METHODS AND PLATFORMS FOR DRUG DISCOVERY

• US 20100240090A1
• Filed: 02/19/2010
• Published: 09/23/2010
• Est. Priority Date: 06/15/2007
• Status: Abandoned Application

• Current Assignee: Kyoto University
• Original Assignee: iZumi Bio, Inc. (Bristol-Myers Squibb Company)
• Inventors: Takahashi, Shunichi, Ishikawa, Tetsuya, Sakurada, Kazuhiro, Masaki, Hideki
• Application Number:
  US12/709,379
• Publication Number:
  US 20100240090A1
• Time in Patent Office: Days
• US Class Current: 435/29
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C12N 15/85 for animal cells
• CPC Class Codes: C12N 2501/602 Sox-2
• CPC Class Codes: C12N 2501/603 Oct-3/4
• CPC Class Codes: C12N 2501/604 Klf-4
• CPC Class Codes: C12N 2501/606 c-Myc
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 2799/027 where the vector is derived from a retrovirus
• CPC Class Codes: C12N 5/0696 Artificially induced pluripotent stem cells, e.g. iPS

Abstract

The present invention involves methods for identifying an agent that corrects a phenotype associated with a health condition or a predisposition for a health condition. The invention also involves methods for identifying a diagnostic cellular phenotype, determining the risk of a health condition in a subject, methods for reducing the risk of drug toxicity in a human subject, and methods for identifying a candidate gene that contributes to a human disease. The invention also discloses human induced pluripotent stem cell lines.

Claims

1. A method for identifying an agent that corrects a phenotype associated with a health condition or a predisposition for the health condition, comprising:

(i) contacting a first population of cells from a human induced pluripotent stem cell line, or cells differentiated from the human induced pluripotent stem cell line, with a candidate agent;

(ii) contacting a second population of cells from the human induced pluripotent stem cell line, or cells differentiated from the human induced pluripotent stem cell line, with a negative control agent;

(iii) assaying the phenotype in the first population and second population after the contacting steps; and

(iv) identifying the candidate agent as correcting the phenotype if the assayed phenotype of the first population after the contacting step is closer to a normal phenotype than the phenotype of the second population after the contacting step;

wherein the cells in the first and second populations of human induced pluripotent stem cells;

(a) comprise at least one endogenous allele associated with the health condition or the predisposition for the health condition;

or

(b) are generated from a subject suffering from the health condition or the predisposition for the health condition.

2-46. -46. (canceled)

47. A method for evaluating a physiological function of a compound comprising treating cells obtained by inducing differentiation of an induced pluripotent stem (iPS) cell with the compound, wherein the iPS cell is obtained by nuclear reprogramming of a somatic cell, which comprises contacting a nuclear reprogramming factor with the somatic cell to obtain an induced pluripotent stem cell.

48. A method for evaluating the toxicity of a compound comprising treating cells obtained by inducing differentiation of an induced pluripotent stem (iPS) cell with the compound, wherein the iPS cell is obtained by nuclear reprogramming of a somatic cell, which comprises contacting a nuclear reprogramming factor with the somatic cell to obtain an induced pluripotent stem cell.

49. A method for evaluating the effect of a compound on a cellular phenotype comprising treating cells obtained by inducing differentiation of an induced pluripotent stem (iPS) cell with the compound, wherein the iPS cell is obtained by inducing pluripotency of a somatic cell, which comprises contacting an induction factor with the somatic cell to obtain an induced pluripotent stem cell.

50. A method for evaluating the toxicity of a compound comprising treating cells obtained by inducing differentiation of an induced pluripotent stem (iPS) cell with the compound, wherein the iPS cell is obtained by inducing pluripotency of a somatic cell, which comprises contacting an induction factor with the somatic cell to obtain an induced pluripotent stem cell.