Small Molecule Modulators of iPSC-Derived Hepatocyte and Neuronal Calcium Signaling

NON-COMPETITIVE
COMBINED SYNOPSIS / SOLICITATION
Title: Small Molecule Modulators of iPSC-Derived Hepatocyte and Neuronal Calcium Signaling

(i) This is a combined synopsis/solicitation for commercial items prepared in accordance with the format in Subpart 12.6 as supplemented with additional information included in this notice. This announcement constitutes the only solicitation; proposals are being requested and a written solicitation will not be issued.

(ii) The solicitation number is 75N95019Q00282 and the solicitation is issued as an request for quotation (RFQ).

This acquisition is for a commercial item or service and is conducted under the authority of the Federal Acquisition Regulation (FAR) Part 13-Simplified Acquisition Procedures and FAR Part 12-Acquisition of Commercial Items, and is not expected to exceed the simplified acquisition threshold.

THIS IS A NON-COMPETITIVE (NOTICE OF INTENT) COMBINED SYNOPSIS SOLICITATION TO AWARD A CONTRACT OR PURCHASE ORDER WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION (INCLUDING BRAND-NAME).

The National Institute on Drug Abuse (NIDA), NIDA Office of Acquisitions - NCATS Section, on behalf of the National Center for Advancing Translational Sciences (NCATS), intends to negotiate and award a purchase order without providing for full and open competition (including brand-name) to Applied Stemcell, Inc., 521 Cottonwood Drive, Suite 111, Milpitas, CA 95035 for two iPSC lines.

This acquisition is conducted as non-competitive for a commercial item or service and is conducted under the authority of the FAR Subpart 13.5-Simplified Procedures for Certain Commercial Items and 13.501 Special documentation requirements and the authority of 41 U.S.C. 1901 and the FAR Subpart 13.106-1(b) Soliciting from a single source.

Pursuant to FAR Subpart 13.501 (a)(1)(iv) the rationale for the brand name justification is that Applied Stemcell, Inc. has generated the specific iPSC line in house and their use of IPSC protocols shard by NCATS SCTL. Applied Stemcell also utilizes footprint-free, feeder-free culturing and maintenance protocols that are used in the SCTL lab.

(iii) The solicitation document and incorporated provisions and clauses are those in effect through Federal Acquisition Circular 2019-02, dated May 6, 2019.

(iv) The associated NAICS code is 541714 and the small business size standard is 1000 employees. No set-aside restriction is applicable.

(v) NCATS SCTL is in need of CRISPR/cell cloning to generate two custom iPSC reporter cell lines for small molecule screening projects. These cell lines include: (1) a custom dual gene knock-in ALB-2A-secNLuc and AFP-2A-eGFP iPSC reporter cell line encoding the aforementioned reporter sequences at their endogenous genomic loci; (2) a custom gene knock-in GCaMP iPSC reporter cell line encoding a GCaMP calcium indicator into a genomic "Safe Harbor" locus. The parental iPSC cell line will be provided by the contractor. These cell lines are critical for identifying chemical modulators of (1) iPSC-derived hepatocyte differentiation and maturation and (2) calcium signaling in iPSC-differentiated neurons. It is a priority for NCATS SCTL to discover, validate, and disseminate small molecule reagents to replace expensive recombinant proteins, xenogenic material and undefined media components in cell differentiation protocols.

(vi) The stages of this contract work will be delivered within the following timeline milestones:

Project 1: Dual gene knock-in ALB-2A-secNLuc and AFP-2A-eGFP iPSC reporter cell line
1. ALB-2A-secNLuc gene knock-in
a. iPSC cell line purchase and sequencing of targeted regions: 2-3 weeks
b. CRISPR vector construction: 2-3 weeks
c. Reagent validation and donor plasmid construction: 4-6 weeks
d. Transfection of targeting vectors: 2-4 weeks
e. Cell confirmation and expansion: 3-4 weeks
2. AFP-2A-eGFP gene knock-in
a. iPSC cell line purchase and sequencing of targeted regions: 2-3 weeks
b. CRISPR vector construction: 2-3 weeks
c. Reagent validation and donor plasmid construction: 4-6 weeks
d. Transfection of targeting vectors: 2-4 weeks
e. Cell confirmation and expansion: 3-4 weeks
3. Project 1 total: 26-40 weeks
Project 2: Gene knock-in GCaMP iPSC reporter cell line
a. iPSC cell line purchase and sequencing of targeted regions: 2-3 weeks
b. CRISPR vector construction: 2-3 weeks
c. Reagent validation and donor plasmid construction: 4-6 weeks
d. Transfection of targeting vectors: 2-4 weeks
e. Cell confirmation and expansion: 3-4 weeks
4. Project 2 total: 13-20 weeks

Specific Requirements
This contract should provide CRISPR-mediated genome editing for the following projects in iPSC cell lines: (1) a custom dual gene knock-in ALB-2A-secNLuc and AFP-2A-eGFP iPSC reporter cell line encoding the aforementioned reporter sequences at their endogenous genomic loci; (2) a custom gene knock-in GCaMP iPSC reporter cell line encoding a GCaMP calcium indicator into a genomic "Safe Harbor" locus. The vendor should provide two homozygous clones for each project/cell line containing the indicated reporter knock-ins, 2 vials of each clone with 1 x 106 cells/vial. The vendor should also provide milestone updates/reports, as well as a final report with detailed descriptions of each procedure, including targeting vector design, construction and validation, transfection condition, genotyping strategy, and results. Ownership of these cell lines should be exclusive to NCATS SCTL.

Project 1:
Technology Utilized: CRISPR
Gene Name of Knock-In Target #1: ALB (human albumin)
Gene ID of Knock-In Target #1: ENSG00000163631
Gene Name of Knock-In Target #2: AFP (human alpha fetoprotein)
Gene ID of Knock-In Target #2: ENSG00000081051
Intended Modifications for Target #1: Directly after the endogenous ALB gene, knock in a 2A "slipstreaming" sequence followed by secreted NanoLuc, with the intention of having endogenous ALB and secreted NanoLuc expression controlled by the same ALB endogenous promoter.
Intended Modifications for Target #2: Directly after the endogenous AFP gene, knock in a 2A "slipstreaming" sequence followed by eGFP (or brighter monomeric derivative), with the intention of having endogenous ALB and eGFP expression controlled by the same AFP endogenous promoter.

Project 2:
Technology Utilized: CRISPR
Gene Name of Knock-In: Next-generation GCaMP genetically encoded calcium indicator; specific GCaMP indicator TBD
Gene ID of Knock-In: N/A; gene is synthetic
Intended Modification: Knock in a next-generation GCaMP genetically encoded calcium indicator into a genomic "Safe Harbor" locus

(vii) DELIVERY OR DELIVERABLES
Two CRISPR genome-edited iPSC reporter cell lines: (1) a custom dual gene knock-in ALB-2A-secNLuc and AFP-2A-eGFP iPSC reporter cell line encoding the aforementioned reporter sequences at their endogenous genomic loci; (2) a custom gene knock-in GCaMP iPSC reporter cell line encoding a GCaMP calcium indicator into a genomic "Safe Harbor" locus. The details of each project/cell line are indicated under Specific Requirements. Deliverables for each project/cell line include: two homozygous clones containing the indicated reporter knock-ins; 2 vials of each clone with 1 x 106 cells/vial; milestone updates/reports; a final report with detailed descriptions of each procedure, including targeting vector design, construction and validation, transfection condition, genotyping strategy, and results. Ownership of these cell lines should be exclusive to NCATS SCTL.

REPORTING REQUIREMENTS
All electronic reports should be delivered to Michael Iannotti (mike.iannotti@nih.gov) and Ilyas Singeç (ilyas.singec@nih.gov) at NCATS via email following timely completion of above research milestones as indicated in deliverables.

(viii) The provision at FAR clause 52.212-1, Instructions to Offerors - Commercial Items, applies to this acquisition.

(ix) Offers will be evaluated for technical criteria, price, and past performance. Technical criteria consist of matching the line items identified above. Technical and past performance, when combined, are significantly more important than price.

OR The provision at FAR clause 52.212-2, Evaluation - Commercial Items, applies to this acquisition.

(a) The Government will award a contract resulting from this solicitation to the responsible offeror whose offer conforming to the solicitation will be most advantageous to the Government, price and other factors considered. The following factors shall be used to evaluate offers:

(i) technical evaluation criteria and/or technical capability of the item offered to meet the Government requirement
(ii) price
(iii) past performance [see FAR 13.106-2(b)(3)]

Technical and past performance, when combined, are significantly more important than cost or price.

(b) Options. The Government will evaluate offers for award purposes by adding the total price for all options to the total price for the basic requirement. The Government may determine that an offer is unacceptable if the option prices are significantly unbalanced. Evaluation of options shall not obligate the Government to exercise the option(s).

(c) A written notice of award or acceptance of an offer, mailed or otherwise furnished to the successful offeror within the time for acceptance specified in the offer, shall result in a binding contract without further action by either party. Before the offer's specified expiration time, the Government may accept an offer (or part of an offer), whether or not there are negotiations after its receipt, unless a written notice of withdrawal is received before award.

(x) Offerors are to include a completed copy of the provision at FAR clause 52.212-3, Offeror Representations and Certifications-Commercial Items, with offers.

(xi) The FAR clause at 52.212-4, Contract Terms and Conditions - Commercial Items, applies to this acquisition. The following addendum applies:

SOLICITATION PROVISIONS INCORPORATED BY REFERENCE (FEB 1998)

This solicitation incorporates one or more solicitation provisions by reference, with the same force and effect as if they were given in full text. Upon request, the Contracting Officer will make their full text available. The offeror is cautioned that the listed provisions may include blocks that must be completed by the offeror and submitted with its quotation or offer. In lieu of submitting the full text of those provisions, the offeror may identify the provision by paragraph identifier and provide the appropriate information with its quotation or offer. Also, the full text of a clause may be accessed electronically at these addresses:

For FAR clauses: https://www.acquisition.gov/browsefar

For HHSAR clauses: https://www.hhs.gov/grants/contracts/contract-policies-regulations/hhsar/index.html

(end of clause)

The following FAR provisions or clauses are 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 Entity Code Reporting (Jul 2016)
52.204-18, Commercial and Entity Code Maintenance (Jul 2016)

52.212-4(g), Invoice, is supplemented by the NIH Invoice and Payment Instructions (2/2014).

(xii) FAR clause at 52.212-5, Contract Terms and Conditions Required to Implement Statutes or Executive Orders-Commercial Items, applies to this acquisition.

52.204-10 Reporting Executive Compensation and First-Tier Subcontract Awards (Oct 2018) (Pub. L. 109-282) (31 U.S.C. 6101 note).
52.219-28 Post Award Small Business Program Representation (Jul 2013) (15 U.S.C. 632(a)(2))
52.222-3 Convict Labor (June 2003)
52.222-19 Child Labor-Cooperation With Authorities and Remedies (Jan 2018)
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 (Jul 2014)
52.222-50 Combating Trafficking in Persons (Mar 2015)
52.223-18 Encouraging Contractor Policies to Ban Text Messaging While Driving (Aug 2011)
52.225-13 Restrictions on Certain Foreign Purchases (June 2008) (E.O.'s, proclamations, and statutes administered by the Office of Foreign Assets Control of the Department of the Treasury)
52.232-33 Payment by Electronic Funds Transfer-- System for Award Management (Jul. 2013)

(xiii) There are no additional contract requirement(s) or terms and conditions applicable to this acquisition.

(xiv) The Defense Priorities and Allocations System (DPAS) are not applicable to this requirement.

(xv) 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 sufficient information to establish the interested parties' bona-fide capabilities of providing the product or service.

The price quote shall include: 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.

Respondents that believe that they are manufacturers or authorized resellers of the brand-name product specified in this announcement must provide, as part of their response: (a) product, catalog, model, and/or part number(s); (b) product description; (c) all relevant information and documentation that the item(s) offered meets the salient physical, functional, or performance characteristics as specified in the purchase description; quantity; estimated price or cost; shipping, handling, and/or installation charges; and delivery date after receipt of order.

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 whether to compete this proposed contract based upon responses to this notice is solely within the discretion of the Government. Information received will be considered to determine whether to proceed on a non-competitive basis as indicated above, or to conduct a competitive procurement.

All responses must be received by August 15th, 2019 at 5:00pm, Eastern Standard Time and reference solicitation number 75N95019Q00282. Responses must be submitted electronically to Jessica Adams at jessica.adams@nih.gov.

Fax responses will not be accepted.

(xvi) The name and email address of the individual to contact for information regarding the solicitation: Jessica Adams at jessica.adams@nih.gov.

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