75N95021Q00190

Post Date/ Solicitation Issue Date

May 17, 2021 12:00 pm

Closing Response Date

May 28, 2021 3:00 pm

Proposed Award Date

June 7, 2021 12:00 pm

Project Title

D2/D3 Ex-Vivo Receptor Occupancy in Brains of Sprague Dawley Rats

Contracting Office

National Center for Advancing Translational Sciences (NCATS)

Small Business Size Standard

$16.5 Million

FPDS Classification Code

Q301 - Medical - Laboratory Testing

Estimated Period of Performance

8 weeks after award

Competition Status

Non-Competitive

Single-Sole Source Determination

The Non-Competitive (Single-sole Source (Including brand-name)) Determination is based upon the market research conducted. Specifically, only one source is capable of providing the supplies or services required pursuant to FAR 13.106-1(b)(1)(i), only one source is reasonably available.

Background/Description of Requirement

IMPORTANT: This is a request for quotations. If you are unable to quote, please so indicate in a reply email to the point of contact cited herein.  This request does not commit the Government to pay any costs incurred in the preparation of the submission of a quotation or to contract for supplies or service. Supplies are of domestic origin unless otherwise indicated by quoter. Any representations and/or certifications attached to this Request for Quotation must be completed by the quoter.

Description of Requirement:

The National Center for Advancing Translation Sciences (NCATS) is in need of services to evaluate displacement/competition of a radiolabeled ligand by two D3 selective antagonist and one D2/D3 non-selective antagonist in an ex-vivo rat brain slice model to mimic the in-vivo receptor occupancy.

The biogenic amine dopamine is an essential neurotransmitter in the brain and periphery. The cerebral dopaminergic system is implicated in a variety of physiological and pathophysiological processes. It comprises the regulation of motion, emotion and cognition. An imbalance in the dopaminergic neurotransmission and dopamine receptors underlies manifold neurological and psychiatric disorders. All drugs of abuse either directly or indirectly increase dopamine levels in the mesolimbic regions of the brain. The dopamine receptor subtype D3 is localized in the key neurocircuits that underlie motivation and cognition, and in contrast to D2R do not appear to play a major role in movement. Hence, D3R has been proposed as a promising target for development of psychostimulant addiction and relapse pharmacotherapy. Also, seminal reports have shown increased D3R subtype in the basal ganglia in post-mortem brains of cocaine and methamphetamine overdose victims using PET studies thus further validating this approach. 

TRND at NCATS in collaboration with the investigators at NIDA has emabarked on a journey to find novel D3R antagonists while displaying significant selectivity from the highly homologous D2 receptors. Working on the bitopic ligands identified by earlier inevstigations, the team has identified several lead chemotypes that display around a 500 fold selectivity over D2R in the binding assays. These lead molecules occupy an orthosteric binding site (OBS) at D3R and also connect to a secondary binding pocket (SBP), via a 4 carbon linker, responsible for achieving selectivity amongst the dopamine receptor subtypes. The lead molecules from different chemotype series, identified by the team are being considered for development. 

Towards a successful translation of these lead molecules and to study pharmacodynamics of these compounds, the team has proposed ex-vivo and in-vivo receptor occupancy studies in Sprague Dawley rats. In this study, we will determine the differential binding of D3 selective antagonists and D2/D3 non-selective antagonsts in D2 and D3 receptor rich regions. We plan to use ex-vivo rat brain slice model. We plan to exploit the differential localization of D2 and D3 receptors in the rat striatum, Substantia Nigra, Ventral Tegmental Area, Olfactory tubercle, and Cerebellum lobes 9 and 10. While Substantia Nigra, VTA, OT and Cerebellar lobes 9 and 10 have been shown to be rich in D3R receptor expression, the receptor binding in the striatum can serve as the D2 rich control. Dose dependent competition/displacement of the D3 antagonist bound in the sectioned tissue by the appropriate radioligand will be taken as a measure of the receptor occupancy.

General Requirements:

Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work below:

Specific Requirements:

1) 3 NIH compounds will be evaluated for D2/D3 ex-vivo receptor occupancy in brains of Sprague Dawley rats.

2) Displacement/competition experiments to be performed with 125-I-Sulpiride.

3) Three concentrations per compound to be used.

4) 3 rats per dose to be used in the experiment.

5) Compounds to be administered via PO/IP/SC dosing and the brains to be removed after a predetermined time point. Brains to be frozen and stored until the imaging day.

6) 10-slides to be prepared from each block.

7) Slide Assay for D2/D3 binding to be performed with 125-I-Sulpiride.

8) Autoradiography and analysis to be performed and results to be reported as percentage occupancy at the administered doses.

Special Contract Requirements:

1. Contractor Requirements. The services under this contract involves live vertebrate animals. Respondents must have:

1. An active OLAW Animal Welfare Assurance

2. Institutional Animal Care and Use Committee (IACUC) project approval for this work. The date of IACUC approval must not be more than 36 months prior to the anticipated date of award.

2. Animal Welfare. All research involving live, vertebrate animals shall be conducted in accordance with the Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS Policy). The PHS Policy can be accessed at: http://grants1.nih.gov/grants/olaw/references/phspol.htm. In addition, the research involving live vertebrate animals shall be conducted in accordance with the description set forth in the Vertebrate Animal Section (VAS) of the contractor’s quotation.

3. Vertebrate Animals Section (VAS). It is intended that live vertebrate animals will be used during performance of this contract. The Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals (authority derived from the Health Research Extension Act of 1985) specifies that certain information is required from offerors in contract proposals submitted to the NIH that will use live vertebrate animals.

The VAS should be no more than two (2) pages and must address the following criteria:

1. Description of Procedures. Provide a concise description of the proposed procedures to be used that involve vertebrate animals in the work outlined in the Statement of Work. Identify the species, strains, ages, sex and total number of animals by species to be used in the proposed work.

2. Justifications. Provide justification that the species are appropriate for the proposed research. Explain why the research goals cannot be accomplished using an alternative model (e.g., computational, human, invertebrate, in vitro).

3. Minimization of Pain and Distress. Describe the interventions including analgesia, anesthesia, sedation, palliative care and humane endpoints to minimize discomfort, distress, pain and injury.

4. Euthanasia. State whether the method of euthanasia is consistent with the recommendations of the American Veterinary Medical Association (AVMA) Guidelines for the Euthanasia of Animals. If not, describe the method and provide a scientific justification.

For more discussion regarding the VAS, see NIH Guide Notice NOT-OD-16-006 at:

http://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-006.html.

The VAS Worksheet is provided as an attachment to this solicitation to assist in the preparation of the VAS.

Government Responsibilities:

Providing compounds for the study

Delivery or Deliverables:

The contractor shall complete the work within 8 weeks after award.

Reporting Requirements:

The contractor shall provide the result of study to NCATS through a written report.

Data Rights:

The right to all data belongs to NCATS.

Publications and Publicity:

The result of study will not be published at the moment.

Confidentiality of Information:

Any information provided to the contractor by NCATS or collected by the contractor on behalf of NCATS shall be used only for the purpose of carrying out the provisions of this contract and shall not be disclosed or made known in any manner to any persons except as may be necessary in the performance of the contract.

Quoter Terms and Conditions (To be completed by the Offeror):

1. Period of Performance OR Delivery Date After Receipt of Order:
2. Shipping Point (F.O.B. OR Destination):
3. Payment Discount Terms:
4. NIH BPA Number
5. DUNS No:
6. Name of Company:
7. Street Address, City, State, Zip code:
8. Name of Person Authorized to Provide Quote:
9. Telephone Number and Email Address of Person Authorized to Provide Quote:

Contract Type:

A Fixed-Price type of Purchase Order award not exceeding the Simplified Acquisition Threshold is anticipated for any contract resulting from this requirement. The anticipated award date is June 7, 2021.

ADDITIONAL TERMS AND CONDITIONS, PROVISIONS, AND REPRESENTATIONS

The FAR Clauses are incorporated by reference and are provided in full text at https://www.acquisition.gov/

1. The provisions of FAR Clause 52.212-1 Instructions to Offerors—Commercial Items (Jun 2020) is applicable to this solicitation.
2. The provisions of FAR Clause 52.212.2 Evaluation—Commercial Items (Oct 2014) is applicable to this solicitation. The Government will evaluate quotations or offers in accordance with FAR 13.106-2 and award a purchase order from this solicitation to the responsible offeror whose quote conforming to the solicitation will be most advantageous to the Government, price and other factors considered. The following factors shall be used to evaluate quotes:
   1. Technical capability of the service offered to meet the Government requirement;
   2. Price; and
   3. Past performance [see FAR 13.106-2(b)(3)].
3. The provisions of FAR Clause 52.212-3, Offeror Representations and Certifications—Commercial Items (Feb 2021), is applicable to this solicitation.
4. The provisions of FAR Clause 52.212-4, Contract Terms and Conditions—Commercial Items (OCT 2018) with Addenda: Stop Work Order, FAR Clause 52.242-15 (August 1989) is applicable to this solicitation.
5. The provisions of FAR clause at 52.212-5, Contract Terms and Conditions Required to Implement Statutes or Executive Orders—Commercial Items (Jan 2021) is applicable to this solicitation:

52.219-28 Post Award Small Business Program Rerepresentation (Nov 2020) (15 U.S.C. 632(a)(2)). May require contractor completion.

52.222-3 Convict Labor (Jun 2003)

52.222-19 Child Labor-Cooperation With Authorities and Remedies (Jan 2020)

52.222-21 Prohibition of Segregated Facilities (Apr 2015)

52.222-26 Equal Opportunity (Sep 2016)

52.222-36 Equal Opportunity for Workers With Disabilities (Jun 2020)

52.222-50 Combating Trafficking in Persons (Oct 2020)

52.223-18 Encouraging Contractor Policies to Ban Text Messaging While Driving (Jun 2020)

52.232-33 Payment by Electronic Funds Transfer-- System for Award Management (Oct 2018)

6. The provisions of HHSAR 352.270-5a Notice to Offerors of Requirement for Compliance with the Public Health Service Policy on Humane Care and Use of Laboratory Animals (December 18, 2015) and HHSAR 352.270-5b, Care of Live Vertebrate Animals (December 18, 2015) are applicable to this solicitation.

In addition, the following FAR provisions are applicable to this solicitation and incorporated by reference:

52.204-7 System for Award Management (Oct 2018),

52.204-13 System for Award Management Maintenance (Oct 2018),

52.204-16 Commercial and Government Entity Code Reporting (Aug 2020),

52.204-18 Commercial and Government Entity Code Maintenance (Aug 2020).

The following provisions and clauses apply to this acquisition and are incorporated as an attachment. Responses must include the Dun & Bradstreet Number (DUNS), the OLAW Animal Welfare Assurance number, a Vertebrate Animal Section (VAS), and a quotation.

1. FAR 52.204-24, Representation Regarding Certain Telecommunications and Video Surveillance Services or Equipment (Oct 2020)
2. FAR 52.204-25, Prohibition on Contracting for Certain Telecommunications and Video Surveillance Services or Equipment (Aug 2020)
3. FAR 52.204-26, Covered Telecommunications Equipment or Services-Representation (Oct 2020)
4. NIH Invoice and Payment Provisions

DELIVERY DATE:  8 weeks after award. Inspection and acceptance will be performed at NCATS located at 9800 Medical Center Drive, Rockville, MD 20852.  A firm fixed price type order is anticipated to be awarded as a result of this RFQ.

SUMMARY STATEMENT:

Responses to this notice must include sufficient information to establish the interested parties’ bona-fide capabilities of providing the product or service.  The response shall include: the unit price, list price, shipping and handling costs, delivery days after contract award, delivery terms, prompt payment discount terms, F.O.B. Point (Destination or Origin), product or catalog number(s); product description; and any other information or factors that may be considered in the award decision.  Such factors may include: past performance; special features required for effective program performance; trade-in considerations; probable life of the item selected as compared with that of a comparable item; warranty considerations; maintenance availability; and environmental and energy efficiency considerations.