Non-human transgenic mammal expressing a human FcRn on its mammary gland cells and expressing a transgenic protein-human Fc-domain fusion
View Patent ↗The invention provides, in part, methods for the production of proteins in a transgenic non-human mammal, wherein the proteins are transported from the blood to the mammary gland for secretion in milk. The transport of the protein to the mammary gland and/or milk is facilitated by binding to a transport receptor in the mammary gland.
1. A non-human transgenic mammal whose genome comprises a DNA sequence encoding human FcRn and a DNA sequence encoding beta-microglobulin operably linked to a mammary gland-specific promoter, and further comprises a DNA sequence encoding a transgenic protein comprising a human Fc-domain operably linked to a non-mammary gland-specific promoter.
2. The non-human mammal of claim 1 , wherein the non-mammary gland-specific promoter is a liver-specific promoter.
3. The non-human mammal of claim 2 , wherein the liver-specific promoter is an albumin promoter.
4. The non-human mammal of claim 1 , wherein the transgenic protein is an antibody.
5. A composition comprising milk obtained from the non-human mammal of claim 1 .
6. A method for obtaining a transgenic protein comprising a human Fc-domain, comprising:
generating a non-human transgenic mammal whose genome comprises a DNA sequence encoding human FcRn and a DNA sequence encoding beta-microglobulin operably linked to a mammary gland-specific promoter, and further comprises a DNA sequence encoding transgenic protein comprising a human Fc-domain operably linked to a non-mammary gland-specific promoter,
wherein the transgenic protein comprising a human Fc-domain binds the functional human FcRn via the human Fc-domain,
collecting milk from the non-human mammal, and
separating the transgenic protein comprising a human Fc-domain from the milk.
7. The method of claim 6 , wherein the non-mammary gland-specific promoter is a liver-specific promoter.
8. The method of claim 7 , wherein the liver-specific promoter is an albumin promoter.
9. The method of claim 6 , wherein the transgenic protein comprising a human Fc-domain is an antibody.
10. A composition comprising the collected milk of the method of claim 6 .
11. A composition comprising milk from a non-human transgenic mammal whose genome comprises a DNA sequence encoding human FcRn and a DNA sequence encoding beta-microglobulin operably linked to a mammary gland-specific promoter, and further comprises a DNA sequence encoding a transgenic protein comprising a human Fc-domain operably linked to a non-mammary gland-specific promoter.
12. The composition of claim 11 , wherein the glycosylation pattern of the transgenic protein is different from the glycosylation pattern of the protein when expressed in the mammary gland of the non-human mammal.