Merck Patent Gmbh

Medarex Inc.

Amgen Research (munich) Gmbh

Micromet Ag

Biovation Limited

Stephen Williams

Anita Anne Hamilton

Francis Joseph Carr

Francis J Carr

Graham Carter

Stephen D Gillies

David J King

Christopher Robert Bebbington

Josephine M Cardarelli

Sarah Lee Pogue

Tim Jones

Tseng-hui Timothy Chen

Matthew Baker

Robert Hofmeister

John Watkins

Birgit Kohleisen

Patrick Bäuerle

Christian Itin

Ulla Lenkkeri-Schütz

Marian Hanlon

Jones Tim

Jeffrey Charles Way

Fiona Suzanne Adair

Jeffrey C Way

David King

The present invention provides a cytotoxically active CD3 specific binding construct comprising a first domain specifically binding to human CD3 and an Ig-derived second binding domain. Furthermore, a nucleic acid sequence encoding a CD3 specific binding construct of the invention is provided. Further aspects of the invention are vectors and host cells comprising said nucleic acid sequence, a process for the production of the construct of the invention and composition comprising said construct. The invention also provides the use of said constructs for the preparation of pharmaceutical compositions for the treatment of particular diseases, a method for the treatment of particular diseases and a kit comprising the binding construct of the invention.

Multispecific deimmunized CD3-binders

Humanized monoclonal antibodies which bind to IFNAR-1, and related antibody-based compositions and molecules, are disclosed. Also disclosed are pharmaceutical compositions comprising the humanized antibodies and therapeutic and diagnostic methods for using the humanized antibodies.

Humanized antibodies to interferon alpha receptor-1 (IFNAR-1)

A method of treating an autoimmune disease comprising administering to a patient a therapeutically effective amount of a CD20-binding polypeptide composition comprising a combination of a modified heavy chain variable region polypeptide and a modified light chain variable region polypeptide. The combination can be (a) a modified 2B8 antibody heavy chain variable region polypeptide of SEQ ID NO: 48; and a modified 2B8 antibody light chain variable region polypeptide of SEQ ID NO: 49; or (b) a modified Leu16 antibody heavy chain variable region polypeptide of SEQ ID NO: 50; and a modified Leu16 antibody light chain variable region polypeptide of SEQ ID NO: 51.

CD20-binding polypeptide compositions for treating autoimmune disease

A CD20-binding polypeptide composition comprising a combination of a modified heavy chain variable region polypeptide and a modified light chain variable region polypeptide. The combination can be (a) a modified 2B8 antibody heavy chain variable region polypeptide of SEQ ID NO: 48; and a modified 2B8 antibody light chain variable region polypeptide of SEQ ID NO: 49; or (b) a modified Leu16 antibody heavy chain variable region polypeptide of SEQ ID NO: 50; and a modified Leu16 antibody light chain variable region polypeptide of SEQ ID NO: 51.

CD20-binding polypeptide compositions and methods

The present invention provides a cytotoxically active CD3 specific binding construct comprising a first domain specifically binding to human CD3 and an IG-derived second binding domain. Furthermore, a nucleic acid sequence encoding a CD3 specific binding construct is provided. Further aspects of the invention are vectors and host cells comprising the nucleic acid sequences, a process for the production of the construct and composition comprising the construct. The invention also provides the use of the constructs for the preparation of pharmaceutical compositions for the treatment of particular diseases, a method for the treatment of particular diseases and a kit comprising the binding construct of the invention.

Multispecfic deimmunized CD3-binders

The invention relates to artificial modified proteins, preferably fusion proteins, having a reduced immunogenicity compared to the parent non-modified molecule when exposed to a species in vivo. The invention relates, above all, to novel immunoglobulin fusion proteins which essentially consist of an immunoglobulin molecule or a fragment thereof covalently fused via its C-terminus to the N-terminus of a biologically active non-immunoglobulin molecule, preferably a polypeptide or protein or a biologically active fragment thereof. In a specific embodiment, the invention relates to fusion proteins consisting of an Fc portion of an antibody which is fused as mentioned to the non-immunological target molecule which elicits biological or pharmacological efficacy. The molecules of the invention have amino acid sequences which are altered in one or more amino acid residue positions but have in principal the same biological activity as compared with the non-altered molecules. The changes are made in regions of the molecules which are identified as T-cell epitopes, which contribute to an immune reaction in a living host. Thus, the invention also relates to a novel method of making such fusion proteins by identifying said epitopes comprising calculation of T-cell epitope values for MHC Class II molecule binding sites in a peptide by computer-aided methods.

Artificial proteins with reduced immunogenicity

This invention relates to a novel approach for identification of T-cell epitopes, that give rise to an immune reaction in a living host. By means of this novel method biological compounds can be generated which have a no or at least a reduced immunogenicity when exposed to the immune system of a given species and compared with the relevant non-modified entity. Thus the invention relates also to novel biological molecules, especially proteins and antibodies, obtained by the method according to the invention.

Method for identification of t-cell epitopes and use for preparing molecules with reduced immunogenicity

A method of preparing a modified granulocyte colony stimulating factor (G-CSF) protein having reduced immunogenicity relative to human G-CSF comprises the steps of (i) identifying one or more potential T-cell epitopes within the amino acid sequence of human G-CSF (SEQ ID NO:); (ii) designing at least one sequence variant of at least one potential T-cell epitope identified in step (i), wherein the sequence variant eliminates or substantially reduces the MHC class II binding activity of the potential T-cell epitope; (iii) preparing, by recombinant DNA techniques, at least one modified G-CSF protein including a sequence variant designed in step (ii); (iv) evaluating at least one modified G-CSF protein prepared in step (iii) for G-CSF activity and immunogenicity; and (v) selecting a modified G-CSF protein evaluated in step (iv) that has substantially the same therapeutic G-CSF biological activity as, but substantially less immunogenicity than, human G-CSF.

Method of preparing a modified granulocyte colony stimulating factor (G-CSF) with reduced immunogenicity

Anti-KSA/IL-2 fusion proteins with reduced immunogenicity

The present invention relates to antibodies which are directed to the EGF receptor (HER1) to be administered especially to humans and in particular for therapeutic use in tumors. The antibodies are modified whereby the modification results in a reduced propensity for the antibody to elicit an immune response upon administration to the human subject. The invention in particular relates to the modification of anti-EGFR antibody 425 in its different forms and fragments thereof to result in Mab 425 variants that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo.

Modified anti-EGFR antibodies with reduced immunogenicity

This invention provides methods of protein/polypeptide screening based on the provision of libraries of individual proteins/polypeptides, which in turn can be screened for a number of activities, including cell binding and biological activity. Methods for recovering genes encoding such proteins/polypeptides are also provided.

Methods for protein screening

Growing community of inventors

Aberdeenshire, United Kingdom

Stephen Williams