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AssigneePharming B.V.
InventorsHerman A. DeBoer, Rein Strijker, Herbert L. Heynecker, Gerard Platenburg, Sang Ha Lee, Frank Pieper, Paul J.A. Krimpenfort
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Transgenes for producing recombinant polypeptides transgenic bovine species. A transgene for producing recombinant polypeptides in the milk of transgenic bovine species comprises at least one expression regulation sequence, a secretory DNA sequence encoding a secretory signal sequence which is functional in mammary secretory cells of the bovine species and a recombinant DNA sequence encoding the recombinant polypeptide. Also included are methods for producing transgenic bovine species. The method includes introducing the above transgene into an embryonal target cell of a bovine species, transplanting the transgenic embryonic target cell formed thereby into a recipient bovine parent and identifying at least one female offspring which is capable of producing the recombinant polypeptide in its milk. The invention also includes transgenic bovine species capable of producing recombinant polypeptides in transgenic milk as well as the milk from such transgenic bovine species and food formulations containing one or more recombinant polypeptide. Methods are also provided for producing transgenic non-human mammals having a desirable phenotype. The method comprises first methylating a transgene followed by introduction into fertilized oocytes. The oocytes are then cultured to form pre-implantation embryos. Thereafter, at least one cell is removed from each of the pre-implantation embryos and the DNA digested with a restriction endonuclease capable of cleaving the methylated transgene but incapable of cleaving the unmethylated form of the transgene. Those pre-implantation embryos which have integrated the transgene contain DNA which is resistant to cleavage by the restriction endonuclease in the region containing the transgene.
A transgene for producing a recombinant polypeptide in transgenic bovine species comprising at least one expression regulation DNA sequence functional in at least one cell-type of said bovine species operably linked to a recombinant DNA encoding a recombinant polypeptide, wherein said transgene is capable of directing the expression of said recombinant DNA sequence in at least said one cell-type of a bovine species containing said transgene to produce said recombinant polypeptide.
A transgene for producing a recombinant polypeptide in the milk of transgenic bovine species comprising at least one expression regulation DNA sequence functional in the mammary secretory cells of said bovine species, a secretory DNA sequence encoding a secretory signal sequence also functional in the mammary secretory cells of said bovine species and a recombinant DNA sequence encoding a recombinant polypeptide, wherein said secretory DNA sequence is operably linked to said recombinant DNA sequence and to form a secretory-recombinant DNA sequence said at least one expression regulation sequence operably linked to said secretory-recombinant DNA sequence, such that said transgene is capable of directing the expression of said secretory-recombinant DNA sequence in mammary secretory cells of bovine species containing said transgene to produce a form of recombinant polypeptide which when secreted from said mammary secretory cells produces recombinant polypeptide in the milk of said bovine species.
A transgenic bovine species capable of producing a recombinant polypeptide in at least one cell type of said animal.
A transgenic bovine species capable of producing recombinant polypeptide in the milk of said transgenic species.
Milk from transgenic bovine species containing a recombinant polypeptide.
A food formulation comprising transgenic milk containing a recombinant polypeptide.
A method for producing a transgenic non-human mammal having a desirable phenotype comprising:
A transgene for producing a recombinant polypeptide in the milk of transgenic bovine species comprising:
A transgenic bovine species capable of producing a recombinant polypeptide in saliva.
The semen of a transgenic bovine.
A transgene for producing a recombinant polypeptide in the milk of transgenic bovine species comprising:
A method for expressing a human polypeptide in the milk of a bovine comprising:
A transgene for producing a recombinant polypeptide in the milk of transgenic bovine species, said transgene comprising:
Dependencies are inferred from the claim text.