Abstract: The invention in particular relates to the modification of human factor IX to result in factor IX 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 epitope sequences deriving from human factor IX, which are immunogenic.

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: 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: 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 protamine to result in protamine proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo.

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 insulin to result in insulin proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo.

Abstract: The present invention relates to antibodies which are directed to the EGF receptor (HER 1) 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: 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 ciliary neutrophic factor (CNTF) to result in CNTF proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo.

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 Fe 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 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 interleukin-1 receptor antagonist (IL-1RA) to result in IL-1RA proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo.

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 thrombopoietin (TPO) to result in TPO proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used <i>in vivo<i/>.

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 brain-derived neutrophic factor (BDNF) to result in BDNF proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo.

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 obesity protein (leptin) to result in leptin proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo.

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 granulocyte colony stimulating factor (G-CSF) to result in granulocyte colony stimulating factor (G-CSF) proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo.

Abstract: The present invention relates to methods to determine peptides presented on the surface of mammalian cells following addition to the cells of a protein. The present invention also relates to diagnostic tests based on the determination of such peptides or modified molecules resulting from determination of such peptides, such as pharmaceutical entities preferably having specific biological activity and reduced or enhanced immunogenicity when compared with the corresponding non-modified molecules. The methods according to this invention are preferably established with tools using mass spectroscopy (MS).

Abstract: A refrigerator handle assembly includes a main handle member, upper and lower extensions, and a base member. The main handle member is formed with an elongated upper cleat over which the upper extension snaps, an intermediate gripping portion, and a lower connecting portion including a cantilevered finger beneath which the base member extends. Each of the upper and lower portions of the main handle member is formed with slots which receive projections provided on the upper and lower extensions respectively. Detents provided on the upper and lower extensions are received beneath respective portions of the cleat and the base member in order to snap-fittingly interconnect the upper and lower extensions. The lower extension actually extends around both the terminal end of the main handle member and the base, while the upper extension extends about the elongated cleat. A tab formed on the cleat projects through a cut-out formed in the second extension.

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: A refrigerator handle assembly includes a main handle member, upper and lower extensions, and a base member. The main handle member is formed with an elongated upper cleat over which the upper extension snaps, an intermediate gripping portion, and a lower connecting portion including a cantilevered finger beneath which the base member extends. Each of the upper and lower portions of the main handle member is formed with slots which receive projections provided on the upper and lower extensions respectively. Detents provided on the upper and lower extensions are received beneath respective portions of the cleat and the base member in order to snap-fittingly interconnect the upper and lower extensions. The lower extension actually extends around both the terminal end of the main handle member and the base, while the upper extension extends about the elongated cleat. A tab formed on the cleat projects through a cut-out formed in the second extension.

Abstract: A method of controlling the growth of bacteria and algae in the water of swimming pools by adding to the water a specified concentration of a polymeric biguanide. Has the advantage over chlorination that at the low concentration employed the polymeric biguanide is non-toxic, non-irritant, tasteless and odorless. The anti-bacterial and anti-algal effect is also highly persistent.