TOOLS FOR INSERTIONAL MUTAGENESIS IN THE MOUSE:  SBIR/STTR INITIATIVE

Release Date:  January 25, 2001

RFA:  RFA-DA-01-012

National Institute on Drug Abuse
 (http://www.nida.nih.gov)
National Institute on Aging
 (http://www.nih.gov/nia/)
National Institute on Dental and Craniofacial Research
 (http://www.nidcr.nih.gov)
National Institute on General Medical Sciences
 (http://www.nigms.nih.gov)
National Institute of Mental Health
 (http://www.nimh.nih.gov)
National Eye Institute
 (http://www.nei.nih.gov)
National Institute on Deafness and Other Communication Disorders
 (http://www.nidcd.nih.gov)
National Human Genome Research Institute
 (http://www.nhgri.nih.gov)
National Center for Research Resources
 (http://www.ncrr.nih.gov)
National Institute of Diabetes and Digestive and Kidney Diseases
 (http://www.niddk.nih.gov)
National Institute on Alcohol Abuse and Alcoholism
 (http://www.niaaa.nih.gov)
National Institute of Child Health and Human Development
 (http://www.nichd.nih.gov)
National Institute of Environmental Health Sciences
 (http://www.niehs.nih.gov)
National Institute of Allergy and Infectious Diseases
 (http://www.niaid.nih.gov)
National Institute of Neurological Disorders and Stroke
 (http://www.ninds.nih.gov)

Letter of Intent Receipt Date:  March 11, 2001
Application Receipt Date:       April 11, 2001

PURPOSE

This Request for Applications (RFA) solicits proposals for development of 
tools and techniques for the establishment of random and targeted sequence-
tagged insertion libraries of embryonic stem (ES) cells that can be used to 
generate mutant mice in which the expression of the tagged gene could be 
controlled temporally and spatially.  The development of such a resource for 
wide distribution to the scientific community would make it possible to scan 
the sequence database for any gene of interest and order the corresponding 
targeted ES cell line.  Ideally, the insertional mutagenesis system developed 
would permit a wide range of genetic analyses and manipulations, including 
enhancer-trapping, conditional knockouts, conditional expression or 
overexpression, etc.  It also would permit the larger community of 
investigators to utilize genomic resources efficiently.

This effort complements ongoing National Institutes of Health (NIH) efforts 
to create and characterize induced point mutations in mice using 
ethylnitrosourea (ENU) and provides a functional genomics tool to translate 
the information from the Mouse Genome Sequencing Project.  Further 
information about NIH initiatives on mouse genomics and genetics resources is 
available at http://www.nih.gov/science/mouse.

Because this initiative deals with the development of technology-driven 
commercial products, this initiative will use the Small Business Innovation 
Research/Small Business Technology Transfer Research (SBIR/STTR) programs.  
This RFA provides a flexible system within the SBIR/STTR programs to cover 
the research steps needed to develop and validate technology to generate 
insertional mutations in mouse ES cells.  It will be run in parallel with a 
program of identical scientific scope utilizing the research project grant 
(R01) and for exploratory/development grant (R21) (see 
http://grants.nih.gov/grants/guide/rfa-files/RFA-DA-01-011.html) mechanisms.  

HEALTHY PEOPLE 2010

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2010," a PHS-
led national activity for setting priority areas.  This RFA, "Tools for 
Insertional Mutagenesis in the Mouse:  SBIR/STTR Initiative," is related to 
several of the priority areas.  Potential applicants may obtain a copy of 
"Healthy People 2010" at http://www.health.gov/healthypeople/.

ELIGIBILITY REQUIREMENTS

Eligibility requirements are described in the Omnibus Solicitation of the 
Public Health Service, Centers for Disease Control and Prevention, and Food 
and Drug Administration for Phase I SBIR/STTR Grant Applications (PHS 2000-2) 
(Omnibus Solicitation) 
(http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf).  Each 
organization submitting an SBIR/STTR grant application must qualify as a 
small business concern in accordance with the definition given in Section III 
of the Omnibus Solicitation.

MECHANISM OF SUPPORT

This RFA invites grant applications for Small Business Innovation 
Research/Small Business Technology Transfer (SBIR/STTR) projects with award 
duration and amounts greater than those routinely allowed under the SBIR 
program.  This RFA must be read in conjunction with the Omnibus Solicitation 
(http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf)  and with the 
instructions for Phase II SBIR/STTR Grant Applications 
http://grants.nih.gov/grants/funding/sbir2/index.htm and 
http://grants.nih.gov/grants/funding/sttr2/index.html).  All instructions and 
information in these documents also apply to applications in response to this 
RFA.  The NIH has announced that applicants may request a larger budget and 
period of support if necessary for completion of the project.  See NIH Guide 
for Grants and Contracts, February 13, 1998 at: 
http://grants.nih.gov/grants/guide/notice-files/not98-014.html.

This RFA is a one-time solicitation.  Responsibility for the planning, 
direction, and execution of the proposed project will be solely that of the 
applicant.  Awards will be administered under NIH grants policy stated in the 
NIH Grants Policy Statement, NIH publication 99-8, October 1998.

A.  Fast-Track Applications.  Applications may be submitted for the Fast-
Track review option.  Information on the Fast-Track process may be found at: 
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf.
 
To be eligible for the Fast-Track option, the Phase I SBIR/STTR application 
must include well-defined, quantifiable milestones that will be used to judge 
the success of the proposed research, as well as a credible plan to apply the 
selected technology in a pilot study of interest to exposure assessment 
research for the Phase II R44 or R42 application.  The Fast-Track application 
must have a section labeled Milestones at the end of the Research Plan Phase 
I.  This section must include well-defined, quantifiable milestones for 
completion of Phase I, a discussion of the suitability of the proposed 
milestones for assessing the success in Phase I, and a discussion of the 
implications of successful completion of these milestones on the proposed 
Phase II.

Applications submitted through the Fast-Track option are subject to the same 
total cost limits per year as when submitted outside of the Fast-Track 
option, as described below in the PROJECT PERIOD AND AMOUNT OF AWARD section.

B.  Individual Phase I Applications.  Phase I applications in response to 
this RFA will be funded as Phase I SBIR Grants (R43) or STTR Grants (R41) 
with modifications as described below.  Applications for Phase I grants 
should be prepared following the directions for Phase I SBIR/STTR 
applications as described in the Omnibus Solicitation.  The Omnibus 
Solicitation is available on the Internet at 
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf.

C.  Individual Phase II Applications.  Phase II applications will not be 
accepted in response to this RFA unless they are submitted for Fast-Track 
review.  They will only be accepted as competing continuations of Phase I 
SBIR awards funded under this initiative. 

PROJECT PERIOD AND AMOUNT OF AWARD

Applicants planning to propose research in excess of the limits (duration and 
amount) stated below must obtain agreement from Institute staff (named under 
INQUIRIES below) that the application will be accepted for consideration.  
The applicant must identify, in the cover letter that is sent with the 
application, the staff member and Institute who agreed to accept the 
application.

Phase I:
 
Because of the challenges that may be involved in the development and 
evaluation of insertional mutagenesis technology, the participating 
Institutes will entertain well-justified Phase I applications for an 
SBIR/STTR award with a project period up to two years and a budget not to 
exceed a total cost of $100,000 per year. 

Consultant and contractual costs associated with Phase I:

The total amount of all consultant costs and contractual costs normally may 
not exceed 33 percent of the total costs requested for Phase I SBIR/STTR 
applications.  However, well-justified Phase I applications for an SBIR/STTR 
award with greater than 33 percent contractual costs will be considered when 
those costs are necessary to support the development and evaluation of tools 
for insertional mutagenesis.

Page limitations:

The 25-page limitation for Phase I applications applies (see Omnibus 
Solicitation).
Phase II:

This solicitation is only for Phase I or Fast-Track SBIR applications.  Phase 
II applications that result from funded Phase I studies under this RFA will 
be awarded as Phase II SBIR (R44) or STTR (R42) grants with modifications as 
described below.  In addition, Fast-Track Phase I and Phase II applications 
will be accepted as described above.

Project period and amount of award:

Because of the challenges that may be involved in the development and 
evaluation of insertional mutagenesis technology, the participating 
Institutes will entertain well-justified Phase II applications for an 
SBIR/STTR award with a project period up to two years and a budget of no more 
than $500,000 per year for STTR and $750,000 for SBIR awards.

Consultant and contractual costs:

For SBIR projects, the total amount of all contractual costs and consultant 
fees normally may not exceed 33 percent of the total costs requested for 
Phase I projects and 50 percent of total costs requested for Phase II 
projects.  However, well-justified Phase II applications for an SBIR award 
with greater contractual costs will be considered when those costs are 
necessary to support the development, evaluation, and validation of tools for 
insertional mutagenesis.

FUNDS AVAILABLE

It is expected that 10-20 awards will be made during FY 2001 and FY 2002, and 
approximately $3.15 million from the SBIR set-aside of the participating NIH 
Institutes and Centers will be designated for this purpose.  The number of 
awards will be dependent upon receipt of a sufficient number and diversity of 
applications with high scientific merit.

RESEARCH OBJECTIVES

Background

The use of transposon tagging and retroviral insertional mutagenesis in model 
organisms such as Drosophila, C. elegans, and zebrafish has greatly 
facilitated the characterization of gene function and permitted rapid cloning 
of the mutated gene.  This approach has complemented analysis of gene 
function using chemically and X-ray-induced mutations where great effort is 
expended in positional cloning of the mutant gene.  Insertional mutagenesis 
in mice is made practical by the availability of efficient methods of 
transfecting ES cells, the production of a 2.5 to 3.5X draft of the mouse 
genome using C57BL/6 by February 2001, polymerase chain reaction (PCR), and 
automated sequencing methods.

The development of both random and targeted sequence-tagged insertion 
libraries in mouse ES cells would greatly facilitate analysis of gene 
function in mice and permit the rapid development of mouse models for human 
genetic disease.  Not only would such an approach create induced mutation 
methodologies, but it would also permit analysis of patterns of gene 
expression.   The value of this resource would be greatly enhanced by the use 
of site-specific gene recombination systems or trans-acting factor binding 
sites that would allow the expression of the tagged gene to be controlled 
temporally and spatially.

Two recombination systems currently used to create conditional mutations or 
knockouts in mice are the cre-lox and FLP-FRT site-specific recombination 
systems.  The usefulness of these recombination systems in vertebrate systems 
is dependent on the activity of the recombinase and the ability to drive the 
expression of the recombinase with non-mammalian promoters, such as ecdysone 
or tetracycline-sensitive promoters.  The ability to control the spatial 
expressions of the recombinase is limited by the lack of well-characterized 
enhancers that control gene expression.  To overcome these obstacles, 
modifications of these recombinase systems, as well as the development of new 
ones, are needed.  In addition, the flexibility of existing systems can be 
enhanced through the use of inducible promoters or fusion-protein 
recombinases that are activated by ligands such as steroids.

The creation of appropriate insertional mutagenesis vectors containing site-
specific recombination targets will also aid in the generation of chromosomal 
deletions, duplications, and inversions when another genetic locus is tagged 
with a vector containing the same target sequence.  Chromosomal aberrations 
are an important tool for selecting and mapping mutations in a specific 
chromosomal region and for positional cloning, as well as for the study of 
position effects and contiguous gene syndromes.  In addition, inversions can 
be combined to produce balancer chromosomes.  Balancer chromosomes carrying 
dominant phenotypic markers simplify the maintenance of recessive mutations 
and combinations of alleles from generation to generation because the 
balancer prevents recombination.  Balancer chromosomes also facilitate 
isolation and high-throughput screening for new recessive mutations.

Current estimates are that a total of 500,000 ES cell lines may be needed to 
tag every single mouse gene.  Thus, high-throughput methods are needed to 
automate the processing of large numbers of clones and to identify the site 
of insertion.

The use of C57BL/6 ES cells will speed the distribution of mice in a defined 
isogenic background by eliminating the need to cross sv129 mice over 
successive generations into C57BL/6.  Many of the current sv129 cell lines in 
use are derived from different strains of sv129 mice, making comparisons 
among the various targeted mutations difficult until transferred to a defined 
genetic background.  Moreover, much of the public chemical mutagenesis and 
sequencing effort is being done in C57BL/6.  Thus, crosses between C57BL/6 
mice carrying mutations created by ENU and C57BL/6 mice carrying a targeted 
deletion can be performed in a single generation without concern about the 
effects of genetic background.  

It is anticipated that the results of funded research projects will 
eventually lead to production of new libraries of ES cells with random or 
targeted insertional mutations for wide distribution to the research 
community.

Examples of research that may be considered responsive to this RFA include, 
but are not limited to, those listed below.

o Feasibility studies for the establishment of sequence-tagged insertional 
libraries of C57BL/6 ES cells in which the expression of the tagged gene can 
be controlled temporally and spatially.

o The development of new or modified site-specific recombination systems for 
efficient random and targeted insertional mutagenesis and enhanced control of 
conditional expression.

o The development of novel vectors that allow imaging of specific cell types 
or tissues, metabolic activity, or other cellular or physiological functions.

o The invention of efficient systems for transposon tagging in mammalian 
systems for the wide use of the scientific community.

o The development of vectors for identification ("trapping") of promoters and 
enhancers that could be used for tissue-specific and temporal expression of 
recombinases and for the study of gene expression patterns.

o Methods to automate the processing of large numbers of clones and to 
identify the sites of insertion.

SPECIAL REQUIREMENTS

It is the policy of the NIH to make available to the public the results and 
accomplishments of the activities it funds [NIH Grants Policy Statement 
(http://grants.nih.gov/grants/policy/nihgps; Principles and Guidelines for 
Recipients of NIH Research Grants and Contracts on Obtaining and 
Disseminating Biomedical Research Resources:  Final Notice, December 1999 
(http://www.nih.gov/od/ott/RTguide_final.htm)].  Biomaterials and other 
patentable research resources (e.g., mutagenesis protocols, vectors, 
embryonic cell lines, etc.) produced in projects funded by this RFA are 
expected to be made available and distributed to the broader scientific 
community.

The NIH encourages the commercialization of research products and allows 
grantee organizations to make materials available to others for commercial 
purposes with appropriate restrictions and licensing terms. Where the product 
of research developed with federal funding is a patentable but unpatented 
research product, the terms of a license must be no more restrictive than 
they would have been if the product had been patented.

Plan to Share Resources and Handle Intellectual Property Rights

NIH is interested in ensuring that the research resources developed through 
this RFA become readily available to the research community.  Therefore, 
applicants are required to include in their applications a specific plan by 
which they will make research resources available to the wider scientific 
community.  The plan must also address how they will exercise their 
intellectual property rights while making available to the broader scientific 
community patentable research resources.  

The scientific review group will evaluate the adequacy of the proposed plan 
for access and for handling intellectual property rights.  Comments on the 
plan and any concerns will be presented in an administrative note in the 
Summary Statement.  The adequacy of the plan will be considered by NIH 
program staff and will be important in determining whether the grant shall be 
awarded.  The plan as approved, after negotiation with the applicant when 
necessary, will be a condition of the award.  Evaluation of non-competing 
continuation applications will include assessment of the effectiveness of 
research resource release and of the awardee’s adherence to the proposed plan 
to handle intellectual property rights.

Disclosure of Invention

Applicants also are reminded that the grantee institution is required to 
disclose each subject invention to NIH within two months after the inventor 
discloses it in writing to grantee institutional personnel responsible for 
patent matters.  The awarding Institute reserves the right to monitor awardee 
activity in this area to ascertain if patents or patent applications on 
mutagenesis protocols, cell lines, vectors, or other patentable subject 
matter are adversely affecting the goals of this RFA.

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained within 
specified page limitations.  Unless otherwise specified in an NIH 
solicitation, Internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no obligation 
to view the Internet sites.  Reviewers are cautioned that their anonymity may 
be compromised when they directly access an Internet site. 

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes a 
descriptive title of the proposed research; the name, address, and phone 
number of the Principal Investigator; the identities of other key personnel 
and participating institutions; and the number and title of the RFA in 
response to which the application may be submitted.  Although a letter of 
intent is not required, is not binding, and does not enter into the review of 
a subsequent application, the information that it contains allows NIH staff 
to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the letter of intent receipt date 
listed to:

Dr. Rebekah S. Rasooly
Division of Neuroscience and Behavioral Research
National Institute on Drug Abuse/NIH
6001 Executive Boulevard, Room 4260, MSC 9555
Bethesda, MD  20892-9555
Phone: 301-443-6300
Fax: 301-594-6043

APPLICATION PROCEDURES

Applicants should follow the instructions for SBIR/STTR Phase I submission 
with the modifications as noted in this RFA.  A sample Phase I SBIR 
application can be found at 
http://www.nhlbi.nih.gov/funding/sbir/modelsbi.htm.

This RFA must be read in conjunction with the Omnibus Solicitation of the 
Public Health Service for SBIR/STTR Applications (PHS 2000-2).  All of the 
instructions within the Omnibus Solicitation apply with the following 
exceptions:

- Special receipt date
- Additional award considerations
- Increased award amount and duration

Applications received in response to this RFA are to be prepared as described 
in the Omnibus Solicitation for the SBIR/STTR program.  Omnibus Solicitations 
are available electronically through the NIH Office of Extramural Research 
"Small Business Funding Opportunities" at 
http://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf.

Applications in response to this RFA are to be submitted on the applicable 
grant application forms as follows: SBIR Phase I - PHS 6246-1 (1/98) or STTR 
Phase I – PHS 6346-3 
(http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf).  The application 
forms are also located in the back pages of the Omnibus SBIR/STTR 
Solicitation.  The RFA title and number must be typed in line 2 on the face 
page of the application form.

Applications must be received by the application receipt date listed in the 
heading of this RFA.  If an application is received after that date, it will 
be returned to the applicant without review.

The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
review, unless the applicant withdraws the pending application.  The CSR will 
not accept any application that is essentially the same as one already 
reviewed.  This does not preclude the submission of substantial revisions of 
applications already reviewed, but such applications must include an 
introduction addressing the previous critique.

SBIR/STTR projects submitted in response to this RFA must contain a Phase I 
feasibility segment that must be successful prior to a Phase II award.  
Applications can be submitted for Phase I support, or as a combined Phase I 
and II (Fast-Track).  Phase II applications will be accepted April 1, August 
1, and December 1 after completion of the Phase I applications supported by 
this RFA or as part of a Fast-Track application.

Projects may be presented for SBIR/STTR support at all stages of insertional 
mutagenesis tool development.  Projects will be evaluated on overall 
innovation and success potential of the product/technology.  Larger budgets 
and longer project periods may be considered if required for conduct of the 
research and appropriately justified in the application.  Applicants planning 
to propose research in excess of the limits (duration and amount) listed 
earlier in this RFA must obtain agreement from Institute staff (named under 
INQUIRIES below) that the application will be accepted for consideration.  
The applicant must identify, in the cover letter that is sent with the 
application, the staff member and Institute who agreed to accept the 
application.

Fast-Track Applications: 
It is recommended that only well-defined and more advanced projects be 
proposed for support through this mechanism.  Fast-Track applications must 
specify clear, measurable goals for Phase I that should be achieved prior to 
Phase II funding.  Failure to provide measurable goals in the Phase I 
application and/or sufficient detail in the Phase II application may be 
sufficient reason for the peer review committee to exclude the Phase II 
application from consideration.  If so, the applicant may apply later for 
Phase II support.  Special provisions described in this RFA pertaining to 
Phase I and Phase II also apply to Fast-Track applications.

Submit a signed, typewritten original of the application, including the 
Checklist, and one signed, photocopy, in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

For purposes of identification and processing, the title and number of this 
RFA must be shown in item 2 on the face page of SBIR Phase I applications.  
Follow the mailing instructions in the Omnibus Solicitation for Phase I or 
Fast-Track applications. 

At the time of submission, one additional copy of the application must be 
sent to:

Dr. Rebekah S. Rasooly
Division of Neuroscience and Behavioral Research
National Institute on Drug Abuse/NIH
6001 Executive Boulevard, Room 4260, MSC 9555
Bethesda, MD  20892-9555
Phone: 301-443-6300
Fax: 301-594-6043

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the Center 
for Scientific Review and for responsiveness by NIDA staff.  Incomplete 
applications will be returned to the applicant without further consideration.

Applications will be reviewed for scientific and technical merit by an 
initial review group convened by the Center for Scientific Review, in 
accordance with the standard NIH peer review procedures.  As part of the 
initial merit review, all applications will receive a written critique and 
may undergo a process in which only those applications deemed to have the 
highest scientific merit will be discussed and assigned a priority score.

REVIEW CRITERIA

Review criteria are described in the Omnibus SBIR Solicitation.  Additional 
review criteria are that the proposal must produce a product or technology 
that will improve mouse insertional mutagenesis and that the applications 
must address the evaluation and validation of the product using C57BL/6 ES 
cells.  The Phase I application should specify clear, measurable goals 
(milestones) that should be achieved prior to initiating Phase II.

Review criteria are described in the NIH Omnibus Solicitation and are 
available on the Web at the following URL address: 
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf.  The goals of NIH-
supported research are to advance our understanding of biological systems, 
improve the control of disease, and enhance health.  The reviewers will 
comment on the following aspects of the application in their written 
critiques in order to judge the likelihood that the proposed research will 
have a substantial impact on the pursuit of these goals.  Each of these 
criteria will be addressed and considered by the reviewers in assigning the 
overall score, weighting them as appropriate for each application.  Note that 
the application does not need to be strong in all categories to be judged 
likely to have a major scientific impact and thus deserve a high priority 
score. 

(1) Significance: Does this study address an important problem?  Does the 
proposed project have commercial potential to lead to a marketable product or 
process?  What may be the anticipated commercial and societal benefits of the 
proposed activity?  If the aims of the application are achieved, how will 
scientific knowledge be advanced?  Does the proposal lead to enabling 
technologies (e.g., instrumentation, software) for further discoveries?  Will 
the technology have a competitive advantage over existing/alternate 
technologies that can meet the market needs? 
 
(2) Approach: Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project?  Is the proposed plan a sound approach for establishing technical 
and commercial feasibility?  Does the applicant acknowledge potential problem 
areas and consider alternative strategies?  Are the milestones and evaluation 
procedures appropriate? 
 
(3) Innovation: Does the project challenge existing paradigms or employ novel 
technologies, approaches, or methodologies?  Are the aims original and 
innovative? 
 
(4) Investigators: Is the Principal Investigator capable of coordinating and 
managing the proposed SBIR/STTR?  Is the work proposed appropriate to the 
experience level of the Principal Investigator and other researchers, 
including consultants and subawardees (if any)? 
 
(5) Environment: Is there sufficient access to resources (e.g., equipment, 
facilities)?  Does the scientific and technological environment in which the 
work will be done contribute to the probability of success?  Do the proposed 
experiments take advantage of unique features of the scientific environment 
or employ useful collaborative arrangements?

In accordance with NIH policy, all applications will also be reviewed with 
respect to the following:

o The adequacy of the proposed protection for animals or the environment to the 
extent they may be adversely affected by the project proposed in the application. 
 
o The appropriateness of the proposed budget and duration in relation to the 
proposed research. 

The following evaluation criterion will be presented in an administrative 
note in the Summary Statement and will not factor into the numerical score:

o The adequacy of plans to make the methods and materials generated in the 
project widely available in a timely fashion to the scientific community, 
given the proposed plan to exercise (or not to exercise) intellectual 
property rights.

Phase II Applications 
 
In addition to the above criteria, to what degree was progress toward the 
Phase I objectives met and feasibility demonstrated in providing a solid 
foundation for the proposed Phase II activity?  

Phase I/Phase II Fast-Track Applications 
 
For Phase I/Phase II Fast-Track applications, the following additional 
criteria will be applied: Does the Phase I application specify clear, 
measurable goals (milestones) that should be achieved prior to initiating 
Phase II?  Did the applicant submit a concise Product Development Plan that 
adequately addresses the four areas described in Section VI, item G, of the 
Omnibus Solicitation?  To what extent was the applicant able to obtain 
letters of interest, additional funding commitments, and/or resources from 
the private sector or non-SBIR/STTR funding sources that would enhance the 
likelihood for commercialization? 
 
AWARD CRITERIA

When making funding decisions, the awarding components take into 
consideration the following: (1) ratings resulting from the scientific and 
technical evaluation process; (2) areas of high program relevance; (3) 
program balance (that is, balance among areas of research); (4) available 
funds; (5) the commercialization status where the small business concern has 
received more than 15 Phase II awards in the prior five fiscal years, if 
applicable (see this application requirement under "Prior SBIR Phase II 
Awards" found in the "Introduction and Application Instructions" portion of 
the Omnibus Solicitation); (6) adequacy of plans to make widely available to 
the research community all research resources developed during this project; 
and (7) adequacy of plans to exercise (or not exercise) intellectual property 
rights while permitting wide availability to the research community of 
patentable research resources developed during this project.  The awarding 
component will notify the Principal Investigator and the applicant small 
business concern of the final disposition of the application. The National 
Institute of Mental Health will support only SBIR grants under this RFA.
ADVICE ON SUBMITTING APPLICATIONS

Potential applicants are strongly encouraged to contact program staff for 
pre-application guidance and/or for more specific information on the research 
topics described in this RFA.  They are also encouraged to read the advice 
and information on SBIR programs located on the Internet at: 
http://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf.

SCHEDULE

Letter of Intent Date:     March 11, 2001
Application Receipt Date:  April 11, 2001
Review by Council:         September 2001
Earliest Award Date:       September 30, 2001

INQUIRIES

Written and phone inquiries are encouraged.  The opportunity to clarify any 
issues or questions from potential applicants is welcome.  Inquiries 
regarding programmatic issues may be directed to:

Dr. Rebekah S. Rasooly
Division of Neuroscience and Behavioral Research
National Institute on Drug Abuse/NIH
6001 Executive Boulevard, Room 4260, MSC 9555
Bethesda, MD  20892-9555
Phone:  301-443-6300
Fax:  301-594-6043
Email:  rr185i@nih.gov

Dr. Cathrine Sasek
SBIR/STTR Coordinator
Office of Science Policy and Communications
National Institute on Drug Abuse/NIH
6001 Executive Boulevard, Room 5237, MSC 9591
Bethesda, MD  20892-9591
Phone:  301-443-6071
Fax:  301-443-6277 
Email:  csasek@nih.gov

Dr. Rochelle K. Small
Craniofacial Anomalies and Injuries Branch
National Institute of Dental and Craniofacial Research/NIH
Natcher Building, Room 4AN-24K
Bethesda, MD 20892
Phone:  301-594-9898
Fax:  301-480-8318
Email:  rochelle.small@nih.gov

Dr. Bernard Janicki
SBIR/STTR Coordinator
National Institute of Dental and Craniofacial Research/NIH
Building 45/4AN-12B
Bethesda, MD 20892-2190
Phone:  301-594-4861
Fax:  301-480-8318
Email:  bj68j@nih.gov

Dr. Anna M. McCormick
Chief, Genetics and Cell Biology Branch
Genetics Program Director
Biology of Aging Program
National Institute on Aging/NIH
Gateway Building, Suite 2C231
7201 Wisconsin Avenue
Bethesda, Maryland  20892 (20814 for express deliveries)
Phone:  301-496-6402
Fax:  301-402-0010
Email:  mccormia@exmur.nia.nih.gov 

Dr. Miriam F. Kelty
National Institute on Aging/NIH
Gateway Building, Rm 218C
7201 Wisconsin Avenue
Bethesda, MD 20892
Phone:  301-496-9322
Fax:  301-402-2945
Email:  mk46u@nih.gov

Dr. Judith H. Greenberg
Director, Division of Genetics and Developmental Biology
National Institute of General Medical Sciences/NIH
Natcher Building, Room 2As25
45 Center Drive, MSC 6200
Bethesda, MD 20892-6200
Phone:  301-594-0943
Fax:  301-480-2228
Email:  greenbej@nigms.nih.gov

Dr. Paul Wolfe
SBIR Program Administrator and Program Contact 
National Institute of General Medical Sciences/NIH
Natcher Building, Room 2As25
45 Center Drive, MSC 6200
Bethesda, MD 20892-6200
Phone:  301-594-0943
Fax:  301-480-2228
Email:  wolfep@nigms.nih.gov

Dr. Michael F. Huerta
Associate Director
Division of Neuroscience and Basic Behavioral Science
SBIR/STTR Coordinator
National Institute of Mental Health/NIH
6001 Executive Boulevard, Room 7202, MSC 9645
Bethesda, MD  20892-9645
Phone:  301-443-3563 
Fax:  301-443-1731
Email:  mhuerta@helix.nih.gov

Dr. Bettie Graham
Division of Extramural Research
SBIR/STTR Coordinator
National Human Genome Research Institute/NIH
Building 31, Room B2B07
Bethesda, MD 20892-2033
Phone:  301-496-7531
Fax:  301-480-2770
Email:  bettie_graham@nih.gov

Dr. Thomas M. Johnson
Program Director
Scientific Programs Branch
National Institute on Deafness and Other Communication Disorders/NIH
Executive Plaza South-400C
6120 Executive Boulevard
Bethesda, MD 20892-7180
Phone:  301-402-3461
Fax:  301-402-6251
Email:  tj65y@nih.gov

Dr. Lynn E. Luethke
SBIR/STTR Coordinator
National Institute on Deafness and Other Communication Disorders/NIH
6120 Executive Boulevard, MSC 7180
Bethesda, MD  20892-7180
Phone:  301-402-3458
Fax:  301-402-6251
Email:  lynn_luethke@nih.gov

Dr. Sheryl Sato
Division of Diabetes, Endocrinology, and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases/NIH
6707 Democracy Plaza, Room 601
Bethesda, MD  20892-5460
Phone:  301-594-8811
Fax:  301-480-3503
Email:  satos@extra.nddk.nih.gov

Dr. Judy Podskalny
SBIR/STTR Coordinator
National Institute of Diabetes and Digestive and Kidney Diseases/NIH
6707 Democracy Plaza, Room 667 
Bethesda, MD  20892-5450
Phone:  301-594-8876
Fax:  301-480-8300
Email:  jp53s@nih.gov

Dr. Peter A. Dudley
Division of Extramural Research 
National Eye Institute/NIH
6120 Executive Boulevard, Suite 350, MSC 7164
Bethesda, MD  20892-7164
Phone:  301-496-0484
Fax:  301-402-0528
Email:  pad@nei.nih.gov

Dr. Ralph Helmsen
SBIR/STTR Coordinator
National Eye Institute/NIH
6120 Executive Boulevard, Suite 350, MSC 7164
Bethesda, MD 20892-7164
Phone:  301-496-5301
Fax:  301-402-0528
Email:  rjh@nei.nih.gov

Dr. Franziska Grieder
Comparative Medicine
SBIR/STTR Coordinator
National Center for Research Resources/NIH
One Rockledge Center
6705 Rockledge Drive, Suite 6050
Bethesda, MD 20892-7965
Phone:  301-435-0744
Fax:  301-480-3819
Email:  GriederF@ncrr.nih.gov

Dr. Robert W. Karp
Division of Basic Research
National Institute on Alcohol Abuse and Alcoholism/NIH
6000 Executive Boulevard, Suite 402, MSC 7003
Bethesda, MD  20892-7003
Phone:  301-443-2239
Fax:  301-594-0673
Email:  rkarp@willco.niaaa.nih.gov

Dr. Michael Eckardt
SBIR/STTR Coordinator
National Institute on Alcohol Abuse and Alcoholism/NIH
6000 Executive Boulevard, Suite 409, MSC 7003
Bethesda, MD 20892-7003
Phone:  301-443-6107
Fax:  301-443-6077
E-mail:  meckardt@willco.niaaa.nih.gov

Dr. Steven Klein
Developmental Biology, Genetics and Teratology Branch
National Institute of Child Health and Human Development/NIH
6100 Executive Boulevard, Room 4B01
Bethesda, MD  20892
Phone:  301-496-5541
Fax:  301-480-0303
Email:  KleinS@Exchange.nih.gov

Dr. Louis A. Quatrano
Director, Behavioral Science and
   Rehabilitation Engineering Program
SBIR Coordinator
National Institute of Child and Health and Human Development/NIH
6100 Executive Boulevard, Room 2A-03
Bethesda, MD  20892
Phone:  301-402-4221
Fax:  301-402-0832
Email:  lq2n@nih.gov

Dr. Jerry Heindel
Scientific Program Administrator
SBIR/STTR Coordinator
Division of Extramural Research and Training
National Institute of Environmental Health Sciences/NIH
P.O.B. 12233
101 T. W. Alexander Drive
Research Triangle Park, NC 27709
Phone:  919-541-0781
Fax:  919-541-5064
Email:  heindelj@niehs.nih.gov

Dr. Alison Deckhut
Basic Immunology Branch
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases/NIH 
6700-B Rockledge Drive, Room 5138, MSC 7640 
Bethesda, MD 20892-7640 
Phone: 301-496-7551
Fax:  301-402-2571
Email: adeckhut@niaid.nih.gov
 
Dr. Greg Milman 
Director, Innovation and Special Programs 
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases/NIH
6700-B Rockledge Drive, Room 2140, MSC 7610 
Bethesda, MD 20892-7610 
Phone: 301-496-8666 
Fax: 301-402-0369 
Email: gm16s@nih.gov

Thomas Miller, Ph.D.
SBIR Program Analyst
Technology Development
National Institute of Neurological Disorders and Stoke/NIH
6001 Executive Boulevard, Room 2139
Bethesda, MD 20892
Phone: 301-496-1779
Fax: 301-402-1501
Email: tm208y@nih.gov

Direct inquiries regarding fiscal matters to:

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse/NIH
6001 Executive Boulevard, Room 3131, MSC 9541
Bethesda, MD  20892-9541
Phone:  301-443-6710
Fax:  301-443-6847
Email:  gf6s@nih.gov

Mr. Martin Rubinstein
Grants Management Branch
National Institute of Dental and Craniofacial Research/NIH
45 Center Drive, Room 4AN-44
Bethesda, MD 20892-6402 
Phone:  301-594-4800
Fax:  301-480-8301 
Email:  Martin.Rubinstein@nih.gov 

Ms. Linda Whipp
Grants and Contracts Management Office
National Institute on Aging/NIH
Gateway Building, Suite 2N212, MSC 9205
7201 Wisconsin Avenue
Bethesda, MD 20892-9205 (20814 for Express deliveries)
Phone:  301-496-1472
Fax:  301-402-3672
Email:  whippl@nia.nih.gov 

Ms. Marcia Cohn
National Institute of General Medical Sciences/NIH
Building 45, Room 2An24
45 Center Drive, MSC 6200
Bethesda, MD 20892-6200
Phone:  301-594-3918
Fax:  301-480-2554
Email:  cohnm@nigms.nih.gov

Ms. Diana S. Trunnell
Grants Management Branch
National Institute of Mental Health/NIH
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD  20892-9605
Phone:  301-443-2805
Fax:  301-443-6885
Email:  Diana_Trunnell@nih.gov

Ms. Jean Cahill 
Grants Administration Branch 
National Human Genome Research Institute/NIH 
Building 31, Room B2-B34
Bethesda, MD 20892-2031 
Phone:  301-402-0733 
Fax:  301-402-1951
Email:  jc166o@nih.gov

Ms. Sara Stone
Chief, Grants Management Office
Division of Extramural Research
National Institute on Deafness and Other Communication Disorders/NIH
Executive Plaza South-400B
6120 Executive Boulevard
Bethesda, MD 20892-7180
Phone:  301-402-0909
Fax:  301-402-1758
Email:  stones@nidcd.nih.gov

Mr. George Tucker
Grants Management Branch
National Institute of Diabetes and Digestive and Kidney Diseases/NIH
6707 Democracy Boulevard, Rm. 654, MSC 5456
Bethesda, MD 20892-5456
Phone:  301-594-8853
Fax:  301-480-3504
Email:  gt35v@nih.gov

Mr. William Darby
Grants Management Officer
National Eye Institute/NIH
Executive Plaza South, Suite 350
Bethesda, MD  20892-7164
Phone:  301-496-5884
Fax:  301-496-9997
Email:  wwd@nei.nih.gov

Mr. Bryan Clark
Office of Grants Management
National Center for Research Resources/NIH
One Rockledge Center, Suite 6174
6705 Rockledge Drive
Bethesda, MD 20892
Tel:  301-435-0835
Fax:  301-480-3777
Email:  ClarkB@ncrr.nih.gov

Ms. Linda Hilley
Office of Planning and Resource Management
National Institute on Alcohol Abuse and Alcoholism/NIH
6000 Executive Boulevard, Suite 504, MSC 7003
Bethesda, MD  20892-7003
Phone:  301-443-4703
Fax:  301-443-3891
Email:  lhilley@willco.niaaa.nih.gov

Mr. Edgar D. Shawver
Grants Management Branch
National Institute of Child Health and Human Development/NIH
6100 Executive Boulevard, Rm. 8A07
Bethesda, MD  20892
Phone:  301-496-5001
Fax:  301-496-0915
Email:  ShawverD@exchange.nih.gov

Ms. Carolyn Winters
Grants Management Specialist, SBIR/STTR
Division of Extramural Research and Training
National Institute of Environmental Health Sciences/NIH
P.O.B. 12233
101 T.W. Alexander Drive
Research Triangle Park, NC 27709
Phone:  919-541-7823
Fax:  919-541-2860
Email:  mwinters@niehs.nih.gov

Ms. Pamela Fleming
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases/NIH
6700-B Rockledge Drive, Room 2119, MSC 7614 
Bethesda, MD  20892-7614 (Regular Mail) 
Bethesda, MD  20817 (Express Mail) 
Phone: 301-402-6580 
Fax: 301-493-0597 
Email: pf49e@nih.gov

Ms. Joellen Harper
Grants Management Branch
National Institute of Neurological Disorders and Stoke/NIH
6001 Executive Boulevard, Room 3290
Bethesda, MD 20892
Phone: 301-496-9231
Fax: 301-402-0219
Email: jh41m@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance Nos. 
93.279 (NIDA), 93.866 (NIA), 93.862 (NIGMS), 93.121 (NIDCR), 93.242 (NIMH), 
93.172 (NHGRI), 93.371 (NCRR), 93.173 (NIDCD), 93.273 (NIAAA), 93.847 
(NIDDK), 93.867 (NEI), 93.864 and 93.865 (NICHD), 93.113 (NIEHS), 93.855 
(NIAID), and 93.853 (NINDS).  Awards are made under authorization of the 
Public Health Service Act, Title IV part A (Public Law 78-419 as amended by 
Public Law 99-158, 42USC 241 and 285) and administered under NIH grants 
policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74.  This 
program is not subject to the intergovernmental review requirements of 
Executive Order 12372 or Health Systems review.

The PHS strongly encourages all grant and contract recipients to provide a 
smoke-free workplace and promote the non-use of all tobacco products.  In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking 
in certain facilities (or in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care, or early 
childhood development services are provided to children.  This is consistent 
with the PHS mission to protect and advance the physical and mental health of 
the American people.


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