RFQ 75N91024Q00094 - SOW.pdf

STATEMENT OF WORK

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National Institutes of Health / National Cancer Institute / Office of Acquisitions

1 TITLE

Synthesis Services for Custom Biomolecules for Detection of Mutation-Reactive T cells in Patients With Metastatic Cancers

2 BACKGROUND

The Surgery Branch (SB) at the Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), is a combined laboratory and clinical research unit devoted to the development of innovative, highly personalized immunotherapies. One major therapeutic approach at this Branch is T cell therapy, which utilizes the patient’s own anti-tumor T cell lymphocytes. SB continuously develops this therapy to treat late-stage cancer patients who do not respond to standard treatments. The therapeutic process begins with the resection of tumors from patients enrolled in SB clinical trials and subsequent extraction of those T cells that reside within the tumor (tumor infiltrating lymphocytes, TILs). These TILs are expanded in cell culture while also being investigated for their individual somatic mutations through whole-exome and whole-transcriptome sequencing at SB. Afterwards, the reactivity of the patients’ TILs is being tested in vitro against biomolecules (customized gene constructs and peptides) with these somatic mutations. Mutation-reactive TILs which can recognize the mutations on the biomolecules are then selected, isolated, grown to large numbers, and used to treat the patients.

2.1 OBJECTIVE

The objective of this purchase order is to obtain high-quality, error-free, custom biomolecules (biotechnological products, i.e., gene constructs and peptides), in large quantities and in an expeditious manner. These biomolecules are needed to identify mutation-reactive immune cells for personalized T cell therapy of late-stage cancer patients enrolled in NCI/SB clinical trials.

2.2 SCOPE

The scope of work to be performed includes the expeditious production and delivery of high-quality, error-free custom biomolecules (gene constructs and peptides) in large quantities and involves synthesis/cloning, purification, and quality control (QC) analyses.

3 CONTRACT REQUIREMENTS

Note: Inquiries for the production of gene constructs and peptides will be submitted by SB clinical research staff (in here, “Requester”). The delivery address for the products will be provided by the NCI Technical Point of Contact (TPOC, see Section 9.0 below).

All data shared, or otherwise generated throughout the duration of this Purchase Order shall remain or become the sole property of the U.S. Government.

The Contractor shall notify the TPOC immediately via e-mail or phone call on any unusual problems, such as failure of analytical and quality control procedures, breakdown of freezers, instrumentation and equipment, and major changes in personnel that would produce delays or that would adversely influence the quality of the laboratory performance.

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National Institutes of Health / National Cancer Institute / Office of Acquisitions

Independently and not as an agent of the Government, the Contractor shall provide all labor, materials, and equipment required to perform the following tasks:

3.1 TASK 1: PRODUCTION OF CUSTOMIZED GENE CONSTRUCTS

The Requesters will provide lists of the required gene constructs and/or peptides to the Contractor in MS Word or MS Excel format via email. All sequences will be de-identified.

Prior production, the Contractor shall optimize all insert sequences received for increased in vitro and in vivo activity in retroviral mammalian expression vectors and provide the optimized sequences to the Requester for review and approval. All gene constructs must be prepared on GenScript’s mammalian expression vector construct platform pipeline, from cloning to sequencing, to ensure uniform expression during SB’s screening assay and full comparability with previous constructs. The Contractor shall Sanger sequence each construct to verify the sequence correctness of the resultant construct.

3.1.1 Tandem Minigene (TMG) Fragments

The Contractor shall provide tandem minigene (TMG) fragments to the Government. These TMG fragmens shall encode normal endogenous gene sequences and those with tumor mutations embedded in tandem.

3.1.2 TCRα/β Inserts

The Contractor shall then provide retroviral mammalian expression vectors containing antigen specific T-cell receptor (TCR) inserts for the TCR-alpha/beta chains (TCRα/β) to the Requester.

Upon submission of clinical-grade TCR order by the SB Requester, the Contractor generate constructs under prior FDA approval in compliance with respective Surgery Branch/NCI clinical trials at the NIH.

3.1.3 Task 1 Deliverable

The Contractor shall send the constructs on dry ice to the Requester. The constructs shall be delivered within 20 business days of inquiry. The sequencing files for each construct shall be sent in printed format together with the construct as well as via email in pdf format to the Requester. The sequencing files shall include electropherograms showing the DNA sequence with the cloning sites and the full length inserts.

3.2 TASK 2: CUSTOM PEPTIDE SYNTHESIS

The Requester will provide a list of the required peptide with the required concentration to the Contractor in MS Word or MS Excel format via email. Requesters may require reconstituted or lyophilized peptides which may be between 8 to 25 amino acids in length and may have different levels of purity (>75% - immuno grade; >85% - biochemistry grade; or >95% - high purity grade) and varying concentrations (4mg to 100mg). All peptides must be synthezised on

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National Institutes of Health / National Cancer Institute / Office of Acquisitions

GenScript’s peptide pipeline, from production to analysis, to ensure uniform results and full comparability with SB’s previous peptide screening assays.

3.2.1 Custom Peptides

The Contractor shall produce peptides that encode normal endogenous protein sequences and those with tumor mutations embedded. The Contractor shall use protocols that are optimized to reduce the level of peptide contamination. The Contractor shall perform mass spectrometry (MS) analysis on all peptides to verify their amino acid composition.

3.2.2 Task 2 Deliverable

The Contractor shall send reconstituted peptides on dry ice to the Requester; lyophilized peptides may be shipped at room temperature. The MS analysis result for each peptide shall be sent in printed format together with the peptides as well as via email in pdf format to the Requester.

Peptides shall be delivered within 20 business days of inquiry. The NCI Technical Point of Contact (TPOC) may authorize longer lead times, depending on sequence complexity and peptide length.

4 PERIOD OF PERFORMANCE

The Period of Performance shall be twelve months, with two (2) twelve-month Option Period as follows:

Base Period: September 24, 2024 – September 23, 2025 Option Period 1: September 24, 2025 – September 23, 2026 Option Period 2: September 24, 2026 – September 23, 2027

5 PLACE OF PERFORMANCE

All work shall be performed at the Contractor’s facilities.

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National Institutes of Health / National Cancer Institute / Office of Acquisitions

6 DELIVERY SCHEDULE

The below table outlines the deliverables which the Contractor is responsible for fulfilling throughout the requirement. All submittals will be submitted electronically to the Technical Point of Contact (TPOC) and individuals identified below for inspection and acceptance.

Section Description Due Date

1.2.3 Custom constructs (tandem minigene fragments and/or TCRa/b inserts); solved/reconstituted; to be shipped on dry ice; to include sequencing file.

Within 20 business days of inquiry.

1.3.1 Custom peptides; to be shipped in dry ice

(lyophilized products may be shipped at room temperature); to include QC analysis file.

Within 20 business days of inquiry.

6.1 TECHNICAL POINT OF CONTACT

The Technical Point of Contact (TPOC) will serve as the Governments primary point of contact for coordination of all required efforts covered under the scope of the purchase order.

Additionally, all services shall be delivered to the TPOC for final inspection and acceptance upon completion. All deliverables will have been deemed accepted fifteen (15) calendar days after date of delivery, except as otherwise specified in this purchase order if written approval or disapproval has not been given within such period.

The following individual shall be the Technical Point of Contact (TPOC) for this purchase order:

Name: TBD [provided upon award] Email:

Phone:

The TPOC role is limited to the authorities specified herein. The TPOC does not have the authority to issue directions that:

1) Constitutes a change of assignment or additional work outside the statement of work;

2) Constitutes a change as defined in clause 52.212-4 (c) "Changes";

3) In any manner causes an increase or decrease in the purchase order price, or the time required for performance.

4) Changes any of the terms, conditions, or requirements of the purchase order;

5) Interferes with the Contractor's right to perform under the terms and conditions of the purchase order; or

6) Directs, supervises, or otherwise controls the actions of the Contractor's employees.

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National Institutes of Health / National Cancer Institute / Office of Acquisitions

If at any time the Contractor feels that such direction listed above has been given, they must contact the Contracting Officer immediately.

6.2 INSPECTION AND ACCEPTANCE

Pursuant to FAR clause 52.212-4, all work described in the SOW to be delivered under this purchase order is subject to final inspection and acceptance by an authorized representative of the Government. The authorized representative of the Government is the NCI Technical Point of Contact (TPOC) who is responsible for inspection and acceptance of all services, materials, or supplies to be provided by the Contractor.

Regardless of format, all digital content or communications materials produced as a deliverable under this purchase order, shall conform to applicable Section 508 Standards to allow Federal employees and members of the public with disabilities to have access to and use of information and data that is comparable to the access to and use of information and data by Federal employees or by members of the public who are not individuals with disabilities. Remediation of any materials that do not comply with the applicable Section 508 requirements as set forth below, shall be the responsibility of the Contractor.

HHS guidance regarding accessibility of documents can be found at:

https://www.hhs.gov/web/section-508/making-files-accessible/create-accessiblepdfs/index.html.

Federal Government-wide guidance regarding accessibility of documents can be found at https://www.section508.gov/, including the documents describing the preferred method of authoring and testing documents produced in Microsoft Word 2013 or later, Microsoft Excel, and files formatted as PDF.

All written drafts and final deliverable products shall be submitted as an electronic copy in draft format for review, comment, and approval by the TPOC. Final copies of approved drafts shall be delivered to the TPOC within 3 business days after receipt of the Government’s comments. If requested, final deliverable products shall be submitted in an electronic format. Other quantities and formats may be submitted after prior approval from the TPOC.

All deliverables shall be sent electronically as; Microsoft Excel 2013, Microsoft Excel, or Adobe Portable Document Format (PFD), unless otherwise approved by the TPOC.

7 PAYMENT

Payment shall be made upon completion and submission of all deliverables. Payment authorization requires submission and approval of invoices to the Technical Point of Contact and

NIH OFM.