SMALL BUSINESS INNOVATION RESEARCH: ANIMAL MODELS OF HCV INFECTION

Release Date:  November 30, 1999

RFA:  AI-00-008

National Institute of Allergy and Infectious Diseases
National Cancer Institute
National Institute of Alcohol Abuse and Alcoholism
National Center for Research Resources

Letter of Intent Receipt Date:  January 24, 2000
Application Receipt Date:       February 24, 2000

PURPOSE

This is a multi-Institute solicitation targeting the 
development/identification of one or more small animal models of 
hepatitis C infection and disease progression including acute and 
chronic states, fibrosis/cirrhosis, and liver tumor development-not 
necessarily all in the same model.  Identification of a small, 
inexpensive, reproducible, well-defined, and non-endangered mammalian 
animal model for hepatitis C research is critical to the progress of 
exploration of this pathogen. It is needed to study the pathogenesis, 
immunology, natural history, and viral replication of hepatitis C as 
well as to act as a model for the testing of new therapies and, 
hopefully, vaccine candidates. To date, the chimpanzee, expensive and of 
limited access, is the only non-human model. This Request for 
Applications invites grant applications for Small Business Innovation 
Research (SBIR) 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 of 
the Public Health Service (Omnibus Solicitation) for Phase I SBIR Grant 
Applications (PHS 98-2) and the instructions for Phase II Grant 
Applications revised March 1998.  All instructions and information in 
these documents also apply to applications.  Recently 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 provides a flexible system within the SBIR program to cover the 
extensive needs and complex development processes needed to 
identify/define and develop a novel animal model of a hazardous 
infection-hepatitis C.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2000," a 
PHS-led national activity for setting priority areas.  This RFA, SBIR: 
Animal Models of HCV Infection, is related to the priority areas of 
immunization and infectious diseases, HIV infection, sexually 
transmitted diseases, clinical preventive services, maternal and infant 
health, diabetes and chronic disabling conditions, and surveillance and 
data systems. Potential applicants may obtain a copy of "Healthy People 
2000" at http://odphp.osophs.dhhs.gov/pubs/hp2000.

ELIGIBILITY

Eligibility requirements are described in the Omnibus Solicitation. Any 
small business, independently owned and operated by United States 
citizens or permanent resident aliens may apply.  It must be organized 
for-profit, cannot be dominant in its field of expertise, and must have 
its principal place of business in the United States.  Including any 
affiliates, the company can be the employer of no more than 500 people.

MECHANISM OF SUPPORT - PHASE I

Phase I applications in response to this RFA will be funded as Phase I 
SBIR Grants (R43) with modifications as described below. Responsibility 
for the planning, direction, and execution of the proposed research will 
be solely that of the applicant.  Applications for Phase I grants should 
be prepared following the directions for Phase I SBIR applications as 
described in the Omnibus Solicitation.  Phase II applications in 
response to this RFA will only be accepted as competing continuations of 
previously funded NIH Phase I SBIR awards. 

The Phase II application must be a logical extension of the Phase I 
research. The Omnibus Solicitation and information on the FAST-TRACK 
process are available on the Internet at: 
http://grants.nih.gov/grants/funding/sbir1/SBIR.HTM

A limited number of hard copies of the Omnibus Solicitation are 
available from:

PHS SBIR/STTR Solicitation Office
13685 Baltimore Avenue
Laurel, MD  20707-5096
Telephone:  (301) 206-9385
FAX:  (301) 206-9722
Email:  a2y@cu.nih.gov

PROJECT PERIOD AND AMOUNT OF AWARD

PHASE I:
Because the length of time and cost of research involving development 
and evaluation of animal models for infectious diseases often exceeds 
that routinely awarded for SBIR grants, the participating Institutes 
will entertain well-justified Phase I applications for an SBIR award 
with a project period up to two years and a budget not to exceed a total 
cost of $300,000 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% of the total costs requested for Phase I SBIR 
applications. However, we will entertain well-justified Phase I 
applications for an SBIR award with greater than 33% contractual costs 
when those costs are necessary to support development and evaluation of 
animal models.

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

PHASE II:
Phase II applications in response to the second release of this RFA will 
be awarded as Phase II SBIR grants (R44). Phase II applications in 
response to this RFA will only be accepted as competing continuations of 
previously funded NIH Phase I SBIR awards.

Applications for Phase II awards should be prepared following the 
instructions for NIH Phase II SBIR applications. The Phase II SBIR 
instructions and application may be found on the Internet at:
http://grants.nih.gov/grants/funding/sbir2/index.htm

Project Period and Amount of Award:  Because the length of time and cost 
of research involving animal model development projects often exceeds 
that routinely awarded for SBIR grants, participating Institutes will 
entertain well-justified Phase II applications for an SBIR award with a 
project period up to three years and a budget not to exceed $1 million 
per year total cost.

Consultant and contractual costs:  The total amount of all consultant 
costs and contractual costs normally may not exceed 50% of the total 
costs requested for Phase II SBIR applications.  However, participating 
Institutes will entertain well-justified Phase II applications for an 
SBIR award with greater than 50% contractual costs when those costs are 
necessary to support animal model development and evaluation, including 
clinical studies in academic institutions.

FUNDS AVAILABLE

It is expected that approximately 10 awards will be made in FY2000. $3.2 
million from the SBIR set-asides of the participating Institutes 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

The participating Institutes invite applications for SBIR awards in the 
following areas:

A.  Identification/creation of suitable animal models for studying one 
or more key aspects of HCV infection, replication, and pathogenesis.  
Suitability includes animals that are easily housed and subject to 
experimental manipulation, not protected species, and to the maximum 
extent possible small, inexpensive, and easily procurable.

B.  Development and testing of animal models for HCV infection 
identified in part A, from initial infection through chronic infection, 
liver disease, cirrhosis, and liver cancer.  Such models should ideally 
mimic the full range of the disease spectrum or, more realistically, one 
or more critical aspects of the following phases of human disease by 
HCV: initial/acute infection; chronicity; disease stages and progression 
including inflammation, fibrosis, cirrhosis and other aspects of 
morbidity; and mortality causes such as liver failure or hepatocellular 
cancer.

C.  Validation of such model systems, including the applicable 
properties indicated in part B, by qualified independent investigators.

LETTER OF INTENT

Prospective applicants are asked to submit, by the receipt date listed 
at the beginning of this RFA, a letter of intent that includes a 
descriptive title of the proposed research, the name, address, and 
telephone 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 NIAID staff to estimate the potential review 
workload and avoid conflict of interest in the review.

The letter of intent is to be sent (fax, e:mail, or post) to Dr. Leslye 
D. Johnson, NIAID, at the address listed under INQUIRIES.

APPLICATION PROCEDURES

Applicants should follow the instructions for SBIR Phase I or Phase II 
submission with the modifications as noted in this RFA.  An example of 
an outstanding SBIR application can be found on the Web at
http://www.nhlbi.nih.gov/nhlbi/sbir/modelsbi.htm

This RFA must be read in conjunction with the OMNIBUS SOLICITATION OF 
THE PUBLIC HEALTH SERVICE FOR SMALL BUSINESS INNOVATION RESEARCH GRANT 
(SBIR) APPLICATIONS (PHS 98-2).  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 SOLICITATIONS for the SBIR program.  OMNIBUS 
SOLICITATIONS are available electronically through the NIH, Office of 
Extramural Research "Small Business Funding Opportunities" Website:
http://grants.nih.gov/grants/funding/sbir.htm.  Hard copies, subject to 
availability, may be obtained from the PHS SBIR/STTR Solicitation 
Office, phone (301) 206-9385; FAX (301) 206-9722; email a2y@cu.nih.gov.  
Helpful information in preparation of the application can be obtained:
http://grants.nih.gov/grants/funding/sbirsttradvice.htm

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)
http://grants.nih.gov/grants/funding/sbir1/SBIR.HTM

SBIR Phase II - PHS 6246-2 (1/98)
http://grants.nih.gov/grants/funding/sbir2/index.htm

The application forms are also located in the back pages of the OMNIBUS 
SOLICITATIONS.  Applications will be accepted on or before February 24, 
2000.  The RFA title and number must be typed in line 2 on the face page 
of the application form.

The sample RFA label available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been 
modified to allow for this change.  Please note this is in pdf format.

If an application is received after the application receipt 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.  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 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 or Phase II support, or as a 
combined Phase I and II (FAST TRACK).  Phase II applications will only 
be accepted as continuations of previously funded Phase I grants.  The 
Phase II proposal must be a logical extension of the Phase I research 
but not necessarily a Phase I supported in response to this RFA.

Projects may be presented for SBIR support at all stages of the HCV 
animal model discovery and development process.  Projects will be 
evaluated on overall innovation and success potential of the research 
path proposed to animal model identification/development.

Larger budgets could be considered for phase I if required for conduct 
of the research and appropriately justified in the application.  The 
second year of support will be contingent upon NIAID (or appropriate 
Institute) programmatic evaluation to ensure that investigators are 
accomplishing milestones and time lines presented in the original 
application.

PHASE II: Continuing support for development of HCV animal infection 
models and for establishment of model validity by in-house and by 
independent investigators knowledgeable of animal model characteristics. 
Potential animal model candidates may extend to assessment for use in 
studies in immunology including autoimmune diseases, alcohol and drug 
abuse, pathogenesis, natural history studies, antiviral screenings, etc.  
This may include the identification of surrogate endpoints to define 
success of therapeutic treatments or efficacy of vaccine candidates.  
Outside of presently licensed therapies, NIAID has the potential to 
provide novel antiviral compounds for testing in proven models.

Phase II awards may be for up to three years at $1 million, total costs, 
per year.  As with Phase I, requests for larger budgets may be 
considered, and support for years four and five is dependent upon 
Institute Programmatic review of progress and achievement of proposed 
milestones and evaluation of additional information not required in the 
original application.

FAST TRACK: Due to the complex nature of the HCV animal 
identification/development process, 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 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.

The completed original application and two single sided copies must be 
sent or delivered 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 the SBIR Phase I 
applications and in item 1A of the face page of Phase II grant 
applications (i.e., "SBIR: HCV Animal Models of Infection," AI-00-008).  
Follow the mailing instructions in the Omnibus Solicitation for Phase I 
applications.  Follow the mailing instructions in the Phase II 
application package for Phase II applications.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the NIH 
Center for Scientific Review.  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 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 Solicitation.  The Phase I 
application should specify clear, measurable goals (milestones) that 
should be achieved prior to initiating Phase II.

AWARD CRITERIA

The following will be considered when making funding decisions: quality 
of the proposed project as determined by peer review, program balance 
among research areas of the announcement, the availability of funds, and 
the commercialization status where the small business concern has 
received more than 15 Phase II wards in the prior five (5) 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).

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

INQUIRIES

Written and telephone 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. Leslye D. Johnson
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
6700B Rockledge Drive, Rm. 3209 MSC 7630
Bethesda, MD  20892-7630
Telephone:  (301) 496-7051
FAX:  (301) 402-1456
Email:  lj7m@nih.gov

Dr. John Cole III
Division of Cancer Biology
National Cancer Institute
Executive Plaza North, Room 540
Bethesda, MD  20892-7209
Telephone:  (301) 496-1718
FAX:  (301) 496-2025
Email:  jc121b@nih.gov

Dr. Thomas Kresina
Biomedical Research Branch
National Institute of Alcohol Abuse and Alcoholism
6000 Executive Blvd, 402
MSC 7003
Bethesda, MD 20892
Telephone:  (301) 443-6537
FAX:  (301) 496-0537
Email:  tk13v@nih.gov

Dr. Raymond O’Neil
Director, Chimpanzee Management Plan (ChiMP)
Comparative Medicine, NCRR, NIH
Suite 6030  
6705 Rockledge Drive
Bethesda, MD  20892-7965	
Telephone: (301) 435-0744
FAX :(301) 480-3819 
Email: raymondo@ncrr.nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Mary Kirker
Grants Management Branch
National Institute of Allergy and Infectious Diseases
6700B Rockledge Drive, Room 2116 MSC 7610
Bethesda, MD  20892-7610
Telephone:  (301) 496-7075
FAX:  (301) 480-3780
Email:  mc40u@nih.gov

AUTHORITY AND REGULATIONS

This program is supported under authorization of the Public Health 
Service Act, Sec. 301(c), Public Law 78-410, as amended.  The Catalogue 
of Federal Domestic Assistance Numbers are 93.855 and 93.856.  Awards 
will be administered under PHS 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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