Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	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 (NIDDK) on behalf of the NIH.
Funding Opportunity Title	Technology Development for New Affinity Reagents Against the Human Proteome (U54)
Activity Code	U54 Specialized Center- Cooperative Agreement
Announcement Type	New
Related Notices	December 3, 2010 - Notice of Pre-application Teleconference for Request for Applications. See Notice NOT-RM-11-003.
Funding Opportunity Announcement (FOA) Number	RFA-RM-10-018
Companion FOA	RFA-RM-10-017
Number of Applications	Only one application per institution is allowed Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestics Assistance (CFDA) Number(s)	93.310
FOA Purpose	The NIH Common Fund Protein Capture Program aims to develop over time the capacity to generate a community resource of high quality renewable affinity reagents for all human proteins (see http://nihroadmap.nih.gov/proteincapture). This Funding Opportunity Announcement (FOA) is a component of the Protein Capture Program, and is designed to solicit grant applications that would develop and/or improve approaches for obtaining protein affinity reagents at high throughput and low cost. Applications should describe an approach for improving and/or developing protein affinity reagent technologies that can be ready for proteome scale projects within three to five years. However, it is expected that the technologies proposed have already shown solid proof of principle, yet need additional funds to demonstrate scalability. It should also be noted that the main goal of this solicitation is to improve the overall production pipeline from targets selection to the validation of the protein affinity reagents; thus applications should discuss their development efforts within a production pipeline context. However, the proposed improvements or developments could be across the entire process or have a main focus on specific aspects of the process.

Posted Date	December 3, 2010
Open Date (Earliest Submission Date)	Not Applicable
Letter of Intent Due Date	January 4, 2011
Application Due Date(s)	February 4, 2011
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	June-July 2011
Advisory Council Review	August, 2011
Earliest Start Date(s)	September, 2011
Expiration Date	February 5, 2011
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 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. While some links are provided, 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 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

There are about 20,500 protein-coding human genes. However, for a very large portion of these genes there are few tools that enable the 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.

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 identify the expression level of proteins in samples of interest, including biological fluids and tissue/cellular samples; to identify 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 of therapeutic intervention.

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. These and other technologies have been applied to developing protein affinity reagents, and in many cases high quality reagents have been generated and used in basic research and clinical applications.

However, the present cost for generating these types of protein affinity reagents is very high, and the cost of generating a single renewable affinity reagent (e.g. a monoclonal antibody) is between $5,000 and $15,000 or more depending on the amount of characterization and validation. Furthermore, the generation of these reagents takes anywhere from 3 to 9 months for complete production. It should also be noted that in most cases it would be useful to have more than one affinity reagent per protein so as to probe different epitopes, isoforms, and modification states. Different end-uses (e.g., detection in a sample vs. cellular localization vs. immunoprecipitation) might also require specific affinity reagents. So, while a number of approaches to generating protein affinity reagents exist, current limitations of cost and throughput represent significant roadblocks to the development of a comprehensive and broadly available resource of renewable affinity reagents to all human proteins at a reasonable cost - the long-term aim of the NIH Protein Capture Program.

The challenge to developing approaches that could be scaled to develop a comprehensive and broadly available affinity reagent resource resides also in the development of a pipeline that goes from the selection of protein targets to the validation of the produced reagents. For this purpose this FOA encourages technology developments that can be used in the context of a pipeline. However, applications may focus on one or more components of the process (e.g. library generation, selection, validation) or in the overall integration of the various components that are required for the production of well characterized and validated renewable protein affinity reagents.

This initiative should produce advances in affinity capture technologies that will put the NIH and the research community in a position to decide whether and how to develop a comprehensive and broadly available resource.

This solicitation is part of a Protein Capture Program that includes an effort to be funded by another FOA that is specifically aimed to the production of high quality affinity reagents against all human transcription factors (see http://nihroadmap.nih.gov/proteincapture).

Guidance to Applicants

The goals for this specific FOA are to develop new technologies and approaches that could substantially increase the throughput and reduce the cost of generating renewable affinity capture reagents in a relatively short time period. Thus responsive applications are most likely to be using an approach that is already well past the proof-of-principle stage, and which needs additional funds to demonstrate scalability.

It should be noted that proposed approaches must be cast within the conceptual context of a production pipeline for developing affinity reagents, so that the effects on the pipeline can be evaluated, and so that any proposed development of individual components can be related to and informed by the process as a whole.

Because the emphasis of this FOA is on technology development rather than production, NIH does not expect these development centers to necessarily realize the scaled cost, quality, or utility benefits during the period of the award. However, once the proposed work is completed, the effort should provide the basis to argue convincingly the benefits for a production pipe line.

Specific topics that would be responsive to this FOA include, but are not limited to:

1) Pilot efforts to develop a pipeline for affinity reagents, where there is currently insufficient data to adequately understand pipeline performance, and/or where integration has not been achieved. Such applications should also feature an approach (for example, a type of reagent, or a pipeline design) that is different from currently mature approaches. Applicants must explain why their approach is significantly different from mature approaches, what advantages it could offer, and why it is at the stage that needs pilot development.

2) Significant development and integration of a new pipeline component or components within the context of an existing production pipeline or otherwise mature approach. Applicants must explain why the area of focus is likely to result in an improvement (is it a cost-driver? Will it improve quality or throughput?).

3) Development of significant process improvements, such as robotics/automation, multiplexing, microfluidics, within the context of an existing pipeline.

NIH expects that responses to this FOA will encompass approaches that are at different levels of maturity towards development of a scalable production pipeline. However, applications that only focus on technologies that are unlikely to be able to be integrated into a pipeline, or which will not establish data to demonstrate the potential to scale, within the term of the award are unlikely to be responsive. For example, early-stage development of a new type of affinity reagent is not appropriate for this FOA.

To provide guidance to the applicant, we provide an outline of a typical Research Strategy consisting of four components. All of these components should be addressed. However, applicants are free to organize their applications differently as long as the developmental aspects are emphasized within the context of a production process, so that it is clear how proposed developments would affect an eventual scaled pipeline.

I. Choice of targets and antigens production

Applicants should justify their choice of targets against which affinity reagents will be developed in terms of several factors, including: the range of classes, and number of target proteins needed to demonstrate that the proposed development will result in a significant improvement in cost, efficiency, quality, utility, comprehensiveness; classes of proteins that can be targeted (e.g., specific protein families, specific post-translational modifications). The choice of targets should also be balanced against the funds available under this FOA.

If the proposed approach requires the proteins (or portions thereof) to be used as antigens the applicant should provide plans for producing or acquiring them. Applicants may acquire antigens from other sources or use presently available resources for this purpose. For example, numerous cDNA expression constructs can be available through the ORFeome Collaboration (http://www.orfeomecollaboration.org/), the Arizona State University plasmid repository (http://dnasu.asu.edu/DNASU/Home.jsp), and commercial sources.

If the approach proposed does not require a purified antigen the application should describe in detail how this would be obviated, and what advantages result.

Applicants may, but are not required to have as one of the main aims the improvement of throughput or the development of technology for generating antigens.

Applicants should consider the choice of targets and antigens production/acquisition in the context of the overall pipeline and the potential scalability in 3 to 5 years.

II. Renewable protein affinity reagents

In addition to traditional monoclonal antibody several other technologies have been used for generating renewable reagents. These include antibody-like molecules, novel protein scaffolds and synthesis of oligomers (e.g., RNA and DNA aptamers, native or synthesized amino acid polypeptides, and various hybrids of these forms). Although some of these technologies may be easily adapted to high throughput production, the integration of these high throughput technologies within a complete pipeline that goes from target selection to the validation of the generated reagents might need to be developed.

Applicants are not limited to proposing approaches that have been mentioned here and should rely on their own creativity and ideas to accomplish the FOA goals.

Applicants should describe and justify the affinity reagent type(s) that they will use, and the advantages that they could offer. Justifications must consider advantages in the context of the entire production pipeline for example, will the underlying reagent technology offer advantages for overall cost? Quality? Utility? Throughput? Higher success rates? Tunable to specific classes of proteins or epitopes? Eases requirements for antigens? Eases expensive characterization and validation?

III. Characterization and validation

The characterization and validation steps constitute one of the major bottlenecks for generating high quality reagents at a high throughput and low cost.

Applicants should clearly describe their characterization and validation plans, in relation to the other proposed steps in reagent generation. If the application proposes substantial improvements in characterization and or validation, the advantages should be clearly described in terms of cost, quality, utility, throughput, range of end-uses (e.g., immunohistochemistry, immunofluorescence, immunoprecipitation), etc.

It is difficult to generally define the characteristics of high quality protein affinity reagents because these depend on the proposed end-use. However, there are some characteristics, including nanomolar-range affinity and high specificity that are often common in high quality reagents. Applicants are therefore strongly encouraged to determine at least the affinity and specificity of each reagent.

Ideally the use of the generated reagents is going to be as broad as possible, but it is expected that some reagents might work better in some applications rather than others. Applicants should validate the generated reagents for at least one specific end-use.

Several ongoing efforts within the scientific community are aimed to standardize criteria for reporting quality, specificity, and the overall characteristics of an affinity capture reagent. The NIH is not endorsing a specific reporting model, but applicants must clearly state their proposed quality criteria in the application. Furthermore, incorporation of criteria that can be widely used and accepted by the scientific community is strongly encouraged.

IV. General production information

Although this FOA does not seek per se the development of scaled production pipelines, it does seek applications that will have the potential to improve such pipelines over time. The applicants should justify the proposed approaches in terms of their likely effect on cost, quality, throughput, utility, or other limiting factor of current approaches. Thus successful applications are likely to have at least features of an early pilot production effort.

Because this is not a production FOA, the evaluation of the applications, and the ongoing evaluation of the funded development efforts, will not be based on absolute cost terms, but rather in terms of potential for cost-improvement over the grant term. Thus applications should present a clear basis for judging whether their development efforts will represent improvements, when evaluated over time. Therefore, all applicants should define the metrics that they will apply. For example, if the major intent of the proposed improvement is quality, the applicant should carefully define and justify quality metrics that will be used. Cost metrics should be similarly defined.

Any proposed automation, robotics, informatics, or other process components should be carefully justified in terms of their eventual advantages for cost, quality, utility, etc.

Production timelines (e.g., for successive steps in a pipeline) may or may not be relevant, depending on the proposal. However, applicants should present development timelines and milestones.

Additional information requested

Applicants should provide timelines and relevant milestones (for example, quality milestones) for all critical aspects of the proposed project.

Applicants should discuss personnel, including center leadership and staffing.

The applicant should include an overall Management Plan for the center and a Resource Distribution Plan for any reagent that is generated. The Resource Distribution Plan and the Management Plan must be included in a separate section of the application and should be no more than six pages total.

The Principal Investigator of a center should plan to devote at least 3 person/months r) and effort to this Cooperative Agreement. The management plan should include the management structure and lines of authority, a description of how decisions will be made, and a discussion about how all components of the funded activity will be integrated. This section should also discuss how any subcontracts will be managed, how those components will be integrated, and how communications between them will be managed.

Distribution of protein affinity reagents:

Although the main goal of this specific FOA is technology development it is expected that some high-quality affinity reagents will be produced. The applicants should include a Resource Distribution Plan for making the produced reagents broadly available and accessible to the scientific community consistent with the goal of establishing a community resource project.

As one of the essential goals of this program, the NIH intends that the reagents be distributed at minimal cost, and without undue intellectual property constraint, so that it can be as widely used as possible, and that creative scientists be enabled to perform experiments and to devise creative downstream applications for the reagents.

In order to ensure that intellectual property rights will not impair or impede the development of the next generation of proteomic platforms and that the reagents can be readily available to the scientific community, applicants are expected to submit a Resource Distribution Plan to address how they will meet the goals of this funding initiative. Applicants should also be familiar with the NIH statements regarding intellectual property of resources developed with Federal funds (http://grants.nih.gov/grants/intell-property_64FR72090.pdf) and other related NIH sharing policies (http://sharing.nih.gov).

In order to realize their different advantages for reagent distribution, NIH has been advised to seek parallel distribution mechanisms, both non-profit (to ensure the availability of the basic resource), and for-profit (which could add further value to commonly used reagents). Applicants may, but are not required to, identify specific distributors. However, they should discuss how their distribution plans are consistent with both mechanisms. Final distribution plans are subject to approval by the NIH.

Potential sites and web portals that the applicants can consider for distributions include, but should not be limited to, the Proteome Binder consortia (http://www.proteomebinders.org/), the University of Iowa hybridoma bank (http://dshb.biology.uiowa.edu/), The Protein Atlas (http://www.proteinatlas.org). 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. Finally, applicants should also consider the possibility of depositing resources into a centralized repository that may be established or otherwise designated in the future for this funding initiative by the NIH to maximize availability and accessibility of these resources and furthering research, consistent with achieving the goals of this project.

Because of the multiple components that are involved in the overall Common Fund Protein Capture Program and risk entailed in this pilot effort, any award issued under this FOA will be a Cooperative Agreement. The NIH will evaluate the funded award(s) in an ongoing way, with an assessment in the second year of funding to determine the level of success.

We recognize that the collection of grants funded under this award may be diverse, emphasizing different approaches and aspects of a future production pipeline, and at somewhat different stages of maturity towards developing a pipeline. This will present a challenge to evaluating them on an ongoing basis. Ongoing evaluation, discussion of common goals, coordination (for example on exchange of immunogens/targets) will be done collaboratively in the context of a research network of Cooperative Agreements, as part of the overall Protein Capture Program. See Terms &Conditions under the Award Administration Information session below.

The NIH encourages all proposed programs to foster the participation of individuals from diverse backgrounds underrepresented in biomedical and behavioral research, including individuals from underrepresented racial and ethnic groups,individuals from disadvantaged backgrounds, and individuals with disabilities.

See Section IV.2 Content and Form of Application Submission Other Submission for specific information about page lengths and application organization.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities. .
Application Types Allowed	New The OER Glossary and the PHS398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The National Institutes of Health anticipate making 3-5 awards and intend to commit $5.0M total funds for this FOA in FY 2011. Although the financial plans of the NIH 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 applications.
Award Budget	Support may be requested for no more than $1,000,000 in direct costs per year.
Award Project Period	Because the nature 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. However, up to three years of funding may be requested.

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.

Higher Education Institutions:

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions

Nonprofits Other Than Institutions of Higher Education

• 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

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American tribal organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)

Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her 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.

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 PHS398 Application Guide.

The lead Principal Investigator must devote at least 3 person/months and effort to this Cooperative Agreement.

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

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

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

It is critical that applicants follow the instructions in the PHS398 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.

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 research
Name, address, and telephone number of the PD(s)/PI(s)
Names of other key personnel
Participating institutions
Number and title of this funding opportunity

The letter of intent should be sent to:

Salvatore Sechi, Ph.D.
Director, Proteomic Program
Director, Diabetes Systems Biology Program
Division of Diabetes, Endocrinology, and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd. Room 797
Bethesda, MD 20892-5460
TEL: 301-594-8814
FAX: 301-480-3503
[email protected]

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and five signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

All page limitations described in the PHS398 Application Guide must be followed with the following exceptions or additional requirements:

• Applications in response to this FOA should include a Research Plan section and a separate section containing a Resource Distribution Plan and Management Plan. The Research Strategy within the Research Plan section should be no more than 30 pages. The Resource Distribution Plan and Management Plan together should be no more than six pages total. Details are provided in the Research Plan section below.

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

I. The Research Strategy (no more than 30 pages) should include a description of relevant past work (preliminary results) and a plan for all aspects of the center described in the section above entitled " Funding Opportunity Description" with the exception of the Resource Distribution Plan and the Management Plan.

II. The application is expected to contain a separate Resource Distribution Plan and a Management Plan (no more than six pages total) consistent with the discussion in the above section "Funding Opportunity Description ".

IIa Resource Distribution Plan:

The NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community.

Applicants are expected to include discussion of:

• Availability of the reagents;
• Availability of information about the reagents (validation, characterization data); this may require a basic implementation of a Web portal. Alternately, if there is a community database suitable for these data, the applicant should identify it and provide data;
• Availability of protocols for validations/characterization;
• Availability of any software tools developed for this award using NIH funds.

Resource distribution plans should include discussion of how any intellectual property will be managed. It is intended that the tools of scientific discovery necessary to rapidly and effectively develop new diagnostics, therapeutics and other medical applications be widely available for research use. Accordingly, awardees will be expected to manage intellectual property in a way that is consistent with achieving the goals of the initiative and in accordance with applicable NIH guidelines and best practices. Resource distribution plans should assure that licensing and sharing practices ensure the availability of data and research resources for future use by the scientific community, and that research collaboration or sponsorship agreements are consistent with the requirements of the Protein Capture program and meeting its programmatic goals.

Restrictive licensing and sharing practices for this program could substantially diminish the value and public benefit provided by this 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 Distribution Plan how their strategies will achieve the desired public benefit and programmatic goals through effective sharing of resources generated under this award.

The adequacy of the Resource Distribution Plan will be considered in the review, with respect to how readily the reagents can be distributed, the consistency of the plans with the ability to broadly distribute through multiple mechanisms, and the plans for providing access to the validation and characterization data that will accompany the reagents.

Specific Resource Distribution plans, once approved, will also become Terms and Conditions of award.

IIb Management Plan

Applicants must describe the organizational infrastructure to support and coordinate project administration within the proposed center.

In this section, applicants must address the following elements:

• A description of the project leadership and key personnel, and their responsibilities. The PI is expected to devote at least 3 person/months time based on a 12-month calendar to this award;
  
  
• A description of how the various components of the center 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 components 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 immunogens/reagents, distribution). Applicant Management Plans should anticipate the need for this level of collaborative activity among the Protein Capture Program components;
  
  
• The management plan should include its own budget request and justification, including funds for coordination among components and travel (including travel for key personnel to Steering Committee meetings; see below).

In addition to the instructions above regarding the Research and Management Plans the application should include the following.

Resource Sharing Plan

Individuals are expected 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 PHS398 Application Guide.

Appendix

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide.

Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the PHS398 Application Guide.

Part I. Overview Information contains information about Key Dates.

Information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

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 received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115

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/priority 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 develop an approach that would substantially improve the throughput or reduce the cost of the pipeline that is presently used for producing high quality and validated protein affinity reagents?

Will the approach proposed be amenable to a proteome scale project in three to five years and can this be achieved at a substantially lower cost and/or higher throughput than today?

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/PIs, 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 clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Is there an adequate management plan appropriate to the scope of the proposed work? Will the various components--including subcontracts--proposed be well-integrated?

Are the milestones proposed for assessing progress adequate?

Are the validation assays proposed adequate for assessing the quality of the reagents that will be produced and overall the technology developed?

Is the distribution plan adequate with respect to broad availability and distribution of the reagents that are produced during the technology development of the project consistent with achieving the goals of the program?

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/priority 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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

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

Not applicable

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/priority score.

Resource Distribution Plan:

Reviewers should consider and comment on the aspects of the Distribution plan including licensing and intellectual property issues that may not be consistent with the goals and the long term intent of the Protein Capture Program that is to create a resource that is broadly available and readily usable by the community.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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).

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 (assignments will be shown in the eRA Commons), in accordance with NIH peer review policy and procedures, using the stated review criteria.

As part of the scientific peer review, all applications will:

• Undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review), will be discussed and assigned an overall impact/priority score.
• Receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center and 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 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, CCR 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.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (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 grant administration policies.

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 P.I. 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 P.I. 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 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;
• Submit data for assessment in any manner specified by the Steering Committee or the External Scientific Consultants (ESC) to the program;
• Submit progress reports as agreed upon by the Steering Committee and the ESC;
• Accept and implement any other common guidelines and procedures developed for the NIH Protein Capture Reagents program and approved by the Steering Committee and the ESC;
• Accept and participate in the cooperative nature of the Protein Capture research network;
• Coordinate and collaborate with other U.S. and international groups engaged in similar large affinity reagent generation projects;
• Inform the 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 through 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 Protein Capture research network and that NIH staff will be given the opportunity to offer input to this process.
• NIH Project Scientists shall participate in the Steering Committee and will collectively have one vote.

The Project Scientist 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;
• Serve as a liaison between the awardees and the ESC, 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 ESC and the Steering Committee; serve as liaison between the Steering Committee and the ESC;
• Serve on subcommittees of the Steering Committee and the ESC, 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 ESC, 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, an 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 ESC meetings.
• An 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.

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) and the P.I. of each awarded cooperative agreement, for all (Affinity Reagent Production, Immunogen Production, and Technology Development) components of the Protein Capture Program. 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 ESC, 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 goals of various technology development projects;
• Develop recommendations for uniform procedures and policies necessary to meet the goals of the NIH Protein Capture 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 ESC;
• 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), 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 a group of External Scientific Consultants (ESC).

• The ESC will be responsible for reviewing and evaluating the progress of the members of the Research Network toward meeting their individual and collective goals. The ESC will provide recommendations to the Protein Capture Common Fund Working Group, the Directors of NHGRI, NIDCD, NIGMS, 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 Technology Development for New Affinity Reagents will receive a critical evaluation in the second year of the award specifically to evaluate the interim success of the program. The ESC is composed of four to six senior scientists with relevant expertise who are not P.I.s of a cooperative agreement involved in the Protein Capture Research Network. The membership of the ESC may be enlarged permanently, or on an ad hoc basis, as needed.
• The ESC 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 ESC will make recommendations regarding progress of the Research Network and present advice about changes, if any, which may be necessary in the Protein Capture program to the Protein Capture Common Fund Working Group, the Directors of NHGRI, NIDCD, NIGMS, and DPCPSI as well as the Directors of all other participating NIH Institutes and Centers.
• The Working Group consists of program staff from each of the NIH Institutes and Centers supporting the Protein Capture Research Network. The purpose of the Protein Capture Working Group will be to disseminate information about the progress of the Protein Capture Research Network to the participating Institutes and Centers and to provide a forum for the Working Group to discuss issues related to the Protein Capture 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 Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

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.

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

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]

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

Joseph D. Mosca, Ph.D., M.B.A.
Center for Scientific Review
National Institutes of Health
Phone: 301-408-9465
E-mail: [email protected]

Craig E. Bagdon
Grant Management Branch (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.