1841

Subject Index a Abacavir 59, 82 Acute lymphoid leukemia, see ALL ABCA1 58 Acute myelogenous leukemia (AML) 502 ABCB1 54, 58 – radioimmunotherapy of 505 Abciximab 21, 462, 1086, 1117, 1153 – antibody treatment for 1121 – half-life in plasma 1167 Ad5FGF-4 (Adenovirus 5 fibroblast growth Abscisic acid, responsive element 980 factor-4) Absorption enhancer 1464 – analytical assay 161 – efficacy 1465 – analytical techniques for 164 N-Acetylglucosamine (GlcNAc) 679, 764, 849, – clinical study 175 938 – dose-response 174 N-Acetylglycosaminyl transferase 924 – genome structure 157 N-Acetylmannosamine 1047 – production 158 N-Acetylmuramic acid 938 – toxicology study 174 N-Acetylneuramic acid 811, 1047 Ad5FGF-4 (Adenovirus 5 fibroblast growth N-Acetylneuraminic acid 772 factor-4) vector Acetylphosphate 1075 – isolation of 156 Acetylcysteine – production 156 – in drug delivery 1375 Ad5LacZ 172 Acinar formation assay 643 Adagen 475, 1399, 1401, 1411 Acinetobacter calcoaceticus 706 Adalimumab 22, 455, 1086, 1118, 1150, 1156, Acquired immuno deficiency syndrome, see AIDS 1163 Acromegaly 15 Adeno-associated viral vector (AAV) 317 Actilyse 461 Adenosine deaminase (ADA) 429 Actimmune 17, 467 – deficiency 1401 Actinorhodin 1807 Adenovirus plasmid 156 – structure 1814 Adenovirus serotype 5 (Ad5) 155 Activacin 461 Adjuvants 1423 Activase 11, 461, 726 – for human vaccination 1425 Activase-rtPA 746 – mode of action 1424 Activated clotting time 1012 – ADMET (absorption, distribution, metabolism, Activated partial thromboblastine time (aPTT) excretion and toxicity) 1604, 1773 198 – assessment 1604, 1628 Activated protein C 457 – basic principles 1786 Activator protein-1 236 – models 1786 Actrapid 13, 470 – prediction system 1785 Acute lymphoblastic leukemia, see ALL – prediction tools 1796 Acute lymphocytic leukemia, see ALL – profiling 1785

Modern Biopharmaceuticals. Edited by J. Knäblein Copyright © 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-31184-X 1842 Subject Index

– properties 1775 Alpha-glucosidase 861 – value of prediction 1798 Alpha-iduronidase 862 Adenosine triphosphate (ATP) AlphaNine SD 459 – regeneration system 1074 Alphaparin 457 ADR (adverse drug reactions) 76 Alpha-synuclein 329 Adult respiratory distress syndrome 1009 Altemol 467 Advaferon 467 Alteplase 11, 461 Advate 421, 459 Alternating tangential filtration 1087 Adverse drug reaction 51 Alzheimer disease (AD) 77, 1781 Aequorea victoria 1628 – targeting 1286 AERx-dornase alfa 475 – pathways and targets for 625 Affinity chromatography – epidemiology 326 – characterization of antibodies by 797 Amantadin 330 Aflatoxin B1 AMAXA system 632 – CYP3A4 activated 1586 Ambirix 19 AFP 482 Ames false negatives 1625 Agalsidase alpha 475 Ames false positives 1625 Agalsidase beta 475 Ames II 1527, 1633 Agarose 1380 Ames test 1632 AGENT (angiogenetic GENe therapy) trial 175 Amevive 454–455, 1119 – safety 177 Amiloride 1525 AGENT 2 trial 176 Amino acid depletion – safety 177 – with glutaDON 537 Age-related macular degeneration 1280 Aminoacyl-tRNA synthetase 1068 Agrobacterium tumefaciens 903, 950 Amino-3,8-dimethylimidazoquinoxaline 1634 AIDS (acquired immuno deficiency syndrome) Amino-hydroxybenzoic acid 1823 14 (2-Amino)isobutyric acid 413 – gene therapy 549 Aminolevulinic acids 1617 – vaccine 1164 (3-Aminomethyl)benzenesulfonylglycine 407– Airway hyper responsiveness 234 408 Akanthamoeba castellanii 685 Amino-3-methyl-imidazoquinoline 1634 Aktraphane 13 Aminopeptidase 1379 Alamar blue dye metabolism 168 2-O-Aminopropyl oligoribonucleotide 261 Albuterol 59 Amiodarone Aldurazyme 24, 475 – clearance of 1594 Alefacept 455 – CYP2C9 inhibitor 1590 Alemtuzumab 22, 455, 479, 1086, 1156 Amitriptyline Alfaferone 467 – CYP3A4 activated 1586 Alfatronol 17, 468, 480 Ammonium tartrate 922 Alferon LDO 467 Amoxibeta T1000 1352 Alferon N 467 Amoxicillin 1352 Alglucerase 475 Amphotericin B 1370 Alkaline phosphatase 712 Ampicillin 610 – secreted 731 – resistant plasmids 1024 ALL (acute lymphoid leukemia) 76, 202 Amyloid precursor protein (APP) 1782 – murine model 203 – processing scheme of 1783 Alosetron 52 Amyloidosis 1286 Alpha-1 464 Anact C 454, 457 Alpha-1 antitrypsin 463 ANAFP (a novel antifungal peptide) 483 – from transgenic system 858 Anakinra 17, 464, 1118 Alpha-defensin 383 Analytical assay validation Alphaferon 467–468, 480 – regulations 1650 Alpha-fetoprotein 862 Analytical methods Subject Index 1843

– in quality control 1557 – epitope/paratope interaction 1108 – in vivo 1572 – fully human 1111, 1113, 1157 – specifications for drug substances – half-lives of therapeutic 1166 and products 1561 – humanized 1153 – validation 1567 – immunogenic 1150 Analytical protein A chromatography (APAC) – in disease targeting 1273 – characterization of antibodies by 797 – isotope conjugates 1174 Angelmann syndrome (AS) 219 – libraries 1157 Anger position network 1221 – linking of phenotype and genotype in selection Angioblasts systems 1161 – for angiogenesis 319 – marker for autoimmune disease 1189 Angiogenesis 1235 – murine 1156 – markers of 1281 – naked 1169 – non-tumor 1280 – on the market 1151 – related disease 1278 – pharmacological characteristics of 1114 Angioedema, hereditary 859 – protective function of 1166 Angiogenetic switch 1279 – polyclonal 1109 Angiogenic GENe therapy, see AGENT – radiotracer 1258 Angiomax 461 – screening technologies 1160 Angiostatin 381 – single chain 1115 Angiotensin-converting enzyme (ACE) 78, 317 – single domain 1115 Angiox 461 – synthetic 1176 Animal models Antibody-antigen interaction 1190 – selection 1658 Antibody-dependent cellular cytotoxicity 733, Animal rule 1662 1274 Animal, transgenic 29 Antibody-directed enzyme prodrug therapy – biopharmaceuticals from 833, 995 (ADEPT) 1277 Anion-exchange HPLC 164 Antibody fragments 1113 Anistreolase 461 – manufacture in microbial systems 1088 Annexin 5 detection assay 644 – pharmacokinetics of 1116 Annexin A1 1281 Antibody library technology 1163 Annexin V 1262 Antibody response 1199, 1500 – for SPECT studies 1263 Antibody technology 1147 ANP, see atrial natriuretic peptide Antibody, therapeutic Antegren 1122 – productivity advantages 1726 Anthracycline 139 Anticoagulants 454 Anthrax 1489 Antide structure 1408 – toxine 1166 Antiepileptic drugs 58 Antibiotic resistance gene 299 Antigen-nanoparticle conjugate 1310 Antibody 454 Antigen-presenting cell 191, 360 – against infectious disease 1175 Antihemolytic factor VIII, see fVIII – anti-neutrophil cytoplasmic 1195 Antihemophilia agents 454 – anti nuclear 1190 Antinuclear autoantibodies, mononuclear 1371 – binding haptens, peptides or proteins 1154 Antiperinuclear factor 1192 – binding site 1163 Antisense RNA – bispecific 1174 – for gene silencing 633 – categories 1150 – plasmid-borne 671 – chimeric 7, 1109, 1153 Antisense technology 31 – class determination 1107 Antithrombic agents 460 – combining site 1190 Antithrombin (AT) 29, 995 – complexes of 1155 – anti-inflammatory activity 1009 – different fragments and formats 1274 – hereditary deficiency 997, 1014 – epitope 1190 – human 1001 1844 Subject Index

– recombinant production of 998 Ascorbate peroxidase 977 – serpin 996 – ROS scavenger 979 – vector construction 999 Asialoglycoprotein 716, 1512 Antithrombin III 458, 996 Asialoorosomucoid 1512 – human 855 Asparaginase, PEGylated 543 Antithrombin transgene 999 Aspergillus giganteus 482 Anti-thymocyteglobulin 456 Aspergillus terrus 1804 Antitrypsin 463–464, 858 Astemizole 52 Anti-tumor agent 474 Atenativ 458, 1006 Antiviral agents Atherosclerosis 313 – RNA-based 570 – targeting 1281 Antril 464, 1117 Atomoxetine 57, 61, 64 AP 486 – label recommendation 56 AP-1 233 Atorvastatin 58 Apcitide 1283 Atrial natriuretic peptide (ANP) 290 APEX 84 Atrioventricular block 298 Apidaecins 486 Atriplex gmelini 974 Apidra 13, 469 ATryn 29, 855, 995 Aplysia kurodai 482 – clinical studies 1011 Apolipoprotein E (APOE) Auerbach plexus 327 – locus 78 Auger electron emitter 500 – satin system 78 – targeted radiotherapy with antibodies 524 Apoptosis 644 Auger electron radiotherapy – delaying 819 – antitumor effects 519 – imaging 1238, 1262, 1284 – gene-targeted 525 Aprepitant 1538 – In-DTPA-D-Phe-octreotide 519 AproliZean 903 Auristatin derivatives – Apronexin NP 854 – cytotoxic 1172 Aprotinin 904, 1470, 1472 Autoantibody – from transgenic system 854 – antinuclear, mononuclear 1371 – variants 1027 – pathogenic 1188 Aptamers 635 – responses 1187 Arabidobsis thaliana 869, 921, 950, 973 Autoantibody-autoantigen complexes Aralast 463 – characterization of 1199 Aralia elata 482 Autographa californica Aranesp 8, 472 – nuclear polyhedrosis virus 1046 Arcitumomab 21 Autoimmune disease 1187 Ardeparin sodium 458 Autoimmune encephalomyelitis (EAE) 1200 Area under the curve (AUC) 438 Autologous stem cell 500 Argatroban 413 Auxotrophic marker 766 Argonaute protein family 222 Available chemical directory (ACD) 1790 Argoproteins 245 Avakine 456 Arixtra 457 Avastin 143, 454–455, 479, 1121, 1169 ARMS 84 Average internal stability profile 250 Aroclor 1254, 1626 Avidin from transgenic systems 852 ARPE-19 168 Aviptadil 1742 Array-on technology 88 – dosage 1748 Arterial re-stenosis 313 – effects 1748 Arthrobacter globiformis 977 – in PAH 1743 Arthrobacter panescens 977 – increase in CRE binding 1746 Artificial neural network 1789 – pharmacology 1744 – for CNS activity prediction 1794 – release 1748 – topology of three-layer 1790 – secretion enhancement 1748 Subject Index 1845

Avonex 17, 467, 1404 Beromun 23, 463, 479 5-Azacytidine 320 Beta-cyclodextrin 407 5-Aza-2-deoxycytidine 294 Betaferon 4, 17, 467 Beta-glucocerebrosidase 861 b Beta-grasp motif 383 Baby hamster kidney cell line (BHK) 762 Betaine aldehyde dehydrogenase 976 BACE (beta-amyloid converting enzyme) 1773 Betaine synthesis 977 – complex 1784 Betaseron 17, 467, 1404 – inhibitor 1781 Beta-tryptase 405 Bacillus subtilis 1823 – diketopiperazine-based bibasic inhibitors of Bacillus thuringiensis toxin 898 412 Bacitracin 1472 – inhibition by cyclodextrin-based inhibitors BacPac rapid titer kit 1046 408 Bacterial activator 381 – inhibition by PEG-linked inhibitors 406 Bacterial artificial chromosome (BAC) 656 Bevacisumab 143, 455, 479 Bacteriophages – effect by blocking a growth factor 1169 – therapeutic use 1751 – cancer treatment 1280 Bac-to-Bac 1046 Bexxar 454–455, 479, 501, 1086, 1121, 1169 Bactosomes 1613, 1618 – application 1278 Bactotryptone 681 Bioassay BaculoDirect 615, 1046 – cell culture-based 1565 Baculosomes 1613 – quality characterization of biopharmaceuticals Baculovirus transgenic 1046 1565 Baculovirus expression vector system Bioclate 10, 454, 459 (BEVS) 1045 Bioequivalence 1756 BacVector-3000 105 Biogamma 467, 479 Balke protocol 175 Biogenerics 1662, 1728, 1756 Basic local alignment search tool, see BLAST – EU regulations 1700 Basiliximab 21, 456, 1086 – market 1722 BAY-14-2222 459 Bioinformatics 255, 1771 Baycol 52 Bioleukin 464, 479 BayerHealthCare pharma biotechnology 1021 Biological products regulations 1686 Bayovac CSF E2 26 Biologics license application (BLA) 1126, 1638 BC1 217 Bioluminescence applications 1224 BC200 217 Biomarker BCMS 220 – exploratory 58 B-cell chronic lymphocytic leukemia 222–223 – DNA-based 57 B-cell epitopes 1119 – genomic 56 B-cell neoplasia-associated gene with multiple – pharmacogenomic 59 splicing 216 Biomarker patterns software 1332, 1336 Bcl-2 317 Biomek 1332 – antiapoptotic properties 819 BioMEMS 1542 – Becaplermin 465 Bionanotechnology 1537 Beckwith-Widemann syndrome (BWS) 219 Biopharmaceutical advantages 1725 Benefix 10, 459 Biopharmaceutical approval p-Benzamidine 699 – for post-translational modification 7 Benzobromarone – for veterinary use 25 – CYP2C9 inhibitor 1590 – of proteine engineered products 6 Benzonase 158 – PEGylated 1412 Benzotriazoyl carbonate 1398 – products for human use 9 7-Benzyloxy-4-trifluoromethylcoumarin Biopharmaceutical development (BFC) 1610 – good manufacturing practice (GMP) 1661 Bergmann reaction 1125 – regulations 1689 1846 Subject Index

– US federal laws for 1640 – fed-batch 824 Biopharmaceutical drugs 453 – hollow-fibre 738 – approval system in EU 1684 – large-scale transient expression 744 – BLA/NDA stage 1644 – moss 919 – classes of 1560 – perfusion 1050 – design of novel 1775 – photo 922 – development of 1090 – preparation of drug metabolites 1622 – EU regulations 1669 – stirred-tank 739, 1050 – half life of 1363 Bioreactor process – handling 1570 – development efforts 750 – IND stage 1643 – regulatory issues 745 – innovate around existing 1730 – risc of bacterial contamination 746 – innovative approaches 1732 – risc of viral contamination 747 – marketing of 1736 – scale-up 740 – PEGylated and kinetic parameters 1403 Bioseb 1087 – post-approval 1644 Biosensors 1544 – prescription 1736 Biosimilar medicinal product guidelines 1707 – price increase 1715 Biostim 463 – protect exclusivity of 1730 Biotech – radiolabeling 1251 – development 1654 – registration and marketing 1697 – procedure 1683 – scheme of pharmacokinetics 1365 – products registered in EU 1675 – withdrawals from market 1604 Biotechnological products Biopharmaceutical manufacturing – EU adopted guidelines 1705 – common errors in 1659 Biotechnology quality working party – inspectional authorities 1653 (BWP) 1670 – process validation 1653 BioTropin 14, 476 – virus safety 1650 Biphasic human insulin 469 Biopharmaceutical production Biphasic insulin aspart 470 – from cereal grains 931 Biphasic insulin lispro 469 – in culture plant cells 949 Biphasic porcine insulin 471 – in the desert 967 Bispecific T cell engager 1175 – new cell lines 761 BiSphere 1305 – using insect cell culture 1045 BiSteel 871 – using transgenic animals 995 Bitistatin 1283 – using yeast 1033 Bivalent ligand binding 396 Biopharmaceutical proteins Bivalrudin 461 – manufacture of recombinant 723 BLAST (basic local alignment search tool) 105, – PER.C6 779 108, 255 Biopharmaceuticals BlastX analysis 108 – definition 2 Blasticidin 666 – first generation 1759 Blasticidin deaminase 766 – follow-on market 1729 – marker 767 – generic threat for 1729 Bleeding episodes treatment 441 – global sales 1759 Blood-brain-barrier 1771, 1783, 1791, 1795 – veterinary 25 B-lymphocyte stimulator 505 Bioreactor BM185 cell 204 – adherent-cell culture in 739 Bombesins 486 – annual output using 10´ fed-batch 1092 Bombinins 486 – annual output using 10´ perfusion 1091 Bone marrow transplant (BMT) 1757 – batch perfusion 741 Bone morphogenic protein (BMP) 294 – continuously perfused production 743 Bongard problem 1773 – extended-batch perfusion 741 Boost Plus 1454 Subject Index 1847

Boroleucine 1472 – CYP3A4 activated 1587 Botulinum type A toxin 463 Calcitonin 1376, 1467 Bovine herpes virus (BHV) 27 Calcium concentration-time profiles in plasma Bovine serum albumin (BSA) 269, 957 1468 Bovine somatotropin 25 Calf intestinal alkaline phosphatase, see cIAP Bovine spongiform encephalopathy (BSE) 747, Calichemicin 1125 1007 Calmette-guerin vaccine 1430 Bovine viral diarrhea virus (BVDV) 434 Calnexin 420, 427 Boyden chamber assay 643 Calogen 477 BR96 Calreticulin 420, 427, 1435 – in cancer treatment 1172 Campath 22, 455, 479, 811, 1086 Bradykinins 486 cAMP (cyclic adenosine monophosphate) Bradyphrenia 328 318 Brain capillary endothelium 1517 Camptothecin 1367 Brain-derived neurotrophic factor (BDNF) 77 Cancer 238 Brambell receptor 1167 – therapy 127, 1243, 1276 Brassica juncea 977 – cells, in folate receptor-mediated gene transfer Brassica napus 973, 977 1515 Bravelle 464 – vaccine 864 Breast cancer 143, 239 Cancer research UK pharmacokinetic and – EGFR-positive 524 pharmacodynamic technologies advisory – ER-positive 524 committee 1250 Breast Cancer International Research Group Candida albicans 1285, 1435 (BCIRG) 144 Canferon A 468, 480 Boehringer Ingelheim high expression system/ Capan-1 1319 chinese hamster ovary cell 1094 Capecitabine 1252 Bromfenac 52 Capillary zone electrophoresis (CZE) 162 Bromodeoxyuridine (BrdU) 641, 1261 Capsella bursa pastoris 486 6-Bromoindirubin-3-oxime 288 CAPSIT protocol 347 Brutons tyrosine kinase variant (BTK) 1053 Carbamazepine BSE see Bovine spongiform encephalopathy – clearance of 1594 B-type polymerase – CYP3A4 activated 1587 – structural features of 710 Carbon nanotubes 1548 Buerger’s disease 307 Carboplatin 131 Bullous pemphigoid 1193 Carbopol 1380 Bundesinstitut für Arzneimittel und Medizin- Carboxyfluorescein 1467, 1480 produkte 1679 Carcinoembryonic antigen 1123, 1234, 1277 Bupropion, hydroxylation 1618 Cardiac specific proteins 290 Burkitt’s lymphoma cell 1029 Cardiac transcription factors 290, 293 Butyrophilin 1205 Cardiac troponin 293 Butyrylcholinesterase 870 Cardiomyocytes 289, 320 Buzerelin 1376 – clinical applications of hES derived 293 BYK150640 chemical structure 410 – differentiation system 293 BYK76935 chemical structure 410 – enrichment and purification 298 Bypass graft failure 313 – hES cell derived 292 Cardiopulmonary bypass c – trials with rhAT 1011 C1I-Immuno 859 Cardiovascular disease 305 cA2 456 – pathways and targets for 625 CABG (coronary artery bypass grafting) 154, – targeting 1281 237, 312 CaroRx 865 Caenorhabditis elegans 571 Caruleins 486 Caffeine CASE 1624 1848 Subject Index

Casein 998 Center for drug evaluation and research – peptone 681 (CDER) 49, 1765 Caspase activation assay 644 Center for food safety and applied nutrition Catechol-O-methyltransferase 330 (CFSAN) 1639 Catharanthus roseus 950 Center for veterinary medicine (CVM) 1639 Cathelicidins 1433 Center of biologics evaluation and research Cathepsin B 1282 (CBER) 1639 Cathepsin B2 1285 Center of devices and radiological health Cathflo Activase 461 (CDRH) 1639 Cationic liposomes 1510 Center of disease control 1752 Cationic antimicrobial peptides 1419 CenTNF 456 – artificial 1433 CentoRx 462 – as vaccine adjuvants 1433 Centoxin 455, 1117 – subgroups 1433 Central nervous system 1791 Cationic peptides – active drugs 1794 – delivery system 1419, 1437 Centuximab 455 – vaccine adjuvant 1426 Ceprotin 454, 457 CATS descriptors 1797 CeramTec 681 CB03 769 Ceredase 475, 862 CD105 1281 Cerezyme 8, 23, 475, 862 CD20 1278 Cerius 1610 CD25 20 Cerivastatin 52 Cdc13 43 Certification of suitability 1680 Cdc13p 40 Certoparin sodium 457 CEA-scan 21 Cetrolix 476 C/EBP 233 Cetrotide 476 Celeuk 463, 479 Cetuximab 479, 1121 Cell concentration cGMP (current good manufacturing practice) – maximum 816 749, 949, 1126, 1641, 1654, 1661 – viable 816 Chaperones 1072, 1074 Cell cycle Cheloidonium maius 482 – manipulation of 820 Chemical exchange-dependent saturation – mutants 822 transfer 1217 Cell engineering 819 Chemistry manufacturing and control Cell free reaction (CMC) 1126 – pH 1073 Chemotherapy 1272 Cell graft 295 Chimeric antibody 7, 1109, 1153 Cell line Chimeric mice 657 – generation 727 Chitin 1374 – generation timeless 788 Chitosan 1374, 1380 – regulations for qualification 1645 – solution 1378 – stability 818 Chlamydomonas reinhardtii 898 Cell migration 642 Chloramphenicol acetyl transferase (CAT) 1075, Cell (specific) perfusion rate (CSPR) 794 1532 Cell proliferation 821 Chloronema cell 920 Cell retention device 1087 4-(4-Chlorophenyl)imidazole CellBag – CYP2B4 inhibitor 1597 – cultivation of Sf-9 cells in 1056 Chloroxozone hydroxylation 1618 Cellferon 467 CHO (Chinese hamster ovary cell) 433 Cellular lactate dehydrogenase 1427 – cell line 762 Cellular transformation 642 – quality control 435 Celmoleukin 463, 479 Cholesteryl ester transfer protein (CETB) 78 Centaxarin 458 Cholesterylhemisuccinate 1523 Subject Index 1849

Choline dehydrogenase 977 Coded spheres 84 Choline monooxygenase 976 Codeine 57 Choline oxidase 977 – metabolized by CYP3A4 1585 Choriogonadotropin alfa 477 Codon Chromatographic assay 164 – adaptation index 1023 Chromatographic methods – usage, of IL-4v gene 1024 – for analytical properties of biopharmaceutical Cognate factor VIII 743 material 1562 Collagen 872 Chromogenic ISH (CISH) 134 – matrix assay 643 Chromogenics kit 1006 – induced arthritis 235 Chronic disease era 103 Collimator types 1220 Chronic myeloid leukemia treatment 506 Colony-stimulating factor (CSF) 466 Chronic myocardial ischemia 151 Combinatorial chemistry (CC) 101 Chronic obstructive pulmonary disease 1344 Comet assay 1626 – IMS chromatogram 1351 Committee for proprietary medicine products Chrysamine G 1287 (CPMP) 434, 1670, 1675 Chrysanthemum morifolium 894 Committee for human medicinal products Chymotrypsin, inhibition by aprotinin 1027 (CHMP) 1670, 1678 Cialic acid 772 Committee for orphan medicinal products cIAP (calf intestinal alkaline phosphatase) 714 (COMP) 1678–1679 – expressibility of, in E. coli 714 Committee for veterinary medicinal products – variance of 714 (CVMP) 1678 3,4,5-Cimethylthiazol-2yl-2,5-diphenyl tetrazolium Common technical document (CTD) bromide, see MTT – electronic 1699 Cimetidine – format 1698 – CYP2C9 inhibitor 1590 Complete Freund’s adjuvant 194 Ciphergen biomarker 1338 Complex disease 77 CiphergenExpress 1332 Computer-aided drug design (CADD) 1607 Circular dichroism Comvax 18 – conformation of hAT analyzed by 1004 Concanavalin A 484 – insulin proteolysis investigated by 1474 Confocal image assisted 3-dimensionally Circulins 484 integrated quantification (CIDIQ) 1526 Cisapride 52, 1605 Congestive heart failure (CHF) 318 Cisplatin 131, 136, 1250 Congo Red 1287 Citrullinated peptide antibodies, anti cyclic 1189 Connective tissue disease (CTD) 1750 Cleactor 461 Connexin43 320 Clean in place (CIP) 746 Connexin45 292 Clexane 457 Constitutive androstane receptor (CAR) 1788 Clinical trial assay (CRA) 133 Contergan 1675 Clinical trial authorization application Continuous (chemostat) perfusion cell 430 (CTA) 1697 Contract manufacturing Clinical trial protocol (CTP) 1697 – client contracting 1095 Clivarine 457, 1750 – integrating 1089 Cloning Contract manufacturing organization – reproductive 365 (CMO) 1083, 1093 – therapeutic 365 Contrast agents ClustalW algorithm 110 – for imaging modalities 1213 CMPD 220 – for molecular imaging 1225 c-Myc 42 – for optical imaging 1223 Coagulation 377 – for SPECT 1222 – factors 379 – for ultrasound imaging 1219 Coagulation factor IXa, see fIXa – smart ultrasound 1303 Code of federal regulations (CFR) 1641 Copper bis-thiosemicarbazones 1264 1850 Subject Index

CORINA program 1777, 1797 CYP2A6 58, 1618, 1621 Corixa 502 CYP2B 121 Coronary artery bypass grafting, see CABG CYP2B4 1621 COSMIC program 1797 – apo-form 1598 Costilate 473 – inhibitors 1597 Coulyflower mosaic virus 894, 954, 981 – structure of 1597 Coumarin hydroxylation 1618 CYP2B6 58, 1618 CpG-ODN 1424 CYP2C19 57, 61, 76, 1618, 1620 CRA-2059 chemical structure 407 – molecular model 1611 Creatine phosphate 1075 CYP2C3 CREB phosphorylation 1746 – chimeric 1595 Creon 860 – isoforms 1595 Crescormon 476 CYP2C5 1610 CRESTOR 55 – Co-complexes 1596 Creutzfeld-Jakob disease 424, 747, 872 CYP2C8 58, 1609, 1618 – new variant 1007 – active sites 1594 – pathways and targets for 627 – inhibitors 1594 Critical flooding temperature 1316 – pharmacophore 1595 Crohn’s disease 21 CYP2C9 57, 76, 1609, 1618 – fragment for treatment 1116 – crystal structures 1590 Cross-fire effect from beta particle emitters 500 – flurbiprofen complex 1591, 1593 Cryptococcus neoformans 686 – in drug metabolism 1590 Cryptotope 1191 – inhibitors 1590 cTnI 290 – isoforms 1589 Current good manufacturer practice, see cGMP – molecular model 1611 Cyanovirin 1406 – S-warfarin complex 1591 – immunologic response in mice 1407 CYP2D6 51, 57, 61, 76, 1618, 1620–1621 Cyanovirin-N 483 – molecular model 1611 Cycas revoluta 484 CYP2E1 1615, 1618 Cyclic adenosine monophosphate, see cAMP CYP3A 121 Cyclic response element 233, 239 CYP3A4 54, 58, 1584, 1615, 1618, 1788 Cyclin-dependent kinase 219, 821 – activity 1587 Cyclin kinase inhibitor 763 – allosteric nature 1586 Cyclo18 256 – Co-complex structures 1588 Cyclo50 256 – isoforms 1584 Cyclo66 256 – molecular model 1610 Cyclo80 256 – structure of 1585 Cyclodextrin 407 – subfamily 1585 Cyclohexylalanine 413 CYP3A5 58, 1618 Cyclohexylglycine 413 Cysteine knot motif 484 Cyclophilin-B 257 Cysteine thiols 1400 Cyclophosphamide 503 Cystic fibrosis 1751 – hydroxylation catalyzed by CYP2B4 1597 Cytochrome metabolism 1609 Cyclosporine 55, 58 Cytochrome P450 76, 329 – metabolized by CYP3A4 1585 – active site 1584 Cycloviolins 484 – bacterial expression of human 1615 CYP gene testing kit 78 – classification 1582 CYP102 1609 – crystal structures 1581 CYP17A 1616 – genetic polymorphism of human 1583 CYP17A1 1616 – GloTM-assay system 1613 CYP1A2 1618, 1621 – microsomal 1581 – molecular model 1612 – prokaryotic 1584 CYP1B1 1620 – structure of soluble 1584 Subject Index 1851

Cytochrome P450, human Denileukin diftitox 456, 480 – associated with drug metabolism 1617 Deoxycoformycin (dCF) 429 Cytochrome P450 reductase (CPR) 1615 6-Deoxyerythronolide B synthase, see DEBS Cytodex 739 DepoInterferon alpha 468, 480 Cytogenetics of CHO cell lines 735 DEREK 1624 Cytokine immunostimulatory 1173 Dermatan sulfate 458 Cytolytic T lymphocytes 1489 Dermorphins 486 Cytomegalovirus (CMV) 188, 1489 Desirudin 462 – enhancer 299 Desmin 290 – human 764 Desmopressin 1376 – promoter 156 Desoxyribonucleic acids, see DNA Cytopathic effect 166 Dexamethasone 896 Cytoplasmic microinjection 1531 Dexfenfluramine 52 Cytotoxic T lymphocytes 199, 1175 Dextromethorphan hydroxylation 1618 Cytotoxicity DGCR5 220 – antibody dependent cellular 1107, 1156, 1274 D-HPLC, see denaturating high-performance – complement dependent 1107 liquid chromatography – cell-mediated 924 DHFR (Dehydrofolate reductase) 725, 1079 – CHO system 812 d – expression system 813 1D09C3 (anticancer antibody) 1177 – generation of stable cell lines 733 Daclizumab 21, 456, 1086 Diabetes 1445 Dalteparin sodium 457 – latent autoimmune in adults 1198 Danau plexipis 1047 – type 1 1033, 1451 Darbepoietin 16 – type 1 treatment 1454 Darbepoietin alfa 472 – type 2 1033, 1446 DARWINIZER 1779 Diabetes Control and Complications Trial Dash 84 (DCCT) 1446 Daudi B-cell lymphoma 526 Diabetes mellitus 13 Daunomycin 1814 – pathways and targets for 626 Daunorubicin 1370 – treatment 1473 DD3 gene 220 Diabetes patients DEAE chromatography 166 – meal study in type 1 1455 DDAB, see Didodecyldimethylammonium bromide – meal study in type 2 1456 DEBS (6-Deoxyerythronolide B synthase) 1813 Diagnostic assay multi-marker-based DEBS system 1815 1325 DEBS AT module 1815 Diagnostic protein DEBS pathway 1819 – directed evolution 705 DEBS1 1816 – rational design 705 DEBS2 1816 Diatin 476 DEBS3 1817 Diazepam 61 Decay accelerating factor (hDAF) 355 – CYP3A4 activated 1587 Decoy oligodeoxynucleotides, see dODN – metabolized by CYP2C9 1590 Deep brain stimulation 331 6-Diazo-5-oxo-L-norleucine see DON Deep-vein thrombosis Dibotermin alfa 464 – trials with ATryn 1011 Dicer ribonuclease 222 Defensins 383, 486, 1433 Dicialoganglioside 1173 Defibrotide 461 Diclofenac Dehybridization detection 86 – CYP2C5 co-complex 1596 Dehydration response element 981 – hydroxylation 1618 Dehydrobenzene 1125 Dictyostelium discoideum Dehydrofolate reductase, see DHFR – in biomedical research 685 Denaturing high-performance liquid chromatog- – cells 665 raphy (D-HPLC) 86 – retrotransposon 689 1852 Subject Index

6A,6D-Dideoxy-6A,6D-diamino-beta- – polymers for 1491 cyclodextrin 407 – efficacy 1489 Didodecyldimethylammonium bromide – incorporated in polymer microspheres 1492 (DDAB) 1508–1509 – mechanism of action 1489 Diethyl maleate 1466 DNA-vector complex 1490 Diethylentriaminepentaacetate 1123 Docetaxel 131, 141, 1251 Diffuse optical tomography (DOT) 1223 – in cancer treatment 1172 DiGeorge syndrome 220 dODN (decoy oligodeoxynucleotide) 231 Digitalis 835 – therapeutic application 232 Digoxin 58 Dolabella auricularia 482 N-[2-(Dimethylamino)ethyl]acridine-4-carboxamide Dolabellanin B2 486 1250 Domperidone 1795 Dimethylsulfoxide 957 DON (6-diazo-5-oxo-norleucine) 537 Dioleoylphosphatidylethanolamine (DOPE) – antitumor effect of 538–539 1508–1509, 1523 – efficacy of 539 N-[1-(2,3-Dioleyloxy)propyl]N,N,N-trimethyl- – inhibition of sarcoma 180 tumor cell ammonium chloride, see DOTMA growth 541 Diphenhydramine 61 – treatment of mouse tumors 541 Diphtheria 18 – tumor cell line sensitivity 539 Directed molecular evolution 709 Dopamine producing cell, transplantation DISC1 (disrupted in schizophrenia 1) 221 of human non-neural 333 DISC2 (disrupted in schizophrenia 2) 220 Dopamine transporter (DAT) gene 329 Disease DOPE, see dioleoylphosphatidylethanolamine – genes 73 Doppler effect 1218 – classes of 1276 Doppler frequency shift 1218, 1304 Disintegrins 1283 Doppler image, two-dimensional 1315 Diseminated intravascular coagulation (DIC), Doppler mode 1308 sepsis induced 997 Doppler ultrasound imaging 1238 Dithiothreitol (DTT) 1073 Dornase alfa 475 Dixon test 168 Dose determination 1566 DLG2 221 DOTA-biotin 514 6-DMAP (6-dimethylaminopurine) 272 DOTMA (N-[1-(2,3-Dioleyloxy)propyl]N,N,N-tri- DMEM (Dulbecco’s modified eagle medium) 740 methylammonium chloride) 1508–1509 DMRIE-C transfection reagent 1030 Double stranded RNA, see dsRNA DNA (desoxyribonucleic acid) 628 Double emulsion technique – dumbbell 1532 – preparation of microcapsules 1373 – exogenous 1529 Doxorubicin 131, 1253, 1370, 1814 – fragmentation assay 644 – in cancer treatment 1172 – linear template 1067 – use 1804 – microarrays 672 DoxoRx 866 – naked 1490 DRAGON descriptors 1797 – release kinetic 1497 Drotrecogin alfa (activated) 465 – residual 167 Drug – shuffling 590, 706 – biopharmaceutical 453 DNA databank of Japan (DDBJ) 255 – development 54 DNA plasmid – labeling 63 – conformation of release 1498 – therapeutic range 54 – release kinetics from microspheres 1498 Drug classes DNA polymerase – central nervous system active 1792 – engineering of enzymatic activities 711 Drug conjugates DNA vaccination 199 – low molecular weight 1171 – for tumor suppression 1501 Drug costs 1717 DNA vaccine delivery 1487, 1490 – cost-benefit evaluation 1720 Subject Index 1853

– cost-conscious prescribing 1721 – necessary cause model 114 – in America 1717 – sufficient component cause model 113 – in Europe 1717 Drug therapy for Parkinson disease 329 – population ageing, impact on 1718 dSLIM (double-stem loop immunomodulator) – price reduction 1719 183 – pricing pressure 1724 – application of 198 – R&D spending 1723 – immunization pathways using 200 Drug delivery – production 197 – bionanotechnology in 1540 – properties 197 – with ultrasound 1315 dsRNA (double stranded RNA) 244 Drug delivery system 1361 – in vitro dicing 631 – administration sites for 1364 Dukoral 19 – bucal 1379 Dundee P450 system 1614, 1619, 1623 – colon specific 1381 Duract 52 – conjugates for 1366 Duteplase 462 – forms of 1369 Dynamic light scattering 162 – nasal 1377 Dynepo 472 – non invasive 1375 Dyskeratosis congenita 41 – oral 1380 Dyskinesia 332 – PEG in 1393 Dysport 463 – pulmonary 1378 – polymer based 1361 e – transdermal 1382 E1 protein Drug development 1147 – induced cell proliferation 782 – molecular imaging for 1230 – of human adenovirus 782 – P450 for 1582 E1A protein 783 – phases in 1231 E1B protein 783 – protein kinase in 639 – E2F 233 – siRNA based 264 Ebstein-Barr virus 1029, 1153 Drug discovery Ebiratide 1469 – basic concepts of virtual 1773 EBNA1 (Epstein-Barr virus nuclear antigen) – phases 1774 expression 1029 Drug discovery process Ebola virus 484, 1407, 1488 – cell based assay 640 Echogen 1305 – for chronic disease 100 Echovist 1305 Drug-drug interaction 1787 Ecokinase 11, 462 – metabolic prediction 1621 Econazole 1370 Drug evaluation and research (CDER) 1639 Ectoine synthesis 978 Drug interaction 60 Edrecolomab immunotherapy 1278 – effect of genotypes on 61 Efalizumab 456 Drug metabolism 1608, 1787 Efavirenz 58 – contribution of genetic polymorphism to 57 EGF (epidermal growth factor) 238, 463 – CYP2C9 in 1590 EGFR (epidermal growth factor receptor) 59, – CYP3A4 in 1584 105, 623 Drug metabolizing enzymes 52 Elastase 380 Drug metabolites 1622 Elcatonin 476 Drug product 1561 Elcitonin Inj. 20S 476 Drug release by ultrasound 1316 Electromechanical (NOGA) mapping 155 Drug response 50 Electron spray ionization (ESI) 1564 Drug substance 1561 Electronic standards for transmission Drug substances coordinating committee of regulatory information (ESTRI) 1699 (DSCC) 1765 Electrophoretic methods Drug target validation 110 – in quality control 1563 1854 Subject Index

Electroporation 1382 Enterolactone 943 – DNA transfer into mammalian cells 729 Entrez Gene 255 ELISA (enzyme-linked immunosorbent Enzymatic degradation 1363 assay) 166, 168, 172, 1563 Enzyme 474 – characterization of antibodies by 797 – activity, imaged by NIR 1283 – of soluble protein from rice grain 940 – drug-metabolized 1608 – protein levels of rhVEGF measured by 923 – endoproteolytic 1194 – sandwich 1564 – mutant 711 ELIspot responder rate 1432 – strategy for evolution directing 706 Elitec 475 – wild type 711 Elitex 24 Enzyme immunoassay test (EIA) 1190 Ellman reagent 1415 Enzyme-linked immunosorbent assay, see ELISA Elspar 537 EpCAM 1278 ELUTES trial 315 Epidermal growth factor, see EGF Embryoid body 286 Epidermal growth factor receptor, see EGFR Embryonic antigen 288 Epirubicin 131 Embryonic development 287 Epithelial cellular-adhesion molecule 862 Embryonic germ (EG) 278 Epitope 1190 Embryonic renal progenitor 357 – blocking 1163 – organogenesis 366 – classification 1191 Embryonic stem (ES) 269 – continuous 1192 Embryonic stem cell 286, 319 – continuous helical 1193 – cardiomyocyte differentiation 289 – cryptic 1197 – characterization of human SCNT 276 – discontinuous 1194 – human 269, 287 – linear 1195 – marker 276 – mapping 1192 Embryotoxicity – post-translationally modified 1192 – use of D. discoideum for testing 687 – proteinaceous 1193 Emend 1538 – specificity 1163 Eminase 461 – visualization 1195, 1198 Enbrel 7, 24, 463, 1118 Epoade 472 Encephalomyocarditis virus 766 Epoetin delta 472 Encoded self-assembling chemical libraries Epogen 3, 16, 472, 738 (ESACHEL) 1275 Epogen Herceptin 737 End stage renal disease (ESRD) 354 Epogin 472 Endocytosis 1426, 1490 Epopen 472 Endoglin 1281 Epothilone 1804 Endosomal escape 1530 Eprex 472, 1656–1657, 1762 Endosperm cell 935 ErbB1(epidermal growth factor receptor) 129 Endothelial cell adhesion molecules 1282 ErbB2 129 Endothelial progenitor cell (EPC) 285, 319 ErbB3 129 Endotheline 235 ErbB4 129 Endotoxemia 1009 Erbitux 454–455, 479, 1121 End-point dilution (EPD) assay 166 ERGIC-53 420 Engerix B 18, 1639 Ergotamine 330 Enhanced permeability and retention effect Erlotinib 143 (EPR) 1366 Erypo 472 Eniluracil 1253 Erythrocytes 1173 5-Enolpyruvyl-shikimate3-phosphate Erythroid membrane associated protein 1205 synthase 898 Erythromycin Enoxaparin 457 – biosynthesis steps 1811 Enterobacter aerogens 1352 – by DEBS’3 1815 Enterodiol 943 – derivatives 1813 Subject Index 1855

– metabolized by CYP3A4 1584 European bioinformatics institute 255 – pathway 1821 European commission (EC) 1760 – use 1804 European community pharmaceutical Erythropoietin (EPO) 466, 737 directive 1675 Erythropoietin alfa 472 European council regulation 1677 Erythropoietin beta 472 European department for the quality of medicine Escherichia coli 1135, 1351, 1401 (EDQM) 1680 – cell free expression of biopharmaceuticals European federation of pharmaceutical using 1063 industries and associations 1643 – expression platform 1022 European market, generic conversion rates – extracts 1070–1071 and price 1766 – G-CSF produced by 1757 European medicines evaluation agency – in biosynthesis of insulin 1034 (EMEA) 434, 1559, 1643, 1677 – plasmid DNA templates for 1066 – key tasks 1678 – transgenic genomes from 1046 European molecular biology institute 255 Escherichia coli system European nutrigenomics organization 93 – coupled transcription/translation from 1076 European organization for the treatment – reaction conditions 1075 of cancer (EORTC) 1233 Esperamycin 1125 European pharmacopoeia 1680 Espo 472 European public assessment report Est1p (ever shorter telomeres) 40 (EPAR) 1688 Est2p 39 EuroPHARM database 1677 Est3p 40 Evalizumab 1086 Estrogen response element 233, 239 Evans blue 1472 Etanercerpt 463, 1118, 1163 Exercise treadmill test (ETT) 175 Ethoxyresorufin 1618 Exogenous DNA 1529 Ethyl-(diamethylaminopropyl)carbodiimide 1310 Exon 2 653 Ethylenediamine tetraacetic acid 1466 Exopeptidase 1379 N-Ethylmaleinimide 403 Expanded bed absorption Etoposide 131, 503 – biopharmaceutical production in cultured EU authorities plant cells 960 – bioproduct definition 1681 Experimental autoimmune encephalomyelitis EU concept papers 1706–1707 (EAE) 1237 EU directives 1703 Expressed sequence tag (EST) 105, 630 EU draft guidelines 1706–1707 Expression difference mapping 1330 EUDRACT database 1697 ExpressTec 931 EUDRALex 1670, 1677, 1682 – development 933 EUDRANet 1677 – protein expression in grains 945 EUDRATrack 1677 Extracellular matrix EudraVigilance 1677 – imaging 1256 EU guidelines – modified 1276 – adopted for biosimilar medicinal Extracellular superoxide dismutase (ecSOD) 317 products 1707 Extrachromosomal palindrome 664 – adopted for biotechnology medicinal products 1705 f Euglycemic clamp study fVIIa 459 – dose ranging 1451 fVIII 459 Eukaryotic transcription factor 235 – biosynthesis 427 EU regulations 1703 – by perfusion technology 743 – for biopharmaceuticals 1669 – development of recombinant 428 – laws 1676 – production of recombinant 430 Eurifel FELV 26 – protein 424 Eurifel RCPFEVL 26 – secretion and activation 426 1856 Subject Index

– structure and function 425 – CYP2C9 inhibitor 1590 fIX 495, 695 – radiolabeled 1285 – activated 699 Fluoracil 510 – human 459 5-Fluorouracil 76 – protein, exon, domain and structure of 696 Fluorescein isocyanate 1472 – zymogen form 697 Fluorescein isothiocyanate (FITC) 363 Fabrase 475 Fluorescein isothiocyanate-Tat-Peptide 637 Fabrazyme 23, 475 Fluorescence-activated cell sorting (FACS) 299, Fabry disease 23, 861 1112, 1431 – pathways and targets for 625 – for screening of cell lines 816 fC 459 Fluorescence-mediated tomography FACS, see fluorescence-activated cell sorting – protease activity imaging 1282 FANTOM2 dataset 217 Fluoro-deoxy-arabinofuranosyl-iodouracil Fasturtec 24, 475 (FIAU) 1254 Fatty acid oxydation 121 Fluorodeoxyglucose 499, 1226 FCGR3A 59 Fluoroestradiol 1256 FDA, see Food and Drug Administration Fluoroethanidazole 1264 FD&C Act 1641 Fluoroethylspiperone (FESP) 1254 Feline immunodeficiency virus (FIV) 202, [(Fluorohexenyl)benzene-sulfonylamino]-3-butyric 556 acid 1257 Fenfluramine 52 (Fluoro-hydroxy methyl butyl) guanine 1254 Feron 467 Fluoro-methyldeoxyuracil- Fertinex 464 arabinofuranoside 1261 Fertinorm 464 Fluoromizonidazole 1264 Fetal bovine serum (FBS) 785 Fluorophores 1227 Fevaxyn Pentofel 25 Fluorothiol 1259 Fexofenadine 58, 1788 Fluorothymidine 1261 FGF (fibroblast growth factor) 153, 307 Fluorouracil 131, 1250 FGF-4 172 – radiolabeled 1253 – pACSR/FGF-4 156 Fluoxetine 61 – proteine, production of 168 Flurbiprofen FGF-5 172 – CYP2C9 complex 1593 Fibrin 1283 – metabolism 1593 Fibrin clot lysis assay 1565 Fluvoxamine 61 Fibrinogen 1283 – Fluxum 457 – expression of, in rice grain 940 Follicle-stimulating hormone (FSH) 4 – recognition exo-site 413 Follistim 15, 465 – recognition site 412 Follistim AQ 465 Fibrinolysis 377, 1009 Follitropin alpha 463 Fibronectin 738, 1283 Follitropin beta 465 Fiducial limit 168 Fondapparin sodium 457 Field flow fractionation, see FFF Food and drug administration (FDA) 49, 1559, Filgrastim 4, 16, 473, 1406, 1755 1639, 1765 Firefly luciferase 1228 – guidance 1642 FirtEF algorithm 108 – regulatory authority for monoclonal FISH (fluorescence in situ hybridization) 134, antibodies 1085 728, 736 Forcalcitonin 477 – analysis of BC6 transgene 1002 Forcaltonin 15 – semiquantitative 1002 Formivirsen 24 FK506 1805 Forskolin 292 Flavodoxin 1616 Forsteo 15, 477 Flock haus virus (FHV) 263 Forteo 15, 476 Fluconazole Fortical 477 Subject Index 1857

Fourier transform ion cyclotron resonance – PEGylation 1404 (FTICR) 1564 – PEGylation sites and relative yields 1405 FP-TDI 84 – production 1756 Fractogel-DEAE chromatography 158 Gefitinib 59, 76 Fragment antigen binding 1088 Gelatin 872, 957, 1380 Fragmin 457 – microcarriers 336 Fraxiparine 457 Gemeinsamer Bewertungsausschuss 1720 Fraxodi 457 Gemfibozil Free induction decay (FID) 1216 – CYP2C8 inhibitor 55, 1594 Freud’s adjuvant, complete 194 Gemtuzumab 455 Frone 467 Gemtuzumab ozogamicin 480, 1086 1,2-Fucosyltransferase 355 – in cancer treatment 1172 3-Fucosyltransferase 925 Gemtuzumab zogamicin 22 Fusigenic-hemagglutinating-virus 307 Genasense 633 Fusogenic lipids 1523 GenBank sequence 170 Gene structure g – analysis of 651 G protein-coupled receptor (GPCR) 664 Gene amplification 733 G418 299, 785 Gene cloning, full length 109 GA (glutaminase-asparaginase) 540 Gene correction 1531 – inhibition of sarcoma 180 – efficiency 1534 – tumor cell growth 541 – site specific 1533 – treatment of mouse tumors 541 Gene delivery 153, 1318 Gag proteins 551 – bionanotechnology in 1543 Galactosidase 1500 – liposomal 1507 3-Galactosyltransferase 355 – scheme for hepatocyte selective 1512 4-Galactosyltransferase 925 – system 1521 Gallivac HVT IBD 26 Gene expression Gamma-aminobutyric acid (GABA) 1198 – heterologous 769 Gamma scintigraphy of oralin deposition 1450 – chip 1613 Gancyclovir 313 – heterohybridoma 769 GAP31 482 Gene identification 105 Gas chromatography/mass spectrometry Gene mining (GC/MS) – de novo prediction 107 – of Mathay resinol 945 – homology/orthology mining 105 – in lung cancer detection 1344 – in silico prediction 107 Gastric lipase deficiency 859 – integrated approaches 108 GATA4 290 – splice variants 108 Gateway bacteriophage 610 – transcript 107 Gateway cloning 614 Gene recombination 706 – three-fragment multisite 618 Gene replacement (knock-out) 666, 669 Gateway-enabled baculovirus expression – at predefined locus 767 system 615 Gene silencing 258 Gateway entry clones 611 – antisense oligos 633 Gateway, multisite 616 – antisense RNA 633 Gateway reactions 610 – post transcriptional 634, 896 Gateway recombinatorial cloning system 606 Gene targeting Gateway vector system 611 – in CHO cells 768 Gaucher’s disease 8 – genetically modified mice 651 G-CSF (granulocyte colony-stimulating factor) 4, Gene therapy 31, 1521 321, 1755 – adenovirus-based 151 – dosage 1757 – and regenerative cardiovascular medicine 319 – function 1757 – cytotoxic 313 1858 Subject Index

– DNA-based molecules for 183 Globuren 472 – for cardiovascular disease 305 Glomerular basement membrane 1197 – for myocardial failure 318 Glucagen 14 – for myocardial protection 317 GlucaGen 476 – of AIDS 553 Glucagon G Novo 476 – radiation 313 Glucagon rDNA 476 – somatic 689 Glucocerebrosidase 861 – therapeutic angiogenesis 307 Glucose – vector 155, 184 – concentation-time profile in plasma 1471, 1476 Gene transcription 933 – concentration after kitosan capsule Gene transfer 733 administration 1483 – anti-thrombogenic 315 Glucose metabolism – cationic 1510 – PET imaging of 1260 – for rapid re-endothelialization 314 Glucosidase 861 – in cancer cells 1515 GlutaDON therapy 537 – nitric oxide 314 Glutamate decarboxylase 65 – to brain 1517 – modeling 1198 – to prevent matrix remodeling 315 Glutamate synthetase 734 Gene trap 669 Glutamic acid carboxylase 905 GeneChips 84, 1750 Glutaminase synthetase, see GS Gene-environment interactions 75 Glutaminase asparaginase, see GA Generic biopharmaceuticals 30 Glutamine synthetase (GS) Generic conversion rate 1766 – expression vector 812 Generic price 1766 – /CHO cell system 1094 Gene-targeted mice 658 Glutathione Genetic background 73 – reduction in transgenic plants 979 Genetically modified mice 649 – reductase 1073 Geneticin 785 Glutelin 933 Genetonorm 476 gly 219 700 Genome analysis 170 Glyburide 1457 Genome-wide variant pattern (GVP) 80 Glycan analyse 800 Genomic information Glycan structure – translation of 83 – differences in 773 Genomics 30 Glycinebetaine 976, 988 Genosensors 1545 Glycogen synthase kinase 3 inhibitor 288 Genotoxicity N-Glycolyl neuraminic acid 772, 811, 849 – in silico 1624 Glycosylation 678 – in vitro 1624 Glycosyl phosphatidylinositol (GPI) 674 – prediction 1624 – anchor 716 – screening 1627 Gold in drug delivery 1540 Genotropin 14, 476 Gold standard 87, 201 Genotropin Miniquick 476 Golgi apparatus 427 GenScan mining 108 Gonadorelin 1376 Gentel 463 Gonal F 9, 15, 463 Geref 476 Good laboratory practice (GLP) 1640 Gibberellic acid 957 Good manufacturing practice (GMP) Gingko biloba 61 – in transgenic systems 851 Gleevec 639 Goodpasture disease 1197 Glial fibrillary acidic protein promoter 1517 Goserelin 478 Glial-derived nerve growth factor (GDNF) 333 Gosher’s disease 23, 1513 G-line 772 – test on enzyme therapy 905 Glioblastoma multiforme 509 Government printing office 1640 Gliptide 463 GPS (Global Pharma Specialist), XXV 1833 Subject Index 1859

G-proteine coupled receptor (GPCR) 105 Healthcare Gram-negative pathogen 686 – costs 1715 Gram-negative bacteria 485 – economics 1762 Gram-positive bacteria 381, 485 – environment 1733 Gran 473 – payors 1718 Granocyte 473 – reform legislation 1718 Granulocyte-colony stimulating factor, see G-CSF Heamin 957 Granulocyte-macrophage colony-stimulating Heart failure, targeting 1284 factor (GM-CSF) 6, 1429 Heat shock proteins Granulokine 473 – levels of expression of different 984 Graves disease 1188 – synthesis and regulation of cytoplasmic 983 Green fluorescent protein reporter 1627 HEK 293, 156, 744, 775 GreenScreen 1608 HeLa cells 614 GreenScreen GC 1624 Helicobacter pylori 869 – assay 1630 Heliotis virescens 483 – genotoxicity tests 1627 Helixate 10, 459 – industrial validation studies 1633 Helixate FS 459 – molecular genetics 1628 Helixate NexGen 10, 459 – proof of concept 1631 Hemagglutinating virus of Japan 236 Grepafloxacin 52 Hemangiomas 312 Growject 476 Hematopoietic agent 466 Growth factor 154 Hematopoietic stem cell (HSC) 554 GRTPA 461 Hemolysin 383 GS (Glutamine synthetase) 809 Hemo-oxygenase-1(HO-1) 317 – schematic of a cell line selection program 817 Hemophilia A 10 GS-CHO cell lines 812 – therapy 421 GS-NS0 cell lines 812 Hemophilia B 10 Hemostasis 444 h Hemotaxis 643 H19 220, 277 Hemiptera 486 HA-1A 455 Hepacare 19 HAART (highly active antiviral therapy) 549, 558 Heparansulfateproteoglycan 1007 Haemate HS 454, 459 Heparin 997, 1370 Haemate P 459 – binding affinity of rhAT 1005 Haemophilus influenzae 1421 Heparin affinity chromatography 1003 Haemophilus influenzae B 18 Heparin resistance 1012 Hairy cell leukemia 17 – in CABG patients 1013 Haliclona cratera 482 Hepatic metabolic clearance 1796 Halomonias elongata 978 Hepatitis B 17 Ham F12 740 Hepatitis C 17, 263 HAMA 7 – virus vaccine 1430 Hamster antibody production test (HAP) 434 Hepatocyte HANC 220 – asialoglycoprotein receptor mediated 1512 Hansenula polymorpha 1135 Hepatocyte growth factor, see HGF Hapase 461 HER1 129 Haplotype blocks 81 HER2 (human epidermal growth factor Haplotype tag 81 receptor 2) 21, 128 Hartmannella vermiformis 685 – indicators of 129 Hatch-Waxman Act 1722, 1765 – testing 133 Hayflic limit 44 – testing, algorithm 135 HBVAXPRO 19 – /neu oncogene 1277 Health care reform act 1719 HER3 129 Health products and food branch (HPFB) 1762 HER4 129 1860 Subject Index

HERA trial 144 – combinatorial RNA-based therapy 569 HercepTest 77, 134 – gag protein 551 Herceptin 22, 64, 77, 128, 455, 479, 526, 1086, – genes and life cycle of 551 1121 – pol protein 551 – adjuvant trials 144 – provirus 551 – antitumor effect 132 – tat protein 219, 553 – combination with chemotherapeutic drugs 131 – toxic genes therapy 555 – development hallmarks 137 – vector mobilization 575 – duration of response 137 – vectors used in gene therapy 556 – in early breast cancer 143 HIV-2 (human immunodeficiency virus – mechanism, on cellular processes 130 type 2) 556 – monotherapy 138 HKB11 (hybrid of human kidney and B cell) – quality of life 137 – expression platform 1029 – time to progression 137 HLA (human leucocyte antigen) 80 – time to treatment failure 137 HLA-B57 82 Hereditary angioedema 859 HMG-CoA 59 HERG 59 Hoechst epi-fluorescence technique 321 Hetero duplex analysis 86 Holoenzymes 1620 Heterobifunctional inhibitor 403 Homo-arginine 413 Heterochromatin 730 Host cell Heterogeneous nuclear hnRNA 628 – engineering 732 Heterohybridoma CB03 – protein 166, 1131 – chromosome analysis of 770 Host Response Protein Amplification Cascade Hexadecyltrimethyl ammonium bromide 1493 1338 Hexavac 19 HOST2 220 Hexosaminidase inhibitor 1047 HOXB8 223 HGF (hepatocyte growth factor) 307 HPAEC-PAD (high-performance anion exchange hGH (human growth hormone) 14, 476 chromatography with pulsed amperometric – deficiency 14 detection) 800 HIF (hypoxia inducible factor) 307 – glycan profile of human IgG 801 HighFive 1047 HPIEC, see high-performance ion-exchange Highly active antiviral therapy, see HAART chromatography High-performance capillary electrophoresis HPLC, see high-performance liquide chromatog- (HPCE) 1563 raphy High-performance ion-exchange chromatography HPSEC, see high-performance size-exclusion (HPIEC) 1562 chromatography High-performance liquid chromatography HuCAL (HPLC) 84, 1563 – design modularity 1176 High-performance size exclusion chromatography – GOLD antibody library 1159 (HP-SEC) 798, 1562 – library 1177 – High-resolution computed tomography HUM195 506 (HRCT) 1750 Huma ES system 290 High-throughput cloning 605, 615 Humalog 12–13, 469, 1456 High-throughput screening (HTS) 101, 1606 Humalog MIX 469 Hirschsprung’s disease 77 Human actrapid 470 Hirudin 412 Human adenovirus 782 Hirulog 461 Human anti-mouse antibody (HAMA) 7, 1109 Hismanal 52 Human anti-streptavidin antibody (HASA) 513 HIV (human immunodeficiency virus) 263, Human antithrombin 1513 – conformation analysis 1004 – antiviral gene therapy 554 – establishment of transgenic herd 1001 HIV-1 (human immunodeficiency virus type 1) – glycosylation 1005 549, 556 – purification 1003 Subject Index 1861

Human antithrombin III Human-ether-a go-go-related (hERG) potassium – from transgenic system 855 channel 1796 Human antithrombin process Humaspect 22 – viral removal or inactivation by 1007 Humate P 459 Human C1 inhibitor Humatrope 14, 476 – from transgenic system 859 Humira 22, 455, 864, 1086, 1112, 1118 Human cell Humulin 12–13, 452, 1449 – for organogenesis 353 – 50/50 469 – for transplantation 353 – 70/30 469 Human chorionic gonadotropin 1326 – I 469 Human cytomegalovirus 764 – L (Lente) 469 Human embryonic retina (HER) cell 783 – M 469 Human embryonic stem cell (hES) 269, 287 – M1 469 – derivation of 286 – M2 469 Human epidermal growth factor receptor 2, – M3 469 see HER2 – M4 469 Human fetal mesencephalic cell – M5 469 – transplantation of 331 – N 469 Human foreskin fibroblast cells (HFF) 637 – R 470 Human genome project 230, 622 – S 470 Human genome sequencing consortium – U 469 214 – Zn 469 Human germ line structure 771 Huntington’s disease Human growth hormone, see hGH – pathways and targets for 625 Human immunodeficiency virus, see HIV Hyaluronic acid 1380 Human immunodeficiency virus type 1, Hybridoma cells 433 see HIV-1 Hybridomas 820 Human Insulatard 471 Hydrohermatic feed system 160 Human insulin Zn suspension 469–470 3-Hydroxyacyl-CoA dehydrogenase II 328 – 30/70 470 Hydroxycyclophosphamide 131 – protamine 471 N-(Hydroxypropyl)methacrylamide Co-polymer Human lactoferrin, expression of, in rice grain 1367 940 Hydroxysuccinimide ester 1403 Human leucocyte antigen, see HLA 7-Hydroxy-4-trifluoromethylcoumarin Human liver microsomes 1618 (HFC) 1610 Human lysozyme Hygromycin 771 – expression 935 Hygromycin B 1030 – recombinant 939 – phosphotransferase 766 Human monotard 470 Hymenoptera 486 Human neutral insulin 470 Hyperplasia Human papilloma virus 263 – cytotoxic strategies to reduce neointimal 313 Human phosphoglycerate kinase (PGK) – gene transfer to reduce neointimal 314 promoter 783 – neointimal 319 Human platelet-derived growth factor, see PDGF Hyperuricaemia 24 Human protein processing 774 Hypoglycemia 14 Human retinal pigment epithelial (hRPE) 325 Hypoxia 1263 Human serum albumin (HSA) 275 Hypoxia inducible factor (HIF) 154, 307, 1279 Human somatic cell nuclear transfer 273 Human tissue plasminogen activator i – from transgenic system 836 IBMX (3-Isobutyl-1-methylxanthine) 292 Human umbilical vein endothelial cell (HUVEC) Ibraxion 26 1008 Ibritumomab tiuetan 456, 480 Human velosulin 471 Ibritumomab tiuxetan 22, 1086 1862 Subject Index

– half life 1168 Immunohistochemistry (IHC) 116 – in radiotherapy 503 Immunoliposomes 1517 – radio active labeled 501 Immunomodulatory molecule 193 IC31 1440 – adjuvants 194 IC41 1430 – DNA-based 195 ICH (international conference on harmonisation) Immunomodulation 939 1567 Immunoscintigraphy with radiolabeled – guidance for assay validation 1568 ABS 1123 – parties 1680 Immunostaining 772 – process 1681 Immunosuppressive drugs 1804 ICH Guidance 1642 Immunotoxin, first generation 1125 ICH guidelines 434 Implants 1546 – for developed biotech products 1707 – drug delivery system 1369 ICH Q5A 1570 – polymeric solutions building in situ 1374 ICH Q5B 1572 IMS (ion mobility spectrometer) 1343, 1345 ICH Q5C 1572 – adaptation to MCC-Ni 1347 ICH Q5D 1572 – chromatogram examples 1350 ICH Q5E 1572 – chromatogram of human exhaled air 1349 ICH Q6B 1572, 1691 – sources for 1345 ICH S6 1692 – working principle of 1346 ICH S7A 1692 Imukin 1 467 Identity assay 1566 Imunace 464, 479 Idiopathic pulmonary arterial hypertension, In situ hybridisation (ISH) 134 see IPAH IND (investigational new drug) 50 Idiopathic pulmonary fibrosis (IPF) 1750 – applications 742 Idotamoxifen – submission of pharmacogenetics data to 62 – in breast cancer 524 Indimacis 122 22 Iduronidase alpha 862 indirect immunofluorescence (IIF) 1190 Ifosfamide indium-111 zevalin 456, 480 – hydroxylation catalyzed by CYP2B4 1597 InductOs 24, 464 Igef 463 Infanrix 18 IgG, light and heavy chains 785 Infection, targeting 1285 Igovomab 22 Infectious disease era 103 IHC (immunohistochemistry) 133 Inferax 467 Imagent 1305 Infergen 17, 467 Imiglucerase 475 Inflammatory bowel disease 1117, 1285 Iminase 461 Inflammatory cytokines 197 ImmobaSil carrier 682 Infliximab 21, 59, 456, 1086, 1118, 1153, 1163 Immukin 467 Influenza virus 484, 1488 Immune response 1425 InFuse 464 – type 1 and 2 1424 Injection, drug delivery system 1369 Immune globulin intravenous (IGIV) 1109 Inner cell mass 286 Immuneron 468 Inositol-1,4,5-triphosphate 688 Immunoassays 171 Insect cell culture 1047 Immunoblotting 1563 – glycosylation 1047 Immunogenicity 1656 – in biopharmaceutical production 1045 – of antibodies 1153 – process cost calculations for 1059 Immunoglobulin 198, 1107 – protease activities in infected 1049 – subclasses 1424 Insertions or deletions (InDel) mutations 75 – locus 769 Inspectional authority for biopharmaceuti- – bivalent 1166 cals 1653 – post translational modifications 1132 Institut für Pflanzengenetik und Naturpflanzen- Immunoglobulin G 862 forschung 869 Subject Index 1863

Institut für Qualität und Wirtschaftlichkeit – alfa-2b 468, 480 im Gesundheitswesen 1721 – alfacon-1 467 Insulatard 13 – alfa-n1 468 Insulatard NPH 471 – alfa-n3 467 Insulin 466, 1376, 1449, 1451, 1465 – beta 467 – analogues 1034 – beta-1a 467 – biosynthetic, human 1034 – beta-ser 467 – effect of protease inhibitors on intestinal – gamma 468, 1750 absorption 1471 – gamma-1a 467, 479 – human 470, 1034 – gamma-1b 467 – industrial scale 1033 – gamma-n1 468 – intestinal absorption using kitosan capsules Interferon regulatory factor-1 (IRF-1) 233 1482 Interleukin (IL) 190, 201, 329, 905 – isophane 469 – expression system 1022 – kitosan capsules for delivery of 1480 – IL-2 465 – lipophilic index 1473 – IL4v expression plasmids 1026 – meal 1454 – IL-10 59 – native 1474 Internal ribosome entry site (IRES) 765 – precursor molecule 1036 International biopharmaceutical reference – production of 1041 material (IBRM) 1569 – structure and its acyl derivatives 1474 International conference on harmonization, Insulin acyl derivatives see ICH – activity and lipophilic index 1475 International HapMap consortium 77 – half lives for proteolysis of 1475 Intestine trifoil factor (ITF) 942 Insulin aspart 13, 470, 1039 – expression of, in rice grain 941 – biphasic 470 Intron A 17, 468, 480, 1402 Insulin caproyl derivatives 1476 Invader 84 – transport of 1477 Investigational medicinal product dossier Insulin degradation (IMPD) 1697 – effect of protease inhibitor on 1469 Investigational new drug (IND) 1121, 1638 Insulin derivatives – application 865 – circular dichroic spectra of 1476 Invitrogen 1028 Insulin determir 13, 470 Iodine 499 Insulin glargine 13, 470 Iodoacetamide 1073 Insulin glulisine 13, 469 Iododeoxyuridine 1261 Insulin injection 1455 – radioactive labeled 519 Insulin lispro 12, 469 Iodogen 1254 – biphasic 469 Ion homeostasis 971 Insulin precursor expression system 1039 Ion mobility spectra 1348 Insulin-like growth factor type 2 receptor Ion mobility spectrometer, see IMS (IGF2R) 218 Ionomycin 272 Insuman 13, 470 Iontophoresis 1382 Insuman basal 469 IPAH (idiopathic pulmonary arterial hyper- Interaction discovery mapping 1325 tension) 1743 Interannular heterobivalent inhibitor 403 – aviptadil treatment 1750 Interannular homobivalent inhibitor 400 – causes 1750 interferon (IFN) 4, 466, 1253 Ipsalazide 1381 – for in situ radiotherapy 510 IPW 220 – PEGylation 1401, 1404 IRES element 766 – PEGylation by two step approach 1405 Iressa 76 Interferon Irinotekan 57 – alfa 467 Iron protoporphyrin IX 1582 – alfa-2a 468, 480 Iron-transferrin complex 1426 1864 Subject Index

Ischemia-reperfusion 317 Kogenate SF 459 Isoelectric focusing (IEF) 798 Kozak sequence 107, 814 – capillary 798 Kringle 5 383 – in purity and homogenicity control 1563 Kunitz-type inhibitor 1027 – profile of purified human IgG from PER.C6 Kupfer cells 1511 cell 799 KvLQT1 59 Isoelectric point 1563 Kybernin 458, 1004 Isophane insulin 469 Kybernin P 1008 Isopropyl-thiogalactopyranoside 1022, 1617 KyberSept trial 997 Itraconazole 55 Kyoto encyclopedia of genes and genomes (KEGG) 624 j Japan pharmaceutical manufacturers association l 1643 Label-free hybridization 87 Jervell syndrome 220 Label-free pyrosequencing 87 LACK antigen 201 k Lactate dehydrogenase 1326 22k48 220 – Lactoferrin 866 K422 526 Lambda recognition recombination reaction 610 Kalikrein 1005 Lambda system 609 – inhibition by aprotinin 1027 Lange-Nielsen syndrome 220 Kanamycin 1024 Langerhans cell 1429 Kaposy sarcoma 156 Langerhans islet 1033 Kaulonemea cell 920 Lantus 13, 470 KCNH2 59 LARGE 116 KCNQ1 59 Large degradation clearance 1479 Keksin Large scale biology corporation (LSBC) 861, 864 – cleavage 1037 Larmor frequency 1215 – processing site 1038 Laronidase 475 Ketoconazole Lauryl-maltopyranosidase 1465 – CYP2C9 inhibitor 1590 L-CDR1 1177 Ketoreductase domain 1810 L-CDR3 1177 Ketosynthase domain 1807 L-DOPA 325, 332 Kidney – dose 343 – allograft transplantation 354 – in Parkinson treatment 330 – xenotransplants 354 – therapy 342 Kidney precursor 359 LEA protein 980 – by nuclear transfer 365 Lecithin microemulsion, hydrogenated 1550 – functionality after transplantation 363 Legionella pneumophila 685 – in vitro propagation 364 Legionellae 685 – reduced immunogenicity 362 Legioner’s disease 685 Kineret 17, 464, 1118 Leishmaniasis 201 Kitosan capsule Lemna 897 – cross-section of 1481 Lentiviral vector 557 – degradation of 1482 – production of 576 – for insulin delivery 1480 Lentivirus 551, 574 – gastrointestinal transit of 1481 Lepirudin 462 – release of carboxyfluorescein of 1482 Lernogastrim 473 Klexane 457 Leucine enkephalin 1376 KLKL5KLK 1434, 1440 – analog 1473 – type 2-inducing adjuvant 1435 Leucomax 472 Kogenate 10, 459 Leukemia inhibitory factor (LIF) 288 KoGENate 1639 Leukemic stem cells 505 Kogenate FS 459 Subject Index 1865

Leukine 6, 16, 472 Liprolog 12–13, 469 Leukoprol 473 Liquid chromatography (LC) LeukoScan 22 – for peptide mapping 802 Leuprolide 1378 Liquid chromatography/mass spectrophotometry Levemir 8, 12–13, 470 (LC/MS) Levis Y carbohydrate antigen 1172 – amino acid determination by 1004 Levovist 1305 LIT1 220 Levulinic acid 400 LMAN1 427 Lewis molecular model 1623 LMW heparin 458 Lewis P450 molecular model 1609 Locus control region 765 Lewy body 326–327 Long QT syndrome (LQTS) 1605 Lewy neurite 329 Longastatin LAR 478 Lhadi 464 Longastatina 478 Ligand 1273 5'-Long-terminal-repeat (5'-LTR) promoter 552 Ligand-based targeting 1272 Loperamide 1795 Ligand-binding assay Lotronex 52 – in biopharmaceutical quality control 1563 Lovastatin 101, 1804 Lignan – metabolized by CYP3A4 1584 – biosynthetic pathway 943 Lovenox 457 – expression of, in rice grain 943 Low molecular mass permeation enhancer 1376 Lilium brownii 483 Lower limit of quantification (LLOQ) 1575 Limit of detection (LOD) 1568 Lowhepa 457 Limit of quantification (LOQ) 1568 Lowmorin 457 Limulus amoebocyte lysate (LAI) 197 Luciferase 1224 – test 1565 Luciferin 1224 Limulus polyphemus 1565 Lufa cylindrica 484 LINK program 1614 Lugol’s iodine 502 Linkage disequilibrium (LD) 81 Lung Linker – toxicological effect of nanoparticles 1548 – inter-polypeptide 1812 Lung cancer – intra-polypeptide 1812 – detection by GC/MS 1344 Linoleic acid 1466 – early detection 1343 Lipid Lung tumor – film hydration method 1522 – PEG-PGA+DON treatment 542 – folate modified 1516 Luteinizing hormone (LH) 4 Lipobay 1604 Luteinizing hormone releasing hormone LipofectAmine Plus 1526 (LHRH) 1361 – transgene expression 1528 – PEGylation 1407 Lipofectin in gene delivery 1543 Lutropin alfa 464 Lipolex 1526 Luveris 15, 464 Lipoplex 1510 LX1 116 Lipopolysaccharide (LPS)-mediated inflammatory Lycopersicon cheesmanii 970 response 716 Lycopersicon esculentum 970 Liposome Lycopersicon pennellii 970 – asialofetuin-labeled 1512 Lycopersicon pimpinellifolium 970 – cationic 1510 Lyme disease vaccine 18 – complex 1516 Lymerix 18 – drug delivery system 1369 Lypolex – in nanobiotechnology 1549 – galactosylated 1513 – unilamellae 1370 – mannosylated 1514 5-Lipoxygenase activating protein (FLAP) 82 lys224 700 Liposomal gene delivery 1507 lys98 698 Liposomal parenteral drugs 1370 Lysergic acid diethylamide 101 1866 Subject Index

LysoTracker 1499 Manufacturers working cell bank (MWCB) 158, Lysozyme 1473 746 – antilysozyme antibody 936 Manufacturing – expression 937 – expression systems for 1093 – expression of human, in rice grain 938 – costs 1093 – recombinant human 936 – strategy 1089 MAP30 482 m Marker M195 506 – assisted selection 970 MA 148 539 – for angiogenesis 1281 mab17-1a 456 – in human blood 1326 Mabcampath 22, 455, 479 – tumor associated 1276 MabTera 22, 456, 480, 1121 Market health products directorate Macrolin 465, 480 (MHPD) 1762 Macrophages Marogen 472 – gene transfer to 1513 Mass Array 84 – synovial 1284 Mass spectrometry (MS) 1564 Macropinocytosis 1525, 1530 – for peptide mapping 802 Macropinosomes 1525 – tandem 1564 Macugen 1394 Mast cell beta-tryptase 405 Mad1 42 Master cell bank (MCB) 784, 1645 Magainins 486 Master virus bank (MVB) 157 Magnetic resonance imaging, see MRI Master working cell bank (MWCB) 746, 1129 Magnevist 1217 Mastocytomas 1429 MagnICON 902, 909 MAT (malonyl-CoA:ACP transacylase) 1814 Major histocompatibility complex (MHC) 290, – structure 1815 361, 905, 1489 Mathay resinol 943 – MHCII antigen 300 Matrix metalloproteinase 1227, 1256, 1280 Major intermediate early (MIE) gene 811 Matrix-assisted laser desorption ionization, see MALAD-1 220 MALDI MALDI (matrix-assisted laser desorption Matrix-assisted laser desorption ionization time ionization) 1564 of flight, see MALDI-TOF MALDI-MS (matrix-assisted laser desorption Matrix-assisted laser desorption ionization time of ionization mass spectrometry) 800 flight mass spectrometry, see MALDI-TOF-MS MALDI-TOF (matrix-assisted laser desorption Maximum plasma concentration 51 ionization time of flight) Maytansanoids, cytotoxic 1172 – traces of glycans of antibody B 800 MCFD2 427 – analysis of mPEG MAL-CV-N413 1412 MDR1 58 – galactosylation profile of monoclonal Meal insulin 1454 antibodies 801 Measles-mumps-rubella vaccine 1421 – of mosses 925 Mecasermin 465 MALDI-TOF MS (matrix-assisted laser desorption Medical and scientific advisory council (MASAC) ionization time of flight mass spectrometry) 424 – oligosaccharide profiles determined by Mef2b 294 828 Mef2c 290, 294 Malein imide 1400 MEK1 257 Maleoyl-alanyl-dipeptide aldehyde 404 MEK2 257 Malva parviflora 483 MEKK1 Mammary adenocarcinoma – phosphorylation inhibition of 1746 – treatment with GA and DON 543 Mellaril 64 Mannitol, overexpression 978 Memapsin 1782 Mannose 679, 1513 Membrane lipids Mantle cell lymphoma 222 – levels of 989 Subject Index 1867

MEN1 220 Microinjection, pronuclear 1000 2-Mercaptoethanol 1070 Microneedle 1541 6-Mercaptopurine 64 – system 1383 Meristem 990 Microspheres Mesenchymal stem cell (MSC) 285, 366 – biodegradable 1487 Messenger RNA, see mRNA – hydrophobic 1371 Metabolism prediction – drug distribution in 1372 – computational approaches 1609 – for encapsulated DNA vaccines 1492 – in vitro techniques 1613 – hydrophilic 1374 1-Metaiodobenzylguanidine 499 – immunoresponses 1500 Metalyse 11, 462 – polyorthoesters for 1496 Metastatic colon cancer 206 – uptake by macrophages 1499 Methanethiosulfonate 1400 – using polyesters 1493 Methioninesulfoximine (MSX) 735, 766 Midazolam Methionyl-tRNA transformylase 1068 – metabolized by CYP3A4 1585 Methotrexate (MTX) 76, 131, 734, 766, MIDGE vector (minimalistic immunogenetically 1030 defined gene expression) 183 N-Methyl-aspartate (NMDA) 638 – application of 198 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine – characteristics 189 (MPTP) 327–328 – immunization pathways using 200 Metoprolol 61 – immunomodulating 191 Methylenetetrahydrofolate reductase – production 188 (MTHFR) 76 – smart 191 Metrodin HP 464 – structures 187 Metronidazole Milyzer 461 – CYP2C9 inhibitor 1590 Mimic Sf-9 cell 1047 Mettox Mimotope 1194 – assay 1603, 1608 Minidalton 457 – molecular model 1623 Ministry of health, labour and welfare Metyrapone 1588 (WHLW) 1643 Mevacor 1730 MIRD schema 523 MF59 1425 Mirimostim 473 Miacalcic 477 miRNA (Micro RNA) 222, 628 Miacalcic NS 477 Mistral 458 Mibefradil 52 Mitogen activated protein kinase 1 Micro array analysis (MAPK1) 258 – of gene silencing 258 Mixtard 13 Micro RNA, see miRNA Mobenakin 464, 480 Microbial pathogenesis MOG (myelin oligodendrocyte glycoprotein) – D. discoideum as model for 685 1193 Microbubbles 1282, 1310, 1318 8-18C5 epitope on 1204 – conjugates 1311 – (8-18C5)-fab complex 1201 – for ultrasound imaging 1219 – antibody responses against 1199 – targeting 1319 – structure of 1201 Microcapsules Molecular dynamics 1609 – preparation with a double emulsion technique Molecular imaging 1309 1373 – applications 1235 Microcarrier 739 – contrast agents for 1225 Microciona prolifera 485 – for drug discovery 1230 Microcystis viridis 484 – modality properties 1229 Micro-electrode array mapping technique 292 Molecular rational design Micro-gene-gun 1318 – of product development 703 – non-invasive 1544 Molgramostim 472 1868 Subject Index

Moloney murine leukemia virus (MoMLV) 574 MSCB (master seed cell bank) 746 Momordica charantia 484 MTHFR, see methylenetetrahydrofolate reductase mondoBIOTECH 1741, 1749 MTT (3,4,5-cimethylthiazol-2yl-2,5-diphenyl Monoaminooxidase B 330 tetrazolium bromide) 640 Monoclate 459 Mucolytic enzymes 1376 Monoclate-P 459 Mucopolysaccharidosis 24, 862 Monoclonal antibody (MAb) 20, 1105 Multiangle light scattering (MALS) 162 – analytical methods for 1116 Multilamellae vesicles 1370 – application areas of 1116 Multifunctional-type nanodevice (MEND) 1522 – approved therapeutics 1120 – transfection activities 1524 – by perfusion technology 743 Multilase 461 – CIPP strategy 1128 Multiple sclerosis (MS) 17 – cytotoxic drugs and toxins linked to 1124 – epidemiology 326 – expression systems 1135 Multiplexing strategy 87 – fed-batch and perfusion cultivation 1087 Multiplicity of infection (MOI) 1048 – generation 1109 – determination of high or low 1049 – generic manufacturing strategy 1129 Multi-wavelength anomalous dispersion 1066 – glycosylation of 1135 Murine embryoid body 289 – heavy and light-chain polypeptides 906 Muromomab 1086 – huNR-LU-10 862 Muromomab-CD3 456 – immunogenicity 1657 Murray breast tumor 131 – manufacturing 1083, 1126 Mutagenesis 592, 666 – market demands 1714 – change-of-specificity 1818 – market perspectives 1119 – combinatorial cassette 706 – physical properties of 1128 – loss- and gain-of-function 1817 – release specifications for 1130 – novel polyketides by change-of-specifici- – routine manufacture 1127 ty 1820 – therapeutic 1086 – random oligonucleotide 706 Monophospholipid A 194 Mutual recognition agreement (MRA) 1677 Monotard 13, 470 MVL 484 Monteplase 461 MWCBs see manufacturers working cell bank Moroctocog-a 10 MWCBs see master cell bank Moss Myasthenia gravis 1188 – cell culture 922 Mycobacterium tuberculosis 1422 – glycoengineering in 927 Myelin basic protein 1200 – in biopharmaceutical production 920 Myelin oligodendrocyte glycoprotein, see MOG – transformation 921 Mylotarg 22, 454–455, 480, 1086, 1121, 1125, Mouse antibody production test (MAP) 434 1172 Mouse, chimeric 657 Myoblasts 320 Mouse embryonic fibroblast 286 Myocardial infarction 11 Mouse, gene targeted 649 – imaging by NIR 1284 Mouse lymphage assay 1624 Myocardial regeneration Mouse minute virus (MMV) 434 – strategies 295 Mouse, transgenic 1111, 1162 – using hES 283 6-MP 57 Myocyte enhancer factor 294 MRI (magnetic resonance imaging) 346, 1215 Myomap 1305 – application 1217 MyoSzint 21 – macrophage imaging 1282 Myxococcus xanthus 1824 – paramagnetic agents 1217 – prion disease imaging 1289 n – schematic set-up 1216 Nadroparin calcium 457 – supermagnetic agents 1217 NAF 483 mRNA (messenger RNA) 628 Nanocrystal technology 1538 Subject Index 1869

Nanocrystals Nicotinic acetylcholine receptor 1188 – Quantum dot 1539, 1545 Nifedipine Nanofact 459 – metabolized by CYP3A4 1585 Nanoparticles 1306 NIH3T3 156 – solid lipid 1373 Niphatevirin 485 Nanospheres, hydrophilic 1374 Nitric oxide synthase (NOS) 316 2-Naphthylalanine 413 – endothelial 316 Nartogastrim 473 – inducible 316 Nateplase 461 p-Nitrophenyl phosphate 714 National center of biotechnology information Nkx2.5 290 (NCBI) 254 NMR, see Nuclear magnetic resonance National institute of health (NIH) 1233 Non-Hodgkin lymphoma 21 Natrecor 476 – antibody treatment 1121 N-cadherin 320 – clinical trials of RIT 501 NCE 1685 – radioimmunotherapy 500 NCRMS 220 Non-protein-coding RNA, see npcRNA NCSU-23 275 Nonproteolytic activator 388 Near infrared (NIR) principle 1222 Nonsmall cell lung cancer 222 Nelfinavir 58 Noratak 476 Neo 299 Noravid 461 Neo gene 665 Norditropin 14 Neocarcinostatin chromophore 1125 Norditropin Nordiflex 477 Neocolipor 25 Norditropin SimpleXx 477 Neocormon 16 Normiflo 458 Neokidney 369 Northern blot analysis of ITF levels 942 Neomycin 299 Nostoc elypsosporum 483, 1406 Neomycin phosphotransferase 766, 897 Novact M 459 Neoplastic disease Novetumomab 21 – antibody treatment for 1121 Novolin L 470 Neorecormon 472 Novolin N 471 Nesiritide 476 Novolin R 470 Nespo 8, 16, 472 Novolog 13, 470 Neulasta 16, 473, 1406, 1730 Novolog 70/30 FlexPen 470 Neumega 4, 17, 464 Novolog FlexPen 470 Neupogen 16, 473, 1406, 1755 Novolon 13 Neupopeg 16, 473 NovoMix 30 13, 470 Neurokinin antagonist NovoMix 70 470 – identified by Pep2Lead approach 1781 NovoRapid 13, 470 Neurokinin receptor agonist 1780 – 30Mix 470 Neurokinin receptor antagonist 1779 Novos 464 Neuronal cell line NCA1 775 NovoSeven 10, 459 Neuron-specific enolase 1326 npcRNA (Non-protein-coding RNA) Neutrogin 473 – linked to human disorders 220 Neutrophil 1195 NS0 728, 763 Neu-Up 473 NSCLC 220 New biological entities 1362 Nuclear factor kappa B 317 New drug application (NDA) 50, 1638 Nuclear imaging 1220 – submission of pharmacogenetic data to 62 Nuclear magnetic resonance (NMR) 1066 NiaStase 459 Nuclear polyhedrosis virus (NPV) 27 Nicotiana benthamiana Nuclear translocation 1530 – GNTI from 902, 925 Nutropin 14, 477 Nicotiana tabaccum 950 Nutropin AQ 477 Nicotine 58 Nutropin Depot 477 1870 Subject Index

o – radiolabeled drugs for 1250 OATP-C 58 – therapeutics 1249 OCC1 220 OncoSzynt 21 Octreotide 1376 Oncovirus 551 Oct-4 276 Ononitol, overexpression 978 Octin 464, 480 Ontak 7, 24, 456, 480 Octreoscan 519, 1226 Onzar 456, 480 Octreotide 478 Oocyte ODN see oligonucleotide/oligodeoxynucleotide – in vitro culture 274–275 Office of new drug chemistry (ONDC) 1639 OP-1 464 Office of new drugs (OND) 1639 – implant 464 Office of regulatory affairs (ORA) 1639 Open reading frame, see ORF Office of therapeutics research and review OP/LMWH 457 (OTRR) 1639 Oprelvekin 464 Official control authority batch release Optical imaging 1222 (OCABR) 1680 – applications 1223 Official medicines control laboratories – contrast agents for 1223 (OMCL) 1680 Optisulin 13, 470 OGamma100 468 Oral application Oidragit R 1381 – use of nanoparticles for 1549 Oidragit RL 1381 Oral hypoglycemic agents 1459 Oidragit RS 1381 Oral spray insulin Oif 467 – in diabetes type 2 treatment 1455 OKT3 101 Oralin 1445 Oldenlandia affinis 484 – administration 1451 Oligodeoxynucleotide (ODN) – as meal insulin 1454 – antisense 230, 313–314 – chronic administration 1458 – CG-motifs 195 – delivery 1446 – c-myc antisense 316 – dose-response relationship 1452 – containing CpG motifs 1437 – efficacy 1457 – decoy 314 – mechanism of absorption 1448 – double-stranded decoy 230 – properties 1448 – inhibition of phospholamban 318 – radiolabeled 1450 – mechanism of action 231 Oralin RapidMist delivery device – PT-based 198 1447 – single stranded phosphorodiester based 196 ORF (open reading frame) 170, 248, 605, Oligofectamine 573 610, 1045 Oligonucleotide (ODN) Orgasuline rapide 471 – chimeric 1533 ORMUCS 1787 – mediated polymorphism recombination Orthoclone 21, 456 590 Orthoclone OKT3 454, 456, 1086 – P-labeled 526 Oryctes rhinoceros 486 – single stranded 1533 Osmolytes levels 988 – triplex forming 525, 1533 Osteogenic protein 24 Oligonucleotide ligation assay (OLA) 84 Osteoporosis 15 Olsalazine 1381 Osteotonina 477 Omalizumab 456, 1086 Ovalbumine 234 Omeprazole 61 OVCAR3 539 Oncaspar 475, 480, 543, 1399, 1411 Overall dyskinesia rating scale 339 Oncogenes 732 Overall glycemic control 1457 OncoLAR 478 Ovidrel (Ovitrelle) 477 Oncology Ovitrel 15 – imaging 1249 Oxalis tuberose 483 Subject Index 1871

Oxazaphosphorine PCR (polymerase chain reaction) 134, 607 – hydroxylation catayzed by CYP2B4 1597 – application of B-type DNA polymerase 709 4-Oxo-butyric acid 400 – performance in 712 Oxygen uptake rate 825 – product identity test by 167 Ozogamicin 455 – transgenic animal cell analysis 1000 – quantitative 1564 p PDGF (platelet-derived growth factor) 153 p123 39 Peak cell density 1052 p43 39 PEBBLES technology 1546 Pachymatisma ionstonii 482 PECAM-1 360 Pachymatismin 482 Pediarix 19 Paclitaxel 101, 131, 137, 139, 314, 1367 PEG, see poly(ethylene) – for in situ radiotherapy 510 Pegademase bovine 475 – in cancer treatment 1172 Pegaspartase 475, 480 – metabolized by CYP2C8 1594 Pegasys 17, 468, 1402, 1411 PAGE (polyacrylamide gel electrophoresis) – properties of 1403 – kinetics of thrombin activation 437 Pegfilgrastim 16, 473, 1406 Paget’s disease 15 Peginterferon alfa-2a 468 Palicourea condensata 484 Peginterferon alfa-2b 468 Palicourein 484 PEGIntron 468, 1401–1402 1-Palmitoyl-2-oleoyl-sn-glycerol-3-phosphocho- – properties of 1403 line (POPC) 1508–1509 Peguptanib sodium 1394 Palivizumab 21, 456, 1086 Pegvisomant 478, 1404, 1411 – against infectious disease 1176 Penicyllium nalgiovense 483 Pallidotomy 331 Pep2Lead 1772 Pamiteplase 462 – concept 1778 PAMPA (parallel artificial membrane permeation PepHarvester algorithm 1779 assay) 1787 Peptic agent 474 Panax ginseng 482 Peptide Panorex 456 – active sequence 1779 Parallel line analysis (PLA) 168 – antimicrobial 1286, 1433 Paraquat 328 – aptamers 638 Parathyroid hormone 1378 – design system 1779 Paratope 1190 – directed radiotherapy 516 Parkin gene 329 – effect of protease inhibitors on 1470 Parkinson disease (PD) 77, 325 – FITC-tat 637 – epidemiology 326 – in disease targeting 1275 – pathways and targets for 625 – intestinal absorption 1463 – therapy 329 – leader 1037 Parnaparin sodium 457 – mapping 802, 1195, 1562 Paroxetine 61 – nasal delivery of 1378 Parvovirus MVM 747 – phage libraries 1275 Pathogen-associated molecular pattern – PEGylation of 1407 (PAMP) 194 – radiotracer 1256 Pathogen viruses – spacer 1038 – infection risc attenuation in fVIII concen- – stability 1469 trates 423 – transporter 636–637 Patients’ responsibility 1737 – ubiquicidin-derived 1286 Pattern track process 1334–1335 – vaccination 1429 Paxton ovarian tumor 131 Peptide biopharmaceuticals pBR322 156 – chemical modification 1472 PCGEM1 220 Peptide, cationic PCNA (proliferating cell nuclear antigen) 316 – delivery system 1419, 1437 1872 Subject Index

– vaccine adjuvants 1426 PHACIR (pharmacophore identification Peptide, cationic antimicrobial 1419 routine) 1771, 1778, 1781 – artificial 1433 – concept 1776 – as vaccine adjuvant 1433 Phage artificial chromosome (PAC) 656 – subgroups 1433 Phage display technology 1112 Peptidoglycan 938 Phagocytes 1548 PER.C6 724, 764, 775 Pharmaceutical research and manufacturers – human cell line 779 of America (PhRMA) 1643 PER.C6 cell 728 Pharmaceutically Tractable Genome (PTG) 99 – characterization of antibodies by 797 Pharmacodynamics – fed-batch process development 789 – PET studies 1254 – for manufacture of recombinant protein 784 Pharmacogenetics 49 – generation of 782 – environmental factors and 75 – transfection 785 – terms 74 PER.C6 cell line Pharmacogenetics research network (PGRN) 77 – batch process profiles 791 Pharmacogenomics 49 – continuous perfusion process 794 – environmental factors and 75 – growth data for antibody producing 790 – terms 74 – supplemented batch process 793 Pharmacokinetics PER.C6 clones – intracellular 1526, 1529 – generation of, for monoclonal antibody 784 – in quality control of biopharmaceuticals 1576 Percutaneous transluminal intervention – of biopharmaceuticals 1253, 1365 (PTI) 313 – of gene delivery systems 1254 Percutaneous transluminal coronary angioplasty – of PEG 1396 (PTCA) 236 – of small molecules 1250 Perfusion scintigraphy 1238 Pharmacophore concept 1776 Peripheral blood mononuclear cell (PBMC) Pharmacophore identification routine, 361 see PHACIR Peripheral blood progenitor cell (PBPC) 1757 PharmaCos DG Enterprise 1676 Permeation clearance 1480 Pharmazymes 1613 Peroxidase stress inducible 894 Phenylpropanoid metabolism 943 Personalized medicine 76 Phenytoin Pertussis 18 – metabolized by CYP2C9 1590 Pertuzumab 1164 Phosphato-dihydrofusidate 1376 PET (positron emission tomography) 499, 1220, Phosphinothricin acetyltransferase 898 1243 Phosphoenol pyruvate 1075 – cancer therapy by 1243 Phosphoethanolamine N-methyltransferase 978 – for Alzheimer targeting 1286 Phospholamban 318 – imaging of cancer 1243 Phospholipids 1376 – monitoring of radiolabeled drugs 1252 PHS Act 1640 – radioisotopes for 1244 Physcomitrella patens 905, 919 – radiopharmaceuticals for 1246 – GNTI from 925 – radiotracer 1246 PHYSPROP database 1789 PET (positron emission tomography) imaging Pichia pastoris 713, 1135 – of apoptosis 1262 Picorna virus 766 – of end-points of tumor 1259 PINK1 gene 329 – of gene expression 1255 Pinocytosis 1397 – of glucose metabolism 1260 Pinoresinol 943 PEVKEK region 1199 Pip (pristinamycin-induced proteine) 732 PGA (pseudomonas 7A glutaminase- pIVEX (plasmid for in vitro expression) asparaginase) 539 vector 1066 – antitumor effect of 539 PIVI-Argonaute-Zwille domain (PAZ) 246 – efficacy of 539 pJM17 156 Subject Index 1873

PLA (process licence application) 742 – vaccine adjuvant 1426 – Plasminogen, mini 380 – with CpG-ODN 1437 Plant Polybutylcyanoacrylate 1310 – genetically modified 894 Polycyanoacrylate 1305 – production of recombinant proteins in 893 Polydimensional SNP 88 – production of stress tolerant 974 – microarray 89 – water balance 971 – platform 88 Plant cell Polydimethylsiloxane, nonbiodegradable 1546 – effect of additives on product yields 957 Polyesters – for biopharmaceutical production 949 – for DNA vaccine delivery 1492 – responses to stresses 972 Poly(ethylene glycol) (PEG) 957, 1076 Plant cell suspension cultures – acylating reagents 1398 – recombinant proteins from 951 – conjugates with 1367, 1393 Plant derived biopharmaceuticals – properties 1394 – N-glycosylation 924 – reagents 1397 Plant plasma membrane – reagents for protein PEGylation 1398 – K invard rectifying channel 973 – pharmacokinetic parameters 1396 – K outward rectifying channel 973 PEG8/IGF2AS 220 – voltage independent cation channel 973 PEG-adenosinedeaminase 1411 Plant, transgenic, see transgenic plants PEG-asparaginase 1411 Plasma insulin concentration 1482 PEG-biphalin 1410 Plasmacytoma 763 – preformulation 1410 Plasmid DNA 1532 PEG-conjugates, analysis of 1411 – based vector 186 PEG-CV-N-conjugates, molecular weight analysis – methods for quantifying subcellular of 1413 distribution 1527 PEG MAL-CV-N reverse-phase purification 1414 – purification 1068 PEG-staphylokinase, preformulation 1409 – templates for wheat embryo system 1067 Polyethyleneimine 1316 Plasmid stability – in gene delivery 1543 – of IL4v expression vector 1026 Polyferon 468 Plasmid-encoded selection gene (POD) 1035 Poly(glutamic acid) 1368 Plasmin 1005 Poly(glycolic acid) 1494 – inhibition by aprotinin 1027 Polyglycolide 1305 Plasminer 461 Polyhistidine Plasminogen – in gene delivery 1543 – activation 380 Polyketide 1804 – activator 1074 – biosynthetic gene cluster 1806 – micro 380 – heterologous hosts for production of 1824 Plasmodium falciparum 1422 – key reactions of biosynthesis 1809 Plasmodium falciparum circumsporozoite protein – natural products engineering 1803 (CSP) 682 Polyketide synthase 1804 Plasvata 461 – biosynthesis 1806–1807 Platelet-derived growth factor, see PDGF – classification of 1806 Pleomycin 666 – engineering of novel polyketides 1815, 1820 Pleurotus ostreatus 482 – organization of 1808 Polio 18 – precursor-directed biosynthesis 1819 – virus 263, 766 – production requirements 1822 Polyadenine – tailoring steps in erythromycin synthesis – in gene delivery 1543 1811 Polyarginine 1425 – structure of natural products 1805 – as type I-inducing adjuvant 1429 Poly(lactic acid) 1491, 1495 – CpG-ODN-based vaccines 1439 Poly(lactic-co-glycolic acid) 1492 – stimulatory efficacy on T cells 1431 Polylactide 1305 1874 Subject Index

Poly(lactide-co-glycolide), for peptide Porcine endogenous retrovirus (PERV) 369 encapsulating 1371 Porcine fetal mesencephalic cell Polylysine 1316, 1512 – transplantation of 332 – mannosylated 1514 Porcine isophane insulin 471 – vaccine adjuvant 1426 Porcine neutral insulin 471 Polymer Porcine pseudorabies virus (PRV) 434 – bulk erosion 1491 Pork atrapid 471 – design for DNA vaccine 1493 Pork insulatard 471 – hydrolysis 1491 Pork mixtard 30, 471 – synthetic, biodegradable 1491 Portfolio assessment 1735 Polymer conjugates Posicor 52 – commercially available 1368 Positive transcription elongation factor 219 Polymer erosion rate 1495 Positron emission tomography, see PET Polymer nanoparticles, two-step process 1306 Postcommisural putamen 343 Polymerase Post-glutamyl peptide hydrolysis (PGPH) 398 – II 217 Post-prandial glucose 1456 – III 217 Poststreptococcal glomerulonephritis – Pfu 709 (PSGN) 384 – Taq 709 Post-transcriptional gene silencing (PTGS) 571 – Tgo 709 POT1 (protection of telomeres protein) 43 Polymerase, b-type Prader-Willi syndrome (PWS) – structural features 710 – pathways and targets for 626 Polymerase chain reaction, see PCR Pravastatin 58 Polymeric microsphere 1371 Prediction error sum of squares 1796 Polymeric permeation enhancer 1376 Pregnane X receptor (PXR) 1788 Polymeric solution 1374 Prescription behavior 1736 Polymyositis-scleroderma overlap syn- PREVENT 237 drome 1193 PREVENT-I trial 315 Poly(orthoester) PrexelizuMAb 1116 – cytotoxicity 1499 Primavax 19 – feed composition and characterisation Prion 746 of 1496 – disease targeting 1287 – for DNA vaccine delivery 1494 Pristinamycin-induced proteine (Pip) 732 – microspheres 1487 Pro inflammatory cytokines 1511 – synthesis 1494 Processing procedure Polyoxyethylene 400 – downstream 5 Polyoxyethylene-20-stearyl ether 1376 – upstream 3 Polyoxyethylene-24-cholesterol ether 1376 Prociclide 461 Polypeptide synthase Procomvax 19 – typical structure of 1816 Procrit 3, 16, 472 Poly(styrene-maleic acid anhydride) 1367 Product patents 1758 Polyvinylpyrrolidone 957 Progesterone Pompe disease treatment 861 – CYP3A4 activated 1587 Pondimin 52, 1604 – metabolized by CYP2C3 1595 Pooling strategy 87 Prokine 472 POPC, see 1-palmitoyl-2-oleoyl-sn-glycerol- Prolastin 464, 858 3-phosphocholine Prolastina 464 Population genetics 81 ProLease-rhGH 477 Porcilis AR-T DF 25 Proleukin 17, 465, 480 Porcilis pesti 26 Proliferating cell nuclear antigen, see PCNA Porcilis porcoli 25 Proline 974 Porcine biphasic insulin 471 – catabolism 974 Porcine embryo 275 – dehydrogenase 974 Subject Index 1875

– uptake 1435 Protein-1, activated 236 Pro-opiomelanocortin (POMC) 1327 Protein A, immobilized 1130 Propion aldehyde 1399 Proteinase 3 Propulsid 52, 1605 – peptide mapping of epitopes on 1195 Proquest system 614 Protein C Prostacycline 1007 – activated 457 ProstaScint 21, 744, 1277 – concentrate 457 Prostate cancer ProteinChip array – PGA and DON treatment 540 – antibody-coupled 1337 Prostate-specific membrane antigen – types of 1329 (PSMA) 1277 ProteinChip reader Prostatic acid phosphatase 1326 – sample analysis in 1330 Protamine 1531 ProteinChip system 1325 Protaphane 13 – applications 1334 Protease Protein data bank 380 – baculovirus encoded 1049 Protein disulfide isomerase 1074 Protease inhibitor 395, 1467 Protein diversity – absorption-enhancing mechanism 1472 – generation of 586 – effect on insulin degradation 1469 Protein expression 934 Protein kinase A (PKA) 318 – examples 682, 1094 Protein – for recombinant protein deposition 935 – anti-apoptosis 821 – using ExpressTec in grains 945 – anti-bacterial 485 – using transitional machineries 936 – anti-cancer 481 Protein-fragment – anti-fungal 482 – complementation assay 1161 – anti-viral 483 Protein G 1130 – as disease marker 1337 Protein kinase – based agents 460 – for drug development 639 – Bcl-2 family of 819 Protein L 1130 – biopharmaceuticals 1463 Protein production – body 935 – baculovirus based 1050 – chemical modification 1472 – cell free 1064 – disulfide bonded 1072 – generic protocol 1050 – drug sources 481 – infection kinetics 1052 – endogenous 938 – nutritional/kinetic parameters in baculovirus – heat shock 982 based 1051 – human 774 – protocol for BEVS-based 1057 – identification 1337 Protein, recombinant, see recombinant protein – intestinal absorption 1463 Protein screening – levels 988–989 – high content 594 – marker 1327 – high-throughput 594, 596 – milk expression technology 998 – spectroscopic methods 595 – nasal delivery of 1378 Protein stability – optimized BEVS-based 1048 – factors affecting 956 – production in plants 893 Protein storage vacuole 935 – ribosome-inactivating 482 Protein therapeutic dendrogram 113 – selenium-cysteine labeled 1066 – Protein therapeutics (PT) 104 – selenium-methionine labeled 1066 Protein toxin – storage 938 – conjugates 1173 – synthesis and secretion in cultured plant – linked to MAb 1124 cells 957 Protein transduction domain peptides 1523 – transduction 636 Proteolysis – transgenic derived 870 – intravascular 380 1876 Subject Index

– pericellular 380 Quantitative trade loci 969–970 Proteomics 30 Quixidar 454, 457 Protexia 870 Prothrombin 380 r – activation 379 RACHITT 590 Protropin 14, 477 Radioimmunoassay (RIA) 1563 Pro-urokinase 462 Radioimmunoconjugates 508 Prous Integrity database 453 Radioimmunotherapy (RIT) 498, 1125 Pseudomonas 7A glutaminase-asparaginase, – pre-targeted 512 see PGA – therapeutic index 511 Pseudomonas aeruginosa 686, 1010 Radioisotope – infection 1751 – positron emitting 1244 Pseudomonas exotoxin A 1173 Radiolabeling Pseudomonas syringae 483 – monitored with PET 1251 PsorBan 637 – of anti-cancer drugs 1251 Psoriasis 1285 – iododeoxyuridine 519 pSP65 vector 1067 – of pyrimidine nucleoside 1262 PSZA11q14 220 Radionuclides Pulmonary arterial hypertension (PAH) 1742, – for targeted in situ radiotherapy 499 1749 Radiopharmaceuticals 1246 Pulmonary vascular resistance (PVR) 1749 Radiosynthetic methods 1246 Pulmozyme 23, 475 Radiotherapy 497 Pure System 1068 – biopharmaceuticals for 497 – cell free from E. coli 1069 – HuM195 dose 506 Puregon 15, 465 – ibritumomab tiuxetan dose 504 Puregon Pen 465 – in situ 497 Purinethol 64 – M195 dose 506 Purity – maximum tolerated dose 502 – analytical methods for determination of 1567 – tositumomab dose 503 Puromycin N-acetyl-transferase 766 Radiotracer 1253 Putrescein 1075 – antibodies for 1258 Pyrimidine nucleoside radiolabeled 1262 – peptides for 1258 Pyrococcus furiosus 709 – properties 1248 Pyrogen test 1565 – small molecule 1256 Pyroline-5-carboxylate 975 RAEL 526 Pyrosequencing 87 rAHF-PFM 459 Pyrrhocoricin 486 Raji B-cell lymphoma 526 Pyruvate dehydrogenase 1075 RANTES 363 Pyruvate-formate lyase 1075 Rap1 43 Rap1p 42–43 q Rapacuronium bromide 52 Q6B 1692 Rapamune 1538 Qiagen kit 90 Rapamycin 101, 314–315, 1804, 1818 QS21 1424 Raphanus sativus 483 QSAR equation 1787 Rapid amplification of cDNA ends (RACE) 109 QT genes 59 RapidMist Quality control – accuracy of dose delivery 1449 – analytics in 1557 – device 1449 – international guidelines 1571 Rapilysin 11, 462 Quantison 1305 Raplon 52 Quantitative structure-activity relationship 1611 Raptiva 454, 456, 1086 Quantitative structure-property relation- Rasburicase 475 ship 1791 Rat antibody production test (RAP) 434 Subject Index 1877

Raxar 52 Refludan 23, 462 RAY1/ST7 220 REGENT-I trial 316 Rayleigh scattering 1305 Regranex 24, 465 RB69-polymerase 710 Regulations RCR (recombination chain reaction) – EU-US comparability guidelines 1693 – homologous recombination by 591 – for biological products 1686 R&D portfolio 1733 – for biopharmaceuticals 1641, 1682 Reactant ion peak 1347 – for cell lines 1645 Rebetron 17 – for dosage forms 1646 Rebif 17, 467, 1404 – for drug product 1647 RecDNA somatotropin 477 – for drug substance 1648 Receptor tyrosine kinase (RTK) 639 – for formulation components 1646 RECIST criteria 1259 – for manufacturing process 1647 Recombinant Antihemophilic Factor VIII 424 – for purification phase 1646 Recombinant blood factor 9 Regulatory bodies 1676 Recombinant factor VIII (rFVII) 420, 459 REM sleep disorder 328 Recombinant HB 1422 Remicade 21, 456, 864, 1086, 1118–1119 Recombinant hematopoietic growth factor 15 Renal cell carcinoma 17 Recombinant hepatitis B surface antigen Renal cell replacement (rHBsAg) 3 – strategies for 368 Recombinant hormone 14 Renal toxicity Recombinant human vascular endothelial – from PDRT of malignancies 517 growth factor, see rhVEGF ReoPro 462, 1086, 1117 Recombinant IFN 16 Reovirus type 3 (REOV-3) 434 Recombinant IL 16 Repaglinide 58 Recombinant insulin 12 Repeat induced point mutation 244 Recombinant protein 189 Replagal 23, 475 – companies using plant based 904 Replication competent adenovirus (RCA) 166 – expressed in cultured plant cells 952 Reporter gene assay, non-invasive 1228 – from nuclear transgenes 895 Reporter genes 671 – in cereal grains 932 Residual DNA 167 – in plastids 898 Respiratory syncytial virus (RSV) 263, 454 – plant made, commercially available 903 Respitin 463 – PER.C6 cell for 784 Re-stenosis 235 – post translational modifications of 955 – arterial 313 – production 672, 907, 1726 Restriction endonucleases 168 – transient expression levels 901 Restriction enzyme-mediated integration – vectors for 730 (REMI) 667 Recombinant thrombolytics 11 Restriction fragment length polymorphism Recombinate 10, 421, 459 (RFLP) 84 Recombinate rAHF 1639 Retavase 11, 462 Recombination chain reaction, see RCR Reteplase 11, 462 Recombivax 18 Reticulo endothelial system 1366 Recombivax HB 1639 – in DNA vaccine delivery 1490 Recormon 472 Retinal pigment epithelial cell, see RPE RECTSER 76 Retinoic acid 294 Redux 52, 1604 Retrovirus 31, 551, 574 ReFacto 10, 459 RETTAU 77 ReFacto AF 459 Revasc 23, 462 Reference sequence 255 Reverse phase high-performance liquid – database 110 chromatography, see RP-HPLC Reference standards Reverse transcriptase polymerase chain reaction – for analytical testing 1569 (RT-PCR) 290 1878 Subject Index

Reversible perfusion defect size (RPDS) 177 Roferon 1411 Reviparin sodium 457 Roferon A 17, 468, 480 Rev protein 552 Roller bottle Rev response element (RRE) – optimum MOI, TOI and TOH in 1053 Rezulin 52 – process 737 rf9a 699 Romano-Ward syndrome 220 R-Ferone 467 Rosiglitazone clearance 1594 Rhabdomyosarcoma 222 Rosuvastatin RheoPro 21 – label recommendations 55 Rheumatoid arthritis 17, 24, 79 Rotenone 327–328 – pathways and targets for 626, 1284 Rous sarcoma RhinoRx 866 – retrovirus 764 rhVEGF (recombinant human vascular – virus 263 endothelial growth factor) RPE (retinal pigment epithelial cell) – moss derived 923 – human 333 Ribavirin 17 – location and anatomy of 335 Ribonucleic acid, see RNA – microcarrier bound 338 Ribosomal binding site 1023 – PD treatment of 336 Ribosomal RNA, see rRNA RP-HPLC (reverse-phase high-performance liquid Ribosome display 1112 chromatography) 164, 436, 1562 Ribozymes 570 rRNA (ribosomal RNA) 628 Rice endosperm, expression of lignan 944 Rs-AFP2 483 – fusion strategy to express small peptide RTQ-PCR 116 in 942 RU-41740 463 Ricinus communis 1173 Rush dyskinesia scale 340 Rif1 43 Russel-Silver syndrome 220 Rif1p 43 Rybozyme 634 Rif2p 43 Risperidone 101 s Rituxan 21, 456, 480, 503, 526, 1086 Saccharomyces cerevisiae 399, 1021, 1033, 1422, – application 1278 1628, 1824 Rituximab 21, 456, 480, 503, 526, 1086, 1164 – expression platform 1027 – cell killing trigger 1169 – expression vector 1035 RNA (ribonucleic acid) 628 Saccharopolyspora erythraea 1804 – see also under special RNA types Sacrophaga peregrine 1434 – -based therapy for HIV 569 Safety working party (SWP) 1670 – micro- 216 Saizen 14, 477 – steroid receptor activator 218 Salmon calcitonin 477 – transfer- 215 Salmonella typhimurium 1011, 1625 – ribosomal- 215, 628 Sandoparin 454, 458 RNAi (RNA interference) 31, 244 Sandostatin 478 – diversity of viral targets 571 Sandostatin LAR 478 – expression of vector-based approaches for 631 Sanitation era 103 – in treatment of viral infection 262 Sapecin B 1434 – mechanism 245 Saponaria officinalis 484 – pathway 629 Sargramostim 472 – silencing 571 Satin/APOE system 78 – silencing genes as tools and therapeutics 624 SCA8 220 – therapeutic applications 259, 570 Schizophrenia RNA-induced silencing complex (RISC) 571, – pathways and targets for 627 629 Schizosaccharomyces pombe 571 RNase inhibitors 1079 – TPI1 gene from 1035 Roceron-A 468, 480 SciTropin 476 Subject Index 1879

Scleroderma autoantigen centromer pro- Serum amyloid A 1337 tein 1191 Serum amyloid protein 1287 SCN5A 59 Serzone 1604 SCNT (somatic cell nuclear transfer) Severe combined immunodeficiency (SCID) 361 – embryo 279 SHARP 218 – oocytes 272 Shepheridin 1 486 Scopolamine 1382 Shepheridin 2 486 Scytovirin 484 Shikamate-chorismate pathway 943 SDS-PAGE (sodium dodecyl sulfate-polyacryla- Short tandem repeat 277 mide gel electrophoresis) 725, 1563 shRNA (short hairpin RNA) 243, 247, 573 – antibody detection 1077 Shuttle vector 156 – of human IgG produced in PER.C6 cells 798 Sical 477 – of total soluble protein from rice grain 940 siD direct 255 – of total soluble protein from transfected siFect system 632 Nicotiana leaves 909 Signalling pathways, and their disease – PEG-conjugate analysis 1411 implication 625 Secoisolariciresinol 943 Silicon, in drug delivery 1540 beta-Secretase 1782 Silteplase 461 – enzyme assay 1784 Simian immunodeficiency virus (SIV) 556 – virtual screening 1784 Similar Biological Medicinal Products Legislation Seldane 52 (SBMPL) 1764 SELDI (surface-enhanced laser desorption Simulect 21, 456, 1086 ionization) process 1335 Simvastatin 58 – distinctions of 1333 Single nucleotide polymorphism, see SNP SELDI TOF-MS (surface-enhanced laser Single photon emission computed tomography, desorption ionization time-of-flight mass see SPECT spectrometry) 1325 SIP1 42 Selective combinatorial randomization SIRAN 681 (SCR) 592 siRNA (small interfering RNA) 573 Selectively infective phages 1112 – biopharmaceutical drugs 632 Seleparina 457 – characteristics 630 SELEX technique 635 – chemical synthesis 631 Self-organizing maps 1797 – delivery of 632 SEM micrograph of microcapsules 1373 – design parameters 248 Sendai virus liposome 235 – individual 257 Sensitive particle acoustic quantification 1308 – interaction with RISC 249 – procedure 1313 – in vitro transcription of 631 Sepsis 24 – mechanism of action 630 Sequencing – off-target effects 256 – by hybridization 84 – peptide based 573 – for structure determination 1562 Sirolimus 314 Sequential random mutagenesis 705 Sjörgen syndrome 1190 SERCA2a 318 Skeletal myoblast 285 Serine protease inhibitor 1005 Small cell lung cancer 21 Serine proteinase Small fragment homologous replacement – activation mechanism 390 method 1533 – cascades 379 Small interfering RNA, see siRNA – mechanism 377 Small molecule therapeutic target (SMT) 104 – trypsin-like 378 Small nucleolar RNA, see snoRNA Sermorelin acetate 476 Small nucleolar RNP, see snoRNP Seronos follicle-stimulating hormone 9 Small organic molecules, in disease targeting Serostim 14 1275 Serotim 477 Small pox 1488 1880 Subject Index

Small temporal RNA, see stRNA – transgenic animal cell 1000 Small-vessel vasculitis 1195 – of IgG expressing PER.C6 clones 786 Smith-Watermann, dynamic programming Southern hybridization sequence alignement algorithm 255 – of genomic DNA 736 SMP-140 477 Soybean trypsin inhibitor 1470, 1472 Snakin proteins 485 SPECT (single photon emission computed SNaPshot 84 tomography) 177, 261, 1220 Snell law 1218 – applications 1222 snoRNA (small nucleolar RNA) 215, 628–629 – contrast agents for 1222 snoRNP (small nucleolar RNP) 41 – for Alzheimer targeting 1286 SNP (single nucleotide polymorphism) 71 – principles and instrumentation 1220 – analysis 85 – spatial resolution 1221 – scan 77 Spermidine 1075 – technology 83–84 Spheramine 325 SNP-IT 84 – dosing 344 Sodium 5-methoxysalicylate 1465 – microcarrier 336 Sodium caprate 1376 – treatment 344 Sodium deoxycholate 1465 Sphingosine kinase-1 (SPHK-1) 218 Sodium dodecyl sulfate-polyacrylamide Spinal muscle dystrophy (SMA) 78 gel electrophoresis, see SDS-PAGE Spin-lattice relaxation time 1216 Sodium glycocholate 1465 Spin-spin relaxation time 1215 Sodium glycodeoxycholate 1376 Spiramycin 1818 Sodium salicylate 1376, 1466 Spodoptera frugiperda 1047 Sodium taurodihydrofusidate 1376 Squamous cell carcinoma 238 Softenon 1675 SRA-Del 220 Solanum lycopersicum 970 SSCP 84 Solanum tuberosum 485 SSEA-1 276 Solclot 462 SSEA-3 276 Solid tumor 1174 SSEA-4 276 – RIT of 507–508 Sso polymerase 711 Solinase 462 Staphylocoagulase, prethrombin-2 complex 387 Soluble insulin 471 Staphylocoagulase SC 386 Somatic cell nuclear transfer, see SCNT Staphylococcus aureus 1129, 1350 Somatomedin-1 463 Staphylokinase, plasminogen complex 384 Somatonorm 477 Staphylokinase (SAK) 381, 383 Somatostatin receptor STAT-1 233 – in peptide directed radiotherapy 516 STAT-3 233 Somatotropin 477 Stem cell, myocardial regeneration, using 320 Somatrem 477 – neural 332 Somatropin 476–477 Sterilize in place (SIP) 746 – recombinant 477 Stimulated acoustic emission 1308 Somavert 15, 478, 1404, 1411 – principle of 1309 Somazon 465 Stiripentol Sonavist 1305 – CYP2C9 inhibitor 1590 Sonoporation 1318, 1382 Stop codon suppression 667, 670 SonoVue 1305 Strattera 56, 64 Sorangium cellulosum 1804 Streptavidin 511 SOS stress response 1627 – coupling to microcapsules 1310 SOS-umuC assay 1627 Streptococcus mutans 865 – industrial validation studies 1633 Streptococcus pneumoniae 1421 Sotalol hydrochloride 1605 Streptococcus pyogenes 1130, 1422 Sotocor 1605 Streptokinase, plasminogen complex 385 Southern blot 83, 134, 654 Streptokinase (SK) 381, 384 Subject Index 1881

Streptomyces avidinii 511 Synthetic oviductal fluid Streptomyces coelicolor 1823 – modified with amino acids 269, 274 Streptomyces lividans 1824 Synuclein alpha 329 Streptomyces peucetius 1804 Stromal antigen 1281 t stRNA (small temporal RNA) 628 T cell StSN1 485 – activation 1501 StSN2 485 – adjuvant 1431 Substrate recognition site 1584 – lymphoma 24 SUBSTRUCT Tac 20 – analysis 1794 Tachypleus tridentatus 1565 – classification of CNS activity 1795 Tacrolimus 58 – classification with 1792 Tagging gene disruption (knock-in) 670 – fragmentation scheme of propanol 1793 Taillefer selectivity 1283 Succinimidyl carbonate 1398 Tamoxifen 61 Succinimidyl propionate 1398 – metabolized by CYP3A4 1584 Succinimidyl succinate 1398 Tandem MS QSTAR 1335 Succinylcholine 74 Tanimoto index 1777 Sucrose acetateisobutyrate 1374 TAP 29 484 SUDHL-1 515 TaqMan 84 Sulesomab 22 TAR RNA decoys 231 Sulfaphenazole derivative Tarceva 143, 1122 – co-complex with CYP2C5 1596 Tasonermin 463, 479 Sulfasalizine 1381 Taste blindness 74 Sulfhydryl redox potential 1073 TATA box 764 Sulfolobus solfataricus 711 Taurodeoxycholate 1376 Sulfglycotide 463 Taxanes 140, 1252 Sulfurhexafluoride 1305 Taxol 314, 835 Suniferon MP 468 Taxotere 101 Supermagnetic iron oxide, ultra small 1218 Taxus cuspidata 950 Superoxide dismutase TAXUS trial 315 – ROS scavengers 979 Taz1 43 Superparamagnetic iron oxide 1218 TBlastN algorithm 108 Supersomes 1613, 1618 TBP 764 Surface-enhanced laser desorption ionization, Teceleukin 464, 479 see SELDI Tecnemab KI 22 Surface-enhanced laser desorption ionization Telomerase 38 time-of-flight mass spectrometry, see SELDI – human 42 TOF-MS 1325 – reaction cycle 40 Surface-enhanced Neat Desorption (SEND) 1337 – regulation of 42 Surgical therapy in Parkinson treatment 331 – RNA functions 41 Survival motor neuron (SNM) gene 78 Telomerase reverse transcriptase (TERT) 39 SV40 764 Telomere SW620 116 – alternative lengthening of 44 S-warfarin – protection 43 – CYP2C9 complex 1591 Temozolomide 1251 – forms of 1593 – radiolabeled 1253 – metabolism 1592 Tenascin 509 – therapeutic effect 1591 Tenecteplase 11, 462 Swiss biotech BOUTIQUE 1741 Tepase 461 SwissPro database 170 Teratoma cells 299 Sybyl 1610 Terfenadine 52, 1788 Synagis 21, 454, 456, 1086, 1121, 1176 Terfenamide 1795 1882 Subject Index

Teriparatide 476 Thyrotropin-a 14 Terminal deoxynucleotide transferase dUTP nick Thyrotropin-releasing hormone 1473 and labeling 644 TILLING 990 Testosterone 58, 1589 Time of harvest (TOH) 1053 – hydroxylation 1618 Time point of infection (TOI) 1048 Tetanus 18 TIN2 43 Tetracycline (TET) 732, 896 Tisokinase 461 – system 632 Tissue inhibitor of metalloproteinase – use 1804 (TIMP) 811, 813 12-O-Tetradecanoylphorbol-13-acetate 223 Tissue plasminogen activator (tPA) 6, 1280 Tetragastrin 1473, 1477 – human 836 – permeability 1479 – recombinant 746 – structure 1478 TNF, see tumor necrosis factor Tetragastrin acyl derivatives 1478 TNKase 11, 462, 744 – acid-output time curves 1479 Tobacco cultivars Bright Yellow 2 950 Tetrahymena enzyme 38 – suspension cells 951 Tetrahymena thermophila 685 Tobacco mosaic virus (TMV) 864 Tev-Tropin 476 – vectors 900 Texas Red 1427 Tolbutamide, metabolized by CYP2C9 1590 TGGE 84 Toll-like receptor (TLR) Therapeutic angiogenesis 153 – in DNA vaccine 1490 – human clinical trials for 309 Tomieze 462 Therapeutic cloning 269 Tonocalcin 477 Therapeutic drug monitoring 1574 TOPAS algorithm 1774 Thermococcus gorgonarius 709 TOPKAT 1624 Thermoplasma acidophilum 399 TOPO 611 Thermus aquaticus 709 Torasemide Thienylalanine 413 – metabolized by CYP2C9 1590 Thioepa 131 Tositumomab 104, 455, 479, 1086 Thioflavin T 1287 – half life 1168 Thiomedazine 64 – in radiotherapy 502 4-Thio-oligoribonucleotide 261 – radio active labeled 501 Thiopurine methyltransferase (TPMT) 57 Total soluble protein 933 Thioredoxin reductase 1073 – from rice grain 940 Thrombate III 454, 458, 855, 1004 Toxicity Thrombin 380 – complement directed 1156 – heterobivalent inhibition 411 Toxins, bacterial 1125 – imaging 1283 TRA-1-60 276, 288 – inhibition assay 1006 TRA-1-81 276, 288 Thrombin-antithrombin (TAT) complex 997 TRAFFIC trial 307 Thrombin inhibitor 1778 TRAIL 264 – design of 1780 Transannular heterobivalent inhibitor 399 Thrombolyse 462 Transcription activator protein 1428 Thrombosis, targeting 1282 Transcription gene silencing (TGS) 571 Thrombospondin th-1 (TSP1) 263 Transdermal therapeutic system 1382 Thymalfasin 478 Transfectants Thymidine 1261 – selection conditions 815 – action of radiolabeled 1263 Transfection 727 Thymoglobuline 456 Transfer RNA, see tRNA Thyrogen 14 Transferin receptor 1517 Thyroid cancer 14 Transferins 1517 Thyroid stimulating hormone (TSH) receptor Transfersomes 1382 1189 Transforming (tumor) growth factor (TGF) 294 Subject Index 1883

Transgene 156 Tripartite proteine 1166 Transgene combining ability (TCA) 990 Tritanrix-HB 18 Transgene expression 1531 tRNA (transfer RNA) 628 Transgenic animals 29 – amber suppressor 674 – biopharmaceuticals from 833, 995 TRNG10 220 Transgenic derived biopharmaceuticals Troglitazone 52 – oral vaccines from 867 – clearance of 1594 – trials as anti-infective agents 865 Troparin 457 Transgenic derived pharmaceuticals Trophectoderm 275 – trials for autoimmune treatment 862 Trovert 478 – trials for cancer treatment 862 Trudexa 22, 455 Transgenic mice 1111, 1162 Trypanosoma brucei 571 Transgenic plants 29 Trypsin 1005 – biopharmaceuticals from 833 – alpha-antitrypsin 463 – draught and salt tolerance 969 – inhibition by aprotinin 1027 – expressing genes involved in ion transporter – from transgenic system 853, 858 974 Tryptase, alfa 405 – expressing genes involved in osmolyte – diketopiperacine-based biphasic inhibitor 412 biosynthesis 976 – inhibition by cyclodextrin-based inhibitor 408 – expressing genes involved in redox reac- – inhibition by PEG-linked inhibitor 406 tions 979 Tryptofan fluorescence assay 1006 – high temperature stress 981 TrypZean 854, 903 – production of high temperature stress Tuberculosis 1489 tolerant 985 Tubulin polymerization inhibitor 1172 – production of high temperature tolerant 984 Tumor angiogenesis 1278 – stress tolerance 967 Tumor associated antigen (TAA) 183 Transgenic system Tumor-associated glycoprotein 72, 1276 – and post translational modifications 849 Tumor cell, targeting markers on 1276 – capacity of production 846 Tumor growth index 523 – costs 847 Tumor hypoxia, assessment of 1263 – production strategies and materials used Tumor necrosis factor (TNF) 7, 80, 264, for extraction 837 481 – regulatory experience 850 Tumor therapy 537 – therapeutic proteins derived from 852 – cell based 203 – therapeutic use 857 – DNA based 202 Transillumination 1223 – peptide based 205 Transmembrane semaforines 104 Tumor volume doubling time 1321 Transmissible spongiform encephalopathy Tunnel assay 644 (TSE) 1007 Turbocalcin spray 476 Trastuzimab 479 Turner’s syndrome 14 Trastuzumab 22, 64, 455, 1086, 1164 Twinrix 19 Trasylol 854 tyr177 699 Trehalose synthesis 978 tyr99 697 Treponema pallidum 1422 Tyrosinase 1429 Tresylate 1400 TRF1 43 u TRF2 43 UBE3A 277 Triacelluvax 19 UBE3A-AS 220 Trichloroacetic acid 1077 UBI (ubiquicidin-derived)-peptides 1286 Trichosantes chirilovii 484 UCOE/UCOS (ubiquitous chromatin opening Trichosanthin 482, 484 element) 730, 765 2,5-bis(Trifluoromethyl)-7-benzyloxy-4-trifluorome- UGT1A1 57 thylcoumarine (BFBFC) 1610 UK national health service 1719 1884 Subject Index

UK national institute for clinical excellence – immune response 1421 (NICE) 1720 – targets for therapeutic 1422 Ultrafiltration 159 Vaccine 18 Ultra-high-throughput screening (uHTS) 596 – adjuvants 1419, 1425 Ultrasonic spectroscopy – cellular 1429 – microcapsule formulations 1307 – combination 1421 Ultrasound – DNA based 199 – theranostics 1301 – responder rate 1432 – 3-D imaging 1304 – transgenic derived oral 867 Ultrasound contrast – viral 1421 – encapsulated gas bubbles 1305 Vaccinia topoisomerase 611 Ultrasound contrast agent Valgis 1675 – diagnostic and therapeutic use 1315 Validation characteristics – for gene delivery 1318 – dependent on application 1569 – preparation of drug-loaded 1317 Valproic acid 687 – properties 1308 Vascular cell adhesion molecule-1 (VCAM-1) – target-specific 1314 234 Ultrasound device Vascular proliferative disease 235 – loss of correlation 1308 Vascular re-endothelialization 319 – stimulated acoustic emission 1308 Vascular smooth muscle cell (VSMC) 313 Ultrasound imaging Vasoactive intestinal peptide (VIP) – application 1218 – human 1742 – microbubbles as contrast agents 1219 – molecular mechanism and transcription 1745 – schematic set-up 1220 – structure 1744 Ultratard 13 Vector Umatrope 476 – blastid based 897 Umuline zinc 469 – for expression of recombinant proteins 730 Unified PD rating scale (UPDRS) 337 – for gene therapy 186 UniGene 255 – for production of recombinant proteins in United Kingdom centre doctors’ organization plants 894 (UKHCDO) 424 – for transient transformation 900 United Kingdom prospective diabetes study – non viral 1522 (UKPDS) 1446 – polycistronic 730 United network for organ sharing (UNOS) 354 – systemic viral 901 United States department of agriculture Vector design (USDA) 897 – AIDS therapy 559 – voluntary scrapy flock certification pro- VEGF (vascular endothelial growth factor) 263, gram 1007 307 United States federal laws for biopharmaceuti- – as disease marker 1337 cals 1640 – productivity of mass bioreactor for 905 United States federal register 1641 Veldona 467 United States national hemophilia foundation Velosulin 13 (NHF) 424 Velosulin BR 471 United States prescription drug marketing Venn diagram 111 act 1736 Venous thrombosis 23 Urbason 1314 Verapamil clearance 1594 Urofollitropin 464 Verluma 21 Urokinase 380 Veterinary biopharmaceuticals 25 – -plasminogen activator 1280 Vibragen 26 Ussing chamber method 1479 Vinorelbine 131 Vinplastine 131 v Viola arvensis 484 Vaccination Viraferon 17, 468, 480 Subject Index 1885

ViraferonPeg 468 – translation under reducing/oxidizing condi- Viral vector generation 156 tions 1078 Virosomes 1425 Willebrand factor 425, 1153 Virtron 17, 468 Wilm’s tumor 221, 359 Virus based vector 186 (With-no-lysine) kinase-4 (WNK4) 78 Virus purification 158 Wnt-binding proteine 294 Virus safety 1650 Wolffian duct 355 Visceral endoderm 294 Working Cell Bank (WCB) 1645 Viscum album 482 World Drug Index (WDI) 1790 Visudine 1280 World Health Organization (WHO) 1569 VitoTox 1628 Vitravene 24, 633 x Vivid screening kit 1613 Xanelim 456 VNTR (variable number of tandem repeats) Xenopus laevis 486, 1228 marker 77 Xenotropic leukemia virus (X-MuLV) 434 Volatile organic compounds 1344 Xigris 4, 24, 465 Von Hippel-Lindau disease, pathways and targets X-inactive specific transcript 217 for 628 Xolair 454, 456, 1086 Vorvariella volvaceia 482 X-ray computed tomography (CT) 1213 Votumumab 22 – resolution 1214 VPAC1 receptor 1745 X-ray technique 1213 VPAC2 receptor 1745 – contrast agents for 1214 VSMC (vascular smooth muscle cell) 313 Xylose 849 2-Xylosyltransferase 925 w WalkThrough recombination 706 y – alkaline phosphatase with 712 Yaspin 1 1036 – evolution of cIAP 713 Yeast 20S proteasome 398 WalkThrough technique – inhibition by heterobivalent inhibitors 400 – for optimizing diagnostic proteins 707 – inhibition of PGPH and trypsin activities 404 Warfarine 57 – inhibition by monobivalent inhibitors 401 Watson-Crick base-pairing 38 Yeast agglutinin 1161 Wave bioreactor 1050 Yeast artificial chromosome 1111 – fed-batch conditions 1053 Yeast cell surface display 1112 – oxygen mass transfer coefficients 1055 Yeast expression vector 1028 – oxygen transfer for insect cell culture in Yeast-2-hybrid system 1161 1055 Yeast signal trap 109 – scale up 1053 Yttrium-90 Zevalin 456, 480 Wegener granulomatosis 1195 Yttrium-DOTALAN 518 Wellferon 468 Yttrium-DOTATATE 518 West Nile virus vaccine 779 Yttrium-DOTATOC 516 Western blot 1563 – analysis of alpha-glucosidase 861 z – of rhAT 1001 Zadaxin 478 – of transgenic rice grains carrying ITF Zeemann effect 1215 gene 943 Zemaira 464 Wheat embryo Zenapax 21, 456, 1086 – cell free expression of biopharmaceuticals Zevalin 22, 454, 456, 480, 501–502, 1086, 1121, using 1063 1169, 1234 Wheat embryo extract – application 1278 – composition of media and buffer 1071 Zocor 1730 Wheat embryo system Zoladex 478 – plasmid DNA templates 1067 Zomacton 476 1886 Subject Index

Zona pellucida 276 Zymogen 381 Zopiclone clearance 1594 – activator 388 Zorbtive 477 – form of fIX 697 Zot 1376 Zystic fibrosis 23 Zovant 465