Abstract: The present invention relates to drug fusions that have improved serum half lives. These fusions and conjugates comprise polypeptides, immunoglobulin (antibody) single variable domains and GLP and/or exendin molecules. The invention further relates to uses, formulations, compositions and devices comprising such drug fusions and conjugates.

Abstract: The invention relates to antigen-binding constructs comprising a protein scaffold which are linked to one or more epitope-binding domains wherein the antigen-binding construct has at least two antigen binding sites at least one of which is from an epitope binding domain and at least one of which is from a paired VH/VL domain, methods of making such constructs and uses thereof.

Abstract: The invention relates to anti-VEGF polypeptides and antibody single variable domains (dAbs) that are resistant to degradation by a protease, as well as antagonists comprising these. The polypeptides, dAbs and antagonists are useful for pulmonary administration, oral administration, delivery to the lung and delivery to the GI tract of a patient, as well as for treating cancer and inflammatory disease, such as arthritis.

Abstract: The invention relates to anti-TNFR1 polypeptides and antibody single variable domains (dAbs) that are resistant to degradation by a protease, as well as antagonists comprising these. The polypeptides, dAbs and antagonists are useful for as therapeutics and/or prophylactics that are likely to encounter proteases when administered to a patient, for example for pulmonary administration, oral administration, delivery to the lung and delivery to the GI tract of a patient, as well as for treating inflammatory disease, such as arthritis or COPD.

Abstract: The invention relates to anti-IL-1R1 polypeptides and antibody single variable domains (dAbs) that are resistant to degradation by a protease, as well as antagonists comprising these. The polypeptides, dAbs and antagonists are useful for as therapeutics and/or prophylactics that are likely to encounter proteases when administered to a patient, for example for pulmonary administration, oral administration, delivery to the lung and delivery to the GI tract of a patient, as well as for treating inflammatory disease, such as arthritis or COPD.

Abstract: The invention relates to a method for selecting, isolating and/or recovering a peptide or polypeptide from a library or a repertoire of peptides and polypeptides (e.g., a display system) that is resistant to degradation by a protease such as a protease found in the GI tract or pulmonary tissue of a human. Generally, the method comprises providing a library or repertoire of peptides or polypeptides, combining the library or repertoire with a protease under conditions suitable for protease activity, and selecting, isolating and/or recovering a peptide or polypeptide that is resistant to degradation by the protease and has a desired biological activity. The selected peptides and polypeptides have utility as therapeutics, eg for treating disease or conditions of GI tract or pulmonary tissue in humans.

Abstract: The invention relates to anti-VEGF polypeptides and antibody single variable domains (dAbs) that are resistant to degradation by a protease, as well as antagonists comprising these. The polypeptides, dAbs and antagonists are useful for pulmonary administration, oral administration, delivery to the lung and delivery to the GI tract of a patient, as well as for treating cancer and inflammatory disease, such as arthritis.

Abstract: The present invention provides further developments in the screening of antibody polypeptide libraries. The invention also provides novel isolated antibody polypeptides obtainable by the methods of the invention.

Abstract: The invention provides a dual-specific ligand comprising a first immunoglobulin variable domain having a first binding specificity and a complementary or non-complementary immunoglobulin variable domain having a second binding specificity.

Abstract: The present invention relates to polypeptides e.g. protease resistant polypeptides, immunoglobulin (antibody) single variable domains e.g. which are protease resistant and also to vascular endothelial growth factor (VEGF) antagonists comprising these. The invention further relates to uses, formulations, and compositions comprising such polypeptides e.g. for delivery to the eye.

Abstract: The invention relates to antigen-binding constructs comprising a protein scaffold which are linked to one or more epitope-binding domains wherein the antigen-binding construct has at least two antigen binding sites at least one of which is from an epitope binding domain and at least one of which is from a paired VH/VL domain, methods of making such constructs and uses thereof.

Abstract: Proteins which have activity as anticoagulants and/or serine protease inhibitors and have at least one NAP domain and are described. Certain of these proteins have factor Xa inhibitory activity and others have activity as inhibitors of factor VIIa/TF. These proteins can be isolated from natural sources as nematodes, chemically synthesized or made by recombinant methods using various DNA expression systems.

Abstract: Proteins which have activity as anticoagulants and/or serine protease inhibitors and have at least one NAP domain and are described. Certain of these proteins have factor Xa inhibitory activity and others have activity as inhibitors of factor VIIa/TF. These proteins can be isolated from natural sources as nematodes, chemically synthesized or made by recombinant methods using various DNA expression systems.

Abstract: Herein, immunoglobulin variable region polypeptides are fused at their N-terminus to a bacterial signal sequence. In one embodiment, the immunoglobulin variable region polypeptides are fused to a tag that that is placed in between a bacteriophage signal sequence and the N-terminus of the immunoglobulin variable region polypeptide. In another embodiment, the N-termini of single-domain antibodies (dAb) are fused to a bacterial signal sequence in the absence of a tag. In a further embodiment, the immunoglobulin variable region antibody fusion proteins are fused to a bacteriophage coat protein and expressed on the surface of bacteriophage providing an efficient way to select small antibody fragments that are labeled and that have high affinity to target ligand.

Abstract: An in vitro method for constructing a concatenated head-to-tail repertoire of target nucleic acid sequences is revealed. In particular, the method relates to cycles of concatenation whereby after a single cycle of concatenation, not more than two identical copies of each target nucleic acid sequence are linked together head-to-tail on the same molecule of DNA. The present method ensures that each molecule of a concatenated repertoire is derived from a single template target sequence of the starting repertoire.