Method of predicting a behavior of one or more drugs
AssigneeGene Stream Pty Ltd.
InventorJohn Michael Daly
Life of this patent
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Abstract
The present invention is directed to the production, breeding and use of transgenic non-human animals such as mice in which specific genes or portions of genes have been replaced by homologues from another animal to make the physiology of the animals so modified more like that of the other animal with respect to drug pharmacokinetics and metabolism. The invention also extends to the use of the genetically modified non-human animals of the invention for pharmacological and/or toxicological studies.
Claims38
A method of predicting a behavior of a single drug or a plurality of drugs in a human, as part of a drug screening or evaluation process, comprising:
- administering the single drug or the plurality of drugs to a transgenic mouse comprising in its genome a homozygous disruption of an endogenous mouse cytochrome P450 (CYP) gene and a stably integrated nucleotide sequence that encodes a human CYP polypeptide operably linked to a promoter, wherein the expression of an endogenous CYP polypeptide from the endogenous CYP gene is abrogated, and wherein the human CYP polypeptide is a homolog of said mouse CYP polypeptide and is other than the intended target of the single drug or plurality of drugs, and wherein expression of the nucleotide sequence that encodes the human CYP polypeptide provides a mouse that predicts behavior of a drug in a human, and
- conducting an analytical test to determine the behavior of the single drug or the plurality of drugs in the transgenic mouse, the results of which have a higher correlation to the behavior of the drug in the human than the results obtained from a wild type mouse;
- wherein the human CYP polypeptide is from a CYP family selected from the group consisting of:
- CYP 1, CYP 2, and CYP 3.
A method of predicting a behavior of a single drug or a plurality of drugs in a human, as part of a drug screening or evaluation process, comprising:
- administering the single drug or the plurality of drugs to a transgenic mouse comprising in its genome a homozygous disruption of an endogenous mouse cytochrome P450 (CYP) gene and a stably integrated nucleotide sequence that encodes a human CYP polypeptide operably linked to a promoter, wherein the expression of an endogenous CYP polypeptide from the endogenous CYP gene is abrogated, and wherein the human CYP polypeptide is a homolog of said mouse CYP polypeptide and is other than the intended target of the single drug or plurality of drugs, and wherein expression of the nucleotide sequence that encodes the human CYP polypeptide provides a mouse that predicts behavior of a drug in a human, and
- conducting an analytical test to determine the behavior of the single drug or the plurality of drugs in the transgenic mouse, the results of which have a higher correlation to the behavior of the drug in the human than the results obtained from a wild type mouse;
- wherein the human CYP polypeptide is from a CYP family selected from the group consisting of:
- CYP3A4, CYP2C9, and CYP2D6.
Dependencies are inferred from the claim text.