Animal models and methods for sepsis
AssigneeXenogen Corporation
InventorsCarole Bellinger-Kawahara, Pamela R. Contag, Alan Hubbard
Life of this patent
Estimating the term…
Abstract
Methods for selecting a candidate drug for treating sepsis are disclosed. The methods involve labeling a sepsis-causing pathogen with a reporter and monitoring the progress of infection by detecting levels of the reporter in animals treated with test compounds or drugs. The comparisons may be made between experimental and control animals, as well as within a single animal or group of animals. Also disclosed is a method for predicting an expected time of death of an experimental animal in a model system of sepsis using data generated in the initial part of the experiment.
Claims60
A method for selecting a candidate drug for treating sepsis, comprising:
- (i) selecting a model system of sepsis, said model system comprising an animal species and a pathogen species capable of causing sepsis in said animal species, in which model system a critical rate of pathogen load increase has been ascertained;
- (ii) infecting an experimental animal of said animal species with a dose of reporter-labeled pathogen of said pathogen species, where said dose is sufficient to result in a rate of pathogen load increase exceeding said critical rate;
- (iii) administering a test drug to said experimental animal;
- (iv) measuring the level of said reporter in said experimental animal;
- and
- (v) selecting said test drug as a candidate drug for treating sepsis if said test drug is effective to decrease the rate of pathogen load increase in the experimental animal below said critical rate of pathogen load increase.
A method for selecting a candidate drug for treating sepsis, comprising:
- (i) selecting a model system of sepsis, said model system comprising an animal species and a pathogen species capable of causing sepsis in said animal species, in which animal species a time of onset of terminal sepsis, in response to a selected dose of said pathogen species, has been ascertained;
- (ii) infecting experimental and control animals of said animal species with a reporter-labeled pathogen of said pathogen species;
- (iii) administering a test drug to said experimental animals;
- (iv) measuring the level of reporter in said experimental and said control animals at a selected time after onset of terminal sepsis;
- and
- (v) selecting said test drug as a candidate drug for treating sepsis if said test drug is effective to cause a statistically-significant reduction in the level of reporter in said experimental animals as compared with said control animals.
A method for selecting a candidate drug for treating sepsis, comprising:
- (i) selecting a model system of sepsis, said model system comprising an animal species and a pathogen species capable of causing sepsis in said animal species, in which animal species (a) a time of onset of terminal sepsis in response to a selected dose of said pathogen species, and (b) a critical infection level of said pathogen species, have been ascertained;
- (ii) infecting an experimental animal of said animal species with a dose of reporter-labeled pathogen of said pathogen species, where said dose is sufficient to cause the onset of terminal sepsis in an untreated animal;
- (iii) administering a test drug to said experimental animal;
- (iv) measuring the level of said reporter in said experimental animal at a selected time after onset of terminal sepsis, where said level of reporter corresponds to the level of infection in said experimental animal;
- and
- (v) selecting said test drug as a candidate drug for treating sepsis if said test drug is effective to drop the level of infection below said critical infection level.
A method of predicting an expected time of death of an experimental animal in a model system of sepsis, comprising:
- (i) selecting a model system of sepsis, said model system comprising an animal species and a pathogen species capable of causing sepsis, in which animal species a death expectation curve at a selected time has been constructed;
- (ii) infecting an experimental animal of said animal species with a reporter-labeled pathogen of said pathogen species;
- (iii) measuring the level of said reporter in said experimental animal at said selected time;
- and
- (iv) predicting said expected time of death from the level of said reporter and said death expectation curve.
A method of predicting an expected time of death of an experimental animal in a model system of sepsis, comprising:
- (i) selecting a model system of sepsis, said model system comprising an animal species and a pathogen species capable of causing sepsis, in which model system a correlation between actual time of death and a function of the rate of pathogen load increase has been established;
- (ii) infecting an experimental animal of said animal species with a reporter-labeled pathogen of said pathogen species;
- (iii) measuring the level of said reporter in said experimental animal at said selected time;
- and
- (iv) predicting said expected time of death from the level of said reporter and said correlation.
Dependencies are inferred from the claim text.