Constitutively open hERG (Kv11.1) mutant channels

Details Constitutively open hERG (Kv11.1) mutant channels Constitutively open hERG (Kv11.1) mutant channels

2008-02-29

2010-10-26

Weber, Jon P (Department: 1657)

Chemistry: molecular biology and microbiology

Animal cell, per se ; composition thereof; process of...

Reexamination Certificate

active

07820437

ABSTRACT:
We disclose a cell having double mutations of the hERG gene that lead to charge reversal amino acid substitutions at residues 466 and 534 of the wild type Kv11.1 channel protein. These double charge reversal mutations result in cells having constitutively open Kv11.1 channels. Such cells could be used in a method of testing development-stage drugs and other compounds for Kv11.1 channel block activity.

REFERENCES:
patent: WO 01/58952 (2001-08-01), None
patent: WO 2004/008103 (2004-01-01), None
Christine A. Klemens, et al. “Intragenic Suppression of a Trafficking-Deficient hERG (Kv11.1) Mutation in the Voltage Sensor Yields a Constitutively Open Channel” (2007) Biophysical Journal, 121A.
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M. Zhang, et al. “Interactions Between Charged Residues in the Transmembrane Segments of the Voltage-Sensing Domain in the hERG Channel” (2005) Journal of Membrane Biology, 207(3):169-181.
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PCT/US2008/055484 International Search Report dated Sep. 25, 2008.
Su Zhi, et al. “Mesoridazine: An open-channel blocker of human ether-a-go-go-related gene K+ channel” (2004) Journal of Molecular and Cellular Cardiology, 36(1):151-160.
Kamiya Kaichiro, et al. “ Open Channel block of HERG K+ channels by vesnarinone” (2001) Molecular Pharmacology, 60(2):244-253.
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PCT/US2008/055484 International Search Report dated Nov. 11, 2008.

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