Animal models for evaluating pharmaceutical compounds
AssigneeImcyse SA
InventorsJean-Marie Saint-Remy, Luc Vander Elst, Vincent Carlier
Life of this patent
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Abstract
The application relates to methods for determining a parameter such as toxicity and pharmacokinetic behavior for a pharmaceutical compound against a disease or disorder. The test animals being used are non-human animals not suffering from or is not showing symptoms or signs of the disorder and which do not provoke an immune response against said pharmaceutical compound. These animals are obtainable by administration of a peptide comprising an oxidoreductase motif further comprising an NKT peptide epitope or an MHC class II T cell epitope of said pharmaceutical compound, wherein said motif and said epitope are separated by a linker of between 0 and 4 amino acids.
Claims18
A method for determining toxicity, pharmacokinetics, half life time, tissue uptake, or metabolism of a polypeptide of interest in a non-human animal, the method comprising the steps of:
- (a) administering a fusion polypeptide to the non-human animal in a sufficient amount to suppress the non-human animal's ability to mount an immune response against the polypeptide of interest, wherein the fusion polypeptide is administered subcutaneously, intraperitoneally, or intravenously;
- (b) administering the polypeptide of interest to the non-human animal;
- and
- (c) determining the toxicity, pharmacokinetics, half life time, tissue uptake, or metabolism of the polypeptide of interest,
- wherein the polypeptide of interest comprises an MHC class II-restricted T cell epitope, and wherein the fusion polypeptide consists of 12 to 50 amino acid residues comprising (i) an oxidoreductase motif of CXXC (SEQ ID NO:
- 10), (ii) an amino acid sequence comprising the MHC class II-restricted T cell epitope of the polypeptide of interest, and (iii) a linker of between 0 and 4 amino acids separating the oxidoreductase motif and the amino acid sequence comprising the MHC class II-restricted T cell epitope of the polypeptide of interest, wherein the oxidoreductase motif is located on either the amino-terminal or carboxy-terminal side of the amino acid sequence comprising the MHC class II-restricted T cell epitope.
A method for determining toxicity, pharmacokinetics, half life time, tissue uptake, or metabolism of a polypeptide of interest in a non-human animal, the method comprising the steps of:
- (a) administering the polypeptide of interest to the non-human animal, wherein the non-human animal has been administered subcutaneously, intraperitoneally, or intravenously a sufficient amount of a fusion polypeptide prior to (a) to suppress the non-human animal's ability to mount an immune response against the polypeptide of interest;
- and
- (b) determining the toxicity, pharmacokinetics, half life time, tissue uptake, or metabolism of the polypeptide of interest,
- wherein the polypeptide of interest comprises an MHC class II-restricted T cell epitope, and wherein the fusion polypeptide consists of 12 to 50 amino acid residues comprising (i) an oxidoreductase motif of CXXC (SEQ ID NO:
- 10), (ii) an amino acid sequence comprising the MHC class II-restricted T cell epitope of the polypeptide of interest, and (iii) a linker of between 0 and 4 amino acids separating the oxidoreductase motif and the amino acid sequence comprising the MHC class II-restricted T cell epitope of the polypeptide of interest, wherein the oxidoreductase motif is located on either the amino-terminal or carboxy-terminal side of the amino acid sequence comprising the MHC class II-restricted T cell epitope.
Dependencies are inferred from the claim text.