Compositions and methods for treating enzyme deficiency
OwnerArnold J.J. Reuser, Ans T. van der Ploeg +1inventors
InventorsArnold J.J. Reuser, Ans T. van der Ploeg, Martin Ph. Verbeet
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Abstract
The invention provides transgenic nonhuman mammals producing phosphorylated lysosomal proteins in their milk, methods of generating the same, pharmaceutical compositions for use in enzyme replacement therapy, and methods of treating Pompe's disease using human acid alpha glucosidase.
Claims61
A transgenic nonhuman mammal having a transgene comprising:
- a promoter and enhancer from the same mammary gland specific gene;
- a secretory DNA segment encoding a signal peptide functional in mammary secretory cells of the transgenic nonhuman mammal, and
- a recombinant DNA segment encoding acid .alpha.-glucosidase operably linked to the secretory DNA segment to form a secretory-recombinant DNA segment, the secretory-recombinant DNA segment being operably linked to the promoter and enhancer, and wherein the secretory DNA segment is an acid a glucosidase secretory DNA segment or is from the same mammary-gland specific gene as the promoter and enhancer;
- wherein the transgene, in an adult form of the nonhuman mammal or a female descendant of the nonhuman mammal, expresses the secretory-recombinant DNA segment in the mamma secretory cells to produce acid .alpha.-glucosidase that is processed and secreted by the mammary secretory cells into milk in a recoverable amount with .alpha.-glucosidase catalytic activity.
A pharmaceutical composition for parenteral administration to a human patient comprising human acid .alpha.-glucosidase with catalytic activity and in a therapeutically effective dosage to treat a patient suffering from Pompe's disease;
- and a pharmaceutical carrier, the composition being free of other human proteins present in its natural environment.
A method of treating a patient with Pompe's disease, comprising:
- administering to the patient a therapeutically effective amount of human acid alpha glucosidase.
A pharmaceutical composition comprising human acid alpha. glucosidase, human serum albumin, and a sugar in a physiologically acceptable buffer in sterile form.
A pharmaceutical composition comprising alpha glucosidase, mannitol and sucrose in an aqueous solution.
A lyophilized composition produced by lyophilizing a pharmaceutical composition comprising human acid glucosidase, mannitol and sucrose in aqueous solution.
A pharmaceutical composition prepared by lyophilizing a first composition comprising human acid alphaglucosidase, mannitol, sucrose and an aqueous solution to produce a second composition;
- and reconstituting the lyophilized composition in saline to produce a third composition.
Dependencies are inferred from the claim text.