Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
2000-05-10
2003-02-25
Jones, W. Gary (Department: 1634)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C435S007100, C536S024310, C536S024330
Reexamination Certificate
active
06524797
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates generally to the fields of medicine and pharmacology and, more specifically, to methods of identifying therapeutic compounds in a genetically defined setting.
In the past, the process of discovering novel therapeutic compounds was slow and laborious, and usually involved administering individually synthesized compounds to experimental animals in the hope of observing a therapeutic effect. Recently, significant advances have been made in medicinal chemistry, resulting in the development of combinatorial chemistry methods that allow the rapid production of enormous libraries of structurally distinct compounds. Additionally, due to recent progress in understanding the underlying molecular mechanisms of many diseases, it has become possible to develop in vitro assays to rapidly screen candidate therapeutic compounds. Automation of these assays using computer-controlled robotic systems in high throughput screening methods has made it possible for biotechnology companies to screen millions of compounds per year.
The identification of therapeutic compounds using automated screening methods requires the development of in vitro assays that accurately predict the therapeutic potential of a compound identified by the assay for treatment of the particular pathological condition. So far, current drug screening methods have fallen short of this goal. For example, a variety of cell-free assays have been developed that focus on interactions of candidate compounds with isolated target molecules. Such assays have been shown to be of limited value, since neither the binding properties nor the expected biological properties of the compounds have usually proven to be relevant in vivo.
In an attempt to overcome the limitations of cell-free assays, a variety of cell-based assays have recently been developed. Such assays detect particular cellular functions believed to be relevant to the underlying disease mechanism. To date, however, most cell-based assays for screening candidate therapeutic compounds have used established cell lines. Established cell lines, as evidenced by their ability to be propagated indefinitely in culture, are highly abnormal and are often neoplastically transformed. Therefore, screening assays using such abnormal cell lines are poorly predictive of the therapeutic efficacy of compounds for affecting cell function in an individual.
Additionally, current cell-based assays to identify therapeutic compounds generally use cell lines established from a single individual, or cell lines established from unrelated normal and diseased individuals. Screening assays using cells from unrelated individuals are likely to identify compounds that alter a cellular function related to the genetic differences between the individuals, rather than compounds that alter a cellular function relevant to the underlying disease mechanism.
Therefore, there exists a need for improved methods of screening candidate therapeutic compounds. Ideally, such methods would use relevant cells and assay conditions so as to be highly predictive of the therapeutic efficacy of the compounds. The present invention satisfies this need and provides related advantages as well.
SUMMARY OF INVENTION
The invention provides a method of identifying a therapeutic compound potentially effective against a predetermined pathological condition. The method consists of contacting a cell indicative of the pathological condition from a diseased individual with a plurality of candidate therapeutic compounds under suitable assay conditions, and also contacting a cell indicative of the pathological condition from a normal individual, who is genetically related to the diseased individual, with the plurality of compounds under the same assay conditions. A compound from the plurality of compounds that preferentially alters a predetermined property of the cell from the diseased individual is identified, and characterized as a therapeutic compound potentially effective against the pathological condition.
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Campbell & Flores LLP
Chakrabarti Arun KR.
Jones W. Gary
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