Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	Office of Strategic Coordination (Common Fund) This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (http://commonfund.nih.gov) through the NIH Office of the NIH Director, Office of Strategic Coordination (http://dpcpsi.nih.gov/osc/). The FOA will be administered by the National Institute of Diabetes and Digestive and Kidney Diseases (www.niddk.nih.gov) on behalf of the NIH.
Funding Opportunity Title	Limited Competition: Renewal Applications for Technology Development for New Affinity Reagents Against the Human Proteome (U01)
Activity Code	U01 Research Project Cooperative Agreements
Announcement Type	New
Related Notices	None
Funding Opportunity Announcement (FOA) Number	RFA-RM-14-002
Companion Funding Opportunity	None
Number of Applications	Only one application per institution is allowed as described in Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.310
Funding Opportunity Purpose	The NIH Common Fund Protein Capture Reagents Program (PCRP) aims to develop over time the capacity to generate a community resource of high quality renewable affinity reagents for all human proteins (see https://commonfund.nih.gov/proteincapture/). This Funding Opportunity Announcement (FOA) is a component of the PCRP, and it seeks renewal applications to cooperative agreements that were funded through RFA-RM-10-018. Novel approaches for producing validated protein affinity reagents have been developed by the presently funded technology centers and have demonstrated potential for substantially reducing cost and increasing throughput. To determine if any of these approaches can be used in a large-scale proteome project, applicants funded through this FOA are expected to demonstrate scalability by generating affinity reagents recognizing at least three hundred human protein targets.

Posted Date	February 12, 2014
Open Date (Earliest Submission Date)	March 25, 2014
Letter of Intent Due Date(s)	March 25, 2014
Application Due Date(s)	April 25, 2014, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	June/July, 2014
Advisory Council Review	August 2014
Earliest Start Date	September 2014
Expiration Date	April 26, 2014
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Background

Protein affinity reagents have been widely used in basic research and clinical applications.  For example, antibodies have been used to label and isolate individual proteins, complexes and groups of proteins, and whole cells; to localize and visualize, in a time resolved manner, individual proteins, complexes and groups of proteins in cells, tissues, organs, and whole organisms for analytical or diagnostic purposes, including clinical diagnostics; to determine the expression level of proteins in samples of interest, including biological fluids and tissue/cellular samples; to characterize the functional state of the protein as evidenced by its conformational status, post-translational modifications or macromolecular interactions, and biological effects; to manipulate the function of the target protein as a potential tool for mechanistic research; and to target specific proteins for therapeutic intervention.

Immunoglobulin G (IgG) antibodies are the most common protein affinity reagents, but several combinatorial display technologies exist where only a fragment of the whole IgG (e.g. the single chain Fv or the Fab) is used for capturing the protein target of interest.  Several other classes of molecules such as aptamers have also been used for generating high quality affinity reagents.  Recent improvements on the production of several types of synthetic and recombinant protein affinity reagents show great promise for substantially reducing cost and increasing throughput and applicability. However, the novel methods and approaches developed within the technology development component of the PCRP have been limited to the generation of a handful of reagents and have not demonstrated scalability. The overall scalability and cost determination in a production pipeline are still to be determined. The generation of hundreds or thousands of reagents in a pilot pipeline would allow an estimate of the cost for a proteome scale project.

There are about 20,500 protein-coding human genes.  However, for a large portion of these genes there are few tools that enable the research community to directly characterize their encoded proteins, for example by identifying and quantifying them in mixtures, by localizing and visualizing them within cells and tissues, or for characterizing the molecular complexes in which they reside. The intent of this solicitation is to develop production pipelines for renewable and validated affinity reagents that can be generated at a cost and throughput that would enable the creation of a community resource of reagents against the human proteome. For this purpose this FOA solicits applications to generate affinity reagents against at least three hundred proteins at a cost below $3,500 per target. The cost and throughput of the production pipeline should be estimated from target selection to reagent validation and distribution. Specific quantifiable milestones should also be used for assessing the actual progress toward the final goal. The results from the projects funded through this initiative should demonstrate if the novel affinity reagents technologies and established pipelines can be used to generate at a reasonable cost a proteome scale resource of renewable and validated affinity reagents for the research community.

The challenge in developing a community resource of high quality renewable affinity reagents for all human proteins resides also in being able to develop a scalable approach that addresses all steps of the pipeline from antigen production to the validation and distribution of the produced affinity reagents.  This FOA seeks to meet this challenge by soliciting projects that can demonstrate the generation of affinity reagents against at least three hundred human proteins at a cost of about $3,500 per target (inclusive of antigen production, affinity reagents production, and their validation).

It is foreseeable that different technologies might be more successful on particular protein families thus more than one approach might be required to achieve the final goal of a proteome scale community resource of renewable affinity reagents.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	Renewals to RFA-RM-10-018 The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The NIH Common Fund intends to commit $6,000,000 in FY 2014 to fund 2-4 awards.
Award Budget	Direct costs requested may not exceed $2,000,000 per year.
Award Project Period	The project period may not exceed two years.

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

Eligibility is limited to cooperative agreement awards that were funded through RFA-RM-10-018 "Technology Development for New Affinity Reagents Against the Human Proteome (U54)."

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligibility is limited to PD(s)/PI(s) of cooperative agreement awards that were funded through RFA-RM-10-018 "Technology Development for New Affinity Reagents Against the Human Proteome (U54)."

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Only one application per institution (normally defined by having a unique DUNS number or NIH IPF number) is allowed.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Salvatore Sechi, Ph.D.
Senior Advisor for Proteomics and Systems Biology
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Room 797
Bethesda, MD 20892-5460
Telephone: 301-594-8814
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

• For this specific FOA, the Research Strategy section is limited to 30 pages.

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

The PD/PI is expected to devote at least 2.5 person/months to this award.

The budget for the management plan should be specified and justified, including funds for coordination among components and travel (including travel for key personnel to Steering Committee meetings; and PCRP annual meetings.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims: The applicant should outline the new aim(s) and how the project proposed in the renewal application will achieve the objectives and scope of this FOA.

Research Strategy: Applications should address all the points listed below.

A. Identification, prioritization, and acquisition of antigens

The selection of the targets (three hundred or more human proteins) is up to the applicants. However, for developing an efficient pipeline, and for maximizing the impact that the project might have on the scientific community, the applicants should consider focusing on functionally relevant human protein families (e.g. proteases, kinases, phosphatases, G-protein coupled receptors, glycosyltransferases) or topic (e.g. nuclear proteins, set of metabolic pathways, mitochondrial proteins) or subsets of proteins with few reliable and renewable affinity reagents available. Multiple targets may be selected for the same gene product. For example, the active and inactive forms of an enzyme or the phosphorylated and non-phosphorylated forms of a specific protein may be considered as separate targets. It should be noted that the NIH might provide a small list of antigens that all awardees will have to work on for comparing different technologies.

The applicants should present data indicating the feasibility of producing or acquiring the antigens needed in the project. If the applicants are planning to produce the antigens, preliminary data generating affinity reagents against these antigens should be presented. If the applicants are planning to acquire the antigens, a letter of commitment specifying cost, format, list of antigens, and timeline should be included in the application. Preliminary data generating affinity reagents using these antigens should also be presented.

The quantities needed for the development of the affinity reagents and for their validation should be considered when estimating cost per target.

The known or estimated success rates in antigen production and generation of affinity reagents against these antigens should be accounted for in the proposed plan and milestones. A contingency plan for reaching the proposed goal and milestones should also be described.

B. Production pipeline

The applicants should provide detailed plans for how they will develop a highly efficient, scalable production pipeline for renewable and validated affinity reagents against at least three hundred human protein targets.

Technical approach. The applicants should describe relevant results from the previously funded period for justifying the basic technical approach to making and selecting affinity reagents (e.g. recombinant antibodies, aptamers, etc.). This approach should be minimally justified in terms of: ability to be used in a high-throughput production pipeline; scalability; cost; technical and practical ability to obtain reagents against a large number of protein targets; ability to validate in a cost efficient manner using applications that are common for affinity reagents (e.g. Immunohistochemistry, Immunoprecipitation, Western Blot, Immunofluorescence); advantages compared to alternative approaches; and usability by the community (including advantages for distribution, availability of secondary reagents, ability to label the reagents for various applications, etc.).

Applicants should include other important information relating to the goal of successfully generating a useful resource. For example, how many affinity reagents should be generated per target in order to optimize utility to the community? NIH has been advised that a minimum of two reagents per target should be sought; however applicants should propose and justify a number balancing quality, scientific utility, and costs.

Pipeline development. The applicants should discuss how production will be assessed, what criteria will be applied to determining success at various stages, and also how the process will be monitored to identify any problems within the pipeline. Applicants should discuss routine pipeline quality control (e.g. quality control for reagents used in the process). Applicants should discuss how standard operating procedures will be developed. Applicants should discuss any laboratory information management systems or other informatics that will support their effort.

The applicants should discuss current state of commercial costs per typical renewable affinity reagent (e.g. mouse monoclonal) and per target. The applicants should discuss their expected costs per reagent and per target at the start of their award and at the end of their two-year funded period. A breakdown of costs for each stage of the process should be detailed (e.g. target selections, acquisition/production of antigens, validation, and distribution). Applicants should specifically outline what is included, and not included, in cost estimates. Applicants should discuss how their cost model might serve as the basis to compare other production platforms against; or suggest a useful cost model for comparative assessment of different platforms.

Applicants should discuss and justify any automation they will use in terms of how it will improve efficiency, cost, quality, or other aspects of production. However, in view of the short term of these awards, where expensive instrumentation might be required, leasing instrumentation or use of facility that can operate on a fee basis as an alternative to purchase is strongly encouraged.

Applicants should provide timelines and quantitative milestones for all critical stages of the pipeline development with particular emphasis on cost and quality.

C. Continuing improvements

The applicants should include a discussion of plans for improving the production pipeline within the proposed budget. Plans for improvements in cost or quality should be discussed, for example, by identifying and addressing important cost-drivers, by modifying protocols or methods, and by cost advantages of scale.

D. Initial characterization and validation

Applicants should propose and justify initial characterization for reagents, including stating criteria for success, based on the importance for assuring a high-quality resource of renewable affinity reagents. It is however expected that at minimum the affinity of the reagent to the target/antigen and the specificity within the context of one application are determined.

Applicants should clearly describe the validation method(s). Although the NIH encourages the generation of reagents that will have the broadest possible utility it is anticipated that particular affinity reagents will not perform optimally for all applications. The choice and number of applications against which the reagents are validated are left to the applicant. 

E. Ability to collaborate productively with other significant public efforts

The NIH acknowledges other international efforts to develop protein affinity reagents for the human proteome and believes these are collaborative opportunities with potentially mutual benefit towards developing a comprehensive resource. The applicants should briefly discuss any plan for present or future collaborations in this field.

F. An effective center management structure

The applicants should include an overall management plan for the center that addresses the following elements:

1) A description of the project leadership and key personnel, and their responsibilities. While it is up to the applicant to provide a specific management structure, this FOA will require dedicated specialized key personnel with appropriate levels of expertise and responsibility overseeing critical aspects of the project. It is expected that these individuals will need to dedicate a significant amount of effort in day-to-day management of the center. For example, the PD/PI may designate someone in the role of a scientific project manager to oversee daily operations. Alternately (or in addition) the PD/PI may choose dedicated experienced individuals to lead critical components of their pipeline. Such individuals are expected to have appropriate expertise in addition to scientific expertise, including knowledge of and experience in project management, ability to use project management tools, leadership skills, ability to maintain and communicate appropriate records, and ability to collaborate with all components of the proposed effort. The management leadership structure, and individuals identified to fulfill those roles, should be justified based on their appropriateness to the proposed effort.

2) A description of how the various elements of the project will be managed in an integrated way. This includes a description of how communications will be handled within the center, lines of authority, and how decisions will be made. It is critical to describe how any collaborations that are at another physical site will be managed and integrated (e.g. subcontracts).

It is highly likely that the formation of project sub-committees or working groups will be recommended by the steering committee to resolve program-wide issues (e.g., quality, validation, exchange of antigens/reagents, distribution). Management plans should anticipate the need for this level of collaborative activity among the program Research Network components.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Within the Research Sharing Plan the applicants are expected to propose a basic mechanism to make the reagents and characterization/validation information broadly available. The PCRP has developed a web portal http://proteincapture.org/ for reagents that have been produced against human transcription factors and it is expected that awardees will use this portal for depositing the affinity reagents characterization data and provide links to distributors where all validated reagents can be obtained, consistent with achieving the goals of this program.
• Applicants are expected to discuss the availability and distribution of the antigens and affinity reagents. NIH notes that there might be some challenges in distributing affinity resources. NIH has been advised to take advantages of the strengths of both the public sector and the private sector in distributing this resource. Ideally, it will be possible for a number of entities to distribute these reagents. Potential sites and web portals that the applicants should consider for distribution include, but should not be limited to: the University of Iowa hybridoma bank (http://dshb.biology.uiowa.edu/), and The DNASU plasmid repository (DNASU). The applicant can also consider the development of an independent site, but interaction with other ongoing efforts in the community is strongly encouraged for maximizing the potential impact of the present effort in the scientific community. Applicants are expected to identify specific distributors, and discuss their distribution plans. Final distribution plans are subject to approval by NIH program staff.

Applicants are expected to discuss how they will make available information about the antigens and affinity reagents (validation and characterization data)

Applicants are expected to discuss how they will make available protocols for validation and characterization.

Applicants are expected to discuss how any software tools developed within this award will be made available.

Applicants are expected to discuss how intellectual property will be managed. The NIH intends that the reagents be broadly available and distributed at minimal cost, and without undue intellectual property constraints. These features should enable creative scientists to develop downstream applications for the reagents. Applicants and their institutions should also be familiar with the NIH statements regarding intellectual property of resources developed with Federal funds (NIH Research Tools Policy (http://grants.nih.gov/grants/intell-property_64FR72090.pdf) and other related NIH sharing policies at http://sharing.nih.gov). In order to ensure that the further development of these reagents is not unduly impaired or impeded, applicants are expected to address how they will manage intellectual properties and also meet the goals of this funding initiative. It is strongly encouraged that distribution sites such as DNASU and DSHB, which distribute reagents and clones at a minimal cost, are used. Restrictive licensing and restrictive sharing practices for this program could substantially diminish the value and public benefit provided by this community resource project. Management practices that would prevent or block access to, or use of, these resources for research use will be considered to be hindering the goals of the program. Applicants are encouraged to clearly demonstrate in their Resource Sharing Plan how their strategies will achieve the desired public benefit and programmatic goals through effective sharing of resources generated under this award

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Is there a high likelihood that the proposed center can produce high-quality affinity reagents to human proteins, based on the applicant’s past experience and the proposed future plans?

Is there a high likelihood that the applicants can accomplish this at levels of throughput, data quality, and cost within the scope and award period anticipated by this FOA?

Is there a high likelihood that the activities of the proposed center will provide useful information about how to pursue a larger-scale effort, for example by providing insight into bottlenecks, cost-drivers, and other significant aspects of scale?

Is there a high likelihood that the proposed project will demonstrate scalability?

Is there a high likelihood that the affinity reagents produced will be of a type that could be widely used by the community, considering all relevant factors such as quality, ability to be used in a range of applications (for example, ease of labeling, existence of secondary reagents)?

Is there a high likelihood that the center will make significant contributions to the state-of-the-art in the production of affinity reagents?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? 

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children 

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS)

Reviewers should consider and comment on, but not score, the aspects of the Resource Sharing Plan that pertain to overall consistency of the intention to create a readily distributable public resource, including licensing and intellectual property issues that need to be consistent with the goals of this FOA for a broadly available resource that is readily usable by the community, as outlined above.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• Will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. 

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.      

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

NIH Cooperative Agreements are subject to terms and conditions in addition to, and not in lieu of, otherwise applicable U.S. Office of management and Budgets (OMB) Administrative Guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local governments are eligible to apply), and other HHS, PHS, and NIH grants administration policies.

Each renewal made under this FOA will be subject to the same terms and conditions specified for the original U54 award. Applicants should consult the Notice of Award for their current U54 for the specifics of those terms and conditions.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

Defining the details for the center within the guidelines of this RFA and for performing the scientific activities. The PD/PI will agree to accept close coordination, cooperation, and participation of NIH staff in those aspects of scientific and technical management of the project as described under "NIH Program Staff Responsibilities."

The PD/PI of a center will:

• Determine experimental approaches, design protocols, set project milestones and conduct experiments;
  
  
• Provide goals for throughput, quality, and cost to the NIH as requested (usually at the outset of the award and annually thereafter, but also at other times as requested by NIH program staff);
  
  
• Ensure that the affinity reagents meets the quality standards and costs agreed upon at the time of award or any improved quality standards and costs negotiated during the award period;
  
  
• Ensure that resources developed as part of this project, and accompanying characterization/validation data, are made broadly available according to NIH policies, and in a manner to be approved by NIH staff, and that results are published in a timely manner, consistent with achieving the goals of this program funding;
  
  
• Adhere to the policies regarding intellectual property and other policies that might be established during the course of this activity;
  
  
• Integrate with the program's process for selecting targets (antigens), and to make best-faith efforts to develop affinity regents to those targets as negotiated with program staff;
  
  
• Submit data for assessment in any manner specified by the Steering Committee or the External Scientific Panel (ESP) to the program;
  
  
• Submit progress reports as agreed upon by the Steering Committee and the ESP;
  
  
• Accept and implement any other common guidelines and procedures developed for the NIH Protein Capture Reagents Program (PCRP) and approved by the Steering Committee and the ESP;
  
  
• Accept and participate in the cooperative nature of the PCRP research network;
  
  
• Coordinate and collaborate with other U.S. and international groups engaged in similar large affinity reagent generation projects;
  
  
• Inform the NIH Program Director of all major interactions of members of the Steering Committee;
  
  
• Attend Steering Committee meetings.
  
  
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies and meeting the goals of this funding initiative.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• During the conduct of this activity provide technical assistance, advice and coordination. However, the role of NIH will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the PCRP research network and that NIH staff will be given the opportunity to offer input to this process;
  
  
• NIH Project Scientist(s) and Program Director(s) shall participate in the Steering Committee and will collectively have one vote.

The Project Scientist(s) and the Program Director(s) will:

• Participate (with the other Steering Committee members) in the group process of setting research priorities, deciding optimal research approaches and protocol designs and contributing to the adjustment of research protocols or approaches as warranted. The Project Scientist will assist and facilitate the group process and not direct it;
  
  
• Negotiate throughput, quality, cost goals, and affinity reagent target (antigens) prioritization with the awardees as necessary;
  
  
• Serve as a liaison between the awardees and the ESP, the Protein Capture Working Group co-chairs, the NIH Common Fund, the appropriate Advisory Councils, and the larger scientific community;
  
  
• Coordinate the efforts of the awardee with others engaged in similar efforts, including other awardees under this program and those awardees involved in related NIH programs, and with the international community involved in creating a public resource of affinity reagents;
  
  
• Attend all Steering Committee meetings as a (single) voting member and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action;
  
  
• Lend relevant expertise and overall knowledge of NIH-sponsored research to facilitate the selection of scientists not affiliated with the awardee institutions who are to serve on the ESP and the Steering Committee; serve as liaison between the Steering Committee and the ESP;
  
  
• Serve on subcommittees of the Steering Committee and the ESP, as appropriate;
  
  
• Provide advice in the management and technical performance of the investigation;
  
  
• Assist in promoting the broad availability of the resources developed in the course of this project to the scientific community at large;
  
  
• Participate in data analyses, interpretations, and where warranted, co-authorship of the publication of results of studies conducted;
  
  
• Assist awardees in the development, if needed, of policies for dealing with situations that require coordinated action;
  
  
• Retain the option to recommend, with the advice of the ESP, the withholding or reduction of support from any cooperative agreement that substantially fails to achieve its goals according to the milestones agreed to at the time of award, fails to maintain state-of-the-art capabilities, or fails to comply with the Terms and Conditions of the award;
  
  
• Additionally, the agency program official or IC Program Director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned program director will coordinate with the NIH Project Scientist, and will attend Steering Committee and ESP meetings.

Areas of Joint Responsibility include:

• Participate in the Steering Committee. A Steering Committee will serve as the main governing board of the Protein Capture program. The Steering Committee membership will include the Project Scientist(s), Program Director(s) and the PD/PI of each awarded cooperative agreement, for all (Affinity Reagent Production, Immunogen Production, and Technology Development) components of the PCRP research network. The Steering Committee Chair will not be an NIH staff member. Additional members may be added by action of the Steering Committee. Other government staff may attend the Steering Committee meetings, if their expertise is required for specific discussions. At the discretion of NIH staff, in consultation with the Steering Committee and the ESP, sub-committees of the Steering Committee may be created in order to focus on topics that are of specific interest to either Production or Technology Development activities, for example in cases where program decisions will substantially affect one activity but not the other. All Steering Committee decisions are subject to final approval by the NIH.

The Steering Committee will:

• Discuss progress in meeting the projects goals;
  
  
• Develop recommendations for uniform procedures and policies necessary to meet the goals of the Research Network, for example for reagent quality measures, validation and assessment, conventions for reagent distribution, or measuring costs and throughput. Adoption of procedures and policies developed by the Steering Committee will require concurrence by the ESP and/or the NIH;
  
  
• Serve as a venue for coordination on the improvement of the development of affinity reagents, for example by disseminating best practices and collectively evaluating new procedures, resources, and technologies;
  
  
• Schedule the time for, and prepare concise (3 to 4 pages) summaries of, the Steering Committee meetings, which will be delivered to members of the group within 30 days after each meeting;
  
  
• Each full member (limited to one person per awarded center, in the case of multiple PI’s per center) will have one vote except NIH Project Scientist(s) and Program Director(s), who will have one collective vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee;
  
  
• Steering Committee meetings will take place by telephone or in person, with at least one in-person meeting per year (see below) and other meetings to be determined by NIH staff in consultation with the Steering Committee. It is highly likely that project sub-committees or working groups will be recommended by the steering committee to resolve program-wide issues (e.g., quality, validation, exchange of immunogens/reagents, distribution);
  
  
• Another area of joint responsibility is that NIH and the grantees will work with and provide information to the ESP;
  
  
• The ESP will be responsible for reviewing and evaluating the progress of the members of the PCRP research network toward meeting their individual and collective goals. The ESP will provide recommendations to the NIH PCRP Working Group, the Directors of NHGRI, NIDCD, and DPCPSI as well as the Directors of all other participating NIH Institutes and Centers about continued support of the components of the research network. The ESP is composed of five to seven senior scientists with relevant expertise who are not PD/PIs of a cooperative agreement involved in the PCRP research network. The membership of the ESP may be changed or enlarged permanently, or on an ad hoc basis, as needed;
  
  
• The ESP will meet at least once a year. During part of this meeting, there will be a joint meeting with the Steering Committee to allow the ESC members to interact directly with the awardees. Annually, the ESP will make recommendations regarding progress of the Research Network and present advice about changes, if any, which may be necessary in the PCRP to the NIH Working Group, the Directors of NHGRI, NIDCD, and DPCPSI as well as the Directors of all other participating NIH Institutes and Centers.
  
  
• The NIH PCRP Working Group consists of program staff from the NIH Institutes and Centers that have been involved in developing the PCRP. The purpose of this Working Group will be to disseminate information about the progress of the PCRP to the NIH and to provide a forum for the Working Group to discuss issues related to the PCRP research network.

Dispute Resolution

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Finding Help Online: http://grants.nih.gov/support/index.html
TTY: 301-451-5939
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
TTY: 301-451-5936
Email: [email protected]

Salvatore Sechi, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8814
Email: [email protected]

Joseph Mosca, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-408-9465
Email: [email protected]

Craig E. Bagdon
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-2115
Email: Craig. [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.