Immortalized hepatocyte cell line secreting modified insulin...

Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing – Genetically modified micro-organism – cell – or virus

Reexamination Certificate

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C424S093200

Reexamination Certificate

active

07919080

ABSTRACT:
The present invention provides a cell line which can be substituted for β cells in human mature pancreatic islets and express insulin in a glucose-concentration dependent manner, and enables the easy obtainment of the number of cells which meets the demand. The present invention also provides a therapeutical cell preparation for treating diabetes. The cell lines of the present invention can be obtained by integrating both a nucleotide sequence encoding tamoxifen-induced Cre recombinase and a nucleotide sequence encoding insulin regulated by glucose-sensitive promoter into the chromosome in a human immortalized hepatic cell line FERM BP-7498 containing the TERT gene inserted in between a pair of LoxP sequences.

REFERENCES:
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patent: 7033744 (2006-04-01), Kobayashi et al.
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patent: WO 00/04171 (2000-01-01), None
patent: WO 00/18239 (2000-04-01), None
Thule, et al. (2000) Gene Therapy, 7: 205-214.
Tuch, et al. (2003) Gene Therapy, 10: 490-503.
Zhang, et al. (1996) Nucleic Acids Research, 24(4): 543-48.
Totsugaya, T. et al., Establishment of hTERT-immortalized human hepatocytes as a source for a hybrid bioartificial liver., Hepatology, 2001, vol. 34, No. 4, Pt.2, pp. 305A, 531.
Lee, H.C. et al., Remission in models ofo type 1 diabetes by gene therapy using a single-chain insulin analogue., nature, 2000, vol. 408, No. 23, p. 483-8.
Cai, J. et al., Construction of a non-tumorigenic rat hepatocyte cell line for transplantation: reversal of hepatocyte immortalization by site-specific excision of the SV40 T antigen., J Hepatol, 2000, vol. 33, No. 5, p. 701-8.
Davies, E. L. et al, Glucose-sensitive insulin-secreting AtT20 cells: A model for insulin delivery by somatic cell gene therapy, Diabetologia, 1996, vol. 39, suppl.1, p. A137, 518.

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