National Research Council of Canada

Cephalon, Inc.

Kristin Kemmerich

Traian Sulea

Danica Stanimirovic

Bernard Massie

Mehdi Arbabi-Ghahroudi

Arsalan S Haqqani

Rénald Gilbert

Adam Clarke

Matthew Pollard

Yves Durocher

Renald Gilbert

Jennifer Stratton

David Wilson

The present invention relates, in general, to polypeptides capable of transmigrating the blood-brain barrier, and uses thereof. More specifically, the present invention relates to polypeptides derived by site-directed mutagenesis of an existing antibody fragment and uses thereof, and methods of making such molecules. The polypeptides of the present invention show enhanced blood-brain barrier crossing and brain exposure levels in vitro and in vivo.

Antibody variants transmigrating the blood-brain barrier and uses thereof

The present invention relates to antibodies and fragments thereof derived by humanization of an existing antibody, and methods of making them. The humanized antibodies of the present invention show enhanced binding to the brain endothelial antigen, improved transmigration across the blood-brain barrier, and increased thermal stability relative to the parent non-humanized antibody.

Humanized antibodies transmigrating the blood-brain barrier and uses thereof

The blood-brain barrier (BBB) prevents transport of molecules larger than 500 Dal tons from blood to brain. Receptor-mediated transcytosis (RMT) facilitates transport across the BBB of specific molecules that bind receptors on brain endothelial cells that form the BBB. An insulin-like growth factor 1 receptor (IGF 1R)-binding antibody or fragment thereof is identified that transmigrates the BBB by RMT. The antibody or fragment is used to deliver a cargo molecule across the BBB, wherein the cargo molecule may be a therapeutic or detectable agent. The antibody is a camelid VHH, prepared by immunizing a llama with a 933-amino acid IGF 1R polypeptide. Humanized forms of the camelid VHH are also generated.

Insulin-like growth factor 1 receptor-specific antibodies and uses thereof

The blood-brain barrier (BBB) prevents transport of molecules larger than 500 Daltons from blood to brain. Receptor-mediated transcytosis (RMT) facilitates transport across the BBB of specific molecules that bind receptors on brain endothelial cells that form the BBB. An insulin-like growth factor 1 receptor (IGF1R)-binding antibody or fragment thereof is identified that transmigrates the BBB by RMT. The antibody or fragment is used to deliver a cargo molecule across the BBB, wherein the cargo molecule may be a therapeutic or detectable agent. The antibody is a camelid VHH, prepared by immunizing a llama with a 933-amino acid IGF1R polypeptide. Humanized forms of the camelid VHH are also generated.

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Ottawa, Canada

Kristin Kemmerich