Abstract: A method is disclosed for inducing cell-mediated immunity against cellular antigens. More specifically, the invention provides for a method for inducing cytotoxic T-lymphocyte immunity against weak antigens, notably self-proteins. The method entails that antigen presenting cells are induced to present at least one CTL epitope of the weak antigen and at the same time presenting at least one foreign T-helper lymphocyte epitope. In a preferred embodiment, the antigen is a cancer specific antigen, e.g. PSM, Her2, or FGF8b. The method can be exercised by using traditional polypeptide vaccination, but also by using live attenuated vaccines or nucleic acid vaccination. The invention furthermore provides immunogenic analogues of PSM, Her2 and FGF8b, as well as nucleic acid molecules encoding these analogues. Also vectors and transformed cells are disclosed. The invention also provides for a method for identification of immunogenic analogues of weak or non-immunogenic antigens.

Abstract: A method is disclosed for inducing cell-mediated immunity against cellular antigens. More specifically, the invention provides for a method for inducing cytotoxic T-lymphocyte immunity against weak antigens, notably self-proteins. The method entails that antigen presenting cells are induced to present at least one CTL epitope of the weak antigen and at the same time presenting at least one foreign T-helper lymphocyte epitope. In a preferred embodiment, the antigen is a cancer specific antigen, e.g. PSM, Her2, or FGF8b. The method can be exercised by using traditional polypeptide vaccination, but also by using live attenuated vaccines or nucleic acid vaccination. The invention furthermore provides immunogenic analogues of PSM, Her2 and FGF8b, as well as nucleic acid molecules encoding these analogues. Also vectors and transformed cells are disclosed. The invention also provides for a method for identification of immunogenic analogues of weak or non-immunogenic antigens.

Abstract: The present invention relates to implants used for alleviating and/or preventing conditions relating to damaged joints involving articulating surfaces. The implants comprise fibre of polymer and/or metal, and can be used as an artificial joint, as part of an artificial joint or as an artificial joint spacer made to replace the missing cartilage or to improve the slidability between two natural and/or artificial components of the body, or between a natural and artificial component. The product of the invention can be used to partly or entirely coat medical products or to make up implant partly or entirely.

Abstract: A modified human TNF? molecule is capable of raising neutralizing antibodies towards unmodified human TNF? following administration of the modified TNF? to a human host, wherein one or more peptide fragments of the human TNF? molecule has been substituted by one or more peptides containing immunodominant T cell epitopes or a truncated form of the molecule containing the immunodominant epitope and one or both flanking regions of the human TNF?-molecule containing at least one TNF? B cell epitope, wherein the substitution introduces a substantial change in the amino acid sequence of any one of the strands of the front ?-sheet, in any one of the connecting loops, or in any one of the B?, I, or D strands of the back ?-sheet.

Abstract: The present invention provides for an immunogenic analogue of a human TNF? protein, wherein said analogue comprises an immunogenized monomeric TNF? polypeptide or TNF? di- or timer, and wherein the analogue further comprises a toxicity reducing or abolishing mutation selected from the group consisting of Y87S, D143N or A145R, the amino acid numbering setting out from the N-terminal valine in human TNF?. The invention also provides for a nucleic acid fragment encoding the analogue as well as to vectors and transformed cells useful in the preparation of the analogue. Also disclosed are methods of down-regulating TNF? in a subject in need thereof.

Abstract: Disclosed are novel methods for increasing muscle mass by means of immunization against Growth Differentiation Factor 8 (GDF-8, myostatin). Immunization is preferably effected by administration of analogues of GDF-8 which are capable of inducing antibody production against homologous GDF-8. Especially preferred as an immunogen is homologous GDF-8 which has been modified by introduction of one single or a few foreign, immunodominant and promiscuous T-cell epitopes while substantially preserving the tertiary structure of the homologous GDF-8. Also disclosed are nucleic acid vaccination against GDF-8 and vaccination using live vaccines as well as methods and means useful for the vaccination. Such methods and means include methods for identification of useful immunogenic GDF-8 analogues, methods for the preparation of analogues and pharmaceutical formulations, as well as nucleic acid fragments, vectors, transformed cells, polypeptides and pharmaceutical formulations.

Abstract: Disclosed are novel methods for increasing muscle mass by means of immunization against Growth Differentiation Factor 8 (GDF-8, myostatin). Immunization is preferably effected by administration of analogues of GDF-8 which are capable of inducing antibody production against homologous GDF-8. Especially preferred as an immunogen is homologous GDF-8 which has been modified by introduction of one single or a few foreign, immunodominant and promiscuous T-cell epitopes while substantially preserving the tertiary structure of the homologous GDF-8. Also disclosed are nucleic acid vaccination against GDF-8 and vaccination using live vaccines as well as methods and means useful for the vaccination. Such methods and means include methods for identification of useful immunogenic GDF-8 analogues, methods for the preparation of analogues and pharmaceutical formulations, as well as nucleic acid fragments, vectors, transformed cells, polypeptides and pharmaceutical formulations.

Abstract: A method is disclosed for inducing cell-mediated immunity against cellular antigens. More specifically, the invention provides for a method for inducing cytotoxic T-lymphocyte immunity against weak antigens, notably self-proteins. The method entails that antigen presenting cells are induced to present at least one CTL epitope of the weak antigen and at the same time presenting at least one foreign T-helper lymphocyte epitope. In a preferred embodiment, the antigen is a cancer specific antigen, e.g. PSM, Her2, or FGF8b. The method can be exercised by using traditional polypeptide vaccination, but also by using live attenuated vaccines or nucleic acid vaccination. The invention furthermore provides immunogenic analogues of PSM, Her2 and FGF8b, as well as nucleic acid molecules encoding these analogues. Also vectors and transformed cells are disclosed. The invention also provides for a method for identification of immunogenic analogues of weak or non-immunogenic antigens.

Abstract: A method is disclosed for inducing cell-mediated immunity against cellular antigens. More specifically, the invention provides for a method for inducing cytotoxic T-lymphocyte immunity against weak antigens, notably self-proteins. The method entails that antigen presenting cells are induced to present at least one CTL epitope of the weak antigen and at the same time presenting at least one foreign T-helper lymphocyte epitope. In a preferred embodiment, the antigen is a cancer specific antigen, e.g. PSM, Her2, or FGF8b. The method can be exercised by using traditional polypeptide vaccination, but also by using live attenuated vaccines or nucleic acid vaccination. The invention furthermore provides immunogenic analogues of PSM, Her2 and FGF8b, as well as nucleic acid molecules encoding these analogues. Also vectors and transformed cells are disclosed. The invention also provides for a method for identification of immunogenic analogues of weak or non-immunogenic antigens.

Abstract: The present invention relatas to novel immunogenic variants of multimeric proteins such as immunogenic variants of interleukin 5 (IL5) and tumour necrosis factor alpha (TNF, TNF&agr;). The variants are, besides from being immunogenic in the autologous host, also highly similar to the native 3D structure of the proteins from which they are derived. Certain variants are monomeric mimics of the multimers, where peptide linkers (inert or T helper epitope containing) ensure a spatial organisation of the monomomer units that facilitate correct folding. A subset of variants are monomer TNF&agr; variants that exhibit a superior capability of assembling into multimers with a high structural similarity to the native protein. Also disclosed are methods of treatment and production of the variants as well as DNA fragments, vectors, and host cells.

Abstract: A method is disclosed for inducing cell-mediated immunity against cellular antigens. More specifically, the invention provides for a method for inducing cytotoxic T-lymphocyte immunity against weak antigens, notably self-proteins. The method entails that antigen presenting cells are induced to present at least one CTL epitope of the weak antigen and at the same time presenting at least one foreign T-helper lymphocyte epitope. In a preferred embodiment, the antigen is a cancer specific antigen, e.g. PSM, Her2, or FGF8b. The method can be exercised by using traditional polypeptide vaccination, but also by using live attenuated vaccines or nucleic acid vaccination. The invention furthermore provides immunogenic analogues of PSM, Her2 and FGF8b, as well as nucleic acid molecules encoding these analogues. Also vectors and transformed cells are disclosed. The invention also provides for a method for identification of immunogenic analogues of weak or non-immunogenic antigens.

Abstract: The present invention relates to a novel method and formulation for the induction of immune responses against polypeptide antigens. In particular, the invention provides a method and formulation for induction of cytotoxic T cell responses against a polypeptide antigen of choice. The formulations are characterized by containing chitosan in admixture with the polypeptide antigen, preferably in the form of microparticles that may be cross-linked.

Abstract: The present invention relatas to novel immunogenic variants of multimeric proteins such as immunogenic variants of interleukin 5 (IL5) and tumour necrosis factor alpha (TNF, TNF&agr;). The variants are, besides from being immunogenic in the autologous host, also highly similar to the native 3D structure of the proteins from which they are derived. Certain variants are monomeric mimics of the multimers, where peptide linkers (inert or T helper epitope containing) ensure a spatial organisation of the monomomer units that facilitate correct folding. A subset of variants are monomer TNF&agr; variants that exhibit a superior capability of assembling into multimers with a high structural similarity to the native protein. Also disclosed are methods of treatment and production of the variants as well as DNA fragments, vectors, and host cells.

Abstract: Biologically active peptides and nucleic acids are identified by a method comprising the following steps: (a) production of a pool of appropriate vectors each containing totally or partly random DNA sequences, (b) efficient transduction of said vectors into a number of identical eukaryotic cells in such a way that a single ribonucleic acid and possibly peptide is expressed or a limited number of different random ribonucleic acids and peptides are expressed by each cell, (c) screening of said transduced cells to see whether some of them have changed a certain phenotypic trait, (d) selection and cloning of said changed cells, (e) isolation and sequencing of the vector DNA in said phenotypically changed cells, and (f) deducing the ribonucleic acid and peptide sequences from the DNA sequence. The peptide sequences may be introduced into or fused to a larger protein, preferably an antibody molecule or a fragment thereof.

Abstract: A novel method for utilizing the immune apparatus to remove and/or down-regulate self-proteins. The method consists in providing a self-protein analog by molecular biological means by substitution of one or more peptide fragments of the self-protein by corresponding number of peptides known to contain immunodominant foreign T-cell epitopes, said substitution being carried out so as to essentially preserve the overall tertiary structure of the original self-protein. This render the self-protein immunogenic and leads to a rapid induction of high-titered autoantibodies against the native self-proteins. The modulated self-proteins can be used to prepare vaccines against undesirable proteins in humans or animals, said vaccine being useful as therapeutics against a number of diseases, e.g. cancer, chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel diseases, allergic symptoms or diabetes mellitus.

Abstract: A library is composed of viral vectors in which each of the vectors (a) involves a peptide expression cassette containing a random nucleotide sequence, (b) transduces a eukaryotic cell to allow expression of the random nucleotide sequence, and (c) is produced by (i) conventional random oligonucleotide synthesis or (ii) random codon synthesis where codons encode an even distribution of random amino acids.

Abstract: A method of modifying the binding properties on a surface of a solid phase on which there are nucleophilic groups, which is characterized in that the surface is treated with a solution of an activated polysaccharide; a method of immobilizing a chemical compound to a solid phase on which there are immobilized activated polysaccharides, whereby the chemical compound is contacted with the surface of the solid phase the binding properties of which are modified by the method according to the invention; an article which is characterized in that to the surface thereof an activated polysaccharide is fixated, such as activated dextran or activated agarose, and use of this article for use in solid phase reactions, in solid phase assay, solid phase peptide synthesis, solid phase nucleotide synthesis, solid phase enzyme processing, and joining of biological surfaces.

Abstract: A method for modifying the surface of a solid polymer wherein the polymer surface is exposed to an aqueous solution containing a two-ring heterocyclic compound that is described in more detail herein. The polymer and the two-ring heterocyclic compound are irradiated with electromagnetic radiation having a wavelength ranging from about 10 nm to about 400 nm to photochemically immobilize the two-ring heterocyclic compound to the polymer.