New Technologies for Liver Disease STTR (R41/R42)

New Technologies for Liver Disease STTR (R41/R42) is sponsored by National Institutes of Health (NIH) - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Cancer Institute (NCI). This opportunity supports mission-aligned projects and measurable outcomes.

Expired PA-09-094: New Technologies for Liver Disease STTR (R41/R42) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Participating Organizations Institutes of Health (NIH) ( http://www.

nih. gov ) Components of Participating Organizations Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), ( http://www2. niddk.

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

nih. gov/ ) Institute of Environmental Health Sciences (NIEHS), ( http://www. niehs.

nih. gov/ ) Institute on Drug Abuse (NIDA), http://www. nida.

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

nih. gov/ Cancer Institute (NCI), http://www. cancer.

gov/ Technologies for Liver Disease STTR (R41/R42) This Funding Opportunity Announcement (FOA) is a reissue of PA-06-396 . Update: The following update relating to this announcement has been issued: August 16, 2010 - IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond.

As of January 25, all corrections must be complete by the due date for an application to be considered on-time. See NOT-OD-10-123 . September 29, 2010 (NOT-OD-11-007) - NIH to Require Use of Updated Electronic Application Forms in 2011.

Adobe B1 forms are required for due dates on or after May 8, 2011. This FOA has been updated to reflect the new requirements from NIH’s Enhancing Peer Review Initiative. The new requirements are effective for submissions intended for due dates January 25, 2010 and beyond.

If submitting an application intended for a due date of January 25, 2010 and beyond, follow the guidance below and be sure to use the Adobe-Forms-B version of the application forms and instructions. If applying for a due date before January 25, 2010, follow the guidance in the archived version of this FOA and be sure to use the Adobe-Forms-A version of the application forms and instructions.

Announcement (PA) Number: PA-09-094 submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants. gov ( http://www. grants.

gov ) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) SBIR/STTR MAY NOT BE SUBMITTED IN PAPER FORMAT. FOA must be read in conjunction with the application guidelines included with this announcement in Grants. gov/Apply for Grants (hereafter called Grants.

gov/Apply) . A registration process in Grants. gov and eRA Commons is necessary before submission.

Applicants are highly encouraged to start the process at least four (4) weeks prior to the grant submission date. See Section IV . Catalog of Federal Domestic Assistance 93.

279, 93. 394, 93. 395, 93.

393, 5, 2009 (Earliest date an application may be submitted to Grants. gov) NOTE: On time submission requires that applications be successfully submitted to Grants. gov no later than 5:00 p.

m. local time (of the applicant institution/organization). Due Date(s): Standard dates apply, please see http://grants1.

nih. gov/grants/funding/submissionschedule. htm AIDS Application Due Date(s): Standard dates apply, please see http://grants1.

nih. gov/grants/funding/submissionschedule. htm#AIDS .

Peer Review Date(s): Standard dates apply, please see http://grants1. nih. gov/grants/funding/submissionschedule.

htm#reviewandaward Council Review Date(s): Standard dates apply, please see http://grants1. nih. gov/grants/funding/submissionschedule.

htm#reviewandaward Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1. nih. gov/grants/funding/submissionschedule.

htm#reviewandaward Additional Information To Be Available Date (URL Activation Date): Not Applicable Purpose.

The purpose of this Funding Opportunity Announcement (FOA) is to solicit Small Business Innovation Research (STTR) grant applications from small business concerns (SBCs) that propose to develop resources, research tools, instrumentations, biomarkers, devices, drugs or new and innovative approaches to diagnosis, monitoring, management, treatment and prevention of liver diseases.

Areas of interest include development of reliable and practical means of diagnosis of liver diseases; biomarkers for disease activity and stage; noninvasive tests for inflammation, fibrosis and fat in the liver; and drugs, complementary and alternative modalities, biologics or molecular reagents for the therapy or prevention of liver diseases.

The goal of this announcement is to enlist members of the small business research community in advancing means of diagnosis, treatment and prevention of liver disease and facilitate the goals outlined in the trans-NIH Action Plan for Liver Disease FOA will utilize the STTR (R41/R42) grant mechanisms for Phase I, Phase II, and Fast-Track applications and runs in parallel with a FOA of identical scientific scope, PA-09-095 , that encourages applications under the Small Business Innovation Research (SBIR) (R43/R44) grant mechanisms .

Funds Available and Anticipated Number issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications. The total amount awarded and the number of awards will depend upon the quality, duration, and costs of the applications received. Project Period.

Phase I awards normally may not exceed $100,000 total for a period normally not to exceed 1 year. Phase II awards normally may not exceed $750,000 total for a period normally not to exceed 2 years. These award levels and project periods are statutory guidelines, not ceilings.

Therefore, applicants are encouraged to propose a budget and project duration period that is reasonable and appropriate for completion of the research project. Phase II Competing Renewal budgets must be submitted in accordance with participating IC-specific budget limitations described in the current SBIR/STTR Program Descriptions and Research Topics of the NIH, CDC and FDA . Eligible Institutions/Organizations.

Only United States SBCs may submit STTR applications and receive STTR awards. A SBC is one that, on the date of award for both Phase I and Phase II funding agreements, meets ALL of the criteria as described in Section III . Eligible Project Directors/Principal Investigators (PDs/PIs).

Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their 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.

On an STTR application, the PD/PI may be employed with the SBC or the single, partnering non-profit research institution as long as he/she has a formal appointment with or commitment to the applicant SBC, which is characterized by an official relationship between the small business concern and that individual. PDs/PIs. More than one PD/PI, (i.e., multiple PDs/PIs), may be designated on the application.

Applications: Applicant SBCs may submit more than one application, provided each application is scientifically distinct. Resubmissions. Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement).

See new NIH policy on resubmission (amended) applications ( NOT-OD-09-003 , NOT-OD-09-016 ). Renewals. Only STTR Phase II awardees are eligible to submit a STTR Phase II Competing Renewal application, which should represent a continuation of support for research and development of the previous work funded by the original STTR Phase II grant.

STTR Phase II Competing Renewal applications will be accepted by only those ICs described in the current SBIR/STTR Program Descriptions and Research Topics of the NIH, CDC and FDA. Application Materials. See Section IV.

1 for application materials. General Information. For general information on SF424 (R&R) Application and Electronic Submission, see SF424 (R&R) Application and Electronic Submission Information: http://grants.

nih. gov/grants/funding/424/index. htm General information on Electronic Submission of Grant Applications: http://era.

nih. gov/ElectronicReceipt/ Telecommunications for the hearing impaired is available at: TTY 301-451- 5936 . II Full Text of Announcement I.

Funding Opportunity Description III. Eligibility Information 2. Cost Sharing or Matching Other - Special Eligibility Criteria IV.

Application and Submission Information Request Application Information Content and Form of Application Submission Submission Dates and Times and Anticipated Start Dates Application Electronically to the NIH 4. Intergovernmental Review 6. Other Submission Requirements and V.

Application Review Information 2. Review and Selection Process 3. Anticipated Announcement and Award Dates VI.

Award Administration Information 2. Administrative and National Policy Scientific/Research Contact(s) 2. Peer Review Contact(s) Financial/Grants Management Contact(s) VIII.

Other Information - Required Federal Citations II - Full Text of Announcement I. Funding Opportunity Description Liver and biliary diseases affect Americans of all ages and all walks of life. Collectively liver and biliary diseases rank in the top 10 causes of mortality in the United States.

Chronic liver diseases affect between 5 and 10 percent of Americans and account for 1 to 2 percent of deaths in the United States. Gallbladder disease affects an estimated 20 million Americans and causes considerable morbidity and occasional mortality. Liver cancer currently ranks 8 th as a cause of cancer deaths and has been increasing markedly as a cause of cancer in the United States over the last decade.

Yearly economic costs for chronic liver disease and cirrhosis are estimated to be $1. 6 billion, for liver cancer $1. 3 billion and for gallbladder disease $6 Liver and biliary diseases can be caused by infectious agents, inherited defects, metabolic disturbances, alcohol, toxins and environmental toxicants.

The most common causes of liver diseases are chronic hepatitis C, alcohol liver disease, nonalcoholic fatty liver disease, chronic hepatitis B, autoimmune liver diseases and drug-induced liver diseases. Many of these conditions can be prevented or treated, but if not, they can lead to progressive liver injury, liver fibrosis and ultimately cirrhosis, portal hypertension, end-stage liver disease and, in some instances, liver cancer.

Currently, the only therapy for end-stage liver disease is liver transplantation. More than 5000 liver transplants are done in the United States each year (including more than 500 in children). At least 17,000 persons are on a waiting list for liver transplantation and as many as 1500 die yearly while waiting.

The needs and challenges in liver disease research are many. Digestive Diseases Interagency Coordinating Committee of the National Institutes of Health (NIH) released a trans-NIH Action Plan for Liver Disease Research. The text of this Action Plan is available on the NIH website at: http://liverplan.

niddk. nih. gov .

development of the Action Plan was to identify areas of greatest scientific opportunity to serve as a stimulus to progress and help direct NIH research resources toward practical but important goals in the prevention and control of liver and biliary diseases. The Action Plan outlined a total of 214 research goals categorized into 16 areas of liver disease research.

Many of these research goals are appropriate for Small Business Innovative Research Grants and represent excellent opportunities for translational research that could be conducted by a small business with expertise and interest in biomedical research.

This announcement summarizes these opportunities and defines the interest of the sponsoring Institutes and Centers in funding such Summary of Priority Areas The objective of this FOA is to encourage and enable scientists at small businesses to develop and evaluate new technologies, drugs, devices, and approaches to diagnosis, management, and prevention of liver disease.

Development of new technologies as well as application of existing technologies may be proposed. Studies may include use of animal models or human participants or both. If appropriate, plans for manufacturing and clinical evaluation of developed technologies, drugs, devices and innovative approaches should be included in the application.

However, clinical trials beyond Phase I studies will not be considered appropriate to this announcement. development and validation under this FOA include, but are not limited to, the following which are categorized into four major areas and which incorporate research goals from the Action Plan for Liver Disease Research: Diagnostic Assays.

A specific diagnosis can be made in most liver diseases but may require specialized testing or an invasive procedure. In some instances, diagnostic assays are not generally available and may lead to delay or mistakes in diagnosis. More accurate, commercially available tests are needed for several liver diseases and conditions.

screening assay for Wilson disease that might be applied to newborns and/or adolescents and adults with this disease. means of assessing copper or iron content of the liver. appropriate molecular tests for diagnosis of the forms of progressive familial intrahepatic cholestasis (caused by mutations in FIC1, BSEP or and reproducible diagnostic test for acetaminophen toxicity and alcoholic Techniques .

Biomarkers and more sensitive imaging techniques may allow for non-invasive means of assessing the liver and obviate the need for liver biopsy in diagnosis, staging and grading biomarkers and imaging methods for liver fibrosis that accurately reflect the stage of liver disease and can detect mild to moderate degrees of fibrosis before the onset of cirrhosis.

Biomarkers could be individual tests on serum or urine or a combination of tests that might be applied in an algorithm to assess degree of fibrosis. signatures of major forms of hepatotoxicity for diagnostic use during genomic, proteomic and/or metabolomic technologies. imaging techniques for visualization of the biliary tree for architecture, motility, inflammation and cancer.

biomarkers or imaging techniques for inflammation and injury in the liver that accurately reflect the activity of liver disease and thus might be used to assess the need for therapy or the adequacy of ongoing biomarkers or imaging methods for the degree of fat in the liver that provide a reliable quantification of steatosis.

Biomarkers that can reliably separate simple fat (steatosis) from fat accompanied by liver injury (steatohepatitis) as well as distinguish fat accumulation due to alcoholic and nonalcoholic causes are particularly needed.

biomarkers and imaging methods for assessment of liver regeneration that can be applied to living donor liver transplantation to both donor and recipients or to patients with severe acute liver injury such as to provide a reliable assessment of the likelihood of recovery and help in the decision to attempt liver transplantation.

biomarkers for assessment of immune tolerance or adequacy of immune suppression that could be applied to patients after liver transplantation to guide the dose of immunosuppressive therapies and whether therapy can be safely withdrawal.

Biomarkers for adequacy of immune suppression and tolerance are also needed in management of autoimmune liver disease to guide dose of prednisone or other immune suppressive agents and the possibility of drug withdrawal. biomarkers and imaging techniques for early and reliable detection of hepatocellular carcinoma and cholangiocarcinoma .

Patients with cirrhosis or advanced chronic liver disease are at high risk for hepatocellular carcinoma and simple, but reliable, serum or urine screening tests are needed to identify liver cancer at an early stage while better imaging techniques are needed to reliably separate benign, regenerating nodules from cancer.

Similarly, in patients with chronic biliary disease such as sclerosing cholangitis or intrahepatic gallstones are at high risk for development of cholangiocarcinoma, and serum or urine assays for early detection and imaging tests for reliable identification of this tumor are biomarkers for hepatotoxicity due to medications, herbals, environmental chemicals or nutritional supplements.

Currently, serum aminotransferase levels are used to monitor or assess liver toxicity from medications, but some elevations in these liver-associated serum enzymes occur commonly but are self-limited and do not signal significant liver injury. More reliable markers for significant liver injury that might be combined with serum aminotransferase levels are needed.

biomarkers of exposure to specific environmental chemicals that cause liver toxicity that could be used to predict future onset of hepatotoxicity and to be able to distinguish hepatotoxicity from transient adaptive of individual liver metabolizing enzyme SNP profiles in animals and humans that could be used to assess sensitivity to specific drugs and environmental Pharmacotherapy.

Safer and more effective disease-specific as well as non-specific therapies for liver disease are needed.

Understanding of pathways of liver cell injury, repair, and regeneration are likely to lead to new and innovative approaches to treat liver biologics, complementary and alternative modalities or molecular therapies that inhibit liver cell injury nonspecifically through inhibition of biologics, complementary and alternative modalities or molecular therapies that safely promote regeneration , particularly in the situation of living donor liver transplantation biologics, complementary and alternative modalities or molecular therapies that inhibit fibrosis or promote fibrolysis in chronic liver biologics, complementary and alternative modalities or molecular therapies that provide liver cell cytoprotection and might be appropriate for therapy of hepatotoxicity or chronic hepatitis.

biologics, complementary and alternative modalities or molecular therapies that ameliorate itching in chronic liver disease through interruption of the pathways that lead to pruritus. biologics, complementary and alternative modalities or molecular therapies that reduce portal pressure in different stages of the development of cirrhosis and portal hypertension.

biologics, complementary and alternative modalities or molecular therapies for the effective noncytotoxic therapy for hepatocellular carcinoma . biologics, complementary and alternative modalities or molecular therapies that inhibit fat accumulation in the liver. biologics, complementary and alternative modalities or molecular therapies that inhibit recruitment of inflammatory cells in the liver.

in current therapy for acute crisis of the hepatic porphyrias . of small molecule therapeutics for viral hepatitis B, C, and D that are also effective in the post liver transplant period. supplements for the therapy of alcohol related liver diseases through the NIAAA such as silymarin, s-adenosylmethionine, betaine, Gene Therapy .

Gene therapy holds enormous promise for therapy and potential cure of many inherited as well as acquired liver diseases. Advances in gene therapy could well replace liver transplantation for several liver diseases. and safer vectors for gene therapy of liver diseases.

of improving homing of vectors to the liver. techniques of gene delivery and cell transplantation. Liver Assist Devices.

Currently there are no means of providing support to liver function in the face of liver failure or after major hepatectomy.

Liver assist devices could be life-saving as a bridge to liver transplantation (while awaiting an appropriate donor liver) in a patient with primary graft non-function or acute liver failure or while awaiting the normal processes of regeneration to occur in acute liver failure or delayed regeneration after partial hepatectomy.

techniques for culture of primary hepatocytes in large volumes with artificial hepatic assist device using either primary human hepatocytes, primary mammalian hepatocytes, transformed human hepatocytes or continuous VIII, Other Information - Required Federal Citations , for policies related to this announcement. 1.

Mechanism(s) of Support This funding opportunity will use the Small Business Technology Transfer (STTR [R41/R42] grant mechanisms. Applications may be submitted for support as Phase I, Phase II, or Fast-Track grants as described in the SF424 (R&R) SBIR/STTR Application Guide. Small business concerns that have received a Phase I STTR grant may apply for Phase II funding of that project.

The Phase II must be a logical extension of the Phase I research but not necessarily as a Phase I project supported in response to this funding opportunity. STTR Phase II applications will compete with all STTR applications and will be reviewed according to the customary peer review procedures.

Applications for STTR Phase II Competing Renewal grants will be accepted by only those ICs described in the current SBIR/STTR Program Descriptions and Research Topics of the NIH, CDC and FDA . Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project. This funding opportunity uses Just-in-Time information concepts.

The modular budget format is not accepted for STTR grant applications. Applicants must complete and submit budget requests using the SF424 Research and Related (R&R) Budget component found in the application package attached to this FOA in Grants. gov/Apply .

All other participating organizations, including the single, partnering research institution, must complete and submit requests using the Research & Related Subaward Budget Attachment(s) Form contained in the SF424 (R&R) application package. issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

The total amount awarded and the number of awards will depend upon the quality, duration, and costs of the applications received. The SF424 (R&R) SBIR/STTR Application Guide indicates the statutory guidelines of funding support and project duration periods for Phase I and Phase II STTR awards. Phase I awards normally may not exceed $100,000 total for a period normally not to exceed 1 year.

Phase II awards normally may not exceed $750,000 total for a period normally not to exceed 2 years. These award levels and project periods are statutory guidelines, not ceilings. Therefore, applicants are encouraged to propose a budget and project duration period that is reasonable and appropriate for completion of the research project.

STTR Phase II Competing Renewal budgets must be submitted in accordance with participating IC-specific budget limitations described in the current SBIR/STTR Program Descriptions and Research Topics of the NIH, CDC and FDA. NIH grants policies as described in the NIH Grants Policy apply to the applications submitted and awards made in response to this FOA. Section III.

Eligibility Information United States small business concerns (SBCs) are eligible to submit STTR small business concern is one that, at the time of award of STTR Phase I and Phase II, meets all of the following criteria: organized for profit, with a place of business located in the United States, which operates primarily within the United States or which makes a significant contribution to the United States economy through payment of taxes or use of American products, materials or labor; in the legal form of an individual proprietorship, partnership, limited liability company, corporation, joint venture, association, trust or cooperative, except that where the form is a joint venture, there can be no more than 49 percent participation by foreign business entities in the joint at least 51 percent owned and controlled by one or more individuals who are citizens of, or permanent resident aliens in, the United States, except in the case of a joint venture, where each entity to the venture must be 51 percent owned and controlled by one or more individuals who are citizens of, or permanent resident aliens in, the United States; and including its affiliates, not more than 500 employees.

SBCs must also meet the other regulatory requirements found in 13 C. F. R.

Part 121. Business concerns, other than investment companies licensed, or state development companies qualifying under the Small Business Investment Act of 1958, 15 U.S.C. 661, et seq.

, are affiliates of one another when either directly or indirectly, (a) one concern controls or has the power to control the other; or (b) a third-party/parties controls or has the power to control both. can be exercised through common ownership, common management, and contractual relationships. The term "affiliates" is defined in greater detail in 13 C.

F. R. 121.

3-2(a). The term "number of employees" is defined in 13 Business concerns include, but are not limited to, any individual (sole proprietorship), partnership, corporation, joint venture, association, or cooperative. Further information may be obtained by contacting the Small Business Administration Office of Size Standards ( http://sba.

gov/size ). of the circumstances that would lead to a finding that an organization is controlling or has the power to control another organization involves sharing common office space and/or employees and/or other facilities (e.g., laboratory space).

Access to special facilities or equipment in another organization is permitted (as in cases where the awardee organization has entered into a subcontractual agreement with another organization for a specific, limited portion of the research project).

However, research space occupied by an STTR awardee organization must be space that is available to and under the control of the STTR awardee for the conduct of its portion of the proposed project . Title 13 CFR 121. 3 also states that control or the power to control exists when key employees of one concern organize a new concern ...

and serve as its officers, directors, principal stockholders, and/or key employees, and one concern is furnishing or will furnish the other concern with subcontracts, financial or technical assistance, and/or other facilities, whether for a fee or otherwise.

Where there is indication of sharing of common employees, a determination will be made on a case-by-case basis of whether such sharing constitutes control or the power to For purposes of the STTR program, personnel obtained through a Professional Employer Organization or other similar personnel leasing company may be considered employees of the awardee. This is consistent with SBAs size regulations, 13 CFR 121.

106 Small Business Size arising under stock options, convertible securities, and agreements to merge: In determining size, SBA considers stock options, convertible securities, and agreements to merge (including agreements in principle) to have a present effect on the power to control a concern. SBA treats such options, convertible securities, and agreements as though the rights granted have been exercised. See http://edocket.

access. gpo. gov/cfr_2005/janqtr/pdf/13cfr121.

103. pdf . STTR grant applications will be examined with the above eligibility considerations in mind.

If it appears that an applicant organization does not meet the eligibility requirements, NIH will request a size determination by the SBA. If eligibility is unclear, NIH will not make an STTR award until the SBA provides a determination.

Note: An applicant organization that has been determined previously by SBA to be other than small for a size standard of not more than 500 employees or for purposes of the SBIR/STTR program, must be recertified by the SBA prior to any 1. B.

Eligible Individuals Any individual with the skills, knowledge, and resources necessary to carry out the proposed research 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.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a team science approach that clearly does not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants. nih.

gov/grants/multi_pi . All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era. nih.

gov/ElectronicReceipt/preparing. htm for instructions). decision of whether to apply for a single PD/PI or multiple PD/PI grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project.

Applications for multiple PD/PI grants will require additional information, as outlined in the instructions below. Each PD/PI is responsible and accountable to the grantee organization, or as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.

nih. gov/grants/multi_pi . For a STTR application, the Project Director/Principal Investigators (PD/PIs) may be employed with the SBC or the single, partnering non-profit research institution as long as s/he has a formal appointment with or commitment to the applicant SBC, which is characterized by an official relationship between the SBC and that individual.

For projects with multiple PD/PIs, the Contact PD/PI may be from either the SBC or the single, partnering research institution. As defined in 42 CFR 52, the PD/PI is the single individual designated by the grantee in the grant application who is responsible for the scientific and technical direction of the project.

When the proposed PD/PI clearly does not have sufficient qualifications to assume this role, the application is not likely to receive a favorable evaluation. PD/PI must commit a minimum of 10% effort to the project and the PD/PI must have a formal appointment with or commitment to the applicant small business concern, which is characterized by an official relationship between the small business concern and that individual.

Such a relationship does not necessarily involve a salary or other form of remuneration. In all cases, however, the PD/PIs official relationship with the grantee must entail sufficient opportunity for the PD/PI to carry out his or her responsibilities for the overall scientific and technical direction of the project.

Documentation (e.g., consultant, consortium and contractual arrangements) describing the official relationship of the PD/PI with the applicant small business concern should NOT be submitted with the grant application, but a copy must be furnished upon the request of the NIH awarding component .

are examples of situations describing the official relationship of the PD/PI with the applicant small business organization: full-time, university appointment may also have appointments with other organizations (with or without salary) and still appropriately consider his or her commitment to the university to be full-time, consistent with the personnel policies and procedures of the university applied on a routine basis.

The PD/PIs commitment to the university and other organizations (including the applicant small business concern) cannot exceed 100% of his or her total full-time, 12-month appointment with a small business concern would be considered to have a commitment to the applicant organization of 100% of his or her total professional effort.

part-time appointment with a small business concern and has concurrent commitments or appointments with organizations in addition to the small business concern would deem each commitment as a portion of 100% of his or her total program does not require cost sharing as defined in the current NIH Grants Policy Other-Special Eligibility Criteria Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement).

Beginning with applications intended for the January 25, 2009 official submission due date (and any other due dates for FY2010 funding and beyond), all original new applications (i.e., never submitted) and competing renewal applications will be permitted only a single amendment (A1). See http://grants. nih.

gov/grants/guide/notice-files/NOT-OD-09-003. html and NOT-OD-09-016 . Original new and competing renewal applications that were submitted for due dates prior to January 25, 2009 will be permitted two resubmissions (amendments A1 and A2).

For these grandfathered applications, NIH expects that any A2 will be submitted no later than January 7, 2011, and NIH will not accept A2 applications after that date. In STTR Phase I and Phase II, at least 40% of the work must be performed by the small business concern and at least 30% of the work must be performed by the single, partnering research institution.

The basis for determining the percentage of work to be performed by each of the cooperative parties will be the total of direct and F&A/indirect costs attributable to each party, unless otherwise described and justified in Item 13, Consortium/Contractual Arrangements, of the PHS398 Research Plan component of the SF424 (R&R) application forms.

Applicants may submit more than one application, provided that each application is scientifically distinct. The NIH will accept as many "different" applications as the applicant organization chooses. However, the NIH will not accept similar grant applications with essentially the same research focus from the same applicant organization.

This includes derivative or multiple applications that propose to develop a single product, process, or service that, with non-substantive modifications, can be applied to a variety of purposes. Applicants may not simultaneously submit identical/essentially identical applications under both this STTR funding opportunity and any other HHS FOA, including the current SBIR identical or essentially identical