MOLECULAR TARGETS FOR CANCER DRUG DISCOVERY: SBIR/STTR

RELEASE DATE:  November 7, 2002

PA NUMBER: PA-03-021

EXPIRATION DATE: April 2, 2003, unless reissued. 

National Cancer Institute (NCI)  
 (http://www.nci.nih.gov/)

APPLICATION RECEIPT DATE:  April 1, 2003  

This Program Announcement (PA) replaces PAR-00-061, which was published 
in the NIH Guide on February 18, 2000.

THIS PA CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PA
o Research Objectives
o Mechanisms of Support 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS PA  

The purpose of this Program Announcement (PA) is to promote full use of 
the base of knowledge of cancer biology for cancer-related target 
validation and drug discovery and development for treatment and 
prevention.   Similar to the Exploratory Grant (R21) initiative 
(http://grants.nih.gov/grants/guide/pa-files/PA-03-020.html), this 
initiative is intended to encourage and support young, upstart 
biotechnology companies and also more established firms to direct their 
efforts into new ventures in cancer therapeutics. That great advances 
have been made in the past decade in our understanding of the cell in 
health and disease is unquestioned.  Many genes that have mutated and 
many molecular processes that have gone awry in a cancer cell have been 
identified, and new information on the difference between a normal and 
a cancer cells continues to be added to this wealth of knowledge.  It 
is now incumbent that this knowledge be used to mount a renewed attack 
on cancer - for its prevention and its treatment.  While the empiric 
approach may have yielded its dividends, the new paradigm demands a 
more reasoned and knowledge-based approach. The search for molecules or 
agents with translational potential that will redirect the behavior of 
the target and subvert its deleterious effect will be an important 
component of this PA. These agents could be chemical or biological, man 
made or naturally occurring, but well characterized or subject to 
characterization as potential therapeutic agents.  The development and 
utilization of modern tools for target validation and drug discovery, 
including combinatorial libraries and high throughput screening, would 
be appropriate.  More information on this program can be found at 
http://dtp.nci.nih.gov and at http://dcp.nci.nih.gov.  For a better 
appreciation of the contextual frame work of this initiative, see the 
NCI document -- The Nation's Investment in Cancer Research: Plans and 
Priorities for Cancer Research -- at http://plan.cancer.gov  

This Program Announcement (PA) must be read in conjunction with the 
current OMNIBUS SOLICITATION OF THE NATIONAL INSTITUTES OF HEALTH, 
CENTERS FOR DISEASE CONTROL AND PREVENTION, AND FOOD AND DRUG 
ADMINISTRATION FORSMALL BUSINESS INNOVATION RESEARCH (SBIR) and SMALL 
BUSINESS TECHNOLOGY TRANSFER (STTR) GRANT APPLICATIONS (see 
http://grants.nih.gov/grants/funding/sbir.htm).
 
RESEARCH OBJECTIVES

Background  

The past decade has witnessed an unprecedented accumulation of 
knowledge of the genetic make up and biological function of the cell. 
In parallel there have been technological advancements allowing ever 
more detailed inquiry into its structure and function.  The deciphering 
of the human genome sequence with its boost to functional genomics and 
proteomics is a harbinger of things to come.  Much is now known about 
the molecules and molecular processes that sustain the life of the 
cell.  The structural and functional differences between a normal and a 
cancer cell are being defined with increasing precision.  A detailed 
understanding of such cellular processes as signal transduction from 
within or without, cell cycle regulation, apoptosis, migration and 
metastasis are revealing new points of potential vulnerability in a 
cancer cell.  The events that occur in the initiation and in the 
maintenance of cancer, including metastasis are being delineated with 
increasing confidence.  Thus, the stage is set for exciting new 
approaches for the discovery and development of drugs for cancer 
prevention and treatment.

Objectives  

The objective of this initiative is to support initial preclinical 
studies towards developing novel drugs for cancer treatment and 
prevention.  The focus will be on new molecular targets and new agents 
that modulate them.  The exploration of new targets will include their 
characterization, and establishment of their relevance to cancer.  
Novel ways of looking at and exploiting previously known targets also 
would be appropriate, but mere extension or reconfirmation of what is 
already known will not be.  These targets may be relevant to any type 
of cancer, including pediatric cancers.  The targets may encompass any 
cellular process, from cell cycle and apoptosis to angiogenesis and 
metastasis, and also the components of the immune system. However, this 
process must be that which is clearly altered in cancer cells and is 
well defined in molecular terms for monitoring and manipulation. The 
development of new assays and innovative technologies for monitoring in 
itself will not be sufficient; their development in conjunction with 
molecular target identification and validation, and drug  discovery and 
development will be appropriate.

For the NCI resources available to qualified investigators in support 
of research, such as the compound libraries and the natural product 
repository, see http://dtp.nci.nih.gov.

The SBIR/STTR mechanism requires that the research be directed toward 
commercialization of a product or a service.

MECHANISMS OF SUPPORT 

Support for this PA is through the SBIR and STTR mechanisms that are 
set-aside programs.  As an applicant, you will be solely responsible 
for planning, directing, and executing the proposed project.

This PA is a one-time announcement that may be reissued.  Except as 
otherwise stated in this PA, awards will be administered under NIH 
grants policy as stated in the NIH Grants Policy Statement, March 2001, 
available at: http://grants.nih.gov/grants/policy/nihgps_2001/

Applications can be submitted for support as Phase I STTR (R41) or 
Phase I SBIR (R43) grants; Phase II STTR (R42) or Phase II SBIR (R44) 
grants; or the SBIR/STTR FAST-TRACK option as described in the OMNIBUS 
SOLICITATION.  Phase II applications in response to this PA will only 
be accepted as competing continuations of previously funded NIH Phase I 
SBIR/STTR awards.  The Phase II application must be a logical extension 
of the Phase I research.  The Phase I research need not have been 
supported by the original issue – PAR-00-61.

Information on the FAST-TRACK process and the OMNIBUS SOLICITATION are 
available at: http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf.    

ELIGIBLE INSTITUTIONS

Eligibility requirements are described in the OMNIBUS SOLICITATION.  
Small business concerns are eligible to submit applications.  A small 
business concern is one that, on the date of award for both Phase I and 
Phase II agreements, meets ALL of the following criteria:

o is organized for profit, with a place of business located in the 
United States, which operates primarily within the United States or 
which makes a significant contribution to the United States economy 
through payment of taxes or use of American products, materials or 
labor;

o is in the legal form of an individual proprietorship, partnership, 
limited liability company, corporation, joint venture, association, 
trust or cooperative, except that where the form is a joint venture (as 
defined in this section) there can be no more than 49 percent 
participation by foreign business entities in the joint venture;

o is at least 51 percent owned and controlled by one or more 
individuals who are citizens of, or permanent resident aliens in, the 
United States; has, including its affiliates, not more than 500 
employees, and meets the other regulatory requirements found in 13 CFR 
Part 121.  Business concerns, other than investment companies licensed, 
or state development companies qualifying under the Small Business 
Investment Act of 1958, 15 U.S.C. 661, et seq., are affiliates of one 
another when either directly or indirectly, (a) one concern controls or 
has the power to control the other; or (b) a third-party/parties 
controls or has the power to control both. Control can be exercised 
through common ownership, common management, and contractual 
relationships.  The term "affiliates" is defined in greater detail in 
13 CFR 121.3-2(a).  The term "number of employees" is defined in 13 CFR 
121.3-2(t).

Business concerns include, but are not limited to, any individual (sole 
proprietorship), partnership, corporation, joint venture, association, 
or cooperative.  Further information may be obtained by contacting the 
Small Business Administration Size District Office at 
http://www.sba.gov/size/. For both Phase I and Phase II, the R&D must 
be performed in its entirety in the United States.  

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to 
carry out the proposed research is invited to work with their 
institution to develop an application for support.  Individuals from 
underrepresented racial and ethnic groups as well as individuals with 
disabilities are always encouraged to apply for NIH programs. On an 
SBIR, the principal investigator must have his/her primary employment 
with the small business at the time of award and for the duration of 
the project.    

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PA and welcome the 
opportunity to answer questions from potential applicants.  Inquiries 
may fall into two areas: scientific/research and financial or grants 
management issues:

o Direct your questions about scientific issues in cancer treatment to:

Suresh K. Arya, Ph.D.
Development Therapeutics Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Boulevard, EPN 8153
Bethesda, MD 20892-7456
(For express/courier service: Rockville, MD 20852)
Tel: 301-496-8783
Fax: 301-402-5200
Email: aryas@exchange.nih.gov

Direct your questions about scientific issues in cancer prevention to:

Winfred F. Malone, Ph.D.
Chemoprevention Agents Development Research Group
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, EPN 200A
Bethesda, MD 20892-7322
(For express/courier service: Rockville, MD 20852)
Tel: 301-594-0460
Fax: 301-402-0553
Email: malonew@mail.nih.gov

o Direct your questions about financial or grants management matters 
to:

Eileen M. Natoli
Grants Administration Branch
National Cancer Institute
6120 Executive Blvd. – EPS 243
Bethesda, MD  20892
Telephone:  (301) 496-8791
Email:  natolie@gab.nci.nih.gov

SUBMITTING AN APPLICATION

The PHS 398 research grant application (rev. 5/2001) must be used.  
Instructions and forms are available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html.   Refer to 
Chapter VI for specific instructions for SBIR and STTR applications.  
Applications will be accepted on the dates listed on the first page of 
this PA.  This version of PHS 398 is available in an interactive, 
searchable PDF and HTML format.  The NIH will return applications that 
are not submitted on the 5/2001 version.  For further assistance 
contact GrantsInfo, Telephone: (301) 435-0714, Email: 
mailto:GrantsInfo@nih.gov. 

The SBIR/STTR OMNIBUS SOLICITATION is available electronically through 
the NIH, Office of Extramural Research Small Business Funding 
Opportunities web site: 
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf.  The 
solicitation contains information about the SBIR and STTR programs, 
regulations governing the programs, and instructional information for 
submission.  Applicants are required to use the PHS398 forms for all 
SBIR and STTR submissions.  Helpful information for preparation of the 
application can be obtained at: 
http://grants.nih.gov/grants/funding/sbirgrantsmanship.pdf. 
THE TITLE AND NUMBER OF THIS PA MUST BE TYPED ON LINE 2 OF THE FACE 
PAGE OF THE APPLICATION.

All instructions within the solicitation apply. 

FAST TRACK: 

The NIH Fast-Track mechanism expedites the decision and award of SBIR 
and STTR Phase II funding for scientifically meritorious applications 
that have a high potential for commercialization.  Fast Track 
incorporates a submission and review process, in which complete Phase I 
and Phase II grant applications are submitted simultaneously and 
reviewed together.  The FAST-TRACK must have a section labeled 
Milestones at the end of the Phase I Research Plan.  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. 
Failure to provide such information 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 from 
consideration.  If so, the applicant may apply later for Phase II 
support.  Such applications will be reviewed by an appropriate 
scientific review group convened by the NIH. 

In addition, the Phase II portion of a Fast Track application must 
include a concise Product Development Plan (limited to ten pages).  
Label this section clearly and include it in Section J of the Phase II 
Research Plan.  More detailed instructions on the preparation of a Fast 
Track application are described in the PHS 398 at 
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf#page=21.

APPLICATION RECEIPT DATE: Applications submitted in response to this 
program announcement will be accepted by the receipt date listed at the 
beginning of this program announcement.

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten 
original of the application, including the checklist, and five signed 
photocopies 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)

APPLICATIONS HAND-DELIVERED BY INDIVIDUALS TO THE CENTER FOR SCIENTIFIC 
REVIEW WILL NO LONGER BE ACCEPTED.  This policy does not apply to 
courier deliveries (i.e. FEDEX, UPS, DHL, etc.) 
(http://grants.nih.gov/grants/guide/notice-files/NOT-CA-02-012.html)

APPLICATION PROCESSING: Applications must be received by or mailed on 
or before the receipt date(s) listed at the top of the first page of 
this PA.  The CSR will not accept any application in response to this 
PA that is essentially the same as one currently pending initial 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 a substantial 
revision of an application already reviewed, but such application must 
include an Introduction addressing the previous critique.

PEER REVIEW PROCESS

Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.  An appropriate scientific review 
group convened in accordance with the standard NIH peer review 
procedures (http://www.csr.nih.gov/refrev.htm) will evaluate 
applications for scientific and technical merit.  

Applications that are complete and adhere to the guidelines of this PA 
will be evaluated for scientific and technical merit and the documented 
ability of the investigators to meet the RESEARCH OBJECTIVES of this PA 
by an appropriate peer review group convened by the Center for 
Scientific Review, in accordance with the peer review criteria listed 
below.

As part of the initial merit review, all applications will:

o  Receive a written critique
o  Undergo a process in which only those applications deemed to have 
the highest scientific merit, generally the top half of the 
applications under review, will be discussed and assigned a priority 
score
o  Those which receive a priority score will undergo a second-level 
review by an appropriate advisory council or board.

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  
In the written comments, reviewers will be asked to discuss the 
following aspects of your application in order to judge the likelihood 
that the proposed research will have a substantial impact on the 
pursuit of these goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
The scientific review group will address and consider each of these 
criteria in assigning your application's overall score, weighting them 
as appropriate for each application.  Your application does not need to 
be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score.  For example, 
you may propose to carry out important work that by its nature is not 
innovative but is essential to move a field forward.

SIGNIFICANCE.  
Does the 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 (instrumentation, software, etc.) for further 
discoveries?   Will the technology have a competitive advantage over 
existing/alternative technologies that can meet the market needs?

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?

INNOVATION.  
Does the project challenge existing paradigms or employ novel 
technologies, approaches or methodologies?  Are the aims original and 
innovative?

INVESTIGATOR.  
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 sub-contractors (if any)?

ENVIRONMENT.  
Is there sufficient access to resources (equipment, facilities, etc.)?  
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?

For 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? Is there a detailed validation plan?

For Phase I/Phase II Fast Track applications, the following additional 
criteria will be applied: Does the Phase I 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 9.j in the 
Instructions for the SBIR/STTR applications?  To what extent was the 
applicant able to obtain letters of interest, additional funding 
commitment and/or resources from private sector or non-SBIR/STTR 
funding sources that would enhance the likelihood for 
commercialization?  The initial review group will evaluate the specific 
goals for both the R43 and R44 phase.  A single priority score will be 
assigned to each application.  The initial review group has the option 
of recommending support for a shorter duration than that requested and 
basing the final merit rating on the recommended portion of the 
application.  For FAST TRACK applications, this may result in a 
recommendation that only the R43 phase be supported. 

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your 
application will also be reviewed with respect to the following:

PROTECTIONS:  
The adequacy of the proposed protection for humans, animals, or the 
environment, to the extent they may be adversely affected by the 
project proposed in the application.

INCLUSION:  
The adequacy of plans to include subjects from both genders, all racial 
and ethnic groups (and subgroups), and children as appropriate for the 
scientific goals of the research.  Plans for the recruitment and 
retention of subjects will also be evaluated. (See Inclusion Criteria 
included in the section on Federal Citations, below).

BUDGET:  
The reasonableness of the proposed budget and the requested period of 
support in relation to the proposed research.

AWARD CRITERIA

Applications submitted in response to a PA will compete for available 
funds with all other recommended SBIR and STTR applications.  Portions 
of the SBIR and STTR allotments will not be designated for this 
initiative.  The following will be considered in making funding 
decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program priorities

FAST TRACK, Phase II applications may be funded following submission of 
the Phase I progress report and other documents necessary for 
continuation.  Phase II applications will be selected for funding based 
on the initial priority score, grant Program staff's assessment of the 
Phase I progress and determination that Phase I goals were achieved, 
the project's potential for commercial success, and the availability of 
funds.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Dates:  March 3, 2003
Application Receipt Dates:  April 1, 2003
Council Review Dates:  September 9, 2003
Earliest Anticipated Award Date:  September 30, 2003

REQUIRED FEDERAL CITATIONS 

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS.   
NIH policy requires education on the protection of human subject 
participants for all investigators submitting NIH proposals for 
research involving human subjects.  You will find this policy 
announcement in the NIH Guide for Grants and Contracts Announcement, 
dated June 5, 2000, at http://grants.nih.gov/grants/guide/notice-
files/NOT-OD-00-039.html.  A continuing education program in the 
protection of human participants in research in now available online 
at: http://cme.nci.nih.gov/

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of 
research on hESCs can be found at 
http://grants.nih.gov/grants/stem_cells.htm and at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  
Guidance for investigators and institutional review boards regarding 
research involving human embryonic stem cells, germ cells, and stem 
cell-derived test articles can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-044.html. Only 
research using hESC lines that are registered in the NIH Human Embryonic 
Stem Cell Registry will be eligible for Federal funding (see 
http://escr.nih.gov).  It is the responsibility of the applicant to 
provide the official NIH identifier(s)) for the hESC line(s) to be used 
in the proposed research.  Applications that do not provide this 
information will be returned without review.

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.  Furthermore, we caution reviewers that their 
anonymity may be compromised when they directly access an Internet 
site.

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 PA is related to one or more of the priority areas. 
Potential applicants may obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance No. 93.395, Cancer Treatment Research, and 
is not subject to the intergovernmental review requirements of 
Executive Order 12372 or Health Systems Agency review.  Awards are made 
under authorization of Sections 301 and 405 of the Public Health 
Service Act as amended (42 USC 241 and 284) and administered under NIH 
grants policies described at 
http://grants.nih.gov/grants/policy/policy.htm  and under Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92..

The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and discourage the 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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, RealPlayer, Video or Flash files, see Help Downloading Files.