Humanization of a Notch 3 Agonist Antibody for Pre-Clinical Development of a CADASIL Treatment

Summary

The project aims to humanize a mouse monoclonal Notch 3 agonist antibody for preclinical development as a treatment for CADASIL, a small vessel disease characterized by stroke and vascular cognitive impairment.

What they want

The project involves generating a panel of agonist Notch3 human monoclonal antibodies (humAbs) by humanizing a mouse monoclonal antibody, screening candidate antibodies using in vitro assays for Notch 3 antigen recognition and activation, preparing a cell line using Switchable Membrane Reporter (SwiMR) technology for lead humAb production, testing the preclinical efficacy of lead humAbs in mouse models of Notch 3 deficiency and CADASIL, and evaluating toxicity and pharmacokinetics of antibody administration in mice.

Deliverables

Panel of agonist Notch3 human monoclonal antibodies (humAbs)
Rank-ordered candidate antibodies based on in vitro assays
Cell line for the production of lead humanized A13 (huA13) antibodies
Preclinical efficacy data of lead Notch 3 humAbs in mouse models
Toxicity and pharmacokinetics evaluation data of antibody administration

Technical requirements

Humanization of mouse monoclonal antibody via grafting of complementarity-determining regions (CDRs) into human framework regions (FRs)
In vitro ELISA test detecting target engagement and activation of human Notch3 receptors via release of the Notch 3 extracellular domain (N3ECD) biomarker
Switchable Membrane Reporter (SwiMR) technology for antibody production
Preclinical in vivo testing in mouse models of Notch 3 deficiency and CADASIL
Evaluation of Notch 3 activation in CNS vessels, crossing the blood-CNS barrier, normalization of N3ECD in blood, and rescue of mural cell loss
Examination of toxicity and pharmacokinetics of increasing single-dose antibody administration in mice

Market context

inferred from NAICS

Professional, Scientific & Technical Services

NAICS 541714

US market size: $2.0T
Typical award: $25K – $50M

Typical buyers

All federal civilianDoDStates

Commonly required

8(a)WOSBSDVOSBPE/PMP

Sector-level estimate — full code lookup not yet in catalog.