collaborative innovation in drug discovery || index
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687
INDEX
Abbott Laboratories, 180, 198, 330Academia-based translational research
centers, see also Academic screening centers
creation of, 649translational research platform, 406–409
Academia–industry disconnect, factor contributing to, 401–403
Academia–industry partnerships, 279, see also Academia–pharma collaborations
facility agreement, 274improving efficiency of, 647–648intellectual property agreement, 274new directions for, 642–643R&D, 267, see also R&Drelationship models, 270–272research agreement, 272–273significance of, 646–647SWOT analysis of, 280–282symbiotic, 647technology transfer role in, 615–616university role in, 615–616
Academia–industry–government (AIG) partnerships, 191–192, 438
Academia–pharma collaborations, 67, 70–71, see also Consortia, drug discovery through; University–industry (U-I) collaboration
data sharing, 67effective management of, 70–71focus of work, 61–64novel pathway identification, 62
Collaborative Innovation in Drug Discovery: Strategies for Public and Private Partnerships, First Edition.Edited by Rathnam Chaguturu.© 2014 John Wiley & Sons, Inc. Published 2014 by John Wiley & Sons, Inc.
open source consortium, see Open source consortium
overall expectation from, 63stem cell-based therapies, 63
Academic drug discovery, 75, 78–79, 81–82, 454, see also Collaborative drug discovery (CDD)
European public data sources for, 506–507institutions in Brazil, 163–165institutions in China, 166–168institutions in India, 161–163institutions in Russia, 168–169
Academic entrepreneurship, 344ALS Biopharma, LLC, 352definition of, 611entrepreneurial academics, 240role of TTOs in, 611–613surveys of activity, 240
Academic high-throughput screening center, 305
Academic institutionsculture of ego-driven departments and labs,
670mission of, 59, 61, 207, 235, 610ownership of intellectual property rights,
60partnerships with industry, see Academia–
pharma collaborationsAcademic performance, 269Academic research, 221
aligned with market needs, 222and commercialization, 235–237competitive, 647
688� INDEX
contributions to pharma, 59–60dwindling funding to, 57ethical and financial obligations, 222and market adoption, gap between, 222,
231, 233–235research for research’s sake, 222for therapeutic targets, 57–58
Academic researchers, 268, 323Academic research institutes, 256
core facilities at, 658–660facility agreement, 274
Academic screening centers, 489–491evolution of, 490growth of, 489–490key elements for, 490“modular designs,” 491screens performed at, 490
Academic Screening Facility Directory, 489–490
Accelerated Research Collaboration™ (ARC™) model
accomplishments, 394–395annual planning process, 403–404collaboration with researchers, 398–399critical elements, 398features, 396goal of, 396–397initial challenges to, 389–390key process elements, 403model graphic, 392monthly collaboration forums, 404principal investigators, 390–391publications, 405research plan implementation, 404–405traditional model of research, 397–398translational research, 407–409
Access Platformbenefits of, 332collaborative activities, 320entrepreneurial nature of, 320integrated partnerships with drug discovery
centers, 322–323mission of, 320–321, 331objectives of, 320strategic aim of, 331valorizing output of, 333–334
Accountable Care Organizations (ACOs), 665, 672
Acetylon Pharmaceuticals, 309Acoustic dispensing systems, 41Acquired immune deficiency syndrome
(AIDS), 375atazanavir for treatment of, 522–523drug development for zidovudine, 522expenditure on R&D for, 381history of, 521prevalence of, 526
ADMET Predictor, 469, 558Administration and collaboration, 13, 17Affordable Care Act (ACA), 665, 672Agency for Healthcare Research and Quality
(AHRQ), 666Agreement negotiations, sponsored, 88, see
also License agreementAirbnb, 654, 655, 659Alliance management, 263–265AlphaBeta Pharma, 574ALS Biopharma, LLC, 352Alzheimer’s Disease Neuroimaging Initiative,
496America Invents Act (AIA), 590–591American Heart Association, 28American Society for Clinical Oncology
(ASCO), 674A.N. Belozersky Institute of Physico-
Chemical Biology, 168Angel Capital Association, 327Angel investments, 327–328Animal models of human disease, 227Anticancer research and drug development,
627Anti-commons problems, 144–145“Anti-Intellectual Effects of Intellectual
Property,” 76–77Antimalarial resistance reversal agents, 306Antivenom, 28Apple Mac, 371Applied research, 242, 247, 347, 402,
518, 525, 542, 628, 647, 682, 684, 685
Artemisia annua L., 167Artemisinin-based combination therapies,
523Artesunate Amodiaquine Winthrop®
(ASAQ), 378Asian Cancer Research Group (ACRG),
262
Academic research (cont’d )
INDEX� 689
Assay development, 207, 453, 455, 478, 480, 511, 525
functional and geographic redundancy in, 459
for HCS, 462for HTS, 101–105, 760NIH molecular libraries, 105–109pharmacodynamic, 141and Prebys Center, see Prebys Centersmall molecule screening, 102symmetry in, 459technical challenges in, 102
Assay signal and detection technologies, 457
Association of University Technology Managers (AUTM), 612
Asterand, 310AstraZeneca
and Columbia University partnership, 63, 65, 69
Compound Management Network, 541and Griffith University, CDD between,
540–542Atazanavir, 522–523Australia, 556–557
conditions facilitating QCL in, 541–542contribution to global medical science,
538–539federal funding schemes, 538HTS introduced into, 540NCRIS scheme, 541Nobel laureates, 538small molecule drug development in,
539–540Australian research organizations, 539AUTM Global Technology Portal, 598Avastin®, 216, 669Ayugenomics, 191Ayurveda, 176, 174, 188–190“AYUSH” acronym, 188
definition of health, 174meaning of, 188and modern drugs, comparison of,
190public acceptance of, 189meaning of, 188and modern drugs, comparison of, 190public acceptance of, 189
AyuSoft, 191
Barter system, 656Basic research, 628Basic research students, training of,
647–648Bayer HealthCare, 179–180, 370
Grants4Targets initiative, 259, 261Innovation Center at Mission Bay, 261,
262strategic alliance, 260, 261
Bayer–University of Cologne collaboration, 280–283, 287–288, see also Graduate program in pharmacology and experimental therapeutics
opportunities, 281privileged partnership, 280risks to, 281strengths of, 281sustainable, 287–288SWOT analysis of, 283weakness of, 281–282
Bayh, Birch, 6Bayh–Dole Act of 1980, 60, 239, 578–579,
583, 611, 628, 665conditions for assignment of title, 6–7,
143paid-up license to federal government,
143–144rise in pharmaceutical research with, 342university patenting and licensing
activities, 342–343BCR-ABL fusion protein, 519–520Benznidazole, 165Berlin University, 4Bilateral collaboration schemes, 187Bill & Melinda Gates Foundation, 307, 309,
595Biochemical FRET-based assays, 511–512Bioclon Institute, 28Biodefense collaborative research case study,
310–311Biogen Idec bi3, 261Biological Innovation for Open Society
(BiOS), 27–28Biological screening, 556Biological software programs, 372Bio-Manguinhos (Immunobiological Institute
of Technology), 165Biomarkers, 407Biomarkers Consortium, 15
690� INDEX
Biomedical collaborations, 14Biomarkers Consortium, 15Predictive Safety Testing Consortium
(PSTC), 15SNP and SAEC Consortia, 15–16
Biomedical innovation ecosystems, 321Biomedical research, sharing practices in,
657Biomedical research institute, 443Biomedical science
drug discovery, 373–374open source model, 371–373
Biopharmaceutical industryacademic research influence on, 624job opportunities, 223–224
Biopharmaceutical research, 32Biopharma Initiative, 507–508Biopolis, 524–525Bioprospecting using traditional knowledge,
189–190Bioseek, 310Biotechnology Center of Bucks County, 351Biotechnology industry, 624Biotechnology Industry Partnership
Programme (BIPP), 186Biotechnology Industry Research Assistance
Council (BIRAC), 186Biotechnology research, 646
collaborations, 347funding schemes for, 186
Biotech parks, 179Biotech ventures, impact of economic
recession on, 58Blockbuster drugs, 24, 116, 148, 203, 205,
210, 245, 255, 521, 615, 659, 668expiring patents on, 57, 58myths and facts about, 203post-approval phase 3 trials of, 205–206
Boronates as pharmaceutical agents, 629Bortezomib
commercial potential of, 637properties of, 630translational research, 629
Bortezomib, discovery and development of, 627, 630–636
collaboration with scientists, 631–632, 642core model, 636–639funding, 633, 635, 636key players in, 639–641
NCI interest in, 637, 641proof-of-concept study, 632–633proteasome research, 630–632therapeutic index, 634trial at UNC, 633–634
Brazil, government-financed drug discovery in
academic institutions, 165Bio-Manguinhos, 165Center for Technological Development in
Health (CTDS), 165challenges to, 160collaboration opportunities, 169Farmanguinhos, 164–165infectious disease research, 164natural product chemistry, 164political priorities and, 171SIBRATEC, 163–164
Break-point cluster region (BCR) gene, 519Breakthrough innovation, 374Breakthrough science, 199–200, 207, 210BRIC countries, drug development activities
acrossBrazil, 163–165, 169–170China, 166–168, 170collaboration opportunities, 169–170India, 161–163, 169–170leveraging experience of, 171nonindustrial institutions, 160–161Russia, 168–170
BRIDGs Program, 673Bristol-Myers Squibb (BMS), 198, 522,
669partnerships, 49–50, 64
Broad Institute, 490Budget, 333–334Burnham Institute for Medical Research,
453–454
Caenorhabditis elegans, 424, 490CALIBR, 208Cambia, 26–28, 378
BiOS licenses, 27–28Cancer, orphan-designated products for, 349Cancer Bioinformatics Grid™(caBIG) and
GSK collaboration, 66Cancer drugs, 624
bortezomib, 627–641clinical trials, 138
INDEX� 691
Iressa, 217monoclonal antibodies in, 624
Cancer drug discovery, 135, 141Avastin, 216evolution of, 31Gleevec®, 46
Cancer Genome Atlas project, The (TCGA), 70
CancerLinQ, 674Cancer Research U.K. projects, 501Cancer therapeutics pipeline and technology
transferCTEP IP Option, 146–149development, 140–141, 145–146NExT Program’s IP structure, 143–144
Cancer Therapy Evaluation Program (CTEP), 138, 141
IP Option, 146–149Cash flow valley of death, 325CDD TB database project, 307–309Celebrex®, 587Cell lines from human solid tumors,
136Center for Innovative Technology (CIT),
596Center for Medical Countermeasures against
Radiation (CMCR), 310Center for Technological Development in
Health (CTDS), 165Center for World Health and Medicine
(CWHM), 127–128Centers for Therapeutic Innovation (CTI),
63, 249–250, 329Central Drug Research Institute (CDRI),
161, 162, 171Central Institutional Review Board (CIRB),
approvals, 666Cerebrospinal fluid (CSF), 415Certified Licensing Professionals (CLP™),
585Checklist, for potential therapeutic
compound, 429ChemBioNet, 502–504ChEMBL, Neglected Tropical Disease
archive, 66ChEMBL databases, 506ChemBridge, 493ChemDiv, 168–169Chemical biology, 45, 78, 534
Chemical Biology Consortium (CBC)Molecular Libraries Screening Network,
144resourcing portion of, 140
Chemical biology platform, implementation of, 490
Chemical compound libraries, 493–495, 540
initiatives for developing, 493–495QCL, see Queensland Compound Library
(QCL)small molecule libraries, 494
Chemical consultants/consulting, 355-365Chemical genomics, 469, 492–493Chemical libraries, see Chemical compound
librariesChemical optimization, 558
of NITD 609, 524of small molecule probes, 110
Chemical Optimization of Small Molecule Probes for the Nervous System, 110–111
Chemical screening projects, 490, see also High content screening (HCS); High-throughput screening (HTS)
Chemical spaceevolution of, 45factoring leading to exclusion of, 494
Cheminformatics tools, 468–469Chemistry space, 80, 82, 83, 547, 555ChemNavigator, 111Chemogenomics, 36–38Chemogenomic screens, 492–493Chemotypes, 43–44Chimeric 14.18 (ch14.18), 154–155Chimiothèque Nationalé, 537China, government-financed drug discovery
in, 160, 166, 170, see also China State Institute of Pharmaceutical Industry (CSIPI); Guangzhou Institute of Biomedicine and Health (GIBH); Institute of Materia Medica (IMM); Shanghai Institute of Materia Medica (SIMM)
China National Biotic Group, 167China State Institute of Pharmaceutical
Industry (CSIPI), 167–168Chloroquine resistance, reversal of, 306Chrome, 371
692� INDEX
Chronic myelogenous leukemia (CML), 519–520
Ciba-Geigy, 519Clinical Advisory Board (CAB), 392Clinical and Translational Science Award
Pharmaceutical Assets Portal (CTSA portal), 69, 77, 100, 131–132, 673
goal of, 116–117IDU contributions to, 129infrastructure of, 117, 118IP restrictions, 127members, 121MTA negotiation, 127–128
Clinical data, termination and return of, 601–602
Clinical supply agreement (CSA), 150Clinical trial
attrition rates, 116limitation of, 230–231
Clinical trial agreements (CTAs), 148vs. CRADAs, 150–151
Clinical Trials Cooperative Group Program, 138
Clinical Trials Registry—India (CTRI), 188
Close contact partnershipbenefits of, 274–275for joint R&D initiative, 271Nordion Inc. and UOHI, 271–274risks and challenges of, 275, 277
Closed business models, factors influencing success of, 58
CMCR screening program, 310–311CoarsucamTM, 378Coartem, 523–524Cohen–Boyer biotechnology patents, 611COHORT, 416Collaboration, 249, 312
in 2012, 49–50alliance network, 208–209for biomedical research, 11, 12challenges in establishing and maintaining,
12, 131checklist for initiation of, 265and competition, 12cross-functional, 217, 218–219definition of, 13, 323effectiveness and durability of, 49elements of, 13
with external partners, 336factors driving, 49fine-grained control, 305governance, 14, 273growth in, 50–51history of, 623human factors and, 17impacts of, 50key success factors for, 263–264principles of, 16–17professional management of, 263–264public–private partnerships, 323–326recent changes in, 49between scientists, significance of, 653value-driven drug development, 215–216
Collaboration agreementdesired outcomes, 527NExT Program MTA, 146ProScript and HMR, 633and TTOs, 580
Collaboration management, 263–264Collaboration models, 12–13
BRIC countries, 169–170consensual decision making, 14funding and resource procurement issues,
14key dimensions of, 13large-scale “industrial” consortia, 17
Collaboration networks, 14, 210Collaborative drug discovery (CDD),
337–338academic case studies
antimalarial resistance reversal, 306tuberculosis research, 306–309
applications of, 304–305between AstraZeneca and Griffith
University, 540–542commercial case studies
Acetylon Pharmaceuticals, 309Bioseek, 310Indel Therapeutics, 310Semafore Pharmaceuticals, 309
community meeting, 78data sharing in, 312–313evolution of
CDD community meeting, 78drug repurposing attempt at Pfizer,
75–76HTS conference of SBS, 76
INDEX� 693
IP and information exchange, 76–77NIH Roadmap for Medical Research, 79
formation of, 77organizational and cultural challenges for,
79bias and error, 81–82biological structure–activity relationship,
80chemistry space, 80hypothesis-driven research, 81medicinal chemistry implication, 80–81molecular weight, 83natural product, 82–83physicochemical properties, 79–80rich or lean mode, 81–82
prerequisites for, 304reasons for collaborating via, 313researcher control, 305user roles and privileges in, 313–314
Collaborative Drug Discovery, Inc. (CDD), 304
Collaborative Drug Discovery Tuberculosis Database (CDD TB), 307
Collaborative economyaccommodation industry, 654, 659barriers to, 660benefits of, 654, 659–660industries transformed by companies
creating, 654–655labor market, 654major driver of, 656of peer-to-peer transactions, 658–659transportation industry, 654widespread adoption of, 654
Collaborative informatics, 305Collaborative models, 208Collaborative relationships, 337Collaborative research, 187
biodefense, 310–311in biomedical industry, 208–209challenges, 12and competitive research, 397–400with QCL, 556–559
Collaborative technologies, 311Collaborators, from NIH Roadmap, 458Collective patient viewpoint, 665Columbia University, and AstraZeneca
partnership, 63, 65, 69Combination therapies, 675
Commercialization, 274, 304, 612critical steps required for, 326driving research, 235–237innovative, 327of invention, 347IP agreements, 238, 240nonpatentable knowledge, 240–241paradigm shift in, 610of university research, practices in,
346–347of university technology, 342
Common Health Index (CHI), 567Communication effectiveness, 618Companies
focus on short-term gains, 668research institutes close to universities,
646COMPARE program, 136Competition, 6, 12Compound attrition, common causes of, 47Compound collection, 40, 45Compound management, 465–467, 535, 541Computer-aided molecular design
approaches, 469CONNECT®, 7–8“Connect and Develop” portal, 94, 259Conrad Prebys Center for Chemical
Genomics, see Prebys CenterConsortia, drug discovery through, 65–67
ChEMBL, Neglected Tropical Disease archive, 66
GSK–caBIG collaboration, 66Innovative Medicine Initiative, 67Merck-Sage Bionetworks, 66Structural Genomics Consortium, 67
“Consortium fatigue,” 660Consulting, see Chemical consultants/
consultingContract research organizations (CROs), 162,
207–208, 309, 411, 658–659Contracts, 7, 28, 58, 70, 88, 92, 95, 111,
136, 138, 140, 143, 146, 148, 161, 162, 166, 169, 179, 180, 235, 244, 246, 247, 264, 280, 360–362, 419–420, 557, 571, 573, 580, 594, 595, 602, 605, 617, 666, 675
Cooperative research and development agreements (CRADAs) vs. CTA mechanism, 150
694� INDEX
Cooperative Research Centre for Cancer Therapeutics (CRC CTx), 540
Copyleft, 371Copyright, 26Core Model
bidirectional interactions, 642implications for economic growth, 635translational research, 634
Cost–benefit assessment, 41Cost estimation studies, 223Coulter Foundation, 595Council of Scientific and Industrial Research
(CSIR), 162NMITLI, see New Millennium Indian
Technology Leadership Initiative (NMITLI)
Open Source Drug Discovery (OSDD), 181–182, 184
COX-2 protein, 535Critical Path Institute (C-Path), 15Cross-functional collaboration, 217, 218–219Cross-sector programs, 446Crowdsourcing, 255
for HT chemical screening, 495–496platforms, 208
Cruz, Oswaldo, 164CTSA•IP (website), 111–112Cure Huntington’s Disease Initiative (CHDI),
411–434Cures Acceleration Network, 327Current Opinion in Computational Biology
(COCB), 76–77Cymbalta, 68Cystic Fibrosis Foundation, 208
Data archiving and selective sharing, “activation barriers” to, 305
Data availability, 305Data modeling, 675Data sharing
in CDD, 312–313fine-grained control for, 305and IP rights, early hit-to-lead
development, 144–145DDT Therapeutic Strategies (book), 77Decision of Exceptional Circumstances
(DEC), 144–145De novo drug development vs. drug
repositioning, 116
Department of Biotechnology (DBT)global partnerships and alliances, 187SIBRI and BIRAC, 186Stanford–India Biodesign (SIB) program,
187Department of Energy, 371Department of Science and Technology
(DST), 184–186Drugs and Pharmaceutical Research
Program (DPRP), 184Good Laboratory Practice (GLP), 186
Digital marketplace model, 658Diminishers, characteristics of, 23“Direct-to-consumer” advertising, 668Disease-focused philanthropies, 248Disease-in-a dish models, 471Diseases, understanding molecular basis of,
648–649Disruptive innovation, 200Division of Cancer Treatment and Diagnosis
(DCTD)Developmental Therapeutics Program
(DTP), 136natural products collection, 137
Dole, Robert, 6Drosophila melanogaster, 424Drug development, 223, see also Drug
discovery and developmentacademic and institutional mistakes,
670–671and academics, 665animal modeling, 227assessment and investment activities
throughout, 242CHDI, see Cure Huntington’s Disease
Initiative (CHDI)clinicians’ role in, 665–666conspiracy theories regarding, 664cost estimation studies, 223and government agencies, 666government mistakes, 671(im)patient side of, 663–664and industry, 666industry and company mistakes,
668–670patient position in, 665patients role in, 666preclinical/early clinical phase of,
135–136
INDEX� 695
timelines of research phases and attrition rates in, 232
unprotected side of, 664Drug Development Group (DDG), 136–137Drug Development Promotion Board, 184Drug Discovery Advisory Board (DDAB),
392Drug discovery and development, 43, 58, 71,
455, 476, 623, see also Nonprofit organizations; R&D
approaches in, 176challenges of, 28, 34changing landscape of, 335clinical trials, 228–230collaborative capabilities for, 312conventional vs. reverse pharmacology
approach, 189cost of, 25, 59, 204–207, 452, 495, 517early phase of, 58error in, 82expenditures on, 59factors influencing success of, 35goals of, 78hit identification, see Hit identificationinformatics requirements, 304innovation in, see Innovationinterconnected processes, 33–34interdisciplinary nature of, 323and internal target validation, 60as iterative process, 45lead optimization, see Lead optimizationlinear rates of, 303manufacturing process optimization,
230–231phases of
discovery/basic research, 226–227manufacturing process optimization,
230–231phase 1 clinical trials, 228–229phase 2 clinical trials, 229phase 3 clinical trials, 229phase 4 clinical trials, 230preclinical testing, 228regulatory review of IND, 230
preclinical assessment, see Preclinical assessment
protection of, 585–590protein kinase inhibitors, 46in public domain, 69–70
and research charities, 501–502regulatory review of IND, 230screening programs, see High content
screening (HCS); High-throughput screening (HTS)
slowdown in, 224target identification and target validation,
see Target identification and target validation
technological advances influence on, 32
technological innovations for, see Technological innovations
through collaborations, 61–64, see also Collaboration
through consortia, 65–67through repurposing strategies, 67–69
Drug Discovery Initiative (PD2), 329Drug Discovery Initiative (TargetD2)
Platforms, 329Drug discovery partnerships, 62, 208,
see also BRIC countries, drug development activities across
Druggable genome, 45Druggable space, 36Drug marketing lore, 203Drug repositioning, 116, see also Clinical
and Translational Science Award Pharmaceutical Assets Portal (CTSA portal)
Drug repurposing, 452, 525, 590, see also Clinical and Translational Science Award Pharmaceutical Assets Portal (CTSA portal)
attempt at Pfizer, 75–76CP-26154, 76and drug transfer MTAs, 127–128funding for, 124–127pharmaceutical industry perspective on,
129–130Drugs
acting on single targets, 175death of, 174–175vs. medicine, 176from poisonous sources, 176withdrawn from market, 175
Drug-seeking campaigns, 356, 357Drugs for Neglected Diseases initiative
(DNDi), 377
696� INDEX
Drug transfer MTAs, 127Duloxetine, see Cymbalta
Early development resources, 140–141Early discovery initiative (EDI), 420Early-stage drug discovery, 159, 168, 343,
344, 477, 535, see also Drug discovery
Early-to-Candidate (E2C) Access Platform, 320–323, 331–334
collaborative activities, 320entrepreneurial nature of, 320partnerships with drug discovery centers,
322–323valorizing output of, 333–334
Echo® 555 acoustic drop ejection technology, 460, 461
Echo Systems, 41Edison, Thomas Alva, 235–236Electric lighting, 236Eli Lilly, 63, 67
aggregate capitalization of, 198Cymbalta, 68InnoCentive platform, 259Open Innovation Drug Discovery Program,
329Phenotypic Drug Discovery (PD2)
Initiative, 63, 537–538Enlight Biosciences, 262, 263Entrepreneurial academics, 240Entrepreneurial activity, surveys of, 240Entrepreneurs, conflict faced by, 603Entrepreneurship, 344Eribulin, 153Established company, licensing to, 602–604Ethics, of consulting, 362–363eTOX program of IMI, 67Etsy, 659EU Innovative Medicines Initiative-Joint
Undertaking (IMI JU), 66–67EU-OpenScreen, 70, 505–506, 536–537European Advanced Translational Research
Infrastructure in Medicine (EATRIS), 505
European Credit Transfer and Accumulation System (ECTS), 288
European Federation of Pharmaceutical Industries and Associations (EFPIA), 499–500
European Infrastructure of Open Screening Platforms for Chemical Biology, 70
European Medicines Agency (EMA), 15, 216, 217, 428
European Molecular Biology Laboratory (EMBL), 506
European Bioinformatics Institute (EMBL-EBI), 78
European public data sourcesCerep BioPrint® in-vitro database,
506–507ChEMBL databases, 506Open PHACTS consortium, 507
European Regional Development Fund grant, 572
European ScreeningPort (ESP), 508biochemical FRET-based assays, 511–512compound reformatting module, 510MesoScaleDiscovery instrument, 511mission of, 509physical access to screening infrastructure,
509physical screening infrastructure, 510–511role in funding procurement, 509“Visiting Scientist Scheme,” 509–510
European Strategy Forum on Research Infrastructures (ESFRI), 504
European TTOs, 244–245European Union (EU)
and India, joint R&D endowment fund of, 185–186
innovative pharmaceutical sector, 223and nongovernmental organizations, 447
European-wide academic infrastructuresEATRIS, 505ESFRI role in, 504EU-OPENSCREEN, 505–506Innovative Medicines Initiative, see
Innovative Medicines Initiative (IMI)and public–private partnerships, 502–504
Experimental Therapeutics (NExT) Programapplication review structure, 141–142applications to, 139case studies
chimeric 14.18, 154–155halichondrin B, 151–153romidepsin, 153–154
CBC Steering Committee, 142Chemical Biology Consortium (CBC), 140
INDEX� 697
criteria for project approval, 139decision-making bodies, 139–140Discovery and Development Committees,
142discovery engine of, 142governance structure, 141–142IND-directed toxicology data, 141IP structure, 143–144, 151oversight and accountability of, 142portfolio of molecularly targeted agents,
138primary impetus for, 138Senior Advisory Committee (SAC), 142Senior Management Committee (SMC),
142Special Emphasis Panel (SEP), 142supported by CTEP, 141technology transfer mechanisms, 143–144
Exubera®, 203
Facile collaboration around data, “activation barriers” to, 305
Faculty inventors, conflict faced by, 603Farmanguinhos (Institute of Pharmaceutical
Technology), 164–165FDA-approved drugs and their status, 669Federal agencies, medical research, 666–667Federally funded research, 59, 60First-in-class drugs, 630, 636
discovery of, 31–32from phenotypic and image-based assays,
462validation for, 628
Flintbox®, 598Foci-of-Expertise (FoX) Synergy Browser,
120–124Food and Drug Administration (FDA), 216,
666NCEs and NMEs approved by, 31–32warnings regarding drugs, 669
Forecasting of blockbuster drugs, 203, 210Fortune 500 company, average life
expectancy of, 199ForwardTrack™ Program, 345Fox Chase Chemical Diversity Center, Inc.,
352Fraunhofer Institute, 246, 247“Free agent” model, 91“FUD” factor and innovation, 23
Fujisawa Pharmaceutical Company, 153–154Fukushima Daiichi nuclear disaster, 310Funding
academic programs, 329for collaboration, 14, 16, 91federal programs, 328for high-risk projects, 180–181industry programs, 329POCCs, 328proposals, 674for R&D, 177recommendations for changes in, 353for translational research, 649venture capital and angel investments,
327–328
Galapagos, 78Gandhian innovation model, 22Gene microarray chips, 35, 36General Public License, 371Genome sequence, 377Georgia Research Alliance (GRA), 596German model, 5Germany, 4
Biopharma Initiative, 507–508history of university research in, 5and India, joint R&D endowment fund of,
185–186Germ theory, 441GlaxoSmithKline (GSK), 204, 370, 496
and caBIG collaboration, 66Discovery Partnerships, 208
Gleevec®, 46, 48, 180, 203, 519–521, 675Global Alliance for TB Drug Development
(GATB), 77GNU Project, 371Goldberg, Alfred, 630–632Good Laboratory Practice (GLP), 186, 228,
273Governance and collaboration, 13, 17Government-financed drug discovery, in
BRIC countriesBrazil, 163–165, 169–170challenges to, 159–160China, 166–168, 170India, 161–163, 169–170leveraging experience of, 171nonindustrial institutions, 160–161Russia, 168–170
698� INDEX
Government mistakes, 671Governments, 8Government-supported venture fund, 169G-protein-coupled receptor (GPCRs), 37–38Graduate program in pharmacology and
experimental therapeutics, 280academic titles, 292agreements on IP and publication rights,
287changes to concept of, 298–300common research areas, 285core scientific and soft skills, 290criteria for inclusion of projects, 285, 288curriculum assessment, 295–298degree procedures, 292–293fundamental research, 286funding structure of, 285governance structure of, 282, 284inter-institutional communication,
288–290obligatory curriculum, 288–290operating sequence of, 285personal communication skills, 291transparency in external communications,
287value recognition, 291–292
Graduate School for Biological Sciences (GSfBS), 288
Graham factors, 587Grants4Targets initiative, 63, 259, 261Griffith University
and AstraZeneca, CDD between, 540–542QCL establishment, 541–542and SSRFF, 541–542
Guangzhou Institute of Biomedicine and Health (GIBH), 166, 171
Halichondria okadai, 151Halichondrin B, 151
as cancer therapeutic, 152–153deep-water collection of, 152–153NCI approval for preclinical development
of, 152Health, definition and determinants of, 174Health and Human Services (HHS), 672, 673Healthcare, 127, 174, 187, 221, 237, 271Health charities, 684–686Health promotion and prevention strategies,
174
Health Science Scotland, 573Health technology assessment bodies (HTAs),
214, 216Herceptin, 215Hereditary Disease Foundation (HDF), 416High content screening (HCS), 462–463,
534, 535, 539ESP, 512Prebys Center, 458, 462–466, 476phenotypic assays, 471, 475
HighRes BioSolutions, 491High-throughput screening (HTS), 32, 489,
534, 537, 539, 588assay analysis instruments, see Chemical
compound librariescrowdsourcing efforts, 495–496decline in investment in, 41definition of, 39evolution of, 40, 42facilities in Australia, 547HTS assays, 39HTS campaigns, 457, 42–43HT screens
chemical compound libraries, see Chemical compound libraries
chemogenomic screens, 492–493sources of error from, 491
rapid expansion and maturation of, 39–40technology enhancements in, 40
High-throughput screening platformsEU-OpenScreen, 70NIH Roadmap initiative, 69
Hit assessment, 42–43, 45Hit confirmation, and SAR support
capabilities, 461–462Hit deconvolution, 105Hit identification, 33–34, 43, 44, 331
HTS assays, 39–42nanodispensing, 41
Hit selection criteria, 43Hits to leads, 366, 480HIV-detection kit, 583HIV infection, 68, 163, 165, 375, 381, 578
antiviral, 522discovery of, 438expenditure on R&D for, 381molecular diagnostics for detection of, 522
HIV protease inhibitors, 522HIV vaccines, phase 1 studies for, 188
INDEX� 699
Hoechst Marion Roussel, 629, 633, 645–646HTT gene, 414Human factors and collaboration, 17Human genome, 36, 51, 61Human Genome Project (HGP), 35, 173,
369, 372, 373, 533, 534, 644“Humanized mouse,” 51Human tissue assays, 407Humboldt, Wilhelm von, 4Huntingtin (HTT) protein, 414Huntington’s disease (HD), 411, 414–416,
427, 431, 433Huntington Study Group, 416Hypothesis-driven research, 81
iBridgeSM Network, 598Image management infrastructure, 465IMI JU, see EU Innovative Medicines
Initiative-Joint Undertaking (IMI JU)IMI NEWMEDS consortium, 503Immunoassay, 141Immuno-oncology, 31Incubator model, 258, 261, 262Indel Therapeutics, 310India
complex problems faced by, 173economic reforms, 177as signatory to WTO, 177Trade-Related Intellectual Property
agreement, 177India, government-financed drug discovery in
academic institutions for, 161–163challenges to, 160collaboration opportunities, 169
Indian Council of Medical Research (ICMR)Bioethics initiative, 188funding programs, 187pharmaceutical and vaccine development,
188research priorities, 187–188
Indian Drugs & Pharmaceuticals Limited (IDPL), 161–162, 171
Indian Institute of Chemical Technology (IICT), 163
Indian National Science Academy, 191–192Indian pharmaceutical industry
associations, 178biotech parks, 179growth of, 178
and intellectual property, 179–180new paradigms of, 180partnership with MNCs, 178–179policy drivers to boost, 178–179post independence, 177scientific institutions, 179SEZ for, 179situation analysis, 178–179structure of, 178
Indo-German Science and Technology Centre, 185
IND studies, 141Industrial Originated Projects (IOPs), 181Industrial Research Institute, 128Industry, 8–9
principles for success of, 9Industry and academy, relationship models
of, see also Academia–industry partnerships
arm’s length model, 270close contact model, 271–275, 277open door model, 270–271separate but equal model, 270
Industry R&D executives, 269–270Industry-standard due diligence review,
345–346Infection, 119, 126, 502, 669, see also HIV
infection; Neglected diseases; Plasmodia
Information dissemination/transfer, 343Information exchange, and IP, 76–77In-licensing, 59, 255, 320, 332InnoCentive platform, 208, 259Innovation, 199, 319, 343
alternative models of, 22in basic lab equipment, 39–40definition of, 22, 256in drug discovery, 24–25and ethics, 202, 204and “FUD” factor, 23future perspectives of, 50–51impediments to, 23importance of, 24vs. invention, 322leadership for, 23motive for, 22myths and facts about, 203–204need for, 24new models for, 207
700� INDEX
priorities for restoring, 210–211strategies for managing, 337strategies to encouraging, 23–24warnings regarding, 24–25in waves separated by long dry spells,
200–201Innovation crisis, 202, 204, 653Innovation deficit, 175–176Innovation hubs, network of, 248–249Innovation networks, 208, 330Innovation sourcing vs. outsourcing,
256Innovative Medicines Initiative (IMI), 67,
261, 263, 502–504Innovative technologies, 33, see also
Technological innovationsfrom target discovery to preclinical
assessment, 34In silico drug repurposing strategy, 306Institute for Quality and Efficiency in
Healthcare, 214Institute of Chemical Biology and
Fundamental Medicine, 168Institute of Materia Medica (IMM), 166,
167, 171Institute of Medicine (IOM), 673Institutional bureaucracy, 660Institutional changes, 674Institutions and researchers, competition
among, 6Institut Pasteur International Network (IPIN),
437–447chronology of, 439goal of, 445growth of, 446Institut Pasteur Paris, 442–443Institut Pasteur policy, 447model, 438pasteurian spirit propagation,
443–445staffs and institutions, 445–446strategies for collaboration and
surveillance, 445Insulin, 518Integrated operating model, 500Integrative medicine, 124, 176
Intellectual property, policies, flexibility in, 617
Intellectual property (IP), 269, 274, 333, 370, 535, 585–587, 630, 665
agreementsand commercialization, 240between companies and universities,
127consulting, 582
all parties contribution to, 569consulting, 582and data rights
for CBC development phase, 144–145clinical candidate, 145–146late-stage development, 146NExT Program, 143–144
definition of, 237and Indian pharma companies, 179–180and information exchange, 76–77maturity of, 238ownership of, 6, 274, 583–584policy, university’s, 582–583policies, flexibility in, 617protection of, see Copyright; Patentresiding in university, 238TTO support to university administration,
581–582and university research, 6–7
Intellectual Property Appellate Board, 179International Clinical Compound Library
(ICCL), 128–129International Clinical Trials Registry Platform
(ICTRP), 188International Genomics Consortium (IGC), 70International Serious Adverse Event
Consortium (iSAEC), 15–16International Trachoma Initiative (ITI), 378Invention disclosures, TTO solicit, 581Invention vs. innovation, 322Investigational new drug (IND), 666
application, 76FDA approval for, 228phase 1 clinical trials, 228phase 2 clinical trials, 229phase 3 clinical trials, 228regulatory review of, 230
Investigator-initiated researchcase study of
chimeric 14.18, 154–155halichondrin B, 151–153Romidepsin, 153–154
Innovation (cont’d )
INDEX� 701
leveraging investment in, 99path of activities leading to, 99–100
Investments, 5, 43, see also FundingIn vitro models, 469, 471In vivo models, 469, 471In vivo murine cell lines, 136iPSCs, 471Ischemia, SPECT myocardial perfusion
images of, 276Ivachtchenko, Alexander, 168
Janssen Pharmaceuticals, 65, 200, 209, 214, 646
Johnson, Wayne, 88Johnson & Johnson, 204Johnson Continuum, 88–90Joint steering committees (JSCs), 421Juvenile Diabetes Research Foundation
(JDRF), 595
Kauffman Foundation, 328“free agent” model, 91iBridgeSM Network, 581
KEGG (Kyoto encyclopedia of genes and genomes), 433
Keystone Edge program, 91–92Kinase drug discovery, 45–47Kinect product, 22Knowledge generation, 610Knowledge transfer, 343Konqueror, 371Kynurenine monooxygenase (KMO), 428
“Land grant” universities, 5Large companies, 93–94Large-scale screening centers, 490–491LaskerDeBakey Clinical Medical Research
Award, 48, 167Lead compounds
development phase of CBC, 144discovery of, 490–491in late-stage clinical trials, 489
Lead discovery and methods, open-source efforts for, 496
Leaders, characteristics of, 23–24Leadership, and innovation, 23–24Lead optimization, 226
chemical series for, 43compound collections during, 45
and hit assessment, 43–44HTS campaigns, 42–43importance of, 42to IND drug discovery processes, 475screening challenges related to, 44in vitro assays for, 44–45
Legal environment, 334Leukemia cell lines, 136LeukoSite/Millennium acquisitions, 627,
634–635Liability insurance, 361License agreement, 600–602License modifications and resolution of
conflicts, 605–606Licensing, 347, 630
socially responsible, 599–600start-ups vs. established companies,
602–605Life science collaboration
and academic entrepreneurship, see Academic entrepreneurship
for bioactive compounds, 70commercialization activities, 87conflict of interest, 92and QCL, see Queensland Compound
Library (QCL)Life Science Development Fund (LSDF),
596Life sciences university research,
613–615Linux, 371Lissodendoryx sp., 152Lupin, 370
Malaria, 375, 379artemisinin-based combination therapies
for, 523Coartem for treating, 523–524prevalence of, 523
Manufacturing process optimization, 230–231
Market access, 213–214, 217Market-driven collaboration, 657, 658,
659–660Marketed drugs
drug repurposing for, 67–69return on investment of, 59
Marketing Authorization Application (MAA), 227
702� INDEX
Market pull and technology push, commercial contrast between, 231, 233
Market risk, 332–333Maryland Industrial Partnerships (MIPS)
program, 90Massachusetts General Hospital (MGH) and
Hoechst, collaborative arrangement between, 645–646
Massachusetts Institute of Technology (MIT), 64, 247, 379, 646
Deshpande Center at, 207Industrial Liaison Program, 95
Material transfer agreements (MTAs), 420for compound transfers, 127–128
Maxwell Biotech Venture Fund, 169Mayo Clinic, 454
research leadership, 477strategic partnership with Prebys Center,
480advantages of, 481cultural factors and governance,
481–482“fast-tracked” proposals, 480–481
translational science activities at, 479–480Medical impact, sources of information
having, 648Medical outcomes, 77, 81, 88, 102, 159, 162,
215–217, 332, 520, 527, 555–557, 664, 666, 669, 672
Medical research system, 664Medicinal chemistry, 78
development phase of CBC, 144expertise for advanced chemical
optimization, 110facility and capabilities, 467–468quality, 81
Medicinediscovery, holistic, 176–177vs. drugs, 176worldwide sales of, 178
Medicines for Malaria Venture (MMV), 523–524
Medicines Research Council, 567Melior Discovery, 76Merck, 63, 66, 198, 200, 209, 330, 370, 640,
646Merck-Sage Bionetworks, 66Mergers, challenges created by, 624MesoScaleDiscovery instrument, 511
Metabolism, 45, 47, 67, 102, 191, 228, 308, 343, 363, 373, 414, 417, 468, 501, 507
Metastatic breast cancerAvastin® for, 669eribulin for, 153
Metcalfe’s law, 303“Me-too” drugs, 668
redundancy of, 59, 60, 61Metrics, for success, 353Michael J. Fox Foundation, 208, 595Michigan University Commercialization
Initiative (MUCI), 596Microbiology, 437, 442, 443, 445, 447Microplate readers, 40Microsoft, 22, 371Millennium Pharmaceuticals, 627, 634Minneapolis (MN), 418Minnesota-Innovation Partnerships (MN-IP),
92Minocycline inhibition of caspase-1, 427Molecular Libraries Initiative (MLI), 453,
493–494Molecular Libraries Probe Production Centers
Network (MLPCN), 69, 101, 493–494, 536
MLPCN program, 477–478Molecular Libraries Program (MLP),
536–537Molecular Libraries Screening Center
Network (MLSCN), 79, 101, 144, 453, 536
Molecular Libraries Small Molecule Repository (MLSMR), 453, 465, 467
Molecularly targeted drugs, validated assays for, 141
Molecular probes, 112Molecular target assays, 108–109Monoclonal antibodies, 624, 625–626Monsanto, 646More Medicines for Tuberculosis (MM4TB)
project, 308Morrill Act, 5–6Multinational companies (MNCs)
balance between, 180partnering in emerging market, 178–179
Multiple myeloma, 627, 629, 630, 634, 642Multiple sclerosis (MS), 393–394, 537Multipliers, 23
INDEX� 703
Muscular Dystrophy Association (MDA), 595
Mutant-HTT-dependent changes, 425Mutuality and collaboration, 13MVA-based vaccine, phase 1 studies for,
188Myelin, 385, 388, 389, 393–394Myelin Repair Foundation (MRF), 385–410
Accelerated Research Collaboration™ (ARC™) model, 385–410
Myocardial perfusion, 267, 275–276Myogenics, 627, 631, 632, 636
Nanodispensing, 41Natco Pharma, 179–180National Autonomous University of Mexico,
28National Cancer Institute (NCI), 110–111,
135, 634Cancer Imaging Program, 141Cancer Therapy Evaluation Program
(CTEP), 138Clinical Trials Cooperative Group
Program, 138collaboration with ProScript, 633early development resources, 140–141IP and data rights for CBC development
phase, 144–145natural products collection, 137NExT Program, see Experimental
Therapeutics (NExT) ProgramNSC program, 136RAND (Rapid Access to NCI Discovery
Resources) program, 137Rapid Access to Intervention Development
(RAID) Program, 136–137, 140somatic cell line panel, 644
National Center for Advancing Translational Sciences (NCATS), 207, 536, 673
National Center for Research Resources (NCRR), 117
National Center for the Advancement of Translational Sciences (NCATS), 454
National Collaborative Research Infrastructure Strategy (NCRIS), 541
National Health Service (NHS) Trust, 566–567, 572
National Institute for Health and Care Excellence (NICE), 213, 216
National Institute of Pharmaceutical Education and Research (NIPER), 163
National Institutes of Health (NIH), 58, 67, 324, 326, 536, 666
Cancer Genome Atlas project, 70Clinical and Translational Science Awards,
69, 100Molecular Libraries Program, see
Molecular Libraries Program (MLP)National Center for Advancing
Translational Sciences (NCATS), 673“New Pathways to Discovery” initiative,
453Roadmap initiative, 69SBIR/STTR program, 328support for academic HTS, 78–79translational research initiatives, 100
National Institutes of Health Small Molecule Repository, 493
National resources and institutional practices, 88
National Science Foundation (NSF), 577National Service Center’s (NSC) screening
program, 136Nation Evolved Projects (NEPs), 181Natural products
collection of NCI, 137drug discovery, 164importance of, 82vs. synthetic compounds, 82–83
Neglected diseasescategory of, 375–377complex diseases, 398geographical distribution, 370open source model, 369, 371, 375–379,
380pharma players, 375–379tropical, 376
Negotiation, licensing agreement, 600–601Network-based phenomena, 303New chemical entities (NCEs)
approval and R&D expenditures, 224approvals from 1982 to 2012, 31–32attrition rate, 47
New drug approvalsand R&D expenditures, 225societal welfare through, 613
New drug development, engines of, 456
704� INDEX
New Millennium Indian Technology Leadership Initiative (NMITLI), 180–183
New molecular entities (NMEs), 669approved by FDA, 32, 38, 342per year vs. total R&D spending, 324rate of successful submissions of, 500
New technology, 597–600New Zealand, 152Nexavar, 179Next-generation sequencing (NGS)
technologies, 36NF-κB activation, 630–631NIH Chemical Genomics Center (NCGC),
116NIH Molecular Libraries Assay Development
for HTS Initiativebiological assay development, 102impact of, 105–109
community engagement and interest, 107
molecular target assays, 108–109phenotypic assay projects, 108–109public interest, 106signal detection methods, 107–108success rate for grant applications, 107supplement programs, 107
pilot phase, 101project proposal, 102–105proposal evaluation, 103–104Track program guidelines, 102
NIH Roadmap initiative, 69–70, 536for Medical Research, 79, 132Molecular Libraries Initiative, 100, 454,
536“New Pathways to Discovery” initiative,
453Prebys Center, 455, 458, 463
Nodes, factors and considerations between, 471
Noncontact liquid transfer, 460Nonindustrial drug discovery programs,
159–160in BRIC countries, see BRIC countries,
drug development activities acrossNonmarket collaboration, 657Nonpatentable knowledge, commercializing,
240–241Nonprofit models, 27–28
Nonprofit organizations, 27–28, 248SRI International, 248
Nordion Inc., 271–274Norms, and collaboration, 13Novartis, 48, 180, 370
artemisinin-based combination therapy, 523
collaboration with University of California, 646
Delphi approach, 217move to share genomics research, 610
Novartis Institute for Tropical Diseases (NITD), 524
NSC 609395, see Halichondrin B
Office of Civil Rights (OCR), 666Office of Human Research Protections
(OHRP), 666Office of the National Coordinator for Health
Information Technology (ONC HIT), 673
Off-patent drugs, 68Open access, 257Open business models, 57–58, 61Open data sharing, 670Open door partnership, 270–271Open drug discovery programs, chemical
consultation in, 358–359Open innovation, 500, 609
concepts, 255definition, 256, 257importance of, 335large companies, 93–94vs. open access, 256
Open Innovation Drug Discovery Platform, 208
Open Innovation Drug Discovery Program, 329
Open innovation model, 256, 624collaboration with external partners, 336crowdsourcing, 257, 259–260incubators, 258, 261, 262industry on campus, 260–261precompetitive consortia, 258, 261–263strategic alliances, 258, 260
Open PHACTS consortium, 507Open screening program, 136Open source, 26–27, 257, see also Open
source models
INDEX� 705
Open source biotechnology platforms, 26–27Open source consortium
EU-OpenScreen, 70IGC, 70NIH Roadmap initiative, 69
Open Source Drug Discovery (OSDD), 26–27, 171, 181–182, 184, 208
fundamental principle governing, 184philosophy, 182, 184
Open Source Initiative, 25Open source models, 25
in biomedical science, 371–374, 379–381drug discovery, Human Genome project,
25Torvalds’ approach, 371
Open Source Science Project, 257Open source software development, 371
and pharmaceutical research, dissimilarities between, 25–26
Organizational autonomy and collaboration, 13–14, 17
Orlando Medicinal Chemistry Facility, 468Orphan-designated products, 349Orphan Drug Act of 1983, 349Oswaldo Cruz Foundation (Fiocruz), 164Out-of-pocket clinical period costs, 362
for drugs approved for rare diseases, 206for investigational compounds, 224
Outsourcing, 657vs. innovation sourcing, 256strategies, 500
Parkinson’s disease, 428Partnering, guiding principles for, 334–335Partnership Continuum, 89, 96Partnership for Cures, 124Pasteurian vision, 437–438, 440, 443–445Pastorian, 443–444Patent, see also Patent system
budget, 592–593cliffs, 71, 180, 653condition for obtaining, 237definition of, 237expiration, 24, 32, 127, 342, 452, 479, 624portfolio, strategic investments in, 581protection, 6, 26, 127, 237, 239–241, 334,
343, 347–349, 489, 586, 587, 615rights, 60, 268, 333, 342, 347, 361, 372,
377, 398, 585
Patent system, 239–240“best mode” disclosure, 591biomarkers, 589budget, 592–593derivation proceedings, 592economic rationale of, 333file system in, 591issues surrounding, 26limits damages, 592linked to innovation, 26patenting basics, 585–587prior user rights, 591prosecution fees, 591reforms, 590–592third party challenges, 592
Patient-Centered Outcomes Research Institute (PCORI), 672
Patient goals, 675Patient groups, 208Patient Impact Initiative (PII), 124, 125, 127Patient Protection and Affordable Care Act,
327Patient-Reported Outcomes (PROs), 673PD2 Initiative, 63Pennsylvania Biotechnology Center (PBC),
342, 344, 351–352Pennsylvania Drug Discovery Institute
(PDDI), 341, 344–346Pennsylvania State University Keystone Edge
program, 91–92Pfizer, 68, 75–77, 198, 329, 370
Biotherapeutics and Bioinnovation Center, 646
Centers for Therapeutic Innovation (CTI), 63
Indications Discovery Unit (IDU), 117, 129Pharma–academia collaborations, see
Academia–pharma collaborationsPharmaceutical companies, see also names of
specific companiesattempt to redesign, 201–202closed business models, 57on compound repositioning, 129–130economic recession impact on, 58innovation challenges, 59market-access challenge, 213–214open business models, see Open business
modelsreturn-on-investment problems, 59
706� INDEX
Pharmaceutical Company Consortium, 128Pharmaceutical conundrum, 322–323Pharmaceutical industry
blockbuster forecasting, 203, 210, 324, 338, 469
in Brazil, 163–165challenges to, 197, 624
cost, 198downsizing of personnel, 341, 342negative return on R&D, 199short-term priorities, 199
in China, 166–168ethics, 202, 204evolution of, 33implosion of, 344in India, 161–163innovation in, see Innovationintegrated operating model, 500job opportunities, 223–224, 499landscape, 178outsourcing strategies, 500portfolio management approaches, 204,
210in Russia, 168–169stagnation, 451–452substantial contraction of, 342transformation of, 199–200trust issues of patients and public
regarding, 668–669Pharmaceutical innovation, see InnovationPharmaceutical patent life cycle, 239Pharmaceutical research
nonprofit organizations, see Nonprofit organizations
and open source software development, dissimilarities between, 25–26
Pharmaceutical Research and Manufacturers of America (PhRMA), 223
Pharmacodynamic assay development, 144Pharmacodynamics, 136, 140, 426Pharmacokinetics, 136, 140, 228, 323, 426Pharmacology facility, 468PharmaTrain consortium, 503Pharma Venture Capital Fund, 177Phase 1 clinical trials, 163, 228–229Phase 2 clinical trials, 213, 217–218, 229Phase 3 clinical trials, 205, 229Phase 4 clinical trials, 230Phenotypes, 428, 648
Phenotypic assay projects, 108–109Phenotypic Drug Discovery (PD2) Initiative,
63, 537–538Phenotypic screening, 38–39, 534, 537, 539Phosphoinositide-3-kinase (PI3K) pathway
compounds, 309Physical library of discontinued clinical
compounds, 128Pipeline, drug, 49, 58, 60, 67, 68, 139, 143,
166, 204, 307, 448, 469development of, 334–335, 337, 394, 403,
482innovation deficit, 175–176LeukoSite, 635MMV, 523–524, 535, 557net present value of, 199SANOFI, 322value of, 213–219
Plasmodia, 167Poly (ADP-ribose) polymerase (PARP)
inhibitor, 141Positron-emission tomography (PET), 418Postlicensing program, importance of,
605–606Postmarketing trials, 230Prebys Center, 455–478Preclinical assessment, 34, 47–48, 228Preclinical drug discovery, 81–82, 427, 495Precompetitive consortia, 258, 262–263Precompetitive data sharing initiatives, 496Precompetitive drug development, public-
private partnerships for, 496Predictive Safety Testing Consortium
(PSTC), 15, 16Principal investigators (PIs), 390, 391“Principles for Responsible Clinical Trial
Data Sharing,” 674Probe discovery in public domain, 69–70Procter & Gamble (P&G), 94
“Connect and Develop” portal, 259Product development partnerships (PDP),
377Professional alliance and collaboration
management, 263–264“Programmrat” (program council), 282Project and portfolio management, 469–470Project management, 13, 14, 16, 17, 70, 71,
139, 260, 281, 290, 295, 421, 469–470, 474, 509
INDEX� 707
Proof of Concept Centers (POCCs), 328, 341–342, 344, 350, 352, 353
Proof-of-principle (POP) work, 100, 627, 649ProScript, 627, 629, 632, 633, 635, 636, 640,
642bortezomib discovery, see Bortezomib
Prostate Cancer Foundation, 633Proteasome, 630–632Protein Data Bank, 372Protein kinases, 45–46Proteomic database, 377Proteomics, 36Prussia, 4–5PsychoGenics, 426PubChem, 494, 536Public Citizen’s Health Research Group, 669Public policy
initiatives, 649recommendations for changes in, 353
Public–private partnership/collaboration, 323–326
Atazanavir for AIDS, 521–523challenges to, 120, 642–643, 645
budget, 333–334intellectual property, 333legal environment, 334market risk, 332–333
Coartem for malaria, 523–524drug repurposing, 525fundamental characteristics of, 518–519Glivec for CML, 519–521impact on pharmaceutical company, 645industry models for, 329–330insulin isolation and production, 518investments, 646novel approaches, 525for precompetitive drug development, 496reciprocal negative attitude and, 642–643in Singapore, 524–525SNP’s Consortium, 644
Published research, improving quality of, 653–654
Quality control, 189, 190, 660, 683“Quantitative proteomics,” 36Queensland Compound Library (QCL),
541–559benefits of, 557–559capacity in 2008, 549
collaborative research facilitation by, 556design, 548establishment of, 541HTS facilities, 547intended outcomes of, 555IP model development for, 543–546microtiter plate storage, 553microtube storage, 549–551national resource usage, 555–556operating model of, 546–547sample processing unit, 551–553sharing of profits generated by, 542stakeholder involvement in, 542–543workstream, 553–555
Rabies, 440Radiation mitigators, development of, 310Radiation reversal agents, 310Radiopharmaceuticals, 271–272Radiotracer development, 273RAND (Rapid Access to NCI Discovery
Resources) program, 137Rapid Access to Intervention Development
(RAID), 136–137, 628R&D
benefits of, 3costs of unnecessary research, 204–205Indian government funding for, 177mobilization of resources for, 526ranking of industrial sectors, 225role of military in, 171to sales, ratio of, 223traditional approaches to, 609
R&D, collaborativejoint endowment funds for, 185–186supported by DPRP, 184
R&D expenditures, 324inflation-adjusted industry, 224and new drug approvals, 225research charities, 501–502transformation of, 500
R&D investments, 499–500large companies, 93strategies, 675
R&D model, 87, 191, 320, 500R&D productivity, 517
decline in, 324–325, 452, 624strategies for improving, 329, 332
Reaume, Andrew, 76
708� INDEX
Red Cross, 28Rediscovery Research projects, 125–126Reductionist drug discovery, 176–177Regimentation and innovation, 203Regional development, 240, 245, 568, 572Regional economic development initiatives,
347Registered Technology Transfer Professionals
(RTTP), 585REGISTRY, 416Reitz, Allen, 352–353Repositioning, see Drug repositioningReproducibility, 71, 295, 664, 670, 674
of experiment results, 407of phenotypic screens, 39
Reproducibility Initiative, 674Repurposing strategies, drug discovery
through, 67–69, see also Drug repurposing
Research agreement, 272–273Research and development, see R&DResearch charities and drug discovery,
501–502Research-intensive universities, 7–8Reserpine, 190RESOLVE model, 263–264Resource procurement, 14Restructuring in biomedical research, 341Return-on-investment problems, 59Reverse pharmacology model for drug
discovery, 189–190Reyataz, 521Rhodanine screening, 80Risk-averse behavior, 668Roadmap initiative of NIH, 69Rock, Kenneth, 631Romidepsin, 153–154Rosenblatt, Michael, 631–632Rusnano, 169Russia, government-financed drug discovery
in, 160, 168–170
SAFE-T consortium, goal of, 66Sage program, 66San Diego Center for Chemical Genomics,
453San Diego Medicinal Chemistry Facility,
467–468
Sanford-Burnham Medical Research Institute, 454, 476, see also Prebys Center
Sanofi, 204, 209, 320–323, 332, 334, see also Early-to-Candidate (E2C) Access Platform
Sanofi-Aventis, 370Schering-Plough, 198Schizophrenia, 200, 646Scholarly investigations, 612Science Exchange, 658, 659“Science for science’s sake” vs. “science for
society’s sake,” 231, 233–235, 241–243
Scientific Advisory Board (SAB), 391Scientific collaboration
barter system, 656research landscape changes, 656tools to facilitate, 657–658types of, 656, 657
Scientific networking, websites for, 658Scientific Review Board, 568Scottish Academic Health Sciences
Collaboration (SAHSC), 572, 573
Scottish Enterprise (SE), 565, 568Scottish Government Health Directorate
(SGHD), 567Scottish NHS, 567Seeding Drug Discovery Initiative, 77–78,
501Selection-based libraries, 494–495Semafore Pharmaceuticals, 309Sematech, 11Semi-Custom Synthesis On-Line Request
Service (SCSORS), 111Separate but equal partnership, 270Shanghai Institute of Materia Medica
(SIMM), 167Shanghai Institute of Pharmaceutical
Industry, 167–168“Shelved development compounds,” 452SIBRATEC, 163–164Signal generation and detection technologies,
457Sildenafil, 68Singapore, 524–525Single-dose studies, 228
INDEX� 709
Single Nucleotide Polymorphisms Consortium (SNP’s Consortium), 15–16, 644
Sinopharm, 167–168, 171Small- and medium-sized enterprises
(SMES), 94Small Business Innovation Research (SBIR)
grants, 328, 351, 594–596Small Business Innovation Research Initiative
(SBIRI), 186Small Business Technology Transfer (STTR)
program, 328, 351, 594–596Small interfering RNAs (siRNAs), 417Small Molecule Repository (SMR), 536Small molecule, 164–165, 279, 288, 306,
311, 501, 502, 505, 509, 533, 540–541, 602, 636
challenge in selection of, 533collections, 493drug manufacturing, 164–165GMP scale-up for, 141internal rate of return, 337libraries, 490–492, 494, 535–537modulators, 534probes, 110–111screening campaigns, 101–102, 106workstream from submission of, 554
Small pharma/biotech companies, 207Smart State Research Facility Fund (SSRFF),
541–542Society for Biomolecular Screening (SBS),
76Society for Laboratory Automation and
Screening directory, 489–490Special economic zones (SEZ), 179SRI International, 248Staffing, 584–585Stanford–India Biodesign (SIB) program,
187Stanford Research Institute (SRI), 27Stanford v. Roche, 583–584Start-up biotechnology company, 347
ALS Biopharma, LLC, 352Fox Chase Chemical Diversity Center, Inc.,
352licensing, 602–605
Staurosporine, 46, 47Steering Committee, 568
Stem cell-based therapies, 63Strategic alliances
professional management of, 263–265between Sanford-Burnham and Mayo
Clinic, 477–478, 480–482Structural biology-based drug discovery
organizations, 501Structural Genomics Consortium (SGC), 67Structure–activity relationship (SAR) studies,
110–111Super-resistant bugs, campaigns about, 669Super Science Initiative (SSI), 541SWOT analysis, 280–282Synthetics compounds vs. natural products,
82–83
TAG4 barcoding array, 492Target–activity relationships (TARs), 39Target identification and target validation, 43
chemogenomic approaches, 36–38in drug development process, 226–227gene microarray chips, 35–36genomics, 35NGS technologies, 36phenotypic screens, 38proteomics, 36
Tata Motor, 22TCGA, see Cancer Genome Atlas project,
The (TCGA)Technological innovations, 34, 305
approach to leveraging, 32–33chemical biology, see Chemical biologycost–benefit assessment of, 41drug innovation with, 32for hit identification, 39–42requirements, 41for target identification and target
validation, 36–38Technology
alliance portfolio, 336commercialization, paradigm shift in, 610key ingredients for evaluating, 326
Technology and Innovation Centers, 248–249
Technology innovation, 496Technology push and market pull,
commercial contrast between, 231, 233
710� INDEX
Technology transfer, 243–244and cancer therapeutics pipeline, see
Cancer therapeutics pipeline and technology transfer
and entrepreneurship, promoting, 349–351marketing, 597process of, 347role in industry collaborations, 615–616,
618–619“valley of death” in, 594
Technology transfer office (TTO), 71, 349, 390, 400, 579–581, 646
and academic entrepreneurship, 611–613activities, 579–582barriers to success of, 246–247in Europe, 245–246functions of, 222, 244newly identified disease target, 587, 590obstacles to, 611performance measurement of, 612philosophy of, 579–582risk tolerance and financial support matrix
for, 599, 599staffing, 584–585TMRI and Wyeth relationship with,
570–571in United States, 244U.S. utility application, 586WARF (Wisconsin Alumni Research
Foundation), 611Tenofovir Gel, safety and acceptability study
of, 188Termination of license agreement, 601–602Thalidomide, 175Therapeutic modalities, selection of, 35Third-party materials, 146Tissue nonspecific alkaline phosphatase
(TNAP) chemical probe ML028, 472–474
TK-inspired drug discovery, 189–190Toxicology studies, 34, 112, 136, 141, 228,
468, 480, 588, 602Traditional Chinese medicine, 176Traditional knowledge (TK), 189–191Traditional Knowledge Digital Library
(TKDL), 189Traditional translational research model,
204Transformational leadership, 14
Translational funding, 593–597push-based model of, 596–597infrastructure, TTO support to, 581SBIR/STTR programs, 594–596state governments, 596scientific vs. commercial milestones,
596–597Translational Medicine Research
Collaboration (TMRC)accomplishments, 571–572business premise, 566–568collaboration with Wyeth, 568–569financial aspects, 572medical schools, 566NHS Trusts, 566–567overview, 565–566participation in, 574project selection, 569–570Scottish Enterprise, 568stakeholders in, 569unrealistic financial expectations, 573
Translational Medicine Research Initiative Ltd. (TMRI), 565
coordinated project leadership approach, 571–572
financial aspects, 572governance structure of, 570Wyeth relationship with, 570–571
Translational research, 386, 627academic scientists participation in,
629–630adoption and funding of, 99ARC model de-risks discoveries,
407–409challenges to, 51, 200core model, 634definition, 628de-risks discoveries, 407–409funding gap for, 628future perspectives of, 51impediments encountered by, 628improving, 649initiatives launched by NIH, 100model for path of, 99–100Myelin Repair Foundation, 405re-focus on patient needs, 671–672
Translational research modeldisruptive nature of, 200focus on breakthrough science, 199–200
INDEX� 711
inherent risk associated with, 200weaknesses of, 200
“Translational triangle,” 471Transparency Life Sciences®, 61, 208Trust issues, 668–669Tuberculosis (TB), 375, 379
CSIR NMITLI program for therapeutics against, 181
drug discovery, collaborative, 306–308FDA-approved drugs, 377
Tu, You-You, 167
UIDP, 128Ultrahigh-throughput screening (uHTS)
system, 458–459, 461Uniform Biology Material Transfer
Agreement (UBMTA), 419United States
economy, university research impact on, 7–8
health expenditure distribution, 238history of university research in
impact on U.S. economy, 7–8intellectual property, 6–7investments in research, 6“land grant” universities, 5Morrill Act, 5–6
universities’ TTOs/TLOs in, 244Universities, 8–9
“one-stop shops” for industry engagement, 95–96
role in collaborations, 615–616role in knowledge economy, 610role in start-ups, 604–605
University champions and individual corporate, 617–618
University–industry (U-I) collaborationchallenges to, 617and conflict of interest, 92–93and export control, 93factors determining success of, 617–618government support for, 90–91guiding principles for, 88initiatives to transform
“free agent” model, 91Keystone Edge program, 91–92MN-IP, 92
mission of, 88phases of, 89
strategies for building, 95–96and university technology transfer,
618–619U.S. corporate investments in, 87
University–Industry Demonstration Partnership (UIDP), 88, 94–95
University intellectual assets, TTO protection to, 580
University IP, 238University of Arizona College of Medicine,
28University of California, Los Angeles
(UCLA), 310–311University of California, San Diego, 7–8University of Cologne, 290–291, see also
Bayer–University of Cologne collaboration; Graduate program in pharmacology and experimental therapeutics
University of Medicine and Dentistry of New Jersey (UMDNJ), 596
University of Michigan (UM), 596University of Ottawa Heart Institute (UOHI),
271and Nordion Inc., 272–274
University patent application, life of, 585University research, 6–8, 321, 331
in Prussia, 4–5in the U.S., 5–8
University technology transfer, see Technology transfer
University technology transfer office, see Technology transfer office (TTO)
Vaccination, immunity, 440Vaginal microbicide, safety and acceptability
study of, 188“Valley of death,” 136, 163, 242, 348–349,
386–387bridging, 326–329cash flow, 325in university technology transfer, 594, 612
“Value-based” payments, 672“Value-based pricing” tactics, 669Value-driven drug development
adaptive design, 217–218collaboration, 215–216, 220compound differentiation, 215governing body, 219
712� INDEX
patient needs identification, 215patient segmentation, 215, 218performance culture, 219phase 2 and phase 3 study, 217–218regulators, HTAs, and payors, 215–216risk mitigation by, 214target product profile, 217team and leadership capabilities, 218–219
Vanderbilt University, and Janssen Pharmaceuticals, collaboration between, 646
Venture capital investment, 327–328Venture capitalists, 247–248Vertex, 208Virtual research institutes, 658–659“Visiting Scientist Scheme,” 509–510Vocational field exploration, 291Volunteer health associations, 28–29
WARF (Wisconsin Alumni Research Foundation), 611
Web-based database technology, 304, 305
Wellcome Foundation, 567Wellcome Trust, 77–78, 501Wellcome Trust–DBT program, 187Windows, 371World Health Organization (WHO), 162,
375, 447on artemisinin-based combination
therapies, 523“collaborating centers,” 538definition of health, 174funding to, 524neglected diseases list, 375smallpox eradication program, 538
Wyeth Pharmaceuticals, 568at Core Laboratory, 572initial relationship with TMRI, 570–571TMRC collaboration with, 568–569
Xigris®, 203
YAC models, 425
Zidovudine, 522
Value-driven drug development (cont’d )
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