nih as a nih as a research partner

NIH as a Research PartnerNIH as a Research Partner::How to Collaborate with & GainHow to Collaborate with & Gain

Access to NIH Intramural ScientistsAccess to NIH Intramural Scientistsand Resourcesand Resources

Claire T. DriscollClaire T. DriscollDirector, Technology Transfer OfficeDirector, Technology Transfer OfficeNational Human Genome Research Institute (NHGRI)National Human Genome Research Institute (NHGRI)National Institutes of Health (NIH)National Institutes of Health (NIH)U.S. Department of Health & Human Services (DHHS)U.S. Department of Health & Human Services (DHHS)

Getting to KnowGetting to Knowthe National Institutes of Healththe National Institutes of Health

Top biomedical research institution in U.S. 2005 budget: $28.6 Billion (= $28,600 Million) An extremely information-rich web site www.nih.gov As a gov. agency we are FAIR (open, unbiased

competition for grants & contracts) and our processesare TRANSPARENT (all evaluation and eligibilitycriteria, policy documents, etc. are posted on our website)

We serve many stakeholders—U.S. taxpayers,Congress, academia, the biopharma industry, etc.

The NIH is BIG, COMPLEX &The NIH is BIG, COMPLEX &INTIMIDATINGINTIMIDATING……..

A HUGE number of general & specialized scientificgrant and contract programs

A lot of MONEY to “give away” each year (~$25B) 60,000+ grants & contracts given to 3,000 organizations/year ~$3B spent “on campus” for research/year

Increased funding of large-scale, multi-party,multi-disciplinary collaborative endeavors andpublic-private partnerships (most of these areinternational in scope)

82% of the U.S. Government82% of the U.S. Government’’s Annuals Annual~$28B Investment in Biomedical~$28B Investment in Biomedical

Research Goes to the NIHResearch Goes to the NIH

Institutes: Understanding theInstitutes: Understanding theNIH StructureNIH Structure

Each NIH Institute (IC) has a unique mission & issemi-autonomous

All the diseases/disorders/research areas covered byan Institute may not be reflected in its name

ICs are structured by disease (Cancer; Diabetes),organ systems (Heart, Lung & Blood;Musculoskeletal), life stage (Aging; Infants &Children) and disciplines (Neurological; InfectiousDisease)

The 27 Institutes and Centers ofthe National Institutes of Health (www.nih.gov)

Why Bother with the NIH?

$ (~$25B/yr) to conduct research in the form ofgrants and contracts

Access to drug screening services, databases,clinical trial testing networks, repositories ofresearch reagents & natural products, etc.

Access to 1,000s of potential top notchcollaborators and deep-pocketed customers

100s of inventions/technologies available forlicensing

NIH Public-Private Partnerships:NIH Public-Private Partnerships:Building on the Success of the HGPBuilding on the Success of the HGP

Human Genome Project (HGP) The SNP Consortium The Pharmacogenetics Research Network The Mammalian Gene Collection (MGC) Haplotype Map Project (HapMap) ENCODE Project (Encyclopedia of DNA Elements) Knockout Mouse Project (KOMP) Molecular Libraries project Genetic Associations Information Network (GAIN) The Cancer Genome Atlas

NIHNIH’’s s ““On CampusOn Campus”” Intramural IntramuralResearch ProgramResearch Program

Intramural budget $3B (=~10% of total) Bethesda, Maryland main campus (plus some

satellite locations)—just outside Washington DC Intramural (on site) = 18,000 employees; 6,000

MDs/PhDs; 2000+ intramural R&D projects Many research collaborations w/ both public and

private sectors scientists Intramural-developed technologies & inventions

are available for licensinghttp://ott.od.nih.gov/techabs.html

Extramural NIH (off site)Extramural NIH (off site)

Extramural = universities, hospitals, non-profitresearch institutions worldwide plus somecompanies (ex. 2.5% of all grant money goes toSmall Business Innovation Research (SBIR)grantees) that receive NIH funding of some kind *SBIR funds limited to small 51% indiv-owned U.S. companies

Extramural = 60,000 awards to 3,000organiz./year Grantees/contractors control their own inventions even

if made using government money There are many non-U.S. grantees and contractors

Technology TransferTechnology TransferMechanismsMechanisms

Scientific publications Informal scientific collaborations Research Collaboration Agreements (RCAs) Confidentiality Disclosure Agreements (CDAs) Memoranda of Understanding (MOUs) Material Transfer Agreements (MTAs) Screening Agreements Clinical Trial Agreements (CTAs)Clinical Trial Agreements (CTAs) CRADAsCRADAs come in 3 come in 3 ““flavorsflavors”” at NIH at NIH

““regularregular”” or standard or standard CRADAsCRADAs, Materials , Materials CRADAsCRADAs (M- (M-CRADAsCRADAs) & Clinical Trial ) & Clinical Trial CRADAsCRADAs (CT- (CT-CRADAsCRADAs))

Licenses

We do A LOT of deals at the NIHWe do A LOT of deals at the NIH

Whether a small deal or a huge one thefundamentals are the same Reach a common understanding (this is the hard part!) Preserve that understanding in writing (not so easy) Use the right legal instrument (getting easier)

Maintain urgency but don’t unduly rush The devil is in the details…sweat the details! Obtain expert help (legal, business

development/commercialization, scientific, etc.)

A clearly written agreement will serve you well in thefuture (minimize use of “legalese”) ….really!

Top 10 Issues in Transactional AgreementsTop 10 Issues in Transactional Agreements(in order of importance/time spent negotiating)(in order of importance/time spent negotiating)

Intellectual Property/Patent Rights (if any) Licensing terms (if any) Publication rights (& pre-publication sharing) Confidentiality terms Indemnification/Liability terms Choice of Law and/or Jurisdiction Conflict Resolution and termination terms Agreement term (how long?) Financial/budget Scientific/technical issues and/or “division of labor”

Genesis of CRADAsGenesis of CRADAs

Gov. mandate (FTTA ‘86 & Exec. Order12591) to encourage and facilitatecollaboration among federal labs, universitiesand the private sector

Why? Help increase U.S. technologicalcompetitiveness and foster the rapid transferof federal“fruits of innovation” tomarketplace

Legal vehicle? Cooperative Research andDevelopment Agreement (CRADA)

Non-CRADAs versus CRADAsNon-CRADAs versus CRADAs

MTAs, CTAs, RCAs, etc. No Funds to NIH No license options or IP

rights Purpose is transfer

materials (MTAs) and/orconduct research(RCAs), clinical studies(CTAs)

Does not and usually isnot collaborative butcan be esp. in case ofRCAs and CTAs

CRADAs Funds can flow to NIH

from collaborators Company gets license

option to yet-to-bediscovered CRADAinventions

Purpose is to conductresearch (of any kind)

Must be a truecollaborative effortwith intellectual inputfrom all parties

CRADA FactsCRADA Facts A legal contract--gives the company the opportunityA legal contract--gives the company the opportunity

to negotiate an EXCLUSIVE license to yet-to-beto negotiate an EXCLUSIVE license to yet-to-bedeveloped inventions made solely or jointly by NIHdeveloped inventions made solely or jointly by NIHscientistsscientists

Research Plans and financial info are CONFIDENTIAL;Research Plans and financial info are CONFIDENTIAL;All staff members associated with the CRADA shareAll staff members associated with the CRADA sharethe responsibility for CONFIDENTIALITYthe responsibility for CONFIDENTIALITY

Any Materials or $ provided under the CRADA are forAny Materials or $ provided under the CRADA are foruse ONLY as specified in the Research Planuse ONLY as specified in the Research Plan

All publications or presentations related to the CRADAAll publications or presentations related to the CRADAare reviewed by the Collaborator prior to disclosureare reviewed by the Collaborator prior to disclosure(but no veto power is ever given)(but no veto power is ever given)

CRADA Facts continuedCRADA Facts continued Often initiated by NIH scientist based on

scientific considerations & desire for public tobenefit from further R&D andcommercialization of NIH research

CRADA Research Plan must be in-line withNIH’s research mission

No restriction on subject matter (see above);RPs must be highly focused with clearobjectives and delineated roles &responsibilities for the Parties

What a CRADA is What a CRADA is NOTNOT A CRADA is NOT the same as a fee-for-service

contract or Sponsored Research Agreement A CRADA is NOT to be used as means for NIH

scientists to supplement their lab funding A CRADA is NOT an open-ended, ill defined,

broad and/or informal collaboration Entering into a CRADA is NOT an

endorsement of a particular company and/orits technology/products by NIH

Why a CRADA?Why a CRADA?NIH and Company Perspectives:NIH and Company Perspectives:

NIH Extensive scientific

expertise and regulatoryat Company

Access to proprietarymaterials

No ability tocommercialize

Access to additionalfunds

Technology transfer is aresponsibility of allFederal labs

Company Opportunity to collaborate

with top research andclinical scientists

Access to uniquetechnologies and materials

Can exclusively license(future) CRADA-derivedinventions

Signing a CRADA may helpCompany to leverage funds(prestige of working withNIH)

Clinical Trial Clinical Trial CRADAsCRADAs (CT- (CT-CRADAsCRADAs))

An expanded, specialized CRADA used for thestudy of vaccines or drugs human clinicaltrials

Key Provisions in a CRADA: IPKey Provisions in a CRADA: IP Intellectual Property (IP):

Pre-CRADA/CTA IP: what’s yours is yours (NIH doesn’twant or expect rights to company-owned IP); what’s oursis ours; Company can license any needed “backgroundrights” owned by NIH in order to conduct the CRADAresearch (if technology/invention is still available)

New Inventions discovered during the CRADA term:what’s yours is yours (but NIH gets non-commercialresearch use); what’s ours is ours (but company hasoption to negotiate an exclusive license to NIH soleInventions=CRADA Subject Inventions); what’s joint isjoint (Company and NIH decide on how to handle)

Key Provisions in a CRADA:Key Provisions in a CRADA:LicensingLicensing

CRADA Collaborator does NOT get anautomatic license to all CRADA SubjectInventions; only an option to negotiate anexclusive (or non-exclusive license) is givenfor sole NIH inventions discovered while theCRADA was active

License is expected to be royalty-bearing andfields of use will be consistent with the scopeof the CRADA research plan (plus companywill need to prove capability esp. in case ofan exclusive)

What is so What is so ““specialspecial”” about a about aCRADA?CRADA?

NIH doesn’t normally execute very many exclusivelicenses (~85% of all NIH licenses are non-exclusive)

Only mechanism available to NIH (or anygovernment agency) to promise licensing rights tofuture, yet-to-be discovered inventions to a companyor collaborator

For non-CRADA NIH inventions that are available forexclusive licensing NIH is required to advertise theopportunity & to advertise the choice of licensee(with time given for objections to the choice to befiled by competitors); there is no such advertisingrequirement for CRADA subject inventions

Non-CRADAs versus CRADAsNon-CRADAs versus CRADAsMTAs, CTAs, etc.

No Funds to NIH No license options or

IP rights Purpose is to conduct

clinical research(and/or transfermaterials)

Does not have to becollaborative

Easier & faster tonegotiate & execute(IC review only)

CRADAs, M-CRADAs, CT-CRADAs

Funds to NIH possible(but not required)

License option to yet-to-be discovered CRADAinventions

Purpose is to conductresearch (of any kind)

Must be a truecollaborative effort

Slower & more difficultto negotiate & execute(NIH central committeereview)

Example NHGRI Example NHGRI CRADAsCRADAs & &CRADA PartnersCRADA Partners

Perlegen Sciences (Mountain View, CA) Evaluating a Region of Chromosome 6 for Association with Type 2

Diabetes Mellitus Key attraction: proprietary high density wafer microarray technology

Sequenom (San Diego, CA) Single Nucleotide Polymorphism Genotyping by Mass Spectroscopy Key attraction: Mass spect-based genotyping expertise

Elixir Pharmaceuticals (Cambridge, MA) Collaborative Effort to Define Variants in the LMNA Gene Associated

with Human Longevity Key attraction: large, well characterized collection of blood & DNA

samples from individuals 95 years of age and older

NHGRI CRADA Partners &NHGRI CRADA Partners &CRADAsCRADAs continued continued

Agilent Technologies (Palo Alto, CA) Oligonucleotide Microarrays for Comparative Genomic Hybridization in

Cancer Key attraction: long oligonucleotide based microarrays and related

technologies including software & bioinformatics expertise Novartis/Genetic Therapy Inc. (Gaithersburg, MD)

Follow-up Studies of ADA (-) SCID Patients Treated by Gene TherapyUsing Retroviral Vectors

Key attraction: retroviral vector/gene therapy expertise Lynx Therapeutics, Inc. (in development; Hayward, CA)

High Throughput Detection of DNAse Hypersensitive Sites by MassivelyParallel Signature Sequencing (MPSS)

Key attraction: MPSS system & MPSS expertise

How do I find the How do I find the ““rightright”” person at person atNIH to talk to about CollaborationNIH to talk to about CollaborationOpportunities?Opportunities?

NIH Staff directory—search by name http://ned.nih.gov/search/search.aspx

Each Institute has a TDC (TechnologyDevelopment Coordinator)—”point” person &liaison for all tech transfer matters http://ott.od.nih.gov/nih_staff/tdc.html

List of IC tech transfer offices’ web sites http://ott.od.nih.gov/nih_staff/tdc.html

Published Federal Register advertisements http://www.gpoaccess.gov/fr/index.html

Getting StartedGetting Started……Do Your HomeworkDo Your Homeworkbefore Contacting Anyone!before Contacting Anyone!

CRISP at http://crisp.cit.nih.gov/ - asearchable database of federally funded biomedicalresearch projects conducted at universities,hospitals, and other research institutions & NIHintramural Search by topic, name or other terms to find NIH-funded

researchers working in extramural community Search by “Z” number (under “Activity” to find

descriptions of Intramural research projects

PubMed/Medline – search by scientist name (oncehave found the experts in areas of interest); retrieve papers http://www.ncbi.nlm.nih.gov/sites/entrez?db=PubMed

Tips for Making a CRADA MatchTips for Making a CRADA Matchwith a NIH scientist or labwith a NIH scientist or lab

No cold calls or “cold” e-mail inquiries Do your homework—is it likely that this person or lab is

interested in collaborating on the project of interest (basedon scientific publications & other info you’ve found on theNIH web site)?

Have your chief scientific officer or a senior scientist make the1st contact—in person at a conference or meeting is alwaysthe best way to go.

If You Get a Bite--Make a Persuasive Pitch (no hype!) Don’t hold back on the scientific/technical details Send copies of peer-reviewed publications; brief bios on

company scientists and/or a clear, concise synopsis ofresearch interests and exactly what you are looking for

Benefits to Collaborating withBenefits to Collaborating withthe NIHthe NIH

We can help you to validate your technologyand/or test your product in humans

We don’t want to own any of your company(we don’t take equity)

We don’t want your Intellectual Property(IP)—what’s yours is yours!

We have incredible resources and talentedresearchers available to you often for FREE

Prestige factor: collaborating w/ NIH givesyour company a higher profile and impressespeople (including investors)

In the World of Life Sciences AllIn the World of Life Sciences AllRoads Lead to & from the NIHRoads Lead to & from the NIH

All the major research universities, hospitals &research institutions have NIH funding

Nearly every single U.S. university & companyhas NIH-trained scientists working for them

Nearly every life sciences company has in-licensed at least one NIH technology orinvention (or licensed one from a NIH grantee)

A large # of US life sciences companies havereceived SBIR or other NIH funding in the start-up phase

For more information:For more information: Technology Transfer Office, NHGRI

5625 Fishers Ln Rm 5N-01/K, Rockville, MD 20852 tel: (301) 402-2537/ (301) 594-2235 fax: (301) 402-9722 e-mail: cdriscol@mail.nih.gov

http://www.genome.gov (then click on Tech Transfer) available NHGRI technologies technology transfer information sources E-mail links to scientific staff

http://ott.od.nih.gov Available NIH technologies (from all 27 ICs) On-line technology transfer training module

Doing Business with NIHDoing Business with NIH Small Business Office

http://sbo.od.nih.gov/

e-Portals in Commerce System (e-PIC) http://epic.od.nih.gov/ virtual marketplace for all sizes and types of organizations to

showcase promotional information, products and services

Contracts and Other Business Opportunities http://www.fedbizopps.gov/ federal business opportunities http://ocm.od.nih.gov/contracts/rfps/MAINPAGE.HTM

Small Business Funding Opportunities(including SBIR grants) http://grants1.nih.gov/grants/funding/sbir.htm#sbir

For more information:For more information: Technology Transfer Office, NHGRI

Building 12A Room 1033 tel: (301) 402-2537/ (301) 594-2235 fax: (301) 402-9722 e-mail: cdriscol@mail.nih.gov

http://www.genome.gov (then click on Tech Transfer) available NHGRI technologies technology transfer information sources E-mail links to scientific staff

http://ott.od.nih.gov Available NIH technologies (from all 27 ICs) On-line technology transfer training module

NIH Research ResourcesNIH Research Resources

For copy of NIH Resources slides and additionalinformation on NIH Resources send an email with “NIH Resources” in Subject Line to Anna Amar

aamar@niaid.nih.gov