Inactive

PURSUANT TO FAR Subpart 5.2-Synopses of Proposed Contract Actions, THIS IS A PRE-SOLICITATION NOTICE OF A PROPOSED CONTRACT ACTION. THIS IS A PRE-SOLICITATION NON-COMPETITIVE NOTICE OF INTENT TO AWARD... PURSUANT TO FAR Subpart 5.2-Synopses of Proposed Contract Actions, THIS IS A PRE-SOLICITATION NOTICE OF A PROPOSED CONTRACT ACTION. THIS IS A PRE-SOLICITATION NON-COMPETITIVE NOTICE OF INTENT TO AWARD A CONTRACT OR PURCHASE ORDER WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION (INCLUDING BRAND-NAME). The National Institute on Drug Abuse (NIDA), Office of Acquisition, Contracts Management Branch Red, NINDS Section on behalf of the National Institute of Neurological Disorders and Stroke (NINDS) intends to negotiate and award a purchase order to New York University to provide Platform Vector Gene Therapy (PaVe-GT) Congenital Myasthenic Syndrome (CMS) Dok7TGCC/TGCC Mouse Models. North American Industry Classification Systems (NAICS) Code The intended procurement is classified under NAICS code 541990 - All Other Professional, Scientific and Technical Services, with a Size Standard of $15 million. Regulatory Authority The resultant contract will include all applicable provisions and clauses of the Federal acquisition Requlation (FAR) in effect through the Federal Acquisition Circular (FAC) 2020-08, dated August 13, 2020. Statutory Authority This acquisition is conducted as non-competitive under the authority of 41 U.S.C. 253(c) under provisions of the statutory authority of FAR Subpart 6.302-1 -- Only One Responsible Source and No Other Supplies or Services Will Satisfy Agency Requirements. This acquisition is conducted under the authority of the Federal Acquisition Regulation (FAR) Part 13-Simplified Acquisition Procedures, Subpart 13.106-1 (b) (1), Soliciting from a single source. Background and Objectives: The Bönnemann lab within the National Institute of Neurological Disorders and Stroke (NINDS) Neuromuscular and Neurogenetics Disorders of Childhood Section will be leading a platform vector gene therapy study which seeks to increase the efficiency of clinical therapeutics development and trial start up by taking advantage of the platform capacity of AAV vectors to treat congential myasthenic syndromes (CMS). The Burden laboratory at New York University has generated a mouse model of one form of CMS (Dok7 deficiency) that has been partially characterized and the Bönnemann lab plans to utilize this as one model evaluate the efficacy of the platform AAV gene therapy approach. Congenital myasthenic syndromes (CMS) are a group of inherited disorders in which there is impairment of the highly specialized neuromuscular junction (NMJ) caused by pathogenic genetic variants in many of the molecular components that make up the NMJ. A total of 32 types of CMS have been described to date, with the number still growing as new ultrarare entities continue to be discovered. Defects in all areas of the NMJ — including the presynaptic cell (nerve), synaptic cleft and postsynaptic cell (muscle) — have been identified as molecular causes for CMS. Although dominantly acting forms exist, most types are inherited in an autosomal recessive pattern (such as Dok7 deficiency) with early onset and loss of function as the mechanism, making them amendable to gene replacement approaches. The NMJ as a specialized structure has been investigated throughout the history of neuroscience and is of paradigmatic value as a prototypical synapse. Thus, its molecular composition and regulation of NMJ specific gene expression, morphology and physiology are well understood and researched, and the clinical consequences of its dysfunction measurable by a number of outcome measures. Dok7 deficiency is caused as a result of mutations in the DOK7 gene. The protein functions as a regulator of AChR assembly in two ways: both as an inside-out activator of the receptor kinase MuSK and as an adapter that participates in signaling downstream from MuSK, and thereby the development and maintenance of the NMJ. The mouse model of the most common disease-causing genetic variants (a 4 bp TGCC duplication) has been generated by NYU. The homozygous mutant line in an inbred background dies at birth due to a dramatic defect in synapse formation and therefore respiratory failure. By crossing the inbred mutant line with other mouse strains, they have preliminarily found that the homozygous outbred mutant line is viable, at least for a short time (~12 days) after birth. The Burden lab continues to study and characterize these mutant mice, which will serve as a basis for the planned gene therapy experiments. Although more severe than the human condition, these mice are crucial to PaVe-GT study to determine the efficacy of a platform-based gene therapy approach. Project Requirements: The Burden laboratory at New York University has generated a mouse model of Dok7 deficiency, encompassing one of the most common human mutations within the gene. This model is used to determine the efficacy of the platform AAV gene therapy approach. The Dok7TGCC/TGCC model has a very specific breeding scheme and these animals are not readily available by any commercial source. The average survival for a limited number of Dok7TGCC/TGCC mice in a mixed C57/CBA strain has been preliminarily determined to be about 12 days. It would take years to recreate this model. The Burden lab has begun characterization of the model, but additional animal model maintenance and care is necessary. In the performance of this contract, NIH requires the breeding/generation of at least 20 Dok7 homozygous mutant mice in the C57/CBA mixed background and model maintenance by the NYU animal facility (cleaning cages, monitoring food/water supply, etc.). Mice shall be maintained at NYU’s animal facility. Anticipated Period of Performance: The anticipated period of performance is one year from the date of award. The estimated time frame of award is on/about September 28, 2020. Closing Statement: This synopsis is not a request for competitive proposals. However, interested parties may identify their interest and capability to respond to this notice. Responses to this solicitation must include clear and convincing evidence of the offeror's capability of fulfilling the requirement as it relates to the technical evaluation criteria. The price proposal must include the labor categories, an estimate of the number of hours required for each labor category, fully loaded fixed hourly rate or each labor category, breakdown and rationale for other direct costs or materials, and the total amount. The technical proposal must include CV information for proposed Key Personnel that meet the minimum requirements specified above. In addition, the Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size must be included in the response. All offerors must have an active registration in the System for Award Management (SAM) www.sam.gov." A determination by the Government not to compete this proposed contract based upon responses to this notice is solely within the discretion of the Government. The information received will normally be considered solely for the purposes of determining whether to proceed on a non-competitive basis or to conduct a competitive procurement. All responses must be received by Wednesday, September 16th at 1:00 PM Eastern Time and must reference number 75N95020R00060. Responses must be submitted electronically to Karen Mahon at karen.mahon@nih.gov. Fax responses will not be accepted. "All responsible sources may submit a capability statement, proposal, or quotation, which shall be considered by the agency."