IN VIVO HIGH THROUGHPUT TOXICOLOGY SCREENING METHOD

Medicilon’s toxicology department has professional teams with rich experience in toxicology studies. We offer high-quality data and rapid turnaround period to support drug discovery and development. Our toxicological studies are conducted in various animal species. The toxicological evaluation from dose design, in-life studies to histology and pathology testing along with toxicokinetics studies are all compliant with GLP or NON-GLP standards. Our study platform is certified as one of the Shanghai Public Service Research Platforms.Email:marketing@medicilon.com.cn Web:www.medicilon.com.

Field of the Invention The field of this invention is toxicology testing, particularly toxicology testing in pharmaceutical research and development

Background of the Invention

During the drug development process, potential therapeutic agents or drug candidates must be demonstrated to be both safe and effective for their intended use pnor to obtaining FDA approval and subsequent commercialization, at least in the United States In drug development processes, potential drug candidates are subjected to mutagenicitv and toxicology assessments in an effort to demonstrate safety Mutagemcity analyses take place in bactena (Ames test), Drosophila (Mueller-5 test), and in mammalian cell culture However, toxicology analyses are limited to rnarnmalian cell culture and animal model studies This scheme requires significant time and money to be invested to analyze the toxicity of a candidate drug As such, toxicology studies are typically performed after successful efficacy assessment for drug candidates

With the advent of high throughput drug discovery, there is great interest in the pharmaceutical and related industries to streamline the toxicology testing segment of the drug development process As the number of drug candidates has exploded from 10's per year to 1.000's per year, the toxicology assessment programs have become a severe bottleneck in the drug development process

Accordingly, there is great interest in the development of new high throughput screening assavs which are capable of rapidly providing toxicity data for a large number of different compounds Of particular interest would be the development of an in vivo high throughput toxicity screening assay

Relevant Literature

High throughput toxicity screening assays are discussed in Kelly, "Advances in HTS Toxicology," Genetic Engineering News, March 1. 1999, pg 14, and Sansome, Drug Discovery

Today (1999) 4 199-201 SUMMARY OF THE INVENTION High throughput toxicology screening assays are provided In the subject methods a plurality of different compound compositions, usually at least 10 different compound compositions, are simultaneously assayed for their toxic activity, if any Each compound composition in the plurality is assayed for toxicity by contacting it with a population of multi-cellular organisms and determining the effect of the compound composition on the multi-cellular organisms Multi-cellular organisms that find use in the subject high throughput screening (HTS) assays are those that are small, have differentiated tissues and organs, have a rapid generation time, and are prolific The subject HTS methods find use in a variety of applications, and are particularly suited for use in the toxicological screening of large numbers of compounds, such as combinatonally produced libraπes of compounds

DESCRIPTION OF THE SPECIFIC EMBODIMENTS:A high throughput toxicology screening method is provided In the subject method, at least 10 different compound compositions are tested simultaneously Each compound composition is tested by contacting it with a plurality, e g from about 10 to 1000, non-mammalian multi-cellular organisms and determining the effect of the compound composition on the organisms The multi- cellular organisms employed in the subject methods are small, have differentiated tissues and organs, have a rapid generation time, and are prolific The subject high throughput screening methods find use in a variety of applications, and are particularly suited for use in the toxicology screening of libraries of compounds, such as libraries of combmatonaHy produced compounds

Before the subject invention is descnbed further, it is to be understood that the invention is not limited to the particular embodiments of the invention descnbed below, as variations of the particular embodiments may be made and still fall within the scope of the appended claims It is also to be understood that the terminology employed is for the purpose of describing particular embodiments, and is not intended to be limiting Instead, the scope of the present invention will be established by the appended claims

In this specification and the appended claims, the singular forms Da,D Dan," and Dthe" include plural reference unless the context clearly dictates otherwise Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this invention belongs As summarized above, the subject invention provides a high throughput screening (HTS) method for simultaneously testing the toxicology of a plurality of different compound compositions The subject HTS assays are in vivo toxicology assays, by which is meant that they determine the effect of a compound on a living, multi-cellular organism. As such, the subject HTS assays are distinguished from in vitro assays, in which cell cultures are employed.

In the subject HTS assays, a plurality of different compounds are simultaneously tested More specifically, a plurality of different compound compositions are simultaneously tested Different compound compositions differ from each other in at least one of the following characteristics (a) they are made up of compounds that differ by molecular formula, or (b) they are made up of compounds of the same molecular formula but the compounds are present in different concentrations In other words, any two given compound compositions are different if they are either made up of compounds that differ by molecular formula or are made up of the same type of compound but differ with respect to concentration of that compound For example, a plurality of different compound compositions may include 4 different types of compounds that differ by molecular formula, where each specific type of compound is present in three different concentrations, such that the plurality is made up of 12 different compound compositions.