SOURCES SOUGHT
Q -- Acquisition, characterization, and optimization of constrained peptides targeting Glypican-3
- Notice Date
- 7/29/2020 4:31:12 PM
- Notice Type
- Sources Sought
- NAICS
- 541380
— Testing Laboratories
- Contracting Office
- NIH National Cancer Institute Rockville MD 20850 USA
- ZIP Code
- 20850
- Solicitation Number
- 75N91020Q00151
- Response Due
- 8/5/2020 8:00:00 AM
- Archive Date
- 08/20/2020
- Point of Contact
- Megan Kisamore, Phone: 2402765261
- E-Mail Address
-
megan.kisamore@nih.gov
(megan.kisamore@nih.gov)
- Description
- 1.0�� �DESCRIPTION This Small Business Sources Sought Notice (SBSS) is for information and planning purposes only and shall not be construed as a solicitation or as an obligation on the part of the National Cancer Institute (NCI). The purpose of this Small Business Sources Sought Notice is to identify qualified small business concerns, including 8(a), HUBZone or Service-Disabled Veteran-owned business concerns, that are interested in and capable of performing the work described herein. The NCI does not intend to award a contract based on responses received nor otherwise pay for the preparation of any information submitted. Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible. An organization that is not considered a small business under the applicable NAICS code should not submit a response to this notice. This requirement is assigned North American Industry Classification System (NAICS) code 541380 with a size standard of $16.5 million is being considered. NCI may issue a request for quotation (RFQ) as a result of this Small Business Sources Sought Notice. THERE IS NO SOLICITATION AVAILABLE AT THIS TIME. However, should such a requirement materialize, no basis for claims against NCI shall arise as a result of a response to this Small Business Sources Sought Notice or the NCI�s use of such information as either part of our evaluation process or in developing specifications for any subsequent requirement. 2.0�� �BACKGROUND The mission of the U.S. Department of Health and Human Services (DHHS), National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research (CCR), Molecular Imaging Program (MIP) is to advance cancer therapies using molecular imaging. �The MIP conducts research in designing, developing and testing new novel targeted imaging agents for the detection and characterization of cancer. �These imaging agents include tissue-specific MRI, Positron Emission Tomography (PET), radionuclide, and optical probes. �The MIP is focused on the clinical translation of targeted imaging agents for cancer imaging. � Within the pre-clinical section of the MIP is the Lab of Molecular Radiotherapy, which is focused on engineering tumor-selective molecular probes for human cancers, with particular interest in hepatobiliary malignancies. Liver cancer is the second leading cause of cancer-related deaths, and Hepatocellular carcinoma (HCC) is the most common type. Therefore, imaging agents are urgently required for the early detection of HCC and for the staging and monitoring of therapeutic approaches of the HCC. Glypican-3 (GPC3), an oncofetal proteoglycan anchored to the cell membrane, is normally detected in the fetal liver but not in the healthy adult liver. However, in HCC patients, GPC3 is overexpressed at both the gene and protein levels, and its expression predicts a poor prognosis. The overexpression of GPC3 in HCC, along with the lack of GPC3 in normal tissue, make GPC3 a useful target for molecular imaging and therapeutic intervention in HCC. Historically, full-length antibodies have been used for these purposes, however, because of their size and long biological half-lives, they are suboptimal for use as imaging scaffolds. To that end, the lab is looking to use peptides, which are smaller molecular weight and present more favorable pharmacokinetics. While linear peptides can bind to targets, the 3D structures that peptides can adopt dictate the manner in which they will interact with potential targets. Accordingly, generating peptide-derived libraries with molecules that have constrained peptides in 3D conformations can more reproducibly identify ones that exhibit robust binding to targets. �Phage display libraries of cyclizable peptides using cysteine-cysteine disulfide bridges within the peptide have been developed and allow for screening of numerous unique peptides. A recent advance on this approach, uses constrained peptides cyclized by using organic molecular cores that can yield on the order of 109 � 1012 unique constrained peptides with additional conformation states not typically available with conventional cysteine-cysteine cyclization for binding to any targets of interest.� Since neither the lab nor the NIH currently has the capabilities to engineer constrained peptide libraries using molecular cores or screening protocols to identify constrained peptide binders, the lab requires a Contractor with expertise with such library and screening techniques in order to meet the MIP�s requirements. � 3.0�� �SCOPE�� � The Contractor shall provide all personnel, labor, facilities, materials and equipment necessary to perform the required tasks in section 4 below. Within 14 business days after award, the MIP will supply the Contractor with Glypican-3 (GPC3), a molecule specific for liver cancer. �The Contractor shall perform a discovery and optimization of constrained peptides targeting Glypican-3 (GPC3) using a chemistry that involves multiple cyclization of linear peptides via a reaction with a small rigid entity (chemical scaffold) that carries 2, 3 or 4 reactive bromides as anchor points. �The bromides react exclusively with the thiols of the cysteines in the peptide and attach to the peptide via multiple covalent bonds. The peptide folds around the scaffold and loses flexibility while adopting a well-defined three-dimensional structure, with the scaffold entity in the center. �Constrained single loop peptides with the ability to target GPC3 will exhibit high affinity and a fast clearance from blood as well as from non-targeted tissues. �This will result in better and more selective imaging. �MIP shall select the top 15 peptides with the highest binding affinities and those peptides shall be re-synthesized at scale (>=2mg) and validated for their ability to bind to GPC3 with MIP. The Contractor shall send the MIP the top 15 candidate purified single loop constrained peptides (>=2mg, 90% purity) targeting GPC3. The cost of shipping samples to/from the Contractor�s facility shall not be included in the quote. �NCI shall ship the initial GPC3 required to begin the project to the Contractor via the NIH shipping service in one shipment.� In summary, the Contractor shall (1) use in-house constrained peptide library to identify peptides that associate with MIP target of interest, GPC3, (2) make the top specific constrained single loop peptide candidates, (3) confirm specific binding of constrained peptides to GPC3, and �(4) ship constrained single loop peptides to the MIP. � � 4.0�� �CONTRACT REQUIREMENTS 4.1�� �TASKS The Contractor shall perform the following tasks: 4.1.1�� �Two different peptide libraries shall be created by combining a ACXXXXXXXXXXCG phage library with either scaffold 1,3-Bis(bromomethyl)benzene [T2-013] or 2,6-Bis(bromomethyl)naphthalene [T2-034]. Phage display selections shall be performed with Glypican-3-Fc and a Fc-protein for deselection (e.g. Glypican-1-Fc or Fc only). During phage display both proteins shall be immobilized on protein-G coated magnetic beads. In total, 3 selection rounds shall be performed. Deliverable: Peptide derived library screening against GPC3. 4.1.2�� �The linear peptide candidates shall be synthetized using Fmoc-based SPPS with a (-terminal linker and Lys(biotin) followed by cyclization of linear peptides via reaction of thiol-functionalities of the cysteines with a small rigid entity. The bromide reacts exclusively with thiols and attaches to the peptide via covalent bonds. The cyclization reaction will be a maximum of 30 min, run at room temperature and no catalysis is required. �Once the cyclization is finished, the peptides shall be either used as crude peptides (B) or after purification by HPLC (C). For ELISA-validation, the constrained peptides shall be captured on a streptavidin-coated ELISA-plate and then probed with Glypican-3-Fc and an Fe negative control. Crude peptides (B) shall be tested at two concentrations of both proteins to detect candidates that show specific binding. The constrained peptide candidates selected by NIH (C) shall be re-tested as HPLC-purified material and ELISA EC50 values shall be determined via titration for affinity-ranking. Deliverable: Synthesis of lead candidates from phage display as crude peptides and binding validation in ELSA/SPR (maximum of 190 candidates). 4.1.3�� �The Contractor shall ship selected constrained peptides to NIH for functional�testing in house and the MIP will select the top 15 candidate peptides with affinity between 0.1 and 10nM. Final constrained peptides shall be single loop with molecular cores and each ?2mg and >90% purity. Deliverable: Synthesis of a maximum of top 15 lead candidates as soluble purified peptides (>=2mg, >90% purity) and ELISA/SPR-like validation (EC50-determination) and proteolytic stability assay of these 15 peptides. 4.1.4�� �The Contractor shall provide biweekly progress updates to the MIP, via email or teleconference, which will allow the MIP to stay up to date and discuss the next steps. If there is an urgent need for the Contractor to contact the MIP, the Contractor will contact via email or phone call. 5.0�� �TYPE OF ORDER This is a firm fixed price purchase order. 6.0�� �NON-SEVERABLE SERVICES� This is a non-severable firm fixed price purchase order. The services specified in each contract line item (CLIN) have been determined to be non-severable services - a specific undertaking or entire job with a defined end product of value to the Government. 7.0�� �PERIOD OF PERFORMANCE Period of performance shall be 12 months from date of award.� 8.0�� �PLACE OF PERFORMANCE All work shall be performed at the Contractor�s facility. 9.0�� �REPORT(S)/DELIVERABLES AND DELIVERY SCHEDULE All deliverables shall be submitted as an electronic copy in the form of PDF files, Excel workbooks or text files for review and comment by the Government�s technical point of contact (TPOC) (TBD at award) for a review period not to exceed thirty (30) business days. Final copies of approved drafts shall be delivered to the TPOC within ten (10) business days after receipt of the Government�s comments. DELIVERABLES�� � �� � � � � � � � � � � �� 1. Task #4.1.1� -� Peptide derived library screening against GPC3 via electronic file. Due: Within 1 month of GPC3 receipt 2. Task #4.1.2��-� Synthesis of lead candidates from phage display as crude peptides and binding validation in ELSA/SPR (maximum of 190 candidates). Both the list of the sequences of the candidates that bind, and the data on binding to be provided via electronic file. Due:�Within 2 months of GPC3 receipt 3.�Task # 4.1.3� -� Synthesis of a maximum of top 15 lead candidates as soluble purified peptides (>=2mg, >90% purity) and ELISA/SPR-like validation (EC50-determination) and proteolytic stability assay of these 15 peptides. Top 15 candidates (physical samples) to be shipped to NCI.��Due:�Within 4 months of GPC3 receipt 10.0�� �SUBMISSION INFORMATION Capability statements shall be submitted via email to Contracting Officer, Megan Kisamore, at megan.kisamore@nih.gov no later than 11:00 A.M. EST on Wednesday, August 5, 2020 (08/05/2020). All information furnished must be in writing and must contain enough detail to allow the NCI to determine if it can meet the unique specifications described herein. Please reference number 75N91020Q00151 on all correspondence.� This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization�s capability. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, an RFQ may be published. However, responses to this notice will not be considered adequate responses to a solicitation(s).
- Web Link
-
SAM.gov Permalink
(https://beta.sam.gov/opp/0c5fce15706d4476802d0df92504b6d9/view)
- Record
- SN05738910-F 20200731/200729230153 (samdaily.us)
- Source
-
SAM.gov Link to This Notice
(may not be valid after Archive Date)
| FSG Index | This Issue's Index | Today's SAM Daily Index Page |