Lysosomal proteins produced in the milk of transgenic animals
AssigneesPharming B.V., Universiteit Leiden, Academic Hospital, Eramus Universiteit
InventorsArnold J. J. Reuser, Ans T. Van der Ploeg, Frank R. Pieper, Martin Ph. Verbeet
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Abstract
The invention provides transgenic nonhuman mammals producing phosphorylated lysosomal proteins in their milk, and methods of generating the same. Phosphorylation occurs at the 6' position of a mannose side chain residue. Also provided are methods of purifying lysosomal proteins from milk, and incorporating the proteins into pharmaceutical compositions for use in enzyme replacement therapy.
Claims20
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 mammary 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.
Dependencies are inferred from the claim text.