Ucbbiopharma Srl

Xiaofeng Liu

Ralph Adams

Terence Seward Baker

Alistair James Henry

Thomas Allen Ceska

James Michael McDonnell

Brian John Sutton

Marta Katarzyna Westwood

Anna Marie Davies

Alastair David Griffiths Lawson

Richard David Taylor

Jiye Shi

Computer-implemented methods of designing an antibody that will bind to a target epitope are disclosed. In one arrangement, the method comprises identifying one or more hotspot residues that will each bind to a corresponding one of one or more hotspot sites on the target epitope. Candidate antibody structures are selected from a database such that characteristic atoms within the antibody structure and hotspot characteristic atoms can be superimposed computationally with an averaged spatial deviation less than a predetermined threshold. A designed antibody is generated by replacing matching residues with different residues such that a predicted affinity is increased.

De novo antibody design

The present invention relates to the area of improved anti-IgE antibodies and antigen binding agents, and compositions thereof, which target IgE, for instance: for use in treating disorders caused by IgE (such as allergic responses, or certain autoimmune responses); and, in particular, disorders caused by the interaction of IgE with the FcεRI receptor. In particular, this invention relates to improved anti-IgE antibodies and antigen binding agents related to novel mutants of omalizumab (Xolair®). The improved anti-IgE antibodies and antigen binding agents of the invention may have improved affinity for IgE and/or an improved interaction with the Cε2 domain of IgE and/or an improved modified epitope on IgE (for instance further involving the Cε2 domain of IgE) and/or the ability to disassociate IgE from the FcεRI receptor for instance at pharmaceutically-relevant concentrations. In one aspect, improved or novel treatments for IgE mediated disorders are disclosed in which IgE is targeted (for instance free IgE and/or IgE complexed with the FcεRI receptor).

Anti-IgE antibodies

The present invention provides antibodies comprising a variable (V) domain and an insert polypeptide, wherein the insert polypeptide is within the framework 3 region of the V domain.

Antibodies comprising a polypeptide inserted in framework 3 region

Methods and associated apparatus involving designing a ligand ab initio that will bind to a binding site of a macromolecular target, or of identifying a modification to a ligand for improving the affinity of the ligand to a binding site of a macromolecular target, comprising using information about non-bonding, intra-molecular or inter-molecular atom to atom contacts extracted from a database of biological macromolecules to identify favoured regions adjacent to the binding site for particular atom types and modifying a candidate ligand to increase the intersection between atoms of the candidate ligand and the favoured regions. One or more steps of the methods may be performed by a computer.

Obtaining an improved therapeutic ligand

The present invention relates to the area of improved anti-IgE antibodies and antigen binding agents, and compositions thereof, which target IgE, for instance: for use in treating disorders caused by IgE (such as allergic responses, or certain autoimmune responses); and, in particular, disorders caused by the interaction of IgE with the Fc&#x3b5;RI receptor. In particular, this invention relates to improved anti-IgE antibodies and antigen binding agents related to novel mutants of omalizumab (Xolair&#xae;). The improved anti-IgE antibodies and antigen binding agents of the invention may have improved affinity for IgE and/or an improved interaction with the C&#x3b5;2 domain of IgE and/or an improved modified epitope on IgE (for instance further involving the C&#x3b5;2 domain of IgE) and/or the ability to disassociate IgE from the Fc&#x3b5;RI receptor for instance at pharmaceutically-relevant concentrations. In one aspect, improved or novel treatments for IgE mediated disorders are disclosed in which IgE is targeted (for instance free IgE and/or IgE complexed with the Fc&#x3b5;RI receptor).

Growing community of inventors

Slough, United Kingdom

Xiaofeng Liu