Transgenic production of antibodies in milk
AssigneeGenzyme Transgenics Corporation
InventorsHARRY MEADE, PAUL DITULLIO, DANIEL POLLOCK
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Abstract
A method for the production of monoclonal antibodies in mammal's milk, through the creation of transgenic animals that selectively express foreign antibody genes in mammary epithelial cells.
Claims18
A method for obtaining heterologous immunoglobulin from the milk of a transgenic mammal comprising the steps of:
- a. introducing into the germline of said mammal DNA comprising the protein-coding sequences of said immunoglobulin, said DNA operatively linked at its 5′ terminus to a promoter sequence that supports the preferential expression of said genes in mammary gland epithelial cells, and said DNA operatively linked at its 3′ terminus to a sequence containing a polyadenylation site, and
- b. obtaining milk from said mammal.
A transgenic non-human mammal all of whose germ cells and somatic cells contain recombinant DNA sequences encoding immunoglobulin heavy and light chains, wherein said sequences are operatively linked at their 5′ termini to a promoter sequence that supports the preferential expression of said genes in mammary gland epithelial cells, and operatively linked at their 3′ termini to a sequence containing a polyadenylation site.
An isolated purified DNA comprising in the 5′ to 3′ direction
- a) 5′ promoter sequences from the beta casein gene,
- b) a unique Xho I restriction site, and
- c) 3′ untranslated sequences from the goat beta casein gene, wherein a) comprises nucleotides −6168 to −1 of the goat beta casein, wherein nucleotide 1 is the first nucleotide of the beta casein translation initation codon, b) comprises the sequence CGCGGATCCTCGAGGACC, and c) comprises the sequence starting at the PpuMI site found at bp648 of the beta casein cDNA sequence, and continuing for 7.1 kb downstream, termininating in the sequence
- 4 TAAGGTCCAGAGACCGAGACCCACTCACTAGGCAACTGGTCCGRCCAGCTGTTAAGTGA.
Dependencies are inferred from the claim text.