-
333253 2005-333254 Amgen 1992 1 Amgen G- CSF 1992 5 Kirin-Amgen 2002 5 Amgen EU Roche Roche 2003 8 Genentech 4704362 5221619 5583013 Amgen CAFC01-1098 Amgen Genentech 2005 35 Amgen 2005 Annual Report Amgen Lenograstim Neutrogin - Aventis Granocyte CHO 174 r-hug-csf 20 kd N 58 1616202 G-CSF 2116515 1708537 1991 1994 1999 1 7 2002 1 2005 12 323 Annual Report 2005 G- CSF EPO 2576200 CHO 2005 12 19.2.27 18 10038 1710732 E.coli 175 19 kd Nartograstim NoiupE.coli N N 5 59 2129167 G-CSF 2673099 2517100 5 1994 4 1 2006 3 46 Annual Report G-CSF
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US5, 442, 049 US5, 595, 978 US5, 442, 049 1 22 GCG TTT GCT CTT CTT CTT GCG US5, 595, 978 1 CMV 1 GCG TTT GCT CTT CTT CTT GCG CMV US5, 595, 978 4 1 GCG TTT GCT CTT CTT CTT GCG Vetravene 21 22 24 21 22 27 EP0544713B1 1 DNA RNA RNA IE1 IE2 DNA RNA DNA GGA CCG GGA CCA CCG TCG TC CGC AAG AAG AAG AGC AAA CGC 2 1 GCG TTT GCT CTT CTT CTT GCG 22 I 1 2.2.1.1 36 6 1 3 L.Gold SELEX DNA RNA RNA RNA http://www.ncbi.nlm.nih.gov VEGF PEG Systematic Evolution of Ligands by Exponential enrichment Gold Larry, Tuerk Craig 1991 6 10 USP5660985 5 2 SELEXUSP563459 SELEXUSP5567588 SELEX SELEX WO91/19813 WO91/19813 SELEX 69 35USC271 e http://www.enzon.com/techonology/peg/peg.htm 3626494 2014 age-related macular degeneration: AMD VEGF WO98/18480 3626503 Orange Book FDA 6 USP5959455 Enzon USP5932462 ShearwaterPolymerUSP6011020 USP6 113906USP6147204 USP6426335 assignee SELEX GOLD
http://www.gilead.com 3463098 HIV-1 HIV-2 Tat 3612551 C NS3 3655550 Raf-1 SELEX BioCentury, THE BERNSTEIN REPORT ON BioBusiness January 22, 2007 Ribomic http://ribomic.com Archemic 3677510 18 1 24 generic name 2004 7 68 80 2006.4.24 biosimilar similar biologics follow-on biologics http://www.emea.europa.eu/htms/human/ humanguidelines/multidiscipline.htm http://www.emea.europa.eu/humandocs/humans/ EPAR/omnitrope/omnitrope.htm. 2003 Nutropin Genotropin http://www.fda.gov/cder/drug/infopage/somatropin/ default.htm. PHSA PHSA FDCA NDA505 b1 ANDA505 j NDA505 b2 ANDA NDA 1 NDA 2007 2 14 Henry Waxman PHSA H.R.1038 EMEA G-CSF biosimilar generic 17 http://www.neupogen.com/ https://www.jpo.go.jp/shiryou/s_sonota/map/ kagaku11/2/2-10-3.htm http://www.neulasta.com http://www.chugai-pharm.co.jp/hc/di/scholar/item/ drug_data/neu/if/neu_if.pdf http://www.nihs.go.jp/dbcb/biologics_forum/ Bioforum-3/3-Kuwabara.pdf 2007.6.18