Abstract: The present invention provides a high affinity, antigen-specific, soluble heavy chain-only antibody which: lacks hallmark camelid-related amino acid substitutions and has FR2 substitutions which are not found in antibodies which comprise heavy and light chain; shows increased net hydrophobicity within CDR1 and an increased number of charged amino acids present in CDR3; and comprises one or more amino acid substitutions within the framework ?-pleated sheet leading to increased net hydrophobicity within FR1 and an increased number of charged amino acids present in FR3. Also provided are VII domains having the same properties, gene segments for their production, methods for their production, transgenic animals and uses of the antibody of the VH domains in therapy.

Abstract: A non-human mammal containing an endogenous lambda light chain gene locus, an endogenous kappa light chain gene locus and an endogenous heavy chain gene locus, each of which can re-arrange so that immunoglobulin heavy and light chain genes are formed and expressed in B-cells following antigen challenge but said loci have been mutated so that the ability to form functional immunoglobulin tetramers comprising re-arranged heavy and light chains produced from said mutated loci has been substantially reduced or eliminated.

Abstract: The present invention relates to the manufacture of a diverse repertoire of functional heavy chain-only antibodies that undergo affinity maturation, and uses thereof. The invention also relates to the manufacture and use of a diverse repertoire of class-specific heavy chain-only antibodies and to the manufacture and use of multivalent polypeptide complexes with antibody heavy chain functionality, preferably antibody heavy chain binding functionality, constant region effector activity and, optionally, additional effector functions. The present invention also relates to a method of generation of fully functional heavy chain-only antibodies in transgenic mice in response to antigen challenge. In particular, the present invention relates to a method for the generation of human antigen-specific, high affinity, heavy chain-only antibodies of any class, or mixture of classes and the isolation and expression of fully functional VH antigen-binding domains.

Abstract: The present invention relates to the manufacture of a diverse repertoire of functional heavy chain-only antibodies that undergo affinity maturation, and uses thereof. The invention also relates to the manufacture and use of a diverse repertoire of class-specific heavy chain-only antibodies and to the manufacture and use of multivalent polypeptide complexes with antibody heavy chain functionality, preferably antibody heavy chain binding functionality, constant region effector activity and, optionally, additional effector functions. The present invention also relates to a method of generation of fully functional heavy chain-only antibodies in transgenic mice in response to antigen challenge. In particular, the present invention relates to a method for the generation of human antigen-specific, high affinity, heavy chain-only antibodies of any class, or mixture of classes and the isolation and expression of fully functional VH antigen-binding domains.

Abstract: The present invention relates to the manufacture of a diverse repertoire of functional heavy chain-only antibodies that undergo affinity maturation, and uses thereof. The invention also relates to the manufacture and use of a diverse repertoire of class-specific heavy chain-only antibodies and to the manufacture and use of multivalent polypeptide complexes with antibody heavy chain functionality, preferably antibody heavy chain binding functionality, constant region effector activity and, optionally, additional effector functions. The present invention also relates to a method of generation of fully functional heavy chain-only antibodies in transgenic mice in response to antigen challenge. In particular, the present invention relates to a method for the generation of human antigen-specific, high affinity, heavy chain-only antibodies of any class, or mixture of classes and the isolation and expression of fully functional VH antigen-binding domains.

Abstract: The present invention relates to the manufacture of a diverse repertoire of functional heavy chain-only antibodies that undergo affinity maturation, and uses thereof. The invention also relates to the manufacture and use of a diverse repertoire of class-specific heavy chain-only antibodies and to the manufacture and use of multivalent polypeptide complexes with antibody heavy chain functionality, preferably antibody heavy chain binding functionality, constant region effector activity and, optionally, additional effector functions. The present invention also relates to a method of generation of fully functional heavy chain-only antibodies in transgenic mice in response to antigen challenge. In particular, the present invention relates to a method for the generation of human antigen-specific, high affinity, heavy chain-only antibodies of any class, or mixture of classes and the isolation and expression of fully functional VH antigen-binding domains.

Abstract: The present invention relates to the manufacture of mono, di and multivalent polypeptide binding complexes, also mono, di or multispecific polypeptide binding complexes and uses thereof. The invention also relates to the manufacture and use of a diverse repertoire of antigen specific VH binding domains derived from phage display libraries, transgenic animals or natural sources. Preferably the VH binding domains and the dimerisation domains comprise human sequences. The polypeptide binding complexes comprise homo or heterodimerisation domains with four antigen binding [VH] domains fused at the amino and carboxyl termini of the dimerisation domains preferably using natural hinge or linker peptides. Where the polypeptide binding complexes lack CH2-CH3 effector functions they are preferably less than 120 kDa in size. Routes of manufacture are described herein.

Abstract: Described and claimed is the combined use of an electric field and ultrasound to ablate a cell or tissue, the use of ultrasound to disrupt a nucleated cell which has previously been electrosensitised by exposure to an electric field, and the use of an electric field for sensitising a nucleated cell to ultrasound. We furthermore disclose the use of electricity to disrupt a nucleated cell which has previously been sensitised by exposure to ultrasound, and the use of ultrasound for sensitising a nucleated cell to electricity.

Abstract: A method is provided for measuring in vivo in a transgenic non-human multicellular organism the activity of a cellular enzyme, which organism is transgenic by virtue of comprising one or more nucleic acid constructs encoding a binding domain and a binding partner thereof wherein: (i) the binding domain and/or binding partner comprise a site subject to post-translational modification by the cellular enzyme; (ii) modification of the site by the enzyme affects the interaction between the binding domain and the binding partner; and (iii) the binding domain and the binding partner each comprise a detectable label such that when the binding domain and binding partner interact, a detectable physical characteristic of one or both of the labels is altered, which method comprises measuring the interaction between the binding domain and the binding partner by measuring changes in the physical characteristic in one or more cells of the transgenic organism. A transgenic non-human multicellular organism is also provided.

Abstract: The invention relates to a method for selectively releasing an agent loaded into a red blood cell, comprising electrosensitising the red blood cell by application of an electric field and subsequently disrupting the cell selectively using ultrasound.

Abstract: Described and claimed is the combined use of an electric field and ultrasound to ablate a cell or tissue, the use of ultrasound to disrupt a nucleated cell which has previously been electrosensitised by exposure to an electric field, and the use of an electric field for sensitising a nucleated cell to ultrasound. We furthermore disclose the use of electricity to disrupt a nucleated cell which has previously been sensitised by exposure to ultrasound, and the use of ultrasound for sensitising a nucleated cell to electricity.

Abstract: The invention encompasses a transfection complex comprising a polypeptide comprising the contiguous 29 amino acids: 6G's, 2F's, 2L's, 1W, 4R's, 2E's, 2N's, 3K's, 1T, 1S, 1A, 1Y, 1M, 1C, and 1I, and having additional cationic residues to provide a net number of positive charges of equal to or greater than 8, and an isolated nucleic acid, and methods of transfecting cells using this transfection complex. The invention also includes a polypeptide having an amino acid composition including these 29 amino acids, as well as mixtures of polypeptides in which this polypeptide is present.

Abstract: A method is provided for measuring in vivo in a transgenic non-human multicellular organism the activity of a cellular enzyme, which organism is transgenic by virtue of comprising one or more nucleic acid constructs encoding a binding domain and a binding partner thereof, wherein: (i) the binding domain and/or binding partner comprise a site subject to post-translational modification by the cellular enzyme; (ii) modification of the site by the enzyme affects the interaction between the binding domain and the binding partner; and (iii) the binding domain and the binding partner each comprise a detectable label such that when the binding domain and binding partner interact, a detectable physical characteristic of one or both of the labels is altered, which method comprises measuring the interaction between the binding domain and the binding partner by measuring changes in said physical characteristic in one or more cells of the transgenic organism. A transgenic non-human multicellular organism is also provided.

Abstract: The invention encompasses a transfection complex comprising a polypeptide comprising the contiguous 29 amino acids: 6G's, 2F's, 2L's, 1W, 4R's, 2E's, 2N's, 3K's, 1T, 1S, 1A, 1Y, 1M, 1C, and 1I, and having additional cationic residues to provide a net number of positive charges of equal to or greater than 8, and an isolated nucleic acid, and methods of transfecting cells using this transfection complex. The invention also includes a polypeptide having an amino acid composition including these 29 amino acids, as well as mixtures of polypeptides in which this polypeptide is present.

Abstract: A method for delivering to a target cell in a population of cells a biologically active agent comprising the steps of exposing the population of cells to a complex comprising the biologically active agent and a ligand capable of binding to the target cell and subjecting the population of cells to an electric field while maintaining cell viability.