kristoff@GENBANK.BIO.NET (Dave Kristofferson) (09/06/90)
REQUEST FOR COOPERATIVE AGREEMENT APPLICATIONS:
RFA: AI-90-09
Re-issuance of RFA 87-AI-24 dated September 25, 1987
NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR THE TREATMENT OF
HUMAN IMMUNODEFICIENCY VIRUS INFECTION
P.T. 34; K.W. 0715008, 0740020, 0755025
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Letter of Intent Receipt Date: October 1, 1990
Application Receipt Date: December 6, 1990
The NIAID invites applications for the establishment of National
Cooperative Drug Discovery Groups for the Treatment of Human
Immunodeficiency Virus Infection (NCDDG/HIV).
The NIAID plans to continue its support of the National Cooperative
Drug Discovery Group (NCDDG) Program. Reissue of this initiative in future
years is anticipated but not certain.
LETTER OF INTENT
Prospective applicants are asked to submit by October 1, 1990, a
letter of intent that includes a descriptive title of the overall
proposed research, the name and institution of the Principal
Investigator, a title for each component research project and brief
descriptions of the proposed projects. Names of prospective
project leaders and other key investigators and their institutions
should be included (maximum of two pages). The letter of intent is
requested in order to provide an indication of the number and scope
of applications to be reviewed and in order to allow early
preparations for review as well as promote early interactions
between applicants and NIAID staff. The letter of intent does not
commit the sender to submit an application, nor is it a requirement
for submission of an application. The letter of intent should be
sent to:
Dr. Nava Sarver
Acting Chief
Targeted Drug Discovery Section
Developmental Therapeutics Branch
Division of AIDS
National Institute of Allergy
and Infectious Diseases
6003 Executive Boulevard, Room 245P
Bethesda, MD 20892
Telephone: (301) 496-8197
I. SUMMARY AND BACKGROUND
Acquired Immune Deficiency Syndrome (AIDS) is a disease that
destroys the body's capacity to overcome a variety of
infections. By April 1990, over 132,000 cases of AIDS had
been reported in the United States and more than 80,000 of
these patients (61%) had died. Recent projections indicate
that between 850,000 to 1,000,000 persons in the United
States may already be infected with HIV, the infectious
virus associated with AIDS. The only drug currently
licensed for the treatment of AIDS is zidovudine (AZT, 3'-
azidothymidine). The search for improved therapies to treat
AIDS is among the highest priorities of the Department of
Health and Human Services.
The NIAID and the PHS Centers for Disease Control are
currently supporting comprehensive extramural and intramural
projects for the study of the etiology, natural history, and
demographics of AIDS; screening of high-risk individuals;
determining means of diminishing the risk of infection;
development of prophylactic vaccines; development of
therapies to treat those with AIDS-related complex (ARC);
and development of therapies that may be useful
chemopreventive or prophylactic agents. Notwithstanding
these efforts, the rapidity of the increase in diagnosed
cases of AIDS and the morbidity of the disease require the
mobilization of the most creative scientific talents,
regardless of their scientific discipline or organizational
affiliations, into groups whose objective is to pursue
aggressively a concerted research effort to discover
entities and strategies for treatment of this disease.
The recognition of HIV as the etiological agent associated
with AIDS, the isolation and characterization of the virus,
the ability to grow HIV on a large scale, and emerging
knowledge of the molecular biology of HIV have made it
possible to screen for potentially effective antiviral
compounds. The possibility of discovering an effective
treatment of the infection based on compounds targeted
against selected steps in the viral replication cycle has
been shown in vitro with several drugs (3'-azidothymidine,
dideoxycytidine, dideoxyinosine, inhibitors of protease) and
other viral functions (soluble CD4). Most of the effort to
date has been made with nucleoside analogues designed to
interfere with HIV-1 reverse transcriptase. Considerable
effort has also been directed toward development of soluble
CD4 and its congeners to block entry of HIV into uninfected
cells or CD4-toxin conjugates to kill cells expressing HIV
gp120 on their surface. While efforts are underway to
design therapies that block other viral specific targets
(e.g., inhibitor of HIV regulatory functions, Tat and Rev) or
use of substrate analogues to interfere with enzymes or
pathways obligatory for virus replication (e.g., inhibitors
of myristoylation), these efforts are insufficient. To
date, not all HIV genes are fully characterized and the
function of some is still enigmatic; further, new gene
products have been identified within the last 12 months
suggesting that other HIV genes are yet to be discovered.
HIV-induced defects in biochemical pathways need be explored
as another approach to counteract the consequences of
infection; and the emergence of drug resistant HIV strains
imposes a constant demand for alternative therapies.
Applications that include a research project or a core
component from the private sector (e.g., pharmaceutical,
chemical, or biotechnological companies) are encouraged.
Research directed toward drug discovery utilizing one or
more of the following approaches will be considered
responsive to this Request for Applications (RFA):
humoral and cellular arms of the
immune system; immune-based therapies; structure,
biophysical and biological properties of cellular or viral
proteins; biochemistry of viral-host interactions;
inhibitors of enzymatic functions and biochemical pathways;
repressors of HIV regulatory elements; drug metabolism; drug
targeting (peptides, nucleic acids, and other compounds);
gene delivery using viral vectors; ribozymes as repressors
of HIV gene function; emergence of drug-resistant strains
and ways to counteract it; viral and cellular parameters
associated with neurological dysfunction; and discovery,
biochemical and biological characterization of promising
naturally occurring products or synthetic chemical
compounds, will be considered responsive to this RFA.
Projects or cores with proposed animal model development or
efficacy testing in animal models must be integrated into
and required to attain the Group's objectives. Funds for
evaluation of new agents in animal models will be withheld
until compounds generated by the Group are available for
animal efficacy studies. Efforts in areas already well
funded, such as the synthesis or development of analogues of
known anti-HIV nucleosides (which includes pharmacology and
testing in cell-based assays) must not exceed 25% of total
direct cost of the Group. Similarly, projects utilizing
non-random cell-based assays for screening natural products,
biologics and/or synthetic compounds must not exceed 25% of
total direct cost of the Group.
While it is recognized that screening is necessary to
evaluate potential anti-HIV agents, a random screening
program is beyond the scope of this RFA. A random screening
program is operated by the National Cancer Institute. For
information contact Dr. Robert Schultz, Drug Synthesis and
Chemistry Branch, National Cancer Institute, Executive Plaza
North, Room 831, Bethesda, Maryland 20892, Telephone:
(301) 496-8795.
For reasons stated below, the following research areas
currently under intense investigation or that have already
been integrated into other National Institutes of
Health (NIH) initiatives are excluded from
this RFA: (i) lipophilic carriers of nucleosides; (ii)
prodrugs of known anti-HIV nucleosides; (iii) evaluation of
recombinant human cytokines; (iv) development of soluble CD4
or its conjugated congeners; (v) large-scale random
screening of compounds with potential activity against HIV
in cell culture-based systems; such a program is operated by
the National Cancer Institute; (vi) research on the
opportunistic infections associated with AIDS; a separate
RFA for the National Cooperative
Drug Discovery Groups for the Treatment of Opportunistic
Infections Associated with AIDS (NCDDG-OI) is being re-
issued.
The
NCDDG/HIV Program will provide assistance to talented
scientists to interact as a unit to carry out the
preclinical research essential for the realization of
project objectives. An NCDDG/HIV could be composed of
scientists from any combination of academic, non-profit
research, and commercial organizations.
Twenty seven NCDDGs are currently funded. Seven of these
Groups are eligible for competitive renewals in fiscal year
1991. Current research pursuits within the NCDDG Program
include synthesis, evaluation, and pharmacology of nucleoside
and non-nucleoside antiviral compounds; purified compounds
from plant and marine sources; lipophilic delivery
systems; regulation of HIV gene expression by Tat and Rev;
interaction of Tat and Rev with their cognate cis elements
(TAR and REV); modulating effect of Nef on HIV growth;
function analysis of ancillary regulatory gene products
(Vif, Vpu, Vpr); X-ray crystallography of HIV protease,
reverse transcriptase, and capsid protein (p24); cell-based
rational and targeted approach to drug therapy [peptidyl and
non-peptidyl inhibitors of HIV protease; inhibitors of
glycosylation; inhibitors of myristoylation; sCD4, CD4-
toxins and immunotoxins as inhibitors of HIV attachment;
dominant repressors of viral functions (Tat, Rev, GAG)];
antisense and ribozyme mediated inhibition of HIV gene
expression; humoral and cellular aspects of immune
dysfunction; immunomodulators; and FeLV, SIV, and murine
animal models of HIV infection.
II. PURPOSE
Many single institutions may not have either the critical
mass of all of the talents or the ancillary resources needed
to translate leads from basic studies into new entities and
strategies for AIDS treatment. A collaborative arrangement
that permits the combination of the highest quality research
expertise from diverse institutions with the facilitating
resources of the NIAID is desirable. Units in which these
research talents and resources are combined are termed
"NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS" (NCDDG). They
are envisioned as having the capacity to generate new
approaches and strategies for the treatment of AIDS and to
rapidly translate their concepts into presumptively
effective treatment. The NCDDG can be focused in one area
(synthetic, immunological, biological) or be a combination
of the above approaches (comprehensive) in composition (see
definition of terms). Results from the research proposed
should be used to identify and develop information for long-
term planning of potential therapeutic approaches or to
recommend new potential treatments worthy of further
development to clinical trial.
To permit rapid and thorough analysis of agents developed by
the NCDDG, applicants are encouraged, but not required, to
include in their application a core for testing such agents
in screening systems. When and where appropriate,
collaborations between funded Groups or with the NCI may be
arranged through the Scientific Coordinator (see Section
VIII, "TERMS OF AWARD: AWARDEE RIGHTS AND RESPONSIBILITIES:
NATURE OF PARTICIPATION OF NIAID STAFF"), these
collaborations would serve to broaden the base of screening
efforts beyond those used by the NCDDG or to confirm the
biological findings of the NCDDG.
Studies required for the clinical development of identified
potential treatments are beyond the scope of this RFA, but
development through private venture capital is encouraged.
Alternatively, an NCDDG may request that the NIAID assist in
these developmental tasks using contracts now in place. The
NIH has a contract program for the preclinical development
of compounds for the treatment of AIDS. The NIAID has
contracts for the evaluation of relevant therapies in
appropriate animal models. In addition, the NIAID has
awarded 47 AIDS CLINICAL TREATMENT UNITS (ACTUs) for Phase
I, Phase II, and Phase III clinical trials at 112 sites. It
is envisioned that these ACTU cooperative agreements will be
available for clinical studies of treatments discovered
under this initiative, upon the recommendation of the NCDDG
and concurrence of the AIDS Clinical Drug Development
Committee and the Division of AIDS.
III. MECHANISM OF SUPPORT
A. Awards will be made as COOPERATIVE AGREEMENTS. NIAID,
in awarding the Cooperative Agreement, anticipates
substantial programmatic staff involvement during
performance of the award. The nature of NIAID staff
assistance to the awardee is described in Section VIII
of this RFA under "TERMS OF AWARD: NATURE OF
PARTICIPATION OF NIAID STAFF". There is no intent,
real or implied, for NIH staff to direct Group
activities or to limit the freedom of investigators.
The interaction of academic and non-profit research
institutions with commercial (including industrial)
organizations and Government is expected to promote and
expedite discoveries of new entities and strategies for
the treatment of HIV infections and will facilitate
their subsequent development to clinical trial.
B. NIAID has set aside $2.5-3.0 million for the initial
year's funding of this RFA. The amount spent will be
dependent on the continuing availability of funds for
this purpose and the quality and diversity of approved
applications. Funding of 3-4 awards is anticipated.
The dollar value of NCDDG awards is subject to the same
limitation governing Program Project grants. Current
limit for a Program Project is one million dollars in
total costs, unless prior approval by NIAID is
obtained. The starting date for the initial annual
period will be on or after June 1, 1991.
[When the applicant institution is outside
the United States, awards will be limited
to three years. When the applicant
institution is within the United States and
the application contains laboratory
projects in a foreign country, the request
for funding may be up to five years.]
C. Awards will be made to successfully competing Groups
rather than to the individual scientists or
institutions comprising the Group. Support of all
Group activities will be coordinated through a Central
Operations Office located within the applicant
organization. Each award will be made only to the
Principal Investigator's institution.
D. Under the Cooperative Agreement, a partner relationship
between the recipient of the award and NIAID exists in
which the Group is responsive to the requirements and
conditions set forth in the RFA. Specifically, the
Principal Investigator defines the details for the
project within the guidelines of the RFA, retains
primary responsibility for the performance of the
scientific activity, and agrees to accept close
assistance in coordination, cooperation, and participa-
tion of NIAID staff in all aspects of scientific and
technical management of the project in accordance with
the terms formally and mutually agreed upon prior to
the award. It is presently envisioned that the NIAID
will be actively engaged in assisting the awardee in
the coordination of all components including:
* cooperative participation in data analysis
and reporting;
* prior approval of changes of key personnel
including the Principal Investigator or
Project Leaders;
* retention of the option to withhold support
if a Project Leader withdraws from the
Group and a suitable replacement of key
personnel is not obtained.
E. All policies and requirements that govern the grant
program of the U.S. Public Health Service and the
NIH apply.
F. Although this program is provided for in the financial
plans of NIAID, the award of Cooperative Agreements
pursuant to this RFA is also contingent upon the
continuing availability of funds for this purpose.
IV. DEFINITIONS
ARBITRATION PANEL - A group composed of the Principal
Investigator or Project Leader of a particular NCDDG as the
"Group" designee, one NIAID designee, and a third designee
with expertise in the relevant area and chosen by the other
two. The interaction of this panel is detailed in Section VIII,
"TERMS OF AWARD".
COOPERATIVE AGREEMENT - An assistance mechanism in which
substantial NIAID programmatic involvement is anticipated
with the recipient organization during the performance of
the planned activity.
CORE COMPONENT - Laboratory facilities for equipment and
services that shall be shared by two or more projects of
the NCDDG. Examples of core components are: screening
studies, toxicology studies, pharmacology studies, scale-up
synthesis of drugs (50 grams or less). The core can be
defined as any project with established techniques and
assays that performs a service function or results in an
economy of effort and savings in the overall costs of the
NCDDG.
DISCOVERY - The term "discovery" is used explicitly to limit
activities of the NCDDG to preclinical identification,
design, and development of new entities. We encourage the
investigator to determine if the drug or biologic proposed
can be used in the treatment of HIV-infected individuals.
INVENTION - A new drug or innovative treatment that is or
may be patentable under Title 35 of the United States Code.
NATIONAL COOPERATIVE DRUG DISCOVERY GROUP (NCDDG) - In this
RFA the terms NATIONAL COOPERATIVE DRUG DISCOVERY GROUP,
NCDDG, and "Group" are synonymous. A number of laboratory
research projects representing diverse scientific
disciplines and organizations that join together under a
single Principal Investigator and that function as a unit
with a common goal: the conceptualization, invention, and
evaluation of new entities and strategies for the treatment
of HIV infection. Groups must consist of at least two
independent Projects conducted by at least two independent
laboratories. A CORE COMPONENT cannot be used toward
fulfillment of the two Projects requirement. The
application must identify the category in which it should
be considered.
a. Immunological - studies that use either the humoral or
the cellular arm of the immune system or both as a
focus for therapy (e.g., monoclonal antibodies, anti-
idiotypic antibodies, immunotoxins, cytotoxic cells,
biological response modifiers alone or in combination
with other therapies).
b. Biological - any approach that focuses on the biology
or molecular biology of the virus or the host and is
not focused on direct effects on the immune system
(e.g., natural products, molecular biology of the
virus, structure of viral proteins for targeted drug
development, purification and characterization of viral
enzymes, ribozymes, or antisense RNA produced from
vectors).
c. Synthetic - any approach which will use or modify
naturally occurring chemicals or biologics or which
involve the use of organic chemistry or medicinal
chemistry to design and synthesize novel "drugs" to
interfere with viral replication.
d. Comprehensive - any approach that will encompass any
combination of the three areas described in a, b, and c
above.
NEW DRUG - In the context of the NCDDG/HIV program, the term
"drug" is used broadly to encompass new synthetic agents,
natural and biological products, as novel therapeutic
strategies or inventions designed to effectively treat AIDS.
NIAID NCDDG PROGRAM DIRECTOR - Member of the NIAID
extramural staff who coordinates NIAID's participation in
the NCDDG Program. This responsibility includes:
(i) overseeing the entire NCDDG/HIV program; (ii) assuring
that Groups' objectives are consistent with Program's and
NIAID mission and goals; (iii) assigning Scientific
Coordinators to appropriate Groups based on scientific
expertise and compatibility with the Group research
interests; (iv) assuring overall scientific balance among
Groups in the NCDDG Program; (v) networking and facilitating
collaboration between Groups and industry to expedite
development of promising anti-HIV agents; (vi) keeping the
NCDDG Program current with regard to scientific developments
and breakthroughs; and (vii) identifying gaps not
adequately pursued.
NIAID SCIENTIFIC COORDINATOR - A member of the extramural
staff of the NIAID who functions as a peer with the
Principal Investigator and Project Leaders and facilitates
the partnership relationship between NIAID and the Group.
The Scientific Coordinator, based on his/hers scientific
expertise, interests, and compatibility with the Group's
areas of research, is assigned to the Group by the NCDDG
Program Director.
PRINCIPAL INVESTIGATOR - The person who assembles the NCDDG,
assembles a single application with the information provided
by the Project Leaders and submits the application in
response to this RFA and who is responsible for the
performance of the Group as a whole and each of the Project
Leaders. The Principal Investigator is strongly encouraged
to lead one of the research projects of the Group and is
expected to coordinate Group activities scientifically and
administratively. The Principal Investigator's (awardee)
institution establishes and operates the Central Operations
Office that funds Group members and is legally and fiscally
accountable for the disposition of funds awarded.
PROJECT LEADER - The leader of one of the scientific
research projects of the NCDDG.
SCIENTIFIC ADVISORS PANEL - A panel, comprised of the
Scientific Coordinator and 2-3 peers from the scientific
community, whose mission is to provide the Principal
Investigator with a comprehensive review of the Group's
activities and progress, consult on future goals and
strategies, and recommend alternative directions, as
appropriate. Selection and appointment of the Panel is the
responsibility of the Principal Investigator. Members of
the Panel will not be affiliated with any of the
institutions comprising the Group. A Scientific Advisors
Panel is required only of Groups funded for more than three
years. The composition of the designated Panel will be
provided to the NIAID in the Noncompetitive Renewal
Application at the completion of year two of funding. The
Panel will provide the Principal Investigator a
comprehensive review of Group's activity in years three and
four of funding. These reviews will encompass timeliness of
progress in individual projects relative to original
projections; progress relative to Group's objectives and
needs; continued relevance of a given project to Group's
goals; continued coordination of Group's objectives with the
objectives of the NCDDG Program; and recommendations for new
directions, as appropriate.
V. COMPOSITION OF AN NCDDG/HIV
A. The NCDDG will consist of the following:
1. Principal Investigator;
2. Project Leaders, each heading a research project.
The research projects will utilize diverse
scientific disciplines or alternative disciplines
that are appropriate to the realization of Group
objectives (e.g., virology, humoral immunology,
cellular immunology, structural biology,
biophysics, biochemistry, medicinal chemistry,
organic chemistry, pharmacology, toxicology, drug
delivery, etc.). Interdisciplinary projects are
encouraged;
3. A Scientific Coordinator designated from the NIAID
extramural staff;
4. (OPTIONAL) Core components that would provide for
laboratory facilities, equipment, and services to
be shared by two or more projects. It may also
include support for the costs of administration,
purchasing, and secretarial services. Items
described above that are included in the
institution's indirect cost rate are subject to
negotiations, based on their applicability as
direct or indirect charges;
5. A Scientific Advisors Panel to be designated at
the end of year two of funding by Groups funded
for more than three years (see Section IV,
"DEFINITIONS: SCIENTIFIC ADVISORS PANEL"). The
Panel will work together with the Group, evaluate
and advise on Group's progress, future goals,
strategies, and new directions, as appropriate.
With the exception of the Scientific Coordinator,
members in the Panel will not be affiliated with
any of the institutions comprising the Group.
B. The Principal Investigator, in addition to providing
scientific and administrative leadership, is encouraged
to have a research project. Project Leaders will be
directly responsible to the Principal Investigator.
The formation of the Group, the application in response
to this RFA, the overall management of the Group, and
the allocation of funds to the various laboratory
projects will be the responsibility of the Principal
Investigator and the Principal Investigator's
institution in accordance with PHS policies.
C. The composition of the Group and its research projects
should depend on the talents required to accomplish its
scientific and technical objectives as perceived by the
Principal Investigator and Project Leaders. The major
consideration in structuring an NCDDG should be the
mobilization of maximum intellectual strength and the
ability to carry out the proposed research.
D. An individual scientist may be proposed as a Project
Leader by more than one applicant as part of a CORE
COMPONENT. Project Leaders who do not have a core
function will not be supported by more than one
Cooperative Agreement awarded under this RFA unless the
research is clearly delineated in separate NCDDG
applications. Individuals currently supported under an
existing HIV NCDDG or other NCDDG may be funded under
this RFA as long as there is no scientific or budgetary
overlap in funded activities.
E. More than one Project Leader of an NCDDG may be
enlisted from a single institution. However, the
varied talents and commitment required for effective
drug discovery are not usually present in most single
institutions, and it is anticipated that the Project
Leaders within a Group will be "enlisted" or come from
several institutions.
F. A minimum of two but no maximum number of research
projects per Group is stipulated. However, the
Principal Investigator could experience difficulty in
providing the desirable level of guidance and Project
Leaders might communicate and collaborate less
efficiently if the Group were to contain more than five
or six research projects, including the Principal
Investigator's project. A CORE COMPONENT cannot be
considered toward fulfilling the required two research
projects per Group.
G. In forming NCDDGs, Principal Investigators should
remain cognizant of the need for communication,
including regular meetings of the members. While it is
not a requirement of this RFA, the formation of Groups
on a geographically regional basis may be advantageous.
This is a particularly important factor to be
considered by applicants from outside the United States
or if the applicant proposes laboratory projects in
foreign countries.
H. An NCDDG is encouraged to consist of scientists from
academia, non-profit institutions, and/or commercial
organizations. The active participation of industry is
encouraged because it will allow this sector of the
scientific community to contribute its intellectual and
material resources and will favor expeditious
development of effective anti-HIV therapies.
VI. RESEARCH GOALS AND SCOPE
A. The goals of the NCDDG/HIV
are:
1. The conceptualization, discovery, and preclinical
development of drugs and strategies designed to
effectively treat individuals infected with the
human immunodeficiency virus;
2. The recommendation of therapies, entities or
strategies for development to clinical trial; and
3. The conduct of biological, biochemical, and
pharmacological studies that will permit the most
enlightened subsequent clinical evaluation
supported by the most sophisticated technology,
and that may provide information leading to the
future discovery of even more effective
treatments.
B. Applications for an NCDDG/HIV should stress creative
approaches to the discovery of effective anti-HIV
therapies and should emphasize the following:
1. Specific objectives of the proposed NCDDG;
2. Research approaches to the realization of
objectives and the provision of comprehensive
information (including citations) in support of
the rationale(s) for the proposed approaches; and
3. The scientific and technical areas of expertise
(Project Leaders) required to attain Group
objectives and the leadership ability of the
Principal Investigator.
C. The Group's objectives and goals should be relevant and
compatible with NIAID Program's missions and directions
as stated in this RFA.
VII. PATENT COVERAGE
Since the discovery of active anti-HIV entities and
strategies is the objective of this effort, and since active
involvement by industrial laboratories is facilitated by the
existence of adequate patent coverage, it is essential that
applicants provide plans to assure such coverage. With
multiple institutions involved, the patent situation could
be complicated. Each applicant Group must, therefore,
provide a detailed description of the approach to be used
for obtaining patent coverage and for licensing where
appropriate, in particular where the invention may involve
investigators from more than one institution. In addition
each Group must provide a detailed description of the
procedures to be followed for the resolution of legal
problems that may develop. All Group members can be full
partners in the research and in any inventions resulting
therefrom. The specific patenting arrangements among the
institutions may vary and could include joint patent
ownership and exclusive licensing arrangements. Applicants
should implement an arrangement that is most suitable for
their own particular circumstances.
The patent agreement, signed and dated by the organizational
officials authorized to enter into patent arrangements for
each Group member and member institution, must be sent
before the application deadline to Dr. Margaret I. Johnston,
Chief, Developmental Therapeutics Branch, Division of AIDS,
6003 Executive Boulevard, National Institutes of Health,
Bethesda, MD 20892.
Federal regulation clause 37CFR401 and HHS Inventions
regulations at 45 CFR Parts 6 and 8 require that NIH be
informed of inventions and licensing occurring under NIH-
funded research. Invention and licensing reports must be
submitted to Extramural Invention Reports Office, Office of
Extramural Research, Building 31, Room 5B41, NIH,
with a copy to Dr. Margaret I. Johnston, Chief, Developmental
Therapeutics Branch, Division of AIDS (as above).
VIII. TERMS OF AWARD: AWARDEE RIGHTS AND RESPONSIBILITIES AND
NATURE OF NIAID PARTICIPATION
Assistance via Cooperative Agreement differs from the
traditional research grant in that, in addition to the normal
programmatic and administrative stewardship
responsibilities, the component awarding the Cooperative
Agreement anticipates substantial programmatic involvement
during performance of the project. However, the applying
Group must define its objectives and approaches in accord
with its own interests and perceptions of novel and
exploitable approaches to the discovery of effective anti-
AIDS treatment and must develop the details of the research
design following the guidance given in this RFA. It is the
primary responsibility of the Principal Investigator to
clearly state the objectives and approaches of the Group, to
plan and conduct the research stipulated in the proposal, and
to ensure that the results obtained are analyzed and
published in a timely manner. The data obtained will be the
property of the awardee.
NIAID shall participate as a member of the Group and shall
be represented by a Scientific Coordinator. The Coordinator
shall be selected from the Developmental Therapeutics Branch
of the Division of Acquired Immunodeficiency Syndrome, which
is an extramural program of the NIAID.
During performance of the award the NIAID Scientific
Coordinator may provide appropriate assistance by
participating in the design of Group activities; advising in
the selection of sources or resources, replacement of staff,
etc.; coordinating or participating in collection and/or
analysis of data; advising in management and technical
performance; or participating in the preparation of
publications. However, the role of NIAID will be to
facilitate and not to direct the activities. It is
anticipated that decisions in all activities outlined below
will be reached by consensus of the Group and that the NIAID
Scientific Coordinator will be given the opportunity to
offer input to this process. The manner of reaching this
consensus and the final decision-making authority will rest
with the Principal Investigator.
Failure to abide by these Terms of Award may result in
withholding of funds by the NIAID.
A. Awardee Rights and Responsibilities
1. The Principal Investigator, Project Leaders, and
the NIAID Scientific Coordinator will meet
periodically to review progress, plan and design
research activities, and establish priorities.
The frequency of meetings (not less than two per
year) shall be determined by the Principal
Investigator who will be responsible for
scheduling the time and place (generally at one of
the performance sites), notifying the Scientific
Coordinator at least forty-five days prior to the
meeting date, and preparing concise proceedings or
minutes which will be delivered to the members of
the Group including the Scientific Coordinator
within thirty days following the meeting. NIAID
Scientific Coordinator will participate but not
chair Group meetings.
2. In addition to these two meetings, one meeting
each year will be held at the NIH Bethesda (or at
a site designated by NIAID) during which all
Principal Investigators and Project Leaders will
present significant findings in symposium format.
The NCDDG annual meeting is one of the central
points for information flow among the Principal
Investigators, NCDDG Program Director, the private
sector, other drug development concerns, and
NIAID. The Program Director consults with the
Groups' key personnel in formulating the overall
agenda, selecting session Chairs, and in identifying
key topics for discussion. Session Chairs select
the workshop participants who constitute the bulk
of invited speakers. This forum is central for
cross fertilization of ideas, integration of
unique anti-HIV strategies, and a critical source
for updating Program and keeping it abreast of
scientific and technological innovation toward the
discovery of new anti-viral modalities. Data
presented at this meeting are selected by the
individual presenters in consultation with their
Principal Investigator thus affording appropriate
protection of proprietary or commercially
sensitive information.
It is expected that selected NIH staff, members of
established committees and advisory boards, and
others active in the process of discovery and
development of therapies for AIDS will be invited
to this meeting. The Principal Investigator will
have control over the data and results presented
by the Group. Funds for attending the three
required meetings should be included in the budget
for each research project. The application should
also include plans for scheduling Group meetings,
notifying Group members including the NIAID
Scientific Coordinator, and documenting and
disseminating Group meeting proceeding.
3. Groups funded for more than three years will
designate a Scientific Advisors Panel by the end
of year two of funding. The Principal
Investigator will convene a meeting, or meetings,
of the Group with the Panel in years three and four of
funding. The Panel will work together with the
Group, and advise the Principal Investigator on
Group's progress, future goals, strategies, and new
directions, as appropriate. Members of the Panel
will not be affiliated with any of the
institutions comprising the Group. Funds to cover
expenses incurred by the Panel should be included
in the Administrative Core component of the
application.
4. A critical determinant of Group's success will be
the degree of communication among its members.
Therefore, additional informal meetings among all
participants as well as regular telephone and
written communication will be important.
B. NIAID Assistance in Implementation and Management of
Research Activities
1. The NIAID Scientific Coordinator, like other Group
members, may suggest studies within the scope of
the Group's objectives and research activities;
may present to the Group experimental findings
from published sources or from contract projects
in support of these suggestions; may participate
in the design and execution of experiments as
agreed to by the Group; and may participate in the
analysis and publication of results.
2. The NIAID Scientific Coordinator may assist the
Group or other individual members in research
planning, particularly with respect to:
a. reduction of duplication of efforts conducted
in other extramural projects;
b. provision of needed resources and information
that may not be otherwise available to the
Group; and
c. provision of data from testing conducted in
resource contract laboratories.
3. The NIAID Scientific Coordinator may serve as a
resource for information, laboratory testing,
animal model testing, and biological supplies, when
such resources are not a normal requirement of the
Group's day-to-day research activities but may be
required on an occasional basis. The following is
a list of some resources
available from the NIAID;
these resources are intended for initial studies and will not
be available on a continual basis:
(i) Reference compounds for standardization of
test systems, as analytical standards and
for related purposes.
(ii) Materials for biological testing.
(iii) Laboratory testing capacity, whenever
appropriate and possible, in a current
contract-based preclinical therapy-related
laboratory testing program or other NCDDGs.
The Groups are expected to provide
sufficient test material for such testing.
(iv) Searches of computer files of chemical
structures and biological activity, if
requests for such searches are sufficiently
focused to avoid excessive costs.
Information given to an NCDDG will be
restricted by any standard confidentiality
agreements between the Government and
suppliers of test materials to the
Government.
(v) Experimental animals, when the occasional
need arises in Groups whose main research
activities do not require these materials on
a regular basis. Groups whose experimental
approach involves studies that require
animals on a regular basis must budget for
costs to be paid from award funding.
(vi) Computer processing and statistical
evaluations if costs are not excessive.
(vii) Networking with other NIH Staff, NCDDGs,
other collaborators, and other Government and
non-Government employees who may provide
guidance, expertise, or resources to
facilitate development of therapies
identified by the Group.
4. The NIAID Scientific Coordinator may assist the
Groups by providing them with compounds for
initial testing and for confirmatory testing. In
testing compounds supplied by the NIAID, the
Groups agree to abide by any confidentiality
agreement between the NIAID and a third party who
has supplied the compounds for testing through
NIAID.
C. Collection and Analysis of Data, Procedures for
Submission of Results to NIAID, and Preparation of
Group Findings for Presentation and Publication
In addition to the special reports and stipulations
described below, reporting requirements will be
identical to those currently in existence for awardees
of traditional NIH research project grants.
1. The principal end product of NCDDG activities will
be the discovery of new entities and strategies
for development to clinical trials against AIDS.
Subsequent developmental work through private
resources is encouraged. Alternatively, the Group
may recommend that development be sponsored by
NIAID. In the latter case, it will be necessary
for the Principal Investigator, appropriate
Project Leaders, and NIAID to collaborate in the
analysis, summarization, preparation, and
presentation of data to the appropriate NIAID
staff.
2. NIAID will retain the option to cross-file or
independently file an application for
investigational clinical trial; e.g., an
Investigational New Drug Application (INDA) to the
United States Food and Drug Administration of any
invention resulting from these NIAID-supported
Cooperative Agreements. Reports of data generated
by the Group or any of its members required for
inclusion in INDAs and Clinical Brochures and for
cross-filing purposes will be submitted by the
Principal Investigator to the Scientific
Coordinator upon request. Such reports will be in
final draft form and include background
information, methods, results, and conclusions.
They will be subject to approval and revision by
NIAID and may be augmented with test results from
other Government-sponsored projects prior to
submission to the appropriate regulatory agency.
3. The Government, via the Program Director or
designated Scientific Coordinator, will have
access to data generated under this Cooperative
Agreement and may periodically review the data and
progress reports. Information obtained from the
data may be used by the Scientific Coordinator for
the preparation of internal reports on the Group's
activities. However, the applicant will retain
rights to the data, and timely publication of
major findings is encouraged.
Publication or oral presentation of work done
under this Agreement is the responsibility of the
Principal Investigator and appropriate Project
Leaders and will require appropriate
acknowledgement of NIAID support.
D. Inasmuch as certain activities under "TERMS of AWARD:
NATURE OF PARTICIPATION OF NIAID STAFF" require
approval by NIAID staff during performance of this
Cooperative Agreement (specifically, reports intended
for inclusion in INDAs and Clinical Brochures, change
in Principal Investigator or Program Leader,
redistribution of biological materials received through
the Scientific Coordinator, and dissemination of
research findings resulting from the use of these
materials), NIAID will establish an arbitration process
to resolve any differences of opinion with regard to
programmatic matter. An arbitration panel, composed of
one Group designee, one NIAID designee, and a third
designee with expertise in the relevant area and chosen
by the other two, will be formed to review any
scientific or programmatic issue that is significantly
restricting progress. This arbitration process in no
way affects the right of an award recipient to appeal
selected post-award administrative decisions in
accordance with HHS, PHS, and NIH regulations and
policies. These special arbitration procedures in no
way affect the awardee's right to appeal an adverse
action in accordance with PHS regulations at 42 CFR
Part 50, Subpart D, and HHS regulations at 45 CFR, Part
16.
E. The special "TERMS OF AWARD: NATURE OF PARTICIPATION
OF NIAID STAFF" described in this section are in
addition to, and not in lieu of, otherwise applicable
OMB administrative guidelines, HHS Grant Administration
Regulations at 45 CFR Part 74, and other HHS, PHS, and
NIH grant administration policy statements.
IX. MINIMUM REQUIREMENTS FOR APPLICATION
Applicants seeking funding as an NCDDG/HIV
must meet
the following requirements:
The application must be from a Group and must:
A. Name a single Principal Investigator who is an employee
of the applicant institution and who will be
responsible for the application, for Group research
activities, and for the support of Group activities
through a Central Operations Office;
B. Identify the single applicant organization (awardee
institution) that will provide the Central Operations
Office and be legally and financially responsible and
be accountable for the use and disposition of funds
awarded on the basis of this RFA; show availability of
personnel and facilities capable of performing and
supporting the administrative functions of the
NCDDG/HIV;
C. Identify the Group as having an approach that should be
reviewed as being comprehensive, immunological,
biological, or synthetic in its approach for the design
of new treatments against HIV infection;
D. Provide a description of the Group's plan for assuring
adequate patent coverage of new inventions that may
issue as a result of Government funding of the proposed
work;
NOTE: A formal statement of Patent Agreement among
all Group members and their institutions, as
well as a detailed description of procedures
to be followed for the resolution of legal
problems that may develop, signed and dated
by the organizational official authorized to
enter into patent arrangements for each Group
member and member institution, is to be
submitted with the application (see Section
VII, "PATENT COVERAGE").
E. Provide a clear, concise plan in narrative and
diagrammatic form that depicts the interrelationships
among the members of the Group and the
contribution of each to fulfillment of Group
objectives; provide an organizational chart of the
Group showing the name, organization, and scientific
discipline of the Principal Investigator and Project
Leaders; provide an organizational chart for each
laboratory project within the Group showing
relationships among the key personnel;
F. Provide a plan to assure the maintenance of close
collaboration and effective communication among members
of the Group which will include letters of commitment
to this plan and a letter accepting the assistance of
the Scientific Coordinator, defined under the "TERMS OF
AWARD", Section VIII.
G. Demonstrate that each component laboratory project
contributes to the attainment of the Group's objectives
and that each has available the professional and
technical personnel to permit efficient and successful
conduct of the proposed research; show that total
personnel of the Group are sufficient in quality and
quantity to assure successful conduct of the proposed
research; and
NOTE: Other activities that are essential to
maintaining or achieving the objectives of
the stated research projects (e.g., large-
scale production of reagents, animal
maintenance) should be included as
subcontracts under the budget for core
resources.
H. Demonstrate that each component laboratory project and
the Group as a whole have available the facilities
required for conduct of the proposed research;
demonstrate that appropriate biohazard facilities and
safety procedures are in place for activities involving
HIV, related viruses and virus-producing cell lines as
outlined in The Federal Register, Volume 49, Number
201, Part 2, Tuesday, October 16, 1984, p. 40556;
include a description of the Institutional Safety
Guidelines and administrative approval procedures for
each proposed laboratory project.
X. REVIEW METHOD AND PEER REVIEW CRITERIA
APPLICATIONS NOT RECEIVED AS A SINGLE PACKAGE FROM
THE PRINCIPAL INVESTIGATOR AND THAT DO NOT CONFORM TO THE
INSTRUCTIONS CONTAINED IN PHS 398 (rev. 10/88 or 9/89)
APPLICATION KIT WILL BE JUDGED NON-RESPONSIVE AND WILL BE
RETURNED TO THE APPLICANT
Applications will be reviewed by NIAID staff to determine
administrative and programmatic responsiveness to this RFA;
those judged to be non-responsive will be returned to the
applicant without review.
Those applications that are complete and responsive may be
subjected to a triage by an NIAID peer review group to
determine their scientific merit relative to the other
applications received in response to this RFA. The NIAID
will withdraw from competition those applications judged to
be noncompetitive for award and will notify the applicant
Principal Investigator and institutional business official.
Those applications judged to be competitive for award will
be further reviewed for scientific and technical merit by a
Review Committee convened by the Division of Extramural
Activities, NIAID, during February 1991. The final level of
review will be provided by the National Advisory Allergy and
Infectious Diseases Council.
REVIEW PROCEDURES AND CRITERIA
Applications will be reviewed in the AIDS Review Section,
NIAID, by an appropriate committee. The application must be
directed towards the attainment of the stated programmatic
goals (see Section VI, "RESEARCH GOALS AND SCOPE"). The
following factors will be considered in the scientific and
technical review of the application:
A. Relevance of applicant's (Group) objectives to the
discovery of new entities and strategies for the
treatment of AIDS;
B. Scientific and technical significance, originality, and
uniqueness of proposed research;
C. Scientific merit of approaches to realization of
objectives;
D. Likelihood that new potential therapy will be
identified during the course of the proposed study;
E. Specific competencies of the Principal Investigator and
Project Leaders to conduct the proposed work: research
experience, commitment, and time availability of
Principal Investigator, Project Leaders, and other key
personnel. While there is no maximum percent effort
set, it is anticipated that, due to the complexity and
time required to maintain a well-coordinated and
productive research effort, a 20% effort by the
Principal Investigator and each Project Leader should
be devoted to the study, unless there is compelling
evidence to the contrary.
F. Technical merit of proposed methods for producing or
obtaining test materials and for their evaluation;
G. Technical sufficiency of methods for evaluation of new
discoveries, laboratory test systems, models, etc.;
H. Administrative experience and competence of Principal
Investigator in the development, implementation, and
management of comprehensive research programs;
I. Plans for effective intra-Group communication and for
assuring Group cohesiveness;
J. Adequacy of existing physical facilities and resources
of the Principal Investigator and Project Leaders
including biohazard containment facilities as
stipulated in Section IX, "MINIMUM REQUIREMENTS FOR
APPLICATION," Part H;
K. Documented commitment of institutions represented by
Group members; documented capability of Principal
Investigator's institution to serve as Central
Operations Office for the Group;
L. Commitment to accept the assistance of NIAID staff in
accordance with the guidelines outlined under Section
VIII, "TERMS OF AWARD: NATURE OF PARTICIPATION OF
NIAID STAFF;"
N. Mechanism for selecting and replacing key professional
or technical personnel using the framework of the RFA;
O. Conformance to "MINIMUM REQUIREMENTS FOR APPLICATION"
(Section IX);
P. Reasonableness of cost.
XI. METHOD OF APPLYING
Before preparing an application, the prospective applicant
should carefully read the NIAID Information Brochure on
Program Project and Center Grants.
The Information brochure may be obtained from:
Ms. Barbara Gunter
Developmental Therapeutics Branch
Division of AIDS
National Institute of Allergy
and Infectious Diseases
6003 Executive Boulevard, Room 243
Bethesda, MD 20892
Telephone: (301) 496-8197
The Information Brochure contains special instructions for
preparing multi-project applications, review procedures,
review criteria, and other important information. It is
important to follow the instructions for preparing the
application as outlined in the Information Brochure.
Failure to do so may result in an application with
insufficient information for appropriate scientific review.
Questions concerning review requirements of a complete
application should be directed to Dr. Hortencia Hornbeak,
(301) 496-0123. Questions regarding responsiveness to the
RFA should be directed to Dr. Nava Sarver, (301) 496-8197.
o Receipt Date
The deadline for receipt of applications is December 6,
1990. Applications received after this date will be
considered as not responsive to this RFA and will be
returned without review.
o General
1. The regular research grant application forms PHS-
398 (rev. 10/88 or 9/89) are available at most
institutional business offices. If not available
there, they may be obtained from:
Office of Grants Inquiry
Division of Research Grants
National Institutes of Health
Westwood Building, Room 449
5333 Westbard Avenue
Bethesda, MD 20892
2. Submit a signed, typewritten original of the
application, including the Checklist, and six
copies to:
Division of Research Grants
Westwood Building, Room 240
Bethesda, MD 20892**
The RFA label available in form PHS-398 (rev.
10/88 or 9/89) must be affixed to the bottom of
the face page of the original signed application.
Failure to use this label could result in delayed
processing of the application such that it may not
reach the committee in time for review.
3. TO ASSURE THE IDENTIFICATION OF YOUR APPLICATION
WITH THIS RFA:
a. The application form must have "NATIONAL
COOPERATIVE DRUG DISCOVERY GROUP FOR
TREATMENT OF HUMAN IMMUNODEFICIENCY VIRUS
INFECTION (NCDDG/HIV)" (RFA AI-90-09) typed
on item 2 of the face page of the application
form; and
4. Prominently label the application according to one
of the following categories in the opening
sentence of the research plan:
a. THIS IS A COMPREHENSIVE NCDDG APPLICATION
b. THIS NCDDG APPLICATION IS IMMUNOLOGIC ONLY
c. THIS NCDDG APPLICATION IS SYNTHETIC ONLY
d. THIS NCDDG APPLICATION IS BIOLOGICAL ONLY
e. THIS NCDDG APPLICATION IS A COMBINATION (two
categories from b, c, and d):
This facilitates assignment of the application to
reviewers with appropriate expertise.
5. SUBMIT 17 EXACT COPIES OF YOUR APPLICATION
DIRECTLY TO
Dr. Hortencia Hornbeak:
Dr. Hortencia Hornbeak
Deputy Chief, Review Branch
Program Project and Review Branch
National Institute of Allergy
and Infectious Diseases
Westwood Building, Room 3A05
Bethesda, MD 20892
Telephone: (301) 496-0123
o Organization of Application and Suggested Modifications
of Form PHS-398 (rev. 10/88 or 9/89)
This RFA requires the submission of a single application for
the proposed NCDDG.
Because of the multi-institutional nature of an NCDDG and the
special requirements in this RFA, additional instructions
regarding format are contained in the NIAID Information
Brochure on Program Project and Center Grants.
The special requirements of this RFA will also necessitate
the following modification. The Introductory Section should
apply to the proposed NCDDG as a whole with respect to
goals, objectives, and overall research plan.
The Introductory Section, not to exceed two pages, should
contain any additional information about the proposed
Principal Investigator or his/her institution as evidence of
capability to carry out the scientific and administrative
duties required in this RFA and the functions of the Central
Operations Office.
In addition, the Introductory Section must include the
following elements to be considered responsive to minimum
requirements (see Section IX, "MINIMUM REQUIREMENTS FOR
APPLICATION," of this RFA):
1. the name of a single Principal Investigator in
accordance with Section IX, Part A;
2. the name of the single applicant organization that will
provide and operate the Central Operations Office in
accordance with Section IX, Part B;
3. a statement assuring adequate patent coverage of new
inventions that may be issued as a result of Government
funding in accordance with Section IX, Part D;
4. a statement of acceptance of the provisions of Section
VIII, "Terms of Award: Awardee Rights and Responsibilities;
Nature of Participation of NIAID Staff;"
5. a description of the interrelationships among
members of the Group and organizational charts in
accordance with Section IX, Part E; and
6. a plan to assure maintenance of close
collaboration and effective communication among
members of the Group in accordance with Section
IX, Part F.
XII. INQUIRIES
Inquiries of the program aspects of this RFA may be
addressed to Dr. Nava Sarver (Section XI, "METHOD OF
APPLYING").
Inquiries regarding matters pertaining to the review of this
application should be addressed to Dr. Hornbeak. Inquiries
regarding fiscal matters may be addressed to Mr. Thompson.
Mr. Gary Thompson Hortencia Hornbeak, Ph.D.
Chief, Grants Management Branch Deputy Chief, Review Branch
Westwood Building, Room 726 Westwood Building, Room 3A05
NIAID, NIH NIAID, NIH
5333 Westbard Avenue 5333 Westbard Avenue
Bethesda, MD 20892 Bethesda, MD 20892
Telephone: (301) 496-7231 Telephone: (301) 496-0123
XIII. OTHER
A separate request for Applications for the National
Cooperative Drug Discovery Groups for the Treatment of
Opportunistic Infections Associated with AIDS (RFA-
AI-90-10) has been issued. To receive a
copy, please contact Ms. Barbara Gunter (see Section
XI, "METHOD OF APPLYING").