Preliminary Data on Preliminary Data on U.S. DNA-Based U.S. DNA-Based

Patents and Plans for a Patents and Plans for a Survey of Licensing Survey of Licensing

PracticesPractices

Robert Cook-Deegan, LeRoy Walters, Derrick Pau, Bi Ade, Robert Cook-Deegan, LeRoy Walters, Derrick Pau, Bi Ade, Stephen McCormack, Janella Gatchalian, and Richard Stephen McCormack, Janella Gatchalian, and Richard BurgessBurgess

Kennedy Institute of Ethics, Georgetown UniversityKennedy Institute of Ethics, Georgetown University

Collaborators are involved in the empirical studies but do not Collaborators are involved in the empirical studies but do not necessarily concur with analysis or conclusionsnecessarily concur with analysis or conclusions

ThemesThemesTrends in US DNA-based Trends in US DNA-based

patentspatentsWhy licensing is where the Why licensing is where the

action isaction isPublic-Private interactions in Public-Private interactions in

genomics, using DNA Patent genomics, using DNA Patent DatabaseDatabase

What is a DNA-based Patent?What is a DNA-based Patent?

One or more claims based on DNA or One or more claims based on DNA or RNARNA

Algorithm initially developed by Algorithm initially developed by James Martinell, USPTO, for OTAJames Martinell, USPTO, for OTA

Revising search algorithm, doing Revising search algorithm, doing sensitivity analysis, improving free sensitivity analysis, improving free public acesspublic acess

Search algorithmSearch algorithm(November 2002)(November 2002)

Patent classesPatent classes 047 (plant), 119 (animal), 260 (food), 426 (organic), 435 047 (plant), 119 (animal), 260 (food), 426 (organic), 435

(molecular biology and microbiology), 536/22.1 through (molecular biology and microbiology), 536/22.1 through 536/25.5 (organic compounds/nucleic acids), and 800 536/25.5 (organic compounds/nucleic acids), and 800 (multi-celled organisms)(multi-celled organisms)

TermsTerms Antisense, cDNA, centromere, deoxyoligonucleotide, Antisense, cDNA, centromere, deoxyoligonucleotide,

deoxyribonucleic, deoxyribonucleotide, DNA, exon, gene or deoxyribonucleic, deoxyribonucleotide, DNA, exon, gene or genes, genetic, genome or genomic, genotype, haplotype, genes, genetic, genome or genomic, genotype, haplotype, intron, mtDNA, nucleic, nucleotide, oligonucleotide, intron, mtDNA, nucleic, nucleotide, oligonucleotide, oligodeoxynucleotide, oligoribonucleotide, plasmid, oligodeoxynucleotide, oligoribonucleotide, plasmid, polymorphism, polynucleotide, polyribonucleotide, polymorphism, polynucleotide, polyribonucleotide, ribonucleotide, ribonucleic, recombinant DNA, RNA, mRNA, ribonucleotide, ribonucleic, recombinant DNA, RNA, mRNA, rRNA, siRNA, snRNA, or tRNA, ribonucleoprotein, hnRNP, or rRNA, siRNA, snRNA, or tRNA, ribonucleoprotein, hnRNP, or snRNP, SNPsnRNP, SNP

Terms tested and rejected after sensitivity Terms tested and rejected after sensitivity analysisanalysis

Seq. ID, sequence, atg*, telomere, dideoxy*Seq. ID, sequence, atg*, telomere, dideoxy*

Source: LeRoy Walters, DNA Patent Database, December 2001

DNA-Based U.S. Patents, 1970-2001

0

1000

2000

3000

4000

5000

600019

70

1971

1972

1973

1974

1975

1976

1977

1978

1979

1980

1981

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

Year

Nu

mb

er

of

DN

A P

ate

nts

Note: searches done using Dec 2001 algorithm

Growth of DNA PatentsGrowth of DNA Patents

Patents IssuedPatents Issued

1970s1970s 292 292

1980s1980s 1,869 1,869

1990s1990s 19,08219,082

DPD Patent Coding SheetDPD Patent Coding Sheet

CategorizesCategorizes Inventor information (#, country of origin)Inventor information (#, country of origin) Patent filing informationPatent filing information Assignee information (#, country of origin, type Assignee information (#, country of origin, type

of organization)of organization) US government involvement (Bayh-Dole)US government involvement (Bayh-Dole) Types of claims (cDNA [gene], vector, Types of claims (cDNA [gene], vector,

transgenic animal, vaccine, etc.)transgenic animal, vaccine, etc.) DNA-based patents issued between 1980-1993 DNA-based patents issued between 1980-1993

were manually coded into the DPDwere manually coded into the DPD Patent Coding SheetPatent Coding Sheet

Patent assignees

US GOV’T 6%

FOR-PROFITCOMPANY

52% PUBLIC UNIVERSITY

9%

PRIVATE UNIVERSITY

14%

NON-PROFIT RESEARCH INSTITUTE

13%

OTHER

6%

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

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 1068 DNA-based patents 1980-1993

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

0

50

100

150

200

250

300

350

400

450

500

US

Gov UC

Incy

teC

hiro

nG

laxo

-SK

Gen

ente

chA

mge

nA

vent

isN

ovo

AH

PL

illy

Hop

kins

Har

vard

Hof

fman

n-L

RM

erck

MIT

Nov

arti

sSt

anfo

rdH

GS

Patents in DNA Patent Database1980-1999 <dnapatents.georgetown.edu>

Data through end of December 1999

Why study licensing?Why study licensing?

Move debate beyond patentabilityMove debate beyond patentability Presumption that patent law should Presumption that patent law should

apply to all kinds of inventions equallyapply to all kinds of inventions equally Question becomes how patent rights Question becomes how patent rights

are exercised, not whether they existare exercised, not whether they exist

What if EPO not patented?What if EPO not patented?

What if Cohen-Boyer licensed What if Cohen-Boyer licensed exclusively?exclusively?

Gedanken experiment: Sanger Gedanken experiment: Sanger sequencing patentsequencing patent

License with provision that sequence License with provision that sequence data be publicly disclosed per Bermuda data be publicly disclosed per Bermuda rulesrulesNo policy change in high-throughput No policy change in high-throughput sequencing centerssequencing centersWhat would Incyte, Human Genome What would Incyte, Human Genome Sciences, Celera, etc., have done?Sciences, Celera, etc., have done?What would universities do with other What would universities do with other sequences outside HGP?sequences outside HGP?

How Do We Know Universities Are How Do We Know Universities Are Important?Important?

Biotech/pharma highest fraction of Biotech/pharma highest fraction of products and services dependent on products and services dependent on academic research (Edwin Mansfield academic research (Edwin Mansfield surveys)surveys)

Patent citation literature (Cockburn, Patent citation literature (Cockburn, Henderson, Jaffe, Trajtenberg)Henderson, Jaffe, Trajtenberg)

Literature citation studies (Narin)Literature citation studies (Narin) Spillovers (Gambardella, Henderson-Spillovers (Gambardella, Henderson-

Cockburn)Cockburn) Synthesis (Nelson, Mowery)Synthesis (Nelson, Mowery)

What’s funny about universities?What’s funny about universities?

Mission = research + teachingMission = research + teaching Some publicly owned, all publicly Some publicly owned, all publicly

supported for researchsupported for research Don’t make productsDon’t make products Do sell services, run component Do sell services, run component

businessesbusinesses Take money > make moneyTake money > make money What to maximize? Net revenue or What to maximize? Net revenue or

net social good?net social good?

Funding Sources for Licensing Funding Sources for Licensing SurveySurvey

U.S. Department of EnergyU.S. Department of Energy National Human Genome Research National Human Genome Research

Institute, U.S. National Institutes of Institute, U.S. National Institutes of HealthHealth

Lori Pressman to do survey; who has Lori Pressman to do survey; who has done AUTM surveysdone AUTM surveys

Licensing SurveyLicensing Survey

24 US and Canadian “academic” 24 US and Canadian “academic” institutions (universities and nonprofit)institutions (universities and nonprofit)

Biggest recipients of US Federal R&DBiggest recipients of US Federal R&D Their U.S. DNA-patent holdingsTheir U.S. DNA-patent holdings Licensing practicesLicensing practices

Complement to Cho/Merz and Complement to Cho/Merz and Mowery/Nelson studiesMowery/Nelson studies

Licensing practicesLicensing practices Exclusive, co-exclusive, non-exclusive Exclusive, co-exclusive, non-exclusive

agreementsagreements Patent clustersPatent clusters Licensing incomeLicensing income Research tools treated differently?Research tools treated differently?

9-10 qualitative case studies of 9-10 qualitative case studies of “interesting” patent clusters or licensing “interesting” patent clusters or licensing practicespractices

Look for patents not reported to federal Look for patents not reported to federal government (cross-check to RaDiUS and government (cross-check to RaDiUS and PubBiomed databases)PubBiomed databases)

Institutions of InterestInstitutions of Interest

Most DNA-based patents:Most DNA-based patents:UC, UTx, Hopkins, Scripps, MassGeneral, UC, UTx, Hopkins, Scripps, MassGeneral,

Harvard, Stanford, Salk, WashU, Columbia, Harvard, Stanford, Salk, WashU, Columbia, MIT, Rockefeller, Cornell, UPenn, UWiscMIT, Rockefeller, Cornell, UPenn, UWisc

High fraction of patents are DNA-basedHigh fraction of patents are DNA-basedSalk, Dana Farber, Baylor, Scripps, Salk, Dana Farber, Baylor, Scripps,

Rockefeller, WashU, Harvard, Jefferson, Rockefeller, WashU, Harvard, Jefferson, MassGeneral, NYU, Yale, Hopkins, Columbia, MassGeneral, NYU, Yale, Hopkins, Columbia, Brigham&Women’sBrigham&Women’s

Valuable Gene PatentsValuable Gene PatentsHuman InsulinHuman InsulinClot-dissolving enzymesClot-dissolving enzymesGrowth FactorsGrowth Factors

– ErythropoietinErythropoietin– White blood cell lineagesWhite blood cell lineages

Gene patent for making Gene patent for making therapeutic proteintherapeutic protein

TechniquesTechniques

Cohen-Boyer rDNACohen-Boyer rDNA Polymerase chain Polymerase chain

reactionreaction 4-color fluorescence 4-color fluorescence

sequencingsequencing Multiplex Multiplex

sequencingsequencing Microarray Microarray

techniquestechniques Gene transferGene transfer

Public domain Public domain technologiestechnologies

Sanger sequencingSanger sequencing Maxam-Gilbert Maxam-Gilbert

sequencingsequencing Monoclonal Monoclonal

antibody antibody productionproduction

DiagnosticsDiagnostics Huntington’s by RFLPHuntington’s by RFLP Cystic FibrosisCystic Fibrosis

– Research exemptionResearch exemption ApoE for Alzheimer’sApoE for Alzheimer’s

– Exclusively licensedExclusively licensed BrCA1 & 2BrCA1 & 2

– One companyOne company HemochromatosisHemochromatosis Many genes and Many genes and

mutationsmutations

Most single Most single nucleotide nucleotide polymorphismspolymorphisms

Many genes and Many genes and mutationsmutations

Patents induce private Patents induce private developmentdevelopment investment investment

Automated sequencingAutomated sequencing Therapeutic proteins: gene patents Therapeutic proteins: gene patents

protect post-discovery development protect post-discovery development investmentinvestment– long clinical trial testing periodlong clinical trial testing period– Trials and manufacturing startup Trials and manufacturing startup

expensiveexpensive Microarray applicationsMicroarray applications

Patents were not essential to Patents were not essential to induce induce health researchhealth research investment investment

BrCA1 & 2 and hemochromatosisBrCA1 & 2 and hemochromatosis Cohen-BoyerCohen-Boyer PCRPCR Sequencing methodsSequencing methods Cell fusion and monoclonal antibody Cell fusion and monoclonal antibody

techniquestechniques Most university-based discoveriesMost university-based discoveries

Patents a source of revenuePatents a source of revenue

Startups (intellectual “capital”)Startups (intellectual “capital”) Universities (licensing income)Universities (licensing income)

Patents a tool for policy changePatents a tool for policy change

PXE International modelPXE International model– Sharon Terry co-inventorSharon Terry co-inventor

Indigenous Peoples movementIndigenous Peoples movement– Licensing rights to accessLicensing rights to access

NIH and universities as major NIH and universities as major “property managers”“property managers”– Create norms through licensingCreate norms through licensing– Increase transparencyIncrease transparency– Initiate pooling?Initiate pooling?

Bayh-Dole Act: PurposeBayh-Dole Act: Purpose

Commercially exploit inventions Commercially exploit inventions developed using federal fundsdeveloped using federal funds

Legal mandate and financial Legal mandate and financial incentive to do business with firms incentive to do business with firms that can develop an invention into a that can develop an invention into a product or serviceproduct or service

Policy Options: Bayh-DolePolicy Options: Bayh-Dole

TransparencyTransparency– Stop flying blindStop flying blind

Research exemption (Dreyfus)Research exemption (Dreyfus) Diagnostic use exemption (Rivers bill)Diagnostic use exemption (Rivers bill) More flexibility to pre-empt patentingMore flexibility to pre-empt patenting

– Lower threshold than “exceptional circumstances” Lower threshold than “exceptional circumstances” (Rai/Eisenberg) (Rai/Eisenberg)

– Simplify process Simplify process Licensing oversight and march-in Licensing oversight and march-in

(McGarey/CellPro)(McGarey/CellPro) Earlier release of sequence data Earlier release of sequence data

(BCD/McCormack)(BCD/McCormack)

Policy Options: UniversitiesPolicy Options: Universities

Informational “markets” on licensing Informational “markets” on licensing termsterms

Explicit attention to where scientific Explicit attention to where scientific and academic norms conflict with and academic norms conflict with business interests and revenue-business interests and revenue-maximizationmaximization

Due diligence on licenseesDue diligence on licensees Patent pools?Patent pools?

Policy options: NIHPolicy options: NIH

Guidance on disposition of research Guidance on disposition of research toolstools

Guidance on licensing practicesGuidance on licensing practices Develop criteria for “exceptional Develop criteria for “exceptional

circumstances”circumstances” Develop criteria for “march-in”Develop criteria for “march-in” Patent pool?Patent pool?

Policy Options: CompaniesPolicy Options: Companies

Consortia for preserving public Consortia for preserving public domain research tools domain research tools – ESTEST– SNPSNP

Patent poolsPatent pools Guidance on licensing practicesGuidance on licensing practices

– BIO and PhRMABIO and PhRMA

Policy Options: IP lawPolicy Options: IP law Research exemption for all patentsResearch exemption for all patents

– What about academic health centers as major service What about academic health centers as major service providers? Exemption kills that market.providers? Exemption kills that market.

Shift to “opposition” rather than re-examinationShift to “opposition” rather than re-examination Data exclusivity for FDA approval as a substitute Data exclusivity for FDA approval as a substitute

for patents (for therapeutics and devices)for patents (for therapeutics and devices) Liability rules and contract practices; unfair Liability rules and contract practices; unfair

competition law (per Reichman/Uhlir)competition law (per Reichman/Uhlir) Database protectionDatabase protection