Abstract: The invention provides modified forms of bouganin protein having biological activity and a reduced propensity to activate human T cells as compared to the non-modified bouganin protein. The invention also provides T-cell epitope peptides of bouganin, and modified T-cell epitope peptides of bouganin which have a reduced propensity to activate human T cells as compared to the non-modified T-cell epitope peptide. The invention also provides cytotoxins having the having a ligand that binds to a cancer cells attached to the modified bouganin proteins. Also provided are methods of inhibiting or destroying mammalian cancer cells using the cytotoxins of the invention and pharmaceutical compositions for treating human cancer.

Abstract: The invention provides modified forms of bouganin protein having biological activity and a reduced propensity to activate human T cells as compared to the non-modified bouganin protein. The invention also provides T-cell epitope peptides of bouganin, and modified T-cell epitope peptides of bouganin which have a reduced propensity to activate human T cells as compared to the non-modified T-cell epitope peptide. The invention also provides cytotoxins having the having a ligand that binds to a cancer cells attached to the modified bouganin proteins. Also provided are methods of inhibiting or destroying mammalian cancer cells using the cytotoxins of the invention and pharmaceutical compositions for treating human cancer.

Abstract: This invention relates to the fields of immunology and protein therapeutics. The therapeutic proteins are polypeptides to be administered especially to humans. The polypeptides are modified whereby the modification results in a reduced propensity for the polypeptide to elicit an immune response upon administration to the human subject. The invention therefor provides methods for the development of therapeutic polypeptides that are less immunogenic than any non-modified counterpart when used in vivo. The modifications used according to this invention relate, for example, to the introduction of protease cleavage sites, attachment of different molecules or insertion of non-natural amino acids.

Abstract: The present invention relates to a synthetic plant-optimized nucleic acid molecule having a Norwalk virus capsid protein coding nucleotide sequence, and nucleic acid constructs, host cells, expression systems, and plants having the plant-optimized Norwalk virus nucleic acid molecule. The present invention also relates to a method of producing Norwalk virus capsid protein virus-like particles in a transgenic plant or transgenic plant seed transformed with a plant-optimized nucleic acid molecule encoding Norwalk virus capsid protein. The plant or a component thereof can be administered to a subject under conditions effective to immunize the subject against disease resulting from infection by a Norovirus, including Norwalk virus. An oral vaccine for immunization of a subject against Norwalk virus infection is also disclosed.

Abstract: The invention provides modified forms of bouganin protein having biological activity and a reduced propensity to activate human T cells as compared to the non-modified bouganin protein. The invention also provides T-cell epitope peptides of bouganin, and modified T-cell epitope peptides of bouganin which have a reduced propensity to activate human T cells as compared to the non-modified T-cell epitope peptide. The invention also provides cytotoxins having the having a ligand that binds to a cancer cells attached to the modified bouganin proteins. Also provided are methods of inhibiting or destroying mammalian cancer cells using the cytotoxins of the invention and pharmaceutical compositions for treating human cancer.

Abstract: This invention pertains to a TNF alpha-binding polypeptide composition comprising at least one of a modified heavy chain variable region polypeptide or a modified light chain variable region polypeptide that is capable of specifically binding to human TNF alpha. The modified heavy and light chain variable region polypeptides of the TNF alpha binding polypeptide are modified by at least one amino acid residue substitution, deletion or addition and are homologous to the heavy and light chain variable regions, respectively, of a non-human monoclonal antibody that specifically binds human TNF alpha. The polypeptide compositions of the invention comprising modified heavy and light chain variable region polypeptides are less immunogenic in a human than are the homologous heavy and light chain variable region polypeptides from a non-human animal.

Abstract: The invention provides modified forms of bouganin protein having biological activity and a reduced propensity to activate human T cells as compared to the non-modified bouganin protein. The invention also provides T-cell epitope peptides of bouganin, and modified T-cell epitope peptides of bouganin which have a reduced propensity to activate human T cells as compared to the non-modified T-cell epitope peptide. The invention also provides cytotoxins having the having a ligand that binds to a cancer cells attached to the modified bouganin proteins. Also provided are methods of inhibiting or destroying mammalian cancer cells using the cytotoxins of the invention and pharmaceutical compositions for treating human cancer.

Abstract: The invention relates to the modification of antibodies reactive to human tumor necrosis factor alpha (TNF alpha) to result in anti-TNF alpha antibodies that are substantially non-immunogenic or less immunogenic than any non-modified parental antibody when used in vivo. The invention relates also to peptide molecules comprising T-cell epitopes of the V-regions of the parental antibody which are modified by amino acid alteration in order to reduce or eliminate said T-cell epitopes.

Abstract: The invention provides modified forms of bouganin protein having biological activity and a reduced propensity to activate human T cells as compared to the non-modified bouganin protein. The invention also provides T-cell epitope peptides of bouganin, and modified T-cell epitope peptides of bouganin which have a reduced propensity to activate human T cells as compared to the non-modified T-cell epitope peptide. The invention also provides cytotoxins having the having a ligand that binds to a cancer cells attached to the modified bouganin proteins. Also provided are methods of inhibiting or destroying mammalian cancer cells using the cytotoxins of the invention and pharmaceutical compositions for treating human cancer.

Abstract: The invention provides modified forms of bouganin protein having biological activity and a reduced propensity to activate human T cells as compared to the non-modified bouganin protein. The invention also provides T-cell epitope peptides of bouganin, and modified T-cell epitope peptides of bouganin which have a reduced propensity to activate human T cells as compared to the non-modified T-cell epitope peptide. The invention also provides cytotoxins having the having a ligand that binds to a cancer cells attached to the modified bouganin proteins. Also provided are methods of inhibiting or destroying mammalian cancer cells using the cytotoxins of the invention and pharmaceutical compositions for treating human cancer.

Abstract: The present invention relates to the expression of peptides on viral particles, and more particularly to the expression of peptides on the interior or the viral capsid. Methods are described for modifying viruses so that exogenous epitopes are expressed on the interior of the viral capsid. Viruses that can be modified include (+) stranded RNA viruses, especially plant (+) stranded RNA viruses such as the cowpea mosaic virus. Internal expression is especially useful for the expression of hydrophobic epitopes. The modified viral particles also find use as vaccines and as such are capable of eliciting an immune response.

Abstract: A TNF alpha-binding polypeptide composition comprises at least one of a modified heavy chain variable region polypeptide or a modified light chain variable region polypeptide that is capable of specifically binding to human TNF alpha. The modified heavy chain variable region polypeptide and the modified light chain variable region polypeptide each are homologous to respective heavy chain or light chain variable regions of a non-human monoclonal antibody that specifically binds to human TNF alpha. The amino acid residue sequence of at least one of the modified heavy chain variable region polypeptide and the modified light chain variable region polypeptide differs from the amino acid residue sequence of the respective non-human monoclonal antibody heavy chain variable regions or light chain variable regions by at least one amino acid residue substitution, deletion or addition.

Abstract: Mucin peptide epitopes are inserted into the coat protein of a plant virus (e.g., a comovirus such as CPMV) having a beta-barrel structure at an immunogenically effective site, such as in a loop connecting beta sheets or at/near the C-terminus. The resulting chimaeric virus particles are extremely immunogenic, giving better results than KLH conjugation and not requiring the addition of exogenous adjuvant. They are effective at mucosal surfaces, particularly when administered intranasally.

Abstract: The invention provides modified forms of bouganin protein having biological activity and a reduced propensity to activate human T cells as compared to the non-modified bouganin protein. The invention also provides T-cell epitope peptides of bouganin, and modified T-cell epitope peptides of bouganin which have a reduced propensity to activate human T cells as compared to the non-modified T-cell epitope peptide. The invention also provides cytotoxins having the having a ligand that binds to a cancer cells attached to the modified bouganin proteins. Also provided are methods of inhibiting or destroying mammalian cancer cells using the cytotoxins of the invention and pharmaceutical compositions for treating human cancer.

Abstract: The present invention relates to a synthetic plant-optimized nucleic acid molecule having a Norwalk virus capsid protein coding nucleotide sequence, and nucleic acid constructs, host cells, expression systems, and plants having the plant-optimized Norwalk virus nucleic acid molecule. The present invention also relates to a method of producing Norwalk virus capsid protein virus-like particles in a transgenic plant or transgenic plant seed transformed with a plant-optimized nucleic acid molecule encoding Norwalk virus capsid protein. The plant or a component thereof can be administered to a subject under conditions effective to immunize the subject against disease resulting from infection by a Norovirus, including Norwalk virus. An oral vaccine for immunization of a subject against Norwalk virus infection is also disclosed.

Abstract: The invention in particular relates to the modification of a bacterial enzyme carboxypeptidease G2 (CPG2) to result in CPG2 proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo. The present invention relates also to T-cell epitope peptides derived from said non-modified protein by means of which it is possible to create modified CPG2 variants with reduced immunogenicity. These polypeptides are suitable particularly for therapeutic use in humans.

Abstract: The invention relates to the modification of antibodies reactive to human tumor necrosis factor alpha (TNF alpha) to result in anti-TNF alpha antibodies that are substantially non-immunogenic or less immunogenic than any non-modified parental antibody when used in vivo. The invention relates also to peptide molecules comprising T-cell epitopes of the V-regions of the parental antibody which are modified by amino acid alteration in order to reduce or eliminate said T-cell epitopes.

Abstract: This invention relates to the fields of immunology and protein therapeutics. The therapeutic proteins are polypeptides to be administered especially to humans. The polypeptides are modified whereby the modification results in a reduced propensity for the polypeptide to elicit an immune response upon administration to the human subject. The invention therefor provides methods for the development of therapeutic polypeptides that are less immunogenic than any non-modified counterpart when used in vivo. The modifications used according to this invention relate, for example, to the introduction of protease cleavage sites, attachment of different molecules or insertion of non-natural amino acids.

Abstract: The present invention relates to methods to determine peptides presented on the surface of mammalian cells following addition to the cells of a protein. The present invention also relates to diagnostic tests based on the determination of such peptides or modified molecules resulting from determination of such peptides, such as pharmaceutical entities preferably having specific biological activity and reduced or enhanced immunogenicity when compared with the corresponding non-modified molecules. The methods according to this invention are preferably established with tools using mass spectroscopy (MS).