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Methods for identifying pathways of drug action

Patent 5965352 Issued on October 12, 1999. Estimated Expiration Date: Icon_subject May 8, 2018. Estimated Expiration Date is calculated based on simple USPTO term provisions. It does not account for terminal disclaimers, term adjustments, failure to pay maintenance fees, or other factors which might affect the term of a patent.

Patent References

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Inventors

Assignee

Application

No. 074983 filed on 05/08/1998

US Classes:

435/4, MEASURING OR TESTING PROCESS INVOLVING ENZYMES OR MICRO-ORGANISMS; COMPOSITION OR TEST STRIP THEREFORE; PROCESSES OF FORMING SUCH COMPOSITION OR TEST STRIP435/6, Involving nucleic acid435/7.1, Involving antigen-antibody binding, specific binding protein assay or specific ligand-receptor binding assay435/91.2, Acellular exponential or geometric amplification (e.g., PCR, etc.)436/501, BIOSPECIFIC LIGAND BINDING ASSAY536/23.1, DNA or RNA fragments or modified forms thereof (e.g., genes, etc.)536/24.3, Probes for detection of specific nucleotide sequences or primers for the synthesis of DNA or RNA700/266, Chemical process control or monitoring system708/400Transform

Examiners

Primary: Fredman, Jeffrey

Attorney, Agent or Firm

Foreign Patent References

  • 0 816 511 A1 EP. 01/12/1996
  • WO 94/17208 WO. 08/12/1994
  • WO 97/10365 WO. 03/12/1997
  • WO 97/27317 WO. 07/12/1997
  • WO 98/06874 WO. 02/12/1998

International Classes

C12Q 001/00
G01N 033/53
G06F 017/14
C12N 015/00

Abstract

The present invention provides methods for identifying and representing the biological pathways of drug action on a cell by: (i) measuring responses of cellular constituents to graded exposures of the cell to a drug of interest; (ii) measuring the responses of cellular constituents to perturbations in one or more biological pathways of the cell; and (iii) scaling a combination of the measured pathway responses to fit the measured drug responses best according to an objective measure. In alternative embodiments, the present invention also provides for assessing the significance of the identified representation and for verifying that the identified pathways are actual pathway of drug action. In various embodiments, the effects on the cell can be determined by measuring gene expression, protein abundances, protein activities, or a combination of such measurements. In various embodiments, perturbation to a biological pathway in the cell can be made by use of titratable expression systems, use of transfection systems, modification to abundances of pathway RNAs, modifications to abundances of pathway proteins, or modifications to activities of the pathway proteins. The present invention also provides methods for drug development based on the methods for identifying biological pathways of drug action, and methods for representing the biological pathways involved in the effect of an environmental change upon a cell.

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