Single-domain brain-targeting antibody fragments derived from llama antibodies

US7943129B2 · kind B2 · utility

Assignee

• National Research Council of Canada · CA

Inventors

• Arumugam Muruganandam · Bengaluru, IN
• Jasmid Tanha · Ottawa, CA
• Saran Narang · Ottawa, CA
• Danica Stanimirovic · Greely, CA

Key dates

• Filing date: May 25, 2001
• Grant date: May 17, 2011
• Expiry date: Mar 7, 2022

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2317/569
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A phage-displayed library of llama single heavy domain antibodies (sdAbs) was enriched for species that selectively bind to and are internalized by human cerebromicrovascular endothelial cells (HCEC). From the enriched library, two sdAbs were selected, sequenced, subcloned, and expressed as fusion proteins with c-myc-His5 tags. Similarly as phage-displayed sdAbs, these soluble tagged sdAbs were shown to selectively bind to HCEC and to transmigrate across in vitro human blood-brain barrier (BBB) model. In contrast to an unrelated llama sdAb, these sdAbs were also detected in the brain after i.v. injection into mice. These small (˜13 kDa) antibody fragments have essential characteristics of brain-specific delivery vectors and can be used to facilitate drug transport across the BBB.