Abstract: The present invention relates to novel osteoprotegerin variant proteins (GYPs) that demonstrate reduced binding affinity for their ligand TRAIL when compared to wild-type osteoprotegerin. Nucleic acids which encode these GYPs are also provided. Recombinant vectors and host cells expressing these GYPs are also encompassed as are methods of producing recombinant GYPs. The present invention also relates to compositions comprising these GYPs, and to methods of treating bone diseases characterised by increased bone turnover and/or loss. The GYPs of the invention are useful for preventing bone resorption and may be used to treat any condition resulting in abnormal bone turnover or bone loss such as osteoporosis, hypercalcemia, Paget's disease of bone, multiple myeloma, bone cancer and bone loss due to rheumatoid arthritis or osteomyelitis, and the like.

Abstract: The present invention relates to novel osteoprotegerin variant proteins (OVPs) that demonstrate reduce binding affinity for their ligand TRAIL when compared to wild-type osteoprotegerin. Nucleic acids which encode these OVPs are also provided. Recombinant vectors and host cells expressing these OVPs are also encompassed as are methods of producing recombinant OVPs. The present invention also relates to compositions comprising these OVPs, and to methods of treating bone diseases characterised by increased bone turnover and/or loss. The OVPs of the invention are useful for preventing bone resorption and may be used to treat any condition resulting in abnormal bone turnover or bone loss such as osteoporosis, hypercalcemia, Paget's disease of bone, multiple myeloma, bone cancer and bone loss due to rheumatoid arthritis or osteomyelitis, and the like.

Abstract: The use of RNA-replicases for introducing mutations into and selecting for improved RNA molecules is described. The use of ribavirin, or a derivative/analogue thereof, in methods for introducing one or more mutations during replication or transcription of a target nucleic acid molecule is also described. These methods can be used to screen for nucleic acids, or proteins encoded thereby, with altered or new activity. Also provided are kits comprising ribavirin, or a derivative/analogue thereof, for use in mutagenesis procedures.

Abstract: The present invention relates to novel osteoprotegerin variant proteins (OVPs) that demonstrate reduced binding affinity for their ligand TRAIL when compared to wild-type osteoprotegerin. Nucleic acids which encode these OVPs are also provided. Recombinant vectors and host cells expressing these OVPs are also encompassed as are methods of producing recombinant OVPs. The present invention also relates to compositions comprising these OVPs, and to methods of treating bone diseases characterised by increased bone turnover and/or loss. The OVPs of the invention are useful for preventing bone resorption and may be used to treat any condition resulting in abnormal bone turnover or bone loss such as osteoporosis, hypercalcemia, Paget's disease of bone, multiple myeloma, bone cancer and bone loss due to rheumatoid arthritis or osteomyelitis, and the like.

Abstract: The present invention relates to binding moieties comprising at least one monomeric V-like domain (VLD) derived from a non-antibody ligand, the at least one monomeric V-like domain being characterised in that at least one CDR loop structure or part thereof is modified or replaced such that the solubility of the modified VLD is improved when compared with the unmodified VLD.

Abstract: The present invention relates to binding moieties comprising at least one monomeric V-like domain (VLD) derived from a non-antibody ligand, the at least one monomeric V-like domain being characterised in that at least one CDR loop structure or part thereof is modified or replaced such that the solubility of the modified VLD is improved when compared with the unmodified VLD.

Abstract: Provided is a method for the mutation, synthesis and selection of a protein of interest, by first incubating a replicable RNA molecule encoding the protein with ribonucleoside triphosphate precursors of RNA and an RNA-directed RNA polymerase, such that the RNA-directed RNA polymerase replicates the RNA molecule but introduces mutations thereby generating a population of mutant RNA molecules. The mutant RNA molecules are then incubated with a translation system under conditions which result in the synthesis of a population of mutant proteins. After translation, the mutant proteins are linked to their encoding RNA molecules, and one or more mutant proteins of interest are selected.

Abstract: The present invention relates to novel osteoprotegerin variant proteins (OVPs) that demonstrate reduce binding affinity for their ligand TRAIL when compared to wild-type osteoprotegerin. Nucleic acids which encode these OVPs are also provided. Recombinant vectors and host cells expressing these OVPs are also encompassed as are methods of producing recombinant OVPs. The present invention also relates to compositions comprising these OVPs, and to methods of treating bone diseases characterised by increased bone turnover and/or loss. The OVPs of the invention are useful for preventing bone resorption and may be used to treat any condition resulting in abnormal bone turnover or bone loss such as osteoporosis, hypercalcemia, Paget's disease of bone, multiple myeloma, bone cancer and bone loss due to rheumatoid arthritis or osteomyelitis, and the like.

Abstract: The invention relates to a chimeric antibody conjugate comprising an antigen binding region of a non-human antibody and an immunoglobulin constant region which comprises at least one CH domain or epitope thereof, with the proviso that the constant region is not a naturally occurring FC fragment. A bifunctional molecule for use in labelling an antibody derived from a first species, the bifunctional molecule comprising a binding region which binds to the antibody of the first species or to one or more groups provided thereon, and a constant region derived from an antibody of a second species, the constant region comprising at least one CH domain or an epitope thereof. The present invention relates to bifunctional molecules and complexes which are useful as positive control reagents in antibody based diagnostic tests. The present invention also relates to polynucleotides encoding these bifunctional molecules, and to diagnostic assays involving the use of these molecules.

Abstract: A chimeric antibody conjugate comprising an antigen binding region of a non-human antibody and an immunoglobulin constant region which comprises at least one CH domain or epitope thereof, with the proviso that the constant region is not a naturally occurring FC fragment. A bifunctional molecule for use in labelling an antibody derived from a first species, the bifunctional molecule comprising a binding-region which binds to the antibody of the first species or to one or more groups provided thereon, and a constant region derived from an antibody of a second species, the constant region comprising at least one CH domain or an epitope thereof. The present invention relates to bifunctional molecules and complexes which are useful as positive control reagents in antibody based diagnostic tests. The present invention also relates to polynucleotides encoding these bifunctional molecules, and to diagnostic assays involving the use of these molecules.

Abstract: The use of RNA-replicases for introducing mutations into and selecting for improved RNA molecules is described. The use of ribavirin, or a derivative/analogue thereof, in methods for introducing one or more mutations during replication or transcription of a target nucleic acid molecule is also described. These methods can be used to screen for nucleic acids, or proteins encoded thereby, with altered or new activity. Also provided are kits comprising ribavirin, or a derivative/analogue thereof, for use in mutagenesis procedures.

Abstract: Provided is a method for the mutation, synthesis and selection of a protein of interest, by first incubating a replicable RNA molecule encoding the protein with ribonucleoside triphosphate precursors of RNA and an RNA-directed RNA polymerase, such that the RNA-directed RNA polymerase replicates the RNA molecule but introduces mutations thereby generating a population of a mutant RNA molecules. The mutant RNA molecules are then incubated with a translation system under conditions which result in the synthesis of a population of mutant proteins. After translation, the mutant proteins are linked to their encoding RNA molecules, and one or more mutant proteins of interest are selected.

Abstract: The present invention provides a method for the mutation, synthesis and selection of a protein which binds to a target molecule, the method comprising: (a) incubating a replicable mRNA molecule encoding the protein with ribonucleoside triphosphate precursors of RNA and an RNA-directed RNA polymerase, wherein the RNA-directed RNA polymerase replicates the mRNA molecule but introduces mutations thereby generating a population of mutant mRNA molecules; (b) incubating the mutant mRNA molecules from step (a) with a translation system under conditions which results in the synthesis of population of mutant proteins such that after translation, mutant proteins are linked to their encoding mRNA molecules thereby forming a population of mutant proteins such that after translation, mutant proteins are linked to their encoding mRNA molecules thereby forming a population of mutant/mRNA complexes; (c) selecting one or more mutant protein/mRNA complex(es) by exposing the population of mutant protein/mRNA complexes from step

Abstract: The present invention relates generally to a method for detecting a nucleic acid molecule having a particular nucleotide sequence. Such a nucleic acid molecule is generally referred to as the “target” sequence or molecule. The method of the present invention generally comprises the use of competitive priming of pre- or post-amplified nucleic acid molecules. The nucleic acid molecules subjected to such primer interrogation are generally immobilized to a solid support by hybridization of a target molecule to a primer anchored to a solid phase. Amplimer-mediated bridging of a particular primer, -labelled or unlabelled, is then used to detect the presence of a primer having a selected sequence. The method of the present invention is useful in a range of applications including inter alia diagnosis, nucleotide sequencing and the screening for nucleic acid-modifying molecules such as carcinogens.