Merck Patent Gmbh

Biovation Limited

Cornell University

Agen Biomedical Ltd.

Amgen Research (Munich) Gmbh

Micromet Ag

Emd Lexigen Research Center Corp.

Merck Patent Gesellschaft MIT Beschraenkter Haftung

Amgen Research Gmbh

Anita Anne Hamilton

Francis Joseph Carr

Stephen Williams

Graham Carter

Stephen D Gillies

Francis J Carr

Jeffrey Charles Way

Fiona Suzanne Adair

Matthew Baker

Neil H Bander

Robert Hofmeister

Tim Jones

Patrick Bäuerle

Birgit Kohleisen

John Watkins

Ulla Lenkkeri-Schütz

Christian Itin

Marian Hanlon

Jones Tim

Jeffrey C Way

Patrick Baeuerle

Ulla Lenkkeri-Schuetz

Fiona Adair

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

Disclosed are compositions and methods for producing fusion proteins with reduced immunogenicity. Fusion proteins of the invention include a junction region having an amino acid change that reduces the ability of a junctional epitope to bind to MHC Class II, thereby reducing its interaction with a T-cell receptor. Methods of the invention involve analyzing, changing, or modifying one or more amino acids in the junction region of a fusion protein in order to identify a T-cell epitope and reduce its ability to interact with a T cell receptor. Compositions and methods of the invention are useful in therapy.

Reducing the immunogenicity of fusion proteins

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 present invention provides for modified forms of anti-CD52 antibodies with reduced numbers of potential T-cell epitopes that are expected to display decreased immunogenicity.

Modified anti-CD52 antibody

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

Modified antibodies, or antigen-binding fragments thereof, to the extracellular domain of human prostate specific membrane antigen (PSMA) are provided. The modified anti-PSMA antibodies, or antigen-binding fragments thereof, have been rendered less immunogenic compared to their unmodified counterparts to a given species, e.g., a human. Pharmaceutical compositions including the aforesaid antibodies, nucleic acids, recombinant expression vectors and host cells for making such antibodies and fragments are also disclosed. Methods of using the antibodies of the invention to detect human PSMA, or to ablate or kill a PSMA-expressing cell, e.g., a PSMA-expressing cancer or prostatic cell, either in vitro or in vivo, are also provided.

Methods of treating prostate cancer with anti-prostate specific membrane antigen antibodies

A target protein is rendered less immunogenic to a given species by (a) determining at least part of the amino acid sequence of the target protein; (b) identifying in the amino acid sequence one or more potential epitopes for T-cells ('T-cell epitopes') of the given species; and (c) modifying the amino acid sequence to eliminate at least one of the T-cell epitopes identified in step (b) to reduce the immunogenicity of the protein when exposed to the immune system of the given species.

De-immunized streptokinase

The present invention relates generally to carrier molecules derived from one animal or avian species or strains and which are substantially non-immunogenic when exposed to an immune system from a species or strain of another animal or avian creature. More particularly, the present invention provides deimmunized immunointeractive molecules and even more particular deimmunized antibodies for use in diagnostic and therapeutic applications.

Carrier molecules

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

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

Protein, or parts of proteins, may be rendered non-immunogenic, or less immunogenic, to a given species by identifying in their amino acid sequences one or more potential epitopes for T-cells of the given species and modifying the amino acid sequence to eliminate at least one of the T-cell epitopes. This eliminates or reduces the immunogenicity of the protein when exposed to the immune system of the given species. Monoclonal antibodies and other immunoglobulin-like molecules can particularly benefit from being de-immunised in this way: for example, mouse-derived immunoglobulins can be de-immunised for human therapeutic use.

Method for rendering streptokinase less immunogenic to a human

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Aberdeen, United Kingdom

Anita Anne Hamilton