NIH Blueprint for Neuroscience Research Grand Challenge: Developing Novel Drugs for Disorders of the Nervous System (U01)

NIH Blueprint for Neuroscience Research Grand Challenge: Developing Novel Drugs for Disorders of the Nervous System (U01) is sponsored by National Institutes of Health (NIH). This opportunity supports mission-aligned projects and measurable outcomes.

Expired RFA-NS-11-002: NIH Blueprint for Neuroscience Research Grand Challenge: Developing Novel Drugs for Disorders of the Nervous System (U01) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Participating Organizations National Institutes of Health (NIH) ( http://www.

nih. gov ) Components of Participating Organizations NIH Blueprint for Neuroscience Research ( http://neuroscienceblueprint. nih.

gov/ )) National Center for Complementary and Alternative Medicine (NCCAM) ( http://nccam. nih. gov/ ) Center for Research Resources (NCRR) ( http://www.

ncrr. nih. gov/ ) National Eye Institute (NEI) ( http://www.

nei. nih. gov/ ) National Institute on Aging (NIA) ( http://www.

nia. nih. gov/ ) National Institute on Alcohol Abuse and Alcoholism (NIAAA) ( http://www.

niaaa. nih. gov/ ) National Institute of Biomedical Imaging and Bioengineering (NIBIB) ( http://www.

nibib. nih. gov/ ) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ( http://www.

nichd. nih. gov/ ) National Institute on Deafness and Other Communication Disorders (NIDCD) ( http://www.

nidcd. nih. gov/ ) National Institute of Dental and Craniofacial Research (NIDCR) ( http://www.

nidcr. nih. gov/ ) National Institute on Drug Abuse (NIDA) ( http://www.

nida. nih. gov/ ) National Institute of Environmental Health Sciences (NIEHS) ( http://www.

niehs. nih. gov/ ) National Institute of General Medical Sciences (NIGMS) ( http://www.

nigms. nih. gov/ ) National Institute of Mental Health (NIMH) ( http://www.

nimh. nih. gov/ ) National Institute of Neurological Disorders and Stroke (NINDS) ( http://www.

ninds. nih. gov/ ) National Institute of Nursing Research (NINR) ( http://www.

ninr. nih. gov/ ) Office of Behavioral and Social Sciences Research (OBSSR) ( http://obssr.

od. nih. gov/ ) Title: NIH Blueprint for Neuroscience Research Grand Challenge: Developing Novel Drugs for Disorders of the Nervous System (U01) Update: The following update relating to this announcement has been issued: March 16, 2011 - This RFA has been reissued as RFA-NS-12-002.

Request For Applications (RFA) Number: RFA-NS-11-002 Catalog of Federal Domestic Assistance Number(s) 93. 213, 93. 389, 93.

867, 93. 866, 93. 273, 93.

286, 93. 865, 93. 173, 93.

121, 93. 279, 93. 113, 93.

859, 93. 242, 93. 853, 93.

361 Release Date: May 5, 2010 Letters of Intent Receipt Date: July 10, 2010 Peer Review Date(s): November/December Council Review Date: January 2011 Earliest Anticipated Start Date: April Additional Information To Be Available Date (Url Expiration Date: August 11, 2010 Purpose .

The National Institutes of Health (NIH) announces a unique opportunity for investigators working with molecular probe compounds to gain access to a robust virtual pharma drug development network to develop neurotherapeutic drugs.

Successful applicants to this initiative will be collaborative participants in this network, receiving both funding and no-cost access to contracted drug development services that are not typically available to the NIH-funded research community. Funding will be provided through a U01 cooperative agreement to conduct biological testing of compound analogs in disease assays and models in the investigator’s laboratory.

No-cost drug development services will also be provided, including medicinal chemistry optimization, IND-directed pharmacology and toxicology, and Phase I clinical testing. Researchers who have disease assays and small molecule compounds that show promise for treating nervous system and psychiatric disorders, but that are not yet suitable for clinical testing, are strongly encouraged to apply.

Investigators funded through this FOA will be active partners in the design and implementation of the drug development strategy in collaboration with an NIH-appointed advisory panel of drug development experts.

This program is structured to allow investigators to maintain control of the intellectual property generated using their assays and starting compounds and to pursue commercialization of compounds that are developed within the program.

This program was established by the NIH Blueprint for Neuroscience and will consider applications for nervous system disorders within the missions of any of the 16 participating NIH Institutes ( http://neuroscienceblueprint. nih. gov/blueprint_basics/about_blueprint.

htm ). Disorders of interest include, but are not limited to, neurological, psychiatric and developmental disorders, dementias of aging, diseases and disorders of the eye or ear, and drug and alcohol dependence and addiction. By initiating development of up to 20 new small-molecule compounds over two years, we anticipate that approximately four compounds will enter Phase 1 clinical trials within this program.

The ultimate goals of this Neurotherapeutics Grand Challenge are to produce at least one novel and effective drug for a nervous system disorder that is currently poorly treated and to catalyze industry interest in novel disease targets by demonstrating early-stage success. Mechanism of Suppor t.

This FOA will use the NIH Research Project Cooperative Agreement (U01) Funds Available and Anticipated Number participating ICs intend to commit up to $1,750,000 in FY 11 to fund up to 10 awards in the first year of this program. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

It is anticipated that funded projects will carry direct costs of up to $125,000 per year for in vitro and/or in vivo and Project Period. Project duration can be up to five years; budgets should be appropriate for the proposed work. The actual duration of individual projects will depend on successful achievement of milestones as described in this FOA.

Research Strategy Length: The U01 Research Strategy section may not exceed 12 pages, including tables, graphs, figures, diagrams, and charts. See Table of Page Institutions/Organizations. Institutions/organizations listed in Section III, 1.

A. are eligible to apply. Directors/Principal Investigators (PDs/PIs).

I ndividuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. of PDs/PIs.

More than one PD/PI (i.e., m u ltiple PDs/PIs), may be designated on the application. of Applications. Applican ts may submit more than one application, provided they are scientifically dis tinct.

Resubmissions. Resubmission applications are not permitted in Renewals. Renewal applications are not permitted in response Date(s).

This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates Application Materials. See Section IV.

1 for Impaired. Telecomm unications for the hearing impaired are available at: TTY: (301) 451-59 36 II Full Text of Announcement Section I. Funding Opportunity Description 1.

Mechanism(s) of Support III. Eligibility Information 2. Cost Sharing or Matching 3.

Other - Special Eligibility Criteria IV. Application and Submission Information 1. Address to Request Application Information 2.

Content and Form of Application Submission 3. Submission Dates and Times B. Sending an Application to C.

Application Processing D. Application Assignment 4. Intergovernmental Review 6.

Other Submission Requirements V. Application Review Information 2. Review and Selection Process 3.

Anticipated Announcement and Award Dates VI. Award Administration Information 2. Administrative and National Policy Requirements Terms and Conditions of Award Investigator Rights and Responsibilities Collaborative Responsibilities 1.

Scientific/Research Contact(s) 2. Peer Review Contact(s) 3. Financial/ Grants Management Contact(s) VIII.

Other Information - Required Federal Citations - Full Text of Announcement Section I. Funding Opportunity Description A. Background and Objectives The NIH Blueprint for Neuroscience Research established the Grand Challenge for Neurotherapeutics in response to the paucity of effective treatments for disorders of the nervous system.

This program intends to develop drugs successfully through clinical Phase I and facilitate industry partnerships for their full development. The long-term goal of this grand challenge is to produce at least one novel and effective medication for a disorder of the nervous system that is currently poorly treated or untreatable. Most promising compounds identified through basic research are not sufficiently drug-like for human testing.

Before a new chemical entity can be tested in a clinical setting, it must undergo a process of chemical optimization to improve potency, activity and drug-likeness and pre-clinical safety testing to meet the standards set by the Food and Drug Administration (FDA) for clinical testing.

These activities are largely the domain of the pharmaceutical industry and contract research organizations, and the necessary expertise and resources are not commonly available to basic researchers.

To address this problem, the NIH Blueprint for Neuroscience Research is establishing a virtual pharma network of contract service providers and consultants with extensive industry experience to enable drug development in the NIH neuroscience research community.

This Funding Opportunity Announcement (FOA) is soliciting applications for U01 cooperative agreement awards from investigators with small molecule compounds that have potential for development into clinical candidates within this network.

This FOA and the Blueprint Neurotherapeutics virtual pharma network is an initiative of the NIH Blueprint for Neuroscience Research, which provides a framework for collaborative activities involving sixteen participating NIH Institutes, Centers, and Offices that support research on the nervous system ( http://neuroscienceblueprint. nih. gov/blueprint_basics/about_blueprint.

htm ).

By pooling resources and expertise, the NIH Blueprint for Neuroscience Research takes advantage of economies of scale, confronts challenges too large for any single Institute or Center, and develops research tools and infrastructure that serve the entire neuroscience To be accepted into the network, applicants to this FOA must have in hand the starting compounds for chemical optimization and bioactivity assays for testing new analog compounds generated through the Blueprint Neurotherapeutics drug development network (see Entry Criteria below for more details).

Successful applicants under this FOA will receive 1) funding for biological assessment of compounds in their laboratories and 2) no-cost access to drug development resources that typically reside in the pharmaceutical industry, including iterative medicinal chemistry optimization, pharmacokinetics, toxicology, manufacture and formulation, and Phase I clinical safety testing.

The budget of the U01 application will support only the work in investigators laboratories, which will involve testing of compounds in biological assays and models related to the target disorder.

Each drug development project will be directed by a collaborative Lead Development Team, co-chaired by the U01 investigator and a consultant with extensive industry expertise identified and supported by the NIH Blueprint for Neuroscience Research. The team will also include consultants with additional expertise, supported by NIH, and NIH staff.

Strategic decisions will be made by this team, with oversight from the Blueprint Neurotherapeutics Steering Committee and, ultimately, the NIH Blueprint for Neuroscience Research Institute This program is structured to allow U01 awardee institutions to retain ownership of intellectual property for compounds developed within the network.

To be considered responsive to this announcement, applicants must have in hand at least one small-molecule compound with well-demonstrated bioactivity that can be further developed as a drug for a disease or disorder of the nervous system. Applicants must also be able to conduct bioactivity and efficacy testing to assess compounds synthesized in the development process and provide all pre-clinical validation for the target disorder.

Entry criteria for these compounds and assays are detailed below. 1. Entry Criteria for Compounds To participate in this program, applicants must have in hand well-characterized bioactive small-molecule compounds that can provide a starting point for medicinal chemistry optimization.

This program is not designed to support biologics development. Applications may propose development of more than one chemical scaffold showing the desired profile of activity against the target of interest. Although it is desirable to have some knowledge of chemical structure activity relationships (SAR) at the target of interest, individual active compounds that are well-characterized biologically are also appropriate for this program.

Compounds proposed for entry into the Blueprint Neurotherapeutics network should possess the following attributes: Activity in a primary assay. Activity in a primary screening assay should be confirmed by repeat dose-response testing. For biochemical assays, compounds should generally show activity at 1 M or below.

For cell-based assays, compounds should ideally show activity at 10 M or below. Activity in secondary/confirmatory assay(s). Activity must be confirmed in at least one secondary assay relevant to the target disorder.

Cellular activity. Compounds should be active in at least one cell-based assay. An IC 50 or EC 50 of M is desirable.

In vivo efficacy. Efficacy in an in vivo model of the relevant disorder or disease is desirable but not required. Determination of identity and purity.

The starting compound(s) should have proof of identity and purity (typically >90%, as determined by, e.g., NMR, melting point, or LC/MS) and biological activity should have been demonstrated with more than one batch of compound. Compound target selectivity. In cases where the molecular target of compound action is known, the applicant should demonstrate the degree of selectivity for the intended target over closely related targets.

Counter-screening to determine selectivity across a broad panel of unrelated pharmacological targets (e.g., G protein-coupled receptors, kinases, etc.) is desirable, but Solubility. Compounds should have reasonable aqueous solubility, typically >1 g/mL at pH7. 4.

Structure-activity relationship (SAR). Demonstration that chemical analogs of a proposed compound show similar biological activity is desirable. Limited SAR information may have been derived from activity of analogs in a screening library or from testing of commercially available analogs.

2. Entry Criteria for Bioactivity Assays This initiative is not intended to support development of new assays, thus the applicant must propose the use of existing, well characterized assays and models. Assays that do not meet all entry criteria may undergo validation as an early stage of the U01, if necessary.

However, proposed primary screening assays should be sufficiently well developed and characterized to demonstrate feasibility for validation and use in a medicinal chemistry SAR effort within one year of the start of the award.

Applicants should have three types of assays in hand: 1) a moderate throughput primary screening assay, 2) one or more secondary assays for confirmation of activity and potential efficacy and 3) counter screening assays for target selectivity, where necessary. For each type of assay, the parameters that should be discussed in the application are outlined below. Primary screening assay.

This must be an assay with moderate throughput or better, e.g., a reporter assay, which will be used to perform routine weekly screening of compounds synthesized for iterative medicinal chemistry. To inform the medicinal chemistry design, the assay must be sufficiently robust and reproducible to reliably rank compounds with similar activities. Ultimately, the primary screening assay should meet the following criteria.

If these criteria are not already demonstrated for the assay when the application is submitted, the application should include data and discussion to support the feasibility of achieving this level of assay validation within the A statistical demonstration of reliability, e.g., a Z score =0.

5 and a coefficient of variation (CV) =20% A reproducible demonstration of dose-response with a positive control compound over at least 3 orders of magnitude (e.g., Throughput of 20-40 compounds per 1-2 weeks, run with sufficient replicates to produce robust and reproducible 10-point Secondary confirmation assays.

The applicant must have one or more secondary assays with sufficient biological validation to confirm the activity of compounds identified in the primary assay and demonstrate potential efficacy in the target disorder. These may be low to moderate throughput assays. Ideally, at least one secondary assay would be capable of generating dose-response data for multiple compounds simultaneously.

The application should contain the following information about secondary screening assays: Relevance to intended biological drug target Throughput and cycle time of each Potential to generate dose response data Reproducibility of the assay with positive control Selectivity and counter-screening assays. Where the molecular target of drug action is known, e.g., a particular kinase, it may bear similarity to other cellular targets.

In these cases, the applicant should describe criteria for compound specificity for these targets and screening assays to determine that specificity. Where aspects of the screening approach are prone to unwanted activities or artifact, counter screens should be available to rule out these unwanted activities.

Counter-screening and selectivity assays should have demonstrated reliability and adequate throughput for their proposed use in the development III. Timeline of Drug Development in the Network and the U01 Investigator’s Role Directing compounds through the drug development pipeline will be a collaborative effort.

After award, each successful applicant will work closely with NIH staff and drug development consultants to finalize a drug development plan involving the Blueprint Neurotherapeutics Network contractors. This plan will define activities and advancement criteria for a series of stages through which compounds will progress during development.

This section outlines the stages and timeline of work that will be conducted throughout the development pipeline, beginning with the entry of a well-characterized hit compound and ending with a novel candidate drug with demonstrated safety in humans. This section also outlines the roles of the NIH Blueprint Neurotherapeutics Network and the U01 investigator in each stage of the pipeline.

In conjunction with the Generic Project Timeline at: http://neuroscienceblueprint. nih. gov/bpdrugs/apply.

htm , this section can be used as a guide to develop the budget for the U01 application, which should include only the activities that will be conducted in the investigator’s laboratory. Activities supported by Blueprint Neurotherapeutics contracts, such as chemistry, pharmacology, toxicology, regulatory activities and clinical testing, should not be included in the U01 1.

Exploratory chemisty/feasibility (for budget purposes, project will undergo a feasibility phase in which investigators will validate their primary screening assays for SAR studies and test a collection of approximately 50-100 chemical compound analogs. These will be primarily identified from commercial sources and supplied to the investigator by NIH Blueprint Neurotherapeutics contractors.

Work in this phase will be directed toward determining whether the compounds and assays are amenable to medicinal 2. Medicinal chemistry optimization (for budget purposes, assume 2 years). If the outcomes of the feasibility studies are successful, compounds will enter a full-scale, iterative medicinal chemistry optimization phase to improve bioactivity, potency and pharmacological properties.

This process of understanding the structure activity relationship (SAR) between the compounds and the desired drug properties typically requires dozens of rounds of compound synthesis and testing. The ultimate goal of the SAR effort is selection of a pre-clinical candidate compound with sufficient bioactivity and drug-likeness to proceed to IND-directed pre-clinical safety assessment.

During this stage, a Lead Development Team will be formed to collaboratively manage and coordinate the progress of compounds through the development pipeline. The team will be co-chaired by the U01 investigator and a drug development consultant identified and supported by the Blueprint Neurotherapeutics program.

The team will include other consultants as needed at each stage of the project to advise on chemistry, biology and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) study design and The major role of the U01-funded investigator in this process is to conduct primary biological assessment of compounds on a regular, one-to-two week schedule to inform the design of subsequent iterations of compound synthesis.

In addition to a regular testing schedule in the primary assay, the PI will provide confirmation of the activity of select compounds in secondary assays and possibly animal models relevant to the drug target. NIH Blueprint Neurotherapeutics contractors will produce compound analogs for SAR testing and provide standard screening services to assess in vitro and in vivo ADMET characteristics of the compounds.

In the first year, medicinal chemistry will be in a hit-to-lead phase, focusing heavily on optimizing activity and potency of compounds in the primary and secondary disease assays. In the subsequent lead optimization phase, SAR will increase emphasis on ADMET properties of the compounds, with continued monitoring and optimization of bioactivity.

If compound testing in in vivo animal models is proposed, this should be limited to testing a small number of selected advanced compound analogs (e.g., 3) in 3. IND-enabling studies (for budget purposes, assume 1. 5 therapeutic candidate is identified which meets the target criteria for activity, efficacy, and favorable physicochemical and ADMET properties, it will move into IND-directed pharmacology and toxicology studies.

Blueprint Neurotherapeutics contractors, with direction from the Lead Development Team, will conduct the preclinical safety studies, GMP synthesis, formulation and other activities required to ready a compound for human testing. Blueprint Neurotherapeutics contractors will provide data and reports in a format suitable for inclusion in an IND application and will assist in the development of the application.

The U01 investigator will be responsible for the submission of the IND application and scheduling 4. Phase I clinical trial (for budget purposes, assume 1 year). Once an IND has been submitted successfully to the FDA, a Phase I clinical trial, typically in healthy volunteer subjects, will be conducted by a Blueprint Neurotherapeutics contractor.

The development of the protocol and conduct of the trial will involve input from a Clinical Development Team, which will include the U01 investigator, clinical consultants identified by the NIH, and Blueprint Neurotherapeutics staff. Costs associated with the conduct of clinical trials will be supported outside the U01 and should not be included in the requested budget.

In most cases, Phase I human studies will be conducted under a contract in the NIH Blueprint Neurotherapeutics Network. Because drug development is an inherently high-risk process, it is anticipated that there will be a significant attrition rate as projects move through the pipeline.

Go/No-Go milestones will be agreed upon at the start of each project and, in consultation with the Lead Development Team, investigators will produce milestone progress reports for independent evaluation by the Blueprint Neurotherapeutics Steering Committee.

If a funded project does not make sufficient progress toward the agreed upon milestones at any stage, funding for the project and access to Blueprint Neurotherapeutics contract resources may be discontinued unless an additional source of funding is identified. V.

Projects Not Responsive to this Announcement: PIs that are seeking only funding for drug development and have sufficient access to medicinal chemistry and drug development expertise should consider funding programs available through the individual NIH Institutes.

Please contact program staff at the relevant Institute for information about available drug development programs for Projects requiring only access to IND-directed preclinical testing for compounds that have already undergone medicinal chemistry optimization are not suitable for this program. The NIH Rapid Access to Interventional Development (NIH-RAID) Program ( www. nihroadmap.

nih. gov/raid ) offers investigators access to IND-directed services on a competitive basis. Development of biomarkers will not be supported through this program.

Please contact program staff at the appropriate Research aims appropriate for an investigator-initiated R01 grant, such as understanding underlying biological mechanisms of disease, should not be included in an application under this FOA. C.

Instructions to Applicants An application to this FOA should address the points Disease of interest : Describe the current state of knowledge of the disease etiology, clinical characteristics, and current and projected disease prevelance. Briefly discuss available treatments and their limitations.

Provide a brief overview of the state of clinical trials research in this disease area, including relevant clinical outcome measures and biomarkers. Describe the clinical feasibility of the target disorder, for example, the availability of clinical trials networks and sites for later-phase clinical trials, and identify any clinical collaborators for this project. Drug Target: Describe the intended molecular or cellular drug target.

Provide evidence for a role of the target in disease pathophysiology, target validation, druggability, and novelty of the target with respect to ongoing biopharma development programs or existing drugs. Describe the expected clinical impact that a drug directed against this target might have on the features of disease and disease progression, e.g., whether the intervention is expected to be palliative or disease-modifying.

Indicate whether there are reliable biomarker(s) available to monitor effects on the target in a clinical or pre-clinical setting. Indicate whether a drug must cross the blood brain barrier to successfully impact this target. Summary of Key Drug Characteristics: Include a table of key properties for the intended drug (see guidance and table template at: http://neuroscienceblueprint.

nih. gov/bpdrugs/apply. htm , including the intended disorder, patient population, mode, duration and frequency of delivery, and standards for efficacy.

In addition to at least one small molecule compound proposed for development, the applicant must provide data demonstrating the suitability of the intended primary and confirmatory assays and models for drug Small molecule compounds proposed for development: Applicants should address the compound entry criteria outlined in the Research Scope section of the FOA.

Applicants may propose the development of more than one chemical scaffold showing the desired profile of activity against the target of interest. Describe the evidence for activity of the compounds(s) on the target and disease of interest. Describe the level of activity and potency (EC 50 or IC 50 ) of the compounds in biochemical and cellular bioassays and the in vitro toxicity (LD 50 ).

In addition to chemical structures, information should be provided on known chemical and physical characteristics of the compound(s), e.g., drug-like properties, solubility, chemical liabilities, etc. Present the results of testing any chemical analogs and inferences about structure activity relationships (SAR). Proposed primary and secondary assays : Describe the primary assay that will be used to inform chemical SAR studies.

Provide justification for the relationship of the primary assay to the disease target. Present data to support validation of the assay for reproducible ranking of similarly active compounds based on activity and potency, addressing the assay entry criteria outlined in section B. II of the Funding Opportunity Description above.

If the primary assay is not fully validated when the application is submitted, discuss the feasibility of achieving these entry criteria within the first year of the Identify secondary and confirmatory assays and models (in vitro and in vivo) for preclinical bioactivity validation of optimized compounds.

Describe the degree of pre-clinical or clinical validation of each assay and model for the disease of interest and the relevance of each to the proposed target of drug action. Provide data to demonstrate the correspondence between results of the primary and secondary assays.

Approach for use of primary and secondary assays: Summarize methods for the primary and secondary assays proposed for compound optimization, including methods for ongoing internal quality control, data analysis and plans for routine submission of data to a centralized Blueprint Neurotherapeutics database. The application should include a Summary Table of Bioactivity Assays (see table template at: http://neuroscienceblueprint. nih.

gov/bpdrugs/apply. htm ) proposed for evaluating the clinical promise of compounds, indicating the throughput for each assay and advancement criteria for progressing compounds from one assay to the next. Describe any potential pitfalls associated with the use of the primary and secondary assays and approaches to their resolution .

Management plan: Describe the roles and extent of participation of key personnel over the course of the small molecule development process, from compound optimization through Phase I clinical trials. Indicate the willingness of the Principal Investigator and key personnel to operate under the cooperative agreement terms and conditions outlined in section VI. 2.

A of the FOA. If needed, describe the availability of a clinical consultant with expertise in the target disorder. Clinical experts should be sought as needed to develop the application (e.g., to determine the Summary of Key Drug Characteristics : http://neuroscienceblueprint.

nih. gov/bpdrugs/apply. htm ), and available after award to aid in determining the goals of the drug development program and to consult on the design of the clinical trial.

Resources: (Note that this is a separate section of the application from the Research Strategy section).

Intellectual property considerations for small molecule compounds proposed for development: Applicants should describe any constraints that they are or may be aware of that would impede use or development of the compound(s) in achieving the program goals (e.g., certain restrictions under transfer or sharing agreements, applicant’s previous or present intellectual property filings Intellectual property considerations for primary and secondary assays: Applicants should describe any constraints that they are or may be aware of that would impede use of the assays and models for research purposes and/or Intellectual property management and commercialization: Applicants should describe their institutions existing or planned infrastructure for bringing the compounds to practical application (e.g., licensing for further drug development, managing intellectual property, commercializing discoveries) consistent with achieving the program goals For a multiple-PI, multiple-institution application, applicants should describe the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing intellectual property) among the institutions consistent with achieving the goals of the program.

VIII, Other Information - Required Federal Citations , for policies related to this announcement. opportunity will use the U01 award mechanism(s). Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

FOA uses Just-in-Time information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants. nih.

gov/grants/funding/phs398/phs398. html ). will use a cooperative agreement award mechanism.

In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative "Cooperative Agreement Terms and Conditions of Award".

participating ICs intend to commit up to $1,750,000 in FY 11 to fund up to 10 awards in response to this FOA. It is anticipated that applications will carry direct costs of up to $125,000 per year for in vitro and/or in vivo screening The estimated amount of funds available for support of up to 10 projects awarded as a result of this announcement is $ 1,750,000 for fiscal year 20 11 .

Future year amounts will depend on annual and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary.

Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004 .

grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA. III. Eligibility Information 1.

A.

Eligible Institutions organizations/institutions are eligible to apply: Public/State Controlled Institutions of Private Institutions of Higher Education Black Colleges and Universities (HBCUs) Colleges and Universities (TCCUs) Alaska Native and Native Hawaiian Serving Institutions Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small (non-U.S.) Entities (Foreign Organizations) Agencies of the Federal Government individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her institution to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH program support. multiple PDs/PIs, may be designated on the application for projects that require a team science approach and therefore clearly do not fit the