Enhanced in vivo uptake of glucocerebrosidase

Details Enhanced in vivo uptake of glucocerebrosidase Enhanced in vivo uptake of glucocerebrosidase

1993-06-21

1996-08-27

Wax, Robert A.

Drug, bio-affecting and body treating compositions

Enzyme or coenzyme containing

Hydrolases

435209, 536232, A61K 3847, C12N 942, C12N 1556

Patent

active

055498922

ABSTRACT:
A pharmaceutical composition comprising remodelled recombinant glucocerebrosidase (GCR) is described that provides a therapeutic effect at doses that are lower then those required using remodelled naturally occurring GCR. A method of treating patients with Gaucher's disease using remodelled recombinant GCR is also provided. In vivo uptake of exogenous molecules can be determined by extracting a mixture of cells from a subject, enriching the target cells in vitro, lysing the cells and determining the amount of exogenous molecules.

REFERENCES:
patent: 4713339 (1987-12-01), Levinson et al.
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Furbish, F. S. et al (1981) "Uptake and Distribution of Placental Glucocerebrosidase in Rat Hepatic Cells and Effects of Sequential Deglycosylation" Biochimica et Biophysica Acta, 673:425-434.
Furbish, F. S. et al. (1977) "Enzyme replacement therapy in Gaucher's disease: Large-Scale purification of glucocerebrosidase suitable for human administration" Proc. Natl. Acad. Sci. USA 74(8) 3560-3563.
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B. M. Martin et al. "Glycosylation and Processing of High Levels of Active . . . " DNA 7(2) 99-106 (Mar. 1988).
M. Bergh et al. "Heterologers Expression at Human Glucocerebrosidase . . . " Absts. Paper. Am. Chem. Soc. 199th Meet. BIOT 51 (Apr. 1990).
M. Bergh et al. "Processing and Glycosylation of Human Glucocerebrosidase . . . " Absts. Papers. Am. Chem. Soc. 200th Meet. BIOT 109 (Aug. 1990).
G. J. Murray et al. "Lectin-Specific Targeting at Lysosomal Enzymes . . . " Meth. in Enzymol 149:25-42 (1987).

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