Abstract: This invention relates to the fields of immunology and protein therapeutics. The therapeutic proteins are polypeptides to be administered especially to humans. The polypeptides are modified whereby the modification results in a reduced propensity for the polypeptide to elicit an immune response upon administration to the human subject. The invention therefor provides methods for the development of therapeutic polypeptides that are less immunogenic than any non-modified counterpart when used in vivo. The modifications used according to this invention relate, for example, to the introduction of protease cleavage sites, attachment of different molecules or insertion of non-natural amino acids.

Abstract: The present invention relates a modified human interferon beta (INF?) which is less immunogenic than human INF? (SEQ ID NO: 1) when administered in vivo to a human. The modified human INF? comprises an amino acid residue sequence that differs from SEQ ID NO: 1 by an amino acid residue substitution selected from the group consisting of L57A, L57C, L57D L57E, L57G, L57H, L57K, L57N, L57P, L57Q, L57R, L57S, and L57T and an additional substitution selected from the group consisting of the H140A, H140C, H140G, and H140P.

Abstract: 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.

Abstract: The present invention relates a modified human interferon beta (INF?) which is less immunogenic than human INF? (SEQ ID NO: 1) when administered in vivo to a human. The modified human INF? comprises an amino acid residue sequence that differs from SEQ ID NO: 1 by an amino acid residue substitution selected from the group consisting of L57A, L57C, L57D L57E, L57G, L57H, L57K, L57N, L57P, L57Q, L57R, L57S, and L57T and an additional substitution selected from the group consisting of the H140A, H140C, H140G, and H140P.

Abstract: 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.

Abstract: 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.

Abstract: 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: 1); (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.

Abstract: A modified interferon beta (INF?) is provided, which is less immunogenic than human INF? (SEQ ID NO: 1) when administered to a human in vivo. The modified INF? comprises an amino acid residue sequence that differs from SEQ ID NO: 1 by a substitution at one or more residues of SEQ ID NO: 1. Preferred substitutions are at residues selected from the group consisting of residue 50, 59, 60, 62, 63, 66, 67, 69, 70, 125, 126, 129, 130, 132, 133, and 138. Examples of suitable substitutions include F50A, L57A, I59A, Y60N, M62A, L63A, I66T, F67H, I69A, F70A, Y125A, Y126A, I129A, L130A, Y132S, L133A, Y138H, and Y138A.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: The present invention relates to polypeptides to be administered especially to humans and in particular for therapeutic use. The polypeptides are modified polypeptides whereby the modification results in a reduced propensity for the polypeptide to elicit an immune response upon administration to the human subject. The invention in particular to the modification of human interferon alpha and specifically interferon alpha 2(INF?2) to result in proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when use in vivo.

Abstract: The present invention relates to the field of immunology. The invention identifies determinants on staphylococcal enterotoxin B (SEB) able to evoke an immune response. In particular the invention is concerned with the identification of epitopes for T-cells in SEB. The invention relates furthermore to T-cell epitope peptides derived from SEB by means of which it is possible to create modified SEB variants with reduced immunogenicity.

Abstract: The present invention provides molecules, preferably designed immunoglubulins, suitable for use as an anti-idiotype vaccine to CEA positive tumours. The molecules induce both an MHC class I and MHC class II mediated immune response to the CEA bearing tumour cells for an efficient and sustained host anti-tumour response. The present invention provides modified versions of anti-idiotype anti-CEA antibodies, preferably mouse antibody 708, with improved vaccination properties. The modifications are related to the introduction of sequences tracts deriving from e.g. CEA, CD55 antigen and CEA cancer-specific MHC epitopes into the variable regions of said antibody molecules.

Abstract: The invention provides methods for the identification of immunogenic regions within the amino acid residue sequence of a polypeptide, such as a therapeutic protein or a fragment thereof.

Abstract: 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.

Abstract: The present invention relates to polypeptides to be administered especially to humans and in particular for therapeutic use. The polypeptides are modified polypeptides whereby the modification results in a reduced propensity for the polypeptide to elicit an immune response upon administration to the human subject. The invention in particular relates to the modification of human interferon beta to result in proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo.

Abstract: The invention relates to the modification of human growth hormone (high) to result in human growth hormone proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in-vivo. The invention relates, furthermore, to T-cell epitome sequences deriving from high, which are immunogenic.