Vol. 18, No. 26, July 28, 1989 NOTICES NIH REGIONAL CONFERENCE IN GRANTS ADMINISTRATION ..........(84/125).......... 1 National Institutes of Health Index: NATIONAL INSTITUTES OF HEALTH DATED ANNOUNCEMENTS (RFPs AND RFAs) DISTRIBUTION OF MOUSE MODELS FOR NEURAL TUBE DEFECTS (RFP) ...(131/165)...... 1 National Institute of Child Health and Human Development Index: CHILD HEALTH, HUMAN DEVELOPMENT NATIONAL COOPERATIVE VACCINE DEVELOPMENT GROUPS FOR THE ACQUIRED IMMUNODEFICIENCY SYNDROME (RFA) .....................(168/193)...... 2 National Institute of Allergy and Infectious Diseases Index: ALLERGY, INFECTIOUS DISEASES NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR THE TREATMENT OF ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS) (RFA) ..(196/295, 644/1738)....... 2 National Institute of Allergy and Infectious Diseases Index: ALLERGY, INFECTIOUS DISEASES ONGOING PROGRAM ANNOUNCEMENTS TECHNOLOGY DEVELOPMENT, MAPPING, AND DNA SEQUENCING IN SUPPORT OF THE HUMAN GENOME PROGRAM ..................................(301/608)......... 3 Office of Human Genome Research Index: HUMAN GENOME PLEASE NOTE: Due to summer vacation schedules, the NIH GUIDE FOR GRANTS AND CONTRACTS will not be published on August 4, 1989. The next issue will be August 11, 1989. ** NOTICES ** NIH REGIONAL CONFERENCE IN GRANTS ADMINISTRATION P.T. 42; K.W. 1014006 National Institutes of Health A two-day conference covering topics related to both program funding and grants administration at the National Institutes of Health is planned for October 18 - 19, 1989, at the University of Missouri-Columbia. The conference is targeted for an audience of researchers and research administrators at institutions in the midwest region which includes Colorado, Illinois, Iowa, Kansas, Missouri, Nebraska, and Oklahoma. Those interested from other states are also encouraged to attend. Investigators and staff from small and minority colleges, for-profit research organizations, hospitals, universities, and research institutes are invited. This two-day conference has a dual focus of interest to both researchers and grants administrators. Discussions of current issues that affect NIH funding and grants administration are included to give conference participants a comprehensive, up-to-date view of NIH-sponsored research. The first day of the conference is devoted to discussions of current interest to the research programs of the various institutes that comprise the NIH. Preparation of an NIH proposal and the NIH review process are included as agenda topics. Program representatives from several NIH institutes are featured speakers. Time will be available for conference participants to meet informally with the NIH representatives and discuss topics of special interest. The program for the second day covers topics associated with pre-award and post-award administration of NIH grants. Policy and procedural issues affecting NIH grants administration form the basis for the program. General discussions on current issues and the changes they precipitate are integrated with more specific discussions regarding special career development programs and lab safety. Mr. Geoffrey Grant, Grants Policy Officer in the Office of Extramural Research at NIH, representatives from the Division of Research Grants, and program and grants management staff of several institutes are featured speakers. Conference schedule and fee information will be mailed out early September. For more information, contact E. Jane Rutter, conference coordinator at (314) 882-9584 or Barry Kling, Director, Continuing Education and Extension for the Health Profession at (314) 882-4105. ** DATED ANNOUNCEMENTS (RFPs AND RFAs) ** DISTRIBUTION OF MOUSE MODELS FOR NEURAL TUBE DEFECTS RFP AVAILABLE: RFP-NICHD-89-25 P.T. 34; K.W. 1002002, 0755020 National Institute of Child Health and Human Development The National Institute of Child Health and Human Development (NICHD) is seeking organizations to maintain and distribute two mouse models for neural tube defects to the scientific community. The mouse models have been developed under two existing contracts with NICHD. The organization needs to have the expertise and the facilities to house and maintain breeding stocks of mutant mice and the capability to distribute them to interested investigators. This announcement is a new solicitation. The issuance of the RFP will be on August 7, 1989, and proposals will be due by 4:00 pm EDT, October 10, 1989. The Institute expects to make one award from this solicitation. Requests for the RFP shall be directed in writing to: Mrs. Lynn Salo NICHD, OGC, CMS Executive Plaza North Bldg., Rm. 515 9000 Rockville Pike Bethesda, Maryland 20892 Vol. 18, No. 26, July 28, 1989 - Page 1 To receive a copy of the RFP, please supply this office with two self-addressed mailing labels. All responsible sources may submit a proposal which will be considered. This advertisement does not commit the Government to award a contract. --------------------------------------------------------------------- NATIONAL COOPERATIVE VACCINE DEVELOPMENT GROUPS FOR THE ACQUIRED IMMUNODEFICIENCY SYNDROME RFA: 89-AI-16 P.T. 34; K.W. 0715008, 0740075, 1002045, 0760080, 1002008, 0710030 National Institute of Allergy and Infectious Diseases Revised Application Receipt Date: December 8, 1989 The National Institute of Allergy and Infectious Diseases has revised the application receipt date for the Request for Applications (RFA) 89-AI-16, National Cooperative Vaccine Development Groups for the Acquired Immunodeficiency Syndrome, from August 10, 1989, to December 8, 1989. The earliest award date is June 1, 1990. Questions concerning this revised due date and requests for copies of the full RFA document may be directed to: Dr. Wayne Koff AIDS Program, NIAID Vaccine Research and Development Branch 6003 Executive Bldg., Room 234P Rockville, Maryland 20892 Telephone: (301) 496-8200 --------------------------------------------------------------------- NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR THE TREATMENT OF ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS) RFA AVAILABLE: 89-AI-19 P.T. 34; K.W. 0715008, 0740020, 0710100, 1003006, 1003002, 1002045, 0710070 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: October 2, 1989 Application Receipt Date: December 8, 1989 The National Institute of Allergy and Infectious Diseases (NIAID) announces availability of a Request for Application (RFA) for funding of the National Cooperative Drug Discovery Groups for the Treatment of Acquired Immune Deficiency Syndrome (NCDDG/AIDS). It is the purpose of this RFA (copies available upon request) to invite applications aimed at the discovery of more effective, selective, and diverse new agents which can be used for the treatment of AIDS. Applications which include a research project or a core component from the private sector (e.g., pharmaceutical, chemical, or biotechnological companies) are encouraged. Research on the use of either the humoral or the cellular arm of the immune system, on the structure and biophysical properties of cellular or viral proteins, the biochemistry of viral-host interactions, drug targeting, ribozymes, drug metabolism, potentially efficacious natural products or certain synthetic chemical approaches may be judged responsive to this RFA. Applications should not include the following research areas which have already been integrated into other NIH initiatives: synthesis or development of analogues of known anti-HIV nucleosides, lipophilic carriers of nucleosides, prodrugs of existing nucleosides, testing in animal retroviral models other than those that utilize HIV, research on the opportunistic infections associated with AIDS, evaluation of recombinant human cytokines, development of glycosylation inhibitors, development of soluble CD4 or CD4 conjugates, and large scale random screening in cell culture-based systems. Specifically excluded from the Group's activities are activities related to clinical evaluation of the drug. (A program for large-scale screening of compounds for activity against HIV is operated by the National Cancer Institute.) For those that propose screening in cell culture-based systems, screening of natural products, biologics and/or synthetic compounds can not exceed 25 percent of the total effort of the Group. A separate Request for Applications (RFA) for the National Cooperative Drug Discovery Groups for the Treatment of Opportunistic Infections Associated with AIDS was issued on June 30, 1989, in the NIH Guide for Grants and Contracts (Vol. 18, No. 22). Vol. 18, No. 26, July 28, 1989 - Page 2 Each NCDDG/AIDS will be assembled by the Principal Investigator to form a multidisciplinary consortium representing the various skills needed to successfully design, synthesize, and evaluate, at the preclinical level, treatment entities and strategies for the treatment of AIDS. Inasmuch as it is unlikely that all of the outstanding talents required to exploit fundamental leads from various scientific disciplines will be found in a single institution, each Group is envisioned as being multi-institutional as well. Thus, each NCDDG/AIDS will be assembled by the Principal Investigator and will consist of a number of research projects representing the scientific disciplines required to attain the Group's goal and objectives. The various research projects, including that of the Principal Investigator, may be mobilized from academia, research institutions, and/or industry. It is expected that the rationale for design of potential treatments, the synthesis of specific agents, and the preclinical models for evaluation will originate within the Group and be based on leads from their own and others' fundamental research. Awards will be made as Cooperative Agreements. The Cooperative Agreement funding mechanism differs from the traditional research grant in that the Government component (NIAID) awarding the Cooperative Agreement anticipates substantial involvement during performance. The nature of NIAID staff participation is described in the RFA. However, the applying Group must define its objectives in accord with its own interests and perceptions of approaches to anti-AIDS treatment. The proposed applicant institution will be responsible for the Group's application. Awards will be made to the applicant institution on behalf of the Group as a whole and not to individual research projects within the Group. The applicant institution will provide a Central Operations Office for the Group. The applicant institution will be responsible for the performance of the entire Group and will be accountable for the funds awarded. The participation of the Government through the NIAID extramural staff is aimed at facilitating a concerted effort by the Group by making available to the Group biological materials for testing, appropriate existing data bases, and appropriate ancillary testing and other resources available under existing contracts. The interaction of academic and non-profit research institutions with commercial organizations and Government is expected to favor efficient invention of anti-AIDS treatment and will facilitate their subsequent development to clinical trial. Applications will be reviewed by the appropriate subcommittee of the NIAID AIDS Research Review Committee. NIAID has set aside $2.3 million for the initial year's funding. The amount spent will be dependent on the continuing availability of funds for this purpose and the quality and diversity of applications recommended for approval. This RFA is available from: Ms. Nancy R. Brown Developmental Therapeutics Branch Division of Acquired Immunodeficiency Syndrome National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 243P Bethesda, Maryland 20892 Telephone Number: (301) 496-0637 ** ONGOING PROGRAM ANNOUNCEMENTS ** TECHNOLOGY DEVELOPMENT, MAPPING, AND DNA SEQUENCING IN SUPPORT OF THE HUMAN GENOME PROGRAM P.T. 34; K.W. 1215018, 0755045, 1002058, 1004017, 1003012, 1002008, 0710030 Office of Human Genome Research This Program Announcement restates the interest of the National Institutes of Health (NIH) in receiving research grant applications for studies related to the Human Genome Initiative. The present announcement supersedes the previous NIH-wide Program Announcement (November 4, 1988) on mapping and determining the DNA sequence of the genomes of the human or of model organisms. The objective is to stimulate creative, innovative research that will substantially improve the rapidity, efficiency and accuracy with which mapping and DNA sequence data can be obtained, analyzed, and distributed. Vol. 18, No. 26, July 28, 1989 - Page 3 BACKGROUND INFORMATION The NIH is currently engaged, along with several other federal, private, and international organizations, in a research program known as the Human Genome Initiative. This program is designed to characterize the human genome and the genomes of selected model organisms. It has several interrelated goals: the construction of high resolution genetic linkage maps; the development of a variety of physical maps; the determination of the complete nucleotide sequence of the DNA of selected organisms; the development of the capability for collecting, storing, distributing, and analyzing the data and materials produced; and the development of appropriate new technologies necessary to achieve these objectives. The information that will be obtained within the genome project will be a resource for studies of gene structure and function and will promote research into the genetic aspects of human disease. In this way, the Human Genome Initiative will serve as an underlying source of information for, and stimulus to, a wide range of studies from the most basic to targeted and clinical programs across the spectrum of NIH interests and responsibilities. In the past two years, several announcements/solicitations for grant applications related to the Human Genome Initiative have been published in the NIH Guide for Grants and Contracts. These include two broad Program Announcements and several Requests for Applications. This Program Announcement consolidates the prior announcements/solicitations in one document and emphasizes the continuing, ongoing interest on the part of the NIH in receiving grant applications for support of research projects that address the goals of the genome program with a wide range of research activities. One area in which research activities are encouraged is the development of improved technology for physical mapping, for the determination of DNA sequences, and for the management of the information that accrues. A separate, but equally important, area includes research projects that seek to increase the information available about specific genomic regions through the expansion of genetic maps, the construction of physical maps, or pilot projects for large-scale DNA sequence determination. Creative, novel approaches in all these areas will be essential to the success of the genome project. To this end, the NIH encourages interdisciplinary programs that draw from fields such as information science, chemistry, physics, and engineering, in addition to the biological sciences. Progress will be accelerated by cooperation and interaction among investigators. Therefore, it is expected that all materials and information derived from this work will be made available to the scientific community in a timely manner, in accord with Public Health Service policy. Within the genome program, awardees will be expected to share information and to work closely with other laboratories involved in related projects. RESEARCH SCOPE This Program Announcement is intended to emphasize the ongoing commitment of the NIH to the specific goals of the genome project and to the development of methodological tools and resources which would support this effort, including the storage and retrieval of materials and data. Applications responsive to this announcement will include a broad spectrum of research approaches to genetic and physical mapping, DNA sequencing, data handling and new methods of data interpretation. Development of new and imaginative technologies needed to support the genome project are especially encouraged. The topics described below are not intended to limit the types of applications that are acceptable in response to this announcement, but rather to illustrate the range of work that will be needed to attain the goals of the genome project. However, research directed toward analysis of the biological function of specific genes or gene systems, or the application of genetic information to the understanding, diagnosis, prevention, or treatment of specific genetic disorders is not within the scope of the genome program. Such work is currently supported by a number of other programs at the NIH. Information about these programs can be obtained from individual Institutes. Potential applicants are encouraged to contact one of the representatives listed below to discuss the proposed research project and for additional information. Technology Development The objective is to stimulate creative, innovative research that will lead to substantial improvements in the speed, efficiency and accuracy with which mapping and DNA sequence data can be obtained, analyzed, and distributed. Such improvements can be achieved through automation of existing methodology, development of new approaches, or both. Multi-disciplinary approaches to the Vol. 18, No. 26, July 28, 1989 - Page 4 attainment of these goals are encouraged. Examples of the problems for which improved technological solutions and/or automation are needed are: o generating, purifying, and cloning large DNA fragments; o constructing physical maps, including long-range restriction maps and overlapping sets (contigs) of DNA fragments that are derived from specific chromosomal regions and are connected into more extensive physical arrays; o determining relationships between genetic and physical maps; o locating specific genes on genetic and physical maps and within regions of sequenced DNA; o determining DNA sequence, including assembling overlapping DNA sequences into longer arrays; o storing, analyzing, and distributing the data obtained in each of these activities; and o storing and distributing the materials generated by all of these activities. Applicants are advised to take several general considerations into account when designing new projects. o Methodological improvements have played an important role in advancing biological research, never more so than in the past twenty years. In general, when technology development has been successful, it has been driven by the desire to solve specific scientific problems. Therefore, it is reasonable to expect that, within the context of the genome program also, the most successful new technologies will come from those endeavors in which the attempt to develop better technology occurs in the context of a specific research problem related to genomic analysis. Applicants are encouraged to clearly define the biological problem for which the technological solution is being devised. Applicants whose expertise is primarily non-biological and who are interested in addressing problems of genome analysis with new, non-biological tools are especially encouraged to interact closely with biologists. o It has been suggested that to significantly increase the rate at which mapping and sequence data can be acquired, efforts should be directed toward improving by three- to five-fold the scale and/or efficiency with which particular steps in mapping, sequence determination, or data analysis can be accomplished. Such an incremental increase can serve as a useful benchmark in designing a research program. o Achievement of such a significant improvement in analytical capability may require entirely new approaches. Methods that have been useful for addressing particular needs in the past, such as determining the sequence of a few kilobases of DNA, may not be adequate for addressing comparable problems on a much larger scale. The NIH recognizes that novel approaches may involve a considerable degree of risk and encourages submission of high-risk, high pay-off projects in response to this announcement. Mapping and DNA Sequencing The objective is to increase our knowledge of the genetic and physical maps and the DNA sequence of selected organisms, leading up to the complete maps of the human genome and the complete human DNA sequence. Research projects in the following areas are encouraged: o expanding the genetic map of the human, or of those model organisms for which such information would serve to promote the objectives of the overall genome program; o constructing physical maps of the chromosomes of the human and of model organisms, including projects for large-scale physical mapping; and o pilot projects for large-scale DNA sequence determination, involving the DNA of model organisms or regions of the human genome. Vol. 18, No. 26, July 28, 1989 - Page 5 The primary goal of research projects proposed under this section will be the generation of a substantial amount of new mapping and/or sequence information. The project may utilize current technology or propose new or improved technology. If current technology is used, it should be used at or near its limits in order to explore its capabilities. Because of the extensive amount of information already available about the genetics and molecular biology of E. coli, S. cerevisiae, D. melanogaster, C. elegans, and M. musculus, the genome program is particularly interested in promoting study of these models. However, research projects that involve other models are also expected to make important contributions to the Human Genome Initiative by means of both development of new technology and improved understanding of genome structure through comparative studies. Thus, no model organism is excluded from the genome program a priori. However, applicants proposing to study models other than those named above must provide a rationale, in terms of the goals of the overall genome program, for the use of such another model. MECHANISMS OF SUPPORT Support for this program will be through research grants, including project grants (R01), program project grants (P01), FIRST awards (R29), resources related research projects and biotechnology resource grants (R24, P41), Research Career Development Awards (K04), conference grants (R13) and Small Business Innovation Research (SBIR) grants (R43, R44). Because not all institutes support all of the above mechanisms, potential applicants are encouraged to contact the representatives listed below for additional information. Policies that govern research grant programs of the NIH apply to this program. Consortium arrangements and collaborative projects among scientists with skills in biological sciences, chemistry, physics, information science, and engineering are encouraged. APPLICATION AND REVIEW PROCEDURES Applications in response to this announcement will be reviewed in accordance with the usual NIH peer review procedures. They will first be reviewed for scientific and technical merit by a special study section in the Division of Research Grants organized for this purpose. Following the initial review, the applications will be considered by the appropriate National Advisory Board or Council. Review criteria that will be used to assess the scientific merit of an application are the following: o Scientific merit; o Potential value of the research for furthering the goals of the genome project; o Feasibility of the research and adequacy of the experimental design; o Significance and originality of the research and methodological approaches, as they relate to the genome project; o Training, experience, research competence, and dedication of the investigator(s); o Adequacy of available facilities; o Provisions for the protection of human subjects, the humane care of animals, and biosafety conditions; o Appropriateness of the requested budget for the work proposed. Because the significance of the proposed research project to the goals of the Human Genome Initiative is a criterion for review, consultants must consider this aspect in the evaluation of an application submitted in response to this Program Announcement. Applicants are, therefore, encouraged to consult with one of the staff listed below before submission, to discuss the relevance of a proposed application to the genome program. METHOD OF APPLYING Applications should be submitted on Form PHS 398 (rev. 10/88). Application kits are available in most institutional business offices and from the Office of Grants Inquiries, Division of Research Grants, Westwood Building, Room 449, National Institutes of Health, Bethesda, Maryland 20892; telephone (301) 496-7441. Vol. 18, No. 26, July 28, 1989 - Page 6 Applications will be accepted in accordance with the usual NIH receipt dates that apply for the various mechanisms listed under MECHANISMS OF SUPPORT. It is essential that applicants type "Technology Development, Mapping, and DNA Sequence Determination in Support of the Human Genome Initiative" in item 2 on the face page of the application form. The original and six copies of the application should be submitted to the following office: Application Receipt Office Division of Research Grants Westwood Building, Room 240 National Institutes of Health Bethesda, Maryland 20892** Telephone: (301) 496-7273 The conventional presentation for grant applications should be utilized. Funding decisions will be based on recommendations of the initial review group and of the National Advisory Council regarding scientific merit and program relevance, as well as on the availability of funds. INQUIRES It is strongly recommended, but not required, that potential applicants contact the Office of Human Genome Research (OHGR) or the staff member at the appropriate NIH institute to discuss research objectives. BID CONTACT BUILDING ROOM TELEPHONE OHGR Bettie Graham, Ph.D. Shannon 201 496-0844 NIDDK Robert Katz, Ph.D. Westwood 607 496-7997 NCI Cheryl Marks, Ph.D. Executive 630 496-7028 Plaza South FIC Lynn Amende, Ph.D. 38A 613 496-6688 DRR Charles Coulter, Ph.D. Westwood 8A11 496-5411 NIA Huber R. Warner, Ph.D. 31 5B39 496-6402 NICHD Delbert Dayton, M.D. Executive 5C19 496-5541 Plaza North NINDS N.C. Myrianthopoulos, Ph.D. Federal 8C04 496-5821 NLM Arthur Broering, Ph.D. 38A 8C16 496-4621 NIDR John Townsley, Ph.D. Westwood 506 496-7807 NIGMS Irene Eckstrand, Ph.D. Westwood 920 496-7137 NIAMS Steven Hausman, Ph.D. Westwood 403 496-7495 NHLBI Carol Letendre, Ph.D. Federal 506 496-6402 NIAID William Duncan, Ph.D. Westwood 754 496-5598 NEI Jack McLaughin, Ph.D. 31 6A08 496-9110 Mailing address for the above offices: Bethesda, Maryland 20892 All Bethesda telephone numbers are in area code 301. **THE MAILING ADDRESS GIVEN FOR SENDING APPLICATIONS TO THE DIVISION OF RESEARCH GRANTS OR CONTACTING PROGRAM STAFF IN THE WESTWOOD BUILDING IS THE CENTRAL MAILING ADDRESS FOR THE NATIONAL INSTITUTES OF HEALTH. APPLICANTS WHO USE EXPRESS MAIL OR A COURIER SERVICE ARE ADVISED TO FOLLOW THE CARRIER'S REQUIREMENTS FOR SHOWING A STREET ADDRESS. THE ADDRESS FOR THE WESTWOOD BUILDING IS: 5333 Westbard Avenue Bethesda, Maryland 20816 Vol. 18, No. 26, July 28, 1989 - Page 7 ** FULL TEXT OF RFAs FOR ONLINE ACCESS ** REQUEST FOR COOPERATIVE AGREEMENT APPLICATIONS: RFA-NIH-NIAID-89-AI-19 Re-issuance of RFA 87-AI-24 dated September 25, 1987 NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR THE TREATMENT OF ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS) P.T. 34; K.W. 0715008, 0740020, 0710100, 1003006, 1003002, 1002045, 0710070 NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES Letter of Intent Date: October 2, 1989 Application Receipt Date: December 8, 1989 The National Institute of Allergy and Infectious Diseases (NIAID) invites applications for the establishment of National Cooperative Drug Discovery Groups for the Treatment of Acquired Immune Deficiency Syndrome (NCDDG/AIDS). The NIAID plans to continue its support of the National Cooperative Drug Discovery Group Program. Reissue of this initiative in future years is anticipated but not certain. LETTER OF INTENT Prospective applicants are asked to submit by October 2, 1989, 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. Margaret I. Johnston Head, 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 Number: (301) 496-8197 I. SUMMARY AND BACKGROUND The Acquired Immune Deficiency Syndrome (AIDS) is a disease that destroys the body's capacity to overcome a variety of infections. 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 sponsoring Institute of the National Institutes of Health (NIH) and the 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. By June 1989, over 94,000 cases of AIDS had been reported in the United States and more than 48,000 of these patients had died. Recent surveillance studies indicate that the total number of AIDS cases has nearly doubled over the last 10 - 12 months, with projections of approximately 140,000 to 200,000 cases by 1991. Recent projections indicate that more than a million persons presently in the United States may already be infected with the Human Immunodeficiency Virus (HIV), the infectious virus associated with AIDS. These figures emphasize the potential risk to the general population. The recognition of HIV as the etiological agent associated with AIDS, the isolation and characterization of the virus, and the ability to grow HIV on a large scale have made it possible to screen for potentially effective antiviral compounds to treat against the infection. The feasibility of discovering an effective treatment of the infection based on compounds targeted with selective cytotoxicity against steps in the viral replication cycle has been shown in vitro with several drugs (3'-azidothymidine, dideoxycytidine, soluble CD4). To date most of the compounds have been nucleoside analogues designed to interfere with the viral enzyme, reverse transcriptase. Considerable effort has also been directed toward development of soluble CD4 and its congeners to prevent entry of HIV into uninfected cells or CD4-toxin conjugates to kill cells expressing HIV gp120 on their surface. Insufficient effort has been made to devise therapies to block other steps in viral replication or to use substrate analogues to interfere with other enzymes or pathways unique to HIV or HIV-infected cells. Applications which include a project or a core component from the private sector (e.g., pharmaceutical, chemical, or biotechnological companies) are encouraged. Research on the use of either the humoral or the cellular arm of the immune system, on the structure and biophysical properties of proteins, the biochemistry of viral-host interactions, drug targeting, drug metabolism, ribozymes, potentially efficacious natural products or certain synthetic chemical approaches may be judged responsive to this RFA. For reasons stated below, the following research areas should not be included in applications responding to this RFA: synthesis or development of analogues of known anti-HIV nucleosides, lipophilic carriers of nucleosides, prodrugs of existing anti-HIV nucleosides, testing in animal retroviral models other than those that utilize HIV, research on the opportunistic infections associated with AIDS, evaluation of recombinant human cytokines, development of glycosylation inhibitors, development of soluble CD4 or CD4 conjugates and large-scale random screening in cell culture-based assay systems. A program for large-scale random screening of compounds for activity against HIV is operated by the National Cancer Institute. For those that propose screening in cell culture-based systems, screening of natural products, biologics and/or synthetic compounds can not exceed 25% of the total effort of the group. A separate Request for Applications for the National Cooperative Drug Discovery Groups for the Treatment of Opportunistic Infections Associated with AIDS was issued on June 30, 1989, in the NIH Guide for Grants and Contracts (Vol. 18, No. 22). The National Cooperative Drug Discovery Group for the Treatment of Acquired Immune Deficiency Syndrome (NCDDG/AIDS) 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/AIDS could be composed of scientists from a combination of academic, non-profit research, and commercial organizations. Currently, there are 28 NCDDGs of which five are eligible to compete for continuation. 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. The National Cancer Institute (NCI) has established contracts for the in vitro screening of candidate agents for activity against HIV. Compounds identified in this program will be developed further using contracts within NCI, NIAID or the private sector. 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 NIAID Scientific Coordinator. 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 NCI 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 45 AIDS CLINICAL TREATMENT UNITS (ACTUs) for Phase I, Phase II and Phase III clinical trials at 106 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 the concurrence by appropriate NIH staff. III. MECHANISM OF SUPPORT A. Awards will be made as COOPERATIVE AGREEMENTS. NIAID, in awarding the Cooperative Agreement, anticipates substantial staff involvement during performance of the award. The nature of NIAID staff assistance to the awardees 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 foster the efficient invention of new entities and strategies for AIDS treatment and will facilitate their subsequent development to clinical trial. B. NIAID has set aside $2.3 million for the initial year's funding. The amount spent will be dependent on the continuing availability of funds for this purpose and the quality and diversity of applications recommended for approval. The starting date for the initial budget period will be on or about June 1990. [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 applicant institutions on behalf of 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 negotiated partner relationship between the recipient of the award and NIAID exists in which the Group meets 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 coordination, cooperation, and participation of NIAID staff in all aspects of scientific and technical management of the project in accordance with the terms formally negotiated and mutually agreed upon prior to the award. It is presently envisioned that the NIAID will be actively engaged in assisting the awardees in the coordination of all components including: o membership in the Group; o collaborative participation in data analysis and reporting; o prior approval of changes of key personnel including the Principal Investigator or Project Leaders; o 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 (PHS rev. 10/88) and the National Institutes of Health (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 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 which 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 which performs a service function or results in an economy of effort and savings in the overall costs of the NCDDG. 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 which join together under a single Principal Investigator and which function as a unit with a common goal: the conceptualization, invention, and evaluation of new entities and strategies for the treatment of AIDS. The application must identify the category in which it wants to 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, cytotoxic cells, biological response modifiers alone or in combination with other therapies). b. Biological - any approach which 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 (e.g., chemically prepared ribozymes or antisense oligonucleotides). d. Comprehensive - any approach which will encompass any combination of the three areas described in a, b, and c above. NEW DRUG - In the context of the NCDDG/AIDS 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. 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. PROJECT LEADER - The leader of one of the scientific research projects of the NCDDG. 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 may lead one of the research projects of the Group and 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. NIAID NCDDG PROGRAM DIRECTOR - Member of the NIAID extramural staff who coordinates NIAID's participation in the NCDDG Program. 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. INVENTION - A new drug or innovative treatment that is or may be patentable under Title 35 of the United States Code. 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 VIII, "TERMS OF AWARD". V. COMPOSITION OF AN NCDDG/AIDS A. The NCDDG will consist of the following: 1. Principal Investigator; 2. Project Leaders, each heading a research project or core. 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; and 3. A Scientific Coordinator designated from the NIAID extramural staff. 4. (OPTIONAL) core components which 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. B. The Principal Investigator, in addition to providing scientific and administrative leadership, may 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 AIDS 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. 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 may be formed by scientists from academia, non- profit institutions, and/or commercial organizations. The active participation of industry is encouraged because it will allow this segment of the scientific community to contribute its intellectual and material resources. VI. RESEARCH GOALS AND SCOPE A. The goals of the NATIONAL COOPERATIVE DRUG DISCOVERY GROUP FOR THE TREATMENT OF AIDS 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 which may provide information leading to the future discovery of even more effective treatments. B. Applications for an NCDDG/AIDS should stress creative approaches to the discovery of effective anti-AIDS 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. VII. PATENT COVERAGE Since the discovery of active anti-AIDS 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 which 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 are encouraged to develop an arrangement that is most suitable for their own particular circumstances. The proposed patent plan among the institutions comprising the Group MUST be included as part of the application. The patent agreement signed and dated by the organizational officials authorized to enter into patent arrangements for each Group member and member institution should be forwarded for filing with Dr. Margaret I. Johnston, Chief, Targeted Drug Discovery Section, Developmental Therapeutics Branch, Division of AIDS, 6003 Executive Boulevard, National Institutes of Health, Bethesda, MD 20892. VIII. TERMS OF AWARD: AWARDEE RIGHTS AND RESPONSIBILITIES: NATURE OF PARTICIPATION OF NIAID STAFF 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, advice, and guidance 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 NIAID staff 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. A. Group Activities, Development of Research Protocols and Evaluation of Results 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, but 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). NIAID Scientific Coordinator will not chair Group meetings. 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. 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 attendance of these three required meetings should be included in the budget for each research project. The application should also include plans for scheduling the group meetings, notifying group memebers including NIAID, and documenting and disseminating group meeting proceedings. A critical determinant of Group 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. 2. 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. 3. 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. 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. B. NIAID Assistance in Implementation and Management of Research Activities NIAID staff, through a designated Scientific Coordinator, may serve as a resource for information, laboratory testing, and biological supplies (e.g., animals), 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 that might be supplied if they become desirable during performance, are not anticipated as a continuing need, and may be available from the NIAID: 1. Reference compounds for standardization of test systems, as analytical standards and for related purposes. 2. Materials for biological testing. 3. 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. 4. 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. 5. 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. 6. Computer processing and statistical evaluations if costs are not excessive. 7. 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. C. NIAID Assistance in the 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. 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 administrative 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. 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 a NATIONAL COOPERATIVE DRUG DISCOVERY GROUP FOR THE TREATMENT OF AIDS must meet the following requirements: The application must be from an organization on behalf of 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/AIDS; 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 for AIDS; 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 which 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. 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 participation of the NIAID Scientific Coordinator; 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 which 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, Tuesday, October 16, 1984, p. 40556; include a copy of the Institutional Safety Manual for each proposed laboratory project. X. REVIEW METHOD AND PEER REVIEW CRITERIA APPLICATIONS WHICH ARE NOT RECEIVED AS A SINGLE PACKAGE FROM THE PRINCIPAL INVESTIGATOR AND WHICH DO NOT CONFORM TO THE INSTRUCTIONS CONTAINED IN PHS 398 (rev. 10/88) 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 a peer review group organized by NIAID to determine their scientific merit relative to the other applications received in response to this RFA. The NIAID will eliminate from further consideration those applications judged to be noncompetitive for award and will notify the applicant and institutional business official. Those applications judged to be competitive for award will be further reviewed for scientific and technical merit by the appropriate subcommittee of the AIDS Research Review Committee convened by the Division of Extramural Activities, NIAID during February 1990. The final level of review will be provided by the National Advisory Allergy and Infectious Diseases Council at its May 1990 meeting. REVIEW CRITERIA 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. Specific competencies of the Principal Investigator and Project Leaders to conduct the proposed work: research experience, competence, commitment, and time availability of Principal Investigator, Project Leaders, and other key personnel; E. Technical merit of proposed methods for producing or obtaining test materials and for their evaluation; F. Technical sufficiency of methods for evaluation of new discoveries, laboratory test systems, models, etc.; G. Administrative experience and competence of Principal Investigator in the development, implementation, and management of comprehensive research programs; H. Plans for effective intra-Group communication and for assuring Group cohesiveness; I. 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; J. Documented commitment of institutions represented by Group members; documented capability of Principal Investigator's institution to serve as Central Operations Office for the Group; K. Commitment to accept the participation and collaboration of NIAID staff in accordance with the guidelines outlined under Section VIII, "TERMS OF AWARD: NATURE OF PARTICIPATION OF NIAID STAFF;" L. Mechanism for selecting and replacing key professional or technical personnel using the framework of the RFA; M. Ability of the Principal Investigator and Project Leaders to devote adequate time to the effective conduct of the study; N. Conformance to "MINIMUM REQUIREMENTS FOR APPLICATION" (Section IX); O. 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 which is available from Ms. Nancy Brown, (301) 496-0637. 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. Hornbeak, (301) 496- 0123. Questions regarding responsiveness to the RFA should be directed to Dr. Margaret Johnston, (301) 496-8197. o Receipt Date The deadline for receipt of applications is December 8, 1989. 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) 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, Maryland 20892 2. Submit a signed, typewritten original of the application, including the Checklist, and six signed, exact, single-sided photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, Maryland 20892** The RFA label available in the application kit PHS-398 (rev. 10/88) 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 THE TREATMENT OF ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS)" (RFA 89-AI-19) 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 (this should be the first 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 (2): This facilitates assignment of the application to reviewers with appropriate expertise. 5. SUBMIT 18 EXACT COPIES OF YOUR APPLICATION DIRECTLY TO Dr. Hortencia Hornbeak Chief, AIDS Review Section Program Project and Review Branch National Institute of Allergy and Infectious Diseases Westwood Building, Room 3A05 Bethesda, MD 20892 (301) 496-0123 o Organization of Application and Suggested Modifications of Form PHS-398 (rev. 10/88) This RFA requires the submission of a single application for the proposed NATIONAL COOPERATIVE DRUG DISCOVERY GROUP. Because of the multi-institutional nature of a 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 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 issue 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. Johnston (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 Chief, AIDS Review Section Westwood Building, Room 726 Westwood Building, Room 3A05 NIAID, NIH NIAID, NIH 5333 Westbard Avenue 5333 Westbard Avenue Bethesda, Maryland 20892 Bethesda, Maryland 20892 Telephone: (301) 496-7231 Telephone: (301) 496-0123