Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
2004-05-10
2009-10-13
Carlson, Karen Cochrane (Department: 1652)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C435S375000, C435S370000, C536S024500
Reexamination Certificate
active
07601494
ABSTRACT:
A method of screening a candidate compound for susceptibility to biliary excretion by a hepatocyte transport protein. The method includes the steps of providing a culture of hepatocytes comprising a transport protein, the culture having at least one bile canaliculus; exposing a candidate compound to the culture; and determining an amount of candidate compound in the at least one bile canaliculus, the amount of candidate compound in the at least one bile canaliculus indicating the susceptibility of the candidate compound to biliary excretion by the transport protein. In some embodiments determining the amount of candidate compound in the bile canaliculus comprises inhibiting expression of the transport protein, measuring the amount of candidate compound in the bile canaliculus and comparing amounts of compound in the canalicules with and without inhibition of the transport protein. A difference in the amount of candidate compound in the canaliculus indicates susceptibility of the candidate compound to biliary excretion by the transport protein. In one embodiment, expression of the transport protein is inhibited through introduction of a RNA having a sequence corresponding to a coding strand of the gene encoding the transport protein into the hepatocyte. Optionally, the culture of hepatocytes is a long-term culture in a sandwich configuration. The method is particularly applicable to the screening of multiple candidate compounds in a single effort.
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Stryer, Lubert,
Brouwer Kim L. R.
Tian Xianbin
Zhang Peijin
Carlson Karen Cochrane
Jenkins Wilson Taylor & Hunt, P.A.
Kosson Rosanne
The University of North Carolina at Chapel Hill
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