Genomics and World Genomics and World Health: Navigating the Health: Navigating the

Information JungleInformation Jungle

From DNA Sequence to Human From DNA Sequence to Human WelfareWelfare

Sources: World Development Report 1993 (World Bank); World Health Organization 1990

Percent of population over 65

Sources of Health R&D Funding 1998

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

40.0

Government, advanced andtransition economies

Government, developingeconomies

Private pharmacueticalR&D

Private nonprofit

Source: Global Forum for Health ResearchMonitoring Financial Flows for Health Research 2001

Health Research Health Research FundingFunding

19407%

38%

55%

1965

68%

8%

24%

1998

46%

5%

49%

Industry

Philanthropy

Government

0

100

200

300

400

500

600

700

USA

Japa

n UKGerm

any

Canada EC

Netherl

ands

France

Sweden

SNP Con

sortiu

m

China

Russia

Korea

Estonia

Belgium

Austra

lia

Government-nonprofit Genomics Research Funding 2000($ million)

Genomics Funding: Genomics Funding: private>publicprivate>public(Year 2000)(Year 2000)

Genomics research funding($ million US)

1,653

2,061

900

0

500

1,000

1,500

2,000

2,500

Gov&nonprofit Genomics firms Pharma&biotech

Source: World Survey of Funding for Genomics ResearchStanford in Washington Programhttp://www.stanford.edu/class/siw198q/websites/genomics/

Government-nonprofit Genomics Funding per GDP(times 1000)

0.000

0.050

0.100

0.150

0.200

0.250

0.300

0.350

0.400

0.450

0.500

Estonia UK

Sweden

Netherl

ands

Japa

nGerm

any

USAFran

ceBelg

ium EC

Korea

Canad

aRus

siaAus

tralia

China

Genomics firms with publicly traded stock

0

20

40

60

80

Year# firms 8 10 14 19 25 28 73

1994 1995 1996 1997 1998 1999 2000

0102030405060708090

100

1994 1996 1998 2000

$B market value

Data through Year 2000Market Cap figures for end of yearNumber of firms at end of each year

Growth of Commercial Genomics

R&D v Market CapR&D v Market CapSum of R&D Expenditures for 15 Genomics Firms

-

200

400

600

800

1,000

1,200

1,400

1,600

1,800

2000 2001 2002

Year

R&D

(Mill

ion

US$)

-

10,000

20,000

30,000

40,000

50,000

60,000

Mar

ket C

ap (M

illio

n U

S$)

Total R&D ExpendituresTotal Market Cap

Number of Patents Retrieved by the Search Algorithm vs. Year of Issue

0

500

1000

1500

2000

2500

3000

3500

4000

4500

500019

7119

7219

7319

7419

7519

7619

7719

7819

7919

8019

8119

8219

8319

8419

8519

8619

8719

8819

8919

9019

9119

9219

9319

9419

9519

9619

9719

9819

9920

0020

0120

0220

03

Year of Issue

Num

ber o

f Pat

ents

Ret

rieve

d by

the

Sear

ch A

lgor

ithm

Source: Io Nami-Wolk and LeRoy Walters, DNA Patent Database, February 2004

Preliminary Data about the 30 Entities Holding the Largest Numbers of DNA-Based Patents (as of 02-05-04)

0 100 200 300 400 500 600 700 800 900 1000

University of CaliforniaUnited States Government

GlaxoSmithKlineIncyte Genomics

AventisChiron

GenentechBayerWyeth

NovartisMerck

University of TexasHuman Genome Sciences

AmgenJohns Hopkins University

AppleraMassachusetts General Hospital

Novo NordiskHarvard University

PfizerStanford University

LillySalk Institute

Cornell UniversityMIT

AffymetrixColumbia University

University of WisconsinWashington University

University of Pennsylvania

Entit

y N

ame

Number of DNA-Based Patents

Academic Institution Government For Profit Firm

This research was supported by Grant No. R03 HG02683-02, “DNA Patent Policies at Academic Institutions,” from the National Human Genome Research Institute, NIH, and Grant No. DE FG 02 01ER63171, “Enhancing the DNA Patent Database,” from the U.S. Department of Energy. Io Nami Wolk 03-03-04

USA

JAPANFRANCE

UKGERMANY

OTHER

USA 80.0%Japan 7.1%France 2.4%UK 2.1%Germany 1.9%Other 7.1%

Ownership (assignee country) of 1078 DNA-based patents 1980-1993

Source: Stephen McCormack and Robert Cook-DeeganDNA Patent Database, August 1999, dnapatents.georgetown.edu

Patent assignees

US Gov’t6%

Public University

9%

Private University

14%

NonprofitResearchInstitute

13%

Other6%

For-ProfitCompany

52%

Source: Stephen McCormack and Robert Cook-DeeganDNA Patent Database dnapatents.georgetown.edu

Distinctive Features of Patents in Distinctive Features of Patents in Pharmaceuticals and BiotechPharmaceuticals and Biotech

Patent protection longer and stronger than Patent protection longer and stronger than other other ““high technologyhigh technology”” sectorssectorsDrug discovery highly dependent on Drug discovery highly dependent on academic researchacademic research

1/4 of products depend on academic research1/4 of products depend on academic researchAnother 1/4 would be long delayed without itAnother 1/4 would be long delayed without itMore patents held by academic institutionsMore patents held by academic institutionsMore citation of academically held patentsMore citation of academically held patentsPatents cite academic science articlesPatents cite academic science articles

Role of patentsRole of patentsImportant for private development of therapeutic Important for private development of therapeutic pharmaceuticals (EPO, pharmaceuticals (EPO, tPAtPA, GM, GM--CSF)CSF)

Is there another path?Is there another path?——not clearnot clearNot needed for tools arising from publicly funded Not needed for tools arising from publicly funded research (Cohenresearch (Cohen--Boyer, Axel) Boyer, Axel) but does but does generataegeneratae research funding for universitiesresearch funding for universitiesCurrent debate: diagnosticsCurrent debate: diagnosticsCan patents hinder innovation sometimes?Can patents hinder innovation sometimes?

AnticommonsAnticommons——HellerHeller--Eisenberg Eisenberg Cost (AxelCost (Axel--2003, Cox inhibitors)2003, Cox inhibitors)——RaiRai--Eisenberg Eisenberg

Obstacles to information flowObstacles to information flow

Securing scientific priority Securing scientific priority Pursuing worldwide patent rights*Pursuing worldwide patent rights*Signing nondisclosure agreementsSigning nondisclosure agreementsRestrictions on data access or control, or Restrictions on data access or control, or on publication (funding agreements)on publication (funding agreements)

*only item pertaining directly to patents*only item pertaining directly to patents

Sir John Sulston and the Open Genomics of the Worm

The Worm ProjectThe Worm Project

Coming: Rachel Ankeny: The Conqueror Worm

Another Success

The Third WayThe Third Way

Celera: Data by subscription

Spectrum of data accessSpectrum of data accessBermuda rules: 24Bermuda rules: 24--hour data releasehour data releaseMerck EST database,Merck EST database, cancer Genome Anatomy cancer Genome Anatomy Program, Mammalian Gene Collection, mouse Program, Mammalian Gene Collection, mouse mutant mutant collectionscollectionsApply for patent and abandon: SNP Apply for patent and abandon: SNP ConsortiumConsortiumCeleraCelera: data by subscription: data by subscriptionUniversities: genes for a license feeUniversities: genes for a license feeIncyteIncyte: high: high--priced multilateralismpriced multilateralismPharmaPharma: publish occasionally: publish occasionallyHGSHGS: trade secrecy plus patent: trade secrecy plus patent

Yellow = private R&D $; White = public $

The practical value of open The practical value of open genomicsgenomics

For the advancement of knowledgeFor the advancement of knowledgeFor technological developmentFor technological development

information flow (e.g., to companies) and information flow (e.g., to companies) and network efficienciesnetwork efficienciespursuing diverse leadspursuing diverse leadsdistributed allocation of workdistributed allocation of work

Efficient information clearinghouse in the Efficient information clearinghouse in the ““national innovation systemnational innovation system”” (how about (how about internationalinternational innovation system?)innovation system?)

Changing academic normsChanging academic normsUniversities seek patentsUniversities seek patentsTechnology licensing officesTechnology licensing officesPinnacles of excellence sustain academic R&D Pinnacles of excellence sustain academic R&D funding (biotech star system)funding (biotech star system)Hot science attracts private capital, as well as Hot science attracts private capital, as well as federal grantsfederal grantsTechnology translation through university Technology translation through university startupsstartupsFederally funded R&D as an exploitable Federally funded R&D as an exploitable resourceresource

Opening Information FlowOpening Information Flow

Use patents to enable earlier disclosure of Use patents to enable earlier disclosure of data (after filing patent applications)data (after filing patent applications)Research exemptions into licensing Research exemptions into licensing agreementsagreements““Humanitarian useHumanitarian use”” exemptionsexemptionsRein in investigators when they get too Rein in investigators when they get too greedygreedy

Duke Center for Public GenomicsDuke Center for Public Genomics

““Open genomicsOpen genomics”” ((RaiRai--Law School)*Law School)*Alternatives to exclusivity (Alternatives to exclusivity (ReichmanReichman/Lewis/Lewis--Law Law and Fuqua)*and Fuqua)*Case histories of DNA sequencing and Case histories of DNA sequencing and microarraymicroarray technologies (technologies (CookCook--DeeganDeegan))DNA Patent Database (DNA Patent Database (WaltersWalters--Georgetown)Georgetown)Interpretative and cultural studies (Interpretative and cultural studies (WaldWald/Mitchell/Mitchell--English)English)

* Initial case studies are relevant for access to * Initial case studies are relevant for access to essential medicines in resourceessential medicines in resource--poor countriespoor countries

Confluence and Confluence and Contrast:Contrast:Infectious Disease Burden and Infectious Disease Burden and

BiodefenseBiodefense

Pathogen sequencing Pathogen sequencing and and microarraysmicroarraysPlatform technologies for Platform technologies for vaccine and biologics and vaccine and biologics and for drug screeningfor drug screeningDrug and vaccine Drug and vaccine ““targetstargets”” in profusionin profusionEmerging infectionsEmerging infections

Many pathogens not on Many pathogens not on ““select agentselect agent”” priority listpriority listFocus on vaccines and Focus on vaccines and treatments for rich treatments for rich countries and soldierscountries and soldiersHealth infrastructure in Health infrastructure in resourceresource--poor countries poor countries not on the agendanot on the agenda

Genomics and World HealthGenomics and World HealthDust off April 2002 reportDust off April 2002 reportFully engage those directly familiar with infectious disease Fully engage those directly familiar with infectious disease catastrophescatastrophesPull out key examples and policies relevant to vaccines, Pull out key examples and policies relevant to vaccines, drugs and biologics in resourcedrugs and biologics in resource--poor countriespoor countriesUpdateUpdate–– BiodefenseBiodefense resources: Sanger Institute, Broad Institute, TIGR, etc.resources: Sanger Institute, Broad Institute, TIGR, etc.–– TRIPSTRIPS–– Alternative development frameworks (Alternative development frameworks (““virtual virtual pharmapharma””))–– Technology Managers for Global HealthTechnology Managers for Global Health–– Open sourceOpen source–– Alternatives to patenting (liability rulesAlternatives to patenting (liability rules——””use now, pay lateruse now, pay later””))

Explicitly link to Explicitly link to ““access to essential medicinesaccess to essential medicines””Include, but do not obsess about, intellectual property Include, but do not obsess about, intellectual property rights in products (Nuffield, UK Commission, etc.)rights in products (Nuffield, UK Commission, etc.)Do focus on information flow in research and developmentDo focus on information flow in research and development