Abstract: The invention provides improved nucleotide sequences and nucleic acids that encode glycine serine linkers and that use an excess of GGA, GGG, and GGT/GGU codons to encode the glycine residues. The invention further relates to nucleotide sequences and nucleic acids that encode (fusion) proteins and polypeptides comprising glycine serine linkers, which nucleotide sequences and nucleic acids comprise such improved nucleotide sequences and nucleic acids of the invention.

Abstract: The present invention relates to stable formulations of polypeptides, e.g. immunoglobulin single variable domains, in particular immunoglobulin single variable domains directed against von Willebrand Factor (vWF). The invention provides formulations which are stable upon storage for prolonged periods of time and over a broad range of temperatures. The formulations of the invention ensure a high stability of the polypeptide, allowing multiple freeze-thaw cycles without chemical or physical deterioration, and provide stability in relation to mechanical stress, such as shake, shear or stir stress. They are suitable for pharmaceutical and diagnostic preparations and compatible with pharmaceutically acceptable diluents.

Abstract: The present invention relates to stable formulations of polypeptides, e.g. immunoglobulin single variable domains, in particular immunoglobulin single variable domains directed against von Willebrand Factor (vWF). The invention provides formulations which are stable upon storage for prolonged periods of time and over a broad range of temperatures. The formulations of the invention ensure a high stability of the polypeptide, allowing multiple freeze-thaw cycles without chemical or physical deterioration, and provide stability in relation to mechanical stress, such as shake, shear or stir stress. They are suitable for pharmaceutical and diagnostic preparations and compatible with pharmaceutically acceptable diluents.

Abstract: Methods for preparing solid formulations of immunoglobulin single variable domains are provided. The methods are based on contacting solid carrier(s) with a liquid comprising the immunoglobulin single variable domains, e.g. by spraying the liquid onto the solid carrier(s), to cause granulation or coating of the carrier(s). During contacting the carrier is agitated, e.g. in a fluid bed, and the mixture of carrier and liquid is exposed to heat, e.g. a heated air stream, to evaporate the liquid.

Abstract: Formulations are provided that contain single variable domains with a good solubility and good stability under different storage, transportation and stress conditions. The formulations are useful as pharmaceutical formulation. The formulation comprises an aqueous carrier with a pH of 5.5 to 8.0, a buffer selected from the group consisting of histidine pH 6.0-6.5, hepes pH 7.0-8.0, MES pH 6.0, succinate pH 6.0-6.5 and acetate pH 5.5-6.0; an excipient; and/or a surfactant selected from polysorbate 80, polysorbate 20 and poloxamers. The formulation is further characterized that it has an inorganic salt concentration of 150 mM or lower. The invention further relates to containers and pharmaceutical units comprising such formulations and to methods for preparing and prophylactic and therapeutic uses of the formulations and pharmaceutical units of the invention.

Abstract: The present invention relates to stable formulations of polypeptides, e.g. immunoglobulin single variable domains, in particular immunoglobulin single variable domains directed against von Willebrand Factor (vWF). The invention provides formulations which are stable upon storage for prolonged periods of time and over a broad range of temperatures. The formulations of the invention ensure a high stability of the polypeptide, allowing multiple freeze-thaw cycles without chemical or physical deterioration, and provide stability in relation to mechanical stress, such as shake, shear or stir stress. They are suitable for pharmaceutical and diagnostic preparations and compatible with pharmaceutically acceptable diluents.

Abstract: Formulations are provided that contain single variable domains with a good solubility and good stability under different storage, transportation and stress conditions. The formulations are useful as pharmaceutical formulation. The formulation comprises an aqueous carrier with a pH of 5.5 to 8.0, a buffer selected from the group consisting of histidine pH 6.0-6.5, hepes pH 7.0-8.0, MES pH 6.0, succinate pH 6.0-6.5 and acetate pH 5.5-6.0; an excipient; and/or a surfactant selected from polysorbate 80, polysorbate 20 and poloxamers. The formulation is further characterized that it has an inorganic salt concentration of 150 mM or lower.

Abstract: The present invention provides methods for the expression and/or production of variable domains with a C-terminal extension that can be used for coupling of the variable domain to one or more further groups, residues or moieties. In the method of the invention a yield of at least 80% of variable domains with a cysteine containing C-terminal extension is obtained. Also variable domains are provided and polypeptides comprising one or more variable domains obtainable by the methods of the present invention, as well as compounds that comprise such variable domains and/or polypeptides coupled to one or more groups, residues or moieties.

Abstract: The present invention provides methods for the expression and/or production of variable domains with a C-terminal extension that can be used for coupling of the variable domain to one or more further groups, residues or moieties. In the method of the invention a yield of at least 80% of variable domains with a cysteine containing C-terminal extension is obtained. Also variable domains are provided and polypeptides comprising one or more variable domains obtainable by the methods of the present invention, as well as compounds that comprise such variable domains and/or polypeptides coupled to one or more groups, residues or moieties.

Abstract: Formulations are provided that contain single variable domains with a good solubility and good stability under different storage, transportation and stress conditions. The formulations are useful as pharmaceutical formulation. The formulation comprises an aqueous carrier with a pH of 5.5 to 8.0, a buffer selected from the group consisting of histidine pH 6.0-6.5, hepes pH 7.0-8.0, MES pH 6.0, succinate pH 6.0-6.5 and acetate pH 5.5-6.0; an excipient; and/or a surfactant selected from Tween 80, Tween 20 and poloxamers. The formulation is further characterized that it has an inorganic salt concentration of 150 mM or lower. The invention further relates to containers and pharmaceutical units comprising such formulations and to methods for preparing and prophylactic and therapeutic uses of the formulations and pharmaceutical units of the invention.

Abstract: The present invention relates to amino acid sequences that are directed against the p19 subunit of IL-23; as well as protein, constructs and compounds comprising the same; and also nucleic acids encoding the same.

Abstract: Biparatopic protein constructs that are directed against IL-23, and in particular against the p19 subunit of IL-23. The constructs comprise at least a first binding domain or binding unit directed against a first defined epitope on p19 and at least a second binding domain or binding unit directed against a second defined epitope on p19 (or the p19/p40 interface). The binding domains or binding units may in particular be a domain antibody, a single domain antibody, a dAb or a Nanobody®. The constructs and pharmaceutical compositions comprising the same can be used for the prevention and/or treatment of diseases and disorders associated with IL-23 or IL-23 mediated signaling, such as inflammation and inflammatory disorders such as colitis, Crohn's disease and IBD, infectious diseases, psoriasis, cancer, autoimmune diseases, sarcoidosis, transplant rejection, cystic Fibrosis, asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, viral infection, and common variable immunodeficiency.

Abstract: Formulations are provided that contain single variable domains with a good solubility and good stability under different storage, transportation and stress conditions. The formulations are useful as pharmaceutical formulation. The formulation comprises an aqueous carrier with a pH of 5.5 to 8.0, a buffer selected from the group consisting of histidine pH 6.0-6.5, hepes pH 7.0-8.0, MES pH 6.0, succinate pH 6.0-6.5 and acetate pH 5.5-6.0; an excipient; and/or a surfactant selected from Tween 80, Tween 20 and poloxamers. The formulation is further characterized that it has an inorganic salt concentration of 150 mM or lower. The invention further relates to containers and pharmaceutical units comprising such formuSations and to methods for preparing and prophylactic and therapeutic uses of the formulations and pharmaceutical units of the invention.

Abstract: The present invention provides methods for the expression and/or production of variable domains with a C-terminal extension that can be used for coupling of the variable domain to one or more further groups, residues or moieties. In the method of the invention a yield of at least 80% of variable domains with a cysteine containing C-terminal extension is obtained. Also variable domains are provided and polypeptides comprising one or more variable domains obtainable by the methods of the present invention, as well as compounds that comprise such variable domains and/or polypeptides coupled to one or more groups, residues or moieties.

Abstract: A method is provided for the screening, diagnosis and/or prognosis of neurological diseases. More specifically, new biomarkers are provided for the screening, diagnosis and/or prognosis in a mammal of Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, vascular dementia and/or depression. The method further provides for the differential diagnosis in a mammal of Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, vascular dementia and/or depression.