NIH as a NIH as a Research Partner

Slide 1: NIH as a Research Partner: How to Collaborate with & Gain Access to NIH Intramural Scientists and Resources Claire T. Driscoll Director, Technology Transfer Office National Human Genome Research Institute (NHGRI) National Institutes of Health (NIH) U.S. Department of Health & Human Services (DHHS)

Slide 2: Getting to Know the 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 processes are TRANSPARENT (all evaluation and eligibility criteria, policy documents, etc. are posted on our web site)  We serve many stakeholders—U.S. taxpayers, Congress, academia, the biopharma industry, etc.

Slide 3: The NIH is BIG, COMPLEX & INTIMIDATING….  A HUGE number of general & specialized scientific grant 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 and public-private partnerships (most of these are international in scope)

Slide 4: 82% of the U.S. Government’s Annual ~$28B Investment in Biomedical Research Goes to the NIH

Slide 5: Institutes: Understanding the NIH Structure  Each NIH Institute (IC) has a unique mission & is semi-autonomous  All the diseases/disorders/research areas covered by an 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; Infectious Disease)

Slide 6: The 27 Institutes and Centers of the National Institutes of Health (www.nih.gov)

Slide 7: Why Bother with the NIH?  $ (~$25B/yr) to conduct research in the form of grants and contracts  Access to drug screening services, databases, clinical trial testing networks, repositories of research reagents & natural products, etc.  Access to 1,000s of potential top notch collaborators and deep-pocketed customers  100s of inventions/technologies available for licensing

Slide 8: NIH Public-Private Partnerships: Building 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

Slide 9: NIH’s “On Campus” Intramural Research 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 licensing http://ott.od.nih.gov/techabs.html

Slide 10: Extramural NIH (off site)  Extramural = universities, hospitals, non-profit research institutions worldwide plus some companies (ex. 2.5% of all grant money goes to Small 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 3,000 organiz./year  Grantees/contractors control their own inventions even if made using government money  There are many non-U.S. grantees and contractors

Slide 11: Technology Transfer Mechanisms  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)  CRADAs come in 3 “flavors” at NIH  “regular” or standard CRADAs, Materials CRADAs (M- CRADAs) & Clinical Trial CRADAs (CT-CRADAs)  Licenses

Slide 12: We do A LOT of deals at the NIH  Whether a small deal or a huge one the fundamentals 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 the future (minimize use of “legalese”) ….really!

Slide 13: Top 10 Issues in Transactional Agreements (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”

Slide 14: Genesis of CRADAs  Gov. mandate (FTTA ‘86 & Exec. Order 12591) to encourage and facilitate collaboration among federal labs, universities and the private sector  Why? Help increase U.S. technological competitiveness and foster the rapid transfer of federal“fruits of innovation” to marketplace  Legal vehicle? Cooperative Research and Development Agreement (CRADA)

Slide 15: Non-CRADAs versus CRADAs MTAs, CTAs, RCAs, etc. CRADAs  No Funds to NIH  Funds can flow to NIH  No license options or IP from collaborators rights  Company gets license  Purpose is transfer option to yet-to-be materials (MTAs) and/or discovered CRADA conduct research inventions (RCAs), clinical studies  Purpose is to conduct (CTAs) research (of any kind)  Does not and usually is  Must be a true not collaborative but collaborative effort can be esp. in case of with intellectual input RCAs and CTAs from all parties

Slide 16: CRADA Facts  A legal contract--gives the company the opportunity to negotiate an EXCLUSIVE license to yet-to-be developed inventions made solely or jointly by NIH scientists  Research Plans and financial info are CONFIDENTIAL; All staff members associated with the CRADA share the responsibility for CONFIDENTIALITY  Any Materials or $ provided under the CRADA are for use ONLY as specified in the Research Plan  All publications or presentations related to the CRADA are reviewed by the Collaborator prior to disclosure (but no veto power is ever given)

Slide 17: CRADA Facts continued  Often initiated by NIH scientist based on scientific considerations & desire for public to benefit from further R&D and commercialization of NIH research  CRADA Research Plan must be in-line with NIH’s research mission  No restriction on subject matter (see above); RPs must be highly focused with clear objectives and delineated roles & responsibilities for the Parties

Slide 18: What a CRADA is NOT  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/or its technology/products by NIH

Slide 19: Why a CRADA? NIH and Company Perspectives: NIH Company  Extensive scientific  Opportunity to collaborate expertise and regulatory with top research and at Company clinical scientists  Access to proprietary  Access to unique materials technologies and materials  No ability to  Can exclusively license commercialize (future) CRADA-derived  Access to additional inventions funds  Signing a CRADA may help  Technology transfer is a Company to leverage funds responsibility of all (prestige of working with Federal labs NIH)

Slide 20: Clinical Trial CRADAs (CT- CRADAs)  An expanded, specialized CRADA used for the study of vaccines or drugs human clinical trials

Slide 21: Key Provisions in a CRADA: IP  Intellectual Property (IP):  Pre-CRADA/CTA IP: what’s yours is yours (NIH doesn’t want or expect rights to company-owned IP); what’s ours is ours; Company can license any needed “background rights” owned by NIH in order to conduct the CRADA research (if technology/invention is still available)  New Inventions discovered during the CRADA term: what’s yours is yours (but NIH gets non-commercial research use); what’s ours is ours (but company has option to negotiate an exclusive license to NIH sole Inventions=CRADA Subject Inventions); what’s joint is joint (Company and NIH decide on how to handle)

Slide 22: Key Provisions in a CRADA: Licensing  CRADA Collaborator does NOT get an automatic license to all CRADA Subject Inventions; only an option to negotiate an exclusive (or non-exclusive license) is given for sole NIH inventions discovered while the CRADA was active  License is expected to be royalty-bearing and fields of use will be consistent with the scope of the CRADA research plan (plus company will need to prove capability esp. in case of an exclusive)

Slide 23: What is so “special” about a CRADA?  NIH doesn’t normally execute very many exclusive licenses (~85% of all NIH licenses are non- exclusive)  Only mechanism available to NIH (or any government agency) to promise licensing rights to future, yet-to-be discovered inventions to a company or collaborator  For non-CRADA NIH inventions that are available for exclusive licensing NIH is required to advertise the opportunity & to advertise the choice of licensee (with time given for objections to the choice to be filed by competitors); there is no such advertising requirement for CRADA subject inventions

Slide 24: Non-CRADAs versus CRADAs MTAs, CTAs, etc. CRADAs, M-CRADAs, CT- CRADAs  No Funds to NIH  Funds to NIH possible  No license options or (but not required) IP rights  License option to yet-to-  Purpose is to conduct be discovered CRADA clinical research inventions (and/or transfer  Purpose is to conduct materials) research (of any kind)  Does not have to be  Must be a true collaborative collaborative effort  Easier & faster to  Slower & more difficult negotiate & execute to negotiate & execute (IC review only) (NIH central committee review)

Slide 25: Example NHGRI CRADAs & CRADA 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

Slide 26: NHGRI CRADA Partners & CRADAs 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 Therapy Using Retroviral Vectors  Key attraction: retroviral vector/gene therapy expertise  Lynx Therapeutics, Inc. (in development; Hayward, CA)  High Throughput Detection of DNAse Hypersensitive Sites by Massively Parallel Signature Sequencing (MPSS)  Key attraction: MPSS system & MPSS expertise

Slide 27: How do I find the “right” person at NIH to talk to about Collaboration Opportunities?  NIH Staff directory—search by name  http://ned.nih.gov/search/search.aspx  Each Institute has a TDC (Technology Development 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

Slide 28: Getting Started…Do Your Homework before Contacting Anyone!  CRISP at http://crisp.cit.nih.gov/ - a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other research institutions & NIH intramural  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 (once have found the experts in areas of interest); retrieve papers  http://www.ncbi.nlm.nih.gov/sites/entrez?db=PubMed

Slide 29: Tips for Making a CRADA Match with 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 (based on scientific publications & other info you’ve found on the NIH web site)?  Have your chief scientific officer or a senior scientist make the 1st contact—in person at a conference or meeting is always the 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 of research interests and exactly what you are looking for

Slide 30: Benefits to Collaborating with the NIH  We can help you to validate your technology and/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 talented researchers available to you often for FREE  Prestige factor: collaborating w/ NIH gives your company a higher profile and impresses people (including investors)

Slide 31: In the World of Life Sciences All Roads Lead to & from the NIH  All the major research universities, hospitals & research institutions have NIH funding  Nearly every single U.S. university & company has NIH-trained scientists working for them  Nearly every life sciences company has in- licensed at least one NIH technology or invention (or licensed one from a NIH grantee)  A large # of US life sciences companies have received SBIR or other NIH funding in the start- up phase

Slide 32: 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

Slide 33: Doing 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

Slide 34: 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

Slide 35: NIH Research Resources For copy of NIH Resources slides and additional information on NIH Resources send an email with “NIH Resources” in Subject Line to Anna Amar aamar@niaid.nih.gov