acquisition of services to research the Biophysics of increasing fetal hemoglobin as therapy for sickle cell disease

INTRODUCTION THIS IS A PRE-SOLICITATION NON-COMPETITIVE (NOTICE OF INTENT) SYNOPSIS TO AWARD A CONTRACT OR PURCHASE ORDER WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION (INCLUDING BRAND-NAME). The National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Office of Acquisitions (OA) on behalf of the on behalf of the National Institute of Digestive, Diabetes & Kidney Diseases intends to award a purchase order without providing for full and open competition (Including brand-name) to DREXEL UNIV for the acquisition of services to research the Biophysics of increasing fetal hemoglobin as therapy for sickle cell disease. NORTH AMERICAN INDUSTRY CLASSIFICATION SYSTEM (NAICS) CODE The intended procurement is classified under NAICS code 541380 with a Size Standard of $16.5. REGULATORY AUTHORITY The resultant contract will include all applicable provisions and clauses in effect through Federal Acquisition Circular 2021-06 Effective July 12, 2021. This acquisition is conducted under the procedures as prescribed in FAR subpart 13'Simplified Acquisition Procedures at an amount not exceeding the simplified acquisition threshold ($250,000). STATUTORY AUTHORITY This acquisition is conducted under the authority of 41 U.S.C. 253(c) under provisions of the statutory authority of FAR Subpart 6.302- FAR 6.302-1'Only one responsible source and no other supplies or services will satisfy agency requirements 41 U.S.C. 253(c)(1). PERIOD OF PERFORMANCE 1 year from date of award to allow for extended collaboration Place of Performance National Institutes of Health National Institute of Digestive, Diabetes & Kidney Diseases 5 Memorial Drive Bethesda MD 20892 ? DESCRIPTION OF REQUIREMENT The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) conducts and supports research on many of the most serious diseases affecting public health. The Institute supports much of the clinical research on the diseases of internal medicine and related subspecialty fields, as well as many basic science disciplines. The Institute's Division of Intramural Research encompasses the broad spectrum of metabolic diseases such as diabetes, obesity, inborn errors of metabolism, endocrine disorders, mineral metabolism, digestive and liver diseases, nutrition, urology and renal disease, and hematology. Basic research studies include biochemistry, biophysics, nutrition, pathology, histochemistry, bioorganic chemistry, physical chemistry, chemical and molecular biology, and pharmacology. NIDDK extramural research is organized into 4 divisions: Diabetes, Endocrinology, and Metabolic Diseases; Digestive Diseases and Nutrition; Kidney, Urologic, and Hematologic Diseases; and Extramural Activities. The Institute supports basic and clinical research through investigator-initiated grants, program project and center grants, and career development and training awards. The Institute also supports research and development projects and large-scale clinical trials through contracts. _________________________ BACKGROUND There is a gigantic gap in our basic knowledge of the inhibition of sickling by fetal hemoglobin. It has long been known that sickle cell patients who have a hereditary persistence of fetal hemoglobin (which is pancellular) have a dramatically milder course of the disease. Treatment with hydroxyurea works by increasing fetal hemoglobin. However, hydroxyurea does not induce fetal hemoglobin in every cell, so it is not curative because a large fraction of cells contain only sickle hemoglobin. For this reason, the major effort by hematologists and pharma is to find ways to induce fetal hemoglobin in all cells. One of the successful gene therapy methods is to infect the patients stem cells with a lentivirus carrying a gene for normal hemoglobin, mutated in a way that it incorporates the amino acid substitution thought to be most pertinent to the inhibition of polymerization by fetal hemoglobin. Another approach is to use Crispr-Cas 9 technology to edit the gene for BC111A so that it does not downregulate fetal hemoglobin production. Despite the importance of understanding the effects of fetal hemoglobin, the data presently available is not sufficient to the task, being internally consistent. As a result, we have been unable to develop a quantitative interpretation of the results of our anti-sickling assay on sickle blood from gene addition patients or with pancellular distribution of fetal hemoglobin. The effects of fetal hemoglobin on sickle hemoglobin polymerization have been studied by examining gelled samples of known mixtures that have been centrifuged to generate a supernatant of unpolymerized material, and a pellet containing all the polymers and some fraction of trapped unpolymerized hemoglobin. The supernatant is easiest to measure, whereas the accurate assessment of the pellet requires a precise knowledge of the fraction of space taken by the polymers. That fraction we and others have found to be highly variable. Even when only supernatant solubility is measured, the likelihood of hybridized molecules to enter the polymer is found to vary considerably among laboratories. Worse yet, probability of finding fetal hemoglobin in the polymer when studying the supernatant disagrees with the probability found from the sedimented fraction. ? PURPOSE AND OBJECTIVES The National Institutes of Health (NIH)s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has a requirement for services to research the Biophysics of increasing fetal hemoglobin as therapy for sickle cell disease. SALIENT / REQUIRED FEATURES AND SPECIFICATIONS Independently, and not as an agent of the Government, the contractor shall perform all of the detailed Task Areas listed below: Determine the fraction of nickel substituted fetal hemoglobin in the solution and polymer phases and the solubility as a function of the total fraction of fetal hemoglobin in a gelled sample of a sickle/fetal hemoglobin mixture. In the Ferrone method, a drop of hemoglobin solution abuts a drop of buffer creating a gradient of concentration. The hemoglobin diffuses into the solution, but the polymers can only grow into regions where their solubility is exceeded. By comparing total concentration with the dichroism signature of the polymers, the solubility is determined. As the polymers grow they align providing the aligned region needed for dichroism measurements. Prepare sickle and fetal hemoglobin for linear dichroism and simultaneous solubility measurements using an E. coli expression system. The iron in the heme should be substituted by Nickel (++) to make the fetal distinguished from the altered optical absorption spectrum. Measurements are to be carried out at 0% oxygen. When fully deoxygenated, nickel-substituted hemoglobin is known to have identical propertied to hemoglobin in the fully T-state conformation. Demonstrate that nickel-substituted fetal hemoglobin is appropriate for the desired result by measuring the solubility of nickel-substituted sickle hemoglobin and determining the three-dimensional structure of nickel-substituted fetal hemoglobin by X-ray crystallography. Specifically, the NIDDK requires the following tasks: Task Area 1 - 1. Fraction of nickel substituted fetal hemoglobin in the solution and polymer phases and the solubility as a function of the total fraction of fetal hemoglobin in a gelled sample of a sickle/fetal hemoglobin mixture at 0% oxygen 2. Solubility of nickel-substituted fetal hemoglobin at 0% oxygen and 37 degrees centigrade 3. X-ray determined three-dimensional structure of nickel-substituted fetal hemoglobin, if possible. Task Area 2 - 1. Preparation of nickel substituted sickle and feta hemoglobin 2. Measurement of linear dichroism on tiny droplets of concentrated hemoglobin solutions with a microspectrophotometer. CONTRACTING WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION (INCLUDING BRAND-NAME) DETERMINATION The determination by the Government to award a contract without providing for full and open competition is based upon the market research conducted as prescribed in FAR Part 10'Market Research. Only one source is available: Per FAR 13.106-1(b)(1) the Contracting Officer has determined DREXEL UNIV to be the only reasonable available source to provide services to research the Biophysics of increasing fetal hemoglobin as therapy for sickle cell disease. This acquisition was pursued on a sole source basis centered on the following: The scientific information provided by the experiments of Prof. Ferrone are absolutely essential for making progress in understanding the basic science of fetal hemoglobin induction by gene therapy as a cure for sickle cell disease. Prof. F. A. Ferrone is the only scientist known with the instrumentation, expertise, and experience to obtain the desired results within the requested 6 month period. 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 notice shall contain sufficient information to establish the interested parties bona-fide capabilities for fulfilling the requirement and include: descriptive literature, delivery timeframe, warranties and/or other information that demonstrates that the offer meets all the foregoing requirements, the prompt payment discount terms, the F.O.B. Point (Destination or Origin), the Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size. 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 to this notice shall be submitted electronically by 9:00 am Eastern Standard Time, on Monday, September 20, 2021 to the Contracting Officer, Amber Harris, at contact@example.gov. Assessment of Capability Lowest Price Technically Acceptable