Deliverables and Timeline. 2.1.1 RESEARCH ACTIVITIES, [ * ] DELIVERABLE 1 (D1)--ISOLATION AND CONFIRMATION OF INHIBITORY PEPTIDES:
(a) [ * ]
(b) [ * ]
2.1.2 RESEARCH ACTIVITIES, [ * ] DELIVERABLE 2 (D2)--IgE SYNTHESIS INHIBITION AND SPECIFICITY OF INDIVIDUAL PEPTIDE HITS: [ * ]
(a) [ * ]
(b) [ * ] D2 CRITERIA: Section 2.1.2(a) shall be known as D2a criteria, and Section 2.1.2(b) above shall be known as D2b criteria. DELIVERABLE 3 (D3)--CLONING OF FULL LENGTH CDNAS OF PROTEINS BINDING OF INHIBITORY PEPTIDES: [ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDED. Rigel will deliver full length sequences of protein binding partners of inhibitory peptides. [ * ]
Deliverables and Timeline. 2.1.1 RESEARCH ACTIVITIES, 0-12 MONTHS: DELIVERABLE 1 (D1)--ISOLATION AND CONFIRMATION OF INHIBITORY PEPTIDES:
(a) (8 MONTHS) Rigel will endeavor to isolate specific peptide inhibitors of IL-4-induced, B cell germline epsilon transcription, from stem loop peptide libraries (2x10(9) component complexity) using a Fas-mediated apoptosis cell survival assay. The greater the number of peptides actually expressed in the reporter cell line, the greater the chances of finding novel Molecular Targets, so every reasonable effort will be made to maximize the representation of the peptide library in the reporter cell line. However, taking transfection efficiency into account, no less than 10(8) components will be have been expressed in the B-cell reporter cell line. The iterative enrichment of inhibitory peptides and their characterization will be carried out by Rigel as shown in Figure 2.
(b) (12 MONTHS) As noted in Figure 2, Rigel will endeavor to confirm that individual peptide inhibitors confer the IL-4 resistant phenotype in a Fas-mediated apoptosis cell survival assay. The capacity of this assay would allow 100+ peptide inhibitors to be taken forward through this assay for confirmation.
2.1.2 RESEARCH ACTIVITIES, 12-18 MONTHS: DELIVERABLE 2 (D2)--IgE SYNTHESIS INHIBITION AND SPECIFICITY OF INDIVIDUAL PEPTIDE HITS: Rigel will endeavor to demonstrate that recovered single peptide hits inhibit IgE synthesis SELECTIVELY over IgG synthesis as follows:
(a) Measure IgE versus IgG secretion/switching inhibition in a cytokine stimulated XX00 X-xxxx line. The goal is that the inhibitory peptide will inhibit IgE levels in the media produced by the IgM+ BL16 cell line stimulated with IL-4 by 20 fold over an irrelevant peptide control. If the peptide also inhibits IL-10 driven IgG levels from the IgM+ BL16 cell line, the goal will be that the peptide will inhibit IgE levels by 20 fold more than IgG. Secreted antibody levels will be measured in the media by ELISA. Because of the higher throughput of the BL16 assay (capacity = 100+ peptides) versus the primary PBL assay (capacity = 10 peptides), it is expected that the BL16 assay will be used to rapidly select peptides that will serve as baits in YTH screening, while the PBL assay will only be performed on those peptides whose ligands are not known components of the IL-4 signaling pathway.
(b) Confirm that the peptide inhibitor meets the same criteria as in D2a in primary cells by performing similar experiments to those in D2a...
Deliverables and Timeline. A. Contractor shall procure, modify, plan, design, develop and/or implement the Deliverables that are identified and described in Table B-1.
Deliverables and Timeline. Begin date: March 1, 2022 Completion date: December 31, 2023
Deliverables and Timeline. Del # Deliverable name Date
Deliverables and Timeline. Deliverable No. 1: Draft and Final Audit Report
Deliverables and Timeline. Deliverable No. 1: Stock Count, Draft and Final Audit Report
Deliverables and Timeline. Deliverables. Acceptance Criteria and required due dates as applicable are specified in the Appendix C, Scope of Work.
Deliverables and Timeline. Deliverables
Deliverables and Timeline. For each of the deliverables below, SC staff will take 2-4 days to review/provide feedback on each draft. SC will remain in conversation with the consultant throughout the consultancy. Dates will be confirmed in consultation with the consultant:
