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 )