The present invention relates to a biotin moiety-conjugated polypeptide and a pharmaceutical composition for oral administration comprising the same, wherein the polypeptide according to the present invention has an excellent in vivo oral bioavailability.

Disclosed are multimeric compounds of K1 domains from the Hepatocyte Growth Factor/Scatter Factor (HGF/SF) being able to induce activation of the tyrosine kinase receptor MET and their uses.

The disclosure provides modified biotin-binding proteins which can be expressed in soluble form in high yield in bacteria. Also provided are fusion proteins comprising the modified biotin-binding protein and an antigen. The disclosure further provides non-hemolytic variants of alpha-hemolysin from S. aureus and fusion protein comprising non-hemolytic variant of alpha-hemolysin and a biotin-binding domains. Immunogenic compositions comprising the proteins are also disclosed and use of such immunogenic compositions for inducing an immune response or for vaccinating a subject are also disclosed.

The present invention provides the modular design and assembly of novel targeting bio-conjugates, exclusively assembled by means of biotin-biotin binding element conjugation, comprising mono-biotinylated cell binding component, a tetrameric biotin-binding element, and mono-biotinylated payload for therapeutic and diagnostic purposes. In addition, there is provided a method of delivering the payload, such as therapeutic oligonucleotides, via mono-biotinylated targeting devices, such as antibodies or ligands, into eukaryotic cells by means of receptor-mediated endocytosis. The targeting bio-conjugates are suitable for use in the areas of medicine, pharmacy and biomedical research.

The present disclosure is directed to a system for displaying antigens. This system includes an outer membrane vesicle comprising a lipid bilayer and a synthetic antigen receptor comprising an outer membrane scaffold protein fused to a biotin-binding protein, where the outer membrane scaffold protein is incorporated in the lipid bilayer and the biotin-binding protein is displayed outside the outer membrane vesicle. Also disclosed are therapeutic compositions, nucleic acid constructs, expression vectors, and methods of eliciting an immune response in a subject.

It is an object of the present invention to provide a conjugate of a duocarmycin derivative and a biotin-modified dimer, which is useful for pretargeting methods. According to the present invention, a compound represented by the following formula (1) or formula (2) is provided:

##STR00001## wherein R.sub.1 and R.sub.2 each independently represent a hydrogen atom, a lower alkyl group, or a lower alkoxycarbonyl group; one of R.sub.3, R.sub.4, and R.sub.5 represents —O-L.sub.7-(Xaa).sub.m-L.sub.6-N.sub.3, and the remaining two each independently represent a hydrogen atom, a lower alkyl group, or a lower alkoxycarbonyl group; X represents a reactive group; L.sub.6 and L.sub.7 each independently represent a divalent linking group; Xaa represents an amino acid residue; m represents an integer of 2 to 10; and Me represents a methyl group.

The invention relates to methods of sonodynamic therapy comprising the co-administration of a microbubble-chemotherapeutic agent complex together with a microbubble-sonosensitiser complex. It further relates to pharmaceutical compositions comprising these complexes and their use in methods of sonodynamic therapy and/or sonodynamic diagnosis. Such methods find particular use in the treatment of cancer, e.g. pancreatic cancer.

The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, and/or treat a blood coagulation disorder in a subject.

The present disclosure provides a method of covalently modifying a biological macromolecule, the method comprising subjecting a reaction mixture comprising: (a) a biological macromolecule comprising one or more thiol groups; and (b) a molecule comprising one or more olefin or alkyne moieties to a radical reaction under conditions sufficient to produce the covalently modified biological macromolecule. The present disclosure also provides a method of covalently modifying a biological macromolecule, the method comprising subjecting a reaction mixture comprising: (a) a molecule comprising one or more thiol groups; and (b) biological macromolecule comprising one or more olefin or alkyne moieties to a radical reaction under conditions sufficient to produce the covalently modified biological macromolecule. The present disclosure further provides a covalently modified biological macromolecule prepared by any of disclosed methods. The covalently modified biological macromolecules may be further crosslinked to form a scaffold.

The present invention relates to non peptidic, heterobivalent molecules (HBM) that are able to simultaneously bind a surface target protein as well as an endogenous or exogenous human antibody protein and induce immune effector function. More specifically, the present invention relates to agents capable of binding to a chemokine receptor and inducing the depletion of chemokine receptor positive subsets of pathogenic cells in a subject for use in the treatment and/or prevention of cancer, inflammatory, autoimmune and allergic disease.