aAbacavir 59, 82ABCA1 58ABCB1 54, 58Abciximab 21, 462, 1086, 1117, 1153– half-life in plasma 1167Abscisic acid, responsive element 980Absorption enhancer 1464– efficacy 1465N-Acetylglucosamine (GlcNAc) 679, 764, 849,

938N-Acetylglycosaminyl transferase 924N-Acetylmannosamine 1047N-Acetylmuramic acid 938N-Acetylneuramic acid 811, 1047N-Acetylneuraminic acid 772Acetylphosphate 1075Acetylcysteine– in drug delivery 1375Acinar formation assay 643Acinetobacter calcoaceticus 706Acquired immuno deficiency syndrome, see AIDSAcromegaly 15Actilyse 461Actimmune 17, 467Actinorhodin 1807– structure 1814Activacin 461Activase 11, 461, 726Activase-rtPA 746Activated clotting time 1012Activated partial thromboblastine time (aPTT)

198Activated protein C 457Activator protein-1 236Actrapid 13, 470Acute lymphoblastic leukemia, see ALLAcute lymphocytic leukemia, see ALL

Acute lymphoid leukemia, see ALLAcute myelogenous leukemia (AML) 502– radioimmunotherapy of 505– antibody treatment for 1121Ad5FGF-4 (Adenovirus 5 fibroblast growth

factor-4)– analytical assay 161– analytical techniques for 164– clinical study 175– dose-response 174– genome structure 157– production 158– toxicology study 174Ad5FGF-4 (Adenovirus 5 fibroblast growth

factor-4) vector– isolation of 156– production 156Ad5LacZ 172Adagen 475, 1399, 1401, 1411Adalimumab 22, 455, 1086, 1118, 1150, 1156,

1163Adeno-associated viral vector (AAV) 317Adenosine deaminase (ADA) 429– deficiency 1401Adenovirus plasmid 156Adenovirus serotype 5 (Ad5) 155Adjuvants 1423– for human vaccination 1425– mode of action 1424– ADMET (absorption, distribution, metabolism,

excretion and toxicity) 1604, 1773– assessment 1604, 1628– basic principles 1786– models 1786– prediction system 1785– prediction tools 1796– profiling 1785

1841

Subject Index

Modern Biopharmaceuticals. Edited by J. KnäbleinCopyright © 2005 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimISBN: 3-527-31184-X

– properties 1775– value of prediction 1798Adenosine triphosphate (ATP)– regeneration system 1074ADR (adverse drug reactions) 76Adult respiratory distress syndrome 1009Advaferon 467Advate 421, 459Adverse drug reaction 51Aequorea victoria 1628AERx-dornase alfa 475Affinity chromatography– characterization of antibodies by 797Aflatoxin B1– CYP3A4 activated 1586AFP 482Agalsidase alpha 475Agalsidase beta 475Agarose 1380AGENT (angiogenetic GENe therapy) trial 175– safety 177AGENT 2 trial 176– safety 177Age-related macular degeneration 1280Agrobacterium tumefaciens 903, 950AIDS (acquired immuno deficiency syndrome)

14– gene therapy 549– vaccine 1164Airway hyper responsiveness 234Akanthamoeba castellanii 685Aktraphane 13Alamar blue dye metabolism 168Albuterol 59Aldurazyme 24, 475Alefacept 455Alemtuzumab 22, 455, 479, 1086, 1156Alfaferone 467Alfatronol 17, 468, 480Alferon LDO 467Alferon N 467Alglucerase 475Alkaline phosphatase 712– secreted 731ALL (acute lymphoid leukemia) 76, 202– murine model 203Alosetron 52Alpha-1 464Alpha-1 antitrypsin 463– from transgenic system 858Alpha-defensin 383Alphaferon 467–468, 480Alpha-fetoprotein 862

Alpha-glucosidase 861Alpha-iduronidase 862AlphaNine SD 459Alphaparin 457Alpha-synuclein 329Altemol 467Alteplase 11, 461Alternating tangential filtration 1087Alzheimer disease (AD) 77, 1781– targeting 1286– pathways and targets for 625– epidemiology 326Amantadin 330AMAXA system 632Ambirix 19Ames false negatives 1625Ames false positives 1625Ames II 1527, 1633Ames test 1632Amevive 454–455, 1119Amiloride 1525Amino acid depletion– with glutaDON 537Aminoacyl-tRNA synthetase 1068Amino-3,8-dimethylimidazoquinoxaline 1634Amino-hydroxybenzoic acid 1823(2-Amino)isobutyric acid 413Aminolevulinic acids 1617(3-Aminomethyl)benzenesulfonylglycine 407–

408Amino-3-methyl-imidazoquinoline 1634Aminopeptidase 13792-O-Aminopropyl oligoribonucleotide 261Amiodarone– clearance of 1594– CYP2C9 inhibitor 1590Amitriptyline– CYP3A4 activated 1586Ammonium tartrate 922Amoxibeta T1000 1352Amoxicillin 1352Amphotericin B 1370Ampicillin 610– resistant plasmids 1024Amyloid precursor protein (APP) 1782– processing scheme of 1783Amyloidosis 1286Anact C 454, 457ANAFP (a novel antifungal peptide) 483Anakinra 17, 464, 1118Analytical assay validation– regulations 1650Analytical methods

Subject Index1842

– in quality control 1557– in vivo 1572– specifications for drug substances

and products 1561– validation 1567Analytical protein A chromatography (APAC)– characterization of antibodies by 797Angelmann syndrome (AS) 219Anger position network 1221Angioblasts– for angiogenesis 319Angiogenesis 1235– markers of 1281– non-tumor 1280– related disease 1278Angioedema, hereditary 859Angiogenetic switch 1279Angiogenic GENe therapy, see AGENTAngiomax 461Angiostatin 381Angiotensin-converting enzyme (ACE) 78, 317Angiox 461Animal models– selection 1658Animal rule 1662Animal, transgenic 29– biopharmaceuticals from 833, 995Anion-exchange HPLC 164Anistreolase 461Annexin 5 detection assay 644Annexin A1 1281Annexin V 1262– for SPECT studies 1263ANP, see atrial natriuretic peptideAntegren 1122Anthracycline 139Anthrax 1489– toxine 1166Antibiotic resistance gene 299Antibody 454– against infectious disease 1175– anti-neutrophil cytoplasmic 1195– anti nuclear 1190– binding haptens, peptides or proteins 1154– binding site 1163– bispecific 1174– categories 1150– chimeric 7, 1109, 1153– class determination 1107– combining site 1190– complexes of 1155– different fragments and formats 1274– epitope 1190

– epitope/paratope interaction 1108– fully human 1111, 1113, 1157– half-lives of therapeutic 1166– humanized 1153– immunogenic 1150– in disease targeting 1273– isotope conjugates 1174– libraries 1157– linking of phenotype and genotype in selection

systems 1161– marker for autoimmune disease 1189– murine 1156– naked 1169– on the market 1151– pharmacological characteristics of 1114– protective function of 1166– polyclonal 1109– radiotracer 1258– screening technologies 1160– single chain 1115– single domain 1115– synthetic 1176Antibody-antigen interaction 1190Antibody-dependent cellular cytotoxicity 733,

1274Antibody-directed enzyme prodrug therapy

(ADEPT) 1277Antibody fragments 1113– manufacture in microbial systems 1088– pharmacokinetics of 1116Antibody library technology 1163Antibody response 1199, 1500Antibody technology 1147Antibody, therapeutic– productivity advantages 1726Anticoagulants 454Antide structure 1408Antiepileptic drugs 58Antigen-nanoparticle conjugate 1310Antigen-presenting cell 191, 360Antihemolytic factor VIII, see fVIIIAntihemophilia agents 454Antinuclear autoantibodies, mononuclear 1371Antiperinuclear factor 1192Antisense RNA– for gene silencing 633– plasmid-borne 671Antisense technology 31Antithrombic agents 460Antithrombin (AT) 29, 995– anti-inflammatory activity 1009– hereditary deficiency 997, 1014– human 1001

Subject Index 1843

– recombinant production of 998– serpin 996– vector construction 999Antithrombin III 458, 996– human 855Antithrombin transgene 999Anti-thymocyteglobulin 456Antitrypsin 463–464, 858Anti-tumor agent 474Antiviral agents– RNA-based 570Antril 464, 1117AP 486AP-1 233Apcitide 1283APEX 84Apidaecins 486Apidra 13, 469Aplysia kurodai 482Apolipoprotein E (APOE)– locus 78– satin system 78Apoptosis 644– delaying 819– imaging 1238, 1262, 1284Aprepitant 1538AproliZean 903– Apronexin NP 854Aprotinin 904, 1470, 1472– from transgenic system 854– variants 1027Aptamers 635Arabidobsis thaliana 869, 921, 950, 973Aralast 463Aralia elata 482Aranesp 8, 472Arcitumomab 21Ardeparin sodium 458Area under the curve (AUC) 438Argatroban 413Argonaute protein family 222Argoproteins 245Arixtra 457ARMS 84Aroclor 1254, 1626ARPE-19 168Array-on technology 88Arterial re-stenosis 313Arthrobacter globiformis 977Arthrobacter panescens 977Artificial neural network 1789– for CNS activity prediction 1794– topology of three-layer 1790

Ascorbate peroxidase 977– ROS scavenger 979Asialoglycoprotein 716, 1512Asialoorosomucoid 1512Asparaginase, PEGylated 543Aspergillus giganteus 482Aspergillus terrus 1804Astemizole 52Atenativ 458, 1006Atherosclerosis 313– targeting 1281Atomoxetine 57, 61, 64– label recommendation 56Atorvastatin 58Atrial natriuretic peptide (ANP) 290Atrioventricular block 298Atriplex gmelini 974ATryn 29, 855, 995– clinical studies 1011Auerbach plexus 327Auger electron emitter 500– targeted radiotherapy with antibodies 524Auger electron radiotherapy– antitumor effects 519– gene-targeted 525– In-DTPA-D-Phe-octreotide 519Auristatin derivatives– cytotoxic 1172Autoantibody– antinuclear, mononuclear 1371– pathogenic 1188– responses 1187Autoantibody-autoantigen complexes– characterization of 1199Autographa californica– nuclear polyhedrosis virus 1046Autoimmune disease 1187Autoimmune encephalomyelitis (EAE) 1200Autologous stem cell 500Auxotrophic marker 766Available chemical directory (ACD) 1790Avakine 456Avastin 143, 454–455, 479, 1121, 1169Average internal stability profile 250Avidin from transgenic systems 852Aviptadil 1742– dosage 1748– effects 1748– in PAH 1743– increase in CRE binding 1746– pharmacology 1744– release 1748– secretion enhancement 1748

Subject Index1844

Avonex 17, 467, 14045-Azacytidine 3205-Aza-2-deoxycytidine 294

bBaby hamster kidney cell line (BHK) 762BACE (beta-amyloid converting enzyme) 1773– complex 1784– inhibitor 1781Bacillus subtilis 1823Bacillus thuringiensis toxin 898Bacitracin 1472BacPac rapid titer kit 1046Bacterial activator 381Bacterial artificial chromosome (BAC) 656Bacteriophages– therapeutic use 1751Bac-to-Bac 1046Bactosomes 1613, 1618Bactotryptone 681BaculoDirect 615, 1046Baculosomes 1613Baculovirus transgenic 1046Baculovirus expression vector system

(BEVS) 1045BacVector-3000 105Balke protocol 175Basic local alignment search tool, see BLASTBasiliximab 21, 456, 1086BAY-14-2222 459Baycol 52BayerHealthCare pharma biotechnology 1021Bayovac CSF E2 26BC1 217BC200 217BCMS 220B-cell chronic lymphocytic leukemia 222–223B-cell epitopes 1119B-cell neoplasia-associated gene with multiple

splicing 216Bcl-2 317– antiapoptotic properties 819– Becaplermin 465Beckwith-Widemann syndrome (BWS) 219Benefix 10, 459p-Benzamidine 699Benzobromarone– CYP2C9 inhibitor 1590Benzonase 158Benzotriazoyl carbonate 13987-Benzyloxy-4-trifluoromethylcoumarin

(BFC) 1610Bergmann reaction 1125

Beromun 23, 463, 479Beta-cyclodextrin 407Betaferon 4, 17, 467Beta-glucocerebrosidase 861Beta-grasp motif 383Betaine aldehyde dehydrogenase 976Betaine synthesis 977Betaseron 17, 467, 1404Beta-tryptase 405– diketopiperazine-based bibasic inhibitors of

412– inhibition by cyclodextrin-based inhibitors

408– inhibition by PEG-linked inhibitors 406Bevacisumab 143, 455, 479– effect by blocking a growth factor 1169– cancer treatment 1280Bexxar 454–455, 479, 501, 1086, 1121, 1169– application 1278Bioassay– cell culture-based 1565– quality characterization of biopharmaceuticals

1565Bioclate 10, 454, 459Bioequivalence 1756Biogamma 467, 479Biogenerics 1662, 1728, 1756– EU regulations 1700– market 1722Bioinformatics 255, 1771Bioleukin 464, 479Biological products regulations 1686Biologics license application (BLA) 1126, 1638Bioluminescence applications 1224Biomarker– exploratory 58– DNA-based 57– genomic 56– pharmacogenomic 59Biomarker patterns software 1332, 1336Biomek 1332BioMEMS 1542Bionanotechnology 1537Biopharmaceutical advantages 1725Biopharmaceutical approval– for post-translational modification 7– for veterinary use 25– of proteine engineered products 6– PEGylated 1412– products for human use 9Biopharmaceutical development– good manufacturing practice (GMP) 1661– regulations 1689

Subject Index 1845

– US federal laws for 1640Biopharmaceutical drugs 453– approval system in EU 1684– BLA/NDA stage 1644– classes of 1560– design of novel 1775– development of 1090– EU regulations 1669– half life of 1363– handling 1570– IND stage 1643– innovate around existing 1730– innovative approaches 1732– marketing of 1736– PEGylated and kinetic parameters 1403– post-approval 1644– prescription 1736– price increase 1715– protect exclusivity of 1730– radiolabeling 1251– registration and marketing 1697– scheme of pharmacokinetics 1365– withdrawals from market 1604Biopharmaceutical manufacturing– common errors in 1659– inspectional authorities 1653– process validation 1653– virus safety 1650Biopharmaceutical production– from cereal grains 931– in culture plant cells 949– in the desert 967– new cell lines 761– using insect cell culture 1045– using transgenic animals 995– using yeast 1033Biopharmaceutical proteins– manufacture of recombinant 723– PER.C6 779Biopharmaceuticals– definition 2– first generation 1759– follow-on market 1729– generic threat for 1729– global sales 1759– veterinary 25Bioreactor– adherent-cell culture in 739– annual output using 10� fed-batch 1092– annual output using 10� perfusion 1091– batch perfusion 741– continuously perfused production 743– extended-batch perfusion 741

– fed-batch 824– hollow-fibre 738– large-scale transient expression 744– moss 919– perfusion 1050– photo 922– preparation of drug metabolites 1622– stirred-tank 739, 1050Bioreactor process– development efforts 750– regulatory issues 745– risc of bacterial contamination 746– risc of viral contamination 747– scale-up 740Bioseb 1087Biosensors 1544Biosimilar medicinal product guidelines 1707Biostim 463Biotech– development 1654– procedure 1683– products registered in EU 1675Biotechnological products– EU adopted guidelines 1705Biotechnology quality working party

(BWP) 1670BioTropin 14, 476Biphasic human insulin 469Biphasic insulin aspart 470Biphasic insulin lispro 469Biphasic porcine insulin 471Bispecific T cell engager 1175BiSphere 1305BiSteel 871Bitistatin 1283Bivalent ligand binding 396Bivalrudin 461BLAST (basic local alignment search tool) 105,

108, 255BlastX analysis 108Blasticidin 666Blasticidin deaminase 766– marker 767Bleeding episodes treatment 441Blood-brain-barrier 1771, 1783, 1791, 1795B-lymphocyte stimulator 505BM185 cell 204Bombesins 486Bombinins 486Bone marrow transplant (BMT) 1757Bone morphogenic protein (BMP) 294Bongard problem 1773Boost Plus 1454

Subject Index1846

Boroleucine 1472Botulinum type A toxin 463Bovine herpes virus (BHV) 27Bovine serum albumin (BSA) 269, 957Bovine somatotropin 25Bovine spongiform encephalopathy (BSE) 747,

1007Bovine viral diarrhea virus (BVDV) 434Boyden chamber assay 643BR96– in cancer treatment 1172Bradykinins 486Bradyphrenia 328Brain capillary endothelium 1517Brain-derived neurotrophic factor (BDNF) 77Brambell receptor 1167Brassica juncea 977Brassica napus 973, 977Bravelle 464Breast cancer 143, 239– EGFR-positive 524– ER-positive 524Breast Cancer International Research Group

(BCIRG) 144Boehringer Ingelheim high expression system/

chinese hamster ovary cell 1094Bromfenac 52Bromodeoxyuridine (BrdU) 641, 12616-Bromoindirubin-3-oxime 288Brutons tyrosine kinase variant (BTK) 1053BSE see Bovine spongiform encephalopathyB-type polymerase– structural features of 710Buerger’s disease 307Bullous pemphigoid 1193Bundesinstitut für Arzneimittel und Medizin-

produkte 1679Bupropion, hydroxylation 1618Burkitt’s lymphoma cell 1029Butyrophilin 1205Butyrylcholinesterase 870Buzerelin 1376BYK150640 chemical structure 410BYK76935 chemical structure 410Bypass graft failure 313

cC1I-Immuno 859cA2 456CABG (coronary artery bypass grafting) 154,

237, 312Caenorhabditis elegans 571Caffeine

– CYP3A4 activated 1587Calcitonin 1376, 1467Calcium concentration-time profiles in plasma

1468Calf intestinal alkaline phosphatase, see cIAPCalichemicin 1125Calmette-guerin vaccine 1430Calnexin 420, 427Calogen 477Calreticulin 420, 427, 1435Campath 22, 455, 479, 811, 1086cAMP (cyclic adenosine monophosphate)

318Camptothecin 1367Cancer 238– therapy 127, 1243, 1276– cells, in folate receptor-mediated gene transfer

1515– vaccine 864Cancer research UK pharmacokinetic and

pharmacodynamic technologies advisorycommittee 1250

Candida albicans 1285, 1435Canferon A 468, 480Capan-1 1319Capecitabine 1252Capillary zone electrophoresis (CZE) 162Capsella bursa pastoris 486CAPSIT protocol 347Carbamazepine– clearance of 1594– CYP3A4 activated 1587Carbon nanotubes 1548Carboplatin 131Carbopol 1380Carboxyfluorescein 1467, 1480Carcinoembryonic antigen 1123, 1234, 1277Cardiac specific proteins 290Cardiac transcription factors 290, 293Cardiac troponin 293Cardiomyocytes 289, 320– clinical applications of hES derived 293– differentiation system 293– enrichment and purification 298– hES cell derived 292Cardiopulmonary bypass– trials with rhAT 1011Cardiovascular disease 305– pathways and targets for 625– targeting 1281CaroRx 865Caruleins 486CASE 1624

Subject Index 1847

Casein 998– peptone 681Caspase activation assay 644Catechol-O-methyltransferase 330Catharanthus roseus 950Cathelicidins 1433Cathepsin B 1282Cathepsin B2 1285Cathflo Activase 461Cationic liposomes 1510Cationic antimicrobial peptides 1419– artificial 1433– as vaccine adjuvants 1433– subgroups 1433Cationic peptides– delivery system 1419, 1437– vaccine adjuvant 1426CATS descriptors 1797CB03 769CD105 1281CD20 1278CD25 20Cdc13 43Cdc13p 40CEA-scan 21C/EBP 233Celeuk 463, 479Cell concentration– maximum 816– viable 816Cell cycle– manipulation of 820– mutants 822Cell engineering 819Cell free reaction– pH 1073Cell graft 295Cell line– generation 727– generation timeless 788– regulations for qualification 1645– stability 818Cell migration 642Cell (specific) perfusion rate (CSPR) 794Cell proliferation 821Cell retention device 1087CellBag– cultivation of Sf-9 cells in 1056Cellferon 467Cellular lactate dehydrogenase 1427Cellular transformation 642Celmoleukin 463, 479Centaxarin 458

Center for drug evaluation and research(CDER) 49, 1765

Center for food safety and applied nutrition(CFSAN) 1639

Center for veterinary medicine (CVM) 1639Center of biologics evaluation and research

(CBER) 1639Center of devices and radiological health

(CDRH) 1639Center of disease control 1752CenTNF 456CentoRx 462Centoxin 455, 1117Central nervous system 1791– active drugs 1794Centuximab 455Ceprotin 454, 457CeramTec 681Ceredase 475, 862Cerezyme 8, 23, 475, 862Cerius 1610Cerivastatin 52Certification of suitability 1680Certoparin sodium 457Cetrolix 476Cetrotide 476Cetuximab 479, 1121cGMP (current good manufacturing practice)

749, 949, 1126, 1641, 1654, 1661Chaperones 1072, 1074Cheloidonium maius 482Chemical exchange-dependent saturation

transfer 1217Chemistry manufacturing and control

(CMC) 1126Chemotherapy 1272Chimeric antibody 7, 1109, 1153Chimeric mice 657Chitin 1374Chitosan 1374, 1380– solution 1378Chlamydomonas reinhardtii 898Chloramphenicol acetyl transferase (CAT) 1075,

1532Chloronema cell 9204-(4-Chlorophenyl)imidazole– CYP2B4 inhibitor 1597Chloroxozone hydroxylation 1618CHO (Chinese hamster ovary cell) 433– cell line 762– quality control 435Cholesteryl ester transfer protein (CETB) 78Cholesterylhemisuccinate 1523

Subject Index1848

Choline dehydrogenase 977Choline monooxygenase 976Choline oxidase 977Choriogonadotropin alfa 477Chromatographic assay 164Chromatographic methods– for analytical properties of biopharmaceutical

material 1562Chromogenic ISH (CISH) 134Chromogenics kit 1006Chronic disease era 103Chronic myeloid leukemia treatment 506Chronic myocardial ischemia 151Chronic obstructive pulmonary disease 1344– IMS chromatogram 1351Chrysamine G 1287Chrysanthemum morifolium 894Chymotrypsin, inhibition by aprotinin 1027Cialic acid 772cIAP (calf intestinal alkaline phosphatase) 714– expressibility of, in E. coli 714– variance of 7143,4,5-Cimethylthiazol-2yl-2,5-diphenyl tetrazolium

bromide, see MTTCimetidine– CYP2C9 inhibitor 1590Ciphergen biomarker 1338CiphergenExpress 1332Circular dichroism– conformation of hAT analyzed by 1004– insulin proteolysis investigated by 1474Circulins 484Cisapride 52, 1605Cisplatin 131, 136, 1250Citrullinated peptide antibodies, anti cyclic 1189Cleactor 461Clean in place (CIP) 746Clexane 457Clinical trial assay (CRA) 133Clinical trial authorization application

(CTA) 1697Clinical trial protocol (CTP) 1697Clivarine 457, 1750Cloning– reproductive 365– therapeutic 365ClustalW algorithm 110CMPD 220c-Myc 42Coagulation 377– factors 379Coagulation factor IXa, see fIXaCode of federal regulations (CFR) 1641

Coded spheres 84Codeine 57– metabolized by CYP3A4 1585Codon– adaptation index 1023– usage, of IL-4v gene 1024Cognate factor VIII 743Collagen 872– matrix assay 643– induced arthritis 235Collimator types 1220Colony-stimulating factor (CSF) 466Combinatorial chemistry (CC) 101Comet assay 1626Committee for proprietary medicine products

(CPMP) 434, 1670, 1675Committee for human medicinal products

(CHMP) 1670, 1678Committee for orphan medicinal products

(COMP) 1678–1679Committee for veterinary medicinal products

(CVMP) 1678Common technical document (CTD)– electronic 1699– format 1698Complete Freund’s adjuvant 194Complex disease 77Computer-aided drug design (CADD) 1607Comvax 18Concanavalin A 484Confocal image assisted 3-dimensionally

integrated quantification (CIDIQ) 1526Congestive heart failure (CHF) 318Congo Red 1287Connective tissue disease (CTD) 1750Connexin43 320Connexin45 292Constitutive androstane receptor (CAR) 1788Contergan 1675Continuous (chemostat) perfusion cell 430Contract manufacturing– client contracting 1095– integrating 1089Contract manufacturing organization

(CMO) 1083, 1093Contrast agents– for imaging modalities 1213– for molecular imaging 1225– for optical imaging 1223– for SPECT 1222– for ultrasound imaging 1219– smart ultrasound 1303Copper bis-thiosemicarbazones 1264

Subject Index 1849

CORINA program 1777, 1797Corixa 502Coronary artery bypass grafting, see CABGCOSMIC program 1797Costilate 473Coulyflower mosaic virus 894, 954, 981Coumarin hydroxylation 1618CpG-ODN 1424CRA-2059 chemical structure 407Creatine phosphate 1075CREB phosphorylation 1746Creon 860Crescormon 476CRESTOR 55Creutzfeld-Jakob disease 424, 747, 872– new variant 1007– pathways and targets for 627Critical flooding temperature 1316Crohn’s disease 21– fragment for treatment 1116Cross-fire effect from beta particle emitters 500Cryptococcus neoformans 686Cryptotope 1191cTnI 290Current good manufacturer practice, see cGMPCyanovirin 1406– immunologic response in mice 1407Cyanovirin-N 483Cycas revoluta 484Cyclic adenosine monophosphate, see cAMPCyclic response element 233, 239Cyclin-dependent kinase 219, 821Cyclin kinase inhibitor 763Cyclo18 256Cyclo50 256Cyclo66 256Cyclo80 256Cyclodextrin 407Cyclohexylalanine 413Cyclohexylglycine 413Cyclophilin-B 257Cyclophosphamide 503– hydroxylation catalyzed by CYP2B4 1597Cyclosporine 55, 58– metabolized by CYP3A4 1585Cycloviolins 484CYP gene testing kit 78CYP102 1609CYP17A 1616CYP17A1 1616CYP1A2 1618, 1621– molecular model 1612CYP1B1 1620

CYP2A6 58, 1618, 1621CYP2B 121CYP2B4 1621– apo-form 1598– inhibitors 1597– structure of 1597CYP2B6 58, 1618CYP2C19 57, 61, 76, 1618, 1620– molecular model 1611CYP2C3– chimeric 1595– isoforms 1595CYP2C5 1610– Co-complexes 1596CYP2C8 58, 1609, 1618– active sites 1594– inhibitors 1594– pharmacophore 1595CYP2C9 57, 76, 1609, 1618– crystal structures 1590– flurbiprofen complex 1591, 1593– in drug metabolism 1590– inhibitors 1590– isoforms 1589– molecular model 1611– S-warfarin complex 1591CYP2D6 51, 57, 61, 76, 1618, 1620–1621– molecular model 1611CYP2E1 1615, 1618CYP3A 121CYP3A4 54, 58, 1584, 1615, 1618, 1788– activity 1587– allosteric nature 1586– Co-complex structures 1588– isoforms 1584– molecular model 1610– structure of 1585– subfamily 1585CYP3A5 58, 1618Cysteine knot motif 484Cysteine thiols 1400Cystic fibrosis 1751Cytochrome metabolism 1609Cytochrome P450 76, 329– active site 1584– bacterial expression of human 1615– classification 1582– crystal structures 1581– genetic polymorphism of human 1583– GloTM-assay system 1613– microsomal 1581– prokaryotic 1584– structure of soluble 1584

Subject Index1850

Cytochrome P450, human– associated with drug metabolism 1617Cytochrome P450 reductase (CPR) 1615Cytodex 739Cytogenetics of CHO cell lines 735Cytokine immunostimulatory 1173Cytolytic T lymphocytes 1489Cytomegalovirus (CMV) 188, 1489– enhancer 299– human 764– promoter 156Cytopathic effect 166Cytoplasmic microinjection 1531Cytotoxic T lymphocytes 199, 1175Cytotoxicity– antibody dependent cellular 1107, 1156, 1274– complement dependent 1107– cell-mediated 924

d1D09C3 (anticancer antibody) 1177Daclizumab 21, 456, 1086Dalteparin sodium 457Danau plexipis 1047Darbepoietin 16Darbepoietin alfa 472DARWINIZER 1779Dash 84Daudi B-cell lymphoma 526Daunomycin 1814Daunorubicin 1370DD3 gene 220DEAE chromatography 166DDAB, see Didodecyldimethylammonium bromideDEBS (6-Deoxyerythronolide B synthase) 1813DEBS system 1815DEBS AT module 1815DEBS pathway 1819DEBS1 1816DEBS2 1816DEBS3 1817Decay accelerating factor (hDAF) 355Decoy oligodeoxynucleotides, see dODNDeep brain stimulation 331Deep-vein thrombosis– trials with ATryn 1011Defensins 383, 486, 1433Defibrotide 461Dehybridization detection 86Dehydration response element 981Dehydrobenzene 1125Dehydrofolate reductase, see DHFRDenaturing high-performance liquid chromatog-

raphy (D-HPLC) 86

Denileukin diftitox 456, 480Deoxycoformycin (dCF) 4296-Deoxyerythronolide B synthase, see DEBSDepoInterferon alpha 468, 480DEREK 1624Dermatan sulfate 458Dermorphins 486Desirudin 462Desmin 290Desmopressin 1376Desoxyribonucleic acids, see DNADexamethasone 896Dexfenfluramine 52Dextromethorphan hydroxylation 1618DGCR5 220D-HPLC, see denaturating high-performance

liquid chromatographyDHFR (Dehydrofolate reductase) 725, 1079– CHO system 812– expression system 813– generation of stable cell lines 733Diabetes 1445– latent autoimmune in adults 1198– type 1 1033, 1451– type 1 treatment 1454– type 2 1033, 1446Diabetes Control and Complications Trial

(DCCT) 1446Diabetes mellitus 13– pathways and targets for 626– treatment 1473Diabetes patients– meal study in type 1 1455– meal study in type 2 1456Diagnostic assay multi-marker-based

1325Diagnostic protein– directed evolution 705– rational design 705Diatin 476Diazepam 61– CYP3A4 activated 1587– metabolized by CYP2C9 15906-Diazo-5-oxo-L-norleucine see DONDibotermin alfa 464Dicer ribonuclease 222Dicialoganglioside 1173Diclofenac– CYP2C5 co-complex 1596– hydroxylation 1618Dictyostelium discoideum– in biomedical research 685– cells 665– retrotransposon 689

Subject Index 1851

6A,6D-Dideoxy-6A,6D-diamino-beta-cyclodextrin 407

Didodecyldimethylammonium bromide(DDAB) 1508–1509

Diethyl maleate 1466Diethylentriaminepentaacetate 1123Diffuse optical tomography (DOT) 1223DiGeorge syndrome 220Digitalis 835Digoxin 58N-[2-(Dimethylamino)ethyl]acridine-4-carboxamide

1250Dimethylsulfoxide 957Dioleoylphosphatidylethanolamine (DOPE)

1508–1509, 1523N-[1-(2,3-Dioleyloxy)propyl]N,N,N-trimethyl-

ammonium chloride, see DOTMADiphenhydramine 61Diphtheria 18Directed molecular evolution 709DISC1 (disrupted in schizophrenia 1) 221DISC2 (disrupted in schizophrenia 2) 220Disease– genes 73– classes of 1276Disintegrins 1283Diseminated intravascular coagulation (DIC),

sepsis induced 997Dithiothreitol (DTT) 1073Dixon test 168DLG2 2216-DMAP (6-dimethylaminopurine) 272DMEM (Dulbecco’s modified eagle medium) 740DMRIE-C transfection reagent 1030DNA (desoxyribonucleic acid) 628– dumbbell 1532– exogenous 1529– fragmentation assay 644– linear template 1067– microarrays 672– naked 1490– release kinetic 1497– residual 167– shuffling 590, 706DNA databank of Japan (DDBJ) 255DNA plasmid– conformation of release 1498– release kinetics from microspheres 1498DNA polymerase– engineering of enzymatic activities 711DNA vaccination 199– for tumor suppression 1501DNA vaccine delivery 1487, 1490

– polymers for 1491– efficacy 1489– incorporated in polymer microspheres 1492– mechanism of action 1489DNA-vector complex 1490Docetaxel 131, 141, 1251– in cancer treatment 1172dODN (decoy oligodeoxynucleotide) 231– therapeutic application 232Dolabella auricularia 482Dolabellanin B2 486Domperidone 1795DON (6-diazo-5-oxo-norleucine) 537– antitumor effect of 538–539– efficacy of 539– inhibition of sarcoma 180 tumor cell

growth 541– treatment of mouse tumors 541– tumor cell line sensitivity 539Dopamine producing cell, transplantation

of human non-neural 333Dopamine transporter (DAT) gene 329DOPE, see dioleoylphosphatidylethanolamineDoppler effect 1218Doppler frequency shift 1218, 1304Doppler image, two-dimensional 1315Doppler mode 1308Doppler ultrasound imaging 1238Dornase alfa 475Dose determination 1566DOTA-biotin 514DOTMA (N-[1-(2,3-Dioleyloxy)propyl]N,N,N-tri-

methylammonium chloride) 1508–1509Double stranded RNA, see dsRNADouble emulsion technique– preparation of microcapsules 1373Doxorubicin 131, 1253, 1370, 1814– in cancer treatment 1172– use 1804DoxoRx 866DRAGON descriptors 1797Drotrecogin alfa (activated) 465Drug– biopharmaceutical 453– development 54– labeling 63– therapeutic range 54Drug classes– central nervous system active 1792Drug conjugates– low molecular weight 1171Drug costs 1717– cost-benefit evaluation 1720

Subject Index1852

– cost-conscious prescribing 1721– in America 1717– in Europe 1717– population ageing, impact on 1718– price reduction 1719– pricing pressure 1724– R&D spending 1723Drug delivery– bionanotechnology in 1540– with ultrasound 1315Drug delivery system 1361– administration sites for 1364– bucal 1379– colon specific 1381– conjugates for 1366– forms of 1369– nasal 1377– non invasive 1375– oral 1380– PEG in 1393– pulmonary 1378– polymer based 1361– transdermal 1382Drug development 1147– molecular imaging for 1230– P450 for 1582– phases in 1231– protein kinase in 639– siRNA based 264Drug discovery– basic concepts of virtual 1773– phases 1774Drug discovery process– cell based assay 640– for chronic disease 100Drug-drug interaction 1787– metabolic prediction 1621Drug evaluation and research (CDER) 1639Drug interaction 60– effect of genotypes on 61Drug metabolism 1608, 1787– contribution of genetic polymorphism to 57– CYP2C9 in 1590– CYP3A4 in 1584Drug metabolizing enzymes 52Drug metabolites 1622Drug product 1561Drug release by ultrasound 1316Drug response 50Drug substance 1561Drug substances coordinating committee

(DSCC) 1765Drug target validation 110

– necessary cause model 114– sufficient component cause model 113Drug therapy for Parkinson disease 329dSLIM (double-stem loop immunomodulator)183– application of 198– immunization pathways using 200– production 197– properties 197dsRNA (double stranded RNA) 244– in vitro dicing 631Dukoral 19Dundee P450 system 1614, 1619, 1623Duract 52Duteplase 462Dynamic light scattering 162Dynepo 472Dyskeratosis congenita 41Dyskinesia 332Dysport 463

eE1 protein– induced cell proliferation 782– of human adenovirus 782E1A protein 783E1B protein 783– E2F 233Ebstein-Barr virus 1029, 1153Ebiratide 1469EBNA1 (Epstein-Barr virus nuclear antigen)

expression 1029Ebola virus 484, 1407, 1488Echogen 1305Echovist 1305Ecokinase 11, 462Econazole 1370Ectoine synthesis 978Edrecolomab immunotherapy 1278Efalizumab 456Efavirenz 58EGF (epidermal growth factor) 238, 463EGFR (epidermal growth factor receptor) 59,

105, 623Elastase 380Elcatonin 476Elcitonin Inj. 20S 476Electromechanical (NOGA) mapping 155Electron spray ionization (ESI) 1564Electronic standards for transmission

of regulatory information (ESTRI) 1699Electrophoretic methods– in quality control 1563

Subject Index 1853

Electroporation 1382– DNA transfer into mammalian cells 729ELISA (enzyme-linked immunosorbent

assay) 166, 168, 172, 1563– characterization of antibodies by 797– of soluble protein from rice grain 940– protein levels of rhVEGF measured by 923– sandwich 1564ELIspot responder rate 1432Elitec 475Elitex 24Ellman reagent 1415Elspar 537ELUTES trial 315Embryoid body 286Embryonic antigen 288Embryonic development 287Embryonic germ (EG) 278Embryonic renal progenitor 357– organogenesis 366Embryonic stem (ES) 269Embryonic stem cell 286, 319– cardiomyocyte differentiation 289– characterization of human SCNT 276– human 269, 287– marker 276Embryotoxicity– use of D. discoideum for testing 687Emend 1538Eminase 461Enbrel 7, 24, 463, 1118Encephalomyocarditis virus 766Encoded self-assembling chemical libraries

(ESACHEL) 1275End stage renal disease (ESRD) 354Endocytosis 1426, 1490Endoglin 1281Endosomal escape 1530Endosperm cell 935Endothelial cell adhesion molecules 1282Endothelial progenitor cell (EPC) 285, 319Endotheline 235Endotoxemia 1009End-point dilution (EPD) assay 166Engerix B 18, 1639Enhanced permeability and retention effect

(EPR) 1366Eniluracil 12535-Enolpyruvyl-shikimate3-phosphate

synthase 898Enoxaparin 457Enterobacter aerogens 1352Enterodiol 943

Enterolactone 943Entrez Gene 255Enzymatic degradation 1363Enzyme 474– activity, imaged by NIR 1283– drug-metabolized 1608– endoproteolytic 1194– mutant 711– strategy for evolution directing 706– wild type 711Enzyme immunoassay test (EIA) 1190Enzyme-linked immunosorbent assay, see ELISAEpCAM 1278Epidermal growth factor, see EGFEpidermal growth factor receptor, see EGFREpirubicin 131Epithelial cellular-adhesion molecule 862Epitope 1190– blocking 1163– classification 1191– continuous 1192– continuous helical 1193– cryptic 1197– discontinuous 1194– linear 1195– mapping 1192– post-translationally modified 1192– proteinaceous 1193– specificity 1163– visualization 1195, 1198Epoade 472Epoetin delta 472Epogen 3, 16, 472, 738Epogen Herceptin 737Epogin 472Epopen 472Epothilone 1804Eprex 472, 1656–1657, 1762ErbB1(epidermal growth factor receptor) 129ErbB2 129ErbB3 129ErbB4 129Erbitux 454–455, 479, 1121ERGIC-53 420Ergotamine 330Erlotinib 143Erypo 472Erythrocytes 1173Erythroid membrane associated protein 1205Erythromycin– biosynthesis steps 1811– by DEBS’3 1815– derivatives 1813

Subject Index1854

– metabolized by CYP3A4 1584– pathway 1821– use 1804Erythropoietin (EPO) 466, 737Erythropoietin alfa 472Erythropoietin beta 472Escherichia coli 1135, 1351, 1401– cell free expression of biopharmaceuticals

using 1063– expression platform 1022– extracts 1070–1071– G-CSF produced by 1757– in biosynthesis of insulin 1034– plasmid DNA templates for 1066– transgenic genomes from 1046Escherichia coli system– coupled transcription/translation from 1076– reaction conditions 1075Esperamycin 1125Espo 472Est1p (ever shorter telomeres) 40Est2p 39Est3p 40Estrogen response element 233, 239Etanercerpt 463, 1118, 1163Ethoxyresorufin 1618Ethyl-(diamethylaminopropyl)carbodiimide 1310Ethylenediamine tetraacetic acid 1466N-Ethylmaleinimide 403Etoposide 131, 503EU authorities– bioproduct definition 1681EU concept papers 1706–1707EU directives 1703EU draft guidelines 1706–1707EUDRACT database 1697EUDRALex 1670, 1677, 1682EUDRANet 1677EUDRATrack 1677EudraVigilance 1677EU guidelines– adopted for biosimilar medicinal

products 1707– adopted for biotechnology medicinal

products 1705Euglycemic clamp study– dose ranging 1451Eukaryotic transcription factor 235EU regulations 1703– for biopharmaceuticals 1669– laws 1676Eurifel FELV 26Eurifel RCPFEVL 26

European bioinformatics institute 255European commission (EC) 1760European community pharmaceutical

directive 1675European council regulation 1677European department for the quality of medicine

(EDQM) 1680European federation of pharmaceutical

industries and associations 1643European market, generic conversion rates

and price 1766European medicines evaluation agency

(EMEA) 434, 1559, 1643, 1677– key tasks 1678European molecular biology institute 255European nutrigenomics organization 93European organization for the treatment

of cancer (EORTC) 1233European pharmacopoeia 1680European public assessment report

(EPAR) 1688EuroPHARM database 1677Evalizumab 1086Evans blue 1472Exercise treadmill test (ETT) 175Exogenous DNA 1529Exon 2 653Exopeptidase 1379Expanded bed absorption– biopharmaceutical production in cultured

plant cells 960Experimental autoimmune encephalomyelitis

(EAE) 1237Expressed sequence tag (EST) 105, 630Expression difference mapping 1330ExpressTec 931– development 933– protein expression in grains 945Extracellular matrix– imaging 1256– modified 1276Extracellular superoxide dismutase (ecSOD) 317Extrachromosomal palindrome 664

ffVIIa 459fVIII 459– biosynthesis 427– by perfusion technology 743– development of recombinant 428– production of recombinant 430– protein 424– secretion and activation 426

Subject Index 1855

– structure and function 425fIX 495, 695– activated 699– human 459– protein, exon, domain and structure of 696– zymogen form 697Fabrase 475Fabrazyme 23, 475Fabry disease 23, 861– pathways and targets for 625fC 459FACS, see fluorescence-activated cell sortingFANTOM2 dataset 217Fasturtec 24, 475Fatty acid oxydation 121FCGR3A 59FDA, see Food and Drug AdministrationFD&C Act 1641Feline immunodeficiency virus (FIV) 202,

556Fenfluramine 52Feron 467Fertinex 464Fertinorm 464Fetal bovine serum (FBS) 785Fevaxyn Pentofel 25Fexofenadine 58, 1788FGF (fibroblast growth factor) 153, 307FGF-4 172– pACSR/FGF-4 156– proteine, production of 168FGF-5 172Fibrin 1283Fibrin clot lysis assay 1565Fibrinogen 1283– expression of, in rice grain 940– recognition exo-site 413– recognition site 412Fibrinolysis 377, 1009Fibronectin 738, 1283Fiducial limit 168Field flow fractionation, see FFFFilgrastim 4, 16, 473, 1406, 1755Firefly luciferase 1228FirtEF algorithm 108FISH (fluorescence in situ hybridization) 134,

728, 736– analysis of BC6 transgene 1002– semiquantitative 1002FK506 1805Flavodoxin 1616Flock haus virus (FHV) 263Fluconazole

– CYP2C9 inhibitor 1590– radiolabeled 1285Fluoracil 5105-Fluorouracil 76Fluorescein isocyanate 1472Fluorescein isothiocyanate (FITC) 363Fluorescein isothiocyanate-Tat-Peptide 637Fluorescence-activated cell sorting (FACS) 299,

1112, 1431– for screening of cell lines 816Fluorescence-mediated tomography– protease activity imaging 1282Fluoro-deoxy-arabinofuranosyl-iodouracil

(FIAU) 1254Fluorodeoxyglucose 499, 1226Fluoroestradiol 1256Fluoroethanidazole 1264Fluoroethylspiperone (FESP) 1254[(Fluorohexenyl)benzene-sulfonylamino]-3-butyric

acid 1257(Fluoro-hydroxy methyl butyl) guanine 1254Fluoro-methyldeoxyuracil-

arabinofuranoside 1261Fluoromizonidazole 1264Fluorophores 1227Fluorothiol 1259Fluorothymidine 1261Fluorouracil 131, 1250– radiolabeled 1253Fluoxetine 61Flurbiprofen– CYP2C9 complex 1593– metabolism 1593Fluvoxamine 61– Fluxum 457Follicle-stimulating hormone (FSH) 4Follistim 15, 465Follistim AQ 465Follitropin alpha 463Follitropin beta 465Fondapparin sodium 457Food and drug administration (FDA) 49, 1559,

1639, 1765– guidance 1642– regulatory authority for monoclonal

antibodies 1085Forcalcitonin 477Forcaltonin 15Formivirsen 24Forskolin 292Forsteo 15, 477Forteo 15, 476Fortical 477

Subject Index1856

Fourier transform ion cyclotron resonance(FTICR) 1564

FP-TDI 84Fractogel-DEAE chromatography 158Fragment antigen binding 1088Fragmin 457Fraxiparine 457Fraxodi 457Free induction decay (FID) 1216Freud’s adjuvant, complete 194Frone 4671,2-Fucosyltransferase 3553-Fucosyltransferase 925Fusigenic-hemagglutinating-virus 307Fusogenic lipids 1523

gG protein-coupled receptor (GPCR) 664G418 299, 785GA (glutaminase-asparaginase) 540– inhibition of sarcoma 180– tumor cell growth 541– treatment of mouse tumors 541Gag proteins 551Galactosidase 15003-Galactosyltransferase 3554-Galactosyltransferase 925Gallivac HVT IBD 26Gamma-aminobutyric acid (GABA) 1198Gamma scintigraphy of oralin deposition 1450Gancyclovir 313GAP31 482Gas chromatography/mass spectrometry

(GC/MS)– of Mathay resinol 945– in lung cancer detection 1344Gastric lipase deficiency 859GATA4 290Gateway bacteriophage 610Gateway cloning 614– three-fragment multisite 618Gateway-enabled baculovirus expression

system 615Gateway entry clones 611Gateway, multisite 616Gateway reactions 610Gateway recombinatorial cloning system 606Gateway vector system 611Gaucher’s disease 8G-CSF (granulocyte colony-stimulating factor) 4,

321, 1755– dosage 1757– function 1757

– PEGylation 1404– PEGylation sites and relative yields 1405– production 1756Gefitinib 59, 76Gelatin 872, 957, 1380– microcarriers 336Gemeinsamer Bewertungsausschuss 1720Gemfibozil– CYP2C8 inhibitor 55, 1594Gemtuzumab 455Gemtuzumab ozogamicin 480, 1086– in cancer treatment 1172Gemtuzumab zogamicin 22Genasense 633GenBank sequence 170Gene structure– analysis of 651Gene amplification 733Gene cloning, full length 109Gene correction 1531– efficiency 1534– site specific 1533Gene delivery 153, 1318– bionanotechnology in 1543– liposomal 1507– scheme for hepatocyte selective 1512– system 1521Gene expression– heterologous 769– chip 1613– heterohybridoma 769Gene identification 105Gene mining– de novo prediction 107– homology/orthology mining 105– in silico prediction 107– integrated approaches 108– splice variants 108– transcript 107Gene recombination 706Gene replacement (knock-out) 666, 669– at predefined locus 767Gene silencing 258– antisense oligos 633– antisense RNA 633– post transcriptional 634, 896Gene targeting– in CHO cells 768– genetically modified mice 651Gene therapy 31, 1521– adenovirus-based 151– and regenerative cardiovascular medicine 319– cytotoxic 313

Subject Index 1857

– DNA-based molecules for 183– for cardiovascular disease 305– for myocardial failure 318– for myocardial protection 317– of AIDS 553– radiation 313– somatic 689– therapeutic angiogenesis 307– vector 155, 184Gene transcription 933Gene transfer 733– anti-thrombogenic 315– cationic 1510– for rapid re-endothelialization 314– in cancer cells 1515– nitric oxide 314– to brain 1517– to prevent matrix remodeling 315Gene trap 669GeneChips 84, 1750Gene-environment interactions 75Generic biopharmaceuticals 30Generic conversion rate 1766Generic price 1766Gene-targeted mice 658Genetic background 73Genetically modified mice 649Geneticin 785Genetonorm 476Genome analysis 170Genome-wide variant pattern (GVP) 80Genomic information– translation of 83Genomics 30Genosensors 1545Genotoxicity– in silico 1624– in vitro 1624– prediction 1624– screening 1627Genotropin 14, 476Genotropin Miniquick 476GenScan mining 108Gentel 463Geref 476Gibberellic acid 957Gingko biloba 61Gleevec 639Glial fibrillary acidic protein promoter 1517Glial-derived nerve growth factor (GDNF) 333G-line 772Glioblastoma multiforme 509Gliptide 463

Globuren 472Glomerular basement membrane 1197Glucagen 14GlucaGen 476Glucagon G Novo 476Glucagon rDNA 476Glucocerebrosidase 861Glucose– concentation-time profile in plasma 1471, 1476– concentration after kitosan capsule

administration 1483Glucose metabolism– PET imaging of 1260Glucosidase 861GlutaDON therapy 537Glutamate decarboxylase 65– modeling 1198Glutamate synthetase 734Glutamic acid carboxylase 905Glutaminase synthetase, see GSGlutaminase asparaginase, see GAGlutamine synthetase (GS)– expression vector 812– /CHO cell system 1094Glutathione– reduction in transgenic plants 979– reductase 1073Glutelin 933gly 219 700Glyburide 1457Glycan analyse 800Glycan structure– differences in 773Glycinebetaine 976, 988Glycogen synthase kinase 3 inhibitor 288N-Glycolyl neuraminic acid 772, 811, 849Glycosylation 678Glycosyl phosphatidylinositol (GPI) 674– anchor 716Gold in drug delivery 1540Gold standard 87, 201Golgi apparatus 427Gonadorelin 1376Gonal F 9, 15, 463Good laboratory practice (GLP) 1640Good manufacturing practice (GMP)– in transgenic systems 851Goodpasture disease 1197Goserelin 478Gosher’s disease 23, 1513– test on enzyme therapy 905Government printing office 1640GPS (Global Pharma Specialist), XXV 1833

Subject Index1858

G-proteine coupled receptor (GPCR) 105Gram-negative pathogen 686Gram-negative bacteria 485Gram-positive bacteria 381, 485Gran 473Granocyte 473Granulocyte-colony stimulating factor, see G-CSFGranulocyte-macrophage colony-stimulating

factor (GM-CSF) 6, 1429Granulokine 473Graves disease 1188Green fluorescent protein reporter 1627GreenScreen 1608GreenScreen GC 1624– assay 1630– genotoxicity tests 1627– industrial validation studies 1633– molecular genetics 1628– proof of concept 1631Grepafloxacin 52Growject 476Growth factor 154GRTPA 461GS (Glutamine synthetase) 809– schematic of a cell line selection program 817GS-CHO cell lines 812GS-NS0 cell lines 812

hH19 220, 277HA-1A 455HAART (highly active antiviral therapy) 549, 558Haemate HS 454, 459Haemate P 459Haemophilus influenzae 1421Haemophilus influenzae B 18Hairy cell leukemia 17Haliclona cratera 482Halomonias elongata 978Ham F12 740HAMA 7Hamster antibody production test (HAP) 434HANC 220Hansenula polymorpha 1135Hapase 461Haplotype blocks 81Haplotype tag 81Hartmannella vermiformis 685Hatch-Waxman Act 1722, 1765Hayflic limit 44HBVAXPRO 19Health care reform act 1719Health products and food branch (HPFB) 1762

Healthcare– costs 1715– economics 1762– environment 1733– payors 1718– reform legislation 1718Heamin 957Heart failure, targeting 1284Heat shock proteins– levels of expression of different 984– synthesis and regulation of cytoplasmic 983HEK 293, 156, 744, 775HeLa cells 614Helicobacter pylori 869Heliotis virescens 483Helixate 10, 459Helixate FS 459Helixate NexGen 10, 459Hemagglutinating virus of Japan 236Hemangiomas 312Hematopoietic agent 466Hematopoietic stem cell (HSC) 554Hemolysin 383Hemo-oxygenase-1(HO-1) 317Hemophilia A 10– therapy 421Hemophilia B 10Hemostasis 444Hemotaxis 643Hemiptera 486Hepacare 19Heparansulfateproteoglycan 1007Heparin 997, 1370– binding affinity of rhAT 1005Heparin affinity chromatography 1003Heparin resistance 1012– in CABG patients 1013Hepatic metabolic clearance 1796Hepatitis B 17Hepatitis C 17, 263– virus vaccine 1430Hepatocyte– asialoglycoprotein receptor mediated 1512Hepatocyte growth factor, see HGFHER1 129HER2 (human epidermal growth factor

receptor 2) 21, 128– indicators of 129– testing 133– testing, algorithm 135– /neu oncogene 1277HER3 129HER4 129

Subject Index 1859

HERA trial 144HercepTest 77, 134Herceptin 22, 64, 77, 128, 455, 479, 526, 1086,

1121– adjuvant trials 144– antitumor effect 132– combination with chemotherapeutic drugs 131– development hallmarks 137– duration of response 137– in early breast cancer 143– mechanism, on cellular processes 130– monotherapy 138– quality of life 137– time to progression 137– time to treatment failure 137Hereditary angioedema 859HERG 59Hetero duplex analysis 86Heterobifunctional inhibitor 403Heterochromatin 730Heterogeneous nuclear hnRNA 628Heterohybridoma CB03– chromosome analysis of 770Hexadecyltrimethyl ammonium bromide 1493Hexavac 19Hexosaminidase inhibitor 1047HGF (hepatocyte growth factor) 307hGH (human growth hormone) 14, 476– deficiency 14HIF (hypoxia inducible factor) 307HighFive 1047Highly active antiviral therapy, see HAARTHigh-performance capillary electrophoresis

(HPCE) 1563High-performance ion-exchange chromatography

(HPIEC) 1562High-performance liquid chromatography

(HPLC) 84, 1563High-performance size exclusion chromatography

(HP-SEC) 798, 1562– High-resolution computed tomography

(HRCT) 1750High-throughput cloning 605, 615High-throughput screening (HTS) 101, 1606Hirschsprung’s disease 77Hirudin 412Hirulog 461Hismanal 52HIV (human immunodeficiency virus) 263,

1513– antiviral gene therapy 554HIV-1 (human immunodeficiency virus type 1)

549, 556

– combinatorial RNA-based therapy 569– gag protein 551– genes and life cycle of 551– pol protein 551– provirus 551– tat protein 219, 553– toxic genes therapy 555– vector mobilization 575– vectors used in gene therapy 556HIV-2 (human immunodeficiency virus

type 2) 556HKB11 (hybrid of human kidney and B cell)– expression platform 1029HLA (human leucocyte antigen) 80HLA-B57 82HMG-CoA 59Hoechst epi-fluorescence technique 321Holoenzymes 1620Homo-arginine 413Host cell– engineering 732– protein 166, 1131Host Response Protein Amplification Cascade

1338HOST2 220HOXB8 223HPAEC-PAD (high-performance anion exchange

chromatography with pulsed amperometricdetection) 800

– glycan profile of human IgG 801HPIEC, see high-performance ion-exchange

chromatographyHPLC, see high-performance liquide chromatog-

raphyHPSEC, see high-performance size-exclusion

chromatographyHuCAL– design modularity 1176– GOLD antibody library 1159– library 1177HUM195 506Huma ES system 290Humalog 12–13, 469, 1456Humalog MIX 469Human actrapid 470Human adenovirus 782Human anti-mouse antibody (HAMA) 7, 1109Human anti-streptavidin antibody (HASA) 513Human antithrombin– conformation analysis 1004– establishment of transgenic herd 1001– glycosylation 1005– purification 1003

Subject Index1860

Human antithrombin III– from transgenic system 855Human antithrombin process– viral removal or inactivation by 1007Human C1 inhibitor– from transgenic system 859Human cell– for organogenesis 353– for transplantation 353Human chorionic gonadotropin 1326Human cytomegalovirus 764Human embryonic retina (HER) cell 783Human embryonic stem cell (hES) 269, 287– derivation of 286Human epidermal growth factor receptor 2,

see HER2Human fetal mesencephalic cell– transplantation of 331Human foreskin fibroblast cells (HFF) 637Human genome project 230, 622Human genome sequencing consortium

214Human germ line structure 771Human growth hormone, see hGHHuman immunodeficiency virus, see HIVHuman immunodeficiency virus type 1,

see HIV-1Human Insulatard 471Human insulin Zn suspension 469–470– 30/70 470– protamine 471Human lactoferrin, expression of, in rice grain

940Human leucocyte antigen, see HLAHuman liver microsomes 1618Human lysozyme– expression 935– recombinant 939Human monotard 470Human neutral insulin 470Human papilloma virus 263Human phosphoglycerate kinase (PGK)

promoter 783Human platelet-derived growth factor, see PDGFHuman protein processing 774Human retinal pigment epithelial (hRPE) 325Human serum albumin (HSA) 275Human somatic cell nuclear transfer 273Human tissue plasminogen activator– from transgenic system 836Human umbilical vein endothelial cell (HUVEC)

1008Human velosulin 471

Human-ether-a go-go-related (hERG) potassiumchannel 1796

Humaspect 22Humate P 459Humatrope 14, 476Humira 22, 455, 864, 1086, 1112, 1118Humulin 12–13, 452, 1449– 50/50 469– 70/30 469– I 469– L (Lente) 469– M 469– M1 469– M2 469– M3 469– M4 469– M5 469– N 469– R 470– S 470– U 469– Zn 469Huntington’s disease– pathways and targets for 625Hyaluronic acid 1380Hybridoma cells 433Hybridomas 820Hydrohermatic feed system 1603-Hydroxyacyl-CoA dehydrogenase II 328Hydroxycyclophosphamide 131N-(Hydroxypropyl)methacrylamide Co-polymer

1367Hydroxysuccinimide ester 14037-Hydroxy-4-trifluoromethylcoumarin

(HFC) 1610Hygromycin 771Hygromycin B 1030– phosphotransferase 766Hymenoptera 486Hyperplasia– cytotoxic strategies to reduce neointimal 313– gene transfer to reduce neointimal 314– neointimal 319Hyperuricaemia 24Hypoglycemia 14Hypoxia 1263Hypoxia inducible factor (HIF) 154, 307, 1279

iIBMX (3-Isobutyl-1-methylxanthine) 292Ibraxion 26Ibritumomab tiuetan 456, 480Ibritumomab tiuxetan 22, 1086

Subject Index 1861

– half life 1168– in radiotherapy 503– radio active labeled 501IC31 1440IC41 1430ICH (international conference on harmonisation)

1567– guidance for assay validation 1568– parties 1680– process 1681ICH Guidance 1642ICH guidelines 434– for developed biotech products 1707ICH Q5A 1570ICH Q5B 1572ICH Q5C 1572ICH Q5D 1572ICH Q5E 1572ICH Q6B 1572, 1691ICH S6 1692ICH S7A 1692Identity assay 1566Idiopathic pulmonary arterial hypertension,

see IPAHIdiopathic pulmonary fibrosis (IPF) 1750Idotamoxifen– in breast cancer 524Iduronidase alpha 862Ifosfamide– hydroxylation catalyzed by CYP2B4 1597Igef 463IgG, light and heavy chains 785Igovomab 22IHC (immunohistochemistry) 133Imagent 1305Imiglucerase 475Iminase 461ImmobaSil carrier 682Immukin 467Immune response 1425– type 1 and 2 1424Immune globulin intravenous (IGIV) 1109Immuneron 468Immunoassays 171Immunoblotting 1563Immunogenicity 1656– of antibodies 1153Immunoglobulin 198, 1107– subclasses 1424– locus 769– bivalent 1166– post translational modifications 1132Immunoglobulin G 862

Immunohistochemistry (IHC) 116Immunoliposomes 1517Immunomodulatory molecule 193– adjuvants 194– DNA-based 195Immunomodulation 939Immunoscintigraphy with radiolabeled

ABS 1123Immunostaining 772Immunosuppressive drugs 1804Immunotoxin, first generation 1125Implants 1546– drug delivery system 1369– polymeric solutions building in situ 1374IMS (ion mobility spectrometer) 1343, 1345– adaptation to MCC-Ni 1347– chromatogram examples 1350– chromatogram of human exhaled air 1349– sources for 1345– working principle of 1346Imukin 1 467Imunace 464, 479In situ hybridisation (ISH) 134IND (investigational new drug) 50– applications 742– submission of pharmacogenetics data to 62Indimacis 122 22indirect immunofluorescence (IIF) 1190indium-111 zevalin 456, 480InductOs 24, 464Infanrix 18Infection, targeting 1285Infectious disease era 103Inferax 467Infergen 17, 467Inflammatory bowel disease 1117, 1285Inflammatory cytokines 197Infliximab 21, 59, 456, 1086, 1118, 1153, 1163Influenza virus 484, 1488InFuse 464Injection, drug delivery system 1369Inner cell mass 286Inositol-1,4,5-triphosphate 688Insect cell culture 1047– glycosylation 1047– in biopharmaceutical production 1045– process cost calculations for 1059– protease activities in infected 1049Insertions or deletions (InDel) mutations 75Inspectional authority for biopharmaceuti-

cals 1653Institut für Pflanzengenetik und Naturpflanzen-

forschung 869

Subject Index1862

Institut für Qualität und Wirtschaftlichkeitim Gesundheitswesen 1721

Insulatard 13Insulatard NPH 471Insulin 466, 1376, 1449, 1451, 1465– analogues 1034– biosynthetic, human 1034– effect of protease inhibitors on intestinal

absorption 1471– human 470, 1034– industrial scale 1033– intestinal absorption using kitosan capsules

1482– isophane 469– kitosan capsules for delivery of 1480– lipophilic index 1473– meal 1454– native 1474– precursor molecule 1036– production of 1041– structure and its acyl derivatives 1474Insulin acyl derivatives– activity and lipophilic index 1475– half lives for proteolysis of 1475Insulin aspart 13, 470, 1039– biphasic 470Insulin caproyl derivatives 1476– transport of 1477Insulin degradation– effect of protease inhibitor on 1469Insulin derivatives– circular dichroic spectra of 1476Insulin determir 13, 470Insulin glargine 13, 470Insulin glulisine 13, 469Insulin injection 1455Insulin lispro 12, 469– biphasic 469Insulin precursor expression system 1039Insulin-like growth factor type 2 receptor

(IGF2R) 218Insuman 13, 470Insuman basal 469Interaction discovery mapping 1325Interannular heterobivalent inhibitor 403Interannular homobivalent inhibitor 400interferon (IFN) 4, 466, 1253– for in situ radiotherapy 510– PEGylation 1401, 1404– PEGylation by two step approach 1405Interferon– alfa 467– alfa-2a 468, 480

– alfa-2b 468, 480– alfacon-1 467– alfa-n1 468– alfa-n3 467– beta 467– beta-1a 467– beta-ser 467– gamma 468, 1750– gamma-1a 467, 479– gamma-1b 467– gamma-n1 468Interferon regulatory factor-1 (IRF-1) 233Interleukin (IL) 190, 201, 329, 905– expression system 1022– IL-2 465– IL4v expression plasmids 1026– IL-10 59Internal ribosome entry site (IRES) 765International biopharmaceutical reference

material (IBRM) 1569International conference on harmonization,

see ICHInternational HapMap consortium 77Intestine trifoil factor (ITF) 942– expression of, in rice grain 941Intron A 17, 468, 480, 1402Invader 84Investigational medicinal product dossier

(IMPD) 1697Investigational new drug (IND) 1121, 1638– application 865Invitrogen 1028Iodine 499Iodoacetamide 1073Iododeoxyuridine 1261– radioactive labeled 519Iodogen 1254Ion homeostasis 971Ion mobility spectra 1348Ion mobility spectrometer, see IMSIonomycin 272Iontophoresis 1382IPAH (idiopathic pulmonary arterial hyper-

tension) 1743– aviptadil treatment 1750– causes 1750Ipsalazide 1381IPW 220IRES element 766Iressa 76Irinotekan 57Iron protoporphyrin IX 1582Iron-transferrin complex 1426

Subject Index 1863

Ischemia-reperfusion 317Isoelectric focusing (IEF) 798– capillary 798– in purity and homogenicity control 1563– profile of purified human IgG from PER.C6

cell 799Isoelectric point 1563Isophane insulin 469Isopropyl-thiogalactopyranoside 1022, 1617Itraconazole 55

jJapan pharmaceutical manufacturers association

1643Jervell syndrome 220

k22k48 220K422 526Kalikrein 1005– inhibition by aprotinin 1027Kanamycin 1024Kaposy sarcoma 156Kaulonemea cell 920KCNH2 59KCNQ1 59Keksin– cleavage 1037– processing site 1038Ketoconazole– CYP2C9 inhibitor 1590Ketoreductase domain 1810Ketosynthase domain 1807Kidney– allograft transplantation 354– xenotransplants 354Kidney precursor 359– by nuclear transfer 365– functionality after transplantation 363– in vitro propagation 364– reduced immunogenicity 362Kineret 17, 464, 1118Kitosan capsule– cross-section of 1481– degradation of 1482– for insulin delivery 1480– gastrointestinal transit of 1481– release of carboxyfluorescein of 1482Klexane 457KLKL5KLK 1434, 1440– type 2-inducing adjuvant 1435Kogenate 10, 459KoGENate 1639Kogenate FS 459

Kogenate SF 459Kozak sequence 107, 814Kringle 5 383Kunitz-type inhibitor 1027Kupfer cells 1511KvLQT1 59Kybernin 458, 1004Kybernin P 1008KyberSept trial 997Kyoto encyclopedia of genes and genomes

(KEGG) 624

lLabel-free hybridization 87Label-free pyrosequencing 87LACK antigen 201Lactate dehydrogenase 1326– Lactoferrin 866Lambda recognition recombination reaction 610Lambda system 609Lange-Nielsen syndrome 220Langerhans cell 1429Langerhans islet 1033Lantus 13, 470LARGE 116Large degradation clearance 1479Large scale biology corporation (LSBC) 861, 864Larmor frequency 1215Laronidase 475Lauryl-maltopyranosidase 1465L-CDR1 1177L-CDR3 1177L-DOPA 325, 332– dose 343– in Parkinson treatment 330– therapy 342LEA protein 980Lecithin microemulsion, hydrogenated 1550Legionella pneumophila 685Legionellae 685Legioner’s disease 685Leishmaniasis 201Lemna 897Lentiviral vector 557– production of 576Lentivirus 551, 574Lepirudin 462Lernogastrim 473Leucine enkephalin 1376– analog 1473Leucomax 472Leukemia inhibitory factor (LIF) 288Leukemic stem cells 505

Subject Index1864

Leukine 6, 16, 472Leukoprol 473LeukoScan 22Leuprolide 1378Levemir 8, 12–13, 470Levis Y carbohydrate antigen 1172Levovist 1305Levulinic acid 400Lewis molecular model 1623Lewis P450 molecular model 1609Lewy body 326–327Lewy neurite 329Lhadi 464Ligand 1273Ligand-based targeting 1272Ligand-binding assay– in biopharmaceutical quality control 1563Lignan– biosynthetic pathway 943– expression of, in rice grain 943Lilium brownii 483Limit of detection (LOD) 1568Limit of quantification (LOQ) 1568Limulus amoebocyte lysate (LAI) 197– test 1565Limulus polyphemus 1565LINK program 1614Linkage disequilibrium (LD) 81Linker– inter-polypeptide 1812– intra-polypeptide 1812Linoleic acid 1466Lipid– film hydration method 1522– folate modified 1516Lipobay 1604LipofectAmine Plus 1526– transgene expression 1528Lipofectin in gene delivery 1543Lipolex 1526Lipoplex 1510Lipopolysaccharide (LPS)-mediated inflammatory

response 716Liposome– asialofetuin-labeled 1512– cationic 1510– complex 1516– drug delivery system 1369– in nanobiotechnology 1549– unilamellae 13705-Lipoxygenase activating protein (FLAP) 82Liposomal gene delivery 1507Liposomal parenteral drugs 1370

Liprolog 12–13, 469Liquid chromatography (LC)– for peptide mapping 802Liquid chromatography/mass spectrophotometry

(LC/MS)– amino acid determination by 1004LIT1 220LMAN1 427LMW heparin 458Locus control region 765Long QT syndrome (LQTS) 1605Longastatin LAR 478Longastatina 4785�-Long-terminal-repeat (5�-LTR) promoter 552Loperamide 1795Lotronex 52Lovastatin 101, 1804– metabolized by CYP3A4 1584Lovenox 457Low molecular mass permeation enhancer 1376Lower limit of quantification (LLOQ) 1575Lowhepa 457Lowmorin 457Luciferase 1224Luciferin 1224Lufa cylindrica 484Lugol’s iodine 502Lung– toxicological effect of nanoparticles 1548Lung cancer– detection by GC/MS 1344– early detection 1343Lung tumor– PEG-PGA+DON treatment 542Luteinizing hormone (LH) 4Luteinizing hormone releasing hormone

(LHRH) 1361– PEGylation 1407Lutropin alfa 464Luveris 15, 464LX1 116Lycopersicon cheesmanii 970Lycopersicon esculentum 970Lycopersicon pennellii 970Lycopersicon pimpinellifolium 970Lyme disease vaccine 18Lymerix 18Lypolex– galactosylated 1513– mannosylated 1514lys224 700lys98 698Lysergic acid diethylamide 101

Subject Index 1865

LysoTracker 1499Lysozyme 1473– antilysozyme antibody 936– expression 937– expression of human, in rice grain 938– recombinant human 936

mM195 506MA 148 539mab17-1a 456Mabcampath 22, 455, 479MabTera 22, 456, 480, 1121Macrolin 465, 480Macrophages– gene transfer to 1513– synovial 1284Macropinocytosis 1525, 1530Macropinosomes 1525Macugen 1394Mad1 42Magainins 486Magnetic resonance imaging, see MRIMagnevist 1217MagnICON 902, 909Major histocompatibility complex (MHC) 290,

361, 905, 1489– MHCII antigen 300Major intermediate early (MIE) gene 811MALAD-1 220MALDI (matrix-assisted laser desorption

ionization) 1564MALDI-MS (matrix-assisted laser desorption

ionization mass spectrometry) 800MALDI-TOF (matrix-assisted laser desorption

ionization time of flight)– traces of glycans of antibody B 800– analysis of mPEG MAL-CV-N413 1412– galactosylation profile of monoclonal

antibodies 801– of mosses 925MALDI-TOF MS (matrix-assisted laser desorption

ionization time of flight mass spectrometry)– oligosaccharide profiles determined by

828Malein imide 1400Maleoyl-alanyl-dipeptide aldehyde 404Malva parviflora 483Mammary adenocarcinoma– treatment with GA and DON 543Mannitol, overexpression 978Mannose 679, 1513Mantle cell lymphoma 222

Manufacturers working cell bank (MWCB) 158,746

Manufacturing– expression systems for 1093– costs 1093– strategy 1089MAP30 482Marker– assisted selection 970– for angiogenesis 1281– in human blood 1326– tumor associated 1276Market health products directorate

(MHPD) 1762Marogen 472Mass Array 84Mass spectrometry (MS) 1564– for peptide mapping 802– tandem 1564Mast cell beta-tryptase 405Master cell bank (MCB) 784, 1645Master virus bank (MVB) 157Master working cell bank (MWCB) 746, 1129Mastocytomas 1429MAT (malonyl-CoA:ACP transacylase) 1814– structure 1815Mathay resinol 943Matrix metalloproteinase 1227, 1256, 1280Matrix-assisted laser desorption ionization, see

MALDIMatrix-assisted laser desorption ionization time

of flight, see MALDI-TOFMatrix-assisted laser desorption ionization time of

flight mass spectrometry, see MALDI-TOF-MSMaximum plasma concentration 51Maytansanoids, cytotoxic 1172MCFD2 427MDR1 58Meal insulin 1454Measles-mumps-rubella vaccine 1421Mecasermin 465Medical and scientific advisory council (MASAC)

424Mef2b 294Mef2c 290, 294MEK1 257MEK2 257MEKK1– phosphorylation inhibition of 1746Mellaril 64Memapsin 1782Membrane lipids– levels of 989

Subject Index1866

MEN1 2202-Mercaptoethanol 10706-Mercaptopurine 64Meristem 990Mesenchymal stem cell (MSC) 285, 366Messenger RNA, see mRNAMetabolism prediction– computational approaches 1609– in vitro techniques 16131-Metaiodobenzylguanidine 499Metalyse 11, 462Metastatic colon cancer 206Methanethiosulfonate 1400Methioninesulfoximine (MSX) 735, 766Methionyl-tRNA transformylase 1068Methotrexate (MTX) 76, 131, 734, 766,

1030N-Methyl-aspartate (NMDA) 6381-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

(MPTP) 327–328Metoprolol 61Methylenetetrahydrofolate reductase

(MTHFR) 76Metrodin HP 464Metronidazole– CYP2C9 inhibitor 1590Mettox– assay 1603, 1608– molecular model 1623Metyrapone 1588Mevacor 1730MF59 1425Miacalcic 477Miacalcic NS 477Mibefradil 52Micro array analysis– of gene silencing 258Micro RNA, see miRNAMicrobial pathogenesis– D. discoideum as model for 685Microbubbles 1282, 1310, 1318– conjugates 1311– for ultrasound imaging 1219– targeting 1319Microcapsules– preparation with a double emulsion technique

1373Microcarrier 739Microciona prolifera 485Microcystis viridis 484Micro-electrode array mapping technique 292Micro-gene-gun 1318– non-invasive 1544

Microinjection, pronuclear 1000Microneedle 1541– system 1383Microspheres– biodegradable 1487– hydrophobic 1371– drug distribution in 1372– for encapsulated DNA vaccines 1492– hydrophilic 1374– immunoresponses 1500– polyorthoesters for 1496– uptake by macrophages 1499– using polyesters 1493Midazolam– metabolized by CYP3A4 1585MIDGE vector (minimalistic immunogenetically

defined gene expression) 183– application of 198– characteristics 189– immunization pathways using 200– immunomodulating 191– production 188– smart 191– structures 187Milyzer 461Mimic Sf-9 cell 1047Mimotope 1194Minidalton 457Ministry of health, labour and welfare

(WHLW) 1643MIRD schema 523Mirimostim 473miRNA (Micro RNA) 222, 628Mistral 458Mitogen activated protein kinase 1

(MAPK1) 258Mixtard 13Mobenakin 464, 480MOG (myelin oligodendrocyte glycoprotein)

11938-18C5 epitope on 1204– (8-18C5)-fab complex 1201– antibody responses against 1199– structure of 1201Molecular dynamics 1609Molecular imaging 1309– applications 1235– contrast agents for 1225– for drug discovery 1230– modality properties 1229Molecular rational design– of product development 703Molgramostim 472

Subject Index 1867

Moloney murine leukemia virus (MoMLV) 574Momordica charantia 484mondoBIOTECH 1741, 1749Monoaminooxidase B 330Monoclate 459Monoclate-P 459Monoclonal antibody (MAb) 20, 1105– analytical methods for 1116– application areas of 1116– approved therapeutics 1120– by perfusion technology 743– CIPP strategy 1128– cytotoxic drugs and toxins linked to 1124– expression systems 1135– fed-batch and perfusion cultivation 1087– generation 1109– generic manufacturing strategy 1129– glycosylation of 1135– heavy and light-chain polypeptides 906– huNR-LU-10 862– immunogenicity 1657– manufacturing 1083, 1126– market demands 1714– market perspectives 1119– physical properties of 1128– release specifications for 1130– routine manufacture 1127– therapeutic 1086Monophospholipid A 194Monotard 13, 470Monteplase 461Moroctocog-� 10Moss– cell culture 922– glycoengineering in 927– in biopharmaceutical production 920– transformation 921Mouse antibody production test (MAP) 434Mouse, chimeric 657Mouse embryonic fibroblast 286Mouse, gene targeted 649Mouse lymphage assay 1624Mouse minute virus (MMV) 434Mouse, transgenic 1111, 11626-MP 57MRI (magnetic resonance imaging) 346, 1215– application 1217– macrophage imaging 1282– paramagnetic agents 1217– prion disease imaging 1289– schematic set-up 1216– supermagnetic agents 1217mRNA (messenger RNA) 628

MSCB (master seed cell bank) 746MTHFR, see methylenetetrahydrofolate reductaseMTT (3,4,5-cimethylthiazol-2yl-2,5-diphenyl

tetrazolium bromide) 640Mucolytic enzymes 1376Mucopolysaccharidosis 24, 862Multiangle light scattering (MALS) 162Multilamellae vesicles 1370Multifunctional-type nanodevice (MEND) 1522– transfection activities 1524Multilase 461Multiple sclerosis (MS) 17– epidemiology 326Multiplexing strategy 87Multiplicity of infection (MOI) 1048– determination of high or low 1049Multi-wavelength anomalous dispersion 1066Murine embryoid body 289Muromomab 1086Muromomab-CD3 456Murray breast tumor 131Mutagenesis 592, 666– change-of-specificity 1818– combinatorial cassette 706– loss- and gain-of-function 1817– novel polyketides by change-of-specifici-

ty 1820– random oligonucleotide 706Mutual recognition agreement (MRA) 1677MVL 484MWCBs see manufacturers working cell bankMWCBs see master cell bankMyasthenia gravis 1188Mycobacterium tuberculosis 1422Myelin basic protein 1200Myelin oligodendrocyte glycoprotein, see MOGMylotarg 22, 454–455, 480, 1086, 1121, 1125,

1172Myoblasts 320Myocardial infarction 11– imaging by NIR 1284Myocardial regeneration– strategies 295– using hES 283Myocyte enhancer factor 294Myomap 1305MyoSzint 21Myxococcus xanthus 1824

nNadroparin calcium 457NAF 483Nanocrystal technology 1538

Subject Index1868

Nanocrystals– Quantum dot 1539, 1545Nanofact 459Nanoparticles 1306– solid lipid 1373Nanospheres, hydrophilic 13742-Naphthylalanine 413Nartogastrim 473Nateplase 461National center of biotechnology information

(NCBI) 254National institute of health (NIH) 1233Natrecor 476N-cadherin 320NCE 1685NCRMS 220NCSU-23 275Near infrared (NIR) principle 1222Nelfinavir 58Neo 299Neo gene 665Neocarcinostatin chromophore 1125Neocolipor 25Neocormon 16Neokidney 369Neomycin 299Neomycin phosphotransferase 766, 897Neoplastic disease– antibody treatment for 1121Neorecormon 472Nesiritide 476Nespo 8, 16, 472Neulasta 16, 473, 1406, 1730Neumega 4, 17, 464Neupogen 16, 473, 1406, 1755Neupopeg 16, 473Neurokinin antagonist– identified by Pep2Lead approach 1781Neurokinin receptor agonist 1780Neurokinin receptor antagonist 1779Neuronal cell line NCA1 775Neuron-specific enolase 1326Neutrogin 473Neutrophil 1195Neu-Up 473New biological entities 1362New drug application (NDA) 50, 1638– submission of pharmacogenetic data to 62NiaStase 459Nicotiana benthamiana– GNTI from 902, 925Nicotiana tabaccum 950Nicotine 58

Nicotinic acetylcholine receptor 1188Nifedipine– metabolized by CYP3A4 1585NIH3T3 156Niphatevirin 485Nitric oxide synthase (NOS) 316– endothelial 316– inducible 316p-Nitrophenyl phosphate 714Nkx2.5 290NMR, see Nuclear magnetic resonanceNon-Hodgkin lymphoma 21– antibody treatment 1121– clinical trials of RIT 501– radioimmunotherapy 500Non-protein-coding RNA, see npcRNANonproteolytic activator 388Nonsmall cell lung cancer 222Noratak 476Noravid 461Norditropin 14Norditropin Nordiflex 477Norditropin SimpleXx 477Normiflo 458Northern blot analysis of ITF levels 942Nostoc elypsosporum 483, 1406Novact M 459Novetumomab 21Novolin L 470Novolin N 471Novolin R 470Novolog 13, 470Novolog 70/30 FlexPen 470Novolog FlexPen 470Novolon 13NovoMix 30 13, 470NovoMix 70 470NovoRapid 13, 470– 30Mix 470Novos 464NovoSeven 10, 459npcRNA (Non-protein-coding RNA)– linked to human disorders 220NS0 728, 763NSCLC 220Nuclear factor kappa B 317Nuclear imaging 1220Nuclear magnetic resonance (NMR) 1066Nuclear polyhedrosis virus (NPV) 27Nuclear translocation 1530Nutropin 14, 477Nutropin AQ 477Nutropin Depot 477

Subject Index 1869

oOATP-C 58OCC1 220Octreotide 1376Oct-4 276Octin 464, 480Octreoscan 519, 1226Octreotide 478ODN see oligonucleotide/oligodeoxynucleotideOffice of new drug chemistry (ONDC) 1639Office of new drugs (OND) 1639Office of regulatory affairs (ORA) 1639Office of therapeutics research and review

(OTRR) 1639Official control authority batch release

(OCABR) 1680Official medicines control laboratories

(OMCL) 1680OGamma100 468Oidragit R 1381Oidragit RL 1381Oidragit RS 1381Oif 467OKT3 101Oldenlandia affinis 484Oligodeoxynucleotide (ODN)– antisense 230, 313–314– CG-motifs 195– c-myc antisense 316– containing CpG motifs 1437– decoy 314– double-stranded decoy 230– inhibition of phospholamban 318– mechanism of action 231– PT-based 198– single stranded phosphorodiester based 196Oligofectamine 573Oligonucleotide (ODN)– chimeric 1533– mediated polymorphism recombination

590– P-labeled 526– single stranded 1533– triplex forming 525, 1533Oligonucleotide ligation assay (OLA) 84Olsalazine 1381Omalizumab 456, 1086Omeprazole 61Oncaspar 475, 480, 543, 1399, 1411Oncogenes 732OncoLAR 478Oncology– imaging 1249

– radiolabeled drugs for 1250– therapeutics 1249OncoSzynt 21Oncovirus 551Ononitol, overexpression 978Ontak 7, 24, 456, 480Onzar 456, 480Oocyte– in vitro culture 274–275OP-1 464– implant 464Open reading frame, see ORFOP/LMWH 457Oprelvekin 464Optical imaging 1222– applications 1223– contrast agents for 1223Optisulin 13, 470Oral application– use of nanoparticles for 1549Oral hypoglycemic agents 1459Oral spray insulin– in diabetes type 2 treatment 1455Oralin 1445– administration 1451– as meal insulin 1454– chronic administration 1458– delivery 1446– dose-response relationship 1452– efficacy 1457– mechanism of absorption 1448– properties 1448– radiolabeled 1450Oralin RapidMist delivery device

1447ORF (open reading frame) 170, 248, 605,

610, 1045Orgasuline rapide 471ORMUCS 1787Orthoclone 21, 456Orthoclone OKT3 454, 456, 1086Oryctes rhinoceros 486Osmolytes levels 988Osteogenic protein 24Osteoporosis 15Osteotonina 477Ovalbumine 234OVCAR3 539Overall dyskinesia rating scale 339Overall glycemic control 1457Ovidrel (Ovitrelle) 477Ovitrel 15Oxalis tuberose 483

Subject Index1870

Oxazaphosphorine– hydroxylation catayzed by CYP2B4 15974-Oxo-butyric acid 400Oxygen uptake rate 825Ozogamicin 455

pp123 39p43 39Pachymatisma ionstonii 482Pachymatismin 482Paclitaxel 101, 131, 137, 139, 314, 1367– for in situ radiotherapy 510– in cancer treatment 1172– metabolized by CYP2C8 1594PAGE (polyacrylamide gel electrophoresis)– kinetics of thrombin activation 437Paget’s disease 15Palicourea condensata 484Palicourein 484

1-Palmitoyl-2-oleoyl-sn-glycerol-3-phosphocho-line (POPC) 1508–1509

Palivizumab 21, 456, 1086– against infectious disease 1176Pallidotomy 331Pamiteplase 462PAMPA (parallel artificial membrane permeation

assay) 1787Panax ginseng 482Panorex 456Parallel line analysis (PLA) 168Paraquat 328Parathyroid hormone 1378Paratope 1190Parkin gene 329Parkinson disease (PD) 77, 325– epidemiology 326– pathways and targets for 625– therapy 329Parnaparin sodium 457Paroxetine 61Parvovirus MVM 747Pathogen-associated molecular pattern

(PAMP) 194Pathogen viruses– infection risc attenuation in fVIII concen-

trates 423Patients’ responsibility 1737Pattern track process 1334–1335Paxton ovarian tumor 131pBR322 156PCGEM1 220PCNA (proliferating cell nuclear antigen) 316

PCR (polymerase chain reaction) 134, 607– application of B-type DNA polymerase 709– performance in 712– product identity test by 167– transgenic animal cell analysis 1000– quantitative 1564PDGF (platelet-derived growth factor) 153Peak cell density 1052PEBBLES technology 1546PECAM-1 360Pediarix 19PEG, see poly(ethylene)Pegademase bovine 475Pegaspartase 475, 480Pegasys 17, 468, 1402, 1411– properties of 1403Pegfilgrastim 16, 473, 1406Peginterferon alfa-2a 468Peginterferon alfa-2b 468PEGIntron 468, 1401–1402– properties of 1403Peguptanib sodium 1394Pegvisomant 478, 1404, 1411Penicyllium nalgiovense 483Pep2Lead 1772– concept 1778PepHarvester algorithm 1779Peptic agent 474Peptide– active sequence 1779– antimicrobial 1286, 1433– aptamers 638– design system 1779– directed radiotherapy 516– effect of protease inhibitors on 1470– FITC-tat 637– in disease targeting 1275– intestinal absorption 1463– leader 1037– mapping 802, 1195, 1562– nasal delivery of 1378– phage libraries 1275– PEGylation of 1407– radiotracer 1256– spacer 1038– stability 1469– transporter 636–637– ubiquicidin-derived 1286– vaccination 1429Peptide biopharmaceuticals– chemical modification 1472Peptide, cationic– delivery system 1419, 1437

Subject Index 1871

– vaccine adjuvants 1426Peptide, cationic antimicrobial 1419– artificial 1433– as vaccine adjuvant 1433– subgroups 1433Peptidoglycan 938PER.C6 724, 764, 775– human cell line 779PER.C6 cell 728– characterization of antibodies by 797– fed-batch process development 789– for manufacture of recombinant protein 784– generation of 782– transfection 785PER.C6 cell line– batch process profiles 791– continuous perfusion process 794– growth data for antibody producing 790– supplemented batch process 793PER.C6 clones– generation of, for monoclonal antibody 784Percutaneous transluminal intervention

(PTI) 313Percutaneous transluminal coronary angioplasty

(PTCA) 236Perfusion scintigraphy 1238Peripheral blood mononuclear cell (PBMC)

361Peripheral blood progenitor cell (PBPC) 1757Permeation clearance 1480Peroxidase stress inducible 894Personalized medicine 76Pertussis 18Pertuzumab 1164PET (positron emission tomography) 499, 1220,

1243– cancer therapy by 1243– for Alzheimer targeting 1286– imaging of cancer 1243– monitoring of radiolabeled drugs 1252– radioisotopes for 1244– radiopharmaceuticals for 1246– radiotracer 1246PET (positron emission tomography) imaging– of apoptosis 1262– of end-points of tumor 1259– of gene expression 1255– of glucose metabolism 1260PEVKEK region 1199PGA (pseudomonas 7A glutaminase-

asparaginase) 539– antitumor effect of 539– efficacy of 539

PHACIR (pharmacophore identificationroutine) 1771, 1778, 1781

– concept 1776Phage artificial chromosome (PAC) 656Phage display technology 1112Phagocytes 1548Pharmaceutical research and manufacturers

of America (PhRMA) 1643Pharmaceutically Tractable Genome (PTG) 99Pharmacodynamics– PET studies 1254Pharmacogenetics 49– environmental factors and 75– terms 74Pharmacogenetics research network (PGRN) 77Pharmacogenomics 49– environmental factors and 75– terms 74Pharmacokinetics– intracellular 1526, 1529– in quality control of biopharmaceuticals 1576– of biopharmaceuticals 1253, 1365– of gene delivery systems 1254– of PEG 1396– of small molecules 1250Pharmacophore concept 1776Pharmacophore identification routine,

see PHACIRPharmaCos DG Enterprise 1676Pharmazymes 1613Phenylpropanoid metabolism 943Phenytoin– metabolized by CYP2C9 1590Phosphato-dihydrofusidate 1376Phosphinothricin acetyltransferase 898Phosphoenol pyruvate 1075Phosphoethanolamine N-methyltransferase 978Phospholamban 318Phospholipids 1376PHS Act 1640Physcomitrella patens 905, 919– GNTI from 925PHYSPROP database 1789Pichia pastoris 713, 1135Picorna virus 766PINK1 gene 329Pinocytosis 1397Pinoresinol 943Pip (pristinamycin-induced proteine) 732pIVEX (plasmid for in vitro expression)

vector 1066PIVI-Argonaute-Zwille domain (PAZ) 246pJM17 156

Subject Index1872

PLA (process licence application) 742– Plasminogen, mini 380Plant– genetically modified 894– production of recombinant proteins in 893– production of stress tolerant 974– water balance 971Plant cell– effect of additives on product yields 957– for biopharmaceutical production 949– responses to stresses 972Plant cell suspension cultures– recombinant proteins from 951Plant derived biopharmaceuticals– N-glycosylation 924Plant plasma membrane– K invard rectifying channel 973– K outward rectifying channel 973– voltage independent cation channel 973Plant, transgenic, see transgenic plantsPlasma insulin concentration 1482Plasmacytoma 763Plasmid DNA 1532– based vector 186– methods for quantifying subcellular

distribution 1527– purification 1068– templates for wheat embryo system 1067Plasmid stability– of IL4v expression vector 1026Plasmid-encoded selection gene (POD) 1035Plasmin 1005– inhibition by aprotinin 1027Plasminer 461Plasminogen– activation 380– activator 1074– micro 380Plasmodium falciparum 1422Plasmodium falciparum circumsporozoite protein

(CSP) 682Plasvata 461Platelet-derived growth factor, see PDGFPleomycin 666Pleurotus ostreatus 482Polio 18– virus 263, 766Polyadenine– in gene delivery 1543Polyarginine 1425– as type I-inducing adjuvant 1429– CpG-ODN-based vaccines 1439– stimulatory efficacy on T cells 1431

– vaccine adjuvant 1426– with CpG-ODN 1437Polybutylcyanoacrylate 1310Polycyanoacrylate 1305Polydimensional SNP 88– microarray 89– platform 88Polydimethylsiloxane, nonbiodegradable 1546Polyesters– for DNA vaccine delivery 1492Poly(ethylene glycol) (PEG) 957, 1076– acylating reagents 1398– conjugates with 1367, 1393– properties 1394– reagents 1397– reagents for protein PEGylation 1398– pharmacokinetic parameters 1396PEG8/IGF2AS 220PEG-adenosinedeaminase 1411PEG-asparaginase 1411PEG-biphalin 1410– preformulation 1410PEG-conjugates, analysis of 1411PEG-CV-N-conjugates, molecular weight analysis

of 1413PEG MAL-CV-N reverse-phase purification 1414PEG-staphylokinase, preformulation 1409Polyethyleneimine 1316– in gene delivery 1543Polyferon 468Poly(glutamic acid) 1368Poly(glycolic acid) 1494Polyglycolide 1305Polyhistidine– in gene delivery 1543Polyketide 1804– biosynthetic gene cluster 1806– heterologous hosts for production of 1824– key reactions of biosynthesis 1809– natural products engineering 1803Polyketide synthase 1804– biosynthesis 1806–1807– classification of 1806– engineering of novel polyketides 1815, 1820– organization of 1808– precursor-directed biosynthesis 1819– production requirements 1822– tailoring steps in erythromycin synthesis

1811– structure of natural products 1805Poly(lactic acid) 1491, 1495Poly(lactic-co-glycolic acid) 1492Polylactide 1305

Subject Index 1873

Poly(lactide-co-glycolide), for peptideencapsulating 1371

Polylysine 1316, 1512– mannosylated 1514– vaccine adjuvant 1426Polymer– bulk erosion 1491– design for DNA vaccine 1493– hydrolysis 1491– synthetic, biodegradable 1491Polymer conjugates– commercially available 1368Polymer erosion rate 1495Polymer nanoparticles, two-step process 1306Polymerase– II 217– III 217– Pfu 709– Taq 709– Tgo 709Polymerase, b-type– structural features 710Polymerase chain reaction, see PCRPolymeric microsphere 1371Polymeric permeation enhancer 1376Polymeric solution 1374Polymyositis-scleroderma overlap syn-

drome 1193Poly(orthoester)– cytotoxicity 1499– feed composition and characterisation

of 1496– for DNA vaccine delivery 1494– microspheres 1487– synthesis 1494Polyoxyethylene 400Polyoxyethylene-20-stearyl ether 1376Polyoxyethylene-24-cholesterol ether 1376Polypeptide synthase– typical structure of 1816Poly(styrene-maleic acid anhydride) 1367Polyvinylpyrrolidone 957Pompe disease treatment 861Pondimin 52, 1604Pooling strategy 87POPC, see 1-palmitoyl-2-oleoyl-sn-glycerol-

3-phosphocholinePopulation genetics 81Porcilis AR-T DF 25Porcilis pesti 26Porcilis porcoli 25Porcine biphasic insulin 471Porcine embryo 275

Porcine endogenous retrovirus (PERV) 369Porcine fetal mesencephalic cell– transplantation of 332Porcine isophane insulin 471Porcine neutral insulin 471Porcine pseudorabies virus (PRV) 434Pork atrapid 471Pork insulatard 471Pork mixtard 30, 471Portfolio assessment 1735Posicor 52Positive transcription elongation factor 219Positron emission tomography, see PETPostcommisural putamen 343Post-glutamyl peptide hydrolysis (PGPH) 398Post-prandial glucose 1456Poststreptococcal glomerulonephritis

(PSGN) 384Post-transcriptional gene silencing (PTGS) 571POT1 (protection of telomeres protein) 43Prader-Willi syndrome (PWS)– pathways and targets for 626Pravastatin 58Prediction error sum of squares 1796Pregnane X receptor (PXR) 1788Prescription behavior 1736PREVENT 237PREVENT-I trial 315PrexelizuMAb 1116Primavax 19Prion 746– disease targeting 1287Pristinamycin-induced proteine (Pip) 732Pro inflammatory cytokines 1511Processing procedure– downstream 5– upstream 3Prociclide 461Procomvax 19Procrit 3, 16, 472Product patents 1758Progesterone– CYP3A4 activated 1587– metabolized by CYP2C3 1595Prokine 472Prolastin 464, 858Prolastina 464ProLease-rhGH 477Proleukin 17, 465, 480Proliferating cell nuclear antigen, see PCNAProline 974– catabolism 974– dehydrogenase 974

Subject Index1874

– uptake 1435Pro-opiomelanocortin (POMC) 1327Propion aldehyde 1399Propulsid 52, 1605Proquest system 614Prostacycline 1007ProstaScint 21, 744, 1277Prostate cancer– PGA and DON treatment 540Prostate-specific membrane antigen

(PSMA) 1277Prostatic acid phosphatase 1326Protamine 1531Protaphane 13Protease– baculovirus encoded 1049Protease inhibitor 395, 1467– absorption-enhancing mechanism 1472– effect on insulin degradation 1469Protein kinase A (PKA) 318Protein– anti-apoptosis 821– anti-bacterial 485– anti-cancer 481– anti-fungal 482– anti-viral 483– as disease marker 1337– based agents 460– Bcl-2 family of 819– biopharmaceuticals 1463– body 935– chemical modification 1472– disulfide bonded 1072– drug sources 481– endogenous 938– heat shock 982– human 774– identification 1337– intestinal absorption 1463– levels 988–989– marker 1327– milk expression technology 998– nasal delivery of 1378– optimized BEVS-based 1048– production in plants 893– ribosome-inactivating 482– selenium-cysteine labeled 1066– selenium-methionine labeled 1066– storage 938– synthesis and secretion in cultured plant

cells 957– transduction 636– transgenic derived 870

Protein-1, activated 236Protein A, immobilized 1130Proteinase 3– peptide mapping of epitopes on 1195Protein C– activated 457– concentrate 457ProteinChip array– antibody-coupled 1337– types of 1329ProteinChip reader– sample analysis in 1330ProteinChip system 1325– applications 1334Protein data bank 380Protein disulfide isomerase 1074Protein diversity– generation of 586Protein expression 934– examples 682, 1094– for recombinant protein deposition 935– using ExpressTec in grains 945– using transitional machineries 936Protein-fragment– complementation assay 1161Protein G 1130Protein kinase– for drug development 639Protein L 1130Protein production– baculovirus based 1050– cell free 1064– generic protocol 1050– infection kinetics 1052– nutritional/kinetic parameters in baculovirus

based 1051– protocol for BEVS-based 1057Protein, recombinant, see recombinant proteinProtein screening– high content 594– high-throughput 594, 596– spectroscopic methods 595Protein stability– factors affecting 956Protein storage vacuole 935Protein therapeutic dendrogram 113– Protein therapeutics (PT) 104Protein toxin– conjugates 1173– linked to MAb 1124Protein transduction domain peptides 1523Proteolysis– intravascular 380

Subject Index 1875

– pericellular 380Proteomics 30Protexia 870Prothrombin 380– activation 379Protropin 14, 477Pro-urokinase 462Prous Integrity database 453Pseudomonas 7A glutaminase-asparaginase,

see PGAPseudomonas aeruginosa 686, 1010– infection 1751Pseudomonas exotoxin A 1173Pseudomonas syringae 483PsorBan 637Psoriasis 1285pSP65 vector 1067PSZA11q14 220Pulmonary arterial hypertension (PAH) 1742,

1749Pulmonary vascular resistance (PVR) 1749Pulmozyme 23, 475Pure System 1068– cell free from E. coli 1069Puregon 15, 465Puregon Pen 465Purinethol 64Purity– analytical methods for determination of 1567Puromycin N-acetyl-transferase 766Putrescein 1075Pyrimidine nucleoside radiolabeled 1262Pyrococcus furiosus 709Pyrogen test 1565Pyroline-5-carboxylate 975Pyrosequencing 87Pyrrhocoricin 486Pyruvate dehydrogenase 1075Pyruvate-formate lyase 1075

qQ6B 1692Qiagen kit 90QS21 1424QSAR equation 1787QT genes 59Quality control– analytics in 1557– international guidelines 1571Quantison 1305Quantitative structure-activity relationship 1611Quantitative structure-property relation-

ship 1791

Quantitative trade loci 969–970Quixidar 454, 457

rRACHITT 590Radioimmunoassay (RIA) 1563Radioimmunoconjugates 508Radioimmunotherapy (RIT) 498, 1125– pre-targeted 512– therapeutic index 511Radioisotope– positron emitting 1244Radiolabeling– monitored with PET 1251– of anti-cancer drugs 1251– iododeoxyuridine 519– of pyrimidine nucleoside 1262Radionuclides– for targeted in situ radiotherapy 499Radiopharmaceuticals 1246Radiosynthetic methods 1246Radiotherapy 497– biopharmaceuticals for 497– HuM195 dose 506– ibritumomab tiuxetan dose 504– in situ 497– M195 dose 506– maximum tolerated dose 502– tositumomab dose 503Radiotracer 1253– antibodies for 1258– peptides for 1258– properties 1248– small molecule 1256RAEL 526rAHF-PFM 459Raji B-cell lymphoma 526RANTES 363Rap1 43Rap1p 42–43Rapacuronium bromide 52Rapamune 1538Rapamycin 101, 314–315, 1804, 1818Raphanus sativus 483Rapid amplification of cDNA ends (RACE) 109RapidMist– accuracy of dose delivery 1449– device 1449Rapilysin 11, 462Raplon 52Raptiva 454, 456, 1086Rasburicase 475Rat antibody production test (RAP) 434

Subject Index1876

Raxar 52RAY1/ST7 220Rayleigh scattering 1305RB69-polymerase 710RCR (recombination chain reaction)– homologous recombination by 591R&D portfolio 1733Reactant ion peak 1347Rebetron 17Rebif 17, 467, 1404RecDNA somatotropin 477Receptor tyrosine kinase (RTK) 639RECIST criteria 1259Recombinant Antihemophilic Factor VIII 424Recombinant blood factor 9Recombinant factor VIII (rFVII) 420, 459Recombinant HB 1422Recombinant hematopoietic growth factor 15Recombinant hepatitis B surface antigen

(rHBsAg) 3Recombinant hormone 14Recombinant human vascular endothelial

growth factor, see rhVEGFRecombinant IFN 16Recombinant IL 16Recombinant insulin 12Recombinant protein 189– companies using plant based 904– expressed in cultured plant cells 952– from nuclear transgenes 895– in cereal grains 932– in plastids 898– plant made, commercially available 903– PER.C6 cell for 784– post translational modifications of 955– production 672, 907, 1726– transient expression levels 901– vectors for 730Recombinant thrombolytics 11Recombinate 10, 421, 459Recombinate rAHF 1639Recombination chain reaction, see RCRRecombivax 18Recombivax HB 1639Recormon 472RECTSER 76Redux 52, 1604ReFacto 10, 459ReFacto AF 459Reference sequence 255– database 110Reference standards– for analytical testing 1569

Refludan 23, 462REGENT-I trial 316Regranex 24, 465Regulations– EU-US comparability guidelines 1693– for biological products 1686– for biopharmaceuticals 1641, 1682– for cell lines 1645– for dosage forms 1646– for drug product 1647– for drug substance 1648– for formulation components 1646– for manufacturing process 1647– for purification phase 1646Regulatory bodies 1676REM sleep disorder 328Remicade 21, 456, 864, 1086, 1118–1119Renal cell carcinoma 17Renal cell replacement– strategies for 368Renal toxicity– from PDRT of malignancies 517ReoPro 462, 1086, 1117Reovirus type 3 (REOV-3) 434Repaglinide 58Repeat induced point mutation 244Replagal 23, 475Replication competent adenovirus (RCA) 166Reporter gene assay, non-invasive 1228Reporter genes 671Residual DNA 167Respiratory syncytial virus (RSV) 263, 454Respitin 463Re-stenosis 235– arterial 313Restriction endonucleases 168Restriction enzyme-mediated integration

(REMI) 667Restriction fragment length polymorphism

(RFLP) 84Retavase 11, 462Reteplase 11, 462Reticulo endothelial system 1366– in DNA vaccine delivery 1490Retinal pigment epithelial cell, see RPERetinoic acid 294Retrovirus 31, 551, 574RETTAU 77Revasc 23, 462Reverse phase high-performance liquid

chromatography, see RP-HPLCReverse transcriptase polymerase chain reaction

(RT-PCR) 290

Subject Index 1877

Reversible perfusion defect size (RPDS) 177Reviparin sodium 457Rev protein 552Rev response element (RRE)Rezulin 52rf9a 699R-Ferone 467Rhabdomyosarcoma 222RheoPro 21Rheumatoid arthritis 17, 24, 79– pathways and targets for 626, 1284RhinoRx 866rhVEGF (recombinant human vascular

endothelial growth factor)– moss derived 923Ribavirin 17Ribonucleic acid, see RNARibosomal binding site 1023Ribosomal RNA, see rRNARibosome display 1112Ribozymes 570Rice endosperm, expression of lignan 944– fusion strategy to express small peptide

in 942Ricinus communis 1173Rif1 43Rif1p 43Rif2p 43Risperidone 101Rituxan 21, 456, 480, 503, 526, 1086– application 1278Rituximab 21, 456, 480, 503, 526, 1086, 1164– cell killing trigger 1169RNA (ribonucleic acid) 628– see also under special RNA types– -based therapy for HIV 569– micro- 216– steroid receptor activator 218– transfer- 215– ribosomal- 215, 628RNAi (RNA interference) 31, 244– diversity of viral targets 571– expression of vector-based approaches for 631– in treatment of viral infection 262– mechanism 245– pathway 629– silencing 571– silencing genes as tools and therapeutics 624– therapeutic applications 259, 570RNA-induced silencing complex (RISC) 571,

629RNase inhibitors 1079Roceron-A 468, 480

Roferon 1411Roferon A 17, 468, 480Roller bottle– optimum MOI, TOI and TOH in 1053– process 737Romano-Ward syndrome 220Rosiglitazone clearance 1594Rosuvastatin– label recommendations 55Rotenone 327–328Rous sarcoma– retrovirus 764– virus 263RPE (retinal pigment epithelial cell)– human 333– location and anatomy of 335– microcarrier bound 338– PD treatment of 336RP-HPLC (reverse-phase high-performance liquid

chromatography) 164, 436, 1562rRNA (ribosomal RNA) 628Rs-AFP2 483RTQ-PCR 116RU-41740 463Rush dyskinesia scale 340Russel-Silver syndrome 220Rybozyme 634

sSaccharomyces cerevisiae 399, 1021, 1033, 1422,

1628, 1824– expression platform 1027– expression vector 1035Saccharopolyspora erythraea 1804Sacrophaga peregrine 1434Safety working party (SWP) 1670Saizen 14, 477Salmon calcitonin 477Salmonella typhimurium 1011, 1625Sandoparin 454, 458Sandostatin 478Sandostatin LAR 478Sanitation era 103Sapecin B 1434Saponaria officinalis 484Sargramostim 472Satin/APOE system 78SCA8 220Schizophrenia– pathways and targets for 627Schizosaccharomyces pombe 571– TPI1 gene from 1035SciTropin 476

Subject Index1878

Scleroderma autoantigen centromer pro-tein 1191

SCN5A 59SCNT (somatic cell nuclear transfer)– embryo 279– oocytes 272Scopolamine 1382Scytovirin 484SDS-PAGE (sodium dodecyl sulfate-polyacryla-

mide gel electrophoresis) 725, 1563– antibody detection 1077– of human IgG produced in PER.C6 cells 798– of total soluble protein from rice grain 940– of total soluble protein from transfected

Nicotiana leaves 909– PEG-conjugate analysis 1411Secoisolariciresinol 943beta-Secretase 1782– enzyme assay 1784– virtual screening 1784Seldane 52SELDI (surface-enhanced laser desorption

ionization) process 1335– distinctions of 1333SELDI TOF-MS (surface-enhanced laser

desorption ionization time-of-flight massspectrometry) 1325

Selective combinatorial randomization(SCR) 592

Selectively infective phages 1112Seleparina 457SELEX technique 635Self-organizing maps 1797SEM micrograph of microcapsules 1373Sendai virus liposome 235Sensitive particle acoustic quantification 1308– procedure 1313Sepsis 24Sequencing– by hybridization 84– for structure determination 1562Sequential random mutagenesis 705SERCA2a 318Serine protease inhibitor 1005Serine proteinase– activation mechanism 390– cascades 379– mechanism 377– trypsin-like 378Sermorelin acetate 476Seronos follicle-stimulating hormone 9Serostim 14Serotim 477

Serum amyloid A 1337Serum amyloid protein 1287Serzone 1604Severe combined immunodeficiency (SCID) 361SHARP 218Shepheridin 1 486Shepheridin 2 486Shikamate-chorismate pathway 943Short tandem repeat 277shRNA (short hairpin RNA) 243, 247, 573Shuttle vector 156Sical 477siD direct 255siFect system 632Signalling pathways, and their disease

implication 625Silicon, in drug delivery 1540Silteplase 461Simian immunodeficiency virus (SIV) 556Similar Biological Medicinal Products Legislation

(SBMPL) 1764Simulect 21, 456, 1086Simvastatin 58Single nucleotide polymorphism, see SNPSingle photon emission computed tomography,

see SPECTSIP1 42SIRAN 681siRNA (small interfering RNA) 573– biopharmaceutical drugs 632– characteristics 630– chemical synthesis 631– delivery of 632– design parameters 248– individual 257– interaction with RISC 249– in vitro transcription of 631– mechanism of action 630– off-target effects 256– peptide based 573Sirolimus 314Sjörgen syndrome 1190Skeletal myoblast 285Small cell lung cancer 21Small fragment homologous replacement

method 1533Small interfering RNA, see siRNASmall molecule therapeutic target (SMT) 104Small nucleolar RNA, see snoRNASmall nucleolar RNP, see snoRNPSmall organic molecules, in disease targeting

1275Small pox 1488

Subject Index 1879

Small temporal RNA, see stRNASmall-vessel vasculitis 1195Smith-Watermann, dynamic programming

sequence alignement algorithm 255SMP-140 477Snakin proteins 485SNaPshot 84Snell law 1218snoRNA (small nucleolar RNA) 215, 628–629snoRNP (small nucleolar RNP) 41SNP (single nucleotide polymorphism) 71– analysis 85– scan 77– technology 83–84SNP-IT 84Sodium 5-methoxysalicylate 1465Sodium caprate 1376Sodium deoxycholate 1465Sodium dodecyl sulfate-polyacrylamide

gel electrophoresis, see SDS-PAGESodium glycocholate 1465Sodium glycodeoxycholate 1376Sodium salicylate 1376, 1466Sodium taurodihydrofusidate 1376Softenon 1675Solanum lycopersicum 970Solanum tuberosum 485Solclot 462Solid tumor 1174– RIT of 507–508Solinase 462Soluble insulin 471Somatic cell nuclear transfer, see SCNTSomatomedin-1 463Somatonorm 477Somatostatin receptor– in peptide directed radiotherapy 516Somatotropin 477Somatrem 477Somatropin 476–477– recombinant 477Somavert 15, 478, 1404, 1411Somazon 465Sonavist 1305Sonoporation 1318, 1382SonoVue 1305Sorangium cellulosum 1804SOS stress response 1627SOS-umuC assay 1627– industrial validation studies 1633Sotalol hydrochloride 1605Sotocor 1605Southern blot 83, 134, 654

– transgenic animal cell 1000– of IgG expressing PER.C6 clones 786Southern hybridization– of genomic DNA 736Soybean trypsin inhibitor 1470, 1472SPECT (single photon emission computed

tomography) 177, 261, 1220– applications 1222– contrast agents for 1222– for Alzheimer targeting 1286– principles and instrumentation 1220– spatial resolution 1221Spermidine 1075Spheramine 325– dosing 344– microcarrier 336– treatment 344Sphingosine kinase-1 (SPHK-1) 218Spinal muscle dystrophy (SMA) 78Spin-lattice relaxation time 1216Spin-spin relaxation time 1215Spiramycin 1818Spodoptera frugiperda 1047Squamous cell carcinoma 238SRA-Del 220SSCP 84SSEA-1 276SSEA-3 276SSEA-4 276Sso polymerase 711Staphylocoagulase, prethrombin-2 complex 387Staphylocoagulase SC 386Staphylococcus aureus 1129, 1350Staphylokinase, plasminogen complex 384Staphylokinase (SAK) 381, 383STAT-1 233STAT-3 233Stem cell, myocardial regeneration, using 320– neural 332Sterilize in place (SIP) 746Stimulated acoustic emission 1308– principle of 1309Stiripentol– CYP2C9 inhibitor 1590Stop codon suppression 667, 670Strattera 56, 64Streptavidin 511– coupling to microcapsules 1310Streptococcus mutans 865Streptococcus pneumoniae 1421Streptococcus pyogenes 1130, 1422Streptokinase, plasminogen complex 385Streptokinase (SK) 381, 384

Subject Index1880

Streptomyces avidinii 511Streptomyces coelicolor 1823Streptomyces lividans 1824Streptomyces peucetius 1804Stromal antigen 1281stRNA (small temporal RNA) 628StSN1 485StSN2 485Substrate recognition site 1584SUBSTRUCT– analysis 1794– classification of CNS activity 1795– classification with 1792– fragmentation scheme of propanol 1793Succinimidyl carbonate 1398Succinimidyl propionate 1398Succinimidyl succinate 1398Succinylcholine 74Sucrose acetateisobutyrate 1374SUDHL-1 515Sulesomab 22Sulfaphenazole derivative– co-complex with CYP2C5 1596Sulfasalizine 1381Sulfhydryl redox potential 1073Sulfolobus solfataricus 711Sulfglycotide 463Sulfurhexafluoride 1305Suniferon MP 468Supermagnetic iron oxide, ultra small 1218Superoxide dismutase– ROS scavengers 979Superparamagnetic iron oxide 1218Supersomes 1613, 1618Surface-enhanced laser desorption ionization,

see SELDISurface-enhanced laser desorption ionization

time-of-flight mass spectrometry, see SELDITOF-MS 1325

Surface-enhanced Neat Desorption (SEND) 1337Surgical therapy in Parkinson treatment 331Survival motor neuron (SNM) gene 78SV40 764SW620 116S-warfarin– CYP2C9 complex 1591– forms of 1593– metabolism 1592– therapeutic effect 1591Swiss biotech BOUTIQUE 1741SwissPro database 170Sybyl 1610Synagis 21, 454, 456, 1086, 1121, 1176

Synthetic oviductal fluid– modified with amino acids 269, 274Synuclein alpha 329

tT cell– activation 1501– adjuvant 1431– lymphoma 24Tac 20Tachypleus tridentatus 1565Tacrolimus 58Tagging gene disruption (knock-in) 670Taillefer selectivity 1283Tamoxifen 61– metabolized by CYP3A4 1584Tandem MS QSTAR 1335Tanimoto index 1777TAP 29 484TaqMan 84TAR RNA decoys 231Tarceva 143, 1122Tasonermin 463, 479Taste blindness 74TATA box 764Taurodeoxycholate 1376Taxanes 140, 1252Taxol 314, 835Taxotere 101Taxus cuspidata 950TAXUS trial 315Taz1 43TBlastN algorithm 108TBP 764Teceleukin 464, 479Tecnemab KI 22Telomerase 38– human 42– reaction cycle 40– regulation of 42– RNA functions 41Telomerase reverse transcriptase (TERT) 39Telomere– alternative lengthening of 44– protection 43Temozolomide 1251– radiolabeled 1253Tenascin 509Tenecteplase 11, 462Tepase 461Teratoma cells 299Terfenadine 52, 1788Terfenamide 1795

Subject Index 1881

Teriparatide 476Terminal deoxynucleotide transferase dUTP nick

and labeling 644Testosterone 58, 1589– hydroxylation 1618Tetanus 18Tetracycline (TET) 732, 896– system 632– use 180412-O-Tetradecanoylphorbol-13-acetate 223Tetragastrin 1473, 1477– permeability 1479– structure 1478Tetragastrin acyl derivatives 1478– acid-output time curves 1479Tetrahymena enzyme 38Tetrahymena thermophila 685Tev-Tropin 476Texas Red 1427TGGE 84Therapeutic angiogenesis 153– human clinical trials for 309Therapeutic cloning 269Therapeutic drug monitoring 1574Thermococcus gorgonarius 709Thermoplasma acidophilum 399Thermus aquaticus 709Thienylalanine 413Thioepa 131Thioflavin T 1287Thiomedazine 644-Thio-oligoribonucleotide 261Thiopurine methyltransferase (TPMT) 57Thioredoxin reductase 1073Thrombate III 454, 458, 855, 1004Thrombin 380– heterobivalent inhibition 411– imaging 1283– inhibition assay 1006Thrombin-antithrombin (TAT) complex 997Thrombin inhibitor 1778– design of 1780Thrombolyse 462Thrombosis, targeting 1282Thrombospondin th-1 (TSP1) 263Thymalfasin 478Thymidine 1261– action of radiolabeled 1263Thymoglobuline 456Thyrogen 14Thyroid cancer 14Thyroid stimulating hormone (TSH) receptor

1189

Thyrotropin-� 14Thyrotropin-releasing hormone 1473TILLING 990Time of harvest (TOH) 1053Time point of infection (TOI) 1048TIN2 43Tisokinase 461Tissue inhibitor of metalloproteinase

(TIMP) 811, 813Tissue plasminogen activator (tPA) 6, 1280– human 836– recombinant 746TNF, see tumor necrosis factorTNKase 11, 462, 744Tobacco cultivars Bright Yellow 2 950– suspension cells 951Tobacco mosaic virus (TMV) 864– vectors 900Tolbutamide, metabolized by CYP2C9 1590Toll-like receptor (TLR)– in DNA vaccine 1490Tomieze 462Tonocalcin 477TOPAS algorithm 1774TOPKAT 1624TOPO 611Torasemide– metabolized by CYP2C9 1590Tositumomab 104, 455, 479, 1086– half life 1168– in radiotherapy 502– radio active labeled 501Total soluble protein 933– from rice grain 940Toxicity– complement directed 1156Toxins, bacterial 1125TRA-1-60 276, 288TRA-1-81 276, 288TRAFFIC trial 307TRAIL 264Transannular heterobivalent inhibitor 399Transcription activator protein 1428Transcription gene silencing (TGS) 571Transdermal therapeutic system 1382Transfectants– selection conditions 815Transfection 727Transfer RNA, see tRNATransferin receptor 1517Transferins 1517Transfersomes 1382Transforming (tumor) growth factor (TGF) 294

Subject Index1882

Transgene 156Transgene combining ability (TCA) 990Transgene expression 1531Transgenic animals 29– biopharmaceuticals from 833, 995Transgenic derived biopharmaceuticals– oral vaccines from 867– trials as anti-infective agents 865Transgenic derived pharmaceuticals– trials for autoimmune treatment 862– trials for cancer treatment 862Transgenic mice 1111, 1162Transgenic plants 29– biopharmaceuticals from 833– draught and salt tolerance 969– expressing genes involved in ion transporter

974– expressing genes involved in osmolyte

biosynthesis 976– expressing genes involved in redox reac-

tions 979– high temperature stress 981– production of high temperature stress

tolerant 985– production of high temperature tolerant 984– stress tolerance 967Transgenic system– and post translational modifications 849– capacity of production 846– costs 847– production strategies and materials used

for extraction 837– regulatory experience 850– therapeutic proteins derived from 852– therapeutic use 857Transillumination 1223Transmembrane semaforines 104Transmissible spongiform encephalopathy

(TSE) 1007Trastuzimab 479Trastuzumab 22, 64, 455, 1086, 1164Trasylol 854Trehalose synthesis 978Treponema pallidum 1422Tresylate 1400TRF1 43TRF2 43Triacelluvax 19Trichloroacetic acid 1077Trichosantes chirilovii 484Trichosanthin 482, 4842,5-bis(Trifluoromethyl)-7-benzyloxy-4-trifluorome-

thylcoumarine (BFBFC) 1610

Tripartite proteine 1166Tritanrix-HB 18tRNA (transfer RNA) 628– amber suppressor 674TRNG10 220Troglitazone 52– clearance of 1594Troparin 457Trophectoderm 275Trovert 478Trudexa 22, 455Trypanosoma brucei 571Trypsin 1005– alpha-antitrypsin 463– inhibition by aprotinin 1027– from transgenic system 853, 858Tryptase, alfa 405– diketopiperacine-based biphasic inhibitor 412– inhibition by cyclodextrin-based inhibitor 408– inhibition by PEG-linked inhibitor 406Tryptofan fluorescence assay 1006TrypZean 854, 903Tuberculosis 1489Tubulin polymerization inhibitor 1172Tumor angiogenesis 1278Tumor associated antigen (TAA) 183Tumor-associated glycoprotein 72, 1276Tumor cell, targeting markers on 1276Tumor growth index 523Tumor hypoxia, assessment of 1263Tumor necrosis factor (TNF) 7, 80, 264,

481Tumor therapy 537– cell based 203– DNA based 202– peptide based 205Tumor volume doubling time 1321Tunnel assay 644Turbocalcin spray 476Turner’s syndrome 14Twinrix 19tyr177 699tyr99 697Tyrosinase 1429

uUBE3A 277UBE3A-AS 220UBI (ubiquicidin-derived)-peptides 1286UCOE/UCOS (ubiquitous chromatin opening

element) 730, 765UGT1A1 57UK national health service 1719

Subject Index 1883

UK national institute for clinical excellence(NICE) 1720

Ultrafiltration 159Ultra-high-throughput screening (uHTS) 596Ultrasonic spectroscopy– microcapsule formulations 1307Ultrasound– theranostics 1301– 3-D imaging 1304Ultrasound contrast– encapsulated gas bubbles 1305Ultrasound contrast agent– diagnostic and therapeutic use 1315– for gene delivery 1318– preparation of drug-loaded 1317– properties 1308– target-specific 1314Ultrasound device– loss of correlation 1308– stimulated acoustic emission 1308Ultrasound imaging– application 1218– microbubbles as contrast agents 1219– schematic set-up 1220Ultratard 13Umatrope 476Umuline zinc 469Unified PD rating scale (UPDRS) 337UniGene 255United Kingdom centre doctors’ organization

(UKHCDO) 424United Kingdom prospective diabetes study

(UKPDS) 1446United network for organ sharing (UNOS) 354United States department of agriculture

(USDA) 897– voluntary scrapy flock certification pro-

gram 1007United States federal laws for biopharmaceuti-

cals 1640United States federal register 1641United States national hemophilia foundation

(NHF) 424United States prescription drug marketing

act 1736Urbason 1314Urofollitropin 464Urokinase 380– -plasminogen activator 1280Ussing chamber method 1479

vVaccination

– immune response 1421– targets for therapeutic 1422Vaccine 18– adjuvants 1419, 1425– cellular 1429– combination 1421– DNA based 199– responder rate 1432– transgenic derived oral 867– viral 1421Vaccinia topoisomerase 611Valgis 1675Validation characteristics– dependent on application 1569Valproic acid 687Vascular cell adhesion molecule-1 (VCAM-1)

234Vascular proliferative disease 235Vascular re-endothelialization 319Vascular smooth muscle cell (VSMC) 313Vasoactive intestinal peptide (VIP)– human 1742– molecular mechanism and transcription 1745– structure 1744Vector– blastid based 897– for expression of recombinant proteins 730– for gene therapy 186– for production of recombinant proteins in

plants 894– for transient transformation 900– non viral 1522– polycistronic 730– systemic viral 901Vector design– AIDS therapy 559VEGF (vascular endothelial growth factor) 263,

307– as disease marker 1337– productivity of mass bioreactor for 905Veldona 467Velosulin 13Velosulin BR 471Venn diagram 111Venous thrombosis 23Verapamil clearance 1594Verluma 21Veterinary biopharmaceuticals 25Vibragen 26Vinorelbine 131Vinplastine 131Viola arvensis 484Viraferon 17, 468, 480

Subject Index1884

ViraferonPeg 468Viral vector generation 156Virosomes 1425Virtron 17, 468Virus based vector 186Virus purification 158Virus safety 1650Visceral endoderm 294Viscum album 482Visudine 1280VitoTox 1628Vitravene 24, 633Vivid screening kit 1613VNTR (variable number of tandem repeats)

marker 77Volatile organic compounds 1344Von Hippel-Lindau disease, pathways and targets

for 628Vorvariella volvaceia 482Votumumab 22VPAC1 receptor 1745VPAC2 receptor 1745VSMC (vascular smooth muscle cell) 313

wWalkThrough recombination 706– alkaline phosphatase with 712– evolution of cIAP 713WalkThrough technique– for optimizing diagnostic proteins 707Warfarine 57Watson-Crick base-pairing 38Wave bioreactor 1050– fed-batch conditions 1053– oxygen mass transfer coefficients 1055– oxygen transfer for insect cell culture in

1055– scale up 1053Wegener granulomatosis 1195Wellferon 468West Nile virus vaccine 779Western blot 1563– analysis of alpha-glucosidase 861– of rhAT 1001– of transgenic rice grains carrying ITF

gene 943Wheat embryo– cell free expression of biopharmaceuticals

using 1063Wheat embryo extract– composition of media and buffer 1071Wheat embryo system– plasmid DNA templates 1067

– translation under reducing/oxidizing condi-tions 1078

Willebrand factor 425, 1153Wilm’s tumor 221, 359(With-no-lysine) kinase-4 (WNK4) 78Wnt-binding proteine 294Wolffian duct 355Working Cell Bank (WCB) 1645World Drug Index (WDI) 1790World Health Organization (WHO) 1569

xXanelim 456Xenopus laevis 486, 1228Xenotropic leukemia virus (X-MuLV) 434Xigris 4, 24, 465X-inactive specific transcript 217Xolair 454, 456, 1086X-ray computed tomography (CT) 1213– resolution 1214X-ray technique 1213– contrast agents for 1214Xylose 8492-Xylosyltransferase 925

yYaspin 1 1036Yeast 20S proteasome 398– inhibition by heterobivalent inhibitors 400– inhibition of PGPH and trypsin activities 404– inhibition by monobivalent inhibitors 401Yeast agglutinin 1161Yeast artificial chromosome 1111Yeast cell surface display 1112Yeast expression vector 1028Yeast-2-hybrid system 1161Yeast signal trap 109Yttrium-90 Zevalin 456, 480Yttrium-DOTALAN 518Yttrium-DOTATATE 518Yttrium-DOTATOC 516

zZadaxin 478Zeemann effect 1215Zemaira 464Zenapax 21, 456, 1086Zevalin 22, 454, 456, 480, 501–502, 1086, 1121,

1169, 1234– application 1278Zocor 1730Zoladex 478Zomacton 476

Subject Index 1885

Zona pellucida 276Zopiclone clearance 1594Zorbtive 477Zot 1376Zovant 465

Zymogen 381– activator 388– form of fIX 697Zystic fibrosis 23

Subject Index1886