Single domain brain-targeting antibody fragments derived from llama antibodies

US8715659B2 · kind B2 · utility

Assignee

• National Research Council of Canada · CA

Inventors

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

Key dates

• Filing date: Feb 22, 2013
• Grant date: May 6, 2014
• Expiry date: Feb 22, 2033

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 (His5 is SEQ ID NO:101). 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.