Toll-like receptor 2 binding epitope and binding member thereto

Inventors

Kuklik, Nils • Schubert, Wolf-Dieter

Assignees

Neuramedy Co Ltd

Abstract

The present invention relates to the identification of a TLR2 binding epitope wherein binding of a binding member to the epitope serves to inhibit TLR2 activation and/or signalling. Polypeptide fragments of TLR2 and three-dimensional structures comprising one or more amino acid residues His318, Pro320, Gln321 or Arg321, Tyr323, Lys347, Phe349, Leu371, Glu375, Tyr376 and His398 of TLR2 which define the identified epitope are provided for use in generating binding members. Also provided are binding members which bind to the identified epitope and methods of using same for the treatment and/or prevention of conditions associated with TLR2 activation and/or signalling.

Core Innovation

The document describes identifying a functional, non-continuous TLR2 inhibitory binding epitope centered on residues His318, Pro320, Gln321 or Arg321, Tyr323, Lys347, Phe349, Leu371, Glu375, Tyr376 and His398. The functional epitope is located outside the extracellular domain and is defined within TLR2 polypeptide fragments other than the extracellular domain.

The functional epitope is bound by TLR2 antagonistic antibody T2.5 and a humanised version thereof designated OPN-305. Binding of the functional epitope by a binding member antagonises TLR2 activation and signalling and relates to antagonistic antibody binding.

The document further provides three-dimensional epitope representations using 3D epitope structures and non-TLR2 scaffolds that define binding rather than using the extracellular domain itself. It states that the defined fragments and 3D epitope form the basis for screening and assay approaches to identify antagonists and block the TLR2 dimerization interface.

Claims Coverage

The partial content provides one independent claim defining a screening method or assay for identifying binding members that antagonise TLR2 activation and signalling, using a defined non-extracellular-domain TLR2 polypeptide fragment comprising a functional epitope bound by T2.5 and OPN-305. The claim set includes dependent refinements that narrow the fragment composition and length and add identity and alternative residue-range constraints.

Across the provided claims, the coverage centers on screening by binding assessment to a defined TLR2 polypeptide fragment, outside the extracellular domain, that presents a functional epitope bound by the TLR2 antagonistic antibodies T2.5 and OPN-305, with fragment length constrained to less than about 200 amino acid residues and antagonism concluded from binding to that epitope.

Stated Advantages

Documented Applications